10.1007@978 3 319 74558 9

Freeman Miller
Steven Bachrach
Nancy Lennon
Margaret E. O’Neil
Editors
Cerebral Palsy
Second Edition
Cerebral Palsy
Freeman Miller • Steven Bachrach
Nancy Lennon • Margaret E. O’Neil
Editors
Cerebral Palsy
Second Edition
With 1503 Figures and 175 Tables

Editors
Freeman Miller Steven Bachrach
Department of Orthopaedics Department of Pediatrics
Nemours/Alfred I. duPont Nemours/Alfred I. duPont
Hospital for Children Hospital for Children
Wilmington, DE, USA Wilmington, USA
Nancy Lennon Margaret E. O’Neil

Nemours/Alfred I. duPont Hospital Columbia University
for Children Irving Medical Center
Wilmington, DE, USA Programs in Physical Therapy
New York, NY, USA
ISBN 978-3-319-74557-2 ISBN 978-3-319-74558-9 (eBook)

ISBN 978-3-319-74559-6 (print and electronic bundle)
https://doi.org/10.1007/978-3-319-74558-9
1st edition: © Springer Science+Business Media, Inc. 2005
2nd edition: © Springer Nature Switzerland AG 2020
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We dedicate this work to the many children, youth, and adults
with cerebral palsy and like conditions, as well as their families,
who have occupied our practice for the past 30 years. We thank
them for entrusting us with their care and for all they have taught
us. It is our goal to transmit this knowledge to a broad range of
health professionals so other individuals affected by this
condition may benefit from the collaborative, comprehensive,
coordinated, and interprofessional approach we use in our
clinical care model.
Foreword
In 2005, Springer published a landmark textbook with the title “Cerebral

Palsy” by Dr. Freeman Miller, Director of the Cerebral Palsy Program at the
world-renowned Alfred I duPont Hospital for Children, Nemours Foundation,
Wilmington, Delaware. This comprehensive text has become a classic in the
field and is highly regarded by physicians from all specialities who care for
children with cerebral palsy. Surgeons have turned to this text when confronted
with perplexing issues in the management of children with cerebral palsy.
They have invariably found authoritative, practical answers to the most diffi-
cult management problems. There seems to be no scenario which Dr. Miller
and his colleagues have not encountered and consequently they are able to give
practical help, when it is most needed. I have turned to this text throughout the
past 14 years on many occasions for advice on how to approach surgery for a
specific child. I have also used it to prepare teaching material for our Residents
and Fellows in Orthopedic Surgery at the Royal Children’s Hospital,
Melbourne.
With such a success story, why a second edition? The field has moved
quickly during the past 14 years and a wealth of new research has been
published in fields from epidemiology, early diagnosis, early intervention,
stem cell therapies, hip surveillance, movement disorder management, medi-
cal care, and surgical techniques. Dr. Miller and his colleagues have contrib-
uted mightily to that worldwide research effort, with numerous publications in
the peer-reviewed literature. The second edition is in three manageable vol-
umes and has combined e-publication, shorter chapters, easier access, and a
wealth of new material from the duPont team and from colleagues from the
USA and around the world. There is no more extensive, up-to-date, and
complete repository of practical information addressing care of the child
with cerebral palsy than this second edition. Given that orthopedic surgeons
should be “physicians who operate,” the new material on the medical care and
perioperative management of children with cerebral palsy will be invaluable.
The emphasis is on care for children with cerebral palsy, but there is invaluable
content dealing with the needs of adolescents, young adults, and the sometimes
perplexing problem of transition to adult services.
Dr. Miller and I were both heavily influenced by the late Dr. Mercer Rang,
when we were fellows at the Hospital for Sick Children in Toronto. The Mercer
Rang influence flows as a current underpinning this text, in terms of clarity,
authority, and humanity.
vii
viii Foreword
Who should read this book and who will find it helpful? The short answer is
all who are involved in contemporary care of children with cerebral palsy. This
includes orthopedic surgeons, neurosurgeons, neurologists, developmental
pediatricians, physiatrists, physiotherapists, and occupational therapists.
I congratulate Dr. Miller and his co-contributors on this mammoth effort.
This book will have a worldwide reach. It will influence a generation of
clinicians and researchers and it will improve the standards of care for children
with cerebral palsy around the globe.
Director, Hugh Williamson Kerr Graham, M.D., FRCS(Ed), FRACS

Gait Laboratory
Orthopaedic Surgeon
Royal Children’s Hospital, Melbourne
Professor of Orthopaedic Surgery
University of Melbourne
Preface
Cerebral palsy is a condition that is life long, affecting the individual, family,
and immediate community. The goal of supporting the individual with cerebral
palsy to live life with the least impact of their disability requires a focus on the
individual’s and the family’s needs and goals. Furthermore, it is important for
society to be sensitive to and accommodate individuals with disabilities by
limiting architectural impediments, having accessible public transportation
and accessible communication available. The educational system provides
the key means for helping the individual function in society to his or her
maximum ability by providing academic and vocational skill building. In
many ways, the medical care system probably has the least significant role in
preparing the child with cerebral palsy to function at his or her best in society.
However, the medical care system is the place where parents receive a diag-
nosis or an explanation about their child’s developmental problem. It is almost
universally the place where parents also expect their child to receive services in
order to achieve the same milestones that children with “typical development”
achieve. Parents want their children to “be normal” like any other child in our
modern society, but this hope is often challenged by the reality of the emerging
disability.
The goal of this text is to provide a resource with updated evidence to
support health professionals in their role as managers of children with disabil-
ities, so that these children can optimize their function and grow into adults
who are as healthy, mobile, and functional as possible, despite their diagnosis.
This is with the knowledge that ideal medical management during growth will
only improve but not cure the condition or remove the impairments that
contribute to the disability. Probably the most significant aspect of good
medical management through childhood is helping the child and family to
maintain realistic goals and hopes during the growth and development years of
the child. This requires the medical practitioner to get to know the child and
family and have honest, realistic expectations of the child’s function, which are
communicated in a compassionate manner. For many reasons, by far the
largest difficulty in providing this kind of care is the limited time spent with
patients in many medical practices. There is also the sense, especially among
some physicians, that cerebral palsy cannot be cured (meaning make the child
normal) and, therefore, it is a frustrating condition to treat. This is often seen in
the statement “don’t torment the poor child with surgery, just let him be.” The
physician who makes this statement communicates hopelessness to the child
ix
x Preface
and to the family. On the other hand, it is also crucial not to fall into the trap of
telling frustrated parents a small surgery or some other invasive treatment can
be done, because they are frustrated that the child is not progressing. All
medical decisions, including “to do and not to do interventions,” should
always consider both the short-term impact and the long-term impact and
outcome. With every decision the medical practitioner should ask “what will
be the impact of this recommendation by the time the child is a mature adult?”
The ability to “prognosticate” what will happen to the child as he or she
matures to adulthood and when to conduct or implement an intervention is
the most difficult component of care, especially for young practitioners who
have little experience to draw upon. It is the goal of this text to provide this
insight and, as much as possible, to guide the reader in the trajectory of the
condition so that interventions are timely and delivered at the most optimal
time for best outcomes.
This brings up the issue of the very poor scientific documentation of the
natural history of cerebral palsy, although there has been increased interest and
publications related to natural history since the first edition of this text 15 years
ago. However, there is still limited scientifically based natural history and few
long-term studies reporting the impact of childhood conditions and interven-
tion outcomes in adults. Due to this deficit, much of what is written in this text
is still expert-based observation. The goal of writing this is not to document
what is currently absolute fact but to provide at least the starting point of
information with the hope that others will be stimulated to ask questions and
pursue research to prove or disprove the concepts presented here on long-term
trajectories and outcomes.
Research to improve treatment and outcomes for children with cerebral
palsy needs to be planned and evaluated, taking into account its long-term
impact on the child’s growth and development. All treatment should also
consider the negative impact on a child’s experience. As an example, the
impact of wearing ankle orthotics is often minimal for the young child, with
an immediate benefit to improvement in the child’s gait. There probably is no
long-term benefit. This cost–benefit ratio is documented with a number of
moderately good studies in which the child is tested with and without the
brace. On the other hand, if the child develops a strong sense of opposition
around brace wear at 10 years of age because of peer pressure, the brace wear
cannot be justified on a cost–benefit analysis. It is also important to consider
the quality of the scientific evidence, ranging from double-blinded protocols to
case reports. However, it is equally important not to get hung up on this being
the final answer. As an example, there are excellent double-blinded studies to
show that botulinum toxin decreases spasticity and improves gait, but only for
a few months. This knowledge has to be kept in the context of our goal, which
is the child’s maximum possible function at full maturity. There is currently
increased evidence to suggest that botulinum toxin has a negative long-term
effect by causing permanent muscle fibrosis. Therefore, the family and physi-
cian should be deciding together whether the short-term gain outweighs the
long-term negative impact of botulinum toxin. A major problem is that the data
to make these choices often have a high subjective element.
Preface xi
You will note that this book is divided into four comprehensive parts:
(1) Etiology of CP, (2) General Medical Concerns, (3) Orthopedic Concerns,
and (4) Therapy Management. It is the goal of this book to stimulate interest
among a wide range of interdisciplinary providers in doing research to
improve the knowledge base that is focused on the long-term outcome of our
treatments. However, just because the scientific knowledge base is poor, does
not mean that we should not be making an effort to apply the best knowledge
available in our clinical management and care. In the last 15–20 years there has
been a significant increase in interest by specialists in the primary and second-
ary conditions and body systems that are impacted by cerebral palsy and
cerebral palsy–like conditions. The current expansion of this text has followed
this interest and we have tried to find experts in each of the body systems to
present the current evidence and state of the art relative to their expertise. Many
of these experts have developed the interest due to seeing an increasing
number of children with cerebral palsy, and a major way the knowledge base
of an individual professional is expanded is by personal experience. This
means the child and family should be followed over time by the same practi-
tioner with good documentation. One of the best sources of information has
been the children that were followed during growth period for 10–20 years
with videotapes every year or two. The review of such video history can be
very educational. Careful ongoing follow-up is also crucial to providing
patient- and family-centered care to address the hopes, needs, and goals of
the families and individuals with cerebral palsy.
Freeman Miller
Steven Bachrach
Nancy Lennon
Acknowledgments
The production of this second edition of the textbook on Cerebral Palsy was
made easier by the work of the many people acknowledged in the first edition.
The major expansion of this second edition required recruitment of many
specialists in other disciplines. We thank the many authors and coauthors of
all the chapters for their participation. In addition, we are very appreciative of
the contributions by artists for illustrations that greatly enhance the submitted
chapters. Erin Brown provided many illustrations for the first edition of the
book. Most of these illustrations are also present in this volume, some of the
illustrations have been updated. Steven Cook has submitted illustrations in the
ear, nose, and throat chapters. The illustrations of Karlee Diane Rogers are
very helpful to understand the anatomy of the bones and muscles in the
respective chapters. The completion of this volume would not have been
possible without the support of the staff at Springer. We especially thank
Barbara Wolf and Veronika Mang for their steadfast guidance and assistance.
Acknowledgments from the First Edition
The support of the administration of the Nemours Foundation, especially the

support of Roy Proujansky and J. Richard Bowen in giving me time to work on
this project was crucial. It was only through the generous support in caring for
my patients by my partners and staff, Kirk Dabney, Suken Shah, Peter Gabos,
Linda Duffy, and Marilyn Boos, that I was able to dedicate time to writing. I
am very grateful for the generous material provided by all the contributors and
for the extensive and extremely important role of the feedback given to me by
the consultants. In spite of having an extremely busy practice, Kirk Dabney
still found time to read all of the first section, making very valuable improve-
ments, and writing major sections of the upper extremity chapter. With his
wide experience, Michael Alexander made an excellent contribution in the
editorial support of the section on rehabilitation. The task of writing and
editing would have been impossible without the dedicated work of Kim
Eissmann, Linda Donahue, and Lois Miller. To add a personal touch to the
cases, a unique name was assigned by Lois Miller. The CD, which accompa-
nied the first edition only required a great effort of technical programming to
make it work intuitively on all computer formats. Tim Niiler patiently persisted
with this frustrating task until it all worked. Videos were masked and formatted
by Robert DiLorio. Production of the graphics was a major effort in
xiii
xiv Acknowledgments
understanding the complex material in which Erin Browne excelled. This

production would have been impossible without her dedication to understand-
ing the concepts and bringing them to visual clarity. I would also like to thank
the staff of Chernow Editorial Services, especially Barbara Chernow. Without
the long support through the evolution of this book by Robert Albano and his
staff at Springer, this project would also have been much more difficult. And
finally, I am most grateful for the many families and children who have
allowed me to learn from them what it is like to live with the many different
levels of motor impairments. It is to the families and children that I dedicate
this work in the hope that it will lead to improved care and understanding by
medical professionals.
Contents
Volume 1
Section 1: Diagnosis and Pathology
Part I Diagnosis and Pathology ............................ 1
1 The Child, the Parent, and the Goal in Treating

Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Freeman Miller
Part II Etiology of Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . 21
2 Cerebral Palsy and the Relationship to Prematurity ...... 23

Michael Favara, Jay Greenspan, and Zubair H. Aghai
3 Genetic Abnormalities and Congenital Malformations
as a Cause of Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . 37
Kristen Ferriero and Pamela Arn
4 Infectious Etiologies of Cerebral Palsy . . . . . . . . . . . . . . . . . . 45
Neil Rellosa
5 Perinatal Stroke as an Etiology of Cerebral Palsy . . . . . . . . . 55
Nidhi Shah and Gregory C. Griffin
6 Problems During Delivery as an Etiology of Cerebral
Palsy in Full-Term Infants . . . . . . . . . . . . . . . . . . . . . . . . . . . 67
Patrick Philpot, Jay Greenspan, and Zubair H. Aghai
7 Postnatal Causes of Cerebral Palsy . . . . . . . . . . . . . . . . . . . . 77
Laura Owens, Eileen Shieh, and Abigail Case
8 Animal Models of Cerebral Palsy: What Can We Learn
About Cerebral Palsy in Humans . . . . . . . . . . . . . . . . . . . . . . 85
Asher Ornoy
9 The Effects of Umbilical Cord Blood and Cord Tissue
Cell Therapies in Animal and Human Models of
Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97
Jessica M. Sun and Joanne Kurtzberg
xv
xvi Contents
10 Risk Factors for Developing Cerebral Palsy . . . . . . . . . . . . . 111

Antigone Papavasileiou and Marianna Petra
Part III Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129
11 Epidemiology of Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . 131

Kate Himmelmann, Sarah McIntyre, Shona Goldsmith,
Hayley Smithers-Sheedy, and Linda Watson
12 Health and Healthcare Disparities in Children with

Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147
Kirk W. Dabney, Ruth Ziegler, and Laurens Holmes
Part IV Pathology ......................................... 175
13 Neuroimaging Pathology in Cerebral Palsy . . . . . . . . . . . . . . 177

Rahul M. Nikam, Arabinda K. Choudhary, Vinay Kandula,
and Lauren Averill
14 Current Imaging: PET Scan Use in Cerebral Palsy . . . . . . . 217

Sreenath Thati Ganganna and Harry T. Chugani
15 Neuromuscular Junction Changes in Spastic

Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227
Karyn G. Robinson and Robert E. Akins
16 Muscle Changes at the Cellular-Fiber Level in

Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 241
Sudarshan Dayanidhi and Richard L. Lieber
17 Muscle Size, Composition, and Architecture in

Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 253
Christopher M. Modlesky and Chuan Zhang
18 Bone Size, Architecture, and Strength Deficits in

Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 269
Part V Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 285
19 When and How to Evaluate the Child with Possible

Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 287
Sonika Agarwal
20 Cerebral Palsy Prognosis Based on the Physical and

Neurologic Examination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297
S. Charles Bean
21 Classification Terminology in Cerebral Palsy . . . . . . . . . . . . 309

Katherine B. Bevans and Carole A. Tucker
Contents xvii
22 Measuring Outcomes in Children with Cerebral Palsy . . . . . 325

Colyn J. Watkins, Rachel L. DiFazio, and Benjamin J. Shore
23 Biomarker Blood Tests for Cerebral Palsy . . . . . . . . . . . . . . 339
Robert E. Akins and Karyn G. Robinson
Section 2: General Medical
Part VI General Medical Concerns . . . . . . . . . . . . . . . . . . . . . . . . . . 347
24 General Nutrition for Children with Cerebral Palsy . . . . . . . 349

Nicole Fragale, Natalie Navarre, and Jaclyn Rogers
25 Managing the Child with Cerebral Palsy Who Has
Medical Complexity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 359
Dennis Z. Kuo, Sara R. Slovin, and Amy E. Renwick
26 Managing Bone Fragility in the Child with
Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 371
Heidi H. Kecskemethy and Steven Bachrach
27 Managing Irritability and Nonoperative Pain in the
Noncommunicative Child with Cerebral Palsy . . . . . . . . . . . 395
Tracy Hills and Steven Bachrach
28 Palliative Care for Individuals with Cerebral Palsy . . . . . . . 413
Elissa Miller, Carly Levy, and Lindsay Ragsdale
29 Aging with Cerebral Palsy: Adult Musculoskeletal
Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 423
M. Wade Shrader
30 Life Care Planning for the Child with Cerebral
Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 433
Doreen Casuto, Andrea Nebel, and Haydee Piña
Part VII Central Neurologic Problems . . . . . . . . . . . . . . . . . . . . . . . 455
31 Epilepsy in the Child with Cerebral Palsy . . . . . . . . . . . . . . . 457

Stephen Falchek
32 Epilepsy Surgery for the Child with Cerebral Palsy . . . . . . . 469
Badal G. Jain and Harry T. Chugani
33 Hydrocephalus in the Child with Cerebral Palsy . . . . . . . . . 483
Jeffrey Campbell
Part VIII Psychologic and Psychiatric Problems . . . . . . . . . . . . . . 495
34 Psychiatric Disorders in Children with Cerebral Palsy . . . . 497

Rhonda S. Walter and Richard S. Kingsley
xviii Contents
35 Autism Spectrum Disorder in the Child with Cerebral

Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 505
Meghan Harrison and Persephone Jones
36 Family Stress Associated with Cerebral Palsy . . . . . . . . . . . . 515
Heidi Fritz and Carrie Sewell-Roberts
37 The Impact of Cerebral Palsy on Siblings . . . . . . . . . . . . . . . 547
Claire Shrader and Stephanie Chopko
Part IX Neuromotor Function .............................. 557
38 Motor Control and Muscle Tone Problems in

Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 559
Freeman Miller
39 Spasticity Assessment in Cerebral Palsy . . . . . . . . . . . . . . . . 585
Lynn Bar-On, Jaap Harlaar, and Kaat Desloovere
40 Medical Management of Spasticity in Children with
Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 601
Maura McManus
41 Focal Management of Spasticity in Cerebral Palsy . . . . . . . . 611
Freeman Miller
42 Intrathecal Baclofen Therapy: Assessment and Medical
Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 629
Maura McManus
43 Intrathecal Medication Administration in
Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 639
Julieanne P. Sees and Freeman Miller
44 Dorsal Rhizotomy for Spasticity Management in
Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 651
P. Nilsson, N. Wesslén, H. Axelsson, G. Ahlsten, and
L. Westbom
45 Dystonia and Movement Disorders in Children with
Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 661
Freeman Miller and Stephen Falchek
46 Deep Brain Stimulation for Pediatric Dystonia . . . . . . . . . . . 679
Michelle A. Wedemeyer and Mark A. Liker
47 Ataxia and Disorders of Balance in Children with
Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 689
Robert O’Reilly and Erin Field
48 Assessing Dynamic Balance in Children with
Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 695
Timothy A. Niiler
Contents xix
Part X Gastrointestinal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 727
49 Overview of Feeding and Growth in the Child with

Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 729
Devendra I. Mehta, Nneka Ricketts-Cameron, and
Heidi H. Kecskemethy
50 Gastrostomy and Jejunostomy Feedings in Children with

Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 741
J. Fernando del Rosario
51 Gastroesophageal Reflux in the Child with Cerebral

Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 751
Arieda Gjikopulli, Erika Kutsch, Loren Berman, and
Sky Prestowitz
52 Medical and Surgical Therapy for Constipation in

Patients with Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . 767
Erin A. Teeple, Roberto A. Gomez Suarez, and
Charles D. Vinocur
Part XI Ear, Nose, and Throat . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 781
53 Medical Management of Sialorrhea in the Child with

Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 783
Jeremiah Sabado and Laura Owens
54 Surgical Options for Sialorrhea Management in

Children with Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . 799
Christopher Tsang, Steven Cook, and Udayan Shah
55 Auditory Rehabilitation in Children with Cerebral

Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 811
Kiley Trott, Amy Powell, Yell Inverso, and William J. Parkes
56 Upper Airway Obstruction in the Child with Cerebral

Palsy: Indication for Adenotonsillectomy . . . . . . . . . . . . . . . 819
Brian Swendseid and Heather C. Nardone
57 Surgical Management of Tracheostomies

and Tracheal Diversion in Children with Cerebral
Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 829
Richard Schmidt, Christopher Tsang, and Patrick Barth
Part XII Genitourinary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 841
58 Toilet Training and Bladder Control in Children

with Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 843
Puneeta Ramachandra and T. Ernesto Figueroa
xx Contents
59 Neurogenic Bladder in Cerebral Palsy: Upper Motor

Neuron . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 853
Hong Truong and Ahmad H. Bani Hani
60 Kidney Stones: Risks, Prevention, and Management in
Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 871
Carlos E. Araya and Ahmad H. Bani Hani
61 Undescended Testis in Boys with Cerebral Palsy . . . . . . . . . 885
Julia Spencer Barthold and Jennifer A. Hagerty
62 Gynecological Issues in Girls and Young Women with
Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 891
Beth I. Schwartz and Chelsea Kebodeaux
Part XIII Pulmonary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 905
63 Bronchopulmonary Dysplasia and Cerebral Palsy . . . . . . . . 907

Frances Flanagan and Anita Bhandari
64 Asthma in a Child with Cerebral Palsy . . . . . . . . . . . . . . . . . 917
Katherine A. King and Dawn Selhorst
65 Aspiration in the Child with Cerebral Palsy . . . . . . . . . . . . . 925
Aaron Chidekel and Lauren Greenawald
66 Medical Management of Tracheostomy in the Child with
Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 937
Jodi Gustave and Ambika Shenoy
67 Obstructive Sleep Apnea in Children with Cerebral
Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 949
Abigail Strang and Aaron Chidekel
Part XIV Endocrine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 957
68 Short Stature in Children with Cerebral Palsy . . . . . . . . . . . 959

Kevin J. Sheridan
69 Growth Attenuation for the Child with Cerebral Palsy . . . . 979
Jonathan M. Miller and Evan Graber
70 Premature and Delayed Sexual Maturation in Children
Kevin J. Sheridan
71 Endocrine Dysfunction in Children with Cerebral Palsy . . . 1003
Hussein Elmufti and Robert C. Olney
Part XV Eyes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1013
72 Testing Visual Function and Visual Evaluation Outcomes

in the Child with Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . 1015
Elise Ciner, Sarah Appel, Marcy Graboyes, and Erin Kenny
Contents xxi
73 Strabismus Management in the Child with

Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1041
Jonathan H. Salvin and Dorothy Hendricks
74 Cortical Visual Impairment in the Child with

Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1049
Sharon S. Lehman
Part XVI Dental . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1057
75 Dental Hygiene for Children with Cerebral Palsy . . . . . . . . . 1059

Nadarajah Ganeshkumar
76 General Dentistry for Children with Cerebral Palsy . . . . . . . 1067

Harvey Levy
77 Management of Skeletal Facial Deformation and

Malocclusion in Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . 1105
Joseph A. Napoli, Stephanie Drew, and Tim C. Jaeger
Part XVII Anesthesia Management . . . . . . . . . . . . . . . . . . . . . . . . . 1121
78 Medical Evaluation for Preoperative Surgical Planning

in the Child with Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . 1123
Emily Fingado and David Pressel
79 Anesthesia in the Child with Cerebral Palsy . . . . . . . . . . . . . 1131

Dinesh K. Choudhry and Mary C. Theroux
80 Postoperative Pain and Spasticity Management in the

Child with Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1145
B. Randall Brenn and Dinesh K. Choudhry
81 Regional Anesthesia in Patients with Cerebral Palsy . . . . . . 1159

Kesavan Sadacharam, Robert P. Brislin, and R. Scott Lang
82 Anesthetic Management of Spine Fusion . . . . . . . . . . . . . . . . 1185

Mary C. Theroux and Sabina Dicindio
83 Postoperative Care of the Cerebral Palsy Patient . . . . . . . . . 1193

Hussam Alharash, Maxine Ames, Smitha Mathew,
David Rappaport, and Nicholas Slamon
Part XVIII Complementary Medical Treatments . . . . . . . . . . . . . 1215
84 Complementary and Alternative Medicine in

Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1217
Rachel M. Thompson and William Lawrence Oppenheim
85 Hyperbaric Oxygen Therapy for Cerebral Palsy:

Definition and Principles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1227
Jenny L. Wilson and Barry Russman
xxii Contents
86 Acupuncture and Traditional Chinese Medicine Used

to Treat Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1237
Shuyun Jiang
87 Osteopathic Manipulative Treatment and Acupuncture
in Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1251
Julieanne P. Sees
Volume 2
Section 3: Orthopedic
Part XIX Gait in Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1255
88 Musculoskeletal Physiology Impacting Cerebral

Palsy Gait . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1257
Freeman Miller
89 Normal Human Gait . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1277
Freeman Miller
90 Cerebral Palsy Gait Pathology . . . . . . . . . . . . . . . . . . . . . . . . 1299
Freeman Miller
91 History and Physical Examination Components of
Gait Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1309
Daveda Taylor
92 Diagnostic Gait Analysis Technique for Cerebral Palsy . . . . 1323
Freeman Miller
93 Kinematics and Kinetics: Technique and Mechanical
Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1339
Kristen Nicholson
94 Foot Kinematics: Models Used to Study Feet in
Children with Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . 1355
John Henley
95 Pedobarograph Foot Evaluations in Children with
Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1373
Freeman Miller
96 Measuring Femoral and Tibial Torsion in Children with
Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1381
Brian Po-Jung Chen
97 Aerobic Conditioning and Walking Activity Assessment
Nancy Lennon and Freeman Miller
98 Gait Analysis Interpretation in Cerebral Palsy Gait:
Developing a Treatment Plan . . . . . . . . . . . . . . . . . . . . . . . . . 1413
Freeman Miller
Contents xxiii
99 Gait Treatment Outcome Assessments in Cerebral Palsy . . . 1429

Freeman Miller
100 Hemiplegic or Unilateral Cerebral Palsy Gait . . . . . . . . . . . . 1437

Freeman Miller
101 Diplegic Gait Pattern in Children with Cerebral

Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1457
Freeman Miller
102 Hip and Pelvic Kinematic Pathology in Cerebral

Palsy Gait . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1471
Freeman Miller
103 Crouch Gait in Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . 1489

Freeman Miller
104 Knee Deformities Impact on Cerebral Palsy Gait . . . . . . . . . 1505

Freeman Miller
105 Foot Deformities Impact on Cerebral Palsy Gait . . . . . . . . . 1517

Freeman Miller
106 Complications from Gait Treatment in Children with

Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1533
Freeman Miller
107 The Evolution of Knee Flexion During Gait in Patients

Reinald Brunner
Part XX Upper Extremity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1557
108 The Upper Extremity in Cerebral Palsy: An Overview . . . . 1559

Freeman Miller
109 Upper Extremity Assessment and Outcome Evaluation

Lena Krumlinde-Sundholm and Lisa V. Wagner
110 Physical Examination and Kinematic Assessment of the

Upper Extremity in Cerebral Palsy . . . . . . . . . . . . . . . . . . . . 1599
Freeman Miller
111 Spasticity, Dystonia, and Athetosis Management in the

Upper Extremity in Cerebral Palsy . . . . . . . . . . . . . . . . . . . . 1609
Freeman Miller
112 Single-Event Multilevel Surgery for the Upper Extremity

Freeman Miller
113 Shoulder and Elbow Problems in Cerebral Palsy . . . . . . . . . 1629

Freeman Miller
xxiv Contents
114 Forearm, Thumb, and Finger Deformities in

Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1643
Jennifer Ty and Freeman Miller
115 Upper Extremity Operative Procedures in Cerebral Palsy . . . 1669
Freeman Miller
Part XXI Spine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1699
116 Spinal Deformity in Children with Cerebral Palsy:

An Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1701
Freeman Miller
117 Cerebral Palsy Spinal Deformity: Etiology, Natural
History, and Nonoperative Management . . . . . . . . . . . . . . . . 1711
Freeman Miller
118 Surgical Treatment of Scoliosis Due to Cerebral Palsy . . . . . 1723
Kirk W. Dabney and M. Wade Shrader
119 Surgical Management of Kyphosis and Hyperlordosis
in Children with Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . 1743
Kirk W. Dabney
120 Early-Onset Scoliosis in Cerebral Palsy . . . . . . . . . . . . . . . . . 1763
Freeman Miller
121 Complications of Spine Surgery in Cerebral Palsy . . . . . . . . 1777
Freeman Miller
122 Neuromonitoring and Anesthesia for Spinal Fusion
Sabina Dicindio, Anthony DiNardo, and Mary C. Theroux
123 Cervical Spine in Children with Cerebral Palsy . . . . . . . . . . 1813
Freeman Miller
124 Pelvic Alignment and Spondylolisthesis in Children
Freeman Miller
125 Infections and Late Complications of Spine Surgery in
Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1833
Freeman Miller
126 Spinal Procedure Atlas for Cerebral Palsy
Deformities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1851
Freeman Miller and Kirk W. Dabney
Part XXII Hip . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1871
127 Hip Problems in Children with Cerebral Palsy:

An Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1873
Freeman Miller
Contents xxv
128 Etiology of Hip Displacement in Children with

Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1881
Freeman Miller
129 Natural History and Surveillance of Hip Dysplasia in
Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1893
Freeman Miller
130 Prophylactic Treatment of Hip Subluxation in Children
Freeman Miller
131 Hip Reconstruction in Children with Cerebral Palsy . . . . . . 1923
Freeman Miller
132 Palliative or Salvage Hip Management in Children with
Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1951
Freeman Miller
133 Anterior Dislocation of the Hip in Cerebral Palsy . . . . . . . . . 1973
Freeman Miller
134 Hypotonic and Special Hip Problems in Cerebral
Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1989
Freeman Miller
135 Femoral Anteversion in Children with Cerebral Palsy . . . . . 2009
Freeman Miller
136 Windblown Hip Deformity and Hip Contractures in
Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2027
Freeman Miller
137 Complications of Hip Treatment in Children with
Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2049
Freeman Miller
138 Surgical Atlas of Cerebral Palsy Hip Procedures . . . . . . . . . 2079
Freeman Miller
Part XXIII Knee . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2117
139 Overview of Knee Problems in Cerebral Palsy . . . . . . . . . . . 2119

Freeman Miller
140 Anterior Knee Pain and Patellar Subluxation in
Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2127
Freeman Miller
141 Knee Flexion Deformity in Cerebral Palsy . . . . . . . . . . . . . . 2137
Freeman Miller
142 Stiff Knee and Knee Extension Deformities in
Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2159
Freeman Miller
xxvi Contents
143 Tibial Torsion and Knee Instability in Cerebral Palsy . . . . . 2171

Freeman Miller
144 Atlas of Knee Operative Procedures in Cerebral Palsy . . . . 2185
Freeman Miller
Part XXIV Ankle, Foot, and Toes . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2209
145 Foot Deformities in Children with Cerebral Palsy:

An Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2211
Freeman Miller
146 Natural History of Foot Deformities in Children with
Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2223
Freeman Miller and Chris Church
147 Ankle Valgus in Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . 2233
Freeman Miller
148 Ankle Equinus in Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . 2243
Freeman Miller
149 Equinovarus Foot Deformity in Cerebral Palsy . . . . . . . . . . 2267
Freeman Miller
150 Planovalgus Foot Deformity in Cerebral Palsy . . . . . . . . . . . 2289
Freeman Miller
151 Forefoot and Toe Deformities in Cerebral Palsy . . . . . . . . . . 2329
Freeman Miller
152 Atlas of Foot and Ankle Procedures in Cerebral Palsy . . . . . 2351
Freeman Miller
Volume 3
Section 4: Therapy Management in Cerebral Palsy
Part XXV Therapy Management in Cerebral Palsy:

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2393
153 Therapy Management of the Child with Cerebral Palsy:

An Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2395
Margaret E. O’Neil and Nancy Lennon
154 Physical Therapy Elements in the Management of the
Child with Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2405
Carole A. Tucker and Katherine B. Bevans
155 Occupational Therapy Elements in the Management of
the Child with Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . 2417
Laura K. Vogtle
Contents xxvii
156 Speech, Language, and Hearing Practice Elements in the

Management of the Child with Cerebral Palsy . . . . . . . . . . . 2431
Mary Jo Cooley Hidecker
Part XXVI Lifespan Approaches and Environmental

Settings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2443
157 Therapies in Newborn and Pediatric Intensive Care

Units for the Neurologic At-Risk Infants . . . . . . . . . . . . . . . . 2445
Rachel Unanue Rose
158 Early Intervention Services for Young Children with
Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2455
Alyssa LaForme Fiss and Lynn Jeffries
159 Innovative Approaches to Promote Mobility in Children
with Cerebral Palsy in the Community . . . . . . . . . . . . . . . . . 2473
James C. (Cole) Galloway
160 Outpatient-Based Therapy Services for Children and
Youth with Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . 2483
Karen Josefyk and Allyson Menard
161 School-Based Therapy Services for Youth with
Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2491
Laurie Ray and Susan K. Effgen
162 Community Resources: Sports and Active Recreation
for Individuals with Cerebral Palsy . . . . . . . . . . . . . . . . . . . . 2507
Maria A. Fragala-Pinkham and Jennifer Miros
163 Clinical Therapy Services for Adults with Cerebral Palsy . . . 2519
Mary Gannotti and David Frumberg
164 Community Engagement for Adults with Cerebral Palsy . . . 2543
Margo N. Orlin and Susan Tachau
Part XXVII Body Structure and Functions . . . . . . . . . . . . . . . . . . . 2563
165 Postural Control in Children and Youth with Cerebral

Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2565
Sandra L. Saavedra and Adam D. Goodworth
166 Selective Voluntary Motor Control in Children and Youth
with Spastic Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . 2587
Theresa Sukal-Moulton and Eileen Fowler
167 Using Hippotherapy Strategies for Children and Youth
Annette M. Willgens and Ellen A. Erdman
168 Muscle Performance in Children and Youth with
Cerebral Palsy: Implications for Resistance Training . . . . . . 2629
Noelle G. Moreau
xxviii Contents
169 Aquatic Therapy for Individuals with Cerebral Palsy

Across the Lifespan . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2641
Deborah E. Thorpe and Emily E. Paul
170 Functional Electrical Stimulation Interventions for
Children and Youth with Cerebral Palsy . . . . . . . . . . . . . . . . 2661
Samuel C. K. Lee, Ahad Behboodi, James F. Alesi, and
Henry Wright
171 Aerobic and Anaerobic Fitness in Children and
Astrid C. J. Balemans and Eline A. M. Bolster
172 Flexibility in Children and Youth with Cerebral
Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2709
Catie Christensen
173 Postsurgical Therapy for the Individual with
Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2733
Karen R. Turner, Betsy Mullan, Nicole Needles, and
Danielle Stapleton
Part XXVIII Activity and Participation . . . . . . . . . . . . . . . . . . . . . . . 2751
174 Fine Motor Skill Development in Children and Youth

with Unilateral Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . 2753
Susan V. Duff and Aviva L. Wolff
175 Functional Mobility and Gait in Children and Youth with
Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2767
Pam Thomason
176 Robot-Assisted Gait Training for Children and Youth
Hubertus J. A. van Hedel and Andreas Meyer-Heim
177 Treadmill Training for Children and Youth with
Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2817
Ann Tokay Harrington
178 Functional ADL Training for Children and Youth with
Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2829
Faithe R. Kalisperis, Kathleen Miller-Skomorucha, and
Jason Beaman
179 Constraint-Induced Movement Therapy for
Children and Youth with Hemiplegic/Unilateral
Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2845
Ann-Christin Eliasson and Andrew M. Gordon
Contents xxix
180 Assessment and Treatment of Feeding in Children and

Marianne E. Gellert-Jones
181 Communication in Children and Youth with

Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2883
Beth A. Mineo
182 Mobility Supports in Educational Curriculum for

Children and Youth with Cerebral Palsy . . . . . . . . . . . . . . . . 2903
Kathleen Benson, Kristin Capone, Kimberly Duch, and
Christine Palmer-Casey
183 Gaming Technologies for Children and Youth with

Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2917
Torey Gilbertson, Lin-Ya Hsu, Sarah Westcott McCoy, and
Part XXIX Adaptive Technology and Supports . . . . . . . . . . . . . . 2947
184 Wheeled Mobility Options and Indications for Children

and Youth with Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . 2949
Maria A. Jones
185 Ambulatory Assistive Devices for Children and Youth

Mary Bolton and Maureen Donohoe
186 Seating and Positioning Approaches for Children and

Elizabeth Koczur, Denise Peischl, and Carrie Strine
187 Activities of Daily Living Supports for Persons with

Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2987
Maureen Donohoe and Patricia Hove
188 Lower Extremity Orthoses for Children and Youth

David Hudson, Heather Michalowski, and
Freeman Miller
189 Upper Extremity Orthotics for Children and Youth with

Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3023
Tracy M. Shank and Charles Cericola
190 Augmentative and Alternative Communication for

Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3041
Mary Jo Cooley Hidecker
xxx Contents
Part XXX Complementary Therapy Approaches . . . . . . . . . . . . . 3051
191 Neurodevelopmental Treatment Clinical Practice

Model’s Role in the Management of Children with
Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3053
Faithe R. Kalisperis, Jeanne-Marie Shanline, and
Jane Styer-Acevedo
192 Complementary Therapy Approaches for Children

and Youth with Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . 3069
Roberta O’Shea and Gina Siconolfi-Morris
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3083
About the Editors
Dr. Freeman Miller was Co-director of the

Cerebral Palsy Program and the Clinical Director
of the Gait Analysis Laboratory at the Alfred
I. duPont Hospital for Children for 30 years. He
continues as an emeritus staff member at Alfred
I. duPont Hospital for Children providing consul-
tative services and is active in the research program.
His clinical practice of pediatric orthopedics is
limited to children with cerebral palsy. For the
past 25 years, Dr. Miller has held Adjunct Professor
appointments in the Departments of Mechanical
Engineering and Physical Education at the Univer-
sity of Delaware. He is also a member of the Uni-
versity BIOMS program, which is an
interdisciplinary graduate program in biomedical
engineering. Current and past research interests
include investigation of surgical outcomes of CP
surgery through gait analysis, mathematical model-
ing of the hip joint in children with CP, hip moni-
toring and management for children with CP, and
management of spinal deformity in CP.
Dr. Miller has published approximately 200 arti-
cles in peer-reviewed journals. He has been invited to
give many lectures in over 35 different countries. As
a coauthor with Dr. Bachrach, he published a book
Cerebral Palsy: A Guide for Caregiving directed at
families and nonmedical care providers, which was
published in 1995, second edition in 2006, and in
2017 was revised and released as the third edition. A
medical textbook, Cerebral Palsy, with 1080 pages
outlining musculoskeletal care of the child with cere-
bral palsy, was written by Dr. Miller and published in
2005 by Springer-Verlag.
xxxi
xxxii About the Editors
Dr. Steven Bachrach was Co-director of the

Cerebral Palsy Program and Chief of the Division
of General Pediatrics at the Nemours/Alfred
I. duPont Hospital for Children in Wilmington,
DE, for nearly 30 years. He is Board Certified in
Pediatrics and Neuro-developmental Disabilities,
and his clinical practice encompassed both gen-
eral pediatrics and the care of children with devel-
opmental disabilities. He continues as an emeritus
staff member at Alfred I. duPont Hospital for
Children, primarily involved in educational and
research efforts. Dr. Bachrach also served for
20 years as Medical Director of the HMS School
for Children with Cerebral Palsy in Philadelphia,
PA, and currently serves on their Board of Direc-
tors. He is also a consultant to the Alyn Hospital in
Jerusalem, Israel.
Dr. Bachrach has a faculty appointment as
Professor of Pediatrics, Clinical and Educational
Scholarship Track, at the Sidney Kimmel Medical
College of Thomas Jefferson University. He has
been a member of the American Academy of
Cerebral Palsy and Developmental Medicine for
over 35 years and has often been a presenter at
their annual meetings. His research focus has been
on children with cerebral palsy, and especially the
evaluation and treatment of osteoporosis in chil-
dren who are non-ambulatory.
Dr. Bachrach has published over 30 articles in
peer-reviewed journals, as well as a number of
book chapters and abstracts. As a coauthor with
Dr. Miller, he published the book Cerebral Palsy:
A Guide for Caregiving, which was aimed at a lay
audience and published by Johns Hopkins Press in
1995, second edition in 2006, and the third edition
in 2017.
Dr. Bachrach has been married for 46 years and
has 4 children and 14 grandchildren, all of whom
he enjoys spending time with.
About the Editors xxxiii
Ms. Nancy Lennon a physical therapist, is the

manager of the Cerebral Palsy (CP) Program at
the Nemours/Alfred I. duPont Hospital for Chil-
dren in Wilmington, Delaware, where she works
with Dr. Miller and Dr. Bachrach. She has many
years of experience in the Gait Analysis Laboratory
and in Nemours Biomedical Research, where she
collaborates with Dr. O’Neil. Ms. Lennon has a
Bachelor of Science degree in physical therapy
from the University of Delaware and a Master of
Science degree from Hahnemann University. She
has 30 years of clinical experience in working with
children and families affected by cerebral palsy,
15 years of experience conducting clinical research,
and 5 years of experience coordinating family
engagement and advisory activities at the hospital.
Margaret E. O’Neil is a Professor in the Pro-

grams in Physical Therapy, Department of Reha-
bilitation and Regenerative Medicine at Columbia
University, Vagelos College of Physicians and Sur-
geons. She conducts research, advises graduate
students, and teaches content in pediatric physical
therapy and research. She has received grant
funding from several federal and professional orga-
nizations. In her research, she examines objective
measures of physical activity for youth with cere-
bral palsy and effectiveness of activity-based inter-
ventions (including active video games and virtual
reality) to promote fitness and activity. She collab-
orates with an interprofessional team to conduct her
research and they have published widely on these
topics.
She co-teaches clinical workshops on measure-
ment and intervention strategies to promote
strength and fitness in children with disabilities.
She serves as a grant reviewer for multiple agen-
cies and is a member of the APTA and AACPDM
where she serves on multiple committees.
Contributors
Sonika Agarwal Division of Neurology, Perelman School of Medicine at

University of Pennsylvania/Children’s Hospital of Philadelphia, Philadelphia,
PA, USA
Zubair H. Aghai Nemours/Thomas Jefferson University, Philadelphia, PA,
USA
G. Ahlsten Department of Pediatrics, University Hospital, Uppsala, Sweden
Robert E. Akins Nemours Biomedical Research, Nemours – Alfred I.
duPont Hospital for Children, Wilmington, DE, USA
James F. Alesi Department of Physical Therapy, University of Delaware,
Newark, DE, USA
Hussam Alharash Critical Care Division, Department of Pediatrics,
Nemours, AI DuPont Hospital for Children, Wilmington, DE, USA
Maxine Ames Division of General Pediatrics, Nemours, AI DuPont Hospital
for Children, Wilmington, DE, USA
Sarah Appel William Feinbloom Vision Rehabilitation Center, The Eye
Institute of Salus University, Philadelphia, PA, USA
Carlos E. Araya Division of Pediatric Nephrology, Nemours Children’s
Hospital, Orlando, FL, USA
Pamela Arn Department of Pediatrics, Nemours Children’s Specialty Care,
Jacksonville, FL, USA
Department of Clinical Genomics, Mayo Clinic, Jacksonville, FL, USA
Lauren Averill Nemours A I duPont Hospital for Children, Wilmington, DE,
USA
H. Axelsson Department of Neuroscience, Neurophysiology, University
Hospital, Uppsala, Sweden
Steven Bachrach Department of Pediatrics, Nemours/Alfred I. duPont Hos-
pital for Children, Wilmington, USA
xxxv
xxxvi Contributors
Astrid C. J. Balemans Department of Rehabilitation Medicine, Amsterdam

Movement Sciences, Amsterdam Public Health, VU University Medical Cen-
ter, Amsterdam, The Netherlands
Center of Excellence for Rehabilitation Medicine, Brain Center Rudolf
Magnus, University Medical Center Utrecht, Utrecht University and De
Hoogstraat Rehabilitation, Utrecht, The Netherlands
Ahmad H. Bani Hani Division of Pediatric Urology, Nemours/Alfred I.

Department of Urology and Pediatrics, Sidney Kimmel Medical college-
Thomas Jefferson University, Philadelphia, PA, USA
Lynn Bar-On Department of Rehabilitation Sciences, KU Leuven, Leuven,

Belgium
Department of Rehabilitation Medicine, Laboratory for Clinical Movement
Analysis, MOVE Research Institute Amsterdam, VU University Medical
Center, Amsterdam, The Netherlands
Patrick Barth Division of Pediatric Otolaryngology, Nemours duPont Hos-

pital for Children, Wilmington, DE, USA
Department of Otolaryngology, Sidney Kimmel Medical College of Thomas
Jefferson University, Philadelphia, PA, USA
Julia Spencer Barthold Nemours Biomedical Research and Department of

Surgery, Division of Urology, Nemours/Alfred I. DuPont Hospital for Chil-
dren, Wilmington, DE, USA
Jason Beaman Nemours/Alfred I. duPont Hospital for Children, Wilming-

ton, DE, USA
S. Charles Bean Emeritus Professor of Pediatric Neurology, Nemours AI

duPont Hospital, Wilmington, USA
Ahad Behboodi Department of Physical Therapy, University of Delaware,

Newark, DE, USA
Kathleen Benson Physical Therapy, John G. Leach School, New Castle, DE,
USA
Loren Berman Division of Pediatric Surgery, Department of Pediatrics,

Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA
Katherine B. Bevans Department of Health and Rehabilitation Sciences,

College of Public Health, Temple University, Philadelphia, PA, USA
Anita Bhandari Department of Pediatrics, Division of Pulmonary Medicine,

Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Eline A. M. Bolster Department of Rehabilitation Medicine, Amsterdam

Movement Sciences, Amsterdam Public Health, VU University Medical Cen-
ter, Amsterdam, The Netherlands
Contributors xxxvii
Mary Bolton Nemours/Alfred I DuPont Hospital for Children, Wilmington,

DE, USA
Robert P. Brislin Division of Surgical Anesthesiology, Department of Anes-
thesiology and Perioperative Medicine, Nemours/Alfred I. duPont Hospital for
Children, Wilmington, DE, USA
Reinald Brunner Children’s University Hospital Basel, Basel, Switzerland
Basel University, Basel, Switzerland
Jeffrey Campbell Nemours/A.I. duPont Hospital for Children, Wilmington,
DE, USA
Kristin Capone Physical Therapy, John G. Leach School, New Castle, DE,
USA
Abigail Case Nemours/AI duPont Hospital for Children, Wilmington, DE,
USA
Doreen Casuto Rehabilitation Care Coordination, American Association of
Nurse Life Care Planners, San Diego, CA, USA
Charles Cericola Nemours A I duPont Hospital for Children, Wilmington,
DE, USA
Brian Po-Jung Chen Department of Pediatric Orthopedics and
Traumatology, Poznań University of Medical Sciences, Poznań, Poland
Aaron Chidekel Division of Pediatric Pulmonology, Nemours A.I. duPont
Hospital for Children, Wilmington, DE, USA
Stephanie Chopko Nemours /Alfred I. duPont Hospital for Children, Wil-
mington, DE, USA
Sidney Kimmel Medical College/Thomas Jefferson University, Philadelphia,
PA, USA
Arabinda K. Choudhary Nemours A I duPont Hospital for Children, Wil-
mington, DE, USA
Dinesh K. Choudhry Department of Anesthesiology and Perioperative Med-
icine, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA
Department of Anesthesiology, Jefferson Medical College, Thomas Jefferson
University, Philadelphia, PA, USA
Catie Christensen Nationwide Children’s Hospital, Westerville, OH, USA
Harry T. Chugani NYU Comprehensive Epilepsy Center, Department of
Neurology, NYU School of Medicine, New York, NY, USA
Chris Church Nemours Alfred I. duPont Hospital for Children, Wilmington,
DE, USA
Elise Ciner Pediatric and Binocular Vision Service, The Eye Institute of
Salus University, Philadelphia, PA, USA
xxxviii Contributors
Steven Cook Division of Pediatric Otolaryngology, Department of Surgery,

Nemours Alfred I. DuPont Hospital for Children, Wilmington, DE, USA
Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia,
PA, USA
Mary Jo Cooley Hidecker Division of Communication Disorders, Univer-
sity of Wyoming, Laramie, WY, USA
Kirk W. Dabney Department of Orthopedics, Nemours/AI DuPont Hospital
Sudarshan Dayanidhi Shirley Ryan AbilityLab, Chicago, IL, USA
J. Fernando del Rosario Pediatric Gastroenterology, Hepatology and Nutri-
tion, Nemours/A.I. DuPont Hospital for Children, Wilmington, DE, USA
Kaat Desloovere Department of Rehabilitation Sciences, KU Leuven, Leu-
ven, Belgium
Sabina Dicindio Department of Anesthesiology and Perioperative Medicine,
Department of Pediatrics, Jefferson Medical College, Thomas Jefferson Uni-
versity, Philadelphia, PA, USA
Rachel L. DiFazio Orthopedic Center, Boston Children’s Hospital, Boston,
MA, USA
Anthony DiNardo SpecialtyCare, Nashville, TN, USA
Maureen Donohoe Nemours/Alfred I DuPont Hospital for Children, Wil-
mington, DE, USA
Stephanie Drew Department of Surgery, Division of Oral and Maxillofacial
Surgery, Emory University School of Medicine, Atlanta, GA, USA
Kimberly Duch Physical Therapy, John G. Leach School, New Castle, DE,
USA
Susan V. Duff Department of Physical Therapy, Crean College of Health and
Behavioral Sciences, Chapman University, Irvine, CA, USA
Susan K. Effgen Department of Rehabilitation Sciences, College of Health
Sciences, University of Kentucky, Lexington, KY, USA
Ann-Christin Eliasson Department of Woman and Child Health, Astrid
Lindgren Children’s Hospital, Karolinska Institutet, Stockholm, Sweden
Hussein Elmufti Division of Endocrinology, Diabetes, and Metabolism,
Nemours Children’s Specialty Care, Jacksonville, FL, USA
Department of Pediatrics, University of Florida, Jacksonville, FL, USA
Ellen A. Erdman Widener University, Chester, PA, USA
Stephen Falchek Division of Pediatric Neurology, Department of Pediatrics,
Contributors xxxix
Michael Favara Nemours/Thomas Jefferson University, Philadelphia, PA,

USA
Kristen Ferriero Alfred I. duPont Hospital for Children, Wilmington, DE,
USA
Erin Field Otolaryngology, Children’s Hospital of Philadelphia, Philadel-
phia, PA, USA
T. Ernesto Figueroa Division of Pediatric Urology, Department of Surgery,
Nemours/Alfred I. DuPont Hospital for Children, Wilmington, DE, USA
Department of Urology and Pediatrics, Sidney Kimmel Medical College of
Emily Fingado Nemours/Alfred I. duPont Hospital for Children, Wilming-
ton, DE, USA
Alyssa LaForme Fiss Department of Physical Therapy, Mercer University,
Atlanta, GA, USA
Frances Flanagan Division of Pulmonary and Respiratory Diseases, Boston
Children’s Hospital, Boston, MA, USA
Eileen Fowler David Geffen School of Medicine University of California at
Los Angeles, Los Angeles, CA, USA
Maria A. Fragala-Pinkham Adaptive Sports and Medical Rehabilitation
Research Center, Franciscan Children’s Hospital, Boston, MA, USA
Nicole Fragale Clinical Nutrition, Nemours/AI duPont Hospital for Chil-
Heidi Fritz Department of Psychology, Salisbury University, Salisbury, MD,
USA
David Frumberg Department of Orthopedics and Rehabilitation, Yale
School of Medicine, New Haven, CT, USA
James C. (Cole) Galloway Department of Physical Therapy, University of
Delaware, Newark, DE, USA
Department of Psychology, University of Delaware, Newark, DE, USA
Department of Linguistics and Cognitive Science, University of Delaware,
Newark, DE, USA
Biomechanics and Movement Science Graduate Program, University of Del-
aware, Newark, DE, USA
Nadarajah Ganeshkumar Dover Pediatric Dentistry, Dover, NH, USA
Sreenath Thati Ganganna Nemours/Alfred I. duPont Hospital for Children,
Nemours Neuroscience Center, Wilmington, DE, USA
Mary Gannotti Department of Rehabilitation Sciences, University of Hart-
ford, West Hartford, CT, USA
xl Contributors
Marianne E. Gellert-Jones Clinical Feeding Specialist/Speech Language

Pathologist, HMS School for Children with Cerebral Palsy, Philadelphia,
PA, USA
Torey Gilbertson Department of Rehabilitation Medicine, Division of Phys-
ical Therapy, University of Washington, Seattle, WA, USA
Arieda Gjikopulli Division of Pediatric Gastroenterology and Nutrition,
Shona Goldsmith Cerebral Palsy Alliance, University of Sydney, Sydney,
NSW, Australia
Roberto A. Gomez Suarez Department of Gastroenterology, Nemours Chil-
dren’s Hospital, Orlando, FL, USA
Adam D. Goodworth Department of Rehabilitation Sciences, University of
Hartford, West Hartford, CT, USA
Andrew M. Gordon Department of Biobehavioral Sciences, Teachers Col-
lege, Columbia University, New York, NY, USA
Evan Graber Nemours A.I. duPont Hospital for Children and Sidney Kim-
mel Medical College, Thomas Jefferson University, Philadelphia, PA, USA
Marcy Graboyes William Feinbloom Vision Rehabilitation Center, The Eye
Institute of Salus University, Philadelphia, PA, USA
Lauren Greenawald Nemours/Alfred I. duPont Hospital for Children, Wil-
mington, DE, USA
Jay Greenspan Nemours/Thomas Jefferson University, Philadelphia, PA,
USA
Department of Pediatrics, Nemours A.I. duPont Hospital for Children, Thomas
Gregory C. Griffin Nemours/Alfred I. duPont Hospital for Children, Wil-
mington, DE, USA
Jodi Gustave Division of Pediatric Pulmonology, Department of Pediatrics,
Nemours/A.I. Dupont Hospital for Children, Wilmington, DE, USA
Jennifer A. Hagerty Nemours Biomedical Research and Department of
Surgery, Division of Urology, Nemours/Alfred I. DuPont Hospital for Chil-
Jaap Harlaar Department of Rehabilitation Medicine, Laboratory for Clin-
ical Movement Analysis, MOVE Research Institute Amsterdam, VU Univer-
sity Medical Center, Amsterdam, The Netherlands
Department of Biomechanical Engineering, Delft University of Technology,
Delft, The Netherlands
Ann Tokay Harrington Physical Therapy, Arcadia University, Glenside,
PA, USA
Contributors xli
Meghan Harrison Department of Pediatrics, Nemours/AI DuPont Hospital

Division of Developmental Medicine, Department of Pediatrics, Nemours/AI
DuPont Hospital for Children, Wilmington, DE, USA
Dorothy Hendricks Division of Ophthalmology, Nemours/A.I. DuPont
Departments of Ophthalmology and Pediatrics, Sydney Kimmel Medical
College/Wills Eye Hospital, Philadelphia, PA, USA
John Henley Alfred I. duPont Hospital for Children, Wilmington, DE, USA
Mary Jo Cooley Hidecker Division of Communication Disorders, Univer-
sity of Wyoming, Laramie, WY, USA
Tracy Hills Department of Pediatrics, Monroe Carell Junior Children’s Hos-
pital, Vanderbilt University, Nashville, TN, USA
Kate Himmelmann Department of Pediatrics at Institute of Clinical Sci-
ences, University of Gothenburg, Gothenburg, Sweden
Laurens Holmes Department of Orthopedics, Nemours/AI DuPont Hospital
Patricia Hove Tower Health Medical Group, Pennsylvania Hand Center,
Paoli, PA, USA
Lin-Ya Hsu Department of Rehabilitation Medicine, Division of Physical
Therapy, University of Washington, Seattle, WA, USA
David Hudson Western Carolina University, Cullowhee, NC, USA
Yell Inverso Nemours/Alfred I. DuPont Hospital for Children, Wilmington,
DE, USA
Tim C. Jaeger Department of Surgery, Division of Oral and Maxillofacial
Surgery, Emory University School of Medicine, Atlanta, GA, USA
Badal G. Jain Division of Neurology, Department of Pediatrics, Nemours/
Alfred. I. duPont Hospital for Children, Wilmington, DE, USA
Lynn Jeffries Department of Rehabilitation Sciences, University of Okla-
homa Health Sciences Center, Oklahoma City, OK, USA
Shuyun Jiang Yueyang Hospital of Integrated Traditional Chinese and West-
ern Medicine, Shanghai University of Traditional Chinese Medicine, Shang-
hai, China
Maria A. Jones Physical Therapy Program, Academic Affairs, Oklahoma
City University, Oklahoma City, OK, USA
Persephone Jones Department of Pediatrics, Nemours/AI DuPont Hospital
Division of Developmental Medicine, Department of Pediatrics, Nemours/AI
DuPont Hospital for Children, Wilmington, DE, USA
xlii Contributors
Karen Josefyk Nemours/A.I. duPont Hospital for Children, Wilmington,

DE, USA
Faithe R. Kalisperis Gait Lab, Nemours/Alfred I. duPont Hospital for Chil-

Vinay Kandula Nemours A I duPont Hospital for Children, Wilmington,

DE, USA
Chelsea Kebodeaux Department of Obstetrics and Gynecology, Christiana

Care Health System, Newark, DE, USA
Heidi H. Kecskemethy Departments of Biomedical Research and Medical

Imaging, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE,
USA
Erin Kenny William Feinbloom Vision Rehabilitation Center, The Eye Insti-
tute of Salus University, Philadelphia, PA, USA
Katherine A. King Sidney Kimmel School of Medicine, Thomas Jefferson

Pulmonary Division, Nemours Alfred I. duPont Hospital for Children, Wil-
mington, DE, USA
Richard S. Kingsley Emeritus Staff, Division of Behavioral Health,

Nemours, Alfred I. duPont Hospital for Children, Wilmington, DE, USA
Elizabeth Koczur Alfred I. duPont Hospital For Children, Wilmington, DE,

USA
Lena Krumlinde-Sundholm Department of Women’s and Children’s

Health, Karolinska Institutet, Stockholm, Sweden
Dennis Z. Kuo Department of Pediatrics, University at Buffalo, Buffalo, NY,

USA
Joanne Kurtzberg Marcus Center for Cellular Cures, Robertson Clinical and
Translational Cell Therapy Program, Duke University Medical Center, Dur-
ham, NC, USA
Erika Kutsch Division of Pediatric Gastroenterology and Nutrition,

R. Scott Lang Division of Surgical Anesthesiology, Department of Anesthe-

siology and Perioperative Medicine, Nemours/Alfred I. duPont Hospital for
Samuel C. K. Lee Department of Physical Therapy, University of Delaware,

Newark, DE, USA
Sharon S. Lehman Nemours Children’s Health System, AI duPont Hospital

Sidney Kimmel Medical College, Philadelphia, PA, USA
Contributors xliii
Nancy Lennon Nemours/Alfred I. duPont Hospital for Children, Wilming-

ton, DE, USA
Carly Levy Department of Pediatrics, Division of Palliative Medicine,

Nemours/AI duPont Hospital for Children, Wilmington, DE, USA
Sidney Kimmel Medical College Thomas Jefferson University, Philadelphia,
PA, USA
Harvey Levy Department of Surgery, Frederick Memorial Hospital, Freder-

ick, MD, USA
University of Maryland School of Dentistry, Baltimore, MD, USA
Richard L. Lieber Shirley Ryan AbilityLab, Chicago, IL, USA
Mark A. Liker Division of Neurosurgery, Children’s Hospital of Los

Angeles, Los Angeles, CA, USA
Department of Neurosurgery, University of Southern California, Keck School
of Medicine, Los Angeles, CA, USA
Smitha Mathew Critical Care Division, Department of Pediatrics, Nemours,

AI DuPont Hospital for Children, Wilmington, DE, USA
Sarah Westcott McCoy Department of Rehabilitation Medicine, Division of

Physical Therapy, University of Washington, Seattle, WA, USA
Sarah McIntyre Cerebral Palsy Alliance, University of Sydney, Sydney,

NSW, Australia
Maura McManus Nemours Alfred I Dupont Hospital for Children, Wil-

mington, DE, USA
Devendra I. Mehta Center for Digestive Health and Nutrition, Arnold

Palmer Hospital for Children, Orlando, FL, USA
The Florida State University, Tallahassee, FL, USA
Allyson Menard Nemours/A.I. duPont Hospital for Children, Wilmington,

DE, USA
Andreas Meyer-Heim Rehabilitation Center for Children and Adolescents,

University Children’s Hospital Zurich, Affoltern am Albis, Switzerland
Heather Michalowski Lawall Prosthetics and Orthotics, Wilmington, DE,

USA
Elissa Miller Department of Pediatrics, Division of Palliative Medicine,

Nemours/AI duPont Hospital for Children, Wilmington, DE, USA
Sidney Kimmel Medical College Thomas Jefferson University, Philadelphia,
PA, USA
Freeman Miller Department of Orthopaedics, Nemours/Alfred I. duPont

xliv Contributors
Jonathan M. Miller Nemours A.I. duPont Hospital for Children and Sidney
Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA,
USA
Kathleen Miller-Skomorucha Nemours/Alfred I. duPont Hospital for Chil-
Beth A. Mineo College of Education and Human Development, University
of Delaware, Newark, DE, USA
Jennifer Miros The Carol and Paul Hatfield Cerebral Palsy Sports Program
and The Cerebral Palsy Center, St. Louis Children’s Hospital, St. Louis, MO,
USA
Christopher M. Modlesky Department of Kinesiology, University of Geor-
gia, Athens, GA, USA
Noelle G. Moreau Department of Physical Therapy, School of Allied Health
Professions, Louisiana State University, Health Sciences Center, New Orleans,
LA, USA
Betsy Mullan Physical Therapy, OPT Therapy Services, Ltd., Wilmington,
DE, USA
Joseph A. Napoli Division of Pediatric Plastic and Maxillofacial Surgery,
Department of Surgery, Nemours/Alfred I. duPont Hospital for Children,
Wilmington, DE, USA
Sydney Kimmel Medical College, Thomas Jefferson University, Wilmington,
DE, USA
Heather C. Nardone Division of Pediatric Otolaryngology, Nemours/Alfred
I duPont Hospital for Children, Wilmington, DE, USA
Otolaryngology and Pediatrics, Thomas Jefferson University, Philadelphia,
PA, USA
Natalie Navarre Clinical Nutrition, Nemours/AI duPont Hospital for Chil-
Andrea Nebel Rehabilitation Care Coordination, American Association of
Nurse Life Care Planners, San Diego, CA, USA
Nicole Needles DPT, Nemours: A.I. duPont Hospital for Children, Wilming-
ton, DE, USA
Kristen Nicholson Nemours/A. I. duPont Hospital for Children, Wilming-
ton, DE, USA
Timothy A. Niiler Gait Laboratory, Nemours/AI duPont Hospital for Chil-
Rahul M. Nikam Nemours A I duPont Hospital for Children, Wilmington,
DE, USA
P. Nilsson Department of Neuroscience, Neurosurgery, University Hospital,
Uppsala, Sweden
Contributors xlv
Margaret E. O’Neil Columbia University, Irving Medical Center, Programs

in Physical Therapy, New York, NY, USA
Robert O’Reilly Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Roberta O’Shea Physical Therapy, Governors State University, University
Park, IL, USA
Robert C. Olney Division of Endocrinology, Diabetes, and Metabolism,
Nemours Children’s Specialty Care, Jacksonville, FL, USA
William Lawrence Oppenheim Ronald Reagan UCLA Medical Center,
Santa Monica, CA, USA
Margo N. Orlin Department of Physical Therapy and Rehabilitation Sci-
ences, Drexel University, Philadelphia, PA, USA
Asher Ornoy Laboratory of Teratology, Department of Medical Neurobiol-
ogy, Israel Canada Research Institute, Hebrew University Hadassah Medical
School, Jerusalem, Israel
Laura Owens Nemours/AI duPont Hospital for Children, Wilmington, DE,
USA
Christine Palmer-Casey Physical Therapy, John G. Leach School, New
Castle, DE, USA
Antigone Papavasileiou Iaso Children’s Hospital, Athens, Greece
William J. Parkes Division of Otolaryngology, Nemours/Alfred I. DuPont
Emily E. Paul UNC Therapy Services, Meadowmont Wellness Center,
Chapel Hill, NC, USA
Denise Peischl Alfred I. duPont Hospital For Children, Wilmington, DE,
USA
Marianna Petra Department of Orthopaedics, Pendeli Children’s Hospital,
Athens, Greece
Patrick Philpot Thomas Jefferson University, Philadelphia, PA, USA
Haydee Piña Rehabilitation Care Coordination, San Diego, CA, USA
Amy Powell Outpatient Therapy Services, Nemours/Alfred I. DuPont Hos-
David Pressel Capital Health, Trenton, NJ, USA
Sky Prestowitz Philadelphia College of Osteopathic Medicine, Philadelphia,
PA, USA
Lindsay Ragsdale Department of Pediatrics, Pediatric Palliative Care, Ken-
tucky Children’s Hospital, University of Kentucky, Lexington, KY, USA
xlvi Contributors
Puneeta Ramachandra Division of Pediatric Urology, Department of Sur-

gery, Nemours/Alfred I. DuPont Hospital for Children, Wilmington, DE, USA
Department of Urology and Pediatrics, Sidney Kimmel Medical College of
B. Randall Brenn Monroe Carrell Children’s Hospital at Vanderbilt, Van-
derbilt University Medical Center, Nashville, TN, USA
David Rappaport Division of General Pediatrics, Nemours, AI DuPont
Laurie Ray Allied Health Sciences, Division of Physical Therapy, Univer-
sity of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Neil Rellosa Nemours/Alfred I. duPont Hospital for Children, Wilmington,
DE, USA
Amy E. Renwick Nemours Alfred I. duPont Hospital for Children, Wilming-
ton, DE, USA
Nneka Ricketts-Cameron Center for Digestive Health and Nutrition,
Arnold Palmer Hospital for Children, Orlando, FL, USA
Karyn G. Robinson Nemours Biomedical Research, Nemours – Alfred I.
Jaclyn Rogers Clinical Nutrition, Nemours/AI duPont Hospital for Children,
Wilmington, DE, USA
Rachel Unanue Rose Maryville University, Physical Therapy Program, St.
Louis, MO, USA
Barry Russman Shriners Hospitals for Children, Portland, OE, USA
Pediatric Neurology, Oregon Health and Science University, Portland, OR,
USA
Sandra L. Saavedra Department of Rehabilitation Sciences, University of
Hartford, West Hartford, CT, USA
Jeremiah Sabado Division of Pediatric Radiology, Department of Medical
Imaging, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE,
USA
Kesavan Sadacharam Division of Surgical Anesthesiology, Department of
Anesthesiology and Perioperative Medicine, Nemours/Alfred I. duPont Hos-
Jonathan H. Salvin Division of Ophthalmology, Nemours/A.I. DuPont Hos-
Departments of Ophthalmology and Pediatrics, Sydney Kimmel Medical
College/Wills Eye Hospital, Philadelphia, PA, USA
Contributors xlvii
Richard Schmidt Division of Pediatric Otolaryngology, Nemours duPont

Department of Otolaryngology, Sidney Kimmel Medical College of Thomas
Beth I. Schwartz Department of Obstetrics and Gynecology, Thomas Jeffer-
son University, Philadelphia, PA, USA
Division of Adolescent Medicine and Pediatric Gynecology, Department of
Pediatrics, Nemours/A.I. duPont Hospital for Children, Wilmington, DE, USA
Julieanne P. Sees Nemours Alfred I. DuPont Hospital for Children, Wil-
mington, DE, USA
Dawn Selhorst Respiratory Care Department, Nemours Alfred I. duPont
Carrie Sewell-Roberts Nemours/Alfred I. duPont Hospital for Children,
Wilmington, DE, USA
Nidhi Shah Nemours/Alfred I. duPont Hospital for Children, Wilmington,
DE, USA
Udayan Shah Division of Pediatric Otolaryngology, Department of Surgery,
Nemours Alfred I. DuPont Hospital for Children, Wilmington, DE, USA
Department of Otolaryngology - Head and Neck Surgery and Pediatrics,
Wilmington, DE, USA
Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia,
PA, USA
Tracy M. Shank Nemours A I duPont Hospital for Children, Wilmington,
DE, USA
Jeanne-Marie Shanline Therapy Services, Nemours Alfred I. duPont Hos-
Ambika Shenoy Division of Pediatric Pulmonology, Department of Pediat-
rics, Nemours/A.I. Dupont Hospital for Children, Wilmington, DE, USA
Kevin J. Sheridan Endocrinology, Gillette Children’s Specialty Hospital,
Saint Paul, MN, USA
Eileen Shieh Nemours/AI duPont Hospital for Children, Wilmington, DE,
USA
Benjamin J. Shore Orthopedic Center, Boston Children’s Hospital, Boston,
MA, USA
Claire Shrader Mississippi College, Clinton, MS, USA
M. Wade Shrader Cerebral Palsy, Nemours A.I. duPont Hospital for Chil-
xlviii Contributors
Gina Siconolfi-Morris Nemours Children’s Health System, Wilmington,

DE, USA
Nicholas Slamon Critical Care Division, Department of Pediatrics,
Nemours, AI DuPont Hospital for Children, Wilmington, DE, USA
Sara R. Slovin Nemours Alfred I. duPont Hospital for Children, Wilmington,
DE, USA
Hayley Smithers-Sheedy Cerebral Palsy Alliance, University of Sydney,
Sydney, NSW, Australia
Danielle Stapleton Nemours: A.I. duPont Hospital for Children, Wilming-
ton, DE, USA
Abigail Strang Division of Pediatric Pulmonology, Nemours A.I. duPont
Carrie Strine Alfred I. duPont Hospital For Children, Wilmington, DE, USA
Jane Styer-Acevedo NDT and Aquatic Therapy, Upper Darby, PA, USA
Physical Therapy Department Arcadia University, Glenside, PA, USA
Neuro-Developmental Treatment Association (NDTA), Laguna Beach, CA,
USA
Theresa Sukal-Moulton Feinberg School of Medicine, Northwestern Uni-
versity, Chicago, IL, USA
Jessica M. Sun Marcus Center for Cellular Cures, Robertson Clinical and
Translational Cell Therapy Program, Duke University Medical Center, Dur-
ham, NC, USA
Brian Swendseid Department of Otolaryngology, Thomas Jefferson Univer-
sity, Philadelphia, PA, USA
Susan Tachau Pennsylvania Assistive Technology Foundation (PATF), King
of Prussia, PA, USA
Daveda Taylor The Gait and Motion Analysis Laboratory, Nemours/Alfred
I. duPont Hospital for Children, Wilmington, DE, USA
Erin A. Teeple Department of Surgery, Nemours/A.I. Dupont Hospital for
Mary C. Theroux Department of Anesthesiology and Perioperative Medi-
cine, Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE, USA
Department of Pediatrics, Jefferson Medical College, Thomas Jefferson Uni-
versity, Philadelphia, PA, USA
Department of Anesthesiology, Jefferson Medical College, Thomas Jefferson
Pam Thomason Hugh Williamson Gait Analysis Laboratory, Royal Chil-
dren’s Hospital, Melbourne, VIC, Australia
Contributors xlix
Rachel M. Thompson Department of Orthopaedics, Orthopaedic Institute

for Children/UCLA, Los Angeles, CA, USA
Ronald Reagan UCLA Medical Center, Santa Monica, CA, USA
Deborah E. Thorpe Division of Physical Therapy, School of Medicine, The
University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Kiley Trott Department of Otolaryngology – Head and Neck Surgery,
Thomas Jefferson University Hospital, Philadelphia, PA, USA
Nemours/Alfred I. DuPont Hospital for Children, Wilmington, DE, USA
Hong Truong Department of Urology, Thomas Jefferson University Hospi-
tal, Philadelphia, PA, USA
Christopher Tsang Division of Pediatric Otolaryngology, Department of
Surgery, Nemours Alfred I. DuPont Hospital for Children, Wilmington, DE,
USA
Carole A. Tucker Department of Health and Rehabilitation Sciences, Col-
lege of Public Health, Temple University, Philadelphia, PA, USA
Karen R. Turner Nemours: A.I. duPont Hospital for Children, Wilmington,
DE, USA
Jennifer Ty AI DuPont Hospital for Children, Wilmington, DE, USA
Hubertus J. A. van Hedel Rehabilitation Center for Children and Adoles-
cents, University Children’s Hospital Zurich, Affoltern am Albis, Switzerland
Charles D. Vinocur Department of Surgery, Nemours/A.I. Dupont Hospital
Laura K. Vogtle Department of Occupational Therapy, University of Ala-
bama School of Health Professions, Birmingham, AL, USA
Lisa V. Wagner Shriners Hospitals for Children, Greenvill, SC, USA
Rhonda S. Walter Retired, Nemours, Alfred I. duPont Hospital for Children,
Wilmington, DE, USA
Colyn J. Watkins Orthopedic Center, Boston Children’s Hospital, Boston,
MA, USA
Linda Watson Western Australian Register of Developmental Anomalies
(WARDA), Western Australian Department of Health, Perth, Australia
Michelle A. Wedemeyer Department of Neurosurgery, University of South-
ern California, Keck School of Medicine, Los Angeles, CA, USA
N. Wesslén Department of Neuroscience, Neurosurgery, University Hospital,
Uppsala, Sweden
L. Westbom Department of Pediatrics, University Hospital, Lund, Sweden
Annette M. Willgens Temple University, Philadelphia, PA, USA
l Contributors
Jenny L. Wilson Shriners Hospitals for Children, Portland, OE, USA

Pediatric Neurology, Oregon Health and Science University, Portland, OR,
USA
Aviva L. Wolff Department of Rehabilitation, Hospital for Special Surgery,
New York, NY, USA
Henry Wright Department of Physical Therapy, University of Delaware,
Newark, DE, USA
Chuan Zhang Department of Kinesiology, University of Georgia, Athens,
GA, USA
Ruth Ziegler Department of Orthopedics, Nemours/AI DuPont Hospital for
Part I
Diagnosis and Pathology
The Child, the Parent, and the Goal
in Treating Cerebral Palsy 1
Freeman Miller
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
How Different Is the Child with CP? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
Family Impacts of the Child with CP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5
Care-Providing Community . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Cerebral Palsy Clinic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Family Care Provider and Professional Care Provider Relationship . . . . . . . . . . . . . . . 8
Family Response Patterns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
Dealing with Blame . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
Giving and Dealing with Prognosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Giving the Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Medical Therapeutic Relationship to Child and Family . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
The Physical Therapist Relationship . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11
When the Doctor–Family Relationship Is Not Working . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
When the Family Chooses Medical Treatment Against the Physician’s Advice . . . 12
Recommending Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
A Plan for Managing Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
When Complications Occur . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
The Final Goal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
Cases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
Keywords
F. Miller (*) Cerebral palsy · Physician · Parent · Child ·
Department of Orthopaedics, Nemours/Alfred I. duPont Complication · Diagnosis · Prognosis
e-mail: freeman.miller@gmail.com
© Springer Nature Switzerland AG 2020 3

F. Miller et al. (eds.), Cerebral Palsy,
https://doi.org/10.1007/978-3-319-74558-9_194
4 F. Miller
Introduction perspective of normal growth and development

similar to any normal children with an illness,
Cerebral palsy (CP) is a childhood condition such as an ear infection, who need medical treat-
in which there is a motor disability (palsy) caused ment. However, keeping the specific problems of
by a static, nonprogressive lesion in the brain children with CP in the proper context is not
(cerebral). The definition from a scientific per- always easy. The significance of this proper con-
spective was last updated in 2017. Cerebral text is somewhat similar to the significance of
palsy describes a group of permanent disorders having a child doing spelling homework on
of the development of movement and posture Wednesday evening to pass a spelling examina-
causing activity limitation that are attributed tion on Thursday. Likewise, practicing the piano
to nonprogressive disturbances that occur in is necessary to succeed in the piano recital. Even
the developing fetal and infant brain. The motor though each of these acts is important toward the
disorders of cerebral palsy are often accompanied final goal of having a confident, educated, and
by disturbances of sensation, perception, cogni- self-directed young adult who is making a contri-
tion, communication, behavior, by epilepsy, bution in society, the exact outcome of each event
and by secondary musculoskeletal problems may not be all that important in the overall goal.
(Rosenbaum et al. 2007). The causative event Often, the success of a minor goal such as doing
has to occur in early childhood, usually defined well on a specific test is less important than a
as less than 2 years of age. Children with CP have major failure, but the measure of failure or success
a condition that is stable and nonprogressive; may be hard to recognize until years later. As with
therefore, they are in most ways normal children many childhood events, the long-term effect may
with special needs. Understanding the medical be determined more by how the event was han-
and anatomic problems in individuals with CP is dled than by the specific outcome of the event.
important; however, it is also important to always Children with CP experience their unique CP
keep in mind the greater long-term goal, which is treatment, in addition to all the typical childhood
similar to that for all normal children. The goal for experiences. Different children may experience
these children, their families, medical care, edu- events, such as surgery and ongoing physical
cation, and society at large is for them to grow and and occupational therapy, very differently. The
develop to their maximum personal capabilities so long-term impact of these events from the chil-
that they may succeed as contributing members of dren’s perspectives is often either negative or
society. This goal is especially important to keep positive, depending on their relationship with
in perspective during the more medical and both therapists and physicians. These children
anatomically detailed concerns discussed in the may have cognitive, behavior, communication,
remainder of this text. The goal of this chapter is and physical problems, which are the major
to consider some aspects of the complex interac- focus of this text; however, CP affects the whole
tion between the family, child, and medical care family and community.
provider in the context of long-term medical treat- The process of growing and developing
ment requirements. involves many factors. One of the most important
factors in children’s long-term success is a family
caretaker. Likewise, for children with CP, families
How Different Is the Child with CP? may be impacted by the CP as much as the chil-
dren with the physical problems. It is very impor-
When addressing each of the specific anatomic tant for medical care providers to see the problems
concerns, the significance of these anatomic prob- related to CP as not only involving the children
lems relative to the whole child’s success needs to but also involving the families. Society is under-
be kept in the proper context. The problems of standing that the education of normal children
children with CP should be evaluated in the works best when the family care providers
1 The Child, the Parent, and the Goal in Treating Cerebral Palsy 5
actively participate. Likewise, providing medical divorce rate for these families is higher than in
care for children with CP must consider their the normal population. Another high time of fam-
whole families. The outcome for these children ily stress is during the teenage or young adult
will be determined largely by their families, just years for those individuals with severe motor dis-
as the success of normal children’s education abilities. Often, as these individuals are growing
is impacted by their families. The importance of to full adult size and the parents are aging, it
family does not provide an excuse for medical becomes very apparent to the parents that this is
care providers or educators to become pessimistic not a problem that is going away nor are these
if they do not perceive the family is doing its part. young individuals capable of going off to college
In this circumstance, professional care providers and making a life of their own.
still must give as much as possible to each child The response of an individual family varies
but recognize their place and limits in the care of greatly with the wide variability of severity of
these children. Medical care providers who fail to CP. Many families develop a stable and very
recognize their own limits in the ability to provide supportive structure for their disabled child.
care often will become overwhelmed by their Physicians and other medical care providers may
sense of failure and will burn out quickly. be amazed at how well these families deal with
very complex medical problems. For many of
these families, however, the medical complexities
Family Impacts of the Child with CP have accumulated slowly and are themselves a
part of the growth and development phenomena.
A healthy liaison should be developed between With multiple medical treatments often provided
children with CP, the family unit, and the medical by many different medical specialists, a high level
care providers. Cerebral palsy is a condition that of stress develops in almost every family. It is
varies extremely from very mild motor effects helpful for the family to have some caregiver
to very severe motor disabilities with many support and help in dealing with the stigma of
comorbidities. In addition, there are great varia- having a child with CP (Ansari et al. 2016).
tions among families. To provide proper care for For the medical professional, continuing to be
children with CP, physicians need to have some aware of this stress and listening for it during
understanding of the family structure in which the contact with families are important. Families
children are living. Because of time pressures, this with less education and limited financial resources
insight is often difficult to develop. Families vary may do remarkably well, whereas a family with
from young, teenage mothers who may have the more education and more financial resources may
support of their families to single-parent families not be able to cope with the stresses of a child with
and to families with two wage earners and other a severe disability. It is extremely difficult to judge
children. All the pressures of caring for a child which family can manage and which family will
with a disability are added onto the other pressures develop difficulty, so it is important not to become
that families of normal children have. Because prejudiced either for or against specific families.
most children with CP develop problems in Medical care providers should continue to be sen-
infancy and early childhood, families grow and sitive to how the family unit is managing to deal
develop within the context of these disabilities. with their stresses (Bartlett et al. 2017). Some
Often, the father and mother will react differ- families will be seen to be doing well and then
ently or come to different levels of acceptance. suddenly will become overwhelmed in the face of
It is our impression that these different reactions other family stress. This stress may be illness in
may cause marital stress leading to high levels of other family members, financial pressures, job
divorce, most frequently when the children are changes, marital stress, and, most commonly, the
1–4 years old. Although this is our impression, effects of aging on the parents, siblings, and indi-
there is no clear objective evidence that the viduals with CP (Bemister et al. 2014).
6 F. Miller
Care-Providing Community primarily the medical issues, so there will be no

specific in-depth discussion of these support ser-
Children with CP develop in supporting commu- vices, except to remind medical professionals that
nities, which vary with each individual child. other services provide crucial roles in the lives of
There are four general segments of these caring children and their families. The organization of
communities, with the family or direct caregivers the medical care system tends to organize around
being the primary relationship. This primary the general medical care and the specialty care for
relationship is surrounded by community support the problems specific to CP.
services, the medical care system, and the educa- It is very important for families to have an
tional system (Fig. 1). The community support established general medical care provider, either
includes many options such as church, scouting, a pediatrician or family practice physician.
camping, respite services, and recreational Families must be encouraged to maintain regular
programs. The educational system includes both follow-up with a primary care physician because
educational professionals and therapeutic profes- very few orthopedists or other specialists have the
sionals, especially physical and occupational ther- training or time to provide the full general medical
apists. The focus of this larger text is to address care needs of these children. Standard
Fig. 1 A large and extensive care team surrounds the specialized medical team, and community support ser-
family with a child who has cerebral palsy. These care vices. Significant overlap and good communication pro-
providers are roughly organized around the educational vide the best resources to the child and the family
system, primary medical care provider, the cerebral palsy
immunizations and well child care examinations CP. One model has a core group of clinicians who
especially may be overlooked. However, most see the children, often including an orthopedist,
families see their child’s most apparent problem pediatrician, physiatrist, social worker, physical
as the visible motor disability and will focus more therapist, and orthotist. The second model con-
medical attention on this disability at the risk of sists of families making separate appointments for
overlooking routine well child care. The physician each required specialist. The advantage of the first
managing the motor disability should remind model is that it helps families coordinate their
parents of the importance of well child care by child’s needs. The major disadvantage is that it is
inquiring if the child has had a routine physical costly and not reimbursed by the fragmented
examination and up-to-date immunizations. American healthcare system. Many families find
A physical or occupational therapist will provide this model to not be time efficient as they often
most of the medical professional special care have duplicated services. The advantage of the
needs related to the CP. The specialty medical second system is its efficiency to families and
care needs are provided in a specialty clinic, healthcare providers; however, there is often less
usually associated with a children’s hospital. communication between healthcare providers,
and the responsibility of coordinating care from
many different specialists tends to fall more to
Cerebral Palsy Clinic families.
From a practical perspective, considering the
Another way to organize the management of these cost restriction of the healthcare environment, the
well child care needs is with a multidisciplinary best system is some blending of the two clinic
clinic in which a primary care pediatrician is pre- models. We use this blended model, and it works
sent. The administrative structure for setting up a for many patients with CP and their families. We
clinic to care for children with CP is not as well schedule outpatient clinics where an orthopedist
defined as it is for diseases such as spina bifida. and pediatrician share the same physical office
Spina bifida, meningomyelocele, or spinal dys- space; however, each child is given an individual
function clinics are all well-established concepts appointment with each physician. If there are only
and are present in most major pediatric hospitals. musculoskeletal concerns, only the orthopedist
These clinics, which are set up to manage children is scheduled to see the child. However, if a child
with spinal cord dysfunction, have a well-defined also has additional medical needs, the pediatrician
multidisciplinary team. This team works very is seen before or after the orthopedic appointment.
well for these children because they all have sim- Orthotics, rehabilitation engineering for wheel-
ilar multidisciplinary needs ranging from neuro- chair services, nutritionists, social workers, and
surgery to orthopedics, urology, and rehabilitation physical and occupational therapy are available
(Brochard et al. 2017). However, this model does in very close proximity to this outpatient clinic.
not work as well for children with CP because If a child had a recognized problem before the
their needs vary greatly. These needs range from a clinic visit, appointments are coordinated to see
child with hemiplegia who is being monitored for other specialists. However, if the problem is found
a mild gastrocnemius contracture only to a child at the current visit, such as an orthosis that is too
who is ventilator dependent with severe osteopo- small, this child can be sent to the orthotist and be
rosis, spasticity, seizures, and gastrointestinal molded on the same day for a new orthotic. This
problems. It is impossible to have all medical clinic also has a special coordinator to help par-
specialists available in a clinic setting, especially ents schedule appointments with other specialists
in today’s environment where everyone has to such as dentistry, gastroenterology, or neurology.
account for their time by doing productive work, This structure is most efficient for medical care
described mainly as billable time. providers; avoids duplication of services, such as
There are two models currently being used in having a physical therapist evaluate a child who is
most pediatric centers for the care of children with getting ongoing community-based therapy; and
8 F. Miller
can potentially provide maximal efficient use of relationship may be somewhat different for edu-
the parents’ time. The main problem arising with cational professionals than for medical care pro-
this system is that it requires cooperation between fessionals. This discussion focuses primarily on
many areas in the hospital. This model only works the medical care professional relationship, specif-
if the needed specialists are all working on the ically on the care of the motor disabilities pro-
same day and are willing to work around each vided by a physician.
other’s schedules. For example, holding the CP The first aspect of treating children with CP is
clinic on a day that the dental clinic is closed or the ensuring that the families have heard and come to
orthotist is not available does not work. Although some level of acceptance that their child has a
individual appointments are made with special- problem called CP, which is permanent and will
ists, schedules often are not maintained perfectly, not go away. Hearing and acknowledging a diag-
so if the orthopedic appointment is for 10 a.m. nosis is a process that requires families first to
but the child is not seen until 11 a.m., the time of come to terms with hearing the words and, sec-
the next appointment with a neurologist, all the ond, to internalize these words. This process may
schedules are affected. Making this system work take many years, with families initially acknowl-
requires flexibility by all involved. edging that there is a problem, but still expecting a
One area of efficiency that the medical care cure soon. In the initial session with families to
system pays little attention to is the parents or discuss this diagnosis, it is important that physi-
caretaker’s time. Most caretakers have to schedule cians allow plenty of time to answer all their
a whole day to take a child to a physician appoint- questions, do not demand that they immediately
ment because it means taking the child out of the accept the physicians’ words, and avoid definitive
school, usually driving some distance, seeing the words that bring a sense of hopelessness to fami-
physician, and then returning home. This system lies. During this discussion with families, there
of actively trying to schedule a number of appoint- is little role for the use of absolutist terms like
ments on the same day allows parents to make “never,” “will not,” “cannot,” “will die,” or “will
use of the whole day, avoiding more days out of never amount to anything.” These terms often
work for the parent and out of school days for the strike families as extremely cruel and threaten to
child. remove all their hope, which they desperately
Coordination between team members is need. Having time to answer all the family’s
accomplished by weekly team meetings where questions and allowing them to have their own
outpatient children with specific needs, along doubts is important. As the physician relationship
with pending and present in-hospital patients, are develops with a family, especially in the context of
discussed. No matter what administrative structure a clinic for CP, the families will slowly come to
is used for the outpatient management of children their own realization. However, this process of
with CP, because of the diverse population and coming to terms with the diagnosis may be
needs, there are always individuals who will not impacted by the circumstances and situations sur-
fit the structure. Therefore, an important aspect of rounding the etiology.
providing medical care to this patient population is
to have flexibility in the delivery system.
Family Response Patterns
Family Care Provider and Professional All families come to terms with their children’s
Care Provider Relationship problems in their own way; however, there are
several problems that are based on mechanisms
The specific organizational model for providing surrounding the inciting event or the time of the
care is not as important as the fact that the medical diagnosis. In general, most families struggle to
care provided to the child with CP must always be understand why this happened to their children
provided to the family–child unit. This and who is at fault.
Obstetric difficulties surrounding delivery can It is important for medical staff to recognize
be the clear cause of CP. However, many of these this pattern of behavior in families and respond
birthing problems are probably due to a fetus very consciously by increasing communication
that was already sick. Nevertheless, the birthing and frequent contact. Again, the primary respon-
problems often focus the parents on looking for sibility for this contact rests with the senior
someone to blame, frequently the obstetrician. treating physician, who must display confidence,
Some families can come to the point where they knowledge, and control of the situation to comfort
can release this need to blame; for others, it may the family. These families are very perceptive of
lead to finding a legal solution by way of bringing physicians and care providers who do not have
a legal suit against the individual or organization experience and confidence in dealing with their
perceived to be at fault. These legal pursuits are children’s problems. Often, these families have
often encouraged by lawyers, and for many fam- considerable experience in hospitals and notice
ilies, this only leads to more disappointment when when things are overlooked or symptoms are not
some of the legal efforts are unsuccessful. For addressed in an appropriate time (Case 1).
families who win legal judgments, there may be
some sense of justice; however, the difficulty of
caring for a child with a disability continues, and Dealing with Blame
the need to come to terms with why this happened
does not disappear by receiving money from a Medical care providers must not get into situa-
successful lawsuit. tions where they inadvertently inflame this need to
Some parents, who have difficulty dealing blame someone for the cause of these children’s
with why this happened to their child, will be CP. When parents give their perception of the
very suspicious of the medical system and will history of the inciting event, it should be accepted
be perceived as being very difficult. There is a as such without comment. Medical care providers
tendency for medical care providers, doctors, should not tell parents how terrible the person they
nurses, and therapists to avoid contact with these blame was or anything else that gives the impres-
families, which often leads to more stress because sion that the CP could have been avoided if only
the families feel that they are being avoided. This this or that were done. This kind of postmortem
kind of very suspicious family, especially with evaluation of past medical events helps medical
underlying unresolved anger related to the initial practitioners to learn; however, a detailed dissec-
diagnosis, needs to be kept exceptionally well tion of long-gone medical events to look for a
informed and have frequent contact with the person to blame seldom helps the families to
senior attending physician. come to terms with their children’s disabilities.
When a child is hospitalized, it is important By far, most of these families’ “need to find some-
to have the attending physician meet with the one to blame” is a stable enduring part of their
family frequently and always keep them appraised lives, and if the treating physician acknowledges
of changes and expected treatment. This level this need and focuses their concerns on the chil-
of communication with families sounds very sim- dren’s current care and situation, the blame issue
ple; however, we have seen many families who tends to fall to the background.
endured a series of terrible events in hospitals, There is no need for the orthopedic physician
such as oversights or staff failure to recognize an caring for these children’s motor disabilities to get
evolving event that the family already pointed out. an extensive history of the birth and delivery
When these situations are brought up with staff, directed at understanding the etiology of the CP
such as nurses and residents, there is a tendency from the families, so long as the diagnosis of CP is
for the response to be “they brought it on them- appropriate. Instead, the families’ mental energies
selves.” This kind of thinking is unacceptable should be directed at the goal, which is to help
because lack of contact with the senior responsi- their children be all they can be, given the current
ble medical staff is usually the main cause. circumstances. However, trying to convince the
10 F. Miller
parents that they have to give up looking for a Giving and Dealing with Prognosis
cause or a person to blame is also futile. If the
parents are totally immobilized and cannot move Another experience frequently reported by par-
forward, arranging psychotherapy may be worth- ents whose children were in neonatal nurseries is
while; however, most parents will perceive this as the comment that the children probably will not
another attempt to sweep away the problem of survive and, if they do, will be vegetables. This
who is responsible. comment has been reported to us by parents of
Another common scenario for the diagnosis of children who end up with hemiplegia as well as
CP is when a parent or grandparent recognizes children with quadriplegia. We believe this com-
some slow development in a child. This child ment stems from the great difficulty of making a
was then taken to see the family doctor or pedia- specific prognosis of outcome in the neonatal
trician who reassured the family that they were period. Also, some physicians tell families the
overreacting. Often, these families end up going worst possible outcome, believing that when the
to their primary care provider two, three, or four children do better, the families will be grateful for
times to hear the same response, that is, that they their good luck. However, this explanation almost
are just overreacting. The child is a little slow, but never has the intended outcome, and much more
there is nothing to worry about. These families commonly the families perceive these comments
often want to lay the blame for the CP upon the as the physician being incompetent or deceitful.
physician, believing that this delayed diagnosis is Often, these families will interpret attempts by
why the child currently is so severe. There is later physicians to discuss prognosis or expected
almost no circumstance where a delayed diagno- results of surgery as being too pessimistic. For
sis will be of any significance. It is important for these families, it is important to be as realistic
these parents to have their concerns about the as possible; however, their optimism may cause
delayed diagnosis acknowledged, but then they some disappointment as their expectations of
must be reassured that this delay did not, in any greater outcomes are not realized. Generally,
way, cause their child to have a greater severity of these families do come to appropriate expecta-
CP. Some of these families will have difficulty tions but continue to have some negative feelings
developing other trusting relationships with phy- about their neonatal experience.
sicians and may call, especially initially, for many An important aspect of giving prognosis or
minor concerns until confidence in their physician information that is requested by families is to
is developed. always acknowledge that it is imperfect. Requests
Sometimes CP is the result of an accident or to know if a child will walk or sit should be
event in childhood, such as a toddler with a near answered as honestly as possible, always avoiding
drowning, or a child with a closed head injury absolutist terms such as “never,” “cannot,” or
from a motor vehicle accident in which the parent “will not.”
was the driver. In these situations, the parents
often feel a substantial amount of blame for caus-
ing their child’s disability. This self-blame and Giving the Diagnosis
guilt may be even more difficult for a parent to
come to terms with than blame focused outward. Another common problem surrounding diagno-
One response to the inwardly focused blame is to sis of children with CP is failure to give the
search for extraordinary cures, demand more ther- parents a diagnosis. A common example of this
apy, or get more devices. This behavior seems to is a mother of a 5-year-old who is unable to sit
be one of “making it up to the child.” It is helpful and brings the child to see the orthopedist to find
to reassure the family that things besides more out why the child cannot walk. The history
therapy or more devices, such as maximizing the reveals a normal pregnancy and delivery; how-
child’s educational ability, will help the child. ever, by age 12 months, the child was not sitting,
so the mother started going to doctors to find out know them best. Often, the parents recognize
what was wrong with the child. She has seen developmental gains and day-to-day variability
three neurologists and a geneticist, has had skin in their child’s function first. Physical therapists
biopsies, muscle biopsies, computed tomogra- will spend the most therapeutic time during treat-
phy (CT) scan, magnetic resonance imaging ment with children and will bring the experience
(MRI) scan, and many blood tests, but every- of similar children. This in-depth experience with
thing is normal. The mother hears from these similar children allows therapists to help parents
doctors that they can find nothing wrong with understand the expected changes as well as teach
her child; however, what the doctors probably parents and children how to maximize their func-
told the mother is that the medical tests are tion. The orthopedist treating the motor disability
normal and they do not know what caused the will have the least experience with an individual
child’s current disability. child but will have the broadest experience with
Families need to be told what is wrong with many children to understand the expectations of
their child. This type of family is easily helped by what will occur. The physician’s experience with
explaining that the child has CP. Physicians each child, however, will be much more superfi-
should clearly explain that even though they do cial, and the physician depends on the parents’
not understand why the child has CP, it is the and therapists’ observations of the children’s
diagnosis, which they know exactly how to treat. function over time and the variability of function
Taking time and providing information to these during the day. Recognizing these individual
families will stop the endless and futile search for strengths will allow the parents’, therapists’, and
“why” and allow them to focus on caring for and orthopedists’ perception of individual children
treating their children. This situation is caused to be combined to make the best therapeutic
almost entirely by physicians not being clear in judgment.
communication with parents and the particular
aversion by some physicians to giving a diagnosis
of CP. This aversion is very similar to wanting to The Physical Therapist Relationship
avoid telling a patient that she has cancer and
therefore telling her that she has a non-benign The role of the primary treating physical therapist,
growth whose cause cannot be explained. In this especially for the young child between the ages of
way, CP is like cancer in that a physician often 1 and 5 years, will incorporate the typical role that
cannot determine the etiology; however, the treat- the grandmother and the general pediatrician play
ment options are well defined and should be for normal children. In addition, the therapist ful-
started immediately. filling this role must have knowledge and experi-
ence in dealing with children with CP. This role
model involves time spent teaching the parents
Medical Therapeutic Relationship how to handle and do exercises with their child.
to Child and Family This role also involves helping the parents sort out
different physician recommendations, encourag-
There are many different types of therapeutic rela- ing the parents, and showing and reminding par-
tionships that work for families and their children; ents of the positive signs of progress in the child’s
however, there are some patterns that work better development. When this role works well, it is
than others. These patterns each have their risks the best therapeutic relationship a family has.
and benefits as well. The major therapeutic rela- The positive aspects of this role are providing
tionships in the treatment of motor problems of the parents with insight and expectations of their
children with CP include the parents, the physical child, reassuring the family that they are providing
therapists, and the physicians. The parents will excellent care and being readily available to
spend the most time with their children and will answer the family’s questions.
12 F. Miller
The “grandmothering” role of the therapist invariably, this same therapist next will com-
has associated risks. One of the greatest risks in plain that the family and child never do the
our current, very unstable medical environment home exercise program or that the child is not
is that a change in funding or insurance coverage brought to therapy regularly. This relationship
may abruptly end the relationship. An abrupt may work for a school-based therapist or a ther-
change can be very traumatic to a family. The apist doing inpatient therapy, but it leads to great
therapist must be careful not to be overly frustration for both the therapist and family
demanding of the family but to help the family when it is applied to an outpatient-based, ongo-
find what works for them. Occasionally, a ther- ing developmental therapy. In this environment,
apist may be fixated on a specific treatment pro- the therapist must try to understand and work
gram and believe that it is best for the child; within the family’s available resources.
however, the parents may not be in a situation
to follow through with all this treatment. The
parents feel guilty, and the therapist may try to When the Doctor–Family Relationship
use this guilt to get them to do more. Is Not Working
The physical therapist in this role as a thera-
peutic “grandmother” can help parents sort out Medical care providers need to understand
what medical care and choices are available. The that personalities are such that one individual
therapist can help parents by attending physician can never meet everyone’s needs. This does not
appointments and making the parent ask the right mean that as soon as the doctor–family relation-
questions, which is often not possible because of ship becomes difficult, it is not working. At this
funding restrictions. The physical therapist must time, the relationship needs to be discussed, and
not give specific medical advice beyond helping the physician should be open about giving the
parents get the correct information. Therapists family permission to go to another doctor. Some
with extensive experience should recognize that families will just leave without saying anything
they have great, detailed, and deep experience and others will feel guilty about wanting to leave.
with a few children and that generalizing from Physicians must be honest with themselves
the experience of one child is dangerous. We because this situation tends to make a physician
have heard therapists tell parents on many occa- feel like a failure. There may be a combined sense
sions that their child should never have a certain of relief that the family left and a sense of failure
operation because the therapist once saw a child and anger that the family does not trust their
who did poorly with that surgery. This type physician. These are normal feelings that the phy-
of advice is inappropriate because one child’s sician should acknowledge and not place blame
experience may have been a rare complication of on themselves or the family.
the operation. Also, there are many different ways
of doing surgery. This would be like telling some-
one to never get in a car again after seeing a When the Family Chooses Medical
car accident. A more appropriate response to the Treatment Against the Physician’s
family would be giving them questions to ask the Advice
doctor specifically about the circumstance with
which the therapist is concerned and has Families may seek a second opinion for a spe-
experience. cific treatment recommendation. This desire to
Another physical therapist therapeutic rela- get a second opinion should not be seen by the
tionship pattern is the purely clinical relation- primary treating physician as a lack of faith or
ship in which the therapist thinks the family is confidence. The family may require a second
incompetent, unreliable, or irresponsible and opinion for insurance purposes or, for many
only wants to deal with the child. Almost families, they just want to make sure they are
getting the correct treatment. Usually, getting a clear documentation of the recommendations,
second opinion should be viewed as a very pru- the physician must let the family proceed as they
dent move on the family’s part and should be choose; however, we always tell them that we
encouraged. Families should be given all the would be happy to see them back at any time.
records and support that are needed for them to When they undergo treatment against their pri-
get a meaningful second opinion. If this second mary physician’s advice and return, usually after
opinion is similar to that given by the primary several years, the physician should not make the
physician, the family is often greatly comforted previous situation a conflict. The family usually
in moving ahead. However, there is still vari- feels guilty and may not want to discuss past
ability in medical treatment for children with CP, events. Occasionally, they will come back and
so depending on the family’s choice of opinions, blame the physician for the problems because
the recommendations may be slightly to diamet- they have transferred the blame for the recommen-
rically opposed. dation. Nothing will be gained by bringing up
In a circumstance where the recommendation these past problems with the family, and the
of another physician differs significantly, the pri- focus should be to move on with the problems at
mary physician must be clear with the family hand as they present themselves.
and place the second opinion in the perspective
of their recommendation. Sometimes the words
used may sound very different, but the recommen- Recommending Surgery
dations are very similar. In other circumstances,
the recommendation may be diametrically For children who have had regular appropriate
opposed, and the primary physician must recog- medical care, the need for specific orthopedic pro-
nize this and explain to the family the reasons cedures is usually anticipated over 1–2 years and
for their recommendation. When recommenda- as a consequence is not a surprising recommen-
tions are diametrically opposed, clear documenta- dation. We prefer to have these discussions in the
tion, including the discussions concerning the presence of the child. For young children, there is
other opinion, is especially important. This situa- no sense that something is being hidden from
tion has a high risk for disappointment. Often, them. Children in middle childhood and young
families have great difficulty in choosing between adulthood can take in as much as possible, allo-
divergent opinions, even when one opinion is wing us, as their physicians, to directly address
based on published scientific data and the other their concerns as well. For younger children, those
opinion is completely lacking in any scientific under age 8 years, their main concern is that they
basis. Therefore, a family may base their decision will be left alone. We reassure them that we make
on other family contacts, a therapist’s recommen- a major effort to allow the parents to stay with
dations, or the personality of the physician. them during preinduction in the surgical suite and
Physicians must understand that it is the again in the recovery room. We also reassure
family’s responsibility and power to make these children that their parents will be with them
choices; therefore, with rare exception, no matter throughout the whole hospitalization. As children
how medically wrong the physician believes these get older, especially at adolescence, there is often
decisions are, the family must be given the right to an adult type of concern about not waking up from
choose. Only in rare, directly life-threatening cir- anesthesia or having other severe complications
cumstances will a child protective service agency leading to death. These individuals may have
even consider getting involved, and then this great anxiety but have few of the adult coping
involvement is usually very temporary. With a skills that allow the rationality to say that this
long and chronic condition such as CP, temporary surgery is done every day and people do wake
intervention by a child protective agency gener- up. Some of these adolescents need a great deal of
ally is of no use in interacting with families. With reassurance, most of which should be directed at
14 F. Miller
trying to get them to use adult rational coping have a large CP practice tend more toward the
skills. If adolescents are having problems with overly optimistic approach in which the outcomes
sleeping or anxiety attacks as the surgery date clearly will be worth the risk of the complications.
approaches, treating them with an antianxiety or The risk of an overly optimistic approach to fam-
sedative agent is very helpful. ilies occurs when there are complications. These
Some adolescents and young adults with cog- families may be surprised and angry and find it
nitive limitations develop substantial agitation difficult to deal with the unexpected. It is difficult
over surgery. Parents of such children are usually for physicians to have the perfect balance, but
very aware of this tendency and may wish to not each physician should be aware of their own ten-
tell them about having surgery until the day before dency. Usually, an honest assessment and feed-
or the day of surgery. Although this is a reasonable back from partners will identify which personality
practice for individuals with severe mental dis- trait, either optimistic or pessimistic, a physician
ability who are not able to cognitively process tends to use when approaching families. By
the planned surgery, approaching children who recognizing this tendency, surgeons can be more
are cognitively able to process the event in this sensitive to what families are hearing and make
way is only going to make them distrustful of their suggestions to moderate this perception.
parents and doctors. There are families who for some reason
In preparing children and families for sur- or another have not been obtaining appropriate
gery, it is important to discuss the expected out- medical care for their children. Then, when
come of the surgery with them. Part of this these children are adolescents, they may come to
discussion must focus on what will not happen, see a CP surgeon with a painful hip dislocation,
specifically that their child will still have CP severe scoliosis, or other deformities that are in a
after the surgery. If the goal is to prevent or severely neglected state. Some of these families
treat hip dislocation, showing radiographs to are surprised to hear that only a surgical procedure
the families helps them understand the plan. will be the appropriate treatment. Some families
They also need to be told what to expect of the may be very resistant to surgery and will want to
procedure from a functional perspective, such as try everything else. These families must under-
“Will the child still be able to stand? Will the stand that only surgery will correct the problem,
child be able to roll? Will the child’s sitting be but the surgery seldom has to occur on an emer-
affected? Will the child’s walking ability be gency basis. If a surgeon perceives a family’s
affected?” For children in whom the surgery is hesitancy and attempts to mollify them by
expected to improve walking, showing families suggesting that a brace, injections, or some other
videotapes of similar children before and after modality be tried even though it will provide no
surgery helps them get a perception of what level long-term benefit, the family will likely hear
of improvement is anticipated. uncertainty in the physician’s approach.
Families may miss the message completely
that only surgery will address the problem
A Plan for Managing Complications when they are appeased by nonsurgical treatment.
Giving children temporizing measures to provide
Discussion of possible complications is also relief of pain is appropriate; however, doctors
important; however, the expected outcome should must be clear to families that these measures are
be honestly approached. Some surgeons tend to only providing temporary pain relief and are not
have very pessimistic expectations with regard to treatments. By giving families a little time with
expected outcome and complications. Surgeons the use of these temporary measures, physicians
with this approach soon overwhelm themselves can develop a relationship with the families. There
and their families with their assessment of the are situations where medical and psychiatric treat-
poor balance between the expected outcome and ment may be required before the surgical treat-
the possible complications. Most surgeons who ment can occur. For all these reasons, it is
important to be clear about the required treatment, should be viewed as learning experiences and
its expected outcomes, and then to outline the full opportunities to teach oneself as well as others.
treatment plan. As this treatment plan is under- A significant number of the case histories in
taken, the relationship a physician has developed this book are careful analyses of complications
with children and families will allow them to be that have occurred in our practice. It is important
confident that the recommended treatment can that the approach to analyzing a complication is to
occur in a safe and effective way. determine the exact cause of the complication
when possible so that it may be avoided in the
future. Saying that “I will never do that operation
When Complications Occur again” is an inappropriate response to complica-
tions. This response comes very close to that of
When treatment of a child does not go well, the people who say they will never get in a car again
physician must first recognize this as a complica- after they have had a car accident. Our goal is to
tion. The judgment of recognizing a complication always have a complication-free treatment and
is one of the most difficult to develop, and some recovery for every patient; however, we learn the
physicians may never do it well. Many complica- most from careful analysis of our complications
tions, especially in orthopedics, do not present and poor outcomes.
with the drama of a cardiac arrest. In orthopedics, Once physicians acknowledge the complica-
a more typical example is the presentation of a tions to themselves, the families then need to be
deep wound infection. Every wound with a little told. Families may react with quiet acceptance,
erythema and a mild superficial drainage is not a frustration, or anger. These feelings are often the
deep wound infection. However, when a deep same feelings that physicians have about the same
wound infection is present, it should be acknowl- complication. If physicians are willing to share
edged as such. These families should be told some of their frustration and concern about the
of the complication, and a definitive treatment complications, it often helps families to put the
plan should be described. For this process to problem in perspective. It is very important to
work, physicians first have to acknowledge explain to families what to expect from a compli-
the complication to themselves. We have seen cation. This explanation should include a detailed
many physicians who cannot bring themselves to outline of the expected treatment plan. If a com-
acknowledge the magnitude of the complication. plication arises that physicians are not comfort-
Likewise, we have seen physicians who overreact able treating, getting a second opinion from, or
to relatively minor problems that will resolve if seeking the help of, another physician is very
left alone. important. This step should be explained carefully
Finding a balance requires physicians to be to families. Frequent contact with families is very
honest with themselves and be aware of their important, especially if they develop considerable
own tendency toward optimistic or pessimistic anger and anxiety, because if they feel that the
ends of the spectrum. The optimist tends to doctor is trying to avoid them, these feelings often
see the complication as minor variance of normal, increase.
whereas the pessimist tends to be overly concer- Complications should be managed very much
ned that any wound change may be a deep wound like the initial decision to have an operation. First,
infection. By being aware of one’s own tendency, specific problems should be carefully defined to
as experience is gained, an approach to diagnos- families. Next, the range of options and expected
ing and acknowledging complications and then outcomes, with respect to the short- and long-term
making specific treatment plans will be devel- implications, should be placed forward as specif-
oped. Complications tend to make physicians ically as possible. As much as possible, families
feel like failures, and a good retrospective evalu- should be told the detailed expected timeline and
ation of the treatment course may demonstrate exact treatments. For instance, if repeat or addi-
errors of judgment or execution. These errors tional surgery is expected in the future as a
16 F. Miller
consequence of a complication, this should be laid first, and then the options should be outlined for
out for families. If antibiotics are to be used, families with a unified recommendation wherever
families should be told for how long and what possible. Giving families different treatment rec-
factors will be monitored to determine a good ommendations and expected treatment outcomes
outcome. This kind of detail gives families a from several different consultants should be
sense that there is someone in charge with expe- avoided.
rience in dealing with these complications and
helps them deal with the fear of the unknown,
which the complications often bring to the The Final Goal
foreground.
Complications need to be recorded in detail in The goal in treating children with CP is for them
the medical record and should reflect all the objec- to grow and develop within the context of a nor-
tive observations and alternatives that were con- mal family. Their medical treatment and medical
sidered. This record is not the place where blame condition should be an experience just as a normal
should be directed. What is observed to have part of who they are. For example, a 6-year-old
occurred should be documented objectively with- child who fractures her femur will have a 6-month
out rewriting history. For example, if the toes are treatment course until most of the rehabilitation is
found to be insensate and without blood flow in completed. This occurrence will remain a definite
a child who has had a cast on a foot following event in the child and family’s growth and devel-
surgery, this should be reflected in the medical opment; however, when she is graduating from
record, followed by a recording of the immediate high school and going off to college, this medical
action taken, such as removing or opening the event probably will have faded into many other
cast, and the outcome of that action, such as growing-up experiences. This is the pattern that
the improved and returned blood flow to the we want to try to mimic in children with CP.
toes. There is no reason to speculate that the cast In the past, children might have spent 30–50%
was applied too tightly, or that the nursing staff of their growing-up years in hospitals having and
failed to elevate the cast, and so forth. This kind of recovering from surgeries trying to make them
analysis is important but should be done after the walk better or to make them straighter, which
patient is treated appropriately, and there has been was very detrimental. Mercer Rang termed this
time to reflect on the whole situation. Often, these the “birthday syndrome,” in which children were
initial assessments are incomplete and wrong and in the hospital for most of their birthdays and
most frequently are written to protect the writer. nurses were baking their birthday cakes and hav-
Later, during a more thorough investigation or ing birthday parties for them rather than their
legal action, these assessments only make it families at home (Rang 1990). Many of these
appear as if the writer was trying to cover up or children came to see the hospital staff as a second
shift blame to someone else. family (Fig. 2). This seldom happens currently
During stressful treatment periods, especially because of greatly shortened hospital stays and
when dealing with difficult complications, it is improved diagnostic studies. For most children
very important to ask partners and other col- with CP, all orthopedic management should ide-
leagues to evaluate the patients and give unbiased ally be done with only two major surgical events
opinions. A treating physician can develop a during their growth and development. This ideal
biased view, especially in the face of complica- is not possible to achieve in all children but should
tions where one would not like to acknowledge continue to be the goal. Striving for decreasing the
personal culpability. Involving other colleagues number of orthopedic operative events in chil-
also gives families the sense that their physician dren’s lives and moderating the amount of other
really is trying to keep all options open. If these medical treatments to only those that will have
consultants do have different opinions, these opin- definite and lasting benefit should be continued.
ions should be discussed between the physicians For example, an ambulatory child with normal
Fig. 2 The typical approach to the surgical treatment of staff would become “pseudoparents,” more often celebrat-
children with CP was to perform a surgery almost every ing birthdays with the children than the children’s own
year. This concept often led to children spending a great families
deal of time in the hospital, to the point where the nursing
cognitive function should not be having physical childhood growing experiences, such as going to
or occupational therapy at any time that interferes the beach, going to Disney World, or other parties
with their education. Therapeutic goals should be and events.
planned during summer months or in ways that do In young adulthood, the success of the whole
not interfere with education. individual with CP is determined much more by
Twenty years ago, the use of inhibition casting the family and the individual’s educational expe-
was popular. It was believed that this technique rience than by the activities of the medical treat-
decreased contractures and managed spasticity. ment. The medical care system can help children
These children were in leg casts for 8 weeks, and families cope with the disability and allow
often requiring trips to the clinic to change the individuals with CP to function at their maxi-
cast every 2 weeks. After 2 or 3 months, the whole mum ability. However, the medical care system
process would have to be repeated. If families also must recognize that too much focus on
could tolerate the stress, although few did, these perfection of function may cause damage to the
children would be in a cast for 30–50% of their growth and development of the children and
growing years. The time and behavioral stress family unit, especially in the social, psycho-
placed on these families meant that a large part logic, and educational domains. Achieving this
of their lives revolved around their children’s balance varies with each child and family. For
medical treatments. When these children gradu- example, many successful young adults without
ated from high school, they tended to see all these disabilities do not have the ideal maximization
casting events as a major focus of their growing- of their physical function because the focus of
up experience instead of the more normal their interests is sedentary activities. Just as with
18 F. Miller
these nondisabled young adults, there is great

variation in how important maximizing physical was hospitalized. During this hospitaliza-
function and appearance is to each individual tion, she had a rather severe overdose of
with CP. When young adults are truly able to antiseizure medication along with other
make informed and well-articulated decisions, subsequent complications and lost the abil-
then they have arrived at a level of success in ity to crawl, roll, and talk. Her parents
young adulthood. Just as with nondisabled ado- started patterning therapy when she did not
lescents and young adults, the medical care pro- rapidly regain these functions. She also
viders should stress the importance of good started to develop increased spasticity and
physical conditioning; however, trying to had more trouble with her trunk control.
enforce a specific level of physical activity By age 6 years, Susan had an adductor
against the person’s wishes tends not to be very lengthening and was developing scoliosis.
productive. Individuals with disabilities should She was started in a body jacket to help
be allowed to make these decisions in the same control her scoliosis, and by age 8 years,
way that individuals without disabilities are she had a painful dislocated hip. After the
allowed to decide, even if their physician thinks family searched for several different opin-
it is not in their best interest. Therefore, the final ions, they elected to go ahead and have
goal is to encourage the development of individ- the hip reconstructed. Because Susan had
ual adults who are as competent as possible to substantial complications with loss of neu-
make their own decisions, who develop the con- rologic function on several previous admis-
fidence to make those decisions, and are then sions, her parents were perceived as being
willing to make decisions and live with the con- extremely anxious during the hospitaliza-
sequences. Always in the context of this final tion. The operative procedure and the
goal, we as orthopedic physicians want the indi- recovery phase of the hip reconstruction
vidual’s physical impairments minimized as went very well, and the family was very
much as technically possible. gracious.
By age 9 years, she needed to have addi-
tional soft-tissue lengthenings of her right
Cases shoulder for a painful dislocation as well as
for progressive varus deformity of the feet.
The family was less anxious during this
procedure than they had been with the
Case 1 Susan
prior procedure because they were more
Susan was born after a normal pregnancy
comfortable with the staff.
and delivery at term and was discharged
By age 12, the scoliosis had progressed
home from the hospital as a normal new-
substantially, requiring a posterior spinal
born. At 3 weeks of age, her grandmother
fusion. The family was very anxious about
thought that her head looked abnormal, and
this very large procedure. Their anxiety
Susan was taken to a pediatrician where a
was perceived by some staff as being over
workup revealed hydrocephalus. A shunt
reactive; however, considering the history
was placed at 4 weeks of age, followed by
of their experience with past medical treat-
some complications. After this time, she
ment, we felt it was appropriate. At the time
was noted by her parents and grandmother
of the posterior spinal fusion, the shunt tub-
to be less strong and less interactive. How-
ing was noted to be broken; however, she
ever, she did well, and by age 3 years was
was no longer dependent on her shunt so
crawling, rolling, and talking. At age
shunt repair was not performed.
3 years, she developed severe seizures and
(continued)
By age 13 years, she developed physicians and nurses, were not aware of
more lethargy and a shunt revision was this history and therefore did not understand
recommended. During this shunt revision, the parents’ anxieties. This anxiety tends to
she had severe complications including an make nursing staff and medical staff try
infection that required the shunt to be exter- to avoid the parents, which just greatly
nalized. The external drainage was not increases their anxiety level. These parents
controlled carefully enough, and, as a con- had more than one hospitalization per year
sequence, the ventricles collapsed, causing on average with their daughter and were
intracranial bleeding. This episode caused very aware of what her proper medical man-
substantial neurologic functional loss, so agement should be. They were very astute
she was now less able to interact socially in picking up inexperience in both the nurs-
with her parents on top of her very severe ing and medical staff and would become
spastic quadriplegic pattern motor disabil- much more anxious when they sensed this
ity. In addition, her seizures increased sub- inexperience or discomfort in dealing with
stantially. This episode made her parents their daughter.
extremely anxious about medical treatment,
especially about the fear of developing
complications and having functional loss. References
Shortly after the shunt problems, she was
noted on routine medical examination to Ansari NJ, Dhongade RK, Lad PS, Borade A, Yg S,
have a retinal detachment requiring surgery. Yadav V, Mehetre A, Kulkarni R (2016) Study of
parental perceptions on health & social needs of
This surgery occurred without any compli- children with neuro-developmental disability and it’s
cations. She continued to have problems impact on the family. J Clin Diagn Res 10(12):
with her seizures, and her parents were anx- SC16–SC20
ious to have control of the seizures while at Bartlett D, Chiarello LA, Hjorngaard T, Sieck Taylor B
(2017) Moving from parent “consultant” to parent “col-
the same time to allow her to regain some of laborator”: one pediatric research team’s experience.
her alertness and contact with her parents, Disabil Rehabil 39(21):2228–2235
which they much enjoyed. Bemister TB, Brooks BL, Dyck RH, Kirton A (2014)
This family was often perceived by Parent and family impact of raising a child with
perinatal stroke. BMC Pediatr 14:182
nurses and house staff as being exceedingly Brochard C, Peyronnet B, Dariel A, Menard H,
difficult to deal with because they were so Manunta A, Ropert A, Neunlist M, Bouguen G,
anxious and always wanted to observe and Siproudhis L (2017) Bowel dysfunction related to
understand specific treatments and know spina bifida: keep it simple. Dis Colon Rectum
60(11):1209–1214
exactly which medications were being Rang M (1990) Cerebral palsy. In: Morrissy R (ed) Lovell
administered. This family was extremely and Winter’s pediatric orthopedics, vol 1. Lippincott,
dedicated to the care of their daughter, and Philadelphia, pp 465–506
the anxieties that they expressed were very Rosenbaum P, Paneth N, Leviton A, Goldstein M,
Bax M, Damiano D, Dan B, Jacobsson B (2007) A
understandable considering their history. report: the definition and classification of cerebral
Often, medical care providers, especially palsy April 2006. Dev Med Child Neurol Suppl
109:8–14
Part II
Etiology of Cerebral Palsy
Cerebral Palsy and the Relationship
to Prematurity 2
Michael Favara, Jay Greenspan, and Zubair H. Aghai
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
Prevalence of Cerebral Palsy in Premature Infant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
Etiologies of Cerebral Palsy Related to Prematurity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
Perinatal and Postnatal Interventions to Reduce the Risk of Cerebral Palsy in
Preterm Infants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
Abstract among extremely low birth weight survivors,

Cerebral palsy (CP) is the most common cause affecting 9–17% of survivors.
of childhood-onset, lifelong physical disability Antenatal and perinatal factors that in-
in most countries around the world. Prematu- fluence the risk of CP include gestational
rity is the leading identifiable risk factor of age at delivery, birth weight, presence of
cerebral palsy and is defined as birth occurring multiple gestation, and chorioamnionitis.
prior to 37 weeks’ gestation. Premature infants Following delivery, there are a number of
are at a much higher risk for developing CP risk factors that contribute to a premature
than full-term infants, and the risk increases as infant’s development of CP. These include
gestational age and birthweight decreases. intraventricular hemorrhage, periventricular
Despite technological advances in neonatal leukomalacia, bronchopulmonary dysplasia,
care over the past several decades, cerebral presence of a patent ductus arteriosus, necro-
palsy remains a major neurologic sequela tizing enterocolitis, hyperbilirubinemia, hypo-
carbia, neonatal sepsis, hypoxia, and apnea.
Interventions to reduce the risk of CP in-
clude antenatal glucocorticoid administration,
M. Favara (*) · J. Greenspan · Z. H. Aghai magnesium sulfate for neuroprotection, and
Nemours/Thomas Jefferson University, Philadelphia, delayed cord clamping at delivery.
PA, USA
e-mail: Michael.Favara@nemours.org;
Jay.Greenspan@nemours.org; zaghai@nemours.org

https://doi.org/10.1007/978-3-319-74558-9_1
24 M. Favara et al.
Keywords Natural History

Cerebral palsy · Preterm infants · Etiology ·
Periventricular leukomalacia · Intraventricular Prevalence of Cerebral Palsy
hemorrhage in Premature Infant
Prematurity is a major contributor to perinatal mor-

Introduction bidity in the United States and around the world. A
normal human pregnancy is estimated to be
Cerebral palsy (CP) is the most common cause 38–42 weeks from the first day of the mother’s
of childhood-onset, lifelong physical disability last menstrual period, with 40 weeks being the
in most countries around the world. It is defined average gestation. Premature birth is defined as
as a disorder of motor behavior attributable to birth occurring prior to 37 completed weeks from
disturbances in the developing fetal or infant the first day of the last menstrual period. Late
brain. It has a reported prevalence of 1.5–4 per preterm births, occurring between 34 and
1000 live births. Prematurity is the leading iden- 36 weeks of gestation, are the fastest growing sub-
tifiable risk factor for development of cerebral set of neonates, accounting for approximately 74%
palsy. Premature delivery is a result of either of all preterm births and about 8% of total births.
premature labor, premature rupture of amniotic The most common risk factor for premature birth
membranes, or maternal or fetal conditions that is a prior history of premature birth, with an esti-
necessitate delivery. The incidence of premature mated 20–40% recurrence rate. Multiple gestation
birth in the United States is approximately 10% pregnancies are also associated with an increased
of all births, and this number increases around risk of premature birth, with an estimated 30–50%
the developing world. Infants born at extreme of multiple gestations delivering prior to 37 weeks,
preterm gestation are at risk for both death and with the higher order of multiple gestations deliv-
disability. Premature birth exposes the fetus to ering earliest. There are significant ethnic and
extrauterine life before it is ready, and this expo- socioeconomic differences in the United States
sure may be particularly harmful to the develop- that contribute to premature delivery, with
ing brain. While the survival rates have African-Americans having twice the incidence of
improved for this population over the past few preterm births than Caucasians. Over the past sev-
decades, a significant improvement in overall eral decades, advances in neonatal and perinatal
neurodevelopmental outcome has not yet been medicine have shifted the limits of viability for
realized. Although preterm infants have a higher prematurity from 28 weeks down to 22 weeks
incidence of all neurodevelopmental disabilities of gestation.
than full-term infants, most preterm infants are As a result of progressive changes in both
free of major disability. CP remains a major perinatal and neonatal management over the last
neurologic sequela among extremely low birth six decades, there has been an increase in survival
weight (birth weight < 1000 grams) survivors, in the smallest and most fragile infants, leading
affecting 9–17% of survivors (Vohr et al. 2000). to a change in the rates of neonatal morbidity,
Overall, approximately one fifth to one quarter brain injury, chronic lung disease, and sepsis.
of extremely premature infants who survive Survival rates for infants born premature, both
have at least one major disability – impaired with and without significant disability, increases
mental development, CP, blindness, or deafness. with each week of completed gestation. Sur-
Impaired mental development is the most prev- vival for infants born at 22 weeks of gestation
alent disability with 17–21% of survivors remains very low, with reported survival without
affected, followed by cerebral palsy, with long-term disability between 0% and 21% in
12–15% of survivors being affected (Lorenz the few studies performed. This survival rate
2001). improves with each increasing week of completed
2 Cerebral Palsy and the Relationship to Prematurity 25
gestation, with an estimated survival of 5–46% in risk factor for the development of cerebral palsy.
infants born between 23 and 24 weeks’ gestation Infants who are characterized as being “very
and 40–59% in infants born between 25 and low birth weight” or VLBW are born less than
26 weeks of gestation. 1500 g. The term “extremely low birth weight” or
Premature infants are at a much higher risk ELBW refers to infants that are less than 1000 g at
for developing CP than full-term infants, and birth. Infants with extremely low birth weight are
the risk increases as gestational age and birth more susceptible to all complications of prema-
weight decreases. The incidence of premature ture birth both in the immediate neonatal period
birth is only 10%, but 40% of children with cere- and after discharge from the nursery.
bral palsy are born prematurely. In a large cohort In 2010, infant mortality rates were 24 times
of children with CP, 25% of children were born higher for infants with low birth weight and
before 32 weeks’ gestation, 10–20% were born 100 times higher for those with very low birth
between 32 and 36 weeks’ gestation, and 60% weight. First year survival was 15.5% for infants
were born after 36 weeks’ gestation (Hirvonen with birth weight less than 500 g. A study in
et al. 2014). In data obtained from Europe and United States found that the prevalence of CP
Australia, the prevalence of CP was between 35.0 was 6.2 per 1000 live births among children
and 79.5 per 1000 live births for children born weighing 1500–2499 g and 59.5 per 1000 live
at 28–31 weeks gestation and 6.1 per 1000 births among children born weighing less than
live births among children born at 32–36 weeks 1500 g, compared with 1.1 per 1000 for children
gestation. This is drastically different than infants born weighing 2500 g or more (Winter et al. 2002).
born at 37 weeks of gestation or greater, where the
risk of CP is 1.1 per 1000 live births. The preva-
lence of CP is much higher in preterm infants born Etiologies of Cerebral Palsy Related
at <28 weeks gestation (Table 1) (Oskoui et al. to Prematurity
2013). Refer to ▶ Chap. 11, “Epidemiology of
Cerebral Palsy” for further information. Prematurity affects every organ system in the
Low birth weight is often a consequence of infant. The premature infant brain is particularly
prematurity because of limited development of vulnerable to prenatal, perinatal, and postnatal
the fetus before its transition to extrauterine life. insults. Premature birth exposes the fetus to extra-
However, there are other causes of intrauterine uterine life before it is ready, and this exposure
growth restriction that are unrelated to prematu- may be particularly harmful to the developing
rity, such as maternal infection or nutritional sta- brain. The premature infant brain has extremely
tus, exposure to substances such as tobacco or fragile blood vessels that frequently bleed. The
cocaine, or congenital anomalies in the infant. white matter of premature infant’s brain is also
The average infant born at term weighs between susceptible to injury due to infection, inflamma-
2500 and 4000 g. Low birth weight, or when an tion, and oxidative stress. Risk factors that may
infant weighs less than 2500 g at birth, is another also contribute toward the development of CP
include multiple gestation pregnancies, infants
Table 1 Extreme premature birth and risk for cerebral born via assisted reproductive technologies, infec-
palsy in survivors tions during pregnancy, medical conditions of the
Gestational age Prevalence of cerebral palsy/1000 mother, and birth complications. All of these risk
(weeks) survivors factors can increase the risk of developing CP in
27 102 the setting of prematurity. A study in Denmark
26 150 found that children born after in vitro fertilization
25 162 were 1.6 times as likely to have CP. This has been
24 207 postulated as being due to the fact that infants who
23 261 are born through assisted reproductive
26 M. Favara et al.
technologies are more likely to be born prema- outcomes. Grade I hemorrhage refers to a bleed
turely or from a multiple pregnancy (Hvidtjorn within the subependymal germinal matrix, a highly
et al. 2006). Following are additional major risk vascular structure that is most prominent between
factors that contribute to the pathogenesis of cere- 24 and 34 weeks of gestation and is almost
bral palsy in premature infants, which are further completely regressed by term (Papile et al. 1978).
described in ▶ Chaps. 4, “Infectious Etiologies Grade II refers to an intraventricular hemorrhage
of Cerebral Palsy,” ▶ 5, “Perinatal Stroke as an occupying 10–50% of the ventricle, but without
Etiology of Cerebral Palsy,” ▶ 6, “Problems Dur- ventricular dilation. Grade III refers to a bleed
ing Delivery as an Etiology of Cerebral Palsy in occupying greater than 50% of the ventricle with
Full-Term Infants,” and ▶ 10, “Risk Factors for associated dilation. Grade IV, which is also known
Developing Cerebral Palsy.” as an intraparenchymal hemorrhage, is the most
severe form, occurring in 3–15% of all hemor-
Intraventricular Hemorrhage (IVH) rhages and refers to bleeding into the white matter.
Intraventricular hemorrhage (IVH) is a leading Most cases of IVH occur within the first 72 h
cause of brain injury in preterm infants. The of life, but can be detected up to 10 days of age.
premature infant brain has extremely fragile The causes of IVH are not entirely known, but
blood vessels that frequently rupture as a result clinical temporal associations have been demon-
of hemodynamic changes or stress in the infant. strated between fluctuations in systemic blood
The germinal matrix, located between the cau- pressure and simultaneous fluctuations in cerebral
date nucleus and thalamus, is the site of origin blood flow. Preterm infants are particularly sus-
for bleeding in premature infants. The germinal ceptible to alteration in cerebral blood flow as
matrix is a highly cellular and vascularized tis- they have impaired cerebral autoregulation com-
sue that is the site of origin for neuron and glial pared to term infants. Hypercarbia, a potent cere-
cells during fetal development. Bleeding into bral vasodilator especially when combined with
this site may interfere with cortical migration severe acidosis, has been associated with the
of neuron and glial cells and cause an increased development of IVH. Additional risk factors that
risk for neurodevelopmental impairment and contribute to IVH in premature infants include
CP. The risk of IVH is inversely proportionate chorioamnionitis, respiratory distress, lack of
to gestational age and birth weight. IVH is com- antenatal steroid exposure, and prolonged neona-
mon in infants born at <32 weeks of gestation tal resuscitation. Infants with the more severe IVH
and risk decreases with increasing gestational frequently exhibit clinical signs such as a bulging
age. A large population-based prospective fontanelle, seizures, a sudden drop in hemoglobin,
observational study of infants born between hyperglycemia, metabolic acidosis, and pulmo-
23 and 32 weeks of gestation reported that the nary hemorrhage. Reported prognostic signifi-
IVH rates decreased 3.5% with each added week cance of the grades of IVH varies greatly, and
of gestation (Bajwa et al. 2011). The incidence the general consensus is that premature infants
of IVH is about 20% in VLBW infants (<1500 g) with no IVH have a better survival prognosis
and 45% in ELBW infants (<1000 g). than those with IVH. The less severe hemorrhages
Over the past few decades, the detection of IVH have a lower risk for the development of cerebral
has been improved by the usage of cranial ultraso- palsy, with studies reporting a risk of 9% in grade I
nography. Routine screening occurs in the inten- and 11% in grade II (Perlman and Volpe 1986). In
sive care unit within the first 10 days of life. Using a large national study, between 28% and 60% of
this technique, sonographers can visualize the ger- infants with grades III and IV IVH developed
minal matrix and intraventricular space via the cerebral palsy at 2 years, compared with 7% of
infant’s open fontanelle. There are four grades of children without IVH (Larroque et al. 2003).
intraventricular hemorrhage, first described by A variety of interventions have been utilized
Papile et al., each increasing in severity as well in the prevention of IVH. A short course of
as the risk for adverse neurodevelopmental antenatal glucocorticoids, as well as the
administration of magnesium sulfate, have been evidence of PVL is seen in as many as 25–75%
shown to result in a significant reduction in the of VLBW infants who died.
development of IVH. Preeclampsia appears to The two common mechanisms for the devel-
have a reduced risk of IVH, possibly as a result opment of PVL are ischemia and infection. Pre-
of enhanced in utero maturation of the fetus. A mature infants are more susceptible to ischemia
large national study in the United States utilized due to vascular, circulatory, and cellular factors.
indomethacin for prophylaxis for IVH; while There is incomplete development of the blood
there was a decreased incidence of IVH, there vessels that penetrate the subcortical white matter
was not a decreased incidence of death or severe in the periventricular area, and these vessels are
disability (Schmidt et al. 2001). With the vulnerable to reduced blood flow. Premature
improvement in general neonatal care, a reduc- infants have impaired cerebral autoregulation
tion in the incidence of IVH has been reported in that can result in reduced cerebral flow when
many large intensive care units without the use systemic hypotension occurs. Hypoxia and hypo-
of any drugs. Delayed cord clamping for carbia, both frequently seen in premature infants,
30–60 s is also associated with a lower risk of can cause vasoconstriction and cerebral ischemia.
IVH (Rabe et al. 2012). Cerebral white matter is also susceptible to dam-
age mediated by various inflammatory cytokines
Periventricular Leukomalacia (PVL) produced as a result of maternal or fetal infections.
The human preterm brain is particularly sus- PVL occurs more frequently in premature infants
ceptible to cerebral white matter injury that dis- born to mothers with chorioamnionitis, prolonged
rupts the normal progression of developmental rupture of membranes, and bacterial vaginosis.
myelination. White matter injury remains a Perinatal events associated with PVL include a
global health problem and the most common history of chorioamnionitis, prolonged rupture of
cause of chronic neurological morbidity from membranes, severe fetal acidemia, sepsis, symp-
cerebral palsy and diverse neurobehavioral dis- tomatic PDA, and postnatal infection, among
abilities. Periventricular leukomalacia (PVL) is others. This white matter injury may also be a
a form of cerebral injury that involves the direct consequence of IVH. The pathogenesis of
periventricular white matter. PVL has long white matter injury following an IVH remains
been regarded as the principal ischemic lesion unclear. This injury may occur either as an appar-
of the premature infant, and is the strongest ent consequence of intraventricular hemorrhage
predictor for the development of cerebral palsy. or as an associated finding.
PVL can be described as being cystic or non- The strongest predictor of CP in the premature
cystic in nature, and can be detected using both infant is the development of PVL. In a large study,
ultrasound and MRI. Preterm infants born less cerebral palsy rates were 75% among children
than 32 weeks of gestation have the greatest risk with bilateral cystic PVL, 35% among children
for development of PVL, and the risk increases with unilateral cystic PVL, and 17% among chil-
with decreasing gestational age and birth dren with persistent echodensities, compared with
weight. PVL is diagnosed in preterm infants by 5% in the absence of PVL (Ancel et al. 2006).
using the cranial ultrasound. In VLBW infants, Two thirds of children with PVL in the parietal or
the incidence of PVL ranges between 5% and occipital lobes were later diagnosed as having
15% when diagnosed on ultrasound (Stevenson cerebral palsy.
et al. 1998). While ultrasound is readily avail- Potential strategies to prevent PVL in preterm
able, magnetic resonance imaging is potentially infants includes preventing cerebral hypoper-
a better imaging study in the diagnosis of PVL as fusion and vasoconstriction by avoiding sys-
it detects both cystic as well as noncystic diffuse temic hypotension, hypoxia, and hypocarbia.
white matter injury. The incidence of PVL based Use of antenatal betamethasone is also associ-
upon MRI findings is higher than the data ated with significant reduction in the risk of
obtained from ultrasound. Neuropathological cystic PVL.
28 M. Favara et al.
Chorioamnionitis compared to those without chorioamnionitis (22%

A known risk factor for the development of CP in vs. 11%) (Soraisham et al. 2009). Cytokines can
the antenatal and perinatal period is the oc- also activate astrocytes and microglial cells in the
currence of chorioamnionitis (Huetz et al. 2016). premature brain. Activation of the fetal cerebral
Chorioamnionitis is a polymicrobial infection immune response results in exaggerated inflam-
of the fetal membranes, including the chorion, mation, free radical production, injury to
which is the outermost membrane, and the pre-oligodendrocytes, and may eventually lead
amnion, which is closest to the infant and is in to white matter injury. It is also thought that the
direct contact with amniotic fluid. Chorio- fetal inflammatory response and subsequent vas-
amnionitis is diagnosed clinically by maternal culitis associated with pathological brain lesions
fever, fetal tachycardia, uterine tenderness, may be involved in the pathogenesis of CP.
and foul-smelling amniotic fluid and histo- A recent meta-analysis of 17 studies report-
logically by examining the placenta. Histological ing CP in children exposed to chorioamnionitis
chorioamnionitis is more frequent in premature showed significantly increased incidence of cere-
births compared to full-term deliveries. Histo- bral palsy in preterm infants diagnosed with his-
logical evidence of chorioamnionitis has been tological chorioamnionitis (RR = 1.34, p < 0.01)
reported in 65% of placentae in deliveries at but not in those diagnosed with clinical chorio-
23–24 weeks gestation and 30% of placentae at amnionitis (Shi et al. 2017). Refer to ▶ Chap. 4,
29 weeks of gestation (Lahra and Jeffery 2004). “Infectious Etiologies of Cerebral Palsy” for fur-
Preterm premature rupture of membranes, or ther information on the role of infection.
PPROM, is defined as the rupture of the amniotic
membranes prior to 37 weeks of gestation, Postnatal Glucocorticoid Therapy
and accounts for up to 20% of premature deliver- Postnatal glucocorticoid therapy has been used
ies. The causes of PPROM are not clearly under- for the past several decades to treat chronic lung
stood, but may be a result of trauma, cervical disease of prematurity. These steroids often
incompetence, and infection. Some bacteria have the short-term effect of improving lung
release proteases which may cause membrane compliance and facilitating ventilator weans. In
weakening and probable early rupture. Chorioam- an animal model, dexamethasone was found to
nionitis occurs in 15–25% of PPROM cases. induce apoptosis in immature cells in the dev-
Funisitis, or an infection in the connective tissue eloping brain (Bhatt et al. 2013). In the 1990s,
of the umbilical cord, is a marker of the fetal between 17% and 28% of very low birth
inflammatory response and has been associated weight infants cared for in the Vermont-Oxford
with both the development of white matter lesions Network, a large network of neonatal inten-
and the occurrence of cerebral palsy. sive care units, received steroids to prevent or
Chorioamnionitis and subsequent systemic treat bronchopulmonary dysplasia (Halliday and
inflammatory response syndrome (SIRS) can Ehrenkranz 2000). However, multiple studies
lead to white matter brain injury by several have been performed highlighting the risk of
mechanisms. Both chorioamnionitis and funisitis development of CP. In a systematic review,
induce a fetal inflammatory cascade, notably IL-1, Barrington reported an increase in the risk of CP
IL-6, IL-8, IL-9, and TNF-alpha. A surge in cyto- and neurodevelopmental impairment associated
kine production can lead to impairment in cerebral with glucocorticoid therapy (Barrington 2001).
autoregulation and alteration in blood-brain bar- Following this, the use of postnatal corticosteroids
rier function. Chorioamnionitis is associated with sharply decreased. Doyle and colleagues later
increased risk for IVH. The severity of IVH is also investigated using lower doses of dexamethasone
increased in preterm infants born to mothers with in a taper fashion to facilitate ventilator weaning
chorioamnionitis. In a large multicenter prospec- in a large, international, controlled trial. Unfortu-
tive study, infants with chorioamnionitis were nately, the study needed to be terminated early due
more likely to have severe IVH (grades III and IV) to declining enrollment and was unable to have
sufficient power to detect long-term neurodeve- ventilation at 36 weeks post-menstrual age was
lopmental outcomes (Doyle et al. 2007). associated with a nearly sixfold increased risk
of quadriparesis and a fourfold increased risk
Bronchopulmonary Dysplasia of diparesis (Van Marter et al. 2011). In a sim-
Bronchopulmonary dysplasia, or BPD, is a ilar study, BPD was independently correlated
chronic lung disease in which infants require with adverse neurodevelopmental outcomes
long-term oxygen and respiratory support. The which included cerebral palsy (OR 2.5, 95% CI
prevalence of BPD in mechanically ventilated 1.9–3.4, p < 0.001) (Schmidt et al. 2003).
infants is, like many other comorbidities associ-
ated with prematurity, inversely related to gesta- Apnea of Prematurity
tional age and birth weight. This strongly Breathing in the neonate, particularly in the pre-
suggests that incomplete development of the mature neonate, is immature. Neonatal respira-
lungs plays a critical role in the pathogenesis of tory activity is characterized by irregularity with
BPD. Over the past several years, there has been spontaneous changes in the breathing pattern
a change in the definition of BPD, moving from with alternating eupnea, apnea, periodic breath-
an etiology of an injury to alveolar structures ing, and tachypnea, as well as a decreased res-
with heterogeneous damage to the lungs, to an ponse to carbon dioxide. Apnea of prematurity is
arrest of alveolar development with a homoge- a common problem affecting premature infants,
nous damage pattern. The incidence of BPD as a result of this immature respiratory control.
varies widely among intensive care nurseries, The incidence of apnea of prematurity is in-
owing to differences in patient susceptibility versely correlated with gestational age and birth
and in management, but also the way that BPD weight. Seven percent of neonates born at
is defined. Premature children who develop 34–36 weeks of gestation, 15% at 32–33 weeks,
severe chronic lung disease may be developmen- 54% at 30–31 weeks, and nearly all infants
tally compromised by exposure to hypoxic epi- born less than 29 weeks of gestation or less than
sodes. There is a range in severity in those infants 1000 g exhibit apnea of prematurity. Severe apnea
diagnosed with BPD, ranging from mild BPD, that lasts longer than 20 s may lead to distur-
in which infants born less than 32 weeks are bances of cerebral hemodynamics by causing
breathing room air at 36 weeks post-menstrual cerebral hypoperfusion, which may contribute
age, to severe BPD, where the same group of to hypoxic-ischemic injury of the immature
infants require greater than 30% oxygen or pos- brain. Multiple hypoxic and bradycardic episodes
itive pressure (either positive pressure ventila- due to apnea of prematurity may contribute to
tion or CPAP) at 36 weeks post-menstrual age. the development of PVL and CP.
There is a correlation between broncho-
pulmonary dysplasia and CP. This may be Neonatal Sepsis
partly because both BPD and CP share many The premature infant has an immature immune
of the same risk factors, including extremely system, and infection is a significant risk. Neona-
preterm birth, cerebral white matter damage, tal sepsis is a systemic infection occurring in
necrotizing enterocolitis, pneumothorax, and infants within the first month of life and is an
prolonged mechanical ventilation. The predictors important cause of morbidity and mortality in
of disability in infants with severe bronchopulmo- newborns, especially in preterm neonates. Early-
nary dysplasia include those who had peri- onset sepsis refers to an infection that occurs
ventricular hemorrhage, ventricular dilation, and within the first 7 days of life, and is typically
sepsis. However, several studies have shown that caused by bacterial pathogens transmitted verti-
BPD is an independent predictor of cerebral palsy cally from mother to infant before or during
and adverse neurodevelopmental outcomes. In delivery. Late-onset sepsis occurs after 7 days of
multivariable analyses that adjusted for potential life up to the age of 90–120 days, and is caused
confounders, BPD accompanied by mechanical by vertically or horizontally acquired pathogens.
30 M. Favara et al.
The incidence of culture-proven early-onset neo- PDA, occurs when the ductus arteriosus fails to
natal sepsis in the United States is estimated to close after birth, and is a common congenital
be 0.77–1 per 1000 live births. The incidence heart defect in premature infants. In term infants,
and mortality are higher in VLBW infants, af- the ductus arteriosus becomes functionally closed
fecting 26 per 1000 and 8 per 1000 live births in by 72 h of age. However, in preterm infants,
those with a birth weight less than 1000 and the closure is delayed, remaining open at 4 days
1500 g, respectively. Bacterial meningitis is of age in approximately 10% of infants born at
more common in the first month of life than at 30 through 37 weeks’ gestation, 80% of those
any other age. Incidence of neonatal bacterial born at 25 through 28 weeks’ gestation, and 90%
meningitis is estimated to be 0.25 per 1000 live of those born at 24 weeks’ gestation (Clyman).
births, and is similar to neonatal sepsis in that While the ductus remains open, blood typically
it can be characterized as being early-onset or flows left-to-right from the aorta into the pul-
late-onset. monary arteries; as pulmonary vascular resis-
Literature has shown that there is an as- tance decreases, the proportion of blood flow
sociation between neonatal sepsis, particularly that is diverted into the pulmonary circulation
early-onset sepsis, with the development of increases. This results in a diversion of blood
brain injury. This pattern of injury is similar to flow from the systemic circulation and may
that which is seen in brain injury following cause compromised perfusion to the bowel, kid-
chorioamnionitis, with activation of ney, and brain. Prolonged patency is associated
pro-inflammatory cytokines. Klinger and col- with prolonged assisted ventilation, pulmonary
leagues demonstrated that early-onset sepsis hemorrhage, necrotizing enterocolitis, impaired
can double the risk of multiple negative out- renal function, intraventricular hemorrhage, peri-
comes, including bronchopulmonary dysplasia, ventricular leukomalacia, and cerebral palsy
periventricular leukomalacia, intraventricular (Benitz WE). Literature has shown that a hemo-
hemorrhage, retinopathy of prematurity, and dynamically significant PDA has been correlated
death (Klinger et al. 2010). Mortality from neo- with lower regional cerebral oxygen saturation
natal meningitis has decreased dramatically and higher fractional oxygen extraction, sup-
over the past several decades, decreasing from porting the hypothesis that prolonged ductal
50% in the 1970s to 10–20% in recent years. patency may have a causal role in adverse out-
However, morbidity continues to be seen among comes including CP.
affected patients, with 24–29% having severe There are both medical and surgical inter-
neurologic sequelae, including developmental ventions available for the treatment of a PDA.
delay, seizures, hydrocephalus, cerebral palsy, The use of nonsteroidal antiinflammatory drugs
blindness, and hearing loss. In a multicenter (NSAIDs) such as indomethacin and ibuprofen
Swiss cohort study on infants born between are effective in reducing rates of persistent PDA,
24 weeks and 0 days and 27 weeks and 6 days, resulting in lower rates of ductal ligation. Surgical
multivariable analysis confirmed that proven ligation is a widely used technique and is reliable
sepsis independently increased the risk of CP and fast, but is associated with significant adverse
(OR: 3.23, 95% CI: 1.23–8.48) (Schlapbach effects. A large, multicentered trial investigated
et al. 2011). the role of prophylactic indomethacin in the pre-
vention of intraventricular hemorrhage and PDA,
Patent Ductus Arteriosus with results showing that 50% of infants born at
The ductus arteriosus is a normal part of fetal 500–999 g never developed signs of a hemody-
physiology and provides a connection between namically significant PDA (Schmidt et al. 2001).
the pulmonary artery and descending aorta, However, medical or surgical treatment of PDA
through which deoxygenated blood returning did not improve neurodevelopmental outcomes
to the right heart is diverted to the placenta including risk for CP. A few studies even reported
for reoxygenation. Patent ductus arteriosus, or a greater risk of adverse neurodevelopmental
outcome when PDA was medically or surgically number of infants studied was small (Logitharajah
treated (Janz-Robinson et al. 2015). et al. 2009).
Hypoxic-Ischemic Encephalopathy Necrotizing Enterocolitis

Hypoxic-ischemic encephalopathy (HIE) is a rec- Necrotizing enterocolitis (NEC) is the most com-
ognizable and defined clinical syndrome in mon gastrointestinal emergency occurring in neo-
term infants that results from a severe or pro- natal intensive care units, and primarily affects
longed hypoxic-ischemic episode before or dur- premature infants. There is an inverse correla-
ing birth, but is not well recognized in the tion between gestational age and development of
premature infant. The human brain undergoes NEC. The incidence of NEC varies between cen-
rapid changes between 24 and 40 weeks of gesta- ters in the United States, ranging between 3% and
tion that make the developing brain vulnerable 28%, with an average of approximately 6–10% in
to injury from hypoxia-ischemia, inflammation, infants born weighing less than 1500 g. Bell and
free radical, and excitotoxic damage. Late pre- colleagues created a classification scheme that
myelinating oligodendrocytes are the predomi- differentiates those infants with suspected NEC
nant cells in developing brain between 23 and (stage I) that have mild systemic signs and ab-
32 weeks of gestation. The mature forms of dominal distention with changes of feeding in-
these cells do not become abundant until after tolerance, to advanced NEC (stage III), in which
term, and tolerate hypoxic insult better than pre- there are significant systemic signs with evidence
myelinating oligodendrocytes. Hypoxic-ischemic of intestinal perforation (Walsh and Kliegman
damage during this vulnerable period leads to 1986). The risk factors for the development
disruption of oligodendrocyte lineage progression of NEC include prematurity, enteral feeding,
and progression of myelination. Through either intestinal asphyxia or ischemia, and bacterial
hypoxia, ischemia, or both, there is a deprivation colonization. The exact mechanism of develop-
of glucose and oxygen supply that causes a pri- ment is unknown, but is thought to be an activa-
mary energy failure that initiates a cascade of tion of the inflammatory cascade as a result of
events leading to cell dysfunction and ultimately mucosal injury.
cell death. Several studies have highlighted the associa-
The definition of HIE in preterm infants varies tion between NEC and neurodevelopmental out-
across studies, but generally involves Apgar comes, including CP. Among preterm infants
scores of less than 5 and 7 at 1 and 5 min, cord followed to almost 2 years corrected age, those
pH less than 7, a sentinel event occurring around who had necrotizing enterocolitis were at higher
delivery, and the need for resuscitation; other risk for poor cognitive and psychomotor develop-
studies also include a base deficit on blood gas ment than those infants without NEC (Hintz et al.
of >15 mmol/L and clinical evidence of enceph- 2005). Furthermore, those infants who had more
alopathy. The reported incidence of HIE among advanced stages of NEC or required surgery had
preterm babies varies between 1.3 and 9 per 1000 worse outcomes. The poor neurodevelopment that
live births. Premature infants with acidotic cord is often seen in infants with NEC may be either a
pH, delayed resolution of acidosis, renal impair- primary consequence of NEC itself, or secondary
ment, raised creatinine, prolonged assisted venti- to comorbidities such as bacteremia. It is theo-
lation, and abnormal neurological examination rized that NEC may lead to white matter injury
can be presumed to have suffered some degree from cytokine mediators involved in the systemic
of hypoxic insult. There are few studies available inflammatory cascade, with surgical intervention
that investigate the long-term neurological out- causing an additional cytokine surge. A study by
comes of preterm infants with HIE. In a study Martin and colleagues demonstrated that children
performed by Logitharajah and colleagues, 29% who had both late bacteremia and surgical NEC
of the premature infants who developed HIE were almost eight times more likely to develop
went on to develop cerebral palsy, although the diplegic cerebral palsy than those who had
32 M. Favara et al.
neither, and twice as likely if they had medical the third day of life in term neonates. This
NEC (Martin et al. 2010). delay is likely secondary to a delay in maturation
of hepatic uridine 50 diphospho-glucuronosyl-
Hypocarbia transferase (UGT) activity. The natural peak bili-
Hypocarbia, or low levels of carbon dioxide in rubin in small premature infants is mainly
the blood, has been associated with the dev- unknown, as small premature infants will gener-
elopment of PVL. The partial pressures of arterial ally be treated with phototherapy at a much lower
carbon dioxide are well known to have an im- threshold and will rarely be allowed to reach the
portant influence on the regulation of cerebral peak total bilirubin thresholds.
blood flow, with hypocarbia causing a decrease The major complication of hyperbilirubine-
in cerebral perfusion. It has been shown that car- mia is bilirubin-induced neurologic dysfunction
bon dioxide is an important regulator of cerebral (BIND). Acute bilirubin encephalopathy (ABE)
blood flow in preterm infants and that cerebral is used to describe the acute manifestations of
blood flow-carbon dioxide sensitivity may be BIND, while kernicterus is the chronic and per-
higher than that of the adult. Previous studies manent neurologic sequelae of BIND. Term
have demonstrated that hypocarbia causes cere- and late preterm infants are at risk for BIND
bral vasoconstriction and diminished cerebral when total bilirubin concentrations are greater
blood flow that may result in watershed hypoxic- than 25 mg/dL, but have been demonstrated in
ischemic lesions. Calvert and colleagues also high-risk, low birth weight infants as low as
demonstrated that infants with cystic PVL had 10–12 mg/d. Bilirubin is a potential neurotoxin
lower mean carbon dioxide values and longer at high levels, and is thought to enter the brain
periods of low carbon dioxide levels (Calvert in a variety of mechanisms, including altering
et al. 1987). the binding capacity of albumin, increasing
Hypocarbia is a frequent complication in CNS permeability secondary to disruption of
those infants who are receiving mechanical ven- the blood-brain barrier, and overwhelming the
tilation; these infants may have hyperventilation normal buffering capacity of blood and tissues.
that causes a resultant hypocarbic alkalosis. Long-term survivors of kernicterus often demon-
Additionally, it is thought that overexpansion of strate choreoathetoid CP, in addition to sensori-
the lung due to mechanical ventilation may pos- neural hearing loss, developmental delays, and
sibly cause ischemia via decreased venous return dental dysplasia. Phototherapy as a treatment for
and subsequent decreased cardiac output. Hypo- neonatal hyperbilirubinemia has become easily
carbia during artificial ventilation therapy was available and widespread, and as a result has
reported to be associated with an increased risk drastically decreased the incidence of bilirubin
of PVL whether a conventional ventilator or a encephalopathy leading to CP.
high frequency jet ventilator was used (Wiswell
et al. 1996).
Treatment
Hyperbilirubinemia
Hyperbilirubinemia is seen in virtually all pre- Perinatal and Postnatal Interventions
term infants born at less than 35 weeks’ gestation. to Reduce the Risk of Cerebral Palsy
Hyperbilirubinemia is more prevalent, severe, in Preterm Infants
and protracted than that in term infants because
of increased immaturity of red blood cells, Antenatal Glucocorticoids
liver, and gastrointestinal tract in the preterm When a mother presents in premature labor or
infant, as well as the delay in enteral feedings there are maternal factors that make a premature
that is common in preterm infants. Physiologic delivery imminent, there are strategies that may
jaundice in premature neonates occurs around improve neonatal outcomes. The antenatal admin-
the fifth day of life, compared with around istration of a single short course of
glucocorticoids to augment pulmonary maturation the same family as aminophylline and theophyl-
has had the positive, unanticipated benefit of a line, and is inhibitor of adenosine receptors. A
significant reduction of severe intraventricular large, international, randomized, controlled trial
hemorrhage, or IVH (Crowley et al. 1990). Cur- was performed that investigated both short- and
rently, the consensus by the American College of long-term outcomes of infants treated with caf-
Obstetricians and Gynecologists recommends that feine for apnea of prematurity, in particular
all women in labor between 24 and 34 weeks of neurodevelopmental disability. The study found
pregnancy be considered candidates for antenatal that caffeine significantly reduced the incidence
corticosteroid therapy. In a meta-analysis, a single of cerebral palsy (4.4% vs. 7.3% in placebo-
course of antenatal corticosteroids was associated treated infants) at a corrected age of 18–21 months
with reduced risk for CP (RR 0.678, 95% CI (Schmidt et al. 2007). However, when assessed at
0.564–0.815) (Sotiriadis et al. 2015). Because 5 years, caffeine therapy was no longer found to
there is evidence suggesting that mortality, respi- have a significantly improved rate of survival
ratory distress syndrome, and IVH are reduced without disability when compared to placebo ther-
even when treatment lasts for less than 24 h, ste- apy (Schmidt et al. 2012).
roids should be given unless delivery is imminent.
However, repeated courses of steroids have been Delayed Cord Clamping
shown to have a detrimental effect on the infant. Delayed cord clamping (DCC) is an obstetric
A trial in 2008 showed that multiple courses practice in which there is a delaying of umbilical
of steroids given every 14 days did not improve cord clamping during delivery. DCC has been
preterm birth outcomes, and were associated with shown to significantly increase the transfer of
decreased weight, length, and head circumference blood from the placenta to the infant, and even a
at birth (Murphy et al. 2008). 30–45-s delay has been shown to have an 8–24%
increase in blood volume. Numerous randomized
Magnesium for Neuroprotection controlled studies have documented the safety
Magnesium sulfate is commonly used in expec- and efficacy of delayed cord clamping, and
tant mothers with hypertension associated with have demonstrated benefits of higher blood pres-
preeclampsia. Magnesium sulfate given prior to sure, higher hematocrit levels, fewer days on oxy-
delivery may possibly reduce the risk of intra- gen and ventilation, fewer transfusions, and lower
ventricular hemorrhage. The mechanism in pre- rates of IVH (Mercer et al. 2006). Although
venting IVH is not clear, but it is thought that DCC has been shown to reduce the risk of IVH
magnesium stabilizes cerebral vasculature and in preterm infants, there is limited data on the
reduces hypoxic effects by mitigating cytokine long-term benefits of this practice. Several studies
damage. A large, randomized controlled trial are in progress to evaluate the neurodevelop-
of magnesium sulfate given to mothers at mental outcomes including the risk of CP in pre-
24–31 weeks of gestation demonstrated a reduced mature infants managed with DCC.
rate of cerebral palsy among infant survivors
(Rouse et al. 2008). Follow-Up of the Premature Infant
Children who are discharged from the intensive
Caffeine for Apnea of Prematurity care unit who are at high risk for the develop-
Apnea is very common in premature infants due to ment of CP or other developmental delays should
immaturity of respiratory control mechanisms. be followed by either a developmental pedia-
Hypoxia and bradycardia associated with apnea trician or a state-run surveillance program. At
of prematurity may contribute to the develop- these programs, children are assessed by spe-
ment of PVL and CP. A medicine commonly cialists, and may also receive occupational,
used to treat apnea of prematurity is caffeine, physical, or speech therapy. The Bayley Scale of
which can be given in parenteral and enteral Infant Development is a common test performed
forms. Caffeine is a methylxanthine derivative in at these visits and assesses developmental
34 M. Favara et al.
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life. The most recent test, or BSID-III, has five Dexamethasone induces apoptosis of progenitor cells
in the Subventricular zone and dentate gyrus of devel-
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guage, fine motor, gross motor, and cognitive. Calvert SA, Hoskins EM, Fong KW, Forsyth SC (1987)
Bayley scores of 100 +/ 15 represent the mean Etiological factors associated with the development
+/ standard deviation of population of normal of periventricular leukomalacia. Acta Paediatr Scand
76:254–259
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infant is classified as having neurodevelopmental J Obstet Gynaecol 97:11–25
Doyle LW, Davis PG, Morley CJ, Mcphee A, Carlin JB,
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moderate to severe CP, MDI or PDI lower than infants from the dart study: a multicenter, international,
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Genetic Abnormalities and Congenital
Malformations as a Cause of Cerebral 3
Palsy
Kristen Ferriero and Pamela Arn
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
Evolving Evidence in the Genetics of Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
Congenital Anomalies and Coexisting Conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
Other Contributing Causes of Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
Single-Gene Causes of Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
Copy Number Variants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
Recommendation for Treatment/Assessments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
Cross-References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
Abstract gene changes and deletions or duplications of

Recent evidence suggests that genetics may genetic material are likely involved in the path-
play a prominent role in the development of ogenesis of disease. Finding a genetic cause
cerebral palsy. Genetics has different avenues may aid in treatment, prognostication, and
by which it may contribute to disease. Several family planning. Thus, in consultation with a
studies have examined how a known risk factor geneticist, it is important to consider a genetic
along with a genetic predisposition may lead to evaluation in patients with cerebral palsy.
cerebral palsy. Others have studied how single-
Keywords
DNA · Inheritance · Mutation · Copy number
variant
K. Ferriero
Alfred I. duPont Hospital for Children, Wilmington, DE,
USA
e-mail: Kristen.Ferriero@nemours.org
P. Arn (*)
Department of Pediatrics, Nemours Children’s Specialty
Care, Jacksonville, FL, USA
Department of Clinical Genomics, Mayo Clinic,
e-mail: Pamela.Arn@nemours.org; parn@nemours.org

https://doi.org/10.1007/978-3-319-74558-9_2
38 K. Ferriero and P. Arn
Introduction (Van Eyk et al. 2018). However, more recent

studies using whole exome sequencing (WES)
Evolving Evidence in the Genetics have found likely pathogenic point mutations in
of Cerebral Palsy 14% of an unselected cohort of cases (McMichael
et al. 2015). Two other studies (Segel et al. 2015;
Cerebral palsy describes a heterogeneous group of McMichael et al. 2014) have shown that 20–31%
disorders. The heterogeneity in brain imaging, of cerebral palsy cases have pathogenic or likely
developmental outcomes, and clinical subtypes pathogenic copy number variants (CNVs).
suggests that there is a complex interplay of caus- Together, a genetic contribution to the cause of
ative factors, including genetic and environmental cerebral palsy is potentially present in up to 45%
triggers (van Eyk et al. 2018). Although hypoxia of cerebral palsy cases. Discovering these genetic
during the birthing process was once thought to be influences is important in not only informing fam-
a major contributor to the development of cerebral ilies why their child has cerebral palsy, but also
palsy, more recent evidence has demonstrated that may help guide treatments and future reproduc-
genetic contributions may be more significant. tive decisions.
Several observations have suggested genetic
involvement in cerebral palsy, including a higher
concordance rate for cerebral palsy in monozy- Natural History
gotic twins compared to dizygotic twins, higher
risk of cerebral palsy in consanguineous families, Congenital Anomalies and Coexisting
frequent co-occurrence of cerebral palsy with con- Conditions
ditions with known genetic contributions, and
identification of single-gene mutations in cerebral Congenital anomalies have long been associated
palsy pedigrees (Van Eyk et al. 2018). Thus, there with cerebral palsy, although the strength of asso-
is emerging evidence that genetics play a signifi- ciation reported varies by study. Although there is
cant role in the development of cerebral palsy. wide variability in the prevalence of congenital
There are four main types of DNA variation anomalies, there is agreement that the prevalence
which may contribute to cerebral palsy. These exceeds that of the general population (Goldsmith
include copy number variants (CNVs), single- et al. 2019). Goldsmith et al. performed a system-
gene mutations, epigenetic modifications, and atic review of the literature on congenital anoma-
changes within mitochondrial DNA (Table 1) lies and cerebral palsy. They found a prevalence of
(Fahey et al. 2017). Similar to many other com- congenital anomalies in 11–32% of children with
plex and heterogeneous conditions, gene associa- cerebral palsy. Differences in the rate of congen-
tion studies have had difficulty determining genes ital anomalies in the studies were attributed to
associated with increased risk of cerebral palsy differences in the definition of congenital anoma-
lies, differences in registers for congenital anom-
alies, and variation in prevalence of congenital
Table 1 Types of genetic variation in cerebral palsy anomalies in different populations. Despite con-
Type of genetic genital anomalies overall being more common in
variation Description premature infants, term children with cerebral
Mitochondrial DNA outside of the chromosomes palsy were more likely than preterm children to
DNA which are inherited from the mother
have congenital anomalies, particularly cerebral
Copy number Affects larger amounts of DNA;
variants consists of duplications or deletions
anomalies. Furthermore, microcephaly was the
Single-gene Variation in a single or small number most common cerebral anomaly described, and
mutations of nucleotides (SNVs) anomalies of the circulatory system were the
Epigenetic Modifications of DNA that do not most common non-cerebral anomalies described
changes affect the nucleotides themselves (Goldsmith et al. 2019). The increased prevalence
(e.g., methylation) of congenital anomalies in children with cerebral
3 Genetic Abnormalities and Congenital Malformations as a Cause of Cerebral Palsy 39
palsy compared to the general population suggests has low reserve and is unable to withstand the
a genetic influence on the development of this stresses of labor or that the ongoing compromise
condition. However, it is important to consider experienced by the fetus is detected during the
that intrauterine infections, nutritional deficien- labor process (MacLennan et al. 2015).
cies, and teratogens may contribute to congenital Distinguishing between these may help guide the
anomalies as well. For example, congenital cyto- management of IUGR fetuses to aid in the pre-
megalovirus is a known cause of microcephaly vention of cerebral palsy.
and may be associated with cerebral palsy. There-
fore, it is important to consider all possible con- Multiple Pregnancy
tributing etiologies (Goldsmith et al. 2019). Multiple pregnancy is associated with increased
risk of cerebral palsy. An epidemiologic study in
Australia found an odds ratio (OR) of 6.62 for
Other Contributing Causes of Cerebral twins (O’Callaghan et al. 2011). This association
Palsy is complicated by the fact that twin and multiple
births are also associated with prematurity, IUGR,
In the past, birth trauma was thought to contribute and obstetric complications, which all contribute
to a significant number of cerebral palsy cases. to cerebral palsy risk.
Recent evidence now suggests that long-standing
intrauterine pathology is more associated with the Intrauterine Infection
development of this condition. Contributing fac- Epidemiologic studies have demonstrated that
tors include intrauterine growth restriction there is an increased risk of cerebral palsy associ-
(IUGR), multiple pregnancy, intrauterine infec- ated with intrauterine infections. In review of
tion, thrombophilia, hypoxia-ischemia, and maternal reports of fever or infection during preg-
prematurity. nancy, a higher association was found with infec-
tions in the second half of pregnancy
Intrauterine Growth Restriction (O’Callaghan et al. 2011). In term infants, histo-
Intrauterine growth restriction increases the risk logic chorioamnionitis or intrapartum fever was
of cerebral palsy in term infants by 10- to 30-fold. associated with a fourfold increase in cerebral
The risk increases with degree of growth restric- palsy risk (MacLennan et al. 2015). Some
tion and rises significantly in infants with researchers have hypothesized that an excessive
birthweight less than the third percentile (Mac- fetal inflammatory response to infection due to a
Lennan et al. 2015). Birth defects and fetal growth genetic predisposition is a mechanism by which
restriction were also more strongly associated perinatal infections may lead to cerebral palsy.
with cerebral palsy than birth asphyxia events, Genetic association studies have shown polymor-
42.3% and 16.5%, respectively, compared to phisms in cytokines, such as interleukin-6, inter-
8.5%. As such, patients with birth defects and leukin-8, tumor necrosis factor, and mannose
growth restriction represent the group most at binding lectin, have been linked to an increased
risk for having cerebral palsy (Mcintyre et al. risk of cerebral palsy (MacLennan et al. 2015).
2013). IUGR may be secondary to several differ-
ent etiologies such as poor placentation due to Thrombophilia
genetic differences or anatomical abnormalities, Mutations in genes within the coagulation cascade
as well as pathologic processes, including pre- that result in a hypercoagulable state have been
eclampsia, diabetes, and systemic lupus. theorized to increase the risk of stroke and, thus,
Although IUGR is known to be associated with cerebral palsy. Perinatal arterial ischemic stroke
cerebral palsy risk, it is unclear when the patho- represents the type of stroke with the highest rate
logic process which causes cerebral palsy occurs. of evolution to cerebral palsy, ranging from 68%
Some IUGR fetuses may show signs of compro- to 78% (Torres and Saddi 2015). Many studies
mise during labor. It is possible that a smaller fetus have examined genes associated with
thrombophilia, including factor V Leiden, pro- Another study published in 2016 (Esih et al. 2016)
thrombin, methylenetetrahydrofolate reductase, also supports this two-hit hypothesis. The
factor VII, fibrinogen, plasminogen activator researchers found that among those patients with
inhibitor 1, and endothelial protein C receptor, the diagnosis of hypoxic-ischemic encephalopa-
and whether patients with these mutations have a thy, carriers of at least one polymorphism of the
higher risk of cerebral palsy (Van Eyk et al. 2018). catalase enzyme, which is involved in protecting
A literature review examining these studies found the brain against oxidative stress, were more
that most did not demonstrate a significant likely to develop cerebral palsy (Esih et al.
increase in risk, suggesting there is not a direct 2016). Thus, cerebral palsy is likely caused by a
effect of thrombophilia on the development of complex interplay of multiple factors. However,
cerebral palsy. Rather, a combination of mutations these studies demonstrate that through further
with clinical risk factors together likely play a role research into the biomolecular pathways involved
in the etiology of cerebral palsy (Torres and Saddi in the development of cerebral palsy, it may be
2015). possible to determine which infants are most at
risk of developing disease and ultimately be able
Hypoxia-Ischemia to alter this cascade of events to prevent disease.
Although once thought to be a major contributor
to cerebral palsy burden, epidemiologic studies Prematurity
have now shown that hypoxia during the birthing Prematurity is a major risk factor for cerebral
process represents only a small proportion of cere- palsy, and there is an inverse relationship between
bral palsy cases. In fact, one study reported only gestational age and cerebral palsy prevalence.
2% of cases were likely due to an acute hypoxic Premature infants are at particularly high risk of
event at birth (Van Eyk et al. 2018). Furthermore, damage to the white matter of the brain, specifi-
intrapartum fetal heart rate monitoring and cally periventricular leukomalacia. Several stud-
increased rates of caesarean deliveries have not ies have examined why premature infants are
affected cerebral palsy prevalence, suggesting susceptible to these events, and some data sug-
more chronic perinatal compromise likely con- gests a neuroinflammatory response may play a
tributes to cerebral palsy (MacLennan et al. key role (Vidak et al. 2017). Cyclooxygenases
2015). Of those infants who do experience a hyp- (COXs) may mediate the inflammatory response
oxic event surrounding birth, it is difficult to pre- at the blood-brain barrier. Therefore, Vidak et al.
dict which patients will go on to develop disease. investigated whether polymorphisms in the COX
This is in part due to the fact that the mechanism genes were associated with susceptibility to cere-
by which hypoxia-ischemia causes cerebral palsy bral palsy in premature infants. Researchers found
is not fully elucidated. With the goal of determin- that there was no statistically significant differ-
ing this causal mechanism, researchers (Vasquez- ence in distribution of COX-1 and COX-2 poly-
Vivar et al. 2017) studied tetrahydrobiopterin morphisms between patients with cerebral palsy
(BH4), an essential cofactor in the synthesis of and those without; however, they did find that in
the neurotransmitters serotonin and dopamine the group of cerebral palsy patients with peri-
and known factor in the development of child- ventricular leukomalacia, the COX-1 high expres-
hood neurologic disorders. Using fetal rabbit sion genotype was more frequent compared to
models, the study found that BH4 is negatively controls. Authors suggested that a genetic predis-
affected by hypoxic-ischemic events. Interest- position for an exaggerated neuroinflammatory
ingly, lower levels of BH4 were also found in response may result in periventricular leukomalacia
premature rabbits. Together, researchers hypothe- and cerebral palsy as a consequence (Vidak et al.
sized that a two-hit model, low BH4 levels inher- 2017). Researchers in obstetrics and gynecology
ent to prematurity and decreased levels caused by have hypothesized that fetal genes may influence
hypoxic-ischemic injury, may lead to the develop- susceptibility to preterm birth and, thus, predispose
ment of cerebral palsy (Vasquez-Vivar et al. 2017). to diseases associated with prematurity, including
cerebral palsy, bronchopulmonary disease, respi- is incompletely understood; however, recent stud-
ratory distress syndrome, and intraventricular ies suggest random mono-allelic expression
hemorrhage. Some candidate haplotypes have whereby only one of the two alleles of a gene is
been identified as associated with preterm birth transcribed and expressed (Fahey et al. 2017).
and lung maturity. Further research must be done Likewise, the study of a consanguineous Jorda-
to identify other genes associated with prematu- nian family identified a homozygous mutation in
rity and cerebral palsy; however, this will likely be ADD3. Phenotypically these patients have mild
difficult due to the interaction of genetics and microcephaly, either hypotonia that progresses to
environment in these complex diseases (Hallman spastic diplegia or spastic quadriplegia, and bor-
2012). derline intelligence or intellectual disability. Sim-
ilar to the KANK1 deletion, excessive actin
filament accumulation may be the mechanism by
Single-Gene Causes of Cerebral Palsy which this mutation affects function (Fahey et al.
2017). Finally, the study of consanguineous fam-
Prior to the use of next-generation sequencing ilies in Pakistan confirmed a homozygous mis-
(NGS) technology, candidate gene association sense mutation in GAD1, which codes for an
studies were performed with inconsistent results. enzyme involved in the production of the neuro-
Now, with whole exome sequencing (WES), transmitter gamma-aminobutyric acid from gluta-
which examines the protein coding regions of mate. These individuals all had a similar
gene, and whole genome sequencing (WGS), phenotype of cerebral palsy, intellectual disability,
which examines protein coding regions as well and sometimes epilepsy (Van Eyk et al. 2018).
as the noncoding regions, disease-causing genes Another promising group of genes found to
are likely to be rapidly identified (Van Eyk et al. cause cerebral palsy affect AP-4 subunits. AP-4
2018). In fact, whole exome sequencing is an adaptor protein complex which helps with
performed on 183 patients with cerebral palsy receptor trafficking of a molecule believed to be
identified de novo variants in 44% of case-parent involved in the development of hypoxic-ischemic
trios. These variants were prioritized for causality, brain injury. Multiple studies of different families
and by strict criteria, 14% of cerebral palsy cases have found mutations in AP4M1, AP4B1, AP4S1,
had a potentially disease-causing variant and AP4E1 in patients with spastic paraplegia and
(McMichael et al. 2015). About half of these quadriplegia. The typical phenotype also includes
variants were novel candidate genes. These characteristic dysmorphic features, intellectual
included AGAP1, JHDM1D, MAST1, NAA35, disability, growth retardation, microcephaly, lack
RFX2, WIPI2, CD99L2, and TENM1. The other of speech, and a pleasant disposition. However,
variants occurred in the known disease genes, whether the receptor trafficking is the mechanism
KDM5C, SCN8A, TUBA1A, L1CAM, and PAK3, by which these mutations cause cerebral palsy
and were predicted to be causative for cerebral remains unclear (Fahey et al. 2017).
palsy (McMichael et al. 2015). A different mode by which researchers have
Other likely monogenic causes of cerebral identified monogenic causes of cerebral palsy is
palsy have been identified by studies of families. by sequencing the genes of a group of patients
Affected individuals in an Israeli family were with a common type of cerebral palsy. De novo
found to have heterozygous deletions in the point mutations have been described in the genes
KANK1 gene, which is involved in the prevention KCNC3, ITPR1, and SPTBN2 in patients with
of uncontrolled actin polymerization. The disease ataxic cerebral palsy. Although these genes have
is characterized by early motor delays and hypo- been implicated in conditions other than cerebral
tonia, followed by spastic quadriplegia, often palsy, heterogeneous presentations are described
severe to profound intellectual disability, and (Fahey et al. 2017).
diminished cortical volumes on brain magnetic Identification of these variants in patients with
resonance imaging (MRI). The inheritance pattern cerebral palsy is promising; however, cellular,
molecular, and animal model functional studies CNVs were more likely de novo (Segel et al.
are needed to confirm pathogenicity and mecha- 2015). The participants in this study were
nism of causation (McMichael et al. 2015). described as having cryptogenic cerebral palsy
as there was no known etiology of their neuro-
logic disorder. Likely due to this selection criteria,
Copy Number Variants Segel et al. found a higher percentage of clinically
significant CNVs with 31% of participants having
Copy number variants (CNVs) are duplications or either a pathogenic or likely pathogenic CNV.
deletions of greater than 1000 base pairs in a DNA Furthermore, those patients with dysmorphic fea-
sequence. CNVs are known to be involved in the tures, as characterized by a geneticist, and those
pathogenesis of other neurodevelopmental disor- with nonmotor comorbidities were more likely to
ders, such as autism, epilepsy, and intellectual have clinically significant CNVs (Segel et al.
disability; thus, they are hypothesized to be 2015). Although this is promising data regarding
involved in cerebral palsy as well (Van Eyk et al. the genetic contributions to disease, the analysis
2018). In 2014, McMichael et al. examined the of CNVs has been difficult due to their rarity and
DNA of a cohort of cerebral palsy patients and their encompassment of multiple genes. There-
found 14 potentially pathogenic CNVs in 10 of fore, it has been challenging to make definitive
the 50 individuals studied (McMichael et al. conclusions about the relationship of CNVs to
2014). Identification of these CNVs is promising disease (Fahey et al. 2017).
as all of the CNVs involve genes expressed in the
brain, several of which have been associated with
neurologic disorders. However, none of the CNVs Recommendation for Treatment/
were de novo, i.e., either the CNVs were identified Assessments
in an unaffected parent or the parents were not
tested. This may be evidence against the relevance A general approach to a patient with cerebral
of these CNVs to disease, but the authors suggest palsy begins with the basic foundations of diag-
that the discordance may be due to variable nostic medicine, starting with a medical and fam-
expressivity, incomplete penetrance, or epigenetic ily history followed by an examination. Based
modifications (McMichael et al. 2014). Other- upon studies of genetic testing performed on cere-
wise, this may give further evidence to the bral palsy patients, certain historical features and
two-hit hypothesis by which the combination of examination findings may lead a clinician to
an inherent genetic susceptibility from CNVs and determine which patients would be most likely
an environmental insult triggers a cascade of to benefit from a genetic evaluation. Discovering
events that leads to cerebral palsy. In contrast to a genetic etiology of a patient’s cerebral palsy
McMichael et al., Oskoui et al. also examined an phenotype is helpful in determining prognosis,
unselected group of patients with cerebral palsy discussing recurrence risk and family planning,
but found de novo CNVs in 7% of those studied. as well as in focusing treatments.
This is similar to other neurodevelopmental con- Recent literature supports a genetic evaluation
ditions, such as autism and epilepsy, which have a in the workup of a patient with cerebral palsy.
de novo CNV rate of 4.7–7.1% and 5%, respec- Namely, Matthews et al. performed WES on
tively (Oskoui et al. 2015). Interestingly, the size 50 patients with atypical cerebral palsy and
of the CNVs was related to the impairment of the established a molecular diagnosis in 65% of the
patient. Those with large CNVs were more likely cases (Matthews et al. 2019). It is likely that the
to be severely impaired (Oskoui et al. 2015). In high diagnostic yield was in part due to the strict
support of Oskoui et al., Segel et al. performed inclusion criteria. Patients included in the study
microarray analysis on a group of 52 patients with had to have impaired motor function within the
cerebral palsy and found that clinically significant first year of life and one or more of the following,
severe intellectual disability, autism spectrum dis- imaging abnormality or clinical features suggests
order, progressive neurologic deterioration, addi- a specific disorder, confirmatory molecular
tional abnormal neurologic findings, genetic testing for that disorder may be performed.
neuroimaging findings not typical of cerebral For example, spasticity may lead a clinician to
palsy, multiorgan disease, major congenital anom- consider testing for hereditary spastic paraplegia.
alies outside of the central nervous system, abnor- In a patient with dystonia or chorea, it is important
mal neurotransmitter profile, or a positive family to consider benign hereditary chorea and Lesch-
history (Matthews et al. 2019). A smaller study Nyhan syndrome as potential causes of cerebral
examined the genomes of 17 patients with a diag- palsy symptoms. Ataxia is an especially important
nosis of cerebral palsy but only included patients clinical feature to consider ruling out genetic
with full-term births and nonspecific brain MRI causes, as less than 5% of cerebral palsy patients
findings. Researchers aimed to increase diagnos- are characterized as having ataxic cerebral palsy
tic yield by excluding premature infants who are (Pearson et al. 2019). If the clinical features are
more susceptible to environmental factors which nonspecific, more comprehensive testing should
may contribute to cerebral palsy and those with an be considered. A DNA microarray, which detects
abnormal brain MRI which may identify other chromosomal microdeletions and duplications, is
causes of cerebral palsy. This led to the detection typically recommended as the first-line genetic
of pathogenic or likely pathogenic variants in testing for those with similar neurodevelopmental
52.9% of cases (Takezawa et al. 2018). The diag- conditions, including autism and developmental
nostic yield of these two studies is significantly delay. Thus, DNA microarray is a reasonable first
higher than the diagnostic yield in the unselected step in the evaluation of selected patients with
cohorts discussed above. Using similar studies, cerebral palsy. If DNA microarray does not estab-
Pearson et al. and Lee et al. have developed a list lish a likely diagnosis, WES may be considered as
of features described in Table 2 that should pro- a next step (Pearson et al. 2019).
mpt a clinician to consider genetic evaluation A consultation with a clinical geneticist will be
(Pearson et al. 2019; Lee et al. 2014). helpful in determining the studies most likely to
After choosing the appropriate patients for test- yield a specific diagnosis. In general, it is reason-
ing, the selection of genetic testing depends on the able to begin with a chromosome microarray.
patient and his or her clinical features. If an Testing for single genes, gene panels, or whole
exome genome sequencing is available. However,
Table 2 Clinical features that should prompt evaluation insurance coverage and expenses vary widely and
for genetic or metabolic conditions are best done in consultation with a geneticist or
Absent history of perinatal risk factors genetic counselor.
Family history of similar neurologic symptoms
Normal brain MRI
Motor symptom onset after initial period of normal Cross-References
development
Developmental plateau or regression ▶ Animal Models of Cerebral Palsy: What Can
Progressive neurologic symptoms We Learn About Cerebral Palsy in Humans
Paroxysmal motor symptoms or marked fluctuation of
▶ Cerebral Palsy and the Relationship to
motor symptoms
Clinical exacerbation in catabolic state
Prematurity
Isolated generalized hypotonia ▶ Infectious Etiologies of Cerebral Palsy
Prominent ataxia ▶ Neuroimaging Pathology in Cerebral Palsy
Signs of peripheral neuromuscular disease ▶ Perinatal Stroke as an Etiology of Cerebral Palsy
Eye movement abnormalities (e.g., oculomotor apraxia ▶ Problems During Delivery as an Etiology of
or repeated eye-head gaze saccades) Cerebral Palsy in Full-Term Infants
Adapted from Table 1 in Pearson et al. (2019) ▶ Risk Factors for Developing Cerebral Palsy
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Infectious Etiologies of Cerebral Palsy
4
Neil Rellosa
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
Epidemiology and Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46
Etiologies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
Cytomegalovirus (CMV) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
Herpes Simplex Virus (HSV) and Other Human Herpes Viruses . . . . . . . . . . . . . . . . . . . . . . . 50
Enteroviruses and Parechoviruses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
Emerging Viruses: Chikungunya Virus and Zika Virus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51
Neonatal Bacterial Pathogens . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
Other Pathogens to Consider . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
Abstract CP-related congenital infections can vary but

Infection occurring during the prenatal, perina- are usually neurotropic viruses including cyto-
tal, and early postnatal periods of life can cause megalovirus (CMV). Maternal bacterial infec-
cerebral palsy (CP). Gestational age may be an tions such as chorioamnionitis or urinary tract
associated risk factor, but both preterm and infection and neonatal bacterial infections such
term infants can be affected. Injury to the as sepsis and meningitis have been associated
brain causing CP can be the result of both with CP and may correlate with specific sub-
direct and secondary pathogenesis from infec- types of CP. Distinct clinical manifestations
tious etiologies. Direct infection of the central and stigmata can help identify these infections,
nervous system, damaging immune-mediated in addition to diagnostics such as serology and
inflammatory response to maternal or congen- molecular testing. However, treatments and
ital infection, or sequelae from infection such therapies can be limited and toxic and may
as hypoxic-ischemic events can all lead to have little direct effect on the development of
insult to the brain. Pathogens causing these CP and its long-term outcomes.
Keywords
N. Rellosa (*) Congenital infection · Cytomegalovirus ·
Nemours/Alfred I. duPont Hospital for Children,
Wilmington, DE, USA Perinatal transmission · Periventricular
e-mail: neil.rellosa@nemours.org leukomalacia · Herpes simplex virus

https://doi.org/10.1007/978-3-319-74558-9_3
46 N. Rellosa
Introduction Cerebral Palsy”). In a study investigating the ante-

cedents of CP according to severity of motor
Infection occurring during the prenatal, perinatal, impairment, congenital infection was significantly
and early postnatal periods of life can cause cere- associated with severe motor impairment in both
bral palsy (CP). Gestational age may be an asso- univariable analysis and multivariable analysis
ciated risk factor, but both preterm and term (Ahlin et al. 2016). Congenital viral infection
infants can be affected (▶ Chap. 2, “Cerebral appears to have a large role in CP development.
Palsy and the Relationship to Prematurity”). A study conducted by Gibson et al. showed an
Injury to the brain causing CP can be the result association between perinatal exposure to neuro-
of both direct and secondary pathogenesis from tropic viruses and the development of
infectious etiologies. Direct infection of the cen- CP. Newborn screening cards of 443 case patients
tral nervous system, damaging immune-mediated with CP and 883 controls were tested for viral
inflammatory response to maternal or congenital nucleic acids from varying enteroviruses and her-
infection, or sequelae from infection such as hyp- pes viruses including CMV; herpes simplex
oxic-ischemic events can all lead to insult to the viruses 1 and 2 (HSV-1 and HSV-2); Epstein-
brain (▶ Chap. 6, “Problems During Delivery as Barr virus (EBV); human herpes viruses 6, 7,
an Etiology of Cerebral Palsy in Full-Term and 8 (HHV-6, HHV-7, and HHV-8); and varicella
Infants”). Pathogens causing these CP-related zoster virus (VZV) by using polymerase chain
congenital infections can vary but are usually reaction (PCR). The results showed a significant
neurotropic viruses including cytomegalovirus association between any viral exposure and CP at
(CMV). Maternal bacterial infections such as all gestational ages and an increased risk of devel-
chorioamnionitis or urinary tract infection and oping all types of CP with detection of herpes
neonatal bacterial infections such as sepsis group B viral nucleic acids (HHV-6, HHV-7, and
and meningitis have been associated with CP and VZV). However, the exact nature of neuronal
may correlate with specific subtypes of CP. Distinct damage was not elucidated in this study (Gibson
clinical manifestations and stigmata can help iden- et al. 2006).
tify these infections in addition to diagnostics such Maternal infections such as bacterial vaginosis,
as serology and molecular testing. However, treat- urinary tract infection (UTI), chorioamnionitis,
ments and therapies can be limited and toxic and and even respiratory infection have also been
may have little direct effect on the development of shown to be a risk factor for the development of
CP and its long-term outcomes. CP (Bear and Wu 2016; Miller et al. 2013;
This chapter will discuss the pathophysiology Neufeld et al. 2005). In a population-based cohort
of infection as it relates to CP and the epidemiol- study conducted in Denmark of 440,546 singleton
ogy and risk factors associated with CP-related births, maternal genitourinary tract infections and
infections. In addition, the chapter will cover the antibiotic use during pregnancy were associated
pathogens that cause these infections including with an increased risk for CP (Miller et al. 2013).
their distinct clinical manifestations outside of In another population-based case-cohort study
CP and specific diagnostics and treatments and conducted in the state of Washington, infants
their impact on CP. of mothers who had infection including UTI,
chorioamnionitis, genitourinary infection, and
maternal or intrapartum fever during their hospi-
Natural History talization for delivery were at an increased risk of
CP (Neufeld et al. 2005). Although there is an
Epidemiology and Pathophysiology increased risk with perinatal infection and CP
with preterm births, in this study and others, the
Infection specifically congenital infection has risk of CP was observed in both term and preterm
shown to be a risk factor for the development of births (Neufeld et al. 2005; Wu and Colford 2000;
CP (▶ Chap. 10, “Risk Factors for Developing Wu et al. 2003).
4 Infectious Etiologies of Cerebral Palsy 47
Much of the recent data has focused on fourfold increase of the relative risk of CP in
chorioamnionitis as a risk factor for CP. very-low-birthweight (VLBW) infants with a
In a meta-analysis conducted in 2000, where history of neonatal sepsis has been reported
19 independent studies were examined, random (Wheater and Rennie 2000).
effects model analysis showed a significant asso- Although there have been several hypotheses,
ciation between clinical chorioamnionitis and the pathophysiology of how infection causes CP
CP or cystic periventricular leukomalacia in both is still not well defined. Varying pathologic mech-
preterm and term infants (Wu and Colford 2000). anisms have been proposed and studied; however,
In addition, in a 2003 case-control study of a none has been definitively proven, and CP caused
large birth cohort in California, clinical chorioam- by infection may be due to multifactorial causes
nionitis was again shown to be an independent (Ahlin et al. 2016; Gibson et al. 2006). Maternal
risk factor for CP and conferred a fourfold overall infections and intrauterine infections with direct
increased risk for term infants (Wu et al. 2003). and indirect brain damage, fetal inflammatory
Other studies have demonstrated the increased response, and hypoxic-ischemic brain injury
risk for CP with histological chorioamnionitis resulting from infection have all been proposed
(Horvath et al. 2012; Shatrov et al. 2010; Shevell as the pathogenesis for infection causing CP
et al. 2014). However, as will be discussed later, (MacLennan et al. 2015; Wu et al. 2003).
the exact pathogenesis is unclear. Once infection has crossed into the placental
There is some evidence that infection may circulatory system, as is the case in congenital or
be a risk factor for specific subtypes of CP in utero infection with viral pathogens, it has the
(▶ Chap. 21, “Classification Terminology in potential to cause direct neuronal damage of the
Cerebral Palsy”). In a case-control study brain or indirect damage via a pro-inflammatory
conducted in Sweden, 309 children with CP cytokine response (Gibson et al. 2006).
born at term were compared to matched controls. There is some evidence of neurotropic viruses,
Infection-related factors including E. coli bacteri- such as CMV, causing direct neuronal and brain
uria during pregnancy, any infection during tissue damage. CMV has been shown to infect
pregnancy, severe infection during pregnancy, neural progenitor cells causing impairment of
antibiotic therapy once or several times during cell growth and differentiation. In addition,
pregnancy and delivery, antibiotics postpartum, cytopathologic lesions and necrosis have been
and postpartum fever were significantly associ- demonstrated in various types of brain cells dur-
ated with spastic hemiplegia versus other CP sub- ing CMV infection (Pass 2018). HSV not only can
types such as dyskinetic cerebral palsy (Ahlin invade the peripheral nervous system but can also
et al. 2013). infect the central nervous system, especially in
The true epidemiology and risk of postnatal the perinatal period, causing direct damage to the
infections such as neonatal sepsis and meningi- brain. Other congenital infections with pathogens
tis as cause for CP are also not well known. such as Toxoplasma and Zika virus may directly
However, in a study from Liverpool, UK, post- affect the developing brain causing microcephaly
natal or “acquired” etiologies of CP were exam- and intracranial calcifications that lead to clinical
ined. Of 147 cases of CP classified as acquired findings consistent with CP.
CP, 63 cases (42.9%) were apparently due to White matter damage or a more specific form
infection. The majority of these infections of white matter disease called periventricular
were infections of the brain or meninges leukomalacia (PVL) is associated with CP.
(Pharoah et al. 1989). It should be noted that Enteroviruses and parechoviruses are known
this study was conducted prior to immuniza- pathogens of neonates causing central nervous
tions against bacteria that cause meningitis in system infection such as encephalitis. This
children such as Haemophilus influenzae type B encephalitis has been associated with magnetic
and pneumococcus, and the incidence of these resonance imaging (MRI) evidence of white mat-
types are significantly rare today. In addition, a ter injury (Verboon-Maciolek et al. 2008;
48 N. Rellosa
Wu et al. 2014). Although not well understood, are static, nonprogressive, and irreversible,
rather than direct damage from the virus itself, it is proper identification and diagnosis can help with
hypothesized that viral infection in the CNS prognosis, predicting long-term outcomes, and
causes pro-inflammatory cytokine production prescribing therapies for both CP-related and
such as interleukin-6 (IL-6), interleukin-1-beta non-CP-related clinical features of the infection.
(IL-1β), and tumor necrosis factor-alpha This section will discuss individual pathogens and
(TNF-α) by various CNS cell types triggering their most common clinical manifestations asso-
lymphocytic infiltration. This immune response ciated with infection. In addition, disease-specific
may then lead to autoimmune-type damage to diagnostic and testing methods, treatments, and
nerve cells and defects to developing vasculariza- prevention will also be discussed.
tion and fetal blood flow and ultimately to white
matter damage (Gilstrap and Ramin 2000;
Horvath et al. 2012; MacLennan et al. 2015; Cytomegalovirus (CMV)
Miller et al. 2013; Verboon-Maciolek et al. 2008).
In addition to congenital infections from CMV is a member of the herpesvirus family,
viral pathogens, bacterial maternal infections Herpesviridae, and the beta-herpesvirus subfam-
have also been associated with the development ily, Betaherpesvirinae. It is a double-stranded
of white matter injury such as PVL and DNA virus that is ubiquitous and causes infection
thus CP. Maternal bacterial infections lead to in all ages. Although asymptomatic infection is
intrauterine infection and thus both a maternal common, symptomatic infection mainly occurs
and fetal pro-inflammatory response. This pro- in the immunocompromised or neonates. Clinical
inflammatory response leads to neurologic dam- manifestations of CMV infection can be wide-
age including intraventricular hemorrhage, white ranging, disseminated, and significantly dis-
matter damage, and PVL (Horvath et al. 2012; abling as in the case of its link to the development
Miller et al. 2013; Wu and Colford 2000). of CP.
Other indirect mechanisms have been pro- Congenital infection with CMV has been
posed as explaining infection’s role in the devel- the type of infection most associated with
opment of CP. Fetal hypoxic-ischemic brain CP. Approximately 1% of all live births are
injury due to interruption of placental gas infected with CMV, making CMV infection the
exchange and blood flow secondary to placental most common congenital viral infection (AAP
inflammation from infection potentially could 2015a). There are higher rates of congenital
lead to CP. Postnatal infections of the neonate CMV infection in developing countries and in
such as early-onset bacterial sepsis or meningitis low-income groups. Rates of CMV infection
can cause neurodevelopmental impairment in closely follow the prevalence of maternal seropos-
early childhood including CP (Edwards and itivity in a given population (Pass 2018).
Baker 2018). Neonatal meningitis can lead to In most cases, congenital infection with CMV
ischemic stroke and cerebral sinovenous throm- is asymptomatic at birth. However, approximately
bosis causing brain injury and possibly CP. 10% of infected infants have symptoms at birth.
Although vertical transmission can occur trans-
placentally and postnatally from ingestion of
Etiologies CMV-positive milk during breastfeeding, early
in utero infection is more often associated with
As alluded to previously, infections from multiple sequelae such as deafness, retinitis, and cognitive
types of pathogens including viruses, bacteria, impairment. In addition, more severe sequelae are
and parasites have been identified as possible associated with primary maternal infection.
infectious etiologies of CP. Although in most The role of congenital CMV infection in CP
cases, consistent with the definition of CP, has been well documented, but the true prevalence
the neurologic deficits related to these infections has not been extensively reported. In a
retrospective observational study of newborns culture. Newer technology such as real-time poly-
who were later diagnosed with CP born from the merase chain reaction (PCR) assay to detect viral
years 1996–2014 in Australia, 9.6% of these chil- DNA in fluids such as blood and cerebrospinal
dren had detectable CMV DNA in their newborn fluid has also been used to help confirm
screening cards. This represented a markedly the diagnosis of congenital CMV infection.
higher proportion as compared to the rate in new- However, shell vial culture remains the gold stan-
borns in the general community (approximately dard. CMV serology of the infant or maternal
0.6%) (Smithers-Sheedy et al. 2017). serology should not be considered diagnostic
Symptoms of congenital CMV infection can because of the ubiquitous nature of CMV. When
vary. Clinical manifestations can include prema- congenital infection has been suspected prena-
turity, intrauterine growth restriction, micro- tally, diagnosis with detection of CMV in amni-
cephaly, seizures, intraventricular calcifications, otic fluid has also been used. Other diagnostics
retinitis, jaundice, purpura, and hepatosple- such as brain MRI that demonstrate characteristic
nomegaly. However, sensorineural hearing loss intracerebral calcifications and an ophthalmologic
is the most common sequela of congenital CMV exam for evidence of retinitis also can be helpful.
infection. Approximately 21% of all hearing loss Treatment with antiviral medication is
from birth is due to congenital CMV infection recommended for symptomatic congenital CMV
(AAP 2015a). disease with or without central nervous system
Specific clinical features of CP have been involvement. Treatment has been shown to
described associated with symptomatic congen- improve auditory and neurodevelopmental
ital CMV infection. In many cases the associa- outcomes at 2 years of age. Intravenous
tion seems to be linked to severe conditions and (IV) ganciclovir has been used in the past; how-
significant impairment. In a study of 35 children ever, significant toxicities such as neutropenia
from Croatia, Hungary, and Slovenia with CP have been seen in infants. More recently, oral
associated with congenital CMV infection, valganciclovir, a prodrug which is metabolized
85.7% had bilateral spastic CP. Approximately to ganciclovir once absorbed, at adjusted dosing
71% were unable to walk, and close to 63% had has been shown to provide similar ganciclovir
fine motor function that was severely affected. exposure to IV ganciclovir and may be better
In addition, many of the children had severe tolerated. A 6-month course with oral
impairment of hearing, vision, speech, and valganciclovir is now recommended for symp-
intellect, while 77.1% suffered from epilepsy tomatic infants, but IV ganciclovir can be
(Dakovic et al. 2014) (▶ Chap. 55, “Auditory substituted initially for patients who cannot
Rehabilitation in Children with Cerebral tolerate enteral administration (AAP 2015a).
Palsy”). Consultation with an infectious diseases specialist
or an expert in the field is recommended for
Testing, Treatment, and Outcomes the diagnosis and treatment of congenital CMV
While recognition of these clinical manifestations infection.
is important to making the diagnosis of congenital Although antiviral medication plays a helpful
CMV infection, there are a number of laboratory role, prevention of the disease remains the
tests that can confirm the diagnosis. Detection of only way to halt the occurrence of congenital
virus in a body fluid within the first 3 weeks of life CMV infection and thus the potential to develop
confirms the diagnosis of congenital CMV. Since CP. The Centers for Disease Control and
infected newborns continue to shed virus for a Prevention (CDC) recommends that pregnant
long period of time, it is easily detected in fluids woman reduce their exposure to CMV and thus
such as urine and saliva. The preferred method of risk of fetal infection with good handwashing,
detection to confirm the diagnosis of congenital minimizing exposure to body fluids that might
CMV infection is urine shell vial culture which contain CMV, and practicing standard precau-
utilizes the cytopathic effect the virus has on tissue tions. The use of CMV immune globulin therapy
50 N. Rellosa
in pregnant women with primary CMV infection area, 79% of those children had CP associated
to reduce fetal transmission and infection is cur- with their infection (Engman et al. 2008).
rently being studied but is not currently routinely In another small study, HSV-2 encephalitis as
administered for prevention (Pass 2018). compared to HSV-1 infection seemed to be more
frequently associated with CP, with 64% of those
infants having CP (Corey et al. 1988).
Herpes Simplex Virus (HSV) and Other Other herpes viruses that have been implicated
Human Herpes Viruses in causing CP in the perinatal period of life based
on isolation of the virus in CSF include VZV,
HSV infection, specifically involving the central EBV, HHV-6, HHV-7, and HHV-8, although
nervous system (CNS) in neonates, has also been data is limited (Gibson et al. 2006; McMichael
associated with CP. Herpes simplex viruses, both et al. 2012).
HSV-1 and HSV-2, are double-stranded DNA
viruses. Although both types can be associated Testing, Treatment, and Outcomes
with maternal genital infection, historically, In addition to clinical correlation, the diagnosis of
HSV-2 has more commonly been found to cause neonatal HSV CNS disease can be made with
disease in neonates. Neonatal HSV infection evidence of the virus in body fluid. Isolation of
can clinically manifest in three different ways: HSV from culture or DNA PCR assay in whole
(1) localized skin, eyes, and mouth disease blood sample; specimens from the mouth, naso-
(SEM disease), (2) disseminated disease involv- pharynx, conjunctivae, and anus; or specimens
ing multiple organ systems usually including the from skin vesicles can confirm the diagnosis.
liver, and (3) CNS disease, or sometimes referred However, specifically with CNS disease, isolation
to as HSV encephalitis. Approximately 30% of of HSV in CSF defines the disease. Additional
all neonatal HSV infections are CNS disease, diagnostics that can be helpful include neuroim-
although 60–75% of all disseminated diseases aging and electroencephalogram (EEG) showing
will have CNS involvement too (AAP 2015a). abnormality or seizure activity usually within the
Transmission of infection from mother to child temporal region of the brain.
usually occurs during the peripartum period (85% Treatment with antiviral therapy may be help-
of the time) with exposure to active maternal ful to the overall outcome of infants affected by
herpes lesions, although often lesions may not be HSV infection. However, infants with CNS dis-
seen. Similar to CMV, the risk of transmission is ease still might suffer from CP despite receiving
greater with maternal primary infection. The risk appropriate antiviral therapy (Corey et al. 1988;
of transmission for mothers with recurrent genital Engman et al. 2008). Current treatment
HSV infection is only 2% (James and Kimberlin recommendations call for parenteral acyclovir
2015a; Brown et al. 2003). (60 mg/kg per day in three divided doses) for a
Neurologic manifestations from CNS disease minimum of 21 days (AAP 2015a). Following
can include microcephaly, intracranial calcifica- initial therapy, suppressive therapy with oral acy-
tions, and hydranencephaly. Clinically, CNS dis- clovir improves neurodevelopmental outcomes
ease presents later than SEM or disseminated and helps prevent recurrence of skin lesions
disease, usually presenting after 2 weeks of life. (Kimberlin et al. 2011). Maternal interventions
Infants with CNS disease may present with irrita- for prevention of transmission include the use of
bility, poor feeding, lethargy, seizures, and fever suppressive acyclovir therapy and Cesarean deliv-
or temperature instability. ery in a mother with active lesions (ACOG Com-
A specific association of neonatal HSV CNS mittee on Practice Bulletins 2007). Recently, the
disease or encephalitis with CP has been American Academy of Pediatrics (AAP) has
described. In a small study conducted in children offered guidance on the management of asymp-
diagnosed with neonatal HSV encephalitis born tomatic neonates born to women with active gen-
over a 12-year period in the Stockholm, Sweden, ital herpes lesions that gives a detailed algorithm
calling for specific diagnostics and treatment of including enteroviruses and parechoviruses from
the exposed infant based on maternal serology and one CSF specimen when meningitis or encephali-
infection classification (Kimberlin et al. 2013). tis is suspected, are now commercially available.
If available, these diagnostics should be utilized
when evaluating neonates with concern for CNS
Enteroviruses and Parechoviruses infection to make a definitive diagnosis of entero-
viral or parechoviral infection. In addition, neuro-
In addition to herpesviruses, members of the imaging looking for white matter damage can be a
Picornaviridae family such as human enterovi- useful tool diagnostically.
ruses and parechoviruses have been associated Although anecdotal use of intravenous immu-
with neonatal infection that leads to the develop- noglobulin therapy has been reported in patients
ment of CP. Enteroviruses, especially group B with severe disease such as severe neonatal infec-
coxsackievirus serotypes 1–5 and echovirus sero- tion, its efficacy has yet to be definitively proven
types 6,9, and 11 are responsible for most neonatal (AAP 2015a). Currently, there are no specific
enteroviral infections (Messacar et al. 2018). therapies for infections from enteroviruses or
More recently, parechoviruses, specifically parechoviruses.
parechovirus serotype 3, have also been reported
to cause infection in neonates clinically similar to
enteroviral infection. Emerging Viruses: Chikungunya Virus
Transmission is usually acquired vertically and Zika Virus
within the first 10 days of life from infected
mothers who may have had a preceding mild Since the early 2000s, there have been several
illness with fever and abdominal pain late in preg- emerging viruses causing serious infections. In
nancy. As opposed to older patients who may addition to the concern for the effect of these
have mild types of infection, in the neonate, infec- infections on the general population, there has
tion with these viruses can be severe and life- been particular concern for their effect on new-
threatening. borns and young infants via vertical transmission.
Clinical presentation in the neonate can Many cases have been reported of perinatal trans-
vary from mild febrile illness, exanthema, and mission of these viruses with neurologic and
aseptic meningitis to more severe cases that can neurodevelopmental effects including CP; how-
include hepatitis, myocarditis, and encephalitis. ever, data remains limited. Here the two most
Encephalitis caused by enterovirus or reported viruses will be discussed: chikungunya
parechovirus has been associated with white mat- virus and Zika virus.
ter damage or PVL based on neuroimaging. Chikungunya virus is an RNA alphavirus
As previously discussed, this damage is not nec- belonging to the Togaviridae family that is trans-
essarily due to direct viral invasion but due to mitted by the Aedes aegypti and Aedes albopictus
pro-inflammatory cytokine response. This white mosquitoes. Although outbreaks have been
matter injury has also been associated with the reported all over the world including countries
development of CP in some neonates (Verboon- in Asia, Africa, and Europe, infections first
Maciolek et al. 2008; Wu et al. 2014). appeared in the Americas in 2013 (Staples and
Powers 2018).
Testing, Treatment, and Outcomes In older people, infection with chikungunya
Detection of viral RNA in body fluids such as usually presents as acute fever and polyarthralgia.
CSF, serum, and respiratory secretions with However, reported presentations in neonates have
specific PCR assays for both enterovirus and included varying symptoms including fever, rash,
parechovirus can confirm the diagnosis when edema, and intracerebral and gastrointestinal
correlated with clinical presentations. Diagnostic hemorrhage. Neurologic findings include enceph-
PCR assay panels that test for multiple pathogens, alitis and severe encephalopathy with associated
52 N. Rellosa
seizures (Staples and Powers 2018). In a recently Neonatal Bacterial Pathogens

reported case, suspected perinatal transmission of
chikungunya was associated with encephalitis Bacterial pathogens that cause maternal infection
leading to microcephaly, optic atrophy, white mat- (chorioamnionitis, vaginosis, genitourinary tract
ter loss, and what the authors describe clinically as infections) leading to perinatal infection including
CP (Ramos et al. 2017). In a cohort study of in the postnatal period (neonatal septicemia
perinatally infected children compared to and meningitis) can be considered infectious etiol-
uninfected matched peers on Reunion Island, ogies of CP (▶ Chap. 7, “Postnatal Causes of Cere-
poor neurocognitive outcomes were significantly bral Palsy”). The most common pathogens to cause
more frequent in infected children, with some early-onset neonatal bacterial infection (within the
children showing white matter damage on MRI first 7 days of life) including sepsis and CNS infec-
and some children meeting the definition for CP tion are Group B Streptococcus (GBS) and
(Gerardin et al. 2014). Escherichia coli. Less common early-onset patho-
Zika virus is a single-stranded RNA flavivi- gens include Listeria monocytogenes, Haemophilus
rus similar to dengue virus and yellow fever influenzae, Enterococcus spp., and other strepto-
virus. In recent years, this virus has been asso- cocci. Common pathogens that cause late-onset
ciated with outbreaks in Asia, Africa, and the neonatal bacterial infection (from 7 to 89 days of
Americas. In 2015, based on data on hundreds life) are coagulase-negative staphylococci and
of thousands of suspected cases of infection in Staphylococcus pneumoniae and Gram-negative
Brazil including perinatal transmissions, an bacteria such as Klebsiella spp. and Enterobacter
association between Zika virus infection and spp. (Edwards and Baker 2018).
microcephaly in children was found (Schuler- Clinical signs of bacterial septicemia and men-
Faccini et al. 2016). Other neurologic findings ingitis in a newborn can vary and can be subtle.
that have been reported have included intracra- Infected neonates commonly present with temper-
nial calcifications, neurodevelopmental delay, ature instability, lethargy, poor feeding, and respi-
and neurocognitive deficits (Jelin et al. 2016). ratory distress.
These findings have led to an increasing con-
cern for a link between Zika infection and the Testing, Treatment, and Outcomes
development of CP in affected children. As Obtaining bacterial cultures from blood, CSF,
more is known about these emerging viruses, urine, and other clinically relevant sites prior
hopefully their relation to CP will be better to the initiation of any antimicrobial therapy
understood. is essential to making the diagnosis. Empiric
broad-spectrum antibiotic therapy should be
Testing, Treatment, and Outcomes initiated, while culture results are pending and
If these viral infections are suspected clinically narrowed to definitive pathogen-specific therapy
and epidemiologically, detection of virus-specific when the bacteria are identified.
antibody in serum, CSF, or other tissues can be Prevention includes early and appropriate
used to confirm the diagnosis. PCR testing has treatment of maternal infections during pregnancy
also been utilized, but it may have limited avail- and, in the case of GBS, administration of
ability. In most cases, coordination with local intrapartum chemoprophylaxis.
or state health departments or national agencies
may be required to perform specific laboratory
diagnostics. Other Pathogens to Consider
Currently there are no antiviral therapies avail-
able for either chikungunya or Zika virus infec- Other pathogens can cause congenital infection
tion. Vaccines are in development, but the main that cause insult to the brain and thus affect
strategy of prevention is avoiding exposure to neurodevelopment and potentially cause CP.
mosquitoes that transmit these viruses. Toxoplasma gondii, Rubella virus, and syphilis
congenital infection can cause cerebral and neu- Bear JJ, Wu YW (2016) Maternal infections during preg-
rologic findings such as microcephaly and calcifi- nancy and cerebral palsy in the child. Pediatr Neurol
57:74–79. https://doi.org/10.1016/j.pediatrneurol.
cations and have also been implicated in the 2015.12.018
development in CP in children (Bale Jr 2009). Brown ZA, Wald A, Morrow RA et al (2003) Effect of
Perinatal infection of human immunodeficiency serologic status and cesarean delivery on transmission
virus (HIV) can cause encephalopathy with asso- rates of herpes simplex virus from mother to infant.
JAMA 289(2):203–209
ciated clinical findings similar to CP such as spas- Corey L, Whitley RJ, Stone EF et al (1988) Difference
tic diplegia (Langerak et al. 2013). However, between herpes simplex virus type 1 and type 2 neonatal
since this encephalopathy is not static and may encephalitis in neurological outcome. Lancet 1
improve with treatment with antiretroviral medi- (8575–6):1–4
Dakovic I, da Graça AM, Folha T et al (2014) Clinical
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Neurol 5:618–623. https://doi.org/10.1016/j.ejpn.
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Edwards MS, Baker JC (2018) Bacterial infections in the
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000000001690
Perinatal Stroke as an Etiology of
Cerebral Palsy 5
Nidhi Shah and Gregory C. Griffin
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
Risk Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56
Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
Acute Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60
Chronic Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
Prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
Complications of Stroke and Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
Abstract thrombophilic microenvironment: infections,

Cerebral palsy is a group of heterogeneous trauma, cardiac disorders, blood disorders,
disorders with a broad range of developmental and placental disorders. Thus, the evaluation
outcomes and a spectrum of neurologic impair- of a pediatric patient with perinatal stroke
ment. In the past, several studies had suggested should include a comprehensive workup
thrombophilia as an etiology for perinatal assessing the mother, infant, and, if possible,
stroke. However, as new evidence accumu- the placenta. Currently, there is no strong evi-
lates, we know that perinatal stroke is due to dence for treatment with antiplatelet or anti-
multifactorial etiologies. Multiple fetal and thrombotic agents for patients with perinatal
maternal risk factors can contribute to a stroke except for those with a cardiac comor-
bidity or venous sinus thrombosis. The overall
treatment is largely supportive care. The focus
N. Shah (*) · G. C. Griffin
Wilmington, DE, USA
e-mail: nidhi.shah@nemours.org; ggriffin8@msn.com

https://doi.org/10.1007/978-3-319-74558-9_5
56 N. Shah and G. C. Griffin
of preventative care is on improving the quality Natural History

of life for the pregnant mother as well as the
child and maintaining a heart-healthy lifestyle Epidemiology
to prevent secondary cardiac etiologies.
Future research is needed to further evaluate Perinatal stroke is the most common cause of
possible etiologies, such as maternal risk fac- hemiplegic cerebral palsy (Kitai et al. 2016). Arte-
tors, environmental risk factors, and fetal risk rial ischemic stroke typically presents within the
factors, as they relate to the timing of insult to first few days of life, while venous infarctions are
the developing fetus. diagnosed later in childhood, usually secondary to
neurologic impairments or developmental delay
Keywords (Curtis et al. 2017). The neonatal period is defined
Thrombophilia · Perinatal · Factor V Leiden · as the period between birth and 28 days of life.
Arterial · Stroke The incidence of neonatal arterial ischemic stroke
is about 1 in 2300 to 1 in 5000 live births. This
etiology is more common in preterm newborns,
Introduction with a male predominance. The diagnosis of peri-
natal ischemic stroke is made based on clinical
Cerebral palsy is a heterogeneous disorder with a signs and symptoms and confirmed via neuroim-
broad range of developmental outcomes from aging or neuropathologic studies on and after the
mild to severe neurologic impairment. There are 29th day of life. Previously, perinatal arterial
many risk factors for cerebral palsy including infarction was labeled as the more common etiol-
infection, genetic abnormalities, maternal compli- ogy, but now perinatal venous infarction is
cations, and stroke. Perinatal stroke has been deemed more common. The incidence of peri-
defined as a cerebrovascular event that occurs ventricular infarction is unclear, but at least
between 28 weeks of gestation and 28 days of two-thirds of pediatric patients with presumed
postnatal age (Lynch et al. 2002). Perinatal stroke periventricular ischemic stroke had perinatal
can be arterial versus venous in origin. Peri- venous infarcts. About 40% of these patients
ventricular venous infarctions (PVI) are typically were born at term, with developmental delay and
much smaller and affect the subcortical white neurologic impairments noted prior to 3 years of
matter in utero. In contrast, lesions secondary to age (Kitai et al. 2016).
arterial ischemic stroke are most commonly due to
large occlusions of the middle cerebral artery ter-
ritory affecting the cortical and subcortical areas, Risk Factors
likely due to insults acquired near the time of birth
(Kuczynski et al. 2016). Thrombophilia in the While individual thrombotic risk factors show no
mother or the child may increase the risk of stroke absolute increased risk in very preterm infants,
in the child. Thrombophilia in the mother may multiple risk factors can contribute to the devel-
have effects on the fetus directly or due to placen- opment of cerebral palsy (Table 1) (Nelson 2006).
tal abnormalities. Maternal thrombophilia, not fetal or childhood
An imbalance of the coagulation cascade thrombophilia, was found to pose a higher risk
can lead to disorders causing thrombophilia or for development of cerebral palsy not associated
bleeding. Some of the more common disorders with a thromboembolic event. This could be due
associated with thrombophilia are activated pro- to increased risk of intervillous or spinal artery
tein C resistance which is most commonly due to thrombosis and placental infarction on the mater-
the factor V Leiden mutation, protein C defi- nal side of the placenta (Reid et al. 2006).
ciency, protein S deficiency, antithrombin III The most common coagulation abnormality
deficiency, and prothrombin gene mutations leading to a clotting disorder is activated protein
(Lynch et al. 2002). C (APC) resistance due to the factor V Leiden
5 Perinatal Stroke as an Etiology of Cerebral Palsy 57
Table 1 Risk factors for development of perinatal stroke 1997). Recent studies have shown that the rate of
Maternal Primiparity the factor V Leiden mutation, either heterozygous
Infertility or homozygous, in term neonates with cerebral
Chorioamnionitis, other infections palsy is comparable to the general population
Prolonged rupture of membranes
Preeclampsia (Curtis et al. 2017; Gibson et al. 2003). However,
Intrauterine growth retardation preterm infants with homozygous factor V Leiden
Exposure to drugs, toxins, alternative mutation may have an increased risk for quadri-
medications plegia (Gibson et al. 2003).
Thrombophilias
Twin-to-twin transfusion syndrome Prothrombin gene 20210 mutation is also
Autoimmune disorders known as factor II mutation (Varga and Moll
Placental Placental thrombi 2004). There is a guanine to adenine substitution
Placental abruption at the 20210 location in the 30 untranslated region
Placental infection of the gene encoding prothrombin, and this causes
Fetomaternal hemorrhage
Placental chorioangioma elevated levels of prothrombin protein. This leads
Neonatal Cardiac abnormalities to a dysregulation in the coagulation cascade lead-
Infections ing to an increased risk of thrombosis (Gibson
Vascular malformations et al. 2003). A homozygous mutation in the
DIC
methylenetetrahydrofolate reductase (MTHFR)
Meconium aspiration
Dehydration gene at C677T location leads to decreased enzy-
Mechanical compression of the superior matic activity and increased levels of homocyste-
sagittal sinus by the occipital bone ine (Cattaneo et al. 1997). The combination of
Thrombophilias
heterozygous prothrombin gene mutation and
– Deficiency of protein C
– Deficiency of protein S homozygous MTHFR C677T polymorphism has
– Factor V Leiden heterozygous mutation been linked to cardiovascular disease and venous
– Prothrombin 20210 heterozygous thromboembolism; it is unclear whether this
mutation
directly leads to the development of cerebral
– MTHFR C677T homozygous mutation
– MTHFR C677T/A1298C heterozygous palsy. About 6–12% of the general population
mutation has MTHFR mutation at the C677T location or
– Elevated serum lipoprotein(a) A1298C location, which is less common (Gibson
– 4G polymorphism of plasminogen
et al. 2003). Data from the study done by Gibson
activator inhibitor 1
– Antiphospholipid antibodies et al. in 2003 showed that the risk for quadriplegic
– Beta-2-glycoprotein antibodies CP increased 5 times in patients of all gestational
Cord abnormalities ages with heterozygous prothrombin gene muta-
Polycythemia
tion and homozygous MTHFR C677T mutation
Others Trauma
Instrument-assisted extraction
when compared to the general population. There
Catheterization was also a positive association between heterozy-
Extracorporeal membrane oxygenation gous prothrombin gene mutation and diplegic CP
(ECMO) in preterm neonates born at 32 to 36 weeks. Sim-
ilar significant positive association was noted
between very preterm infants with homozygous
mutation. The prevalence of APC resistance is MTHFR mutation and CP. However, no associa-
about 2–7%, and it is 10 times more common tion was found between thrombophilia and devel-
than deficiencies of protein C, protein S, or anti- opment of CP in term infants (Gibson et al. 2003).
thrombin III. The factor V Leiden mutation Antiphospholipid antibodies are a group of
replaces the arginine with glutamine at cleavage antibodies that can increase the risk for thrombo-
sites for APC on factor Va. This leads to a mutated sis. Evaluation for antiphospholipid syndrome
factor that has more of a procoagulant activity and includes testing for anticardiolipin antibodies,
is ultimately resistant to APC (Thorarensen et al. beta-2 glycoprotein I (β2GPI), and lupus
anticoagulant. Anticardiolipin antibody has been Pathophysiology

proposed as one risk factor for ischemic stroke in
the fetus and neonate (Golomb et al. 2001). Ele- As noted in Fig. 1, the pathophysiology of throm-
vated titers (>1:100) of antiphospholipid anti- bus formation follows the principles of Virchow’s
bodies have been shown in 13% of children with triad: hypercoagulable state, endothelial injury,
cerebral palsy compared to 0% in controls (Nel- and venous stasis. However, thrombus formation
son et al. 1998). However, recent data shows that and subsequent coagulopathies are complex with
neonatal strokes are not exclusively associated multifactorial etiologies (Wolberg et al. 2012). A
with antiphospholipid antibodies and that other hypercoagulable state is promoted by increased
prenatal and perinatal etiologies are involved procoagulants, such as prothrombin and fibrino-
(Peixoto et al. 2014). gen. Abnormalities of anticoagulant proteins,
The presence of at least one prothrombotic fac- resistance to inactivation, fibrinolysis inhibitors,
tor increases the risk of perinatal stroke in a term and clotting factor activity are also possible
neonate by up to 68% (Fernandez-Lopez et al. contributors to a thrombotic microenvironment.
2014). This risk is further augmented in patients Endothelial injury is mediated by recruitment
with congenital heart disease and maternal history of leukocytes and platelets via cellular
of prothrombotic disorders. Congenital and adhesion molecules, such as P-selectin glycopro-
acquired prothrombotic states have been impli- tein ligand-1. Concurrently, active cellular tissue
cated in up to 50% of neonatal arterial ischemic factor is exposed, signaling the location for
strokes and up to 20% of perinatal venous infarcts assembly of procoagulant complexes. Finally,
(Kirton and deVeber 2006). However, recent data shear stress contributes to the development of
shows no association of factor V Leiden mutation, venous stasis by inducing the expression of vas-
prothrombin gene mutation, or MTHFR mutation cular adhesion molecule-1 and tissue factor
in children with cerebral palsy. While individual (Wolberg et al. 2012).
thrombotic risk factors show no absolute increased There are several proposed mechanisms for
risk in very preterm infants, multiple risk factors ischemic stroke. Thromboembolism from an
can contribute to the development of cerebral palsy intracranial or extracranial blood vessel, congen-
(Nelson 2006). Overall, it appears that hyper- ital heart disease or associated cardiac disorders,
coagulable problems are probably associated with or vascular malformations can all play a role in
stroke and CP when combined with additional creating a disordered microenvironment. Ulti-
factors such as infection. mately, the exact trigger or origin of thromboem-
Infants with congenital heart disease are at an bolism remains unknown (Lynch et al. 2002).
increased risk of thromboembolism due to struc- Subsequent regional ischemia, hypoxia, and
tural abnormalities; the need for diagnostic and infarction lead to a well-defined focal injury to a
surgical procedures further exacerbates this risk. region of the developing brain, sparing the rest of
Older age at time of procedure, longer duration of the parenchyma.
bypass, and reoperation procedures increase the The maternal hemodynamic system is in a
risk of stroke (Lynch 2009). Cardiomyopathy, hypercoagulable state during pregnancy, with
valve disease, and arrhythmias are additional major alterations in the coagulation pathway
factors to consider. Patent foramen ovale, preop- involving decreasing anticoagulation and
erative balloon atrial septostomy, transposition increasing coagulation. There are decreased
of great arteries, single ventricle physiology, levels of protein S and tissue plasminogen
and right-to-left shunts contribute to the develop- along with fibrinolytic activity. There are
ment of venous stroke. Extracorporeal membrane increased levels of factor V; factor VIII, VII,
oxygenation (ECMO) increases the risk of IX, X, and XII; von Willebrand factor; and
development of cerebral sinovenous thrombosis fibrinogen. Thus, the coagulation cascade is
and arterial ischemic stroke (Kirton and tilted in favor of thrombosis (Curry et al. 2007;
deVeber 2009). Fernandez-Lopez 2014; Gibson et al. 2003).
Fig. 1 Virchow’s triad

Venous stasis
Hypercoagulability Endothelial injury
This coagulation pathway can further tilt toward processes (Elbers et al. 2011). A more recent
thrombosis in the setting of other maternal risk report showed that placental pathology is more
factors mentioned in Table 1. Drugs, such as common in stroke cases relative to controls. The
cocaine use in particular, have the potential to lesions are subacute to chronic and are likely due
cause hypertension, leading to vasoconstriction to perinatal insults (Bernson-Leung et al. 2015).
and tachycardia. Subsequent interruption of Neonatal circulation has high hemoglobin and
blood flow to the fetus leads to decreased oxy- hematocrit levels with decreased serum activity
gen delivery with chronic hypoxia and disrup- levels of protein S and protein C. The addition of
tion of normal central nervous system normal shearing forces during labor and delivery
development (Arendt et al. 2013). Infections, creates endothelial injury in a setting of venous
such as chorioamnionitis, activate the inflamma- stasis (Curry et al. 2007; Lehman and Rivkin
tory cascade, causing cerebral infarction through 2014). Post-delivery, the neonatal hemodynamic
cytokine-mediated injury. Hyperthermia causes system undergoes dramatic changes in the cardiac
altered cerebral blow flow and increased cellular and pulmonary functions, due to a decrease in
metabolism, leading to release of inflammatory resistance of pulmonary vasculature and increase
cytokines and excitotoxic products, with hemo- in resistance of cardiac vasculature, leading to an
static changes (Kasdorf and Perlman 2013). increase in oxygen concentration and concomitant
There is an increasing focus on studying pla- closure of the foramen ovale as well as ductus
cental abnormalities contributing to perinatal arteriosus, contributing to a relative hyper-
stroke. A recent study of infants with neurologic coagulable state. As a result, the presence of
impairment secondary to cerebral palsy found that fetal hemoglobin, fetal proteins, and a high hemat-
severe fetal chorioamnionitis, extensive avascular ocrit leads to increased blood viscosity and an
villi, and diffuse chorioamniotic hemosiderosis increased risk of stroke.
were independently associated with neurologic The most common infections of the neonatal
impairment. In addition, fetal thrombotic population are meningitis and sepsis. Perinatal
vasculopathy, chronic villitis with obliterative stroke secondary to infection appears to be medi-
fetal vasculopathy, chorioamnionitis with severe ated through a systemic inflammatory response or
fetal vasculitis, and meconium-associated fetal direct invasion of the endothelium. Common asso-
vascular necrosis were also significantly related ciated viral infections are varicella, human immu-
to developing perinatal stroke and subsequent nodeficiency virus, parvovirus B19, and influenza
neurologic impairment (Lehman and Rivkin A (Pavlakis and Levinson 2009). Most commonly,
2014). Twelve patients with symptomatic cerebral the lesions are left-sided owing to the structurally
arterial ischemic stroke or sinovenous thrombosis straight route through the left common carotid or a
had their placenta available for pathologic exam- patent ductus arteriosus (Wu et al. 2005). Addi-
ination; 10 out of the 12 patients showed placental tional risk factors, as mentioned in Table 1, further
pathology, with 6 having thromboinflammatory augment the likelihood of neonatal stroke.
Diagnosis reproducible and predictive of outcome”

(Kirton et al. 2008).
Older children and adults with arterial ischemic 4. Periventricular venous infarction. This type of
stroke typically have focal weakness and altered infarction may be secondary to germinal
mentation as the major presenting features. How- matrix hemorrhage in preterm infants.
ever, focal weakness is not usually noted in new-
borns with perinatal ischemic stroke. These infants Clinical signs and symptoms as previously
typically have seizures, lethargy, apnea, chewing noted should lead to neuroimaging studies. Cranial
or bicycling movements, feeding difficulty, and ultrasound can be helpful for germinal matrix hem-
poor tone. Occasionally they may have asymmetric orrhage and intraventricular hemorrhage, but it is
tone or asymmetric Moro reflex. It is also important not reliable for other forms of stroke (Kirton et al.
to remember that “infants who are diagnosed with 2008; Lynch et al. 2002). Computed tomography
the clinical syndrome of birth asphyxia may have (CT) may be used for arterial ischemic stroke and
suffered a focal arterial infarction rather than the cerebral sinovenous thrombosis. It does not require
more global pattern of deep gray matter or arterial the use of sedation, but it is problematic from the
watershed injury typically seen in hypoxic- perspective of radiation exposure. Magnetic reso-
ischemic brain injury” (Wu et al. 2005). Later in nance imaging is the best choice for diagnosis/
the first year of life, infants who suffered a stroke follow-up of perinatal stroke (Kirton et al. 2008;
may be noted to have hemiplegia, early handedness Lynch et al. 2002). Diffusion-weighted imaging
(Chen et al. 2015), developmental delay, or spas- (DWI) is especially helpful.
ticity. In that instance, it will be described as pre- Advances in neuroimaging have greatly
sumed perinatal ischemic stroke (Curry et al. 2007; improved our ability to detect perinatal stroke, but
Fernandez-Lopez et al. 2014). Hemorrhagic stroke other information is also important. Figure 2 shows
is commonly seen in newborns less than 32 weeks’ evidence of extensive sinus venous thrombosis on
gestation and is due to intraventricular hemorrhage magnetic resonance imaging (MRI). Figure 3 shows
secondary to germinal matrix bleeding. Hemor- extensive hemorrhages within the supratentorial and
rhagic stroke (intraventricular, intraparenchymal, infratentorial compartments as seen on the MRI
or subarachnoid hemorrhage) is not as common scan. A thorough history and physical exam should
in late preterm or term infants (Bruno et al. 2014). include information on early fetal loss, infertility,
Four clinical patterns of perinatal ischemic infection, bleeding, hypertension, growth, bulging
stroke have been defined (Kirton et al. 2008): fontanel, dilated neck veins, papilledema, seizures,
and focal neurologic findings (Kirton and deVeber
1. Symptomatic neonatal arterial ischemic stroke. 2009). A family history should be obtained with a
This is typically associated with the middle focus on information related to thrombosis or risk of
cerebral artery, especially on the left side. The thrombosis. This should include any family history
incidence is similar in term and preterm of cardiac disease, stroke, deep vein thrombosis
infants, and seizures are the most common (DVT), pulmonary embolism, or sickle cell disease.
presenting symptom. Other evaluations should include an echocardio-
2. Symptomatic neonatal cerebral sinovenous gram and CBC. The need for a hypercoagulable
thrombosis. This may present with seizures or evaluation is controversial.
with symptoms of diffuse neurologic dysfunc-
tion. Venous infarction may lead to central
nervous system (CNS) hemorrhage. Treatment
3. Presumed perinatal ischemic stroke. This
entity usually presents between 4 and 8 months Acute Treatment
with seizures or hemiparesis. The middle cere-
bral artery is most commonly involved, but Acute treatment is mainly supportive. This
“refined classification into middle cerebral includes efforts to maintain a normal blood
artery branch subdivisions appears to be sugar, normal electrolyte levels, normal
Fig. 2 This set of images shows extensive venous transverse sinus involved. Choroid plexus hemorrhage is
thrombosis involving the superior sagittal sinus, right also evident in addition to right frontal lobe intramedullary
transverse, sigmoid, and proximal internal jugular venous thrombosis
veins. There is also a small portion of the left proximal
temperature, and normal respiratory status. It also influence the length of therapy. Given the timing
includes treatment of any seizures (Kirton and of perinatal stroke, the use of thrombolytic ther-
deVeber 2009). There is some evidence that hypo- apy is generally not advised. Recent animal data
thermia may be helpful in terms of reducing the indicates that ADAMTS13 (disintegrin and
risk of seizures after a stroke, and this is important metalloprotease type I motif, member 13)
given that “the presence of seizures is associated controls important steps in vascular remodeling
with worse cognitive outcomes for stroke that after stroke and that recombinant ADAMTS13
presents with encephalopathy” (Harbert et al. improves ischemic neovascularization and vascular
2011). Other neuroprotective therapies have repair (Xu et al. 2017). This may provide some
been utilized including antioxidants, anti- avenues for human therapy in the future.
inflammatory agents, and several agents that are
targeted to reduce excitotoxic damage (e.g.,
topiramate). Combinations of hypothermia and Chronic Treatment
other neuroprotective agents are currently being
investigated (Basu 2014). The risk of recurrent stroke appears to be less than
Anticoagulation therapy should be considered 1–2% in patients with arterial ischemic stroke, and
for neonates with cerebral sinovenous thrombosis chronic anticoagulation is generally not advised
or cardioembolic arterial stroke (Monagle et al. unless there are ongoing risk factors such as con-
2008). This therapy would typically continue for genital heart disease (Kirton and deVeber 2009;
at least 3 months depending on the response as deVeber et al. 2017). If non-CNS locations are
noted on repeat imaging studies. Initially low included, then the risk of recurrent thrombosis
molecular weight heparin or unfractionated hepa- may be approximately 3% (Kurnik et al. 2003).
rin is used. Vitamin K antagonists can be used Long-term rehabilitation is important in helping to
when the patient is more stable. The decision to maximize outcomes. “Targeting treatments such
initiate or continue anticoagulation should as facilitating toy exploration with the upper
include consideration of the presence of hemor- extremity, promoting affected side movements,
rhage and the risk of future hemorrhage. It is and promoting bilateral reaching strategies” may
not clear whether the presence or absence of improve overall function (Chen et al. 2015).
hypercoagulable disorders should influence the Constraint-induced movement therapy (CIMT)
decision to start anticoagulation or should where the more functional arm and hand are
Fig. 3 There is evidence of bilateral supratentorial and ischemic injury involving the periventricular white matter
infratentorial subdural hemorrhages, especially along the bilaterally and extending into the left thalamus
left cerebral convexity. The likely etiology is hypoxic
constrained has shown some success (Basu 2014). There is no useful information about the potential
Contrary to common belief, there is information use of anticoagulation in mothers at high risk
that the immature brain has a reduced capacity for of thrombosis (Wu et al. 2005). A randomized,
recovery compared to adults (Fernandez-Lopez controlled trial of magnesium sulfate did not show
et al. 2014). Animal studies are starting to look a statistically significant reduction in the inci-
at the use of stem cells to reduce the degree of dence of cerebral palsy in premature birth
damage after a stroke (Basu 2014). (24–31 weeks) (Rouse et al. 2008).
Prevention Complications of Stroke

and Treatment
Currently, there is no definitive method for pre-
venting perinatal stroke. However, it is reasonable The complications (outcomes) of stroke primar-
to suggest that pregnant women or women ily depend on the anatomic location of the vas-
attempting to become pregnant who are at risk cular insult. Motor deficits may occur in
for thrombosis due to thrombophilia or known 30–60% of arterial ischemic stroke and
thrombotic events in themselves or genetic rela- 30–50% of cerebral sinovenous thromboses
tives may be counseled regarding weight control, (Kirton and deVeber 2009). They may also
smoking, and immobilization (during lengthy occur in greater than 80% of patients with peri-
travel or otherwise). It is also reasonable to keep ventricular venous infarction and presumed
mothers in labor well hydrated since dehydration perinatal ischemic stroke.
is common during labor and is a known risk factor In presumed perinatal ischemic stroke, a
for thrombosis (Nelson 2007). This is especially scoring system based on the anatomic distribution
important given that pregnancy is associated with has been used to predict outcome (Kirton et al.
relative hypercoagulability (Lynch et al. 2002). 2008), as follows:
1. Proximal M1 (PM1) indicates middle cerebral some studies (Kitai et al. 2016). “Ninety-two per-
artery (MCA) and includes lateral cent of children with PVI presented with isolated
lenticulostriate (LLS) arteries. This leads to motor asymmetry” (Kirton et al. 2008).
infarction of the basal ganglia (BG) and more Motor defects are commonly the focus of stud-
distal MCA territory. ies on the treatment of cerebral palsy (CP). How-
2. Distal M1 (DM1) occurs with distal MCA ever, position sense is also often impaired in
thrombosis that is distal to the LLS. It spares children with CP after arterial or venous stroke
the BG and injures the distal MCA territory. (Kuczynski et al. 2016). This study looked at the
3. Anterior trunk (AT) indicates a superior MCA use of an exoskeleton robotic device to assess
infarction that involves the anterior temporal position sense in children after stroke. It did not
lobe and the frontal lobe. look at other issues of proprioception such as
4. Posterior trunk (PT) involves the inferior MCA kinesthesia and sense of force. Children with arte-
division infarction that leads to posterior tem- rial ischemic stroke had more problems with limb
poral lobe and parietal lobe injury. position sense than patients with periventricular
5. Lateral lenticulostriate infarcts involve the venous infarction. These results should be helpful
basal ganglia and posterior limb of the internal in designing plans for rehabilitation.
capsule (PLIC). Treatments for stroke/CP can also cause poten-
6. Periventricular venous infarction (PVI) tial problems. The use of CIMT may cause devel-
involves unilateral periventricular white matter opmental problems in the higher functioning
(PVWM) medullary venous infarction that (normal) arm/hand unless it is utilized carefully.
involves at least four of the following: Focal The use of hypothermia as treatment for stroke
PVWM encephalomalacia, PLIC T2 prolonga- can cause sinus bradycardia and thrombocytope-
tion, cortex spared, hemosiderin, and basal nia (Basu 2014). Anticoagulation can lead to a
ganglia are relatively spared with most of the central nervous system hemorrhage and bleeding
lesion including the more rostral portions of in other sites, especially in the case of trauma.
the PVWM. Patients can have recurrent thrombosis or exten-
sion of existing clots despite anticoagulation.
PM1, DM1, AT, and PT are considered cortical
lesions; LLS and PVI are considered isolated sub-
cortical lesions. Conclusions
Most of the patients had motor disability. The
patients with problematic hemiparesis had PM1 or Isolated thrombophilia as an etiology for perinatal
PVI thrombotic lesions. Extremity motor impair- stroke with subsequent development of cerebral
ment was more common than facial impairment. palsy remains controversial. The consensus is that
Spasticity, behavioral problems, cognitive prob- there is likely a multifactorial etiology involving
lems, and epilepsy were often present. Visual and maternal risk factors, placental abnormalities, and
language problems were also common. “Seizures fetal or neonatal risk factors. The diagnostic
or developmental delay were more common approach should start with a comprehensive his-
presenting concerns in children with cortical tory and physical examination, with laboratory and
involvement” (Kirton et al. 2008). Visual prob- imaging studies to support the suspected diagnosis.
lems were only seen in the cortical group. Seizures Anticoagulants are generally discouraged in the
that required treatment and speech problems acute setting, but may be useful in the chronic
were much more common in the cortical group. setting especially if there are cardiac comorbidities,
Both cortical and subcortical lesions caused such as congenital heart disease. The use of sup-
hemiparesis. Motor problems and spasticity were portive therapies, such as physical rehabilitation, is
also associated with BG lesions. Periventricular also highly recommended. Complications of stroke
venous infarction (PVI) is the cause of 40% of can lead to neurodevelopmental disabilities. Future
hemiplegic cerebral palsy (HCP) in term infants, research is needed to study the aforementioned risk
and it is more common than arterial infarction in factors in greater detail.
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Problems During Delivery as an Etiology
of Cerebral Palsy in Full-Term Infants 6
Patrick Philpot, Jay Greenspan, and Zubair H. Aghai
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
Problems During Birth as an Etiology of CP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
Perinatal and Postnatal Interventions to Reduce the Risk of Cerebral Palsy . . . . . . . . . . . . 74
Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 74
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75
Abstract remained stable. Sentinel events during the pre-

Cerebral palsy (CP) is the most common partum, intrapartum, and neonatal periods and
neuromotor developmental disability in child- their relationship to CP are complex and not
hood. With advances in maternal and neonatal completely understood. This chapter will present
care, perinatal and neonatal mortality have risk factors that occur specifically during the
decreased, but the overall prevalence of CP has intrapartum period associated with but not nec-
essarily causal of CP in full-term infants.
Hypoxic events continue to be the most
P. Philpot (*) consistently implicated etiology but comprise
Thomas Jefferson University, Philadelphia, PA, USA only a small proportion – less than 10% – of
e-mail: Patrick.Philpot@nemours.org
cases of CP. Markers of fetal stress – abnormal
J. Greenspan fetal heart rate tracing and meconium-stained
Nemours/Thomas Jefferson University, Philadelphia,
PA, USA
amniotic fluid – and subsequent low Apgar
scores have been associated with CP. Direct
Department of Pediatrics, Nemours A.I. duPont Hospital
for Children, Thomas Jefferson University, Philadelphia,
damage to the fetal or neonatal brain through
PA, USA intracranial hemorrhage or stroke is also impli-
e-mail: Jay.Greenspan@nemours.org cated as causes of CP. Complications surround-
Z. H. Aghai ing labor associated with CP include uterine
Nemours/Thomas Jefferson University, Philadelphia, rupture, cord around the neck, prolonged labor,
PA, USA abnormal fetal presentation, multiple gestation,
e-mail: Zubair.Aghai@nemours.org; zaghai@nemours.org

https://doi.org/10.1007/978-3-319-74558-9_6
68 P. Philpot et al.
and chorioamnionitis. Placental compromise Hypoxic-Ischemic Injury

via abruption and infarction plays important Hypoxic-ischemic encephalopathy (HIE) is a
and dynamic roles in the development of brain injury in neonates due to inadequate
CP. Through identification of key risk factors blood flow and oxygen delivery to the neonatal
that cause CP, emphasis can then shift toward brain. The incidence of HIE is 1–3 per thousand
their prevention and hopefully a decrease in the term births in developed countries and up to
overall prevalence of CP. 26 times higher in developing countries
(Kurinczuk et al. 2010). The pathophysiology
Keywords of brain injury during HIE is characterized by
Cerebral palsy · Birth · Delivery · Etiology · two phases of energy failure, primary and sec-
Risk factors ondary (Shankaran 2012). Primary energy fail-
ure occurs within minutes and is characterized
by a reduction in cerebral blood flow and oxygen
Introduction supply, leading to depletion of ATP and intracel-
lular acidosis. If the brain injury is severe, it can
Cerebral palsy (CP) is the most common lead to a secondary energy failure with mito-
neuromotor developmental disability in childhood. chondrial dysfunction and a depletion of ATP
CP describes a syndrome characterized by non- without intracellular acidosis. Secondary energy
progressive, permanent motor dysfunction attribut- failure occurs after a latent period of 6–24 h and
able to disturbances in the developing fetal or infant persists for several days. The brain injury during
brain. With advances in maternal and neonatal care, a secondary energy failure is due
perinatal and neonatal mortality have decreased, but to inflammation, glutamate excitotoxicity, and
the overall prevalence of CP has remained stable at oxidative injury leading to the apoptosis of the
between 2 and 3 per 1000 live births. The underly- brain cells.
ing causes of CP are still poorly understood. Senti- In the past, it was widely assumed that HIE is
nel events during the prepartum, intrapartum, and the major intrapartum complication that leads to
neonatal periods and the relationship to the etiology CP. This led to several clinical practice changes
of CP are complex and not completely understood. focused on the prevention of these events with
This chapter will present risk factors that occur early detection methods. These include the
specifically during the intrapartum period – defined increased use of external fetal monitoring among
as the period from the onset of labor through the other modes of antenatal and intrapartum surveil-
third stage of labor. lance that has ultimately led to an increase in
surgical births. The incidence of CP, despite
these advances, has persisted and has led to
Natural History further evaluation of perinatal and intrapartum
risk factors.
Problems During Birth as an Etiology Evaluation of hypoxic events in CP is diffi-
of CP cult as there is no standardized tool for directly
measuring hypoxia. Nonspecific markers, such
Prematurity as abnormal fetal heart rate (FHR) tracings, low
Preterm birth is a major risk factor for CP, and the Apgar scores, need for respiratory support,
risk greatly increases with decreasing gestational neonatal encephalopathy, and meconium-
age particularly prior to 27 weeks (Himpens et al. stained amniotic fluid, are markers of fetal and
2008). Prematurity less than 34 weeks gestation newborn stress that may not necessarily repre-
contributes about 25% of all new cases of cerebral sent asphyxia, and a particular marker has not
palsy. For a more complete overview of the rela- yet been validated (Paneth 2001). In addition,
tionship between premature birth and CP, refer to these nonspecific factors provide poor informa-
Etiology of Cerebral Palsy: Cerebral Palsy and the tion regarding the timing and duration of an
Relationship to Prematurity (Favara et al. 2018). asphyxiating event and may only play a role
6 Problems During Delivery as an Etiology of Cerebral Palsy in Full-Term Infants 69
as individual steps along a broader causal path- compared to ~31% (127/406) in the normother-
way to CP. This distinction is important, as the mia group (Tagin et al. 2012).
initiating factors of the pathway can be targeted
for primary prevention. Locatelli et al. evalu- Low Apgar Scores
ated risk factors associated with infants diag- Apgar score is a widely utilized tool in neonates
nosed with neonatal encephalopathy (NE) to describe an infant’s condition immediately
(Locatelli et al. 2010). Included were antenatal after birth. Moreover, it helps physicians to
factors: obesity, diabetes, thyroid dysfunction, drive the resuscitation process in the delivery
previous Cesarean delivery, preeclampsia, fetal room. Standard practice today includes assigning
growth restriction, abnormal amniotic fluid Apgar scores at 1 min and 5 min after birth for all
volume, and abnormal FHR tracings, and infants and at 5-min intervals thereafter until
intrapartum factors, acute intrapartum sentinel 20 min for infants with a score less than 7. Low
events, suspicious or ominous FHR tracing, and Apgar scores have been associated with
clinical chorioamnionitis. All factors were sig- CP. Although nonspecific markers of peripartum
nificantly related to neonatal encephalopathy stress, 5-min Apgar scores below 4 in term infants
occurrence. Long-term follow-up was not without congenital anomalies have been associ-
reported, but given the significant association ated with neonatal acidemia due to intrapartum
with NE, these risk factors are likely associated hypoxia and neonatal encephalopathy. Krebs
with the etiology of cerebral palsy secondary et al. noted that the risk of CP was highest
to NE. among infants with low Apgar scores born breech
The pattern of injury secondary to HIE may be but that the greater number of infants in their
evaluated by neuroimaging. The correlation study born with low Apgar scores was reported
between neuroimaging and timing of ischemic to be without disability (Krebs et al. 2001). Four
event is controversial, but the location of injury out of 105 (4.6%) breech cases with 5-min Apgar
is important for determining outcome. Okereafor scores below 7 had CP compared to 1 out of
et al. found that basal ganglia and thalamic lesions 218 (0.5%) children in the control group. Another
are the imaging signature in term neonates study reported a strong association between low
exposed to hypoxic-ischemic sentinel events Apgar score and CP where 11% (39/369) of those
(Okereafor et al. 2008). Additionally, patterns of with a score less than 3 at 5 min were diagnosed
central gray matter and secondary white matter with CP, compared to 0.1% (162/179,515) of
injury were associated with higher risk of severe children with a score of 10 (OR 53; 95% CI
morbidity and death. 35–80) (Lie et al. 2010). Furthermore, they
The term “birth asphyxia” was used in the past found an increased association in normal birth
describing HIE. A review of 23 studies that pro- weight compared to low birth weight infants.
vided data on intrapartum risks of CP reported that Children with a birth weight of 2500 g or more
the proportion of CP with birth asphyxia as a with an Apgar score <4 at 5 min were much more
precursor varied widely between 3% and 50% likely to have CP than those who had an Apgar
(Ellenberg and Nelson 2013). The wide variation score of >8 (OR 125; 95% CI 91–70). The
in exposure rate linking birth asphyxia to CP was corresponding OR in children weighing less
attributed to heterogeneity in defining birth than 1500 g was 5 (95% CI 2–9).
asphyxia. By applying more objective criteria
set by the American College of Obstetricians Abnormal FHR Tracing
and Gynecologist (ACOG), an Australian study FHR tracing was first established to detect varia-
reported that only 2 out of 213 cases of tions indicating fetal hypoxia. The early detection
children with CP had isolated acute intrapartum of hypoxia, in turn, alerts caregivers and enables
hypoxic events (Strijbis et al. 2006). The preva- them to intervene rapidly to prevent brain injury
lence of CP in neonates with moderate to severe and death of the fetus. Nelson et al. found charac-
HIE enrolled in a therapeutic hypothermia trial teristics of FHR associated with increased risk of
was 19% (92/475) in the hypothermia group CP, which included multiple late decelerations
and decreased beat-to-beat variability of the fetal risk in infants with meconium aspiration syn-
heart rate (Nelson et al. 1996). Multiple late decel- drome (all CP, two studies, RR range 10.3–15;
erations were associated with nearly a quadru- term CP, two studies, RR range 25–27) (Mcintyre
pling of the risk of cerebral palsy (OR 3.9; 95% et al. 2013). Although meconium signifies
CI 1.7–9.3) and decreased beat-to-beat variability fetal stress, it is not specific for asphyxia
with nearly a tripling of the risk (OR 2.7; 95% CI (Paneth 2001).
1.1–5.8). They also reported that the occurrence
of multiple late decelerations, decreased beat-to- Intracranial Hemorrhage
beat variability, or both abnormalities was associ- Neonatal intracranial hemorrhage (ICH) has
ated with a marked increase in the risk of CP five major clinical types: subdural hemorrhage
(OR 3.6; 95% CI 1.9–6.7). Similar results regard- (SDH), subarachnoid hemorrhage (SAH), cere-
ing decreased beat-to-beat variability were noted bellar hemorrhage, intraventricular hemorrhage
in a Turkish population of 101 term infants with (IVH), and intraparenchymal hemorrhage. SDH
CP compared to 308 controls ( p < 0.02) (Gurbuz and intraparenchymal hemorrhage are more
et al. 2006). A Japanese study reported signifi- common in term infants. Proposed mechanisms
cantly increased trials of instrumental delivery, for ICH have included tears of the falx and
C-sections, and suboptimal care as defined as tentorium or bridging cortical veins secondary
delayed reaction due to misinterpretation of fetal to stretching, difficult delivery, or abnormal
heart rate (FHR) tracings in infants with neonatal labor. One suggested mechanism of hemorrhage
encephalopathy leading to CP compared to after vaginal delivery is that increased circum-
healthy controls (Yamada et al. 2015). The ability ferential pressure and squeezing of the head in
to monitor for hypoxia showed great promise as a the birthing canal results in overlap at the
means to prevent subsequent morbidity and mor- sutures, mechanical compression, and shearing
tality. However, prevention may only occur for of the bridging veins during delivery, resulting
acute events and may not affect states of chronic in SDH.
hypoxia. With increased use of FHR, the rate of ICH has been shown to have significant effects
Cesarean section increased with a resultant on neurodevelopmental outcome of infants, par-
increase in maternal morbidity without a decrease ticularly those born prematurely. Cranial imaging
in rates of CP (Nelson et al. 1996). Abnormal is not a part of routine clinical management of
FHR may not have led to an overall decrease in infants in the term nursery; therefore the actual
CP rates because it may have been caused by prevalence of ICH in this group is unknown. In
pre-existing brain injury rather than asphyxia. children with CP, the incidence of ICH was 20%
For this reason, the increase in Cesarean section (Looney et al. 2007). Brouwer et al. evaluated
did not have an effect on CP rates. ICH with parenchymal involvement diagnosed
with neuroimaging (Brouwer et al. 2010). They
Meconium-Stained Amniotic Fluid reported a 24.5% mortality rate and the develop-
Meconium-stained amniotic fluid is present in ment of CP in 8.6% of term infants diagnosed with
3–14% of all deliveries. The presence of meco- ICH with parenchymal involvement. They further
nium in the amniotic fluid at the time of delivery showed that infants with supratentorial ICH
has long been known as a marker for fetal distress. trended toward lower mortality rates compared
Meconium-stained amniotic fluid is associated to those with infratentorial ICH and those with
with a significant increase in the risk of spastic a combination of supra- and infratentorial ICH.
CP (Nielsen et al. 2008). McIntyre et al. reported Hirtz et al. found strong associations between CP
similar results in all studies evaluated in their and IVH, periventricular leukomalacia (PVL),
meta-analysis, showing significant increases in and intracerebral echolucency or echodensity
all CP (two studies, RR range 1.8–3.8) and CP diagnosed with cranial ultrasound (Hirtz et al.
in term infant (six studies, RR range 1.3–5.3) 2015). Towner et al. studied the use of instrumen-
related to meconium-stained fluid and a higher tal delivery and the rate of IVH and found that the
rates of ICH were low with all modes of delivery impairment, and 45% with seizures. Similar
but were higher with vacuum extraction, forceps results were found by Senbil et al. where a coag-
delivery, and Cesarean delivery during labor com- ulation abnormality was found in 57% of cases of
pared to spontaneous vaginal delivery (Towner hemiplegic CP in a Turkish cohort (Senbil et al.
et al. 1999). 2007). Reid et al. found a significantly increased
rate of factor V Leiden mutation in children with
Perinatal Stroke CP due to thrombosis compared to the general
Neonatal stroke, including perinatal arterial population but no significant difference when
ischemic stroke and cerebral sinovenous throm- compared to children with CP of other origin
bosis, remains a serious problem in the neonate (Reid et al. 2006). For a more complete overview
and is one of the most common identifiable of the relationship between stroke and CP, refer to
causes of CP. Perinatal stroke is defined as a Etiology of Cerebral Palsy: Perinatal Stroke as an
cerebrovascular event that occurs between Etiology of Cerebral Palsy (Shah and Griffin
28 weeks gestation and 7 days of age and includes 2018).
strokes that occur in utero. Perinatal stroke typi-
cally occurs in term infants and is caused by Abnormal Labor
thromboembolism from an intracranial or extra- Abnormal labor duration has also been shown to
cranial vessel, the heart, or the placenta or results have a noncausal association with a diagnosis of
from vasoconstriction or direct compression of CP. Total length of labor beyond 20 h (OR 3, 95%
intracranial vessels. Hyperviscosity syndromes CI 1.12–8.14) and prolonged second stage of
and coagulation factor abnormalities (protein C labor (OR 2.4, 95% CI 1.12–4.48) were shown
deficiency, increased lipoprotein A, methylene to be significantly associated with spastic CP in
tetrahydrofolate reductase (MTHFR) mutation, term infants (Nielsen et al. 2008). Additionally,
prothrombin 20210A mutation, and factor V Lei- induction of labor has been shown to be signifi-
den mutation) can also lead to clotting or hemor- cantly associated with increased risk of CP
rhage causing stroke. The placenta – as a low (Mcintyre et al. 2013).
pressure system – is a common location of throm-
bosis. Thrombosis on the fetal side can create Umbilical Cord Complications
emboli that can bypass the hepatic and pulmonary Umbilical cord and placental complications con-
circulation and travel to the fetal brain (Lynch and tribute to another group of risk factors included in
Nelson 2001). the pathway to CP. The most common complica-
Golomb et al. evaluated infants from a perina- tion, cord around the neck, has been implicated
tal stroke database in the United States and noted with a significantly increased risk for CP across all
68% of children with perinatal stroke had CP, gestational ages but has been inconsistent in stud-
mostly hemiplegic. Furthermore, their analysis ies involving term infants only. Nielsen et al.
showed that during the neonatal period, bilateral reported a significant increase in CP risk with
infarcts were associated with triplegia or quadri- cord around the neck (OR 1.9, 95% CI
plegia (Golomb et al. 2008). Curry et al. evaluated 1.09–3.21) (Nielsen et al. 2008). McIntyre et al.
the risk factors for perinatal arterial stroke, specif- found inconsistent results in normal birth weight
ically those known to cause thrombotic events term infants (three studies, RR range 1–2.3). Of
(factor V Leiden, prothrombin 20210, MTHFR note, tight nuchal cord, alone, has not been signif-
C677T and A1298C, protein C, protein S, anti- icantly linked to CP (Mcintyre et al. 2013). Other
thrombin III, lipoprotein(a), and maternal anti- umbilical cord problems, such as cord prolapse,
phospholipid antibodies) (Curry et al. 2007). Of true knot in the cord, long cord, or short cord, have
children with perinatal stroke, prothrombotic fac- been associated in some cases of CP but did not
tors were found in 55% of mothers and 50% of reach significance in a study of 271 Danish infants
affected neonates. Of the 60 infants in this study, with CP compared to controls (Nielsen et al.
78% were diagnosed with CP, 68% with cognitive 2008).
Placental Complications with mild-to-moderate fetal vasculitis, and meco-

nium deposition without vascular necrosis (Red-
Placental Abruption line 2005). Overall, one or more of the four
Placental abruption complicates about 1% of pathologies was identified in 51% of the index
pregnancies and is the most common cause of cases compared to 10% in the comparison group,
late pregnancy bleeding. The impact on the fetus and severe fetal vascular lesions were found in
depends on the severity of the abruption and the 52% of placentas from infants who developed
gestational age. Risk factors implicated in placen- CP. Treatments to prevent infarcts, such as mater-
tal abruption include prior history of abruption, nal treatment with heparin, have shown promise
trauma, cocaine, smoking, multiple gestation, pre- (Dodd et al. 2010), but long-term data are limited.
eclampsia, maternal hypertension, The placenta is not routinely sent for pathology,
thrombophilias, preterm premature rupture of and placental evaluation is limited to specialty-
membranes, advanced maternal age, hydramnios, trained pathologists. However, in a recent total
and intrauterine infection. Intrapartum hemor- population case-control study of CP, in those
rhage, and the subsequent anemia, has shown born at or after 35 weeks gestation, macroscopic
mixed results regarding its role along the pathway examination identified 8.8% of those with spastic
to CP. Thorngren-Jerneck et al. showed a signifi- quadriplegia as having placental infarcts com-
cant risk of CP associated with placental abrup- pared with 2% of matched comparison children
tion (OR 8.58, 95% CI 5.63–13.3) but not with a (Wintermark et al. 2010). The placenta remains an
diagnosis of maternal bleeding (OR 0.90, 95% CI area of great interest for ongoing CP research.
0.7–1.06) (Thorngren-jerneck and Herbst 2006).
Similar findings were found with increased OR Uterine Rupture
for CP in infants born to mothers with placental Uterine rupture is a possible maternal intrapartum
abruption within the context of maternal hyper- complication that increases the risk of hypoxic
tension (Stelmach et al. 2005). injury to the neonate. In a recent World Health
Organization review (WHO 2005), the prevalence
Placental Infarction of uterine rupture in developed countries is esti-
Another example of a distal risk factor in the mated at 1% following previous Cesarean section.
pathogenesis of CP is placental abnormality dur- The frequency of uterine rupture without history
ing pregnancy. Placental infarcts comprise a large of C-section was estimated at about 0.0006%.
proportion of prepartum placental complications, Despite the low incidence of uterine rupture, the
but due to inconsistent pathological evaluation, resultant hypoxia and metabolic acidosis and their
the timing of these infarcts has been questionable. significance in the etiology of CP are included in
Nielson et al. found a significant twofold increase this chapter. In a systematic review, McIntyre
in the risk for spastic CP with placental infarction et al. reported one study without a significant
that was independent of gestational age with an increase in the risk of CP with uterine rupture
almost sevenfold increase in the risk for spastic (Mcintyre et al. 2013).
quadriplegia, specifically, in a cohort of
271 infants with CP in Denmark (Nielsen et al. Instrumentation at Delivery
2008). The sources of the infarcts were Instrumental deliveries, including forceps and
undetermined and were diagnosed macroscopi- vacuum extraction, have been identified as risk
cally by attending midwives. In infants factors for CP during the intrapartum period.
36 weeks gestation with neonatal encephalopa- Specifically in the term population, instrumental
thy, CP or other long-term neurologic outcomes, deliveries and emergency Cesarean sections
Redline found significantly increased rates of four have consistently shown significance regarding
large-vessel pathologies that included fetal throm- their association with but not the cause of
botic vasculopathy, villitis of unknown cause with CP (OR range 1.8–6.8, 95% CI range 1.6–16.6)
obliterative fetal vasculopathy, chorioamnionitis (Thorngren-jerneck and Herbst 2006; Stelmach
et al. 2005; Walstab et al. 2004). Most deliveries Multiple Births

involving instrumentation occur secondary to a Multiple gestation births have been associated
prolonged second stage of labor, whereas most with CP as an indirect risk factor. As the majority
emergency Cesarean sections occur due to failure of multiple gestation deliveries occur prematurely,
to progress or as result of fetal stress and possible the risk of CP in this group is more closely related
hypoxia. This observation suggests that preven- to prematurity. Several studies have shown signif-
tion of these types of delivery through more active icantly increased rates of CP in the surviving twin
management or scheduled Cesarean sections may after co-twin fetal death (Pharoah 2001; Scher
decrease the rates of CP. However, with the et al. 2002). Some of the increased risk of CP in
increase in elective scheduled Cesarean sections twins compared with singletons is associated with
over the last several decades, the incidence of this fetal death of one twin and is probably spe-
cerebral palsy has not changed. Additionally, cific to monochorionic twinning. It is likely that
when compared to spontaneous vaginal delivery, CP in the surviving twin is attributable to prenatal
Cesarean delivery – scheduled or not – had an damage arising from complications of placental
increased association with CP in term infants. vascular anastomoses and hemodynamic changes
Therefore, fetal distress does not appear to from twin-twin transfusion (Pharoah 2001).
be directly related to the development of CP
but may instead be a marker for CP of a Chorioamnionitis
different etiology. Chorioamnionitis has been implicated in the path-
ogenesis of CP, but studies have been inconsistent
Fetal Presentation in identifying its actual role. A meta-analysis in
Fetal presentation at the time of delivery has 2000 examined the association of chorioam-
been heavily debated as a risk factor for CP nionitis with CP and cerebral periventricular
(Mcintyre et al. 2013; Krebs et al. 1999). Studies leukomalacia (cPVL) (WU and Colford 2000).
specifically evaluating this association have var- Despite varying definitions of chorioamnionitis,
ied by country of origin. The Term Breech Trial CP, and cPVL, term infants had significantly
(TBT) changed clinical practice in several coun- increased risk of CP based on clinical and histo-
tries across Scandinavia when it reported lower logic diagnoses of chorioamnionitis in two studies
perinatal mortality and morbidity in breech (Nelson and Ellenberg 1986; Nelson and Grether
fetuses following planned Cesarean delivery 1998). No studies were included evaluating
compared with planned vaginal delivery microbiologic chorioamnionitis. The association
(Hannah et al. 2000). A group of experts in of maternal infection – particularly chorioam-
Norway met following the TBT to review the nionitis, with cPVL and CP points toward
literature and concluded that vaginal breech inflammation and subsequent fetal and neonatal
delivery would still be safe, provided there is brain injury (▶ Chaps. 8, “Animal Models of
careful selection of mothers, qualified clinicians, Cerebral Palsy: What Can We Learn About Cere-
and adequate fetal assessment (Haheim et al. bral Palsy in Humans”, and ▶ 4, “Infectious
2004). Bjellmo et al. concluded that vaginal Etiologies of Cerebral Palsy”). Dammann and
breech delivery, whether spontaneous or Leviton hypothesized that elevated blood and
planned, or Cesarean breech delivery was asso- brain cytokines resulting from maternal infection
ciated with excess risk of neonatal mortality, as lead to central nervous system damage in the fetus
well as for a composite outcome of intrapartum and subsequent cerebral palsy (Dammann
death, neonatal mortality, and CP compared to and Leviton 1998). Although, there has been a
vaginal cephalic delivery (Bjellmo et al. 2017). positive association in preterm infants between
However, the study did not show a statistically intra-amniotic fluid inflammatory cytokines
significant increase in CP among children in and CP, a causal relationship has yet to be
breech position compared to children born in established, and data for term infants are
cephalic position regardless of mode of delivery. sparse (Yoon et al. 1997). A more recent meta-
analysis reported increased histological chorio- or short cervix. Additionally, the use of magne-
amnionitis (RR = 4.26, P < 0.05), as well as sium sulfate and prenatal glucocorticoids has
clinical chorioamnionitis (RR=3.06, P < 0.01) in become the mainstay of management of threat-
term/near-term children with CP (Shi et al. 2017). ened preterm labor but has not shown consistency
As more standardization of the diagnosis, treat- in decreasing the risk of cerebral palsy (Rouse
ment, and evaluation of chorioamnionitis occurs, et al. 2008).
the association between maternal infection and A major advancement in the management of
cerebral palsy will hopefully become clarified. term or near-term infants who suffer from neona-
tal encephalopathy is the use of therapeutic hypo-
thermia. The landmark randomized control trial
Treatment by Shankaran et al. showed a 37% decrease in the
risk of cerebral palsy in those infants >36 weeks
Perinatal and Postnatal Interventions gestation receiving 72 h of therapeutic hypother-
to Reduce the Risk of Cerebral Palsy mia (Shankaran et al. 2005). Similar improvement
in the risk of abnormal neurodevelopmental
Studies investigating the risk factors for CP impairment is seen in other therapeutic hypother-
show a significant association of several that mia trials. As the number of term or near-term
occur during the intrapartum period, as noted infants who benefit from therapeutic hypothermia
above. Those risk factors can further be modi- increases, the next area of research includes those
fied, to see if this can prevent cases of CP. As the infants born before 36 weeks gestation. A recent
rates of CP are decreasing in preterm infants and study by Rao et al. raises caution surrounding the
the majority of cerebral palsy cases occur in term safety of this strategy in this age group and
infants, further studies should focus on this latter requires further investigation (Rao et al. 2017).
group.
Among the most important management strat-
egies in the antepartum period to prevent CP is Complications
treatment of perinatal infection and inflammation.
The association of perinatal infection and resul- Hypoxic events continue to be the most consis-
tant brain damage attributed to inflammatory tently implicated etiology but comprise only a
mediators is an ongoing area of research as previ- small proportion of CP. Markers of fetal stress –
ously discussed. Standardization of the definition abnormal fetal heart rate tracing and meconium-
of chorioamnionitis will also improve the man- stained amniotic fluid – and subsequent low
agement of perinatal infection and possibly alle- Apgar scores have been associated. Direct dam-
viate the resultant inflammatory cascades leading age to the fetal or neonatal brain through intracra-
to cPVL and CP in the child. nial hemorrhage or stroke is also strongly
As about 25% of all cases of CP occur in implicated in the pathogenesis of CP. Complica-
premature neonates, it is logical that interventions tions surrounding labor associated with CP
to prolong gestation or decrease the risk of pre- include uterine rupture, cord around the neck,
term delivery may decrease the risk of CP. Those prolonged labor, abnormal fetal presentation,
interventions shown to have higher levels of evi- multiple gestation, and chorioamnionitis. Placen-
dence include limiting the number of embryos tal compromise via abruption and infarction plays
transferred during in vitro fertilization, smoking important and dynamic roles in the development
cessation during pregnancy, treatment of asymp- of CP. Through identification of key risk factors
tomatic bacteriuria, antiplatelet drugs to prevent associated with CP, emphasis can then shift
preeclampsia, 17α-progesterone, and cervical toward their prevention and ultimately a decrease
cerclage in the context of previous preterm birth in the prevalence of CP.
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Postnatal Causes of Cerebral Palsy
7
Laura Owens, Eileen Shieh, and Abigail Case
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
Infectious Causes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
Trauma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
Stroke . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 81
Neoplasms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
Abstract or illness causing motor development prob-

Cerebral palsy (CP) is the most common motor lems up to the age of 2 years. A significant
disability in childhood. The definition of CP number of cases of CP arise in the postnatal
provides a framework for clinical diagnosis. period, with approximately half of the cases of
However, the underlying clinical presentations postnatal CP caused by infections, and with
and etiologies are widely varied. CP is known head injury and medical/surgical vascular epi-
to be a manifestation of intrauterine patholo- sodes noted to be additional significant causa-
gies, intrapartum complications, and injury or tive factors.
illness in the postnatal period. This chapter will
focus on the postnatal causes. While there is no Keywords
strict consensus on exact ages, most literature Cerebral palsy · Postnatal causes · Infection ·
and current cerebral palsy registries generally Trauma · Vascular injury
include children who have incurred an injury
Introduction
L. Owens (*) · E. Shieh · A. Case
Nemours/AI duPont Hospital for Children, Wilmington,
Cerebral palsy (CP) is the most common motor
DE, USA
disability in childhood. CP has been defined as “a
group of permanent disorders of the development
e-mail: laowens@nemours.org; eshieh@nemours.org;
abigail.case@nemours.org of movement and posture, causing activity

https://doi.org/10.1007/978-3-319-74558-9_7
78 L. Owens et al.
limitation, that are attributed to non-progressive been few studies that examined racial/ethnic dif-
disturbances that occurred in the developing fetal ferences in prevalence, a higher prevalence in
or infant brain” (Rosenbaum et al. 2007). black non-Hispanic children compared with
Rosenbaum et al. continue on to note that the white non-Hispanic children has been reported
motor disorders of CP are “often accompanied for major metropolitan US cities (Pakula et al.
by disturbances of sensation, perception, cogni- 2009). Among studies of CP, spastic subtypes
tion, communication, and behavior; by epilepsy, have been found to be more common, with
and by secondary musculoskeletal problems”. fewer percentages of the ataxic and dyskinetic
This definition provides a framework for clinical subtypes. Less is known currently about the prev-
diagnosis; however, the underlying clinical pre- alence of CP in developing countries due to lim-
sentations and etiologies are widely varied. CP is ited study data and lack of formal registries.
known to be a manifestation of intrauterine The complex nature of prenatal and neonatal
pathologies, intrapartum complications, and brain development allows injury and abnormal
injury or illness in the postnatal period. This chap- development to occur at any time, resulting in
ter will focus on the postnatal causes. the varied etiologies and clinical presentations of
While there is no strict consensus on exact CP. A double hit model theory has been proposed,
ages, most literature and current cerebral palsy suggesting that a genetic or intrauterine condition
registries generally include children who have along with intrapartum or postnatal insult lead to
incurred an injury or illness causing motor devel- the development of CP (Stavsky et al. 2017).
opment problems up to the age of 2 years. Some Given this complicated nature, absolute categori-
clinicians and researchers feel such disorders zation by cause is often difficult or unable to be
related to fetal or neonatal onset should be sepa- firmly attained in many cases (Rosenbaum et al.
rately categorized from post-neonatal acquired 2007). Post-natal CP is felt to account for approx-
motor disabilities fitting the above description. imately 5–18% of all cases of CP, with 13 affected
However, at this time, they generally remain infants for every 100,000 live births (Cans et al.
grouped under the same umbrella (Dammann 2004). This number can vary based on location
and Kuban 2007). Cans et al. also noted a differ- and variations in definition of CP. For example,
ence in severity of CP in the 0–24 month and major risk factors for cerebral palsy in Botswana
25–132 month populations, noting decreased differ from those described in high-resource set-
severity of disability in the older onset population, tings. There is some literature to suggest infec-
and recommending an age cut-off of 24 months tious causes are of higher incidence in resource-
(Cans et al. 2004). A variation is the Australian limited areas. Modifiable risk factors such as
registry, applying the diagnosis of cerebral palsy maternal HIV infection should be targeted as a
to any child acquiring a motor disorder due to a potential strategy to reduce the incidence of cere-
brain-damaging event prior to the age of 5 years. bral palsy in lower resource countries like
In these cases, children with documented events Botswana (Monokwane et al. 2017).
occurring between 28 days and 5 years of age are Infections such as bacterial meningitis and
separately labeled as post-neonatally acquired CP encephalitis are responsible for a significant por-
(Blair and Watson 2006). tion of postnatal CP. In the neonatal period, respi-
Across the various surveillance programs in ratory distress syndrome, bacterial meningitis,
developed countries, estimates of CP prevalence and neonatal seizures were associated with an
overall using live births and neonatal survivors increased incidence of a CP diagnosis. Approxi-
have been comparable, most estimates being 2.0 mately, half of the cases of postnatal CP are
per 1000 (Stavsky et al. 2017). Among related to infectious causes, with head injury and
population-based studies of CP, males have been medical/surgical vascular episodes noted to be
found to have a higher prevalence of CP than additional significant causative factors (Cans
females, with sex ratios ranging from 1.1:1 to et al. 2004). Limited research is available linking
1.5:1 (Pakula et al. 2009). Although there have robust data of individual postnatal causes to the
7 Postnatal Causes of Cerebral Palsy 79
diagnosis of CP; however, the current develop- 2006). Infants in the neonatal intensive care unit
ment of CP registries and databases continues to (NICU) have many risk factors for infection.
be helpful in better understanding the prevalence Compared with older children and adults, infants,
and etiologies of postnatally acquired CP. and particularly premature infants, are relatively
immunocompromised. Patients in the NICU have
intrinsic risk factors for infections due to immu-
Natural History nological “deficiencies” or inadequate develop-
ment of mechanical barriers such as skin and
Infectious Causes gastrointestinal tract mucosa. NICU patients
have extrinsic risk factors for infection such as
Infections have been long noted to be a prevalent prolonged hospitalization, invasive procedures,
cause of brain injury and CP diagnosis in the instrumentation, medical treatments, and concom-
newborn period, both as individual events and as itant medical conditions. Compared with healthy
part of a likely multifactorial diagnosis. Studies full-term infants, patients in the NICU develop
have noted a dominant role of infection as well as abnormal flora, which are frequently multidrug-
a more recent decline in relevance, thought to be resistant, developed under the selective pressure
related to improving public health efforts such as of antibiotics and capable of causing invasive
vaccination for haemophilus influenzae and pneu- disease (Saiman 2002). Higher likelihood of inva-
mococcus (Cans et al. 2004). sive infectious disease can lead to higher likeli-
Noting the double hit theory, maternal infec- hood of developing CP.
tion can lead to increases in certain proteins called
cytokines that circulate in the brain and blood of Viral Infections
the baby during pregnancy. These cytokines in Viral Infections acquired at or after birth may be
turn cause inflammation, which can lead to asymptomatic, produce mild illness, or manifest
increased susceptibility to brain damage in the as severe, life-threatening disease with features
neonatal period. Fever in the mother during preg- including meningoencephalitis, hepatitis, myo-
nancy or delivery also can cause this problem and carditis, pneumonia, and coagulopathy, which
is discussed in ▶ Chap. 4, “Infectious Etiologies can lead to sequelae identified with CP. Cytomeg-
of Cerebral Palsy.” alovirus (CMV), herpesvirus (HSV), and entero-
viruses are a major cause of illness and
Neonatal Sepsis hospitalization in young infants. In term infants,
Neonatal sepsis is a very serious infection linked the clinical course of postnatally acquired CMV
to developing CP. Group B streptococcus (GBS) infection is most often asymptomatic or very mild,
is the primary bacterial pathogen affecting neo- in contrast to preterm infants where clinical symp-
nates, making perinatal infection with it a world- toms are more frequent and can in approximately
wide public health problem (Jeffery et al. 1977). 10% of very low birth weight (VLBW) infants
Although there is no safe, immunogenic vaccine, result in sepsis-like symptoms (Vollmer et al.
there is perinatal infection prevention by 2004). Interestingly, the results of Vollmer et al.
intrapartum chemoprophylaxis. This highlights study suggest that early postnatally acquired
the importance that infection control can have CMV infection via CMV-positive breast milk
in reducing the incidence of postnatal CP, pre- does not have a negative effect on
venting infection either by vaccination or by neurodevelopment and hearing in this group of
chemoprophylaxis. patients. Clinical manifestations of enterovirus
There is a positive association with parity and include fever and nonspecific symptoms, respira-
neonatal problems and a negative one with birth tory and gastrointestinal symptoms, herpangina,
weight, suggesting that children “at risk” neona- hand-foot-and-mouth disease, rashes, myocardi-
tally are more susceptible to postnatal brain- tis, meningitis, encephalitis, and paralytic disease.
damaging events like infections (Blair and Watson Cell culture is the standard method of detecting
80 L. Owens et al.
enterovirus infections, but detection of viral RNA (<5 years of age) due to inflicted blunt impact and
by the polymerase chain reaction offers enhanced or violent shaking (Division of Injury Control,
sensitivity and rapid diagnosis. Standard treat- CDC 1990). Patients are diagnosed based on his-
ment of enterovirus infections of newborns and tory, though not always available or accurate, as
infants is supportive (Abzug and Rotbart 1999). well as clinical findings including intracranial hem-
orrhage, encephalopathy, diffuse axonal and hyp-
oxic-ischemic brain injury, retinal hemorrhages,
Trauma and other associated injuries including fractures,
intra-abdominal trauma, etc. (Ewing-Cobbs et al.
Trauma to the early developing brain is a known 1998). Risk factors for AHT include young mater-
cause of CP; however, it is difficult to fully under- nal age, prematurity, and multiple births (Keenan
stand the prevalence due to variations in diagnosis et al. 2003). Keenan et al. also noted in their study
and age limits used. Localized injury to motor of patients in North Carolina a prevalence of 17 per
areas of the brain as well as global injury or 100,000 children under age 2 and an average age of
hypoxia may lead to deficits that are later classi- injury of just under 6 months.
fied as CP. Trauma or asphyxia during delivery are In a study by Ewing-Cobbs et al., children
other known traumatic causes of CP and are cov- with injuries due to AHT were compared with
ered separately in the chapter entitled ▶ Chap. 6, those with non-inflicted TBI. Children with
“Problems During Delivery as an Etiology of AHT were much more likely to have a prior
Cerebral Palsy in Full-Term Infants.” history of cerebral atrophy and subdural hema-
Traumatic brain injury (TBI) causes significant toma found with the current injury than matched
morbidity and mortality in children. The inci- peers with noninflicted trauma. Studies note that
dence of TBI has two peaks in the pediatric pop- up to 25% of infants die due to their injuries and
ulation: under 5 years of age and again in the 25% are discharged from the hospital with min-
adolescent years. It is the leading cause of death imal or no neurologic sequelae, leaving 50% of
in children greater than 1 year of age, causing these infants with significant medical and neu-
approximately 40% of fatalities in children ages rologic morbidity following injury (King et al.
1–4 years, and results in over 216,000 emergency 2003). In addition, children with AHT were
department visits and 18,000 hospitalizations in noted to have less recovery and greater disability
children under age 4 in the United States (Division on the Glasgow Outcome Scale than the children
of Injury Control, CDC 1990). The most common with noninflicted trauma (Ewing-Cobbs et al.
causes of TBI in the infant population is inflicted 1998). In a 2007 study by Hymel et al., infants
or abusive head trauma (AHT, formerly known as with AHT were found to have lower cognitive
non-accidental trauma or “shaken baby syn- and motor development scores 6 months after
drome”), representing 56% of TBI under 1 year injury than matched noninflicted TBI peers
of age. Falls make up the largest percentage of (Hymel et al. 2007). A study of 25 patients by
TBI in the 1–4 year age group, followed by motor Barlow et al. (2005) in Scotland noted that over
vehicle accidents. In children ages 1–4 years, one-third of children with AHT followed a mean
AHT is a smaller proportion representing 5% of of 59 months were noted to have significant
injuries; however, it is associated with dispropor- neurologic disabilities requiring substantial
tionately more severe injury, and accounts for up long-term support.
to 90% of severe brain injuries in this group Despite significant interest and literature cov-
(Division of Injury Control, CDC 1990). ering pediatric TBI, there is limited information
Abusive head trauma is seen in a subset of stratified by injury severity, age at injury, and
young TBI patients with injury due to inflicted functional recovery and outcome data – including
trauma. AHT is defined as injury to the skull or the connection to cerebral palsy (Babikian and
intracranial contents of an infant or young child Asarnow 2009).
Congenital Heart Defects leukomalacia even before surgical intervention

Congenital heart defects and the surgical repairs (Licht et al. 2009). In a study comparing pre-
they require have been linked to development of and postoperative MRIs, over half of patients
CP. However there is limited information on had ischemic changes consistent with peri-
developmental impairment in complex CHD and ventricular leukomalacia, parenchymal hemor-
the incidence of cerebral palsy in children with rhage, or infarct. The study commented on high
CHD. At the authors’ tertiary care institute serv- rates of resolution of these changes a few months
ing over 2000 cerebral palsy patients yearly, there after surgery. However, knowing that there are
anecdotally appears to be a correlation between often no MRI changes in patients with chronic
CHD and the development of cerebral palsy. New hypoxic or anoxic encephalopathy, follow-up stud-
initiatives, such as the Cardiac Neurodeve- ies focusing on the functional status of these
lopmental Outcome Collaborative created in patients would be quite important (Weiss et al.
2010, have been formed to investigate and imple- 2007).
ment best practices for neurodevelopmental ser- A few studies have investigated the incidence
vices for children with complex CHD. In 2012, of motor dysfunction in the pediatric population,
the American Heart Association, with approval with most studies focusing on examining younger
from the American Academy of Pediatrics, children. In the infant and toddler groups, it is
published a scientific statement on neurodeve- difficult to tease apart other factors (prematurity,
lopmental outcomes in children with CHD, prolonged hospital stays) that may be contributing
acknowledging a higher rate of developmental to a child’s motor delay. A study in 2007 looked at
disorders, developmental delays, and disability the risk of motor impairment in 7–12-year-old
(Marino et al. 2012). However, much of the children born with complex CHD (Holm et al.
published information focuses on cognition and 2007). These children were found to be at a
behavior. 6–11-fold increased risk for impaired motor com-
The population of survivors of congenital heart petence in strength, balance, and dexterity.
disease is small but has been growing with the Though they are not often labeled as such, chil-
advancement of medical and surgical technology. dren with complex CHD with these long-standing
Although there are a multitude of complex con- deficits meet diagnostic criteria for CP based on
genital heart defects (CHD), the most common the definition discussed earlier in this text. Cer-
complex anomalies are often referred to as the tainly more studies need to be performed, as there
five T’s: Tetralogy of Fallot, transposition of the are many confounding variables muddling the pic-
great arteries, total anomalous pulmonary venous ture. There will continue to be opportunity to inves-
connection, tricuspid valve abnormalities, and tigate this correlation longterm as more patients
truncus arteriosus. The CDC reports rates of 1 in with complex CHD are now living into adulthood.
2518, 1 in 3300, 1 in 10,000, 1 in 10,000, and <1 in
10,000, respectively, in 2017 (Reller et al. 2008).
The postnatal period in complex CHD patients Stroke
often involves lengthy hospital stays, including
multiple surgeries, sedation time, and need for Strokes are another recognized cause of CP. Like
intensive care. There are a myriad of confounding trauma, there is variability in data regarding the
factors in the development of motor impairments incidence and prevalence of strokes as a common
in the population. Despite a lack of data, it stands cause of CP. Additionally, some providers may be
to reason that children with CHD are at a higher reluctant to use the term “cerebral palsy” in cases
risk for cerebral palsy. Brain maturation is delayed where children with strokes have milder symp-
in infants with complex CHD by an average of toms. In the pediatric population, the two most
1 month compared to normal infants, in turn commonly identifiable risk factors for stroke are
increasing their risk of periventricular cardiac disease and sickle cell disease, though
82 L. Owens et al.
there is an extensive differential including auto- etiology of postnatal CP. Despite educational
immune vasculitis, vasculopathies, structural interventions and improved critical care, trauma
abnormalities such as arteriovenous also results in significant morbidity and diagno-
malformations, and other hematological diseases ses of CP. Data remains limited due to the often
(Riela and Roach 1993). Congenital cardiac dis- complex and multifactorial causes of CP, but
ease has been discussed in detail above and it is current and future registry data will assist in
important to note that acquired heart disease may better understanding the etiologies and to help
also be a cause of stroke. Children with sickle cell aid in prevention of CP. This area will remain an
disease are at risk for both ischemic and hemor- important avenue of research, as many of these
rhagic strokes. Ischemic strokes typically occur causes are preventable.
more frequently in younger children. The inci-
dence of stroke in the pediatric sickle cell popula-
tion is 285 in 100,000, and there is a high Cross-References
incidence of strokes from 2 to 5 years of age
(Earley et al. 1998). The current standard of care ▶ Cerebral Palsy and the Relationship to
is to perform annual transcranial Doppler from 2 to Prematurity
16 years of age. There is no evidence that transfu- ▶ Classification Terminology in Cerebral Palsy
sion is helpful in hemorrhagic stroke prevention, ▶ Epidemiology of Cerebral Palsy
but it is still commonly used. However, regular ▶ Genetic Abnormalities and Congenital
prophylactic transfusion is a well-documented Malformations as a Cause of Cerebral Palsy
therapy for both primary and secondary ischemic ▶ Infectious Etiologies of Cerebral Palsy
stroke prevention and is now standard of care, as it ▶ Perinatal Stroke as an Etiology of Cerebral
has been demonstrated to decrease the risk of Palsy
stroke by 92% (Adams et al. 1998). ▶ Problems During Delivery as an Etiology of
Cerebral Palsy in Full-Term Infants
▶ Risk Factors for Developing Cerebral Palsy
Neoplasms
Central nervous system tumors are the most com-

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10(3):169–176
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153(6):807–813 1992.tb11479.x
Animal Models of Cerebral Palsy:
What Can We Learn About Cerebral 8
Palsy in Humans
Asher Ornoy
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86
Studies in Mice . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
Infection/Inflammation model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
Hypoxic/Ischemic Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88
Studies in Rats . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
Infection/Inflammation Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
Studies on the Effectiveness of Treatment Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
Studies in Rabbits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
Studies in Sheep . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
Studies in Nonhuman Primates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93
Studies in Other Animals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
Abstract
Cerebral palsy (CP) is caused by non-
progressive neurological damage and
A. Ornoy (*)
manifested by disordered movement and pos-
Laboratory of Teratology, Department of Medical
Neurobiology, Israel Canada Research Institute, Hebrew ture, which leads to motor dysfunction. Two of
University Hadassah Medical School, Jerusalem, Israel the known etiologies of CP are perinatal
e-mail: asher.ornoy@mail.huji.ac.il; ornoy@cc.huji.ac.il

https://doi.org/10.1007/978-3-319-74558-9_218
86 A. Ornoy
asphyxia and prenatal/perinatal infection. ischemic, metabolic, infectious, genetic, and other
Attempts to better understand the etiology acquired etiologies. It is one of the “static enceph-
and pathogenesis of CP have brought many alopathies,” but various complications such as
investigators to develop animal models that kyphoscoliosis, joint contractures, and hip dislo-
mimic human CP. Mice and rats were exten- cation can progress with time, hence the severity
sively used but they have several disadvan- of the clinical manifestations may change with the
tages: due to short gestation, the brain at general progression in development of the
delivery is very immature and therefore most affected child. Many neurological functions can
models are of young postnatal animals whose be affected (i.e., speech, cognition) in addition to
brains are at the developmental stage of the the locomotor system, depending on the location
third trimester human fetus. Postnatal young and severity of the brain injury. Prematurity is one
mice and rat offspring are subjected to hyp- of the most common risk factors for CP, and the
oxia/ischemia or infection/inflammation or a lower the gestational age at birth, the higher is the
combination of the two. The clinical presenta- rate of cerebral palsy (Hirvonen et al. 2014;
tion is different compared to human CP, and Kliegman et al. 2016; Moster et al. 2008).
there is a tendency for spontaneous recovery. Periventricular leukomalacia (PVL) is a very
Rabbits have a longer gestation and the injuries common brain injury prevalent in premature
can be produced during the last week of preg- infants, especially if they suffer from perinatal
nancy. Yet, the clinical picture of the induced asphyxia, intraventricular hemorrhage, or infec-
brain damage is different from that in humans, tion/inflammation (Wu and Colford 2000;
and here too, there is a tendency for spontane- Kliegman et al. 2016). These lesions, generally
ous recovery. Sheep have a relatively long manifested by multiple small lesions in the white
gestation and the different models more closely matter of the brain, are a result of severe damage
resemble human CP. Nonhuman primates to the oligodendroglial cells apparently arresting
show similar nonprogressive motor impair- their maturation, resulting in an insufficient num-
ment following either hypoxia/ischemia or ber of mature oligodendrocytes for normal
infection/inflammation. The extent of the myelination. Experimental animal models of CP
brain damage and the clinical findings are sim- often mimic the same injuries (Coq et al. 2016).
ilar to human CP with similar neuropathologi- As with many human diseases, various investi-
cal brain findings and with good possibilities to gators are trying to mimic CP in animal models
assess a variety of treatment modalities. We using the known human etiologic factors. Early
conclude that the animal model of CP should neonatal hypoxia/ischemia or inflammation and
be chosen according to the aims of the study. infection in rodents were the more common
models that were used with the purpose of induc-
Keywords ing the characteristic clinical and neuropathologi-
Cerebral palsy · Animal models · Rodents · cal findings that resemble the human situation. The
Sheep · Primates advantage of such models is the ability to perform
different studies on the pathogenesis and explore
new methods of possible prevention and treat-
Introduction ment. Hence, mice, rats, rabbits, sheep, and mon-
keys have been used for that purpose, taking
Cerebral palsy is defined as a condition caused advantage of the possibility to correlate the motor
by nonprogressive permanent neurological dam- behavioral capacities with the associated neuro-
age, occurring in the fetal stage or early child- pathological changes in the affected areas of the
hood. It is manifested by disordered movement brain. However, a major problem is the fact that in
and posture, which leads to motor dysfunction these models, at least in mice and rats, animals
(Kliegman et al. 2016). This is a group of disor- tend to recover from the injury or die if the lesions
ders caused by a variety of etiologies including are too severe (Wright and Rang 1990).
8 Animal Models of Cerebral Palsy: What Can We Learn About Cerebral Palsy in Humans 87
Since hypoxic ischemic brain injuries (i.e., (i.e., chorioamnionitis), especially in preterm
intraventricular hemorrhage and periventricular infants, there is a high rate of CP generally of a
leukomalacia), often combined with infectious- spastic type (Coq et al. 2016; Wright and Rang
inflammatory changes (i.e., chorioamnionitis), 1990). Infection is generally produced by the
are well proven etiologic factors in CP (Wu and inoculation of bacterial endotoxin or viral parti-
Colford 2000), as well as in other psychiatric and cles. There are also investigators that combined
neurological diseases such as autism and schizo- both types of injuries, where the chance to
phrenia (Boska 2010), many of the investigators develop cerebral palsy is generally higher (Burd
used these injuries to induce CP in the different et al. 2010; Coq et al. 2016).
animal models. Many of the studies in animals There are several measures to assess the type
were carried out during the developmental stages and severity of CP in man. Similar measures were
of the brain that resemble the human fetal brain in also developed in animals. In addition to the use of
the last trimester of pregnancy. Hence, in mice and the Rotarod apparatus and the recording of the
rats this is generally during the first two postnatal motor behavior of the animals in the “free field,”
weeks, facilitating the experimental designs. Basso et al. (2006) developed a specific method
Indeed, hypoxic ischemic injuries were found for the assessment of motor injuries in mice.
to result in the most severe damage in mice and A Rotarod apparatus is a rotating cylinder on
rats when carried out in the first 2–3 postnatal which the mouse or rat is placed. The animals
weeks, demonstrating the high susceptibility of try to stay on the rotating cylinder and avoid
the more developed, but still immature brain to falling to the ground. The length of time that a
hypoxia-ischemia, as observed among premature given animal stays on this rotating rod is a mea-
infants (Yager and Thornhill 1997). sure of motor performance. However, the Rotarod
In this review, we examine the pertinent litera- apparatus measures only basic changes in motor
ture and discuss the more important studies activity and improvement. Basso et al. divided the
describing the different animal models of CP and mouse locomotion into nine categories using the
bring examples of their use to test possible effects “Basso mouse scales” following locomotion mea-
of treatment modalities. surements in the open field. Similar measures
were also developed for rats. This method
improved the ability to record the extent of
Studies in Mice motor injuries and the degrees and steps of recov-
ery, and has been used by several investigators to
One of the first animals used for the induction of assess the type and severity of motor dysfunction.
CP in animal models was the mouse. Generally,
CP-like neurological insults were produced by
different manipulations in young pups. The diffi- Infection/Inflammation model
culties in producing such models lie in the fact that
after various injuries, the animals tend to recover. Infectious models producing CP used lipopoly-
Moreover, often the procedures are so dangerous saccharides obtained from the wall of Gram-neg-
to the animals that there is a high mortality rate. ative bacteria (i.e., E. coli lipopolysaccharides), or
Two main procedures were used: (1). Tempo- viral infections (influenza) or poly IC (poly-
rary brain hypoxia/anoxia and ischemia, such as inosinic polycytidylic acid). They all induce
clamping the common carotid artery stopping immune reactions. These agents were either
arterial blood supply to one side of the brain. given to pregnant dams or directly to offspring
This is generally followed by temporary general in the first two postnatal weeks (Wang et al. 2009).
hypoxia using, for a limited time, low oxygen air. One of the models of infection/inflammation
(2). Infection and inflammation: based on the fact was carried out on 3-day-old mice, by administer-
that in offspring of women with infection/inflam- ing low doses of endotoxins, i.e., E. coli lipopoly-
mation of the placenta and placental membranes saccharides, daily until day 11. On day
88 A. Ornoy
12, pathological changes of cerebral white matter interested in studying the possible beneficial
were found manifested by impaired myelination. effects of constraint of the upper limb in the non-
This model only partially mimics human white affected side (constraint-induced movement ther-
matter damage that leads to CP (Wang et al. 2009). apy) for 2 weeks and/or enriched environment on
The model of inflammation-induced brain the recovery from the motor impairment. Only
damage was used by Burd et al. (2010) to test 50% of the mice had sufficient brain damage to
the neuroprotective effects of magnesium sulfate. continue the study on the effects of constraint as a
They administered E. coli lipopolysaccharides mode of CP treatment. Motor coordination and
(LPS) directly to the uterine horns of pregnant balance were measured using the Rotarod test as
mice on day 15 of gestation, and 6 h after the well as other measures. They found that contralat-
LPS administration, the fetuses were removed eral limb constraint improved the motor perfor-
for the examination of their brains. Some of the mance of the injured limb while enriched
mice also received magnesium sulfate intraperito- environment did not. Constraint also increased
neally to assess the protective effects of this agent neuronal proliferation in the cerebral sub-
on the LPS-induced brain damage. The authors ventricular zone and striatum, as measured by
claim that this model mimics the preterm human bromodeoxyuridine staining.
infant with chorioamnionitis. LPS increased the Skoff et al. (2001) studied some of the cellular
levels of inflammatory cytokines in the fetal brain, and molecular changes occurring in the brain after
and this was not reduced by magnesium. How- hypoxia/ischemia. They ligated the right common
ever, magnesium prevented neuronal injury which carotid artery in 9–10 days old mice, followed by
was observed in culture of neurons from the brain 10% oxygen and 90% nitrogen for 40–70 min and
of LPS-treated mice without magnesium. studied the brain 3 and 24 h after the insult. They
studied the effects on the expression of several
genes related to myelin formation by in situ hybrid-
Hypoxic/Ischemic Model ization and found a reduction in the expression of
the genes for myelin basic protein and proteolipid
Yoshioka et al. (1989) produced cortical cerebral protein in the striatum, external capsule fornix, and
hemorrhage in 1-day-old mice by subjecting them corpus callosum in the ipsilateral (right) injured
to 5% oxygen and 95% nitrogen for 8 h. Only side. They also found by TUNEL staining of apo-
34% of the newborns survived, and among them, ptotic cells increased apoptosis of oligodendroglial
59% developed parenchymal cerebral hemor- cell precursors in the subventricular zone. They
rhage with ensuing severe brain damage and a demonstrated that glial cells are sensitive to hyp-
variety of neurological deficits. However, this oxia, explaining the white matter degeneration that
does not seem to be an appropriate model for CP occurs in hypoxic ischemic insults.
due to the high mortality and severe brain damage. Since the closure of the common carotid artery
Hence, several investigators further developed the followed by hypoxia (hypoxia/ischemia model) is
hypoxic ischemic model in young mice by occlu- not sufficiently accurate and reproducible, Tsuji
sion of the common carotid artery followed by et al. (2013) developed a mouse model where the
short exposures to air containing low oxygen con- middle cerebral artery was permanently occluded
centrations (Rha et al. 2011; Skoff et al. 2001). by electrocoagulation in 12-day-old mice (Middle
The hypoxic ischemic model in mice was used Cerebral Artery Occlusion – MCAO). They com-
for the study of the pathogenesis of the motor pared this method to the method of hypoxia/ische-
impairment as well as effects of treatment modal- mia and found MCAO to be superior by most
ities. For example, Rha et al. (2011) ligated the parameters. MCAO induced brain injuries mimick-
right common carotid artery in 7-day-old mice. ing neonatal stroke in 85% of the mice, evident at
Following ligation, the mice were also adminis- 8 weeks following surgery, with distinct reduced
tered 8% oxygen and 92% nitrogen for 90 min, volume of the ipsilateral brain and specific thalamic
thus producing left hemiparesis. The authors were lesions in all mice. The sensorimotor impairment in
the MCAO mice was more severe compared to the limitations, the mouse models are commonly
mice with hypoxic ischemic injury. This method is used for the experimental studies of different
therefore believed to be more accurate and appro- brain injuries in man, including CP.
priate for CP compared to the traditional hypoxic
ischemic model of brain damage with common
carotid artery occlusion. The typical sensorimotor Studies in Rats
dysfunction was studied by the Rotarod test as well
as by the behavior in the open field. Studies in rats use the same methods as in mice
Kasahara et al. (2013) produced transient but rats are also sensitive to sensorimotor limita-
ischemia in the brains of mice by temporary tions, as sensorimotor restriction of movement in
occlusion of the middle cerebral artery for differ- the limbs of young rats for about one month
ent amounts of time, from 15–360 min. They induces CP-like lesions (Stigger et al. 2011a, b).
found that blood flow is restored once the occlu- Sensorimotor restriction is carried out as follows:
sion is removed if transient occlusion was no more Rat offspring were exposed to 16 h of sensorimo-
than 240 min. Cerebral infarction was observed if tor restriction per day from postnatal days 2–28.
occlusion lasted for more than 25 min. This model Pup’s hind limbs were immobilized by fixing
of cerebral infarction in mice opens new possibil- them together in an extended position. This pro-
ities for numerous studies on the pathogenesis and cedure does interfere with maternal care and nurs-
treatment modalities of transient cerebral ische- ing as well.
mia that generally causes motor impairment in Stigger et al. (2011a) produced CP-like neuro-
humans. logical injuries in rats by several methods: injec-
Very recently, Zaghloul et al. (2017) described tion of E. coli lipopolysaccharides in utero,
a neonatal mouse model of hypoxia/ischemia perinatal anoxia and sensorimotor restriction.
that seems to be a good model for human peri- Animals were tested for their locomotive abilities
ventricular leukomalacia (PVL). They temporar- by Rotarod at 29 and 45 days of age. When using
ily ligated both common carotid arteries in each one of these methods separately, they
5-day-old mice and then subjected them to air observed that the sensorimotor restriction was
with 8% oxygen and 92% nitrogen for 20 min. the most effective way to produce CP-like
The mice suffered hind limb paresis, mimicking changes. Hence, they concluded that early motor
CP, as well as other neurological deficits, as evi- experience is the most important factor in shaping
dent from studies on the Rotarod device 60 days future motor abilities.
following the surgical procedure. The mice had These studies also have the same limitations as
bilateral dilatation of the lateral and third ventri- in mice. There is initial production of CP-like symp-
cles and cortical white matter loss. Neuronal dam- toms, often followed by slow and progressive
age in the cerebral cortex and hippocampus was recovery. Still, these models are used to serve the
manifested microscopically. Cyclic nucleotide same purposes as the mouse models. Since the brain
phosphodiesterase and olig1 were decreased; of the newborn rat is immature, most studies were
the number of periventricular astrocytes was carried out on neonatal and young rats, to mimic the
increased with increased periventricular neuronal third trimester of human fetal brain development.
apoptosis. There was activation of the pro-
inflammatory microglial cells near the lateral
ventricles. All these changes are typical of Hypoxic/Ischemic Model
white-matter injury.
These above-described mouse models and Yager et al. (1996) examined the response of the
several other undescribed models of cerebral brain in rats to hypoxia at different postnatal ages
palsy can be used for different studies, but we and found that the highest susceptibility appears
should remember their limitations for translation in the first few postnatal weeks, with susceptibility
to the human situation. In spite of these declining at older ages. In these experiments, the
90 A. Ornoy
right common carotid artery was ligated followed days 2–28. From postnatal days 31–52, the ani-
by 35 min of 12% oxygen in the air. The degree of mals had locomotor stimulation training on a
brain damage was studied 7 days after the injury treadmill. They observed improvement in the
and was found to be highest in the rats subjected to motor abilities of the trained rats and a normal
hypoxia-ischemia before weanling, which occurs diameter and axon numbers of the sciatic nerve,
during days 20–22. while in the restricted, untrained animals there
The extent of the CP-like damage can be mea- was a reduced size of the sciatic nerve.
sured by the Rotarod apparatus, but, as stated The beneficial effects of treadmill training was
above, this type of measurement is not very accu- also described earlier by Marcuzzo et al. (2008) in
rate. A more accurate measure is the measurement rats subjected to anoxia, sensorimotor restriction,
of locomotion in the open field apparatus and or both types of injury. They measured the mean
accurate recording of gait. Basso et al. (1995) cross-sectional area of the soleus muscle and the
rated the gait by 21 subscores from zero – no muscle fiber density and found that treadmill
movement to 21 – normal gait. This clinical eval- training decreased the number of atrophic muscle
uation of gait is especially important for studies on fibers in comparison to the rats subjected to anoxia
the process of recovery, thus opening the way for and sensory motor restriction, but without the
more accurate evaluation of the success of treat- treadmill training.
ment modalities (Dos Santos et al. 2017). As Marques et al. (2014) produced CP-like inju-
mentioned above, later, Basso et al. (2006) also ries by using all three means of CP induction:
developed a similar method for the evaluation of sensory motor restriction, hypoxia/ischemia, and
motor activity in mice (with 9 subscores of gait). infection/inflammation. They injected E. coli lipo-
polysaccharides prenatally, produced perinatal
anoxia in the offspring and postnatal sensorimotor
Infection/Inflammation Model restriction. Once the CP-like changes were evi-
dent, they used simple environmental enrichment
Dos Santos et al. (2017) also used the triple inju- as a means to speed up the recovery from the
ries model for CP, using postnatal sensorimotor injuries. The enriched environment increased the
restriction in addition to asphyxia (100% of movement abilities in the experimental CP rats,
nitrogen for 20 min immediately after birth) and induced partial reversal of the decrease in the size
infection/inflammation (daily low-dose lipopoly- of motor neurons found in the CP animals, nor-
saccharide injections to the dams from day 17 of malized the soleus muscle cross-sectional area,
pregnancy to term). This triple-injury method of and increased expression of synaptophysin in the
prenatal, perinatal, and postnatal manipulations ventral horn of the spinal cord.
resulted in hind-limb neurological damage on The possible beneficial effects of magnesium
days 29 and 45, resembling those found in para- sulfate in preventing hypoxia-induced CP in rats
plegic CP patients, as observed in an adopted was studied by Hallak et al. (2000). Prenatal hyp-
open-field apparatus using the method described oxia was induced on day 17 of gestation using 9%
by Basso et al. (1995). However, the injuries oxygen, 3% carbon dioxide, and 88% nitrogen for
tended to subside with time as an improvement 2 h. Fetuses were removed on day 20 of preg-
of gait was observed on day 45 compared to day nancy, one day before term, and evaluated for the
29 (dos Santos et al. 2017). extent of brain damage. They found that magne-
sium sulfate was protective, as it reduced the
shrinkage of neurons in the hippocampus and
Studies on the Effectiveness thalamus and the depletion of brain tissue.
of Treatment Methods Many other studies were carried out in CP-like
models of rats for the study of the pathogenesis of
Stigger et al. (2011b) studied the possible benefits the induced neurological damage and methods of
of treadmill training on the motor deficits induced treatment, but this is beyond the scope of this
by sensorimotor restriction in rats during postnatal chapter.
Studies in Rabbits 22 of pregnancy. Their manipulation injured the

subcortical motor pathways causing damage to
As the pregnancy in rabbits is longer compared to the basal ganglia and ventral thalamus. In addi-
mice and rats and the newborn’s brain is more tion, they found an increase in neuronal death in
mature, injuries were generally carried out in the the deep cortical areas.
last week of pregnancy. The more common
methods used maternal hypoxia/anoxia or mater-
nal infection/inflammation as the means to pro- Infection/Inflammation Model
duce cerebral palsy in rabbits.
Yoon et al. (1997) seem to be the first to use
maternal infection in rabbits as a way to produce
Hypoxic/Ischemic Model CP in the offspring. They inoculated E. coli bac-
teria on days 20–21 of pregnancy in rabbits and
Derrick et al. (2004) carried out studies on treated them with ampicillin-sulbactam antibiotics
sustained global hypoxia during the third part of three times a day for the entire experimental
pregnancy in rabbits and studied the neurological period. Animals were killed 5–6 days after the
outcomes in the day one offspring. In addition to inoculation; most of the E. coli inoculated fetuses
a variety of neurological abnormalities including were dead. They found in these animals histopath-
difficulties in sucking and swallowing, they found ological signs of disorganization and rarefaction
increased tone of the limbs and impaired locomo- of the white matter in the brain.
tion, mimicking CP. This was apparently the Saadani-Makki et al. (2009) injected pregnant
first rabbit model of spastic CP. They also found rabbits with E. coli lipopolysaccharides (endo-
histopathological signs of acute injuries in the toxin producing inflammation) on day 28 of
thalamus and basal ganglia. Tan et al. (2005), in gestation and examined the term, 31-day-old
the same group of investigators, produced hyp- fetuses by diffusion tensor magnetic resonance
oxia in pregnant rabbits on days 22, 25, and 28 of imaging (tMRI). They found changes in the peri-
gestation, with the length of pregnancy in rabbits ventricular white matter with increased numbers
about 35 days. This procedure caused a high of activated microglial cells infiltrating the sub-
rate of stillbirth and produced a variety of abnor- ventricular areas. The same group (Balakrishnan
malities of locomotion in the survivors. In the et al. 2013) also investigated the specific changes
offspring prenatally subjected to hypoxia on day in the mature neurons and found reduced number
22 and 25 (but not on day 28), significant hyper- of neurons and neuronal branching in the thala-
tonicity was also evident, thus mimicking human mus as well as reduced dendritic spines in the
CP. The same group published thereafter several retrosplenial areas that receive neurons from the
studies expanding their initial findings and dem- thalamus.
onstrating the different brain lesions by serial
MRIs (Drobyshevsky et al. 2012; Yu et al.
2011). They found that the nature of the CP Studies in Sheep
changes according to the gestational age during
the application of hypoxia. For example, 32 min Sheep have the advantage of having a relatively
of uterine ischemia on day 29 of pregnancy prolong pregnancy of about 145 days, and the term
duced dystonic hypertonia with damage to the fetus is more mature than in rodents. Moreover,
basal ganglia, thalamus, and brain stem, whereas the fetuses can be handled individually, and
earlier hypoxia-ischemia produced a hypotonic because the cerebral white matter in sheep has
type of motor dysfunction. In contrast, Derrick many resemblances to human white matter,
et al. (2004) found increased forelimb muscle sheep mimic the human situation more closely.
tone, locomotor dysfunction, and difficulties in Hence, this model has increasingly been used for
sucking and swallowing in rabbits exposed prena- the study of the etiology, pathogenesis and modes
tally to hypoxia-ischemia for 30–40 min on day of treatment of cerebral palsy (Back et al. 2012).
92 A. Ornoy
Hypoxic/Ischemic Model but without neuronal necrosis. In both groups of

injured fetuses, there was damage to various glial
Mallard et al. (1995) were the first to use repeated cells and microglial activation as a sign of an
asphyxia in fetal sheep in order to produce brain inflammatory response.
damage. They induced fetal asphyxia by four Svedin et al. (2005) injected E. coli LPS into
repeated umbilical cord clamping, each time for sheep fetuses on day 91 (preterm) or day 121 (near
5 min. By immunohistochemistry of the brain, term) of pregnancy. Fetal brains were examined by
they showed that the corpus striatum, the globus various immunohistochemical methods. There was
pallidus and substantia nigra were affected about 40% mortality. In the brains of the surviving
with depletion of neurons. The most significant fetuses treated on day 91, increased microglial cell
effects were observed in the GABAergic system activation and loss of neurofilaments in the subcor-
with specific damage to the striatal projections to tical white matter were evident. From the surviving
the globus pallidum, mimicking CP. The same fetuses treated on day 121, 5 of 7 fetuses showed no
method of umbilical cord clamping was used pathological alterations in the brain, but in the other
later by other investigators (Marumo et al. 2001; 2 fetuses, increased microglial activation and
Ohyu et al. 1999), inducing periventricular reduced expression of neurofilament and myelin
leukomalacia with multiple necrotic foci in the basic protein were observed.
periventricular white matter, thus demonstrating
that hypoxia-anoxia can damage the cerebral
white matter. Studies on the Effectiveness
of Treatment Methods
Infection/Inflammation Model Sheep are more appropriate for the evaluation

of CP treatment modalities than rodents. Hence,
Fetal infection late in pregnancy was also used for studies have been published showing the protec-
the induction of CP-like injuries in sheep. Duncan tive effects of hypothermia, erythropoietin,
et al. (2002) administered intravenous injections of and other methods in the alleviation of the
E. coli lipopolysaccharides into ovine fetuses at the CP-like symptom produced by prenatal hyp-
beginning of the third part of pregnancy daily for oxia/ischemia. Similar studies were also carried
5 days. About 5 days following the last injection, out in search of new treatment modalities. For
brain injury was evident in all treated fetuses, example, Brew et al. (2016) demonstrated the
manifested by diffuse subcortical and peri- effectiveness of dopamine as a neuroprotective
ventricular leukomalacia with a reduction in the agent in experimental CP. The authors produced
size of the corticospinal tract in the brain stem. fetal asphyxia by occluding the umbilical cord
The resemblance to human cerebral palsy prompted (UCO) for 25 min on the 90th day of pregnancy.
investigators to use this model for studies on the Dopamine was then infused for a relatively long
etiology, pathogenesis, and treatment of CP. period of 74 h starting 5 days after UCO. Studies
Mallard et al. (2003) compared two models of the brains 72 h after the termination of dopa-
of CP in sheep; the one induced by infection/ mine infusion revealed that oxidative stress of
inflammation and that induced by hypoxia/ische- the cerebral white matter was alleviated by
mia, as both are known etiologies of PVL in dopamine, and apoptotic cells and microglial
human CP. Fetal sheep had either umbilical cord cell number were reduced almost to the numbers
clamping for 25 min, producing severe hypoxia or found in controls, demonstrating the protective
were administered IV E. coli LPS. One third of the effects of dopamine.
asphyxiated fetuses had typical periventricular As the lesions produced in sheep models of CP
leukomalacia, and the others exhibited diffuse are closer to the lesions seen in human CP, it is
neuronal necrosis. Two of the five fetuses injected expected that sheep will be used more often than
with LPS had cystic periventricular leukomalacia rodents as appropriate models of human CP.
Studies in Nonhuman Primates Infection/Inflammation Model
There are several studies using monkeys as a model Adams Waldorf et al. (2011) induced chorio-
of human cerebral palsy. The two methods used decidual infection in rhesus macaques and pigtail
were also hypoxia/ischemia and infection/inflam- macaques with group B streptococci around day
mation. Generally, the nonhuman primate models 140 of gestation, about 20 days before full-term,
are closer to the human situation than other animals, with the purpose of inducing early labor. Their
but due to the difficulties in performing such stud- main purpose was to evaluate the inflammatory
ies, their number is limited. However, these models changes in the fetus and placenta following the
enable us to study the effects of hypothermia, eryth- induction of early labor via intrauterine fetal
ropoietin, and other modes of treatment on the ascending infection. They observed a marked
alleviation/prevention of CP. increase in intra-amniotic inflammatory cytokines
and elevated prostaglandins that initiated uterine
contractions and early labor. Similarly, the fetuses
Hypoxic/Ischemic Model also exhibited high concentrations of inflamma-
tory cytokines.
McAdams et al. (2017a, 2017b) used a hypoxic Willette et al. (2011) treated rhesus monkeys
ischemic model to induce cerebral palsy in (Macaca Mulata) with low doses of E. coli lipo-
Macaca Enmestrin monkeys. Perinatal asphyxia polysaccharides about 6 weeks before term.
was produced by umbilical cord occlusion for The offspring showed various neurological
15–18 min. They treated the asphyxiated mon- impairments and behavioral disturbances. At one
keys with erythropoietin and hypothermia and year of age, MRI studies showed increased vol-
compared the results with nontreated asphyxi- ume of the head by 5.9% and increased volume of
ated animals. Several of the asphyxiated ani- cerebral white matter by 8.8%. The increase in
mals developed typical moderate to severe white matter was evident in most areas of the
cerebral palsy with damage to the white matter cerebral cortex except the occipital lobes which
tracts, i.e., corpus callosum and internal cap- in the monkeys develop early, apparently
sule. The affected animals also had reduced before lipopolysaccharides were administered.
staining of cortical neurons and increased glial The administration of high concentration of lipo-
scarring. Hypothermia and erythropoietin polysaccharides are known to inhibit neuronal
indeed reduced the severity of the brain pathol- growth, especially in rodents, while, as shown in
ogy (McAdams et al. 2017a). In a different this study, low doses of endotoxins increase the
study, these authors (McAdams et al. 2017b) white matter volume.
also subjected the monkeys that were hypoxic
in utero to postnatal hypoxia – 3 min in breath-
ing air with only 8% oxygen, several times each Studies on the Effectiveness
day for 3 days. The hypoxic animals had low of Treatment Methods
Apgar scores and severe metabolic acidosis. On
postnatal day 8, the brains of the double-injured In recent years, several investigators used non-
monkeys showed severe thalamic injuries, with human primates to study the effectiveness of vari-
neuronal loss and gliosis in the ventrolateral ous treatment modalities. For example, Traudt et al.
thalamus. Several animals also exhibited path- (2013) studied the effects of erythropoietin and
ological changes in the Globus pallidum and hypothermia in the Macaca Nemestrina (pigtailed
putamen. White matter injuries were also dem- macaques) following 15–18 min of umbilical cord
onstrated in some animals. These changes in the occlusion (UCO) (a hypoxic-ischemic model)
brain resemble the changes observed in new- about one week prior to term. They compared the
born infants who suffer severe hypoxia- outcome among monkeys exposed to normal saline
ischemia. only (controls), monkeys exposed to OCU and
94 A. Ornoy
normal saline, monkeys exposed to UCO and hypo- situation, although the clinical findings are often
thermia of 33.5 C for 72 h, and monkeys exposed to different. It seems that of all the animal models,
UCO, hypothermia, and repeated high doses of the monkey model is the most appropriate one for
erythropoietin administered at 30 min 24 h, 48 h, studying the etiology, pathogenesis, and treatment
and 7 days postdelivery. The neurological outcome of human CP.
was evaluated by developmental assessment with
special emphasis on the presence or absence of
CP. In addition, brain MRI and MR spectroscopy
were carried out under sedation at 24 and 72 h and Cross-References
at 9 months of age. OCU caused death or severe CP
in 43% of the monkeys and hypothermia did not ▶ Complementary and Alternative Medicine in
reduce the mortality and/or morbidity that was Cerebral Palsy
44%. However, the combination of hypothermia ▶ Constraint-Induced Movement Therapy for
and erythropoietin significantly reduced mortality Children and Youth with Hemiplegic/Unilateral
and morbidity, in all measures: motor and cognitive Cerebral Palsy
outcome, weight gain, cerebellar and cerebral ▶ Infectious Etiologies of Cerebral Palsy
growth and structure, and none of the monkeys ▶ Perinatal Stroke as an Etiology of Cerebral
died or developed severe CP. Thus, according to Palsy
the authors, these results may have direct implica- ▶ Selective Voluntary Motor Control in Children
tions for the treatment of asphyxiated newborn and Youth with Spastic Cerebral Palsy
infants. ▶ Therapy Management of the Child with Cere-
This example of the use of monkeys to evaluate bral Palsy: an Overview
new treatment methods emphasizes the advantage
of using nonhuman primates over all other animal
models of cerebral palsy. References
Adams Waldorf KM, Rubens CE, Gravett MG (2011) Use
of nonhuman primate models to investigate mecha-
Studies in Other Animals nisms of infection-associated preterm birth. BJOG
118(2):136–144
Andreani JC, Guma C (2008) New animal model to mimic
There are only a few studies using other animals spastic cerebral palsy: the brain-damaged pig prepara-
as models for cerebral palsy. Among these are tion. Neuromodulation 11(3):196–201
dogs (Balasubramaniam and Del Bigio 2006), Back SA, Riddle A, Dean J, Hohimer AR (2012) The
instrumental fetal sheep as a model of cerebral white
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The Effects of Umbilical Cord Blood
and Cord Tissue Cell Therapies in 9
Animal and Human Models of
Cerebral Palsy
Jessica M. Sun and Joanne Kurtzberg
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
Animal Studies of Cell Therapy in Brain Injuries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
Human Studies of Cell Therapy in Brain Injuries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102
Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108
Cross-References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108
Abstract or mother and because they can be routinely

Biologic and cell-based therapies are increas- screened and banked. This chapter will
ingly being developed for a multitude of dis- describe the current state of investigations of
eases. They are being explored in the treatment umbilical cord blood and cord tissue-based
of neurologic conditions, as traditional phar- therapies in the treatment of cerebral palsy
macologic agents typically cannot fully due to an acquired brain injury and highlight
address the pathologic complexity and resul- some of the possibilities and challenges inher-
tant manifestations of injuries and diseases ent in developing and assessing such therapies
affecting the brain. Umbilical cord blood and in this population.
cord tissue are attractive sources of cells for
these therapies as they are readily available and Keywords
easily obtained without risk to the donor infant Cerebral palsy · Cell therapy · Umbilical cord
blood · Mesenchymal stromal cells · Brain
connectivity
J. M. Sun (*) · J. Kurtzberg
Marcus Center for Cellular Cures, Robertson Clinical and
Translational Cell Therapy Program, Duke University
Medical Center, Durham, NC, USA
e-mail: Jessica.sun@duke.edu;
Joanne.kurtzberg@duke.edu

https://doi.org/10.1007/978-3-319-74558-9_223
98 J. M. Sun and J. Kurtzberg
Introduction CP. While several tools have been employed to

quantify motor function in this patient population,
As described throughout this section, the causes most focus on a specific muscle group, limb, or
of cerebral palsy (CP) are heterogeneous, includ- motor task. The Gross Motor Function Measure
ing, but not limited to, genetic and metabolic (GMFM), on the other hand, is a tool designed to
disorders, congenital brain malformations, and assess change in overall gross motor function over
acquired brain injuries, all of which can cause time and is one of the few tools specific to children
static brain lesions and lead to motor impairment. with CP.
In some respects, the etiology of CP is considered To describe the natural history of gross motor
almost irrelevant to the management of the child function in children with CP, the Can Child Centre
with CP. There is some validity to this dogma, as for Childhood Disability Research established
many of the manifestations of CP are treated iden- gross motor function development curves based
tically regardless of the etiology of the inciting on a child’s age, GMFCS level, and score on the
brain pathology, and doing so can have an impor- GMFM-66 (Rosenbaum et al. 2002). Building on
tant impact on the child’s function and quality that work, reference percentiles were developed to
of life. aid in the normative interpretation of GMFM-66
When the goal, however, is to try to improve or scores within GMFCS levels (Hanna et al. 2008).
prevent the manifestations of CP by addressing Unlike GMFCS levels, which are typically stable
the underlying pathology, the etiology of CP is of through childhood and adolescence, GMFM per-
the utmost relevance. This chapter will focus on centile values can be more variable – just as there
CP caused by an acquired brain injury and review is a wide range of “normal” in the typical time
ongoing research investigations attempting to har- course of motor development in children without
ness cell-based therapies to improve or prevent CP, the same holds true for children with motor
the symptoms of CP by promoting repair and limitations. This variability can make quantifying
recovery of the injured brain. the therapeutic effect of interventions designed to
improve overall motor function challenging.
The impact of an early brain injury varies
Natural History depending on its etiology, location, and extent.
Even among children with similar injuries, how-
A child’s motor development during early child- ever, the effect on motor development can differ
hood is one of the most important predictors of significantly and may, in part, be related to both
ultimate motor function. Thus, classifying the the developmental stage at which the injury
motor function of children with CP is useful in occurred and the brain’s response to it. Human
counseling families regarding prognosis and brain development is a complex and long process,
expected motor outcomes. The Gross Motor beginning in the third week of gestation and
Function Classification System (GMFCS), a val- extending through at least adolescence, probably
idated scale of motor development in children into adulthood. While the majority of
with spasticity, is used to classify children with neurogenesis occurs in utero, synaptogenesis and
CP into five levels of gross motor function from myelination continue postnatally, with substantial
level 1 (most able) to level 5 (most limited). This growth and development during the first 6 years of
system has been demonstrated to be both reliable life. Injury to the developing brain not only results
and relatively stable over time (Wood and in loss of normal brain cells and tissue but also
Rosenbaum 2000), i.e., it is unusual for children alters the neuroenvironment, disrupting the intri-
to change GMFCS levels during childhood and cate cellular and environmental interactions
adolescence. Quantifying and predicting precise essential for healthy brain development. The
motor function over time is more challenging most prevalent acquired brain injuries resulting
given the heterogeneous brain pathology and in CP occur in the neonatal or perinatal period
responses to brain injury among children with and include (in order of increasing incidence)
9 The Effects of Umbilical Cord Blood and Cord Tissue Cell Therapies in Animal and Human. . . 99
perinatal stroke, neonatal hypoxic/ischemic cells may be enhanced by the delivery of trophic
encephalopathy (HIE), and prematurity-related factors from cells that provide anti-inflammatory,
intraventricular hemorrhage and periventricular anti-apoptotic, and neuroprotective effects (Llado
leukomalacia. et al. 2004; Vendrame et al. 2005; Borlongan et al.
In addition to the ongoing brain development 2004; Arien-Zakay et al. 2009). Brain plasticity
that naturally occurs throughout early childhood, may also be increased by inducing migration
there has been a growing recognition that the brain and proliferation of endogenous neural stem
possesses an inherent, albeit limited, capacity for cells; by enhancing neurovascular and white
self-renewal and repair. So while the inciting brain matter remodeling via synaptogenesis, angiogen-
injury in young children with CP may be static, esis, and myelination; and by decreasing
their brains are not. In fact, the developing brain inflammatory and immune responses to injury
exhibits remarkable plasticity. In children with (Carmichael 2003; Chen et al. 2003, 2014;
CP, reorganization of central motor pathways has Taguchi et al. 2004). Given their ready availabil-
been demonstrated using transcranial magnetic ity, uncontroversial nature, and biologic
stimulation, electromyography, and functional properties, cells from umbilical cord blood and
MRI (fMRI). In some patients with a unilateral tissues are prime candidates to modulate
lesion involving the motor tracks, motor control neuroinflammation via neuroprotective and/or
of the affected limbs is primarily provided by restorative factors and signal endogenous cells to
abnormal corticospinal projections from either act in a targeted way toward damaged brain tissue.
adjacent areas in the affected hemisphere or dis- Preclinical and early phase clinical trials are
tant regions in the ipsilateral, healthy hemisphere investigating the use of both umbilical cord
(Staudt et al. 2002; Carr et al. 1993; Guzzetta et al. blood (CB) and mesenchymal stromal cells
2007), demonstrating that an unaffected part of derived from umbilical cord blood or cord tissue
the brain is compensating for the injured portion. (UC-MSC) in multiple models of brain injury
Changes in the primary source of cortical activa- relevant to CP.
tion on fMRI have also been described in individ-
ual patients after virtual reality therapy (You et al.
2005) and constraint-induced movement therapy Animal Studies of Cell Therapy in Brain
(Sutcliffe et al. 2007). These observations indicate Injuries
that neural plasticity plays an important role in the
ability of children with CP to recover from early Numerous animal models have demonstrated both
brain injury. Leveraging that plasticity and mod- neurological and survival benefits of cell therapies
ulating it via cellular therapy may enhance func- in the setting of stroke, ischemia, and intracranial
tional recovery. hemorrhage (Vendrame et al. 2004; Chen et al.
2001; Meier et al. 2006; Nan et al. 2005). These
injuries differ in that some are focal (i.e., stroke)
Treatment and others are global (i.e., hypoxia), but all are
typically characterized by immediate damage to
There is a growing evidence that cell therapies all neural cell types within the affected region,
have the ability to influence tissue damage and initiating a cascade of events that lead to demye-
repair in the brain by signaling and activating host lination and necrosis of brain tissue. Inflamma-
cells via trophic and/or paracrine effects. While tion, apoptosis, neuronal and oligodendrocyte
the exact mechanisms of neural sparing and/or death, and astrocytosis contribute to the damage
recovery are still being examined in preclinical caused by these insults. In this setting comprised
investigations, and are probably multiple, several of numerous, complex mechanisms causing and
mechanisms have been implicated (Bliss et al. propagating tissue damage, a cellular approach to
2007; Wagenaar et al. 2017; Castillo-Melendez therapy that could mediate multiple ongoing path-
et al. 2013). The survival potential of host neural ologic processes could potentially have
significant benefit. Neuroprotection, neo- treatment response, as the environment of the

vascularization, and neuronal regeneration have injured brain evolves and changes over time as it
all been demonstrated after cell administration in reacts to the acute injury. In many instances, peri-
various models (Taguchi et al. 2004; Vendrame natal stroke occurs in utero or shortly after birth
et al. 2004). and is not recognized until months later. However,
the majority of animal stroke models have admin-
Animal Studies in Stroke istered cells in the acute or subacute setting,
Neonatal stroke is often caused by middle cerebral immediately to several days after the insult, and
artery occlusion (MCAO). This is also the most results of experiments regarding timing have been
extensively studied stroke model in rats or mice, inconsistent. Some studies have shown greater
in which MCAO may either be permanent or improvement in somatosensory behavior and neu-
transient and is typically accompanied by hyp- rologic dysfunction when cells were administered
oxia. Administration of CB and UC-MSC can earlier (i.e., 1 day versus 7 days after MCAO)
greatly mitigate the damage caused by this type (Chen et al. 2001). However, others have demon-
of acute hypoxic/ischemic brain injury, and strated improvement in functional outcomes in
decreased brain infarct volume, decreased apopto- animals treated in the chronic phase of injury. In
sis and astrogliosis, and improved motor function a rat model of bone marrow MSC infusion
outcomes have all been demonstrated in multiple 1 month after MCAO stroke (Shen et al. 2007),
animal models (Lin et al. 2011; Kim et al. 2012). scar tissue was reduced and the number of prolif-
In addition to evaluating treatment response erating cells and oligodendrocyte precursors in
and further elucidating mechanism of action, the area of injury was increased, possibly indicat-
many preclinical studies have attempted to ing neurogenesis and myelination. This suggests
address other critical aspects of cell administra- that although the ideal timing of cellular therapy
tion, including dose, route of delivery, and timing. for stroke and other brain injury is still unknown,
A dose-dependent relationship between CB cell benefits may be attainable long after a stroke
dose, behavioral improvement, and neuronal spar- occurs.
ing was demonstrated after intravenous adminis-
tration of CB cells after MCAO in rats, reaching Animal Studies in Hypoxic/Ischemic Brain
significance at a dose of 107 cells (Vendrame et al. Injury
2004). A dose effect was also described using Clinically, hypoxic/ischemic encephalopathy
intravenous UC-MSCs in a neonatal mouse (HIE), a common cause of CP in young children,
model 48 h after MCAO. Although the infarct is an acute event and is often recognized immedi-
area did not change in UC-MSC-treated mice, ately, typically at birth, making it suitable for early
there was a decreased accumulation of microglia intervention. Cellular interventions have been
and improved performance on motor function studied in multiple models of HIE. In a newborn
tests in animals that received a high cell dose lamb model of perinatal asphyxia caused by
(105 cells) compared to animals that received a umbilical cord clamping at the time of caesarean
low cell dose (104 cells) or a sham infusion section, CB cells delivered intravenously 12 h
(Tanaka et al. 2018). In addition to the intravenous later reduced brain inflammation, astrogliosis,
route, CB and bone marrow-derived cells have and neuronal apoptosis and restored normal
also been administered intra-arterially, intracere- brain metabolism, providing neuroprotection
brally, and intranasally, among others. In multiple (Aridas et al. 2016). Though they did not assess
experiments, no single mode of delivery has dem- functional measures, many other models have. In
onstrated significant superiority in terms of func- a neonatal rat model that results in severe cerebral
tional outcomes (Willing et al. 2003; Yang et al. damage and contralateral spastic paresis after uni-
2013; Donega et al. 2013). lateral carotid artery ligation on day 7 of life,
As with other interventions for stroke, timing intraperitoneal CB mononuclear cells adminis-
of cell therapy is likely to play an important role in tered 1 day after the hypoxic event migrated to
the area of brain damage and persisted for at least (Drobyshevsky et al. 2015). A possible dose effect
2 weeks. Although the extent of gross morpho- was also observed, with less improvement
logic injury was not altered, treatment with CB detected at lower doses.
cells prevented the development of spastic paresis MSCs have also been studied in various animal
(Meier et al. 2006). In a baby rabbit model of models of HIE. Overall, improvements in both
HIE via uterine artery occlusion (Derrick et al. sensorimotor and cognitive function have been
2007), human CB administered 9 days after repeatedly observed (Archambault et al. 2017).
the injury improved gross motor function in func- In a murine model of HIE, bone marrow-derived
tional assays, with decreases in dystonia and MSCs delivered into the brain parenchyma
spasticity and improvements in posture and resulted in reduced lesion size and improved
walking observed in treated animals (Fig. 1) behavioral outcomes even when treatment was
Fig. 1 Rabbit model of cerebral palsy and intravenous days 5 and 11 in the severe group compared to saline
CB administration Panel A: Experimental model. The and media. Panel C: CB administration improved
uterine artery is occluded 9 days prior to delivery, resulting neurobehavioral scores at days 5 and 11 in the mild
in a cerebral palsy phenotype. Kits are delivered just prior group. *p < 0.05, **p < 0.01 (Drobyshevsky et al.
to term and received IV CB cells on the day of birth. Motor 2015). Panels B & C reproduced with permission from
assessments are performed on days 1, 5, and 11. Panel B: Karger (2018)
CB administration improved neurobehavioral scores at
started 10 days after the insult. Evidence of improved neurobehavioral testing in surviving
increased endogenous cell proliferation and pups (Lei et al. 2015).
decreased microglial proliferation was observed
(van Velthoven et al. 2010). The source and dose Summary of Animal Studies
of cells as well as the route and timing of admin- Preclinical evidence suggests that administration
istration vary among MSC models and require of CB and MSCs in small animal models of neo-
further refinement through additional natal/perinatal brain injury results in improved
investigation. survival and functional outcomes. Optimal dose,
timing, and route of administration as well as
Animal Studies in Intraventricular specifics regarding mechanism of action are still
Hemorrhage (IVH) and Periventricular the subject of preclinical investigations and may
Leukomalacia (PVL) vary based on the type, degree, and timing of both
Intraventricular hemorrhage (IVH) is common in the insult and the intervention. Nonetheless, these
preterm babies and often results in periventricular studies suggest that CB and UC-MSCs have
leukomalacia (PVL) and subsequent development potential as therapeutic interventions for brain
of CP. In a neonatal rat model of IVH induced by injuries sustained early in life.
intraventricular injection of autologous blood,
mice given UC-MSCs intravenously 2 days after
IVH exhibited a decreased amount of reactive Human Studies of Cell Therapy in Brain
gliosis and hypomyelination and significant Injuries
behavioral improvement compared to control ani-
mals (Mukai et al. 2017). In a similar rat model, Based on mounting preclinical evidence of poten-
intraventricular administration of UC-MSCs, but tial efficacy, several early phase clinical trials of
not fibroblasts, 2 days after severe IVH prevented cell therapies have been initiated in people with
post-hemorrhagic hydrocephalus, reduced brain brain injuries, many in adults with stroke. As
inflammation, and improved sensorimotor func- previously described, however, the developing
tion (Ahn et al. 2013). These effects were not brain is substantially different than the adult
observed when the UC-MSCs were delivered at brain. Therefore, results of clinical trials in adults
a later time point of 7 days post-IVH (Park et al. cannot be easily extrapolated to children with CP
2016). and/or brain injury. In fact, one could argue that
Even in the absence of IVH, preterm babies are the inherent plasticity of the pediatric brain may
still at increased risk of PVL and resultant render it more responsive to cell therapies and
CP. Oligodendrocyte precursors prevalent in the may affect the therapeutic windows of such
developing brain between 23 and 32 weeks ges- interventions.
tation are particularly susceptible to inflammatory In conducting clinical trials of cell therapies in
and infectious insults sustained during that time children with CP, multiple issues warrant careful
period. Damage or destruction of consideration. As discussed above, CP is a het-
pre-oligodendrocytes disrupts the normal matura- erogeneous condition with multiple causes, some
tion to oligodendrocyte myelinating cells, leading of which may be more responsive to cell therapies
to hypomyelination and disorganization of white than others. Thus, clearly defining the patient
matter and subsequent motor and cognitive defi- population to be studied is essential. Selecting
cits. Cell therapy for prematurity-related PVL has valid, relevant outcome measures that can reliably
not been extensively studied in animals. In a detect change over time and ideally account for
mouse model of chorioamnionitis, mouse mothers expected gains is challenging but critically impor-
treated with intraperitoneal MSCs had a lower rate tant, particularly given the variability in the pat-
of preterm delivery. They also had decreased tern of involvement and motor function of
levels of inflammatory cytokines, decreased individual patients. And, finally, the safety of the
microglial activation in the fetal brains, and intervention is paramount. Although clinical trials
of cell therapies for children with CP are still in genetic conditions, intractable seizures, or
early phases, they have dealt with many of these severe microcephaly were excluded. Autologous
issues and have demonstrated promising results. CB units had to have a documented pre-
To date, most human studies of cell therapies have cryopreservation total cell dose of 1–5 107/kg,
tested a particular cell product in a variety of negative sterility culture, and negative maternal
patients with CP. As such, the clinical trials infectious disease screening. Subjects were eval-
described below are organized by cell type. uated at baseline, 1 year, and 2 years with motor
evaluations and brain MRI. They were random-
Clinical Trials of Autologous Umbilical ized to the order in which they received CB and
Cord Blood in CP placebo infusions, which were given 1 year apart.
In 2010, our group at Duke University reported The primary endpoint was change in GMFM-66
the safety of intravenous infusion of autologous score 1 year after the initial infusion (CB or pla-
(a child’s own) CB in a series of 184 infants and cebo). Characteristics of the 63 patients and their
children with HIE, CP, congenital hydrocephalus, CB units are shown in Table 1. The two treatment
and other brain injuries (Sun et al. 2010). The groups were balanced with respect to age, gender,
parents of these children had elected to have race, type, and severity of cerebral palsy. The
their CB collected and banked at the time of etiologies of CP included periventricular
their birth at a private family bank (n = 162, leukomalacia (n = 17), in utero stroke or bleed
88%) or had donated it to a public bank from (n = 27), ischemic injury (n = 7), and others
which it was later retrieved (n = 22, 12%). (n = 12).
Patients received one or multiple intravenous There was no difference in change in absolute
infusions of autologous (their own) CB through GMFM-66 scores between placebo and treated
a peripheral IV after premedication with oral groups (6.9 vs. 7.5, p = 0.72) 1 year after the
Tylenol, IV Benadryl, and IV Solu-Medrol. The initial infusion. However, treated subjects who
median cell dose was 2.0 107 total nucleated received above the median infused cell dose of
cells per kilogram (TNC/kg), with a range of 2 107/kg demonstrated greater improvement in
0.1 107 to 13.3 107 TNC/kg. The infusions GMFM-66 scores compared to subjects who
were well tolerated. Three patients (1.5%) experi- received lower cell doses ( p = 0.05) (Fig. 2).
enced infusion reactions during their CB infusion The infused cell dose was not correlated with
characterized by wheezing with or without urti- age ( p = 0.70) or type ( p = 0.32) or severity
caria 2–10 minutes after the IV infusion was ini- ( p = 0.46) of cerebral palsy.
tiated. The reactions resolved after As discussed previously, young children with
discontinuation of the infusion and treatment CP are expected to make some gains in gross
with additional IV Benadryl and bronchodilators. motor function over time. Therefore, the expected
No infections, autoimmune diseases, tumors, or 1-year GMFM-66 score for each patient was also
other adverse events were observed. While anec- calculated based on their baseline GMFM-66
dotal reports of improved function were common, score, GMFCS level, age, and published percen-
formal motor evaluations were not performed in tiles (Hanna et al. 2008). Since such percentile
this study. values are only available for children ages
Based on this initial experience, a phase II 2 years, 1-year-old subjects (n = 25) were not
randomized, double-blind, placebo-controlled, included in this analysis. We then calculated the
crossover study of a single intravenous infusion actual minus ( ) expected GMFM-66 score for
of autologous CB was conducted at Duke in each child. The actual-expected GMFM-66 score
63 children with CP, ages 1–6 years (Sun et al. was defined as the difference between the
2017b). Children were eligible if they were observed GMFM-66 score at 1 year and the
(1) GMFCS level 2–4 or (2) GMFCS level expected GMFM-66 score at that time point.
1 with hemiplegia if they used their affected Again, there was no difference in the median
hand as an assist only. Children with known actual-expected GMFM-66 scores between the
Table 1 Characteristics of patients and autologous CB units in a randomized, double-blind, placebo-controlled trial
Autologous CB group (N = 32) Placebo group (N = 31)
Patient characteristics
Age, years – median (range) 2.1 (1.1–6.2) 2.3 (1.1–7.0)
Sex – no. (%)
Male 20 (62.5) 22 (71)
Race – no. (%)
Caucasian 27 (84.4) 28 (90.3)
Type of cerebral palsy – no. (%)
Hypotonic quadriplegia 1 (3.1) 3 (9.7)
Spastic diplegia 6 (18.8) 6 (19.4)
Spastic hemiplegia 15 (46.9) 15 (48.4)
Spastic Quadriplegia 10 (31.3) 7 (22.6)
GMFCS level* – no. (%)
I/II 21 (65.6) 21 (67.7)
III/IV 11 (34.4) 10 (32.3)
Bayley cognitive score (n = 43)Τ – median (range) 85 (55–110) 90 (55–110)
Cord blood characteristics – median (range)
Collection volume, mL 66 (4.5–146)
Pre-cryo TNCC, 108 4.4 (1.1–15.5)
Pre-cryo cell dose, 107/kg 3.00 (1.11–8.68)
Cell dose infused, 107/kg 1.98 (0.75–4.83)
CD34+ dose infused, 105/kg 0.60 (0.11–3.90)
CFU dose infused, 105/kg 3.91 (0.04–36.21)
Fig. 2 GMFM-66 scores by randomized treatment GMFM-66 change scores based on median cell doses
assignment and infused cell dose. Panel A: Distribution (precryopreservation doses: low, <3 107/kg vs. high,
of GMFM-66 score at baseline and 1 year in patients > = 3 107/kg; infused doses: <1.98 107/kg vs. high:
randomized to placebo and autologous cord blood. Lines > = 1.98 107/kg)
connect the group means (circles) over time. Panel B:
CB and placebo groups. However, when the CB points greater than expected, whereas subjects
group was analyzed by infused cell dose, subjects who received below the median infused dose
who received above the median infused cell dose improved a median of 1.9 points less than
of 2 107/kg (n = 9) improved a median of 4.3 expected (Fig. 3). Data from the 2-year time
Fig. 3 Actual-expected GMFM-66 scores. High dose Panel B: Actual-expected GMFM-66 scores 1 year after
> = 2 107/kg, low dose <2 107/kg. Panel A: treatment in patients >2 years of age at the time of CB
Actual-expected GMFM-66 scores at 1 year in patients infusion
>2 years of age at baseline based on infused cell dose.
point confirmed this dose relationship. Among 1 year after treatment than children who received
subjects 2 years old at the time of CB treatment lower doses (Fig. 4). In the sensorimotor network,
(at baseline or 1 year), those who received nodes with significant increases in connectivity
2 107 cells/kg (n = 23) improved a median that correlated with improvement in GMFM-66
3.6 points greater than expected in the scores included the pre- and postcentral gyri, basal
following year, whereas subjects who received ganglia, and brain stem. Taken together, results of
<2 107/kg did not improve beyond expectation this trial suggest that autologous CB administered
(median 1.1, p = 0.003, Fig. 3). in sufficient doses (>2 107/kg) may improve
The Peabody Developmental Motor Scales-2 motor function in young children with cerebral
(PDMS-2), which assesses motor skills in chil- palsy and that those improvements may be due
dren from birth through age 5, was also evaluated to enhanced brain connectivity.
in 50 subjects and showed the same dose effect.
Patients who received 2 107 cells/kg had a Clinical Trials of Allogeneic Umbilical
greater change in the Gross Motor Quotient both Cord Blood in CP
at 1-year post-randomization and 1-year post-CB Most children will not have a suitable autolo-
infusion, regardless of the timing of the infusion gous CB unit available. Thus, if cell therapies
(3.0 vs. 0, p = 0.02). are effective in improving motor function, allo-
Children in this study also underwent brain geneic products are essential to be able to extend
MRI, and total brain connectivity analyses were treatment to all children who might benefit.
able to be performed in 38 patients (23 treated, Allogeneic CB infusion has been studied in a
15 placebo). Change in GMFM-66 score and total few clinical trials.
brain connectivity were moderately correlated Related donor allogeneic CB infusion in chil-
(Spearman r = 0.53; 95% CI, 0.25, 0.73; dren with CP was tested in a small phase I clinical
p < 0.001) (Englander et al. 2015) and were trial at Duke University using sibling CB (Sun
inversely related to age (younger patients demon- et al. 2017a). Fifteen children (9 female, 6 male),
strated greater increase in connectivity) but not ages 1–6, with spastic CP were enrolled and
related to baseline GMFCS level, typography of treated with a single intravenous infusion of sib-
cerebral palsy, or gender. Patients who received ling CB. Based on the observation of a dose effect
2 107 TNCC/kg demonstrated a greater in the prior autologous study, sibling CB units had
increase in normalized whole brain connectivity to have a precryopreservation total nucleated cell
Fig. 4 Brain Connectivity via MRI/DTI. Panel A: significantly increased improvement in children receiving
Change in normalized whole brain connectivity one year high doses compared to those receiving low doses, as
after treatment. Panel B: Connectome representation. The indicated by the color chart, with insignificant nodes
nodes and edges included are those that demonstrated shown in gray
count (pTNCC) 2.5 107/kg, negative sterility 1.8–5.2). Four CB infusions were full HLA
cultures, and negative maternal infectious disease matches, and 11 were haploidentical. There were
screening and be a 4/8 HLA match with the no adverse events related to the CB infusion,
participant. Participants were evaluated at base- including no acute infusion reactions or unex-
line and 6 months with functional evaluations pected imaging findings. No platelet antibodies,
(GMFM-66, Peabody), brain CT, and laboratory donor-specific HLA antibodies, or donor cells
studies. Safety assessments were conducted 24 h, were detected in peripheral blood 6 months after
2 weeks, and 3, 6, and 12 months post-infusion. infusion. Six months after treatment, participants
The median baseline age of participants was improved a mean of 4.8 (SD 2.5) points on the
3.7 years (range 1.4–6), and sibling CB infusions GMFM-66 and 1 (SD 2.9) point on the Peabody
had a median TNCC of 4.3 107/kg (range Gross Motor Quotient.
Unrelated donor allogeneic CB has also been ages 6 months to 15 years (Wang et al. 2013b).
studied in children with CP. In Korea, 105 children The only side effects reported were transient
with CP were randomized to three treatment low-grade fever and wound aches. A statistically
groups: allogeneic CB + cyclosporine + erythro- significant change in GMFM-66 percentile was
poietin, erythropoietin alone, and a control group demonstrated at 1, 6, and 18 months post-
(Min et al. 2013). There was one death and eight treatment, though there was no placebo or natural
other serious adverse events (pneumonia, four; history cohort for comparison.
seizure, one; influenza, two; urinary tract infec- Another group recently published the results of
tion, one), but none were considered related to the a randomized placebo-controlled trial of
CB. Nonserious adverse events more common in UC-MSCs in 56 children with CP (Huang et al.
the CB group included pneumonia and irritability. 2018). Patients randomized to UC-MSCs received
At 1 year, there were no reported prolonged or two courses of treatment given 3 months apart and
delayed serious adverse events. Greater improve- each course consisted of 4 weekly doses of
ments in cognitive and select motor functions 5 107 UC-MSCs given intravenously. Patients
were observed in children who received CB and randomized to placebo received sham infusions at
erythropoietin versus controls. The same group the same time points. All patients underwent stan-
subsequently conducted a study of allogeneic dard rehabilitation therapy twice daily 6 days per
CB only versus placebo in 36 children with CP week. Participants were evaluated with the
ages 6 months to 20 years (Kang et al. 2015). In GMFM-88with comprehensive functional assess-
this study, the CB group showed greater improvement (CFA) scale at baseline and at 3, 6, 12, and
ments in gross motor performance at 6 months 24 months after completion of the final course of
compared to the placebo group, and motor out- treatment. EEG and MRI were also performed at
comes were positively correlated with the dose of baseline and during follow-up
CB cells. The median baseline age of participants was
In a Russian study, 80 patients with CP, ages 7 years (range 3–12), and risk factors for CP
1–12 years, received one to six intravenous infu- included hypoxia (29%), low birth weight
sions of allogeneic CB with an average dose of (25.8%), and infection (22.6%), among others.
2.5 108 viable cells per infusion (Romanov The majority of adverse events were mild, and
et al. 2015). Most patients who received four or all consisted of typical childhood ailments that
more infusions showed improvement in tone, were not considered related to the UC-MSCs.
motor, and/or cognitive function, but there was There were no significant structural changes on
no control group for comparison. Factors that brain MRI, and the EEG data was limited and
impacted treatment response included age, sever- inconclusive. However, the UC-MSC group con-
ity of brain damage, and number of CB infusions. sistently demonstrated significantly greater
Thus, data from early phase clinical trials improvement in both GMFM-88 and CFA scores
across the globe have demonstrated that CB infu- at each follow-up time point, reflecting superior
sion is safe in young children with cerebral palsy gross motor and functional outcomes in patients
and suggest that it may be effective in improving who received UC-MSCs. The first trial of
motor function when given intravenously at ade- UC-MSCs in the United States is currently under-
quate doses. way (NCT03473301).
Clinical Trials of MSCs in CP Clinical Trials of CB in Babies

MSCs derived from both bone marrow and umbil- with Hypoxic/Ischemic Encephalopathy
ical cord tissue have been investigated in children (HIE)
with CP in a few studies in China (Wang et al. CP is the subsequent motor manifestation of a
2013a, b, 2015). In one study, autologous bone previously acquired injury to the developing
marrow MSCs were injected intrathecally and/or brain and may the first sign that such an insult
into brain parenchyma of 46 children with CP occurred. Thus, treatment of the child who has
developed CP inherently occurs in the chronic immunologically competent patients, longer

phase of the injury, months to years after the insult follow-up will be necessary for confirmation.
occurred. HIE sustained at the time of birth fre-
quently results in CP and typically has a severe,
acute, and recognizable presentation. Therefore, it Summary
may be amenable to early intervention with the
goal of preventing the development of CP or CP is the most common motor disorder of childhood
decreasing its severity. and in many cases is caused by an acquired brain
In phase I trial of newborns with HIE at birth injury sustained in the perinatal or neonatal period.
conducted at Duke, fresh, non-cryopreserved While many interventions exist to help maximize the
autologous CB was infused in one, two, or four functional capabilities and quality of life of children
doses within the first 72 h of life in babies with with CP, there are no therapies available to help
moderate-to-severe encephalopathy qualifying repair the underlying brain injury. Cell therapies,
for systemic hypothermia, the current standard including CB and UC-MSCs, are safe and have
of care intervention for this condition (Cotten shown signs of potential efficacy in animal studies
et al. 2014). These babies (n = 39) were compared and early phase human trials. Data suggest that these
to a concomitant group of babies who were also cell products are likely to act on existing brain cells
cooled at Duke but did not receive CB cells and their neuroenvironment via paracrine mecha-
(n = 146). Infusions were found to be safe in nisms. Additional investigations are underway and
these critically ill babies, and babies receiving are necessary to elucidate the precise mechanisms of
cells had increased survival rates to discharge action, to rigorously evaluate any functional benefits,
(100% vs. 89%, p = 0.03). Of the babies with and to refine issues related to dosing, timing, and
known 1-year outcomes 64% (16/25) of cell recip- route of administration. If effective, these cell thera-
ients survived with scores 85 in all three pies have the potential to significantly impact the
domains of the Bayley III tested (cognitive, lan- lives of patients with CP and their families and
guage, and motor development), compared to provide a significant societal benefit.
40% (25/63) of the cooled-only infants
( p = 0.04). A phase II randomized, placebo-
controlled, multicenter trial is currently underway Cross-References
(NCT02612155).
▶ Animal Models of Cerebral Palsy: What Can
We Learn About Cerebral Palsy in Humans
Complications ▶ Cerebral Palsy and the Relationship to
Prematurity
In humans and animals, administration of autolo- ▶ Measuring Outcomes in Children with Cerebral
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well tolerated. When the product is washed post ▶ Perinatal Stroke as an Etiology of Cerebral
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Risk Factors for Developing
Cerebral Palsy 10
Antigone Papavasileiou and Marianna Petra
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 112
Gestational Age and Birth Weight . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
Prematurity as a Risk Factor for Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113
Prevention of CP in Preterm Infants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114
Birth Weight as Related to Gestational Age . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 115
Prevention of CP in Infants with Deviations from Optimal Intrauterine Growth . . . . . . 115
Twin or Multiple Birth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
Assisted Reproductive Technology and the Risk for CP . . . . . . . . . . . . . . . . . . . . . . . . . . . . 116
Prevention of CP in Twins or Multiple Births . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
Maternal Risk Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117
Prevention of CP Related to Maternal Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118
Congenital Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118
Prevention of CP Related to Congenital Infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
Congenital Malformations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
Prevention of CP Related to Congenital Malformations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
Coagulopathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
Prevention of CP Related to Coagulopathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120
Genetic Variants and CP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
Prevention of CP Related to Genetic Causes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
Perinatal Risk Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121
Prevention of CP Related to Perinatal Causes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123
A. Papavasileiou (*)
Iaso Children’s Hospital, Athens, Greece
e-mail: theon@otenet.gr
M. Petra
Department of Orthopaedics, Pendeli Children’s Hospital,
Athens, Greece

https://doi.org/10.1007/978-3-319-74558-9_219
112 A. Papavasileiou and M. Petra
Neonatal Risk Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123

Prevention of CP Related to Neonatal Causes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124
Post-neonatally Acquired CP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124
Prevention of CP Related to Postnatal Causes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
Epilogue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
Abstract Introduction
Cerebral palsy is a static neurologic condition
resulting from brain injury that occurs before Cerebral palsy (CP) is a highly heterogeneous
cerebral development is complete. The clini- condition in etiology and in clinical presentation.
cal phenotype of cerebral palsy may result The movement and posture abnormalities are var-
from specific etiologies such as congenital iable and they cause activity limitation, while the
anomalies/maldevelopments or from associated disorders of sensation, cognition, com-
acquired brain injury during the prenatal, munication, perception, behavior, as well as epi-
perinatal, or postnatal periods, due to brain lepsy appear in different degrees of severity
ischemia/asphyxia, trauma, hemorrhage, among patients (Bax et al. 2005). The different
infection, or stroke. When the specific etiol- causes underlying the group of disorders called
ogy cannot be accurately diagnosed, the cur- cerebral palsy are static in nature and result in
rent assumption supported by ample variable patterns of neuropathology. The
scientific evidence is that cerebral palsy is etiopathogenesis of CP is diverse and at times unac-
most of the time related to prenatal neuropa- countable. Several causal pathways and structure-
thology resulting from the interplay of function relationships have been elucidated with the
genetic factors and environmental triggers, help of neuroimaging, particularly MRI techniques.
together leading to various pathways of There are some specific etiologies, such as brain
injury. Many risk factors have been impli- maldevelopments or brain injuries acquired during
cated in this process and have been correlated the prenatal, perinatal, or postnatal periods, due to
with increased prevalence of cerebral palsy. ischemia/asphyxia, trauma, hemorrhage, stroke, or
Some of these factors seem to operate in infection. The underlying pathology has been cor-
infants of all gestational ages, and others are related with the clinical subtypes, the associated
only associated with either full-term or pre- manifestations, as well as the prognosis and out-
mature birth. Overall, preterm birth, intra- come of these patients.
uterine growth retardation, perinatal The discussion on risk factors for CP started
infection, and multiple births are considered several decades ago when epidemiologists ana-
the commonest risk factors associated with lyzed variables associated with an increased risk
cerebral palsy. for the appearance of CP, implying correlational
and not necessarily causal relationships. Tedious
Keywords analysis of research data collected through various
Cerebral palsy risk factors · Prematurity · disciplines has confirmed that some risk factors
Intrauterine growth retardation · Multiple are indeed causal determinants of increased rates
birth · Assisted reproductive technology · of some of the types of CP. Others are still con-
Chorioamnionitis · Congenital infections · sidered possible risks since the causal relationship
Coagulopathies · Perinatal hypoxia/ischemia · is still unproven. Furthermore, the interaction of
Neonatal risk factors genetic variants, known to be linked or possibly
10 Risk Factors for Developing Cerebral Palsy 113
associated with adverse neurodevelopment, with reductions were not seen in infants born with
various events or known hazards in the prenatal or normal birth weight or in those with extremely
the perinatal period acting as triggering factors, low birth weight, the prevalence of CP in the latter
may result in serious neurological outcomes groups is not increasing.
including cerebral palsy (MacLennan et al. 2015). Data derived from the latest Australian CP
It appears that the most prevalent risk factors Register Report (Smithers-Sheedy et al. 2016)
may be different in various places around the showed an overall unchanged prevalence of CP
world as well as at different times. It is interesting for 1993–2006. The majority of children with CP
however that even though perinatal and neonatal were born at term (58.6%), and a decreasing rate
mortality have decreased and maternal, perinatal, of CP in children born extremely preterm and a
and neonatal care have undergone major advance- similar declining trend in children of extremely
ments, the overall prevalence of CP appears to low BW were recorded. Spasticity was the pre-
have been fairly stable over the years. CP remains dominant type of motor disorder (86.5%). Dyski-
the most prevalent among the disorders that nesia was reported in 5.9% and ataxia in 5.3%. In
severely impair motor function in young children. the Australian state of Victoria in birth cohort
The worldwide reported prevalence of CP varies years 1983 to 2009, a declining trend of Gross
significantly from 1.1 to 3.9 per 1000 live births, Motor Function Classification Scale (GMFCS)
partly representing different methods of calcula- levels IV and V was attributed to the effects of
tion. In developed countries, the most recent new methods for neuroprotection and ongoing
reported prevalence of CP ranges from 1.8 to improvement of perinatal care.
2.5/1000 live births [Surveillance of Cerebral Risk factors are usually presented according to
Palsy in Europe (SCPE) 2002; Oskoui et al. the timing of their occurrence in the prenatal,
2013; Van Naarden Braun et al. 2016; Smithers- perinatal, and postnatal periods. It has been esti-
Sheedy et al. 2016; Sellier et al. 2016; Hollung mated that about 70–80% of cerebral palsy cases
et al. 2017]. Accurate registration of CP cases and are acquired prenatally and often from unknown
subsequent estimation of CP prevalence rely on a causes (Reddihough and Collins 2003). Birth
combination of uniform and explicit ways of diag- complications, including asphyxia, are currently
nosing CP, as well as active surveillance programs estimated to account for about 6–8% of patients
and population-based or national CP registers pro- with CP (Reddihough and Collins 2003). The
viding complete, valid, and comparable data most prevalent prenatal and perinatal risk factors
(Hollung et al. 2017). for CP have conventionally been considered to be
The discussion on risk factors for CP remained low birth weight and low gestational age (GA),
relevant for several decades because they were while neonatal encephalopathy, multiple preg-
conceptualized from the start as potentially mod- nancy, infection and inflammation, and genetic
ifiable hazards for the health of the mother, the factors are also important to discuss either as real
fetus, and the neonate. However, despite consid- or candidate causes for the pathophysiological
erable progress in obstetric practices and neonatal pathways that underlie some of the types of CP.
intensive care, there are no major changes in the
group of term children with cerebral palsy, in
whom severe disability and different patterns of Gestational Age and Birth Weight
disability seem to be on the rise (Himmelmann
et al. 2009). Sellier et al. in 2016 reported a sig- Prematurity as a Risk Factor
nificant reduction in the prevalence of CP among for Cerebral Palsy
children of birth weight (BW) 1500 to 2499 g and
a further decrease in children with birth weight The length of gestation has traditionally been
1000 to 1499 g as compared with previous reports considered as the strongest determinant of
(1980–1996). Even though similar significant CP. Data from the most recent Australian Cerebral
Palsy Register Report (Smithers-Sheedy et al. European Perinatal Health Report 2008 derived
2016) confirmed a large difference in the preva- from the SCPE database for 1990–1998, children
lence of CP between different gestational age born with a normal birth weight (2500 g or more)
groups. In children born at 28–31 weeks, the accounted for half of the CP cases in nearly all
gestational age-specific prevalence of CP ranged 16 centers, and overall, 20–25% of children with
from 31.6 to 45.1 per 1000 live births and from 0.9 CP were born with a very low birth weight
to 1.3 per 1000 live births in children born at 37+ (VLBW < 1500 g). The prevalence of CP
weeks of GA, for birth years 1995–2009. In among very low birth weight infants fell from
Europe, a similarly significant difference in the 60.6 per 1000 live births in 1980 to 39.5 per
prevalence of CP has been reported between dif- 1000 in 1996 ( p < 0.0004). This significant
ferent gestational age groups. In a recent study drop in CP prevalence was confined to children
from Sweden, the total CP prevalence (including with a BW of 1000–1499 g and was largely related
CP cases of post-neonatal origin) in a group of to a decrease in bilateral spastic CP (Platt et al.
206 children was 2.18 per 1000 live births. The 2007; European Perinatal Health Report 2008).
CP prevalence specific for gestational age was Up until fairly recently, most of the research for
71.4 per 1000 live births for GA <28 weeks and CP was focused on the outcomes of premature
1.41 per 1000 for GA >36 weeks from data infants of less than 32 weeks gestational age.
derived through a population-based study of However, a higher than expected rate of adverse
94,466 live births in 2003–2006 (Himmelmann neurodevelopmental outcomes has been reported
and Uvebrant 2014). In a meta-analytic review in moderately preterm babies, born at
(Himpens et al. 2008), infants born at 32–36 weeks of pregnancy or with a BW between
22–27 weeks gestation had an average CP rate of 1500 and 2500 grams. Moderate prematurity is
146/1000, ranging from 73 to 282/1000. For those not uncommon since 3–10% of newborns are born
born at 24 weeks, the event rate was 181/1000; for 4 to 8 weeks before term or with moderately low
25 weeks, 214/1000; and for 26 weeks, 188/1000, BW. These children have an increased risk of
and at 27 weeks the event rate decreased to getting CP compared with children born at term
133/1000. Overall, premature birth is a major with a normal BW. Various reports estimated that
risk factor for CP, accounting for 35% of all CP children born moderately preterm or with moder-
cases. The lower gestational ages are associated ately low BW account, respectively, for 15–19%
with higher risk, and for infants born at less than and 14–24% of children with CP. During the 1980
33 weeks gestational age, the prevalence has been to 1998 time period, the overall prevalence of CP
estimated to reach 70/1000 births, a number that in moderately preterm children was reported to
corresponds to a 30-fold higher risk than the one decrease significantly, whereas the total preva-
observed in term-born children (MacLennan et al. lence of CP among children with moderately low
2015). In the extremely preterm children, a rise in BW did not (Andersen et al. 2011). More recently,
neurodevelopmental disability and CP in particu- data analyzed from 20 population-based registers
lar, contemporary with an increased survival, has contributing to the SCPE network showed, for the
been reported between the 1980s and the 1990s first time, a significant decline among infants born
and up to the 2000s (Himmelmann 2013). with moderately low BW, resulting in a significant
In parallel, several reports in the early 1990s overall decrease in the prevalence of CP (Sellier
presented epidemiological evidence that CP risk et al. 2016).
increases with decreasing birth weight. SCPE pro-
vided data on over 6000 children with CP from
13 geographically defined populations in Europe Prevention of CP in Preterm Infants
for the period 1980 to 1990. The rate of CP among
children with a birth weight <1500 g was more Recommendations on interventions to improve
than 70 times higher compared with those with a preterm birth outcomes (WHO 2015a) strongly
birth weight 2500 g (SCPE 2002). In the support the use of antenatal corticosteroid therapy
for women at risk of preterm birth from 24 weeks degree of fetal growth restriction; it is already
to 34 weeks of gestation under specific conditions, increased in infants born with BW below the
based on moderate-quality evidence for newborn 20th percentile and escalates significantly in
outcomes. In addition, the use of magnesium sul- infants born with BW under the 3rd percentile
fate is recommended for women at risk of immi- (MacLennan et al. 2015). IUGR has many
nent preterm birth before 32 weeks of gestation known and unknown causes, either fetal or
for prevention of CP. It has been shown that (mostly) maternal, such as poor implantation and
maternal magnesium sulfate infusion during poor placentation from genetic or anatomical
labor may slightly reduce the risk of CP (MacLen- problems of the uterus (uterine fibroids, congeni-
nan et al. 2015). tally abnormal uterus, abnormal placental site,
The introduction of sophisticated neonatal etc.) or maternal general health etiologies (pre-
intensive care techniques has had the greatest eclampsia, diabetes, systemic lupus, etc.) (Mac-
impact on the outcomes of the most preterm Lennan et al. 2015). Blair and Nelson (2015)
infants. Trends in the prevalence of CP indicate found an increased risk of CP in singletons with
that the introduction of assisted ventilation in the IUGR born after at least 35 weeks gestation to
late 1970s and early 1980s increased the propor- normotensive mothers. Furthermore, major birth
tion of those surviving with CP at a greater rate defects were the most important predictors and
than the proportion of those surviving without increased the odds for CP by 30-fold.
CP. However, already in the 1980s, this trend Infants born with a BW about 1 SD above
was reversed for the low BW infants and in the average always had the lowest risk of CP. Jarvis
1990s also for the very low birth weight or very et al. reported in 2003 that the risk of CP, like the
immature infants. A major source of concern is the risk of perinatal death, is lowest in babies who are
outcomes with respect to CP in the group of of above average weight for gestation at birth, but
extremely low birth weight or immature infants, risk rises when weight is well above normal as
because the prevalence remains stable at a high well as when it is well below normal. In a further
level (Krägeloh-Mann and Cans 2009). analysis of data on singletons from nine SCPE
registers, it was shown that the greater the degree
of growth deviation either up or down from opti-
Birth Weight as Related mal birth weight for gestational age, the higher
to Gestational Age was the CP rate, the larger was the proportion of
males, and the more severe was the functional
Deviations of what is considered as appropriate disability. Compared to those with optimum
BW for GA places infants in the high-risk cate- growth, the risk of more severe CP in males was
gory for neurodevelopmental disabilities. Intra- 16 times higher for those with a BW below the 3rd
uterine growth retardation (IUGR) is an centile and four times higher when BW was above
independent risk factor for CP in infants born at the 97th centile (Jarvis et al. 2005). In conclusion,
term or moderately preterm. Infants born at BW exceeding the 97th percentile has been linked
32–42 weeks’ gestation with birth weights below to an increased risk for CP. The risk was smaller
the 10th percentile for gestational age, according than that represented by a BW for gestational age
to fetal growth standards, were 4–6 times more below the 10th percentile but still significant.
likely to have CP than were children with birth
weights between the 25th and 75th percentiles for
gestational age. For infants born at less than Prevention of CP in Infants
32 weeks’ gestation, the relationship between with Deviations from Optimal
weight and risk was less clear (Jarvis et al. Intrauterine Growth
2003). In term infants, IUGR increases the risk
of CP by 10–30 times. Furthermore, the risk of Prevention of IUGR is the first step toward pro-
spastic CP has been found to increase with the phylaxis against adverse neurodevelopmental
outcomes, including CP. General public health Sheedy et al. 2016). In a study from SCPE data,
measures are indeed relevant such as avoiding Glinianaia et al. (2006) reported that for twins
smoking, alcohol consumption, and other toxic born at 32 weeks’ gestation or more, an increased
agents during pregnancy. In addition, close mon- risk of CP was associated with deviations from
itoring of any chronic or emergent health issues of optimal intrauterine growth at about 1 standard
the mother such as hypertension, diabetes, etc. is deviation above mean weight, as was earlier
crucial for the health of the mother and the fetus. reported for singletons. For twins of less than
Earlier delivery of infants with IUGR is com- 32 weeks gestational age, this pattern was only
monly practiced despite the lack of high-quality demonstrable for small for gestational age babies.
evidence supportive of this practice. In addition, In summary, from studies in Europe, Australia,
cesarean delivery is frequently employed for the and the USA, multiple births appear to have four
purpose of protecting a growth-restricted fetus times higher risk for CP as compared to singleton
from the stress of a vaginal labor. Even though births (Scher et al. 2002; Topp et al. 2004;
these practices appear reasonable especially if Smithers-Sheedy et al. 2016). Scher et al. (2002)
they are carried out in an obstetric hospital with also reported an increased risk of CP in surviving
full neonatal support, there is no evidence that twins whose co-twin was stillborn, had died, or
they change the risk of CP in these babies (Mac- had CP.
Lennan et al. 2015).
As for fetuses with increased BW for gesta-
tional age (large for gestational age), the most Assisted Reproductive Technology
important preventative measure for the fetal and the Risk for CP
neurodevelopment is to diagnose gestational
diabetes mellitus, if present, and to systemati- MacLennan et al. (2015) reported that while mul-
cally treat it. Furthermore, planning delivery in a tiple pregnancy increases the risk for CP in each
well-equipped obstetric hospital is important for twin by 2 times, twins derived from in vitro fertil-
the prevention of complications during labor and ization (IVF), each have over 4 times the risk (9.5/
delivery and in the neonatal period, even though 1000). Hvidtjørn et al. (2010) supported that CP
no data are available to support decreased CP risk increases after IVF, as well as after ovulation
risk. induction, and that this is strongly associated with
the high proportion of multiplicity and preterm
delivery in these pregnancies. Similar results
Twin or Multiple Birth were reported by Goldsmith et al. (2017); they
calculated the birth prevalence of CP after assisted
Data from the SCPE Collaborative Group indi- reproductive technology (ART) and compared the
cate that multiple born infants have a four times clinical outcomes of children with CP after ART
higher risk of developing CP than single births, or natural conception. In a total of 211,660 live
mainly due to the higher risk of preterm birth in births, prevalence of CP was increased in children
multiples. The proportion of multiples among born after ART (7.2/1000 live births compared
infants with CP increased in the 1980s at the with naturally conceived births, 2.5/1000). The
same time that the rate of multiples (in the authors believe that the increased birth prevalence
populations studied) doubled (Topp et al. 2004). of CP in babies born after ART is mediated mostly
In accordance to the above, recent data from by preterm and multiple births but also that pre-
Australia confirmed that the proportion of multi- mature birth alone does not account for the dou-
ple births that developed CP was four times bled odds of CP for ART singletons born very
greater than singletons. In the period examined preterm. In a case-control study by Reid et al.
(for the 1993 to 2006 birth cohort), 12% of chil- (2010), it was found that singleton conception
dren with CP were multiple births as compared using ART is not strongly associated with an
with 3.3% of all Australian births (Smithers- increased risk of CP.
Prevention of CP in Twins or Multiple prolonged rupture of membranes. Intrauterine

Births infection indicated by maternal fever exceeding
38 degrees C in labor and/or a clinical diagnosis of
The above observations, according to several chorioamnionitis were reported in 22% of chil-
researchers, give additional justification for pro- dren with CP and in 37% of children with bilateral
moting single embryo transfers in fertility pro- spastic CP, in a population-based case-control
grams (Hvidtjørn et al. 2010; MacLennan et al. study from California (Grether and Nelson
2015). The latest NICE (National Institute for 1997). The study examined the association of
Health and Care Excellence) Clinical Guideline maternal infection during admission for delivery
[CG156] in the UK, published in February 2013 and the occurrence of (otherwise unexplained) CP
and updated in September 2017 [topic 1.12.6.5], in infants of normal birth weight (BW 2500 g).
states that no more than two (fresh or frozen) In a large American case-control study of single-
embryos should be transferred in IVF treatment, ton infants of GA 36 weeks with diagnosed CP
the number (1 or 2) depending on the quality of (excluding those with brain malformation, chro-
embryos and the age of the mother. mosomal anomaly, congenital viral infection, and
postnatal brain injuries), clinical chorioamnionitis
was found to be an independent risk factor asso-
Maternal Risk Factors ciated with a fourfold increased risk of CP
(Wu et al. 2003). Chorioamnionitis and mostly
A systematic review of reports on term babies in necrotizing funisitis (histopathologic diagnosis
developed countries examined, among others, referring to the extension of infection or inflam-
preconceptional risk factors for CP (McIntyre mation to the umbilical cord) indicate the presence
et al. 2013). Prior maternal diagnosis of seizures, of an infection that predates labor (MacLennan
intellectual disability or thyroid disease was et al. 2015). In most epidemiological studies,
strongly associated with an increased risk of chorioamnionitis is associated with an increased
CP. A maternal obstetric history of stillbirth or risk of CP, indicating that some maternal infec-
neonatal death, history of three or more miscar- tions during gestation may be part of a causal
riages, and maternal age over 40 years were also pathway leading to CP. This is true for preterm,
reported to be associated in various degrees with as well as for term or near-term infants (Wu et al.
an increased risk for CP. Fetal exposure to various 2003; MacLennan et al. 2015). Preterm infants
hazards, either exogenous or related to maternal have higher rates of complications of chorioam-
health, has been a matter of long-standing concern nionitis than term infants. These include perinatal
for neurodevelopment. Infections, inflammation, death (25 vs. 6% preterm vs. term), neonatal sep-
teratogenic medications, illicit drugs, alcohol, sis (28 vs. 6%), pneumonia (20 vs. 3%), grade 3 or
toxic environmental agents, and others have 4 IVH (24 vs. 8%), and respiratory distress (62 vs.
been implicated in affecting the healthy or vulner- 35%) (Tita and Andrews 2010). Pappas et al.
able fetus. Among the multiple antenatal events (2014) reported that histological plus clinical
that were examined as possible risk factors in chorioamnionitis was associated with increased
McIntyre’s systematic review, bleeding in the sec- odds of cognitive impairment and death/
ond and third trimesters, hypertension in preg- neurodevelopmental impairment in extremely
nancy, and preeclampsia were associated with preterm infants.
increased risk of CP across all gestations. Abnor- It is important to emphasize that infections in
malities of amniotic fluid volume have been also pregnancy either viral or bacterial may be rela-
identified as a statistically significant risk factor in tively insidious and not readily recognized clini-
studies of all CP, with conflicting evidence for cally. Histologic chorioamnionitis is diagnosed on
term-born infants (McIntyre et al. 2013). the basis of pathologic findings on microscopic
Chorioamnionitis, a common infection of examination of the placenta and may be present
pregnancy, typically occurs when there is not only when clinical chorioamnionitis is evident
but also in subclinical chorioamnionitis (Tita and Prevention of CP Related to Maternal

Andrews 2010). Histological examination of the Factors
placenta for inflammatory pathology is rarely
performed in the absence of suspicion. However, For most of the aforementioned maternal risk
white matter damage may be acquired during an factors, valid data supporting the reduction of
intrapartum infection that affects the fetus and its CP risk through preventive strategies are not
brain and/or during labor or in the neonatal period. available. Preventing fetal exposure to infections,
The mechanism through which this early damage inflammation, teratogenic medications, illicit
to the immature brain occurs in the presence of an drugs, alcohol, toxic environmental agents, and
intrauterine infection/inflammation involves the others is definitely important. In addition, proper
excessive or abnormal production of cytokines management of maternal epilepsy as well as other
in genetically predisposed individuals, after the maternal conditions such as incompetent cervix,
microorganisms or their products gain access to hypertension in pregnancy, and preeclampsia can
the fetus. A systemic response termed FIRS (fetal also reduce the likelihood of fetal and neonatal
inflammatory response syndrome) results from brain injury possibly leading to CP.
the activation of the cytokine network that subse- Detailed recommendations for the prevention
quently may produce damage to the white matter and treatment of maternal peripartum infections
of the fetal brain. In the preterm infant, the imma- have been provided (WHO 2015b), ranging from
ture brain is particularly vulnerable to the hygienic measures to antibiotic use, most based
pro-inflammatory cytokines. FIRS has been on moderate- or low-quality evidence. In
linked in preterms with perinatal death, multi- chorioamnionitis, prompt administration of anti-
organ injury, including chronic lung disease, as biotics to women with preterm premature rupture
well as fetal or neonatal brain injury that leads to of membranes is recommended in order to prevent
periventricular leucomalacia and cerebral palsy both maternal and fetal complications. It has been
(Tita and Andrews 2010). Elevation of cord shown to decrease the incidence of clinical
blood IL-6 in the setting of preterm labor and chorioamnionitis, to prolong the time to delivery,
premature rupture of membranes was originally and to reduce the likelihood of neonatal death,
considered to define FIRS. However, FIRS may chronic lung disease, or major cerebral abnormal-
also occur in term gestations (Tita and Andrews ity on cranial ultrasound. Reduction of the time
2010). Lastly, in the very preterm infant, a “multi- between diagnosis and delivery by performing a
hit” hypothesis for neonatal white matter injury cesarean section (C/S) is not indicated unless there
resulting from the cumulative effects of chronic are other obstetric indications, since time to deliv-
placental inflammation, acute fetal inflammation, ery after institution of antibiotic therapy has not
and postnatal inflammatory events has been pre- been shown to affect morbidities (Tita and
sented (Korzeniewski et al. 2014). Andrews 2010).
In an effort to examine if placental disease may
indicate antepartum conditions that may predis-
pose to intrapartum brain injury, Redline in 2005 Congenital Infections
reported on the findings in the placentas of
125 neurologically impaired term infants and Fetal infections by toxoplasma, cytomegalovirus
250 consecutive singleton deliveries of 36 or (CMV), rubella, and herpes have been implicated
more weeks of gestation. Severe fetal placental as possible causes of abnormal brain develop-
vascular lesions (chronic villitis, large infarcts, ment. A retrospective study on the detection
fetal thrombotic vasculopathy, and meconium- through PCR of viral DNA in newborn screening
associated fetal vascular necrosis) were highly cards of children with CP and controls showed
correlated with neurologic impairment and that of all the viruses tested (herpes simplex
CP. Prevalence of these lesions in the subgroup viruses 1 and 2; varicella zoster virus; Epstein-
of 64 infants with CP was 52%. Barr virus; cytomegalovirus, human herpes
viruses 6, 7, and 8; and parvovirus), evidence of the first two trimesters may be suggested. In
congenital viral infection was uncommon in cases women with primary CMV infection, hyper-
of CP and controls. The exceptions were CMV immune globulins are recommended in order to
and Epstein-Barr virus that were significantly prevent possible viral transmission to the fetus.
associated with CP (McMichael et al. 2012). CMV vaccination, particularly for women in the
Djukik et al. in 2009 presented evidence that reproductive age, has not yet been developed
genetic susceptibility to viral exposure may (Nigro 2016).
increase the risk of cerebral palsy. For infants
born between 32–36 weeks of gestation, they
found a tenfold increase in the risk of quadriplegic Congenital Malformations
CP with homozygous/heterozygous IL-6 gene
polymorphisms. Viral exposure in combination These anomalies are present at birth and they are
with IL-4 gene polymorphisms in preterm infants observed in 2 to 3% of children. They may occur
was associated with a fourfold increased risk of in any body organ, and they are classified as
quadriplegia. They concluded that polymor- recognized syndromes, chromosomal anomalies,
phisms in IL-6 or IL-4 genes, in the presence of cerebral malformations, or non-cerebral
viral exposure, may increase susceptibility for the malformations. In the most recent European Peri-
development of hemiplegic and quadriplegic natal Health Report (2010), the prevalence rate of
CP. Of particular interest in recent years is the all standard congenital anomaly subgroups (major
infection by CMV, the most common cause of structural congenital and chromosomal anoma-
vertically transmitted viral infection, affecting lies) recorded by the European Surveillance of
around 1% of live births. The infection is symp- Congenital Anomalies (EUROCAT) network for
tomatic in about 10% of infected children who are birth years 2006–2010 was 20.89/1000 live births.
at higher risk for severe neurological disorders, A study by Rankin et al. (2010) used electronic
including CP. Early CMV infection has been asso- matching of cases in population-based CP and
ciated with lissencephaly, pachygyria, poly- congenital anomaly registries. Fifteen percent of
microgyria, schizencephaly, calcification, children with CP in the studied population had a
cerebellar hypoplasia, and/or hypoplasia/agenesis diagnosed congenital anomaly (CA), with 8.8%
of the corpus callosum. Late CMV infection has involving the brain, whereas 1.4% involved a
been associated with white matter abnormalities syndrome (not affecting the brain) or chromo-
including disturbed myelination (Dakovic et al. somal anomaly. Children with ataxic CP were
2014). It is believed by many researchers that the diagnosed more frequently with a cerebral mal-
potentially severe effect of CMV on formation (41.7%). The most common congenital
neurodevelopment has not been accurately esti- anomalies (not affecting the brain) were cardiac
mated. In an Australian study, CMV viremia in the (in 12.6% of children with CP and CA), urinary
newborn period, indicating congenital CMV (5.4%), and musculoskeletal (5.4%). Children
infection, was highly prevalent among children born at term had a higher prevalence of brain
with CP (Smithers-Sheedy et al. 2017). malformations (13%) than those born premature
(3.8%). In a population-based registry study, the
incidence of congenital non-CNS malformations
Prevention of CP Related to Congenital among children with CP was considerable; how-
Infections ever, no important differences were detected in
these children as compared to other children
Routine antepartum screening for CMV has been with CP in terms of neurological subtype distri-
discussed, but it does not appear practical. In bution, functional severity, and comorbidities. No
women at high risk for CMV infection, for exam- associations with congenital infections were
ple, daycare workers, serial examinations of found (Self et al. 2012). Congenital anomalies
CMV-specific IgG and IgM antibodies at least in where brain dysgenesis is clear and evident
represent specific prenatal etiologies for cerebral stroke and coagulopathy is still controversial.
palsy and are not considered as risk factors. They Curtis et al. (2017) reported on tests for
are known to be associated with some of the most thrombophilia performed after 12 months of age
important CP risk factors, such as low birth on stroke cases and controls in a prospective
weight, low gestational age, and prenatal infec- population-based study and suggested minimal
tions (Self et al. 2012). association between perinatal stroke and
thrombophilia, without excluding the possibility
of disordered coagulation at the time of stroke.
Prevention of CP Related to Congenital Mutations localized either to the factor V gene
Malformations or in the prothrombin gene have been identified
that predispose heterozygous carriers to venous
The evidence concerning the prevention of birth thrombosis (Reddihough and Collins 2003).
defects (other than neural tube defects) with folate MTHFR C677T mutation approximately doubles
and supplemental vitamins is presently controver- the risk of CP in preterm infants. A combination
sial (McIntyre et al. 2013). Nevertheless, general of homozygous MTHFR C677T and heterozy-
measures such as healthy diet, hygiene, preven- gous PGM mutations increases the risk of quadri-
tion of exposure to toxic agents and other envi- plegia fivefold at all gestational ages (Gibson et al.
ronmental hazards, and prevention of infections 2005). These results derived from a large case-
through immunizations and other public health control study suggest the possibility of a complex
measures are commonly discussed as a means to relationship between inherited thrombophilias
reduce the frequency of certain congenital anom- and subtypes of CP at different gestational ages.
alies. The frequent association of congenital Genetic variants that concern vitamin K-depen-
malformations with fetal growth restriction points dent coagulation, as well as associations with
toward genetic factors; however, nutritional dis- mutations in COLAA1 and COLAA2 genes,
orders, teratogens, and congenital infections are have been associated with risk of IVH in preterms
all important contributors to brain and antenatal porencephaly, respectively (de Vries
maldevelopment (MacLennan et al. 2015). and Heep 2016).
Earlier studies suggested that there is an asso-
ciation between inflammatory mediators and
Coagulopathies markers of autoimmune and coagulation disorders
with CP, through interacting pathways
Unilateral CP is often accompanied by infarcts in (Reddihough and Collins 2003); more recent stud-
the middle cerebral artery distribution, attributed ies are also supportive of this idea, concluding that
to prenatal or perinatal stroke. In children, in carriage of polymorphism in the tumor necrosis
contrast to adults, the underlying etiology of factor-alpha and mannose-binding lectin genes
stroke is usually detectable. Coagulopathy, con- are associated with an increased risk of CP (Mac-
genital heart disease, and an infectious process are Lennan et al. 2015).
common etiological factors. Several early reports
described the relation between neonatal cerebral
infarction, coagulopathies, and a later diagnosis of Prevention of CP Related
hemiplegic CP. In children with hemiplegic CP, to Coagulopathies
when an explanation for the cerebral infarction is
not evident, diagnostic testing for a coagulation The coagulation profile of pregnant women with
disorder such as factor V Leiden deficiency, the prior obstetric history indicating possible coagu-
presence of anticardiolipin or antiphospholipid lation disorder as a contributing factor is usually
antibodies, and protein C or S deficiency may be investigated. In preterm babies, immature hemo-
recommended, even though the existing evidence stasis in association with other perinatal risk fac-
for the association of prenatal or perinatal cerebral tors may adversely affect the vitamin
K-dependent coagulation pathway. It has been where there is genetic susceptibility (MacLennan
concluded, however, that vitamin K given to et al. 2015).
women prior to very preterm birth does not pre-
vent intracranial hemorrhage in the infant or
adverse neurodevelopmental outcome (de Vries Prevention of CP Related to Genetic
and Heep 2016). Causes
Molecular genetic techniques are increasingly

Genetic Variants and CP employed in the assessment of patients with atyp-
ical CP phenotypes and family history of early-
Genetic etiology has been shown in some patients onset neurologic disorder with associated CP, as
of consanguineous origin pointing toward autoso- well as those with normal brain MRIs or neuro-
mal recessive mutations (Moreno-De-Luca et al. imaging findings indicative of a metabolic etiol-
2012; Kruer et al. 2013); however, these findings ogy. A genetic diagnosis in the index case may be
can only explain some very rare mostly familial very important for family counseling. In the
CP cases. Some Mendelian conditions may pre- future, targeted screening of parents for inherited
sent with atypical CP phenotypes; neurogenetic causative genes, embryo preimplantation screen-
syndromes such as Rett (MECP2) and Angelman ing, and early prenatal diagnostic DNA tech-
(UBE3A) syndromes; cerebral dysgenesis such as niques, as well as modern gene therapies, may
classic lissencephaly (PAFAH1B1) and be applied for the prevention of some of the cere-
pontocerebellar hypoplasia type 1 (VRK1); bral palsies (MacLennan et al. 2015). Inborn
neurometabolic disorders including Lesch- errors of metabolism are well-known “CP imita-
Nyhan syndrome (HPRT) and glutaric acidemia tors.” It is important to recognize them early
type 1(GCDH); and heritable thrombophilias, like because they might be treatable, so that neurolog-
protein C deficiency (PROC) (Moreno-De-Luca ical damage can either be reversed or prevented.
et al. 2012). The hereditary spastic paraplegias are
also genomic diseases that may present as
CP. More than 40 loci have been mapped for this Perinatal Risk Factors
group of disorders, inherited in an autosomal
dominant, autosomal recessive, or X-linked fash- Labor and delivery complications are commonly
ion (Moreno-De-Luca et al. 2012). Other genetic found in infants subsequently diagnosed with CP,
causes or associations with increased risk for CP but this does not necessarily imply a causal rela-
are believed to occur infrequently. However, the tionship between the two. There is no doubt that
true incidence is currently unknown, and the chal- adverse labor and delivery events may lead to
lenge of identifying neurogenetic syndromes in perinatal brain injury, but this association has to
patients presenting with static motor disorders be proven beyond any doubt, for the sake of
and associated features consistent with a CP phe- proper diagnosis but also because of ethical and
notype, but otherwise undetermined etiology, is legal reasons. Prenatally acquired vulnerabilities
ongoing. of the fetus due to genetic factors,
In sporadic CP cases, next-generation sequenc- maldevelopment, antenatal hazards, or else may
ing showed that 14% of cases have likely causa- predispose to problems in the course of labor and
tive single-gene mutations and up to 31% have delivery. Nevertheless, Martinez-Biarge et al., in
clinically relevant copy number variations (Mac- 2013, in their analysis of antepartum and
Lennan et al. 2015). It is evident that these hetero- intrapartum events possibly leading to hypoxic-
geneous genetic variants require function ischemic encephalopathy concluded that this con-
investigations to prove causation. Further detailed dition cannot be attributed to antepartum factors
genetic studies are necessary in order to elucidate alone, but these factors could be leading to
if clinical risk factors could act as triggers for CP adverse intrapartum events or increase the
vulnerability of the fetus to perinatal hypoxia and related to preexisting pathology. It is also impor-
ischemia. Intrapartum events such as prolonged tant to note that these criteria as a group have been
membrane rupture, abnormal fetal heart monitor- verified (MacLennan et al. 2015). In addition, new
ing during labor and delivery recorded through studies and systematic reviews continue to
cardiotocography (electronic monitoring of fetal address the topic of intrapartum asphyxia as a
heart beat and uterine contractions), thick meco- causal determinant of CP. In a systematic review
nium, sentinel event, shoulder dystocia, tight from Australia, birth asphyxia, despite the varia-
nuchal cord, and failed vacuum were factors that tions in reporting, was the strongest and most
facilitated the development of hypoxia-ischemia consistent risk factor in CP for term infants.
in the presence of antenatal factors. In an analysis Meconium aspiration was a strong risk factor for
of the effects of multiple pre- and perinatal risk births at all gestational ages. Instrumental deliver-
factors on the occurrence of CP from the Norwe- ies as compared to spontaneous vaginal or elective
gian registry, it was shown that the majority of cesarean section were associated with increased
term children with CP most likely had an antenatal risk of CP, as was breech delivery. Abnormal
or single cause, suggesting individual susceptibil- duration of labor and fetal presentation were sta-
ity to an injury, while the majority of children born tistically significant risk factors in studies consid-
preterm had combinations or sequences of ante- ering all CP, but not in studies of term CP
natal and perinatal risk factors as the most likely (McIntyre et al. 2013). A tight nuchal cord may
cause of CP (Stoknes et al. 2012). In the past, potentially induce chronic asphyxia and has been
before specific diagnostic criteria for intrapartum reported to increase the risk of spastic quadriple-
asphyxia were defined, this diagnosis was seri- gic CP (MacLennan et al. 2015). In a case-control
ously overestimated as a specific etiology for study from Sweden that included 2303 infants
CP. The essential criteria that need to be fulfilled born between1984 and 1998 with a diagnosis of
before cerebral palsy could be attributed to acute CP and 1.6 million infants without this diagnosis,
intrapartum asphyxia have been established (Mac- in term births, low Apgar scores, breech presen-
Lennan et al. 2015) through a slow and tedious tation at vaginal birth, instrumental delivery, and
process that involved internationally recognized emergency cesarean delivery were associated
experts from the American College of Obstetri- with a high risk for CP. Preeclampsia and abruptio
cians and Gynecologists and the International placentae were among the factors that were asso-
Cerebral Palsy Task Force who reviewed these ciated with high risk for CP in preterms
criteria based upon advances in scientific knowl- (Thorngren-Jerneck and Herbst 2006). Pre-
edge. Individually, several of these criteria may be eclampsia increased the risk of CP across all ges-
considered as risk factors, but when they are col- tations (McIntyre et al. 2013). Others believe that
lectively fulfilled, the association of intrapartum the association of preeclampsia and CP is contro-
hypoxic-ischemic insult and CP is likely. These versial and that it is associated with an increased
essential criteria are in fact prerequisites if one is risk of cerebral palsy in term infants, but this
to propose that an intrapartum hypoxic-ischemic association does not seem to exist in preterm
insult has caused a moderate to severe neonatal infants (Reddihough and Collins 2003). In a
encephalopathy that subsequently results in cere- study from the Norwegian CP Registry, exposure
bral palsy. (MacLennan et al. 2015). Intrapartum to preeclampsia was also associated with an
asphyxia is still overdiagnosed in many countries increased risk of CP, but this association was
where the international diagnostic criteria for this mediated through the children being born preterm
diagnosis are not carefully applied. or small for gestational age or both. In term
It is important to emphasize that hypoxia at babies, preeclampsia was a risk factor for CP
birth may be primary or secondary and these when the children were small for gestational age
international consensus criteria help to separate (Strand et al. 2013). Prolonged shoulder dystocia
the limited number of cases of CP that are really is a risk factor for fractures, stillbirth, or severe
attributed to acute intrapartum hypoxia from those acute hypoxia, if severe (McLennan et al. 2015).
Low Apgar scores have been strongly associated for CP. It has been reported that weeks 37 and
with CP in term-born children, even though the 38 have similar risks, both for CP as well as for the
majority of those with a low Apgar score do not general likelihood of delivery problems with
develop CP. Studies in children with low birth weeks 42 and 43, leaving 39 to 41 weeks as the
weight have shown conflicting results on the asso- optimum time for delivery, if all other conditions
ciation between Apgar score and CP. Lie et al. permit (Moster et al. 2010).
(2010) reported that 11% of children with an New interventions such as head or body
Apgar score of less than 4 were diagnosed with cooling have been found to be effective in term
CP, independent of birth weight [but the associa- babies with birth asphyxia as long as the neonate
tion of low Apgar score with CP was high in receives the treatment within hours from the
children with normal BW (2500 g) and modest causal event (McIntyre et al. 2013; MacLennan
in children with low BW (<1500 g)]. et al. 2015). This intervention represents one of
the very few preventive measures for brain injury
in the term neonate.
Prevention of CP Related to Perinatal
Causes
Neonatal Risk Factors
At this point there are no evidence-based obstetric
clinical practices that have been shown to reduce Risk factors in the neonatal period associated with
the risk of CP in term babies. McIntyre et al., in CP include severe infection (sepsis and/or CNS
2013, reviewed the literature in order to identify infection), neonatal seizures, and respiratory dis-
preventable risk factors or strategies that could ease (Reddihough and Collins 2003). In the pre-
reduce the likelihood of their occurrence. She term infant, patent ductus arteriosus, hypotension,
concluded that preventing some “distal” factors blood transfusion, prolonged ventilation, pneu-
on the pathway to brain injury may interrupt the mothorax, sepsis, hyponatremia, total parenteral
process before the injury occurs. For example, if nutrition, neonatal seizures, and parenchymal
placental abnormality is prevented during preg- damage with ventricular dilatation have been
nancy with heparin administration, this could be a associated with increased risk for CP
promising intervention; however, “long-term data (Reddihough and Collins 2003). Several factors
are sparse and insufficient.” She also discussed have been associated with neonatal cerebral hem-
curtailing post-term pregnancy as a means of pre- orrhage. In the very preterm infants born at less
venting meconium aspiration and instrumental than 28 weeks of gestation, increased interleukin-
deliveries as a potential risk for CP and the 6 serum concentrations, a surrogate of early sep-
employment of early introduction of strategies to sis, measured within the first 12 h postpartum,
prevent prolonged labor. The role of C/S, as a were associated with the development and extent
means of avoiding prolonged labor and pre- of germinal matrix and intraventricular hemor-
venting perinatal asphyxia, is also frequently rhage (GMH-IVH) (de Vries and Heep 2016).
discussed; however, no research has been Perinatal trauma and various metabolic derange-
published to provide evidence for this practice. ments such as hypernatremia, commonly found in
C/S is not a risk-free procedure, but it could be extremely preterm newborns (de Vries and Heep
very well indicated for some women and could 2016), untreated hyperbilirubinemia, severe
indeed be a preventative measure for adverse hypoglycemia (Reddihough and Collins 2003),
labor and delivery outcomes. Lastly, because of and vitamin K deficiency have been associated
the increasing number of elective C/S in infants with increased risk for CP. The role of vitamin K
derived from assisted conception or due to mater- in the occurrence or the prevention of neonatal
nal factors, it is important to emphasize that the intracranial bleeding has been discussed with sev-
standard definition of term (37–41 weeks) does eral clinical studies implicating the reduced vita-
not correspond well with the period of lowest risk min K-dependent prothrombin activity in the
pathogenesis of GMH-IVH in preterm infants. the immediate neonatal period, through fluctua-
Furthermore, concurrent perinatal risk factors tions of the intravascular pressure or blood flow in
may adversely affect the vitamin K-dependent the immature preterm brain. The introduction of
coagulation pathway. For term infants, there was noninvasive ventilatory support such as CPAP
conflicting evidence on the risk of hyper- and BIPAP and other improvements in the respi-
bilirubinemia for CP; however, in McIntyre ratory support of the very preterm neonate are likely
et al.’s (2013) systematic review in the two studies to further decrease the incidence of GMH-IVH
that specified the occurrence of severe jaundice, (de Vries and Heep 2016). In addition, postnatal
the risk for CP was significant. Among neonatal surfactant replacement therapy recommended for
risk factors, seizures were the strongest across all intubated and ventilated newborns with respiratory
gestational ages (McIntyre et al. 2013). Garfinkle distress syndrome has been also found to be asso-
and Shevell in 2011 reported that in term infants, ciated with a reduction in GMH-IVH (WHO 2015a;
among other factors, experiencing a seizure dur- de Vries and Heep 2016).
ing the first 24 h of life, having a seizure other than In term infants, no prevention strategies are yet
focal clonic, and showing a moderately or identified for neonatal seizures and hypoglycemia
severely abnormal EEG background were major (McIntyre et al. 2013). Careful diagnosis and
determinants for an adverse outcome defined as management of neonatal seizures are important
death, cerebral palsy, global developmental delay, in preventing further complications in the sick
and/or epilepsy. neonate. Continuous EEG monitoring is impor-
tant in the detection of subclinical seizures that
need to be identified and treated.
Prevention of CP Related to Neonatal
Causes
Post-neonatally Acquired CP
Systematic strategies are employed for the pre-
vention of early-onset and late-onset neonatal Because brain development continues at least
infections. These include prevention of infection during the first 2 years of life, a CP diagnosis is
associated with premature rupture of membranes applied for persistent motor function impair-
and preterm labor, prevention of neonatal group B ments resulting from brain injuries occurring at
streptococcal disease, and prevention of neonatal least until the age of 2 years. In the literature of
nosocomial infections (WHO 2015a, b). the 1980s, these cases were thought to account
In preterm births, prenatal and postnatal phar- for about 10 to 18% of patients under the clinical
macologic agents have been used to prevent phenotype of CP (Reddihough and Collins
GMH-IVH with variable results. Administration 2003), while more recent literature reports that
of corticosteroids antenatally has been shown to about 5% of CP cases are post-neonatally
be the most important protective factor for devel- acquired (Cans et al. 2004; Smithers-Sheedy
opment of GMH-IVH. Antenatal vitamin K et al. 2016). There are various etiologies and
administration to the mother in spite of promising risk factors in the post-neonatal period that
initial reports has not yet proven its value in the have been associated with CP. In developed
prevention of GMH-IVH. Postnatal use of indo- countries, CNS infections, accidents (traumatic
methacin showed a significant reduction in the brain injury and near drowning), and cerebro-
incidence of severe intraventricular hemorrhage vascular events are the prevailing causes of brain
(de Vries and Heep 2016). It has been also injury. In developing countries, other infections
shown that delayed cord clamping was important such as malaria remain important causes of cere-
in preventing cerebral hemorrhage (de Vries and bral palsy acquired in the post-neonatal period
Heep 2016). Attention has been paid to cardiovas- (Reddihough and Collins 2003). From data of
cular and respiratory dysfunction as playing a the SCPE network for children with post-
major role in the development of a GMH-IVH in neonatally acquired CP, born between 1976 and
1990 (Cans et al. 2004), vascular episodes ▶ Perinatal Stroke as an Etiology of Cerebral
accounted for 20% of the cases, head injury for Palsy
18%, and infection for 50%. ▶ Postnatal Causes of Cerebral Palsy
The current Australian CP Registry data (2016) ▶ Problems During Delivery as an Etiology of
for the birth cohort from 1993 to 2006 identified Cerebral Palsy in Full-Term Infants
cerebrovascular accidents (either spontaneous or
associated with surgery or cardiac complications)
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Part III
Epidemiology
Epidemiology of Cerebral Palsy
11
Kate Himmelmann, Sarah McIntyre, Shona Goldsmith,
Hayley Smithers-Sheedy, and Linda Watson
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
Definition and Classification of CP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132
Frequency and Patterns of Occurrence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
Birth Prevalence: Overall Trends . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
Trends by Birth Weight and Gestational Age . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
Trends in Motor Severity and CP Subtypes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137
Accompanying Impairments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 139
Survival in CP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140
Major Risk Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140
Multiple Birth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 140
Congenital Anomalies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
Congenital Cytomegalovirus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
Prevention of CP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 141
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143
Abstract
The epidemiology of cerebral palsy includes
studies across whole populations within a
K. Himmelmann (*)
Department of Pediatrics at Institute of Clinical Sciences, defined geographic area that center on deter-
University of Gothenburg, Gothenburg, Sweden mining the frequency of the condition; identi-
e-mail: kate.himmelmann@vgregion.se fying patterns, risk factors, and causal
S. McIntyre · S. Goldsmith · H. Smithers-Sheedy pathways; and evaluating the effectiveness of
Cerebral Palsy Alliance, University of Sydney, Sydney, interventions for prevention and reducing
NSW, Australia
severity. This chapter uses population data
e-mail: smcintyre@cerebralpalsy.org.au;
sgoldsmith@cerebralpalsy.org.au; from long-standing registers to give an update
hsmitherssheedy@cerebralpalsy.org.au on these studies. The rates of cerebral palsy in
L. Watson developed countries have fluctuated between
Western Australian Register of Developmental Anomalies 1.5 and 3/1000 live births throughout the last
(WARDA), Western Australian Department of Health, 50 years. There have been periods of reducing
Perth, Australia
rates, which have been followed by increases
e-mail: linda.watson@health.wa.gov.au

https://doi.org/10.1007/978-3-319-74558-9_9
132 K. Himmelmann et al.
in rates. We are currently in another decline, Definition and Classification of CP

and the question is as follows: Can this decline
continue under 1.5/1000 live births for the first CP comprises a group of conditions, heteroge-
time? It is now becoming increasingly impor- neous in causation and manifestations. The
tant to measure frequencies in low- and most recent definition of CP includes the naming
middle-income countries, where frequencies of some accompanying impairments as put
are expected to be higher, but with possibilities forward by the participants at an international
for primary prevention. Patterns have emerged workshop on the definition and classification
among gestational age and birth weight cate- of CP, in Washington in July 2004 (Rosenbaum
gories as well as motor type and topographic et al. 2007):
distributions. We understand more about
causal pathways that include preterm birth, Cerebral palsy (CP) describes a group of disorders
of the development of movement and posture, caus-
multiple births, infection, and congenital ing activity limitation, that are attributed to
anomalies which open more doors to primary non-progressive disturbances that occurred in the
prevention and reduced severity than when developing fetal or infant brain. The motor disor-
research was simply focused on birth asphyxia. ders of cerebral palsy are often accompanied
by disturbance of sensation, cognition, communi-
cation, perception, and/or behavior, and/or by a
Keywords seizure disorder.
Cerebral palsy · Epidemiology · Prevalence ·
Risk factors · Prevention This new definition reflects a more comprehen-
sive way of looking at CP. However, the classifi-
cation rests firmly upon the type and distribution
Introduction of motor impairment. Consensus in classification,
regarding both CP definition and the different
The epidemiology of cerebral palsy (CP) is the types (Surveillance of Cerebral Palsy in Europe
study of the distribution and determinants of CP 2002), is important to avoid misconceptions about
in specified geographic populations and the the etiology and severity of the disability (see
application of this study to monitoring the con- ▶ Chap. 21, “Classification Terminology in Cere-
dition and to communicating unexpected bral Palsy”). Figure 1 presents a decision tree
increases and, conversely, expected or unex- developed by the Surveillance of Cerebral Palsy
pected decreases. As such CP epidemiology is in Europe (SCPE) (Surveillance of Cerebral Palsy
important as an indicator of hazards and quality in Europe 2000, 2002) for inclusion or exclusion
care, relevant to maternal, perinatal, and neona- of a child with a motor disorder as appropriate for
tal care (Hagberg et al. 1982). the umbrella term of “cerebral palsy.” Although
Epidemiology of any condition has key pur- there is agreement through Europe for this deci-
poses including the following: to (1) study the sion tree, there are two areas of discrepancy with
natural history; (2) determine the frequency; other surveillance groups across the world
(3) identify the patterns of occurrence; (4) identify (Smithers-Sheedy et al. 2014). In Europe, (1) a
risk factors, potential causes and causal path- child needs to survive until the age of two to be
ways, and opportunities for prevention; and included under the umbrella of CP; and (2) if a
(5) evaluate the effectiveness of preventive and child meets the criteria for CP, has generalized
ameliorating interventions. The ultimate goal of hypotonia and no ataxia, he or she is excluded
epidemiology is to apply this knowledge and to from the umbrella term of CP. These discrepancies
play a role in the improvement of public health. have not hampered research, comparisons, or col-
This chapter will specifically address the fre- laboration, as data sets can be harmonized easily
quency, patterns of occurrence, some risk factors, by removing those who die before the age of two
potential causes, and effectiveness of preventive and those with “hypotonic CP” for specific
measures in CP. projects.
11 Epidemiology of Cerebral Palsy 133
Does the child have a

disorder of movement or EXCLUDE Was the child at least 4 Go back and reassess
Is the child still living?
posture of central origin? years old when assessed? after age 4
Does the child have a Does the child have a

EXCLUDE Did the child die before
disorder of motor function? syndrome/brain anomaly or EXCLUDE
the age of 2 years?
chromosome abnormality?
Is the condition progressive *Recheck - Does the child

(loss of previously acquired EXCLUDE meet the criteria for the Does the child have Are there signs of
skills)? definition of CP? generalized hypotonia? ataxia?
EXCLUDE Look at Classification Tree Ataxic CP EXCLUDE
Fig. 1 Decision tree for cerebral palsy. (Reproduced from SCPE Collaborative Group (2000))
Is there persisting
increased muscle tone in
one or more limbs?
Are both sides of the

body involved? Is the tone varying ?
Is there generalized hypotonia

with signs of ataxia?
Spastic Bilateral Spastic Unilateral Dyskinetic CP* Non-classifiable
Ataxic CP Non-classifiable
Reduced activity Increased activity

- tone tends to be - tone tends to be
increased decreased
Dystonic CP* Choreo-Athetotic CP*
Fig. 2 Classification tree for subtypes of cerebral palsy. (Reproduced from SCPE Collaborative Group (2000))
A common classification has also been (Surveillance of Cerebral Palsy in Europe 2000),
developed by the SCPE (Surveillance of Cerebral is in accordance with the recently proposed defi-
Palsy in Europe 2000, 2002). This classifica- nition and classification of CP (Cans et al. 2007;
tion, illustrated by a classification tree (Fig. 2) Rosenbaum et al. 2007). Besides the dyskinetic
and ataxic subtypes, it includes the concept of white matter, while gray matter lesions and
unilateral and bilateral spastic CP, and it empha- cortical or basal ganglia lesions are associated
sizes and describes the dominant symptoms with lesions arising around term (Fig. 3). Peri-
(Krägeloh-Mann et al. 2003). Spastic CP is the ventricular white matter lesions are associated
most common form and constitutes more than
80% in most series (Reid et al. 2011; Sellier
et al. 2016). The term bilateral spastic CP serves Table 1 The harmonized classification of MRI, based on
pathogenic patterns (MRICS, Magnetic Resonance Imag-
as an alternative to terms such as diplegia, tetra- ing Classification System) proposed by SCPE Network.
plegia, double hemiplegia, and quadriplegia, For categories A2 and D, the findings are to be given as
which have varying definitions and cutoff lines free text. Severity categories of B.1. and C.1. are defined
between countries. Again, other surveillance sys- according to previous publications (Krägeloh-Mann et al.
1995, 2002)
tems and registers around the world have chosen
to keep the terms hemiplegia, diplegia, and quad- A. Maldevelopments
riplegia, but when working with or comparing to A.1. Disorders of cortical formation (proliferation and/or
migration and/or organization)
SCPE, these terms are collapsed into bilateral A.2. Other maldevelopments (e.g., holoprosencephaly,
spastic CP. The recommended age for classifica- Dandy-Walker malformation, corpus callosum agenesis,
tion into CP subtype is not younger than 4–5 years cerebellar hypoplasia)
of age (Krägeloh-Mann et al. 2003). B. Predominant white matter injury
The permanent brain maldevelopment or B.1. Periventricular leucomalacia, PVL (mild/severe)
B.2. Sequelae of intraventricular hemorrhage (IVH) or
lesion that causes CP can usually be visualized
periventricular hemorrhagic infarction (PVHI)
with neuroimaging. The recommended method is B.3. Combination of PVL and IVH sequelae
magnetic resonance imaging, MRI, performed C. Predominant gray matter injury
after 2 years of age, when most of the myelination C.1. Basal ganglia/thalamus lesions (mild/moderate/
of the brain has taken place (Krägeloh-Mann severe)
2004) (see ▶ Chap. 21, “Classification Terminol- C.2. Cortical-subcortical lesions only (watershed lesions
in parasagittal distribution/multicystic
ogy in Cerebral Palsy”). The SCPE has proposed a encephalomalacia) not covered by C3
classification of MRI results based on the timing C.3. Arterial infarctions (middle cerebral artery/others)
of injury (Himmelmann et al. 2017) (Table 1). D. Miscellaneous (e.g., cerebellar atrophy, cerebral
Early compromise affects the development atrophy, delayed myelination,
and organization of the brain, leading to ventriculomegaly not covered by B, hemorrhage not
covered by B, brainstem lesions, calcifications)
maldevelopment. Late second and early third
E. Normal
trimester lesions are found in the periventricular
Fig. 3 Systematic overview on brain development, pathogenic patterns, and timing. (Reproduced from Himmelmann
et al. (2017))
with spastic CP, while basal ganglia lesions are 2016; Himmelmann and Uvebrant 2014). Preva-
frequently found in dyskinetic CP. lence of CP is monitored by a growing number of
Classification measures of function have registers across the world (Goldsmith et al. 2016).
emerged over the past 15 years and facilitate an The overall prevalence of CP appears to have been
overview of the distribution of functional levels, fairly stable over the years although it has fluctu-
change over time, and constitute a basis for the ated between 1.5/1000 live births to 3/1000 live
planning of interventions. The Gross Motor Func- births in long-standing registers where reporting
tion Classification System (GMFCS) has become has occurred for 50 years plus (Fig. 4).
an important and widespread tool to describe Western Sweden and Western Australia are
gross motor function in a child with CP and, in two such long-standing registers, and here we
conjunction with the Gross Motor Function Mea- compare their total birth prevalence since the
sure, prognosis for future gross motor function 1950s. In Western Australia, there was a period
(Rosenbaum et al. 2002). Corresponding classifi- when ascertainment was still increasing, and the
cations for fine motor function are the Bimanual founders of that register believe that ascertain-
Fine Motor Function (Beckung and Hagberg ment was complete from birth years 1963
2002; Elvrum et al. 2016) and Manual Ability onward. It can be seen on the figure that two
Classification System (Eliasson et al. 2006); and very different geographical areas of the world
for communication and speech, the Communica- show similar dips and increase over time, with
tion Function Classification System (Hidecker two differences: (1) an overall higher rate contin-
et al. 2011), Functional Communication Classifi- ually for Western Australia (between 2.1 and 3.2/
cation System (Barty et al. 2016), and the Viking 1000 live births compared to 1.5 and 2.5/1000
Speech Scale (Pennington et al. 2013) have all live births), some of which can be explained by a
been developed and validated. higher rate of post-neonatal CP in Western
Australia, while some is unexplained, and (2) a
slight lag in the dips and following increases,
Frequency and Patterns of Occurrence with Western Australia following the trends of
Western Sweden. The final birth cohort of
Population-based series are necessary for interna- 2007–2010 sees the two areas’ total birth preva-
tional comparisons and epidemiological studies lence is the most similar since the early 1980s.
of trends. The basic measures of frequency in epi- The next two birth cohorts will be important to
demiology are incidence and prevalence. CP epide- see if overall birth prevalence continues to fall or
miology has unique challenges, due to the if another increase commences.
“umbrella” nature of many etiologies, which span In Europe the current overall prevalence of CP
anywhere from the first few weeks of pregnancy to ranges from 1.04 to 2.52/1000 live births (EURO-
2 years’ post-neonatal, and as there is not a test or PERISTAT Project with SCPE EUROCAT and
any point in time that CP becomes CP, it is impos- EURONEOSTAT 2008) and with a reported
sible to report on incidence. Instead we use the term mean rate of 2.08/1000 live births in the birth-
birth prevalence to approximate incidence. By year period 1980–1990 (Surveillance of Cerebral
using this measure, epidemiologists can determine Palsy in Europe 2002). In Australia, the overall
the frequency of CP within populations and com- prevalence of CP between states ranges between
pare differences in CP among populations. 2 and 2.7/1000 live births with a combined rate of
2.1/1000 live births in the birth years 1993–2009
(ACPR Group 2016). From one of few
Birth Prevalence: Overall Trends population-based studies in the United States,
the Center of Disease Control and Prevention in
CP is the most common cause of motor disability Atlanta reported a rate of 2.2/1000 in children
in childhood, affecting about 2/1000 live born born in 1985–2002 at 8 years of age (Van Naarden
children in high-income countries (ACPR Group Braun et al. 2016).
3.5
2.5
Per 1000 live births
1.5
0.5
Birth year groups
Western Sweden Total CP Western Australia Total CP

Fig. 4 Total birth prevalence of cerebral palsy in Western Sweden and Western Australia
In low- and middle-income countries (LMIC), In addition to potential differences in preva-

the rates and etiological spectrum of CP may lence, it seems likely that the etiological profile of
differ considerably from what is reported above; CP may differ in LMIC. In Australia, 5.6% of CP
however research describing this population is was due to post-neonatally acquired causes
both scarce and varying. The few available reports (ACPR Group 2016); however in Northern
of CP prevalence in LMIC settings report a range India, rates of CP are reported to be higher due
of rates. Some are similar to that in high-income to higher frequencies of post-neonatally acquired
countries at around 2.0/1000 live births, such as kernicterus, meningitis, and head trauma (Singhi
that reported from a study from Egypt (El-Tallawy and Saini 2013) (see ▶ Chap. 7, “Postnatal Causes
et al. 2011) and from a large Indian survey of Cerebral Palsy”). Differences or availability of
(Banerjee et al. 2009). Other studies suggest CP neonatal care facilities, in high versus low
may be more prevalent in LMIC settings with resource settings, also likely impact both rates of
estimates from 3.6/1000 live births from another survival and severity of CP (Benfer et al. 2014).
region of Egypt (El-Tallawy et al. 2014), 4.4/1000 However, without population-based surveillance,
live births in Turkey (Serdaroglu et al. 2006), and the epidemiology of CP in LMIC settings remains
up to as high as 10/1000 live births in South Africa largely unknown. Systematic population-based
(Couper 2002). These ranges may be real or rather health surveillance is required to provide real esti-
reflect variation in the inclusion criteria for CP mates of CP prevalence in LMIC settings. It is
and/or the types of research methodologies used, hoped that the recent establishment of new CP
e.g., questionnaires and cross-sectional studies Registers in Bangladesh (Khandaker et al. 2015)
(Gladstone 2010). and Sri Lanka will in the future provide important
insights into both the prevalence and etiology of (Fig. 5). In birth years 2007–2010, the gestational
CP and pave the way for the identification of age-specific prevalence of CP was 5.1/1000 live
appropriate prevention strategies for each region. births in children born 32–36 weeks and 1.2
in children born at term in Western Australia
(ACPR Group 2016) and an even larger difference
Trends by Birth Weight in Western Sweden, with 6/1000 live births and
and Gestational Age 1.2 in children born at term. In children born 28 to
31 weeks’ gestational age, the birth prevalence of
Maternal, perinatal, and neonatal care have under- CP was 47.7/1000 live births, and similar (for the
gone major changes, improving perinatal and neo- first time) in the lowest gestational age, under
natal mortality in high-income countries. 28 weeks at 49.2/1000 live births. Western Swe-
Improved survival rates in low birth weight and den again had a larger difference in birth preva-
preterm infants also increase the birth prevalence lence between these gestational age stratum 45.7/
of CP and other neurodevelopmental conditions 1000 live births in children born at 32–36 weeks
(Wilson-Costello et al. 2005) (see ▶ Chap. 2, and 59/1000 live births in under 28 weeks (Fig. 5).
“Cerebral Palsy and the Relationship to Prematu- Looking 20 years back, the prevalence has varied,
rity”). But, although the new preterm survivors but both in Western Sweden and Western
constitute a high-risk population for various kinds Australia, a decline in CP prevalence in children
of disability, including CP, the advances in neo- born extremely preterm can be seen. There is also
natal intensive care have allowed far more infants a declining trend in term CP. As more children are
to survive without CP than with CP (Hagberg born at term, the latter trend will result in a greater
et al. 1982; Serenius et al. 2013). A recent Western decrease in absolute number of CP cases.
Australian study looking at infants born at border-
line viability showed that 5% of infants survived
at 22 weeks, rapidly increasing to 46% at Trends in Motor Severity and CP
23 weeks, and 77% at 24 weeks (Sharp et al. Subtypes
2017). 78% of the surviving babies were free of
major neurodisability when followed into child- The changes in severity of motor impairment over
hood. It is expected that the proportion expected time are small. About 60% of children with CP
to survive at these gestational ages will continue learn to walk unaided (Fig. 6a, b) (Himmelmann
to increase, and some of these new survivors will et al. 2006; Himmelmann and Uvebrant 2011).
also have a neurodisability. Once again, the comparison between Western
Lower birth weight is correlated with higher Australia and Western Sweden overall shows
CP rate, 48.4/1000 in children with a birth minimal change in severity. But since the late
weight below 1500 g compared to 1.1/1000 in 1980s, there is a consistently higher rate of mod-
children with a birth weight of more than 2500 g erate to severe gross motor function (defined as
in a European report (EURO-PERISTAT Project requiring aids to walk or a wheelchair to ambu-
with SCPE EUROCAT and EURONEOSTAT late) seen in Western Australia (Fig. 6a, b).
2008). In a survey including 16 centers of the The mean proportion of children unable to
SCPE, a decreasing trend in prevalence over walk was 28% in children born 1976–1996 in
time was shown among very low birth weight Europe, with very little variance within the time
children, mainly due to a decrease in the bilateral period (see ▶ Chap. 175, “Functional Mobility
spastic CP subtype (Platt et al. 2007). This trend and Gait in Children and Youth with Cerebral
has been confirmed in later birth-year cohorts Palsy”). Walking ability was strongly correlated
(Sellier et al. 2016) and in Australia (ACPR with CP subtype: 3% of children with unilateral
Group 2016). spastic CP, 10% of the children with ataxia, 43%
There is a large difference in birth prevalence of those with bilateral spastic CP, and 59% of the
of CP between different gestational age groups children with dyskinetic CP did not walk
a 80
70
60
CP per 1000LBs
50
40
30
20
10
0
1995-1998 1999-2002 2003-2006 2007-2010
<28w Western Sweden <28w Western Australia
28-31w Western Sweden 28-31w Western Australia
b 8
7
6
CP per 1000LBs
5
4
3
2
1
0
1995-1998 1999-2002 2003-2006 2007-2010
32-36 Western Sweden 32-36 Western Australia
>36 Western Sweden >36 Western Australia
Fig. 5 Gestational age-specific trends in CP prevalence in Western Sweden and Western Australia
(Beckung et al. 2008). In Western Australia the subtypes are contradictory. In recent European
proportion of severe motor impairment in CP was and Australian studies, decreasing prevalence in
25% (Watson et al. 2006). bilateral spastic CP and a concomitant increase in
Changes have occurred in the various subtypes unilateral spastic CP were reported for children
over time (Cans et al. 2008; Surveillance of Cere- with normal and moderately low birth weights
bral Palsy in Europe 2002). CP is classified into (Sellier et al. 2016) and at term gestational age
subtypes based on predominant neurological find- (Reid et al. 2016; Himmelmann and Uvebrant
ings (Fig. 2). Spastic CP constitutes about 80% of 2014). The proportion of dyskinetic CP, charac-
all CP. It is characterized by a velocity-dependent terized by involuntary postures and move-
increase in muscle tone. A decreasing trend in ments, varies between registers and is reported
preterm bilateral spastic CP has been reported in up to 15% (Monbaliu et al. 2017). After
(Platt et al. 2007), whereas reports on other CP an increase from the 1970s, the prevalence of
Fig. 6 (a) Western Sweden a 3

(above) and (b) Western
Australia (below) trends in
mild, moderate, and severe
Prevalence by 1000 live births

2.5
gross motor function
2
Mild
1.5 Moderate
Severe
0.5
0
59- 63- 67- 71- 75- 79- 83- 87- 91- 95- 99- 03-
62 66 70 74 78 82 86 90 94 98 02 06
Birth year
b 3.0
2.5
2.0
Unknown
1.5 Mild
Moderate
1.0 Severe
0.5
0.0
19 -58
19 -62
19 -66
19 -70
19 -74
19 -78
19 -82
19 -86
19 -90
19 -94
19 -98
20 -02
6
-0
56
59
63
67
71
75
79
83
87
91
95
99
03
19
Birth year groups
dyskinetic CP has remained stable (Himmelmann Accompanying Impairments

et al. 2009; Sellier et al. 2016).
Research is starting to emerge from low- and In addition to neurological symptoms such as
middle-income countries about severity and sub- spasticity, dyskinesia, and ataxia, function and
type differences compared with high-income coun- activity may be hampered by muscle weakness,
tries. In a comparison between Bangladesh and co-contraction, and lack of selective motor control
Australia, dystonia was more prevalent in and balance. In more than half of the children with
the former (Benfer et al. 2014). In India, a decrease CP, there are accompanying impairments, which
in quadriplegia and an increase in diplegia are may impact function and participation more than
reported (Singhi and Saini 2013). In Botswana the motor impairment in some. Screening for
and Uganda, more severe motor impairment and these conditions should be part of the evaluation
higher proportions of accompanying impairments of a child with CP. The occurrence of accompa-
than in Europe and Australia are reported (Bearden nying impairments like epilepsy, impaired vision,
et al. 2016; Kakooza-Mwesige et al. 2015). and intellectual impairment is correlated with
the severity of the motor impairment (see and spastic CP of the most severe motor impair-
▶ Chaps. 31, “Epilepsy in the Child with Cerebral ment. There was also an increased risk of death in
Palsy” and ▶ 72, “Testing Visual Function and all CP subtypes and age groups compared with the
Visual Evaluation Outcomes in the Child with general population (Himmelmann and Sundh
Cerebral Palsy”). Epilepsy has been found in 2015). Respiratory causes are the most common
33–44%, severe visual impairment in 17–20%, causes of death (Himmelmann and Sundh 2015;
and intellectual impairment in 44% with little Reid et al. 2012). In one study the presence of
variation during the last 20 years in Western Swe- gastrostomy was associated with early death
den (Himmelmann et al. 2006; Himmelmann and (Westbom et al. 2011). There is conflicting evi-
Uvebrant 2011; Pueyo et al. 2009; Venkateswaran dence whether survival is improving (Brooks
and Shevell 2008). Motor impairment, epilepsy, et al. 2014; Himmelmann and Sundh 2015; Reid
and intellectual impairment share the same risk et al. 2012). However, CP may well be associated
factors and appear to have different expressions of with full life expectancy.
severity of brain lesions according to a case-
control study (Ahlin et al. 2017). Communication
and feeding may also be hampered, creating a Major Risk Factors
need for alternative and augmentative communi-
cation (AAC) aids and gastrostomy for feeding Multiple Birth
(see ▶ Chaps. 180, “Assessment and Treatment of
Feeding in Children and Youth with Cerebral Infants born as part of a multiple birth are at four
Palsy” and ▶ 190, “Augmentative and Alternative times the risk of CP compared to singletons
Communication for Cerebral Palsy”). More subtle (Scher et al. 2002; Topp et al. 2004) (see
sensory and cognitive problems may become appar- ▶ Chap. 10, “Risk Factors for Developing Cere-
ent at school age. There is emerging evidence of bral Palsy”). Higher order multiples likely have
neuropsychiatric and behavioral disorders (Carlsson a further increased risk compared with twins
et al. 2008; Delobel-Ayoub et al. 2017; Kilincaslan (Petterson et al. 1993; Pharoah and Cooke
and Mukaddes 2009), but it is too early to report 1996). The increased risk may be due to the
trends for these conditions (see ▶ Chaps. 34, “Psy- following: growth deviation, both small and
chiatric Disorders in Children with Cerebral Palsy” large for gestational age (Jarvis et al. 2003),
and ▶ 35, “Autism Spectrum Disorder in the Child co-twin deaths, the higher risk of preterm birth
with Cerebral Palsy”). The growing awareness of in multiples, increasing maternal age at birth,
such conditions may affect future management of and the advent of assisted reproductive technol-
CP and promote early detection. ogy (ART). Overall, ART approximately dou-
bles the risk for CP (Hvidtjorn et al. 2009;
Kallen 2014), while ovulation induction drugs
Survival in CP increase CP risk to a lesser extent (Hvidtjorn
et al. 2010). The increased risk after assisted
Survival in individuals with CP is related to the conception is primarily attributed to the higher
severity of motor impairment and accompanying proportion of multiple and premature births
impairments (see ▶ Chap. 20, Cerebral Palsy Prog- (Hvidtjorn et al. 2010; Kallen et al. 2010). The
nosis Based on the Physical and Neurologic Exam- use of assisted reproductive technologies con-
ination). In a Western Australian study with birth tinues to rise; however as usage varies signifi-
years 1958–1994, Blair found intellectual disabil- cantly around the globe (Dyer et al. 2016), the
ity to be the strongest predictor of mortality, while influence on birth prevalence of CP will also be
severe motor impairment primarily increased early regionally specific. While the recent shift toward
mortality (Blair et al. 2001). A Swedish study single embryo transfer and resulting lower pro-
covering 50 years showed similar results, in addi- portion of multiple births are expected to
tion to a difference in survival between dyskinetic decrease the association with CP (Kallen et al.
2010), in many regions the transfer of multiple Congenital Cytomegalovirus

embryos remains a common practice (Dyer et al.
2016). Congenital cytomegalovirus (cCMV) has been
described as the most important congenital infec-
tion leading to neurological sequelae in the devel-
Congenital Anomalies oped world (Cannon and Davis 2005; Manicklal
et al. 2013) (see ▶ Chap. 4, “Infectious Etiologies
The presence of a congenital anomaly is associ- of Cerebral Palsy”). CMV is a common herpesvi-
ated with an eightfold increase in risk of CP (see rus that can cross the placenta, infect the fetus, and
▶ Chap. 3, “Genetic Abnormalities and Congen- cause damage to the developing central nervous
ital Malformations as a Cause of Cerebral Palsy”) system, resulting in long-term sequelae including
(McIntyre et al. 2016). A congenital anomaly is sensorineural deafness, CP, and learning disability
defined as a structural or functional abnormality (Manicklal et al. 2013). A recent study in
that is present at conception or occurs before the Australia completed molecular testing of the
end of pregnancy, a broader definition than that of stored newborn screening cards of 323 children
maldevelopment. The proportion of children with with CP, and 31 (9.6%, 95% CI 6.2–13.0) tested
pre /perinatally acquired CP and a major con- positive for CMV DNA (Smithers-Sheedy et al.
genital anomaly ranges between 15% and 32% 2017). This proportion was markedly higher than
in total population data linkage studies from that found among newborns in the general com-
regions of Europe and Australia (Blair et al. munity (0.6%) (Kenneson and Cannon 2007).
2007; Rankin et al. 2010). 20% of children with
a post-neonatal cause of CP are also reported to
have a major congenital anomaly (Blair et al. Prevention of CP
2007). While congenital anomalies are generally
associated with preterm birth, the association Recently two overviews of Cochrane Reviews
between anomalies and CP is highest in children have been completed to outline the current
born at term (McIntyre et al. 2016). Children with preventive strategies available for CP (see
a cerebral anomaly have a relative risk for CP of ▶ Chap. 157, “Therapies in Newborn and Pediat-
303 (Blair et al. 2007). Indeed, 9–16% of children ric Intensive Care Units for the Neurologic At-
with pre /perinatally acquired CP have a major Risk Infants”) (Shepherd et al. 2016, 2017).
cerebral anomaly, and cerebral anomalies in CP Figure 7 outlines the key findings. There are
are associated with more severe outcomes (Blair only two interventions in current practice that
et al. 2007; Rankin et al. 2010). Non-cerebral have high-quality evidence to say they are effec-
anomalies are found in 5–16% of children with tive: Magnesium sulfate for the neuroprotection of
pre /perinatally acquired CP (Blair et al. 2007; the preterm fetus and therapeutic hypothermia for
Rankin et al. 2010). term newborns with hypoxic ischemic encepha-
Much of the variation in reported prevalence lopathy. There were a large number of interven-
may be attributed to the lack of a universal tions that had moderate-quality evidence that were
congenital anomaly definition as well as differ- either possibly effective, or no clear differences in
ences in data collection methodology. This is cur- outcome were found. There were also many inter-
rently of high interest to CP Registers and ventions where no conclusions were possible due
congenital anomaly registers in Europe and to low-quality evidence, or no clear difference in
Australia. A large study is currently underway, outcomes was found.
The Comprehensive CA-CP Study (Goldsmith There were two main limitations identified in
et al. 2018 under review), to answer the many these overviews. One was that although CP was
questions around the prevalence of CP with a listed as a primary outcome for over 700 Cochrane
congenital anomaly and to identify opportunities Reviews, only 15% reported long-term outcomes
for primary prevention for these children. that included CP. The length of time it takes to
Hygiene precautions and behavioral interventions
• Do not share food, drinks, or utensils used by young children
• Do not put a child’s dummy/soother/pacifier in your mouth
• Avoid contact with saliva when kissing a child
• Thoroughly wash hands with soap and water for 15 15––20 seconds, especially after changing
nappies/diapers, feeding a young child, or wiping a young child’s nose or saliva
Rawlinson et al 2017, Adler et al 1996, Revello et al 2015, Valoup
Valoup--Fellous et al 2009, Adler et al 2004
Fig. 7 Hygiene precautions and behavioral interventions to reduce risk of CMV in pregnancy
Table 2 Preventive strategies for CP: Cochrane Reviews of antenatal, intrapartum, and neonatal interventions
Intervention RCTs Participants RR (95% CIs)
Effective interventions: high-quality evidence
Magnesium sulfate for the neuroprotection of the preterm fetus 5 6145 0.68
(0.54–0.87)
Therapeutic hypothermia for term newborns with hypoxic ischemic 7 881 0.66
encephalopathy (0.54–0.82)
Possibly effective interventionsa: moderate-quality evidence
Prophylactic methylxanthines (caffeine) for endotracheal extubation in 1 644 0.54
preterm infants (0.32–0.92)
No conclusions possibleb: low- to very low-quality evidence
Antenatal corticosteroids for accelerating fetal lung maturation in the 5 904 0.6 (0.34–1.03)
preterm fetus
Possibly ineffective interventionsa: moderate-quality evidence
Prophylactic antibiotics for mothers in preterm labor with intact 1 3173 1.82
membranes (0.99–3.34)
Preterm babies with suspected fetal compromise being born immediately 1 507 5.88
compared with those for whom birth was deferred (1.33–26.02)
Early (< 8 days of age) postnatal corticosteroids for preventing chronic 12 1452 1.45
lung disease in preterm infants (1.06–1.98)
a
There were no clear differences for cerebral palsy for five neonatal interventions and one antenatal intervention
b
There were no clear differences for cerebral palsy for 27 neonatal interventions and 9 antenatal interventions
RCTs randomized controlled trials, RR relative risk
describe CP in a child (up to 5 years) is a problem Congenital CMV is an important risk factor
for large randomized controlled trial follow-up. for CP not only because it may be more prevalent
Alternative follow-up processes need to be investi- in this population than previously thought but
gated, such as linkage to CP Registers and the use of because it is potentially preventable (see
interim measures, such as the General Movements ▶ Chap. 3, “Genetic Abnormalities and Congen-
Assessment at 3–4 months of age. Secondly, many ital Malformations as a Cause of Cerebral Palsy”).
of these interventions may have a small effect on While there is no available vaccine, there are
CP, but the studies were not powered for CP due to effective public health strategies to reduce mater-
it being such a rare outcome, or because the internal risk of CMV in pregnancy. These preventive
vention was implemented for a more proximal out- strategies consist of simple hygiene precautions
come, e.g., antenatal corticosteroids for lung that have been shown to be both acceptable to
maturation (Table 2). pregnant women and effective in reducing CMV
seroconversion (Revello et al. 2015; Vauloup- Blair E, Watson L, Badawi N, Stanley FJ (2001) Life
Fellous et al. 2009). The recently published con- expectancy among people with cerebral palsy in West-
ern Australia. Dev Med Child Neurol 43:508–515
sensus guideline (Rawlinson et al. 2017) recom- Blair E, Al Asedy F, Badawi N, Bower C (2007) Is
mends that “all pregnant women and health-care cerebral palsy associated with birth defects other than
providers should be educated about congenital cerebral defects? Dev Med Child Neurol 49:252–258.
cytomegalovirus infection and preventive mea- https://doi.org/10.1111/j.1469-8749.2007.00252.x
Brooks JC, Strauss DJ, Shavelle RM, Tran LM,
sures” (Fig. 7). The time has arrived for a public Rosenbloom L, Wu YW (2014) Recent trends in cere-
health campaign to build greater awareness of bral palsy survival. Part I: period and cohort effects.
congenital CMV as a cause of neurodeve- Dev Med Child Neurol 56:1059–1064. https://doi.org/
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Cannon MJ, Davis KF (2005) Washing our hands of
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Health and Healthcare Disparities in
Children with Cerebral Palsy 12
Kirk W. Dabney, Ruth Ziegler, and Laurens Holmes
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 148
The Disabled Population as a Population with Health and Healthcare Disparities . . . . 149
Identifying Vulnerability Causing Health and Healthcare Disparities in the
Cerebral Palsy Population . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153
Strategies to Resolve Healthcare Disparities in the Cerebral Palsy Population . . . . . . . . 156
Quality, Cost, and Value: Their Impact and Importance on Disparities in Children
with Disabilities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162
Value for CSHCN, CMC, and Children with CP: The Patient and Family
Perspective . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 162
Health Policy to Prevent Health and Healthcare Disparities in CSHCN . . . . . . . . . . . . . . . 167
Cases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169
Case 1 (Pre-care Coordination) (Fig. 7) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169
Case 2 (Fig. 8) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 170
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171
Abstract (CP) often represent a subgroup within children

Health and healthcare disparities or inequities with special healthcare needs (CSHCN), chil-
are defined as differences in health and dren with medical complexity, and/or children
healthcare outcomes within certain populations with disabilities and often have overlapping risk
such as race, ethnicity, socioeconomic status, factors for vulnerability. In addition to the level
sexual orientation, geographic location, and/or of motor involvement, and the number of med-
disability and imply that such differences are ical comorbidities in children with CP, the prev-
unfair or unjust. The concept of health equity alence of CP is increased by low socioeconomic
implies giving individuals and/or populations and minority ethnicity/race status. These factors
the necessary resources necessary to achieve further independently lead to health and
equal outcomes. Children with cerebral palsy healthcare disparities and can also result in
poor healthcare access (due to lack of insurance,
transportation, etc.), low English proficiency,
K. W. Dabney (*) · R. Ziegler · L. Holmes and poor health literacy. The greater overlap of
Department of Orthopedics, Nemours/AI DuPont Hospital these risk factors, the more likely the child with
CP is at risk for poor healthcare outcomes. In
e-mail: Kirk.Dabney@nemours.org; ruthmziegler@gmail.
com; Laurens.Holmes@nemours.org order to overcome barriers and achieve

https://doi.org/10.1007/978-3-319-74558-9_210
148 K. W. Dabney et al.
equitable outcomes, a multilayer approach is and Committee on Native American Child Health
required to overcome each risk factor. This 2010). In children, inequities in health and well-
approach is outlined using a vulnerability ness occur from multiple social, environmental,
framework model. and behavioral determinants of health that are not
being adequately addressed by current standards
Keywords of pediatric practice or public practice (Council on
Health disparities · Healthcare disparities · Community Pediatrics and Committee on Native
Disabilities · Children with special healthcare American Child Health 2010). It is impossible to
needs · Care coordination · Children with discuss health and healthcare disparities in chil-
medical complexity · Vulnerable populations dren with cerebral palsy without first discussing
the presence of these disparities in the total dis-
abled population, followed by a discussion of
Introduction their pediatric equivalent, the population of chil-
dren with special healthcare needs (CSHCN). Dis-
Health and healthcare disparities or inequities are parities within cerebral palsy (CP) represent a
defined as differences in health and healthcare subpopulation within both of these larger dispar-
outcomes within certain populations such as ity groups (Fig. 2), and the solutions within these
race, ethnicity, socioeconomic status, sexual ori- larger groups are often also relevant to the CP
entation, geographic location, and/or disability population. After discussing disparities in the CP
and imply that such differences are unfair or population, second it is important to understand
unjust (Carter-Pokras and Baquet 2002). The con- the barriers to health and healthcare that exist
cept of equity is often confused with that of equal- within this vulnerable population and how to
ity (Fig. 1). The fundamental difference between address them. Third, it is important to discuss
the two is crucial to the understanding of potential how to address health disparities in children with
solutions to the health and healthcare disparities cerebral palsy in the context of improving value
discussed later in this chapter. Recently, the Amer- and improving quality while lowering or
ican Academy of Pediatrics announced a policy maintaining cost. Finally, healthcare policy is
statement in order to address the principles and also critical to protect both health and healthcare
practices of child health equity for all children in of children with special healthcare needs. The
order to address the root causes of childhood chapter will therefore conclude with a dialogue
disparities (Council on Community Pediatrics on health policy measures that protect against
Fig. 1 Equality vs. equity: (a) equality is giving each achieve equal outcomes. (Figures drawn and permission
individual equal resource regardless of need; (b) equity is by Courtney Dabney)
giving individuals the necessary resources necessary to
12 Health and Healthcare Disparities in Children with Cerebral Palsy 149
et al. 2009; Altman and Bernstein 2008). These

The Disabled differences in health outcomes are often dismissed
Population by many, with the argument that they do not
represent a true disparity, implying that their
poor health is caused by the condition itself as
CSHCN opposed to it being preventable. More recently,
however, the Agency for Healthcare Research and
CSHCN with
Disability Quality (AHRQ) has confirmed both adults and
and/or Medical children with disabilities as a vulnerable popula-
Complexity tion with health disparities (Agency for
Healthcare Research and Quality 2016). Current
evidence from the disabled population shows dis-
Children parities in health, health behavior, and healthcare
with CP access (National Center for Health Statistics 2010;
Iezzoni et al. 2008; McCarthy et al. 2006; Parish
and Saville 2006), including type of insurance
(Braun et al. 2017; Quick-Stats 2010), preventa-
Fig. 2 Children with special healthcare needs (CSHCN) tive care (Diab and Johnston 2004; Iezzoni et al.
encompass much of the pediatric population with chronic 2000), obesity rates and smoking (Braun et al.
healthcare needs and disability and are a subgroup of the 2017; Disability and Health State Chartbook
disabled population. CSHCN are defined as children “who
2006), victim of a violent crime (Adverse health
have or are at increased risk for a chronic physical, develop-
mental, behavioral or emotional condition and who also conditions and health risk behaviors associated
require health and related services of a type or amount beyond with intimate partner violence—United States,
that required by children generally.” It is helpful to concep- 2005 2008; Rand and Harrell 2007), adequate
tualize this group of children as consisting of subgroups of
social and emotional support (Kinne et al. 2004;
CSHCN with (1) physical disability and/or (2) medical com-
plexity within which children with cerebral palsy (CP) exist. Wilber et al. 2002), and cardiovascular disease
Their need factor and risk for health/healthcare disparities are and newly diagnosed diabetes (Reichard and
dependent upon their motor involvement and coexisting med- Stolzle 2011; Reichard et al. 2011). Disabled indi-
ical comorbidities
viduals also experience disparities in the social
determinants of health including a lower likeli-
disparities in this population, past and present. hood of achieving a high school education,
Knowledge of these policies is important to help lower likelihood to be employed, less Internet
health providers who care for CSHCN to advocate access, inadequate transportation, and a greater
for their patients as well as for future policy likelihood to have an annual household income
changes. less than 15,000 per year (Krahn et al. 2015). The
cerebral palsy (CP) population represents the larg-
est pediatric population with motor disabilities,
The Disabled Population affecting 1.5–4 per thousand live births (Arneson
as a Population with Health et al. 2009; Bhasin et al. 2006; Johnson 2002;
and Healthcare Disparities Paneth et al. 2006; Van Naarden Braun et al.
2016; Winter et al. 2002). Healthcare providers
Individuals with disabilities represent 12–30% of who care for children with cerebral palsy should
the US population and have previously been be knowledgeable of the health and healthcare
unrecognized as a population with healthcare dis- disparities that exist within the pediatric disabled
parities (Krahn et al. 2015; Oreskovich and population. By doing so, providers will better
Zimmerman 2012). Adults with disabilities are understand the barriers to high-quality health out-
four times more likely to report fair to poor health comes that exist within this population. The fol-
compared to those without a disability (Drum lowing sections identify and discuss the
disparities that exist within the larger population chronic conditions further, a meta-analysis of
of children with special healthcare needs 160 studies with data on disabling chronic condi-
(CSHCN), those with and without medical com- tions of childhood in high-income countries found
plexity and with and without disability pediatric these conditions to be associated with social advan-
as well as those specifically in the CP population. tage (Spencer et al. 2015). In an assessment of the
2009–2010 National Survey of CSHCN, there are
Health and Healthcare Disparities six quality indicators: (Carter-Pokras and Baquet
in Children with Special Healthcare 2002) family participation in shared decision-
Needs making (Council on Community Pediatrics and
Specific pediatric populations with disparities in Committee on Native American Child Health
health are often exposed over a life course and 2010); coordinated, ongoing, comprehensive care
therefore are subjected to a cumulative effect. The within a medical home (Krahn et al. 2015); adequate
pediatric disabled population is more commonly private and/or public insurance (Oreskovich and
termed as children with special healthcare needs Zimmerman 2012); screening early and continu-
(CSHCN) and defined as those children “who ously for special healthcare need (Drum et al.
have or are at increased risk for a chronic physical, 2009); organization of community-based service
developmental, behavioral or emotional condition systems so families can use them easily (Altman
and who also require health and related services of a and Bernstein 2008); and receipt of services neces-
type or amount beyond that required by children sary for youth with special healthcare needs to make
generally” (McPherson et al. 1998). As the defini- transitions to adult healthcare (Strickland et al.
tion implies, children with special healthcare needs 2015). Only 17.6% of CSHCN achieved all
are a vulnerable population at increased risk for age-appropriate quality indicators. Nineteen percent
chronic medical complexity and healthcare needs of participants had greater than three unmet quality
indicative of children with disparities in health and indicators. The quality indicator least achieved was
healthcare outcomes. Using the National Health services necessary to make transition into adult
Interview Survey, CSHCN have increased over the healthcare at only 40%. A lower percentage of
past 10 years with a prevalence of 15–18% of US achieving these quality metrics occurred in
children under the age of 18 years (Bethell et al. non-Hispanic Blacks, Hispanics, lower family
2008; Perrin et al. 2007). The surveys have also income, and non-English proficient participants.
shown a higher prevalence for boys, African Amer- Further analysis of access to easy-to-use services
icans, and children from low-income and single- by CSHCN from the 2009–2010 survey showed
parent homes (Bethell et al. 2008; Newacheck that 35.3% of families encounter difficulty in access
et al. 1998). A more recent study of children with to easy-to-use community and health services
chronic healthcare conditions cited Black children (Rosen-Reynoso et al. 2016). “Easy-to-use ser-
with higher rates of cerebral palsy, HIV/AIDS, vices” (community services) that are close to the
emergency department visits, hospitalizations, and child’s community are especially critical for vulner-
higher mortality associated with asthma (Berry et al. able populations with limited resources. Lack of
2010). This study also showed Hispanic children of community services was most prevalent in children
Mexican descent had higher rates of spina bifida, within racial and ethnic minority groups, those with
HIV/AIDS, poorer survival with acute leukemia, poverty, and those with complex emotional/behav-
and higher rates of depression. In another study, ioral/developmental needs and functional limita-
the prevalence of children with special healthcare tions. The highest number of barriers was reported
needs was looked at across three National Surveys in CSHCN who were ages 10–14, Hispanic, Black,
of Children’s Health, 2001–2004 (Bethell et al. non-English proficient, with public insurance, at the
2008). The 2004 survey demonstrated increased lowest poverty level, not in a two-parent home,
prevalence of children with special healthcare without a medical home, and with less than a high
needs in impoverished children. Exploring the rela- school education. Almost 80% of uninsured patients
tionship between poverty and disabled children with had difficulties/delays in receiving “easy-to-use
services.” Therefore, those patients with the most and ethnic groups and children living in poverty
medical and socioeconomic need receive the least (Houtrow et al. 2011). Other risk factors for unmet
community service. need were reported as single parent in the home,
From the numerous studies cited, it is evident those with highest educational attainment in the
that CSHCN have a higher prevalence of subpop- home at less than high school, and those without
ulations already known to independently have insurance or with public insurance (Houtrow et al.
health and healthcare disparities. This places 2011). Taking into account these other risk fac-
many CSHCN into multiple disparity groups, fur- tors, CSHCN with disabilities appear to be a sep-
ther magnifying the vulnerability of these children arate risk factor group for inequities in unmet
(e.g., a Hispanic child with cerebral palsy whose healthcare needs.
family is below the poverty line and is also not CSHCN with medical complexity (CMC) are
English proficient) (Strickland et al. 2015). defined by one study as “those children who require
medical services beyond what is typically required
Health and Healthcare Disparities by CSHCN,” specifically “having need for medical
in Children with Special Healthcare care, having a multitude of need across various
Needs With and Without Disability health service domains, and having seen at least
and/or Medical Complexity two specialists in the previous year” (Kuo et al.
Recently, CSHCN have been subgrouped by 2014). Similar to CSHCN who have disabilities,
some into (1) CSHCN with and without disabil- CSHCN with medical complexity also have ineq-
ities (Houtrow et al. 2011) and (2) CSHCN with uities in unmet healthcare needs. This study com-
and without medical complexity (Kuo et al. 2014). pared unmet healthcare needs among 14 possible
There may be overlap between the two groups. As healthcare needs listed in the National Survey of
with adults with disabilities, each of these groups Children with Special Health Care Needs between
represents separate disparity populations. CSHCN with medical complexity and those without
CSHCN with disabilities are defined as “lim- medical complexity and further analyzed whether
ited in their ability to do what people are typically traditional demographic variables and social deter-
able to do” due to “bodily impairments, activity minants of health associated with disparities such as
limitation or participation restrictions,” conceptu- race/ethnicity, household income, language, and
alized using the International Classification of insurance are influenced by either group. Compared
Functioning, Disability and Health (ICF) (World to CSHCN needs without medical complexity, 44%
Health Organization 2011). When asked about the of CSHCN with medical complexity reported at
severity of their condition, CSHCN with disabil- least one unmet need compared to only 19% of
ities reported at a seven times higher rate that their CSHCN without medical complexity. Three or
condition was severe. They also reported a four greater unmet needs were reported in 11.5% of
times higher risk of feeling anxious or depressed, those with medical complexity compared to only
higher behavioral problems, and more difficulty 2.6% of those without medical complexity. Unmet
with making friends compared to CSHCN without need within the medically complex group was
disabilities (Houtrow et al. 2011). In addition, the unrelated to race/ethnicity or household income.
CSHCN with disability group had a higher rate of However, the study did not differentiate which cat-
missing more than 3 weeks of school (12% egories of the 14 healthcare needs within the survey
vs. 3%) and a higher rate of need and unmet were unmet and whether any single categories were
need compared to CSHCN without disabilities related to race/ethnicity, income, language, etc.
(an approximate 22.8% unmet need or 71% higher Within the medically complex group, only children
unmet need), yet receive less care in a medical without insurance had a greater unmet need
home (38% compared to 51%) and received less (49.2%). On the other hand, a higher unmet need
assistance with care coordination (Houtrow et al. within the group without medical complexity was
2011). Within the CSHCN with disabilities popu- associated with race, ethnicity, income, and insur-
lation was an overrepresentation of minority racial ance coverage.
In a separate study, unmet mental healthcare

needs were also found to be higher in CSHCN
with medical complexity compared to those without
medical complexity (three times higher); however,
disparities in access were highest in CSHCN with
medical complexity in low-income households
(An 2016). In CSHCN, medical complexity is not
only an independent risk factor for inequity in unmet
healthcare needs but also may be independent across
race, ethnicity, language, insurance type, and
income for some types of healthcare services, but
not others (e.g., mental healthcare services).
Health and Healthcare Disparities

in Children with Cerebral Palsy
Cerebral palsy (CP) is a heterogeneous disorder of
movement and posture due to an injury to the pre- Fig. 3 Overlapping factors for vulnerability to poor
mature motor cortex of the brain prior to 2 years of health in children with CP. In addition to the level of
age. The motor deficits that children and adults with motor involvement, and the number of medical
comorbidities in children with CP, the prevalence of CP
cerebral palsy experience can cause barriers to is increased by low socioeconomic and minority ethnicity/
mobility, communication, gaining education/ race status. These factors further independently lead to
employment, and achieving independent living. health and healthcare disparities and also can result in
Due to the child with CP often having associated poor healthcare access (due to lack of insurance, transpor-
tation, etc.), low English proficiency, and poor health liter-
morbidities (e.g., cognitive disability, autism, sei- acy. The greater the overlapping predisposing, enabling,
zure disorder, gastroesophageal reflux, visual and and need factors, the more likely the child with CP is at risk
hearing disability, etc.), other layers of complexity for poor health outcomes
often confront the cerebral palsy population and
their families. Often occurring in the CP child with compared to their White counterparts. Socioeco-
the greatest motor involvement, many children with nomic disadvantage and perinatal factors were
CP also fall into the subgroups of CSHCN with identified as likely mediators in this association
developmental, functional disabilities and/or (Wu et al. 2011; Durkin et al. 2015; Solaski et al.
CSHCN with medical complexity. Many CP chil- 2014). When both socioeconomic status and peri-
dren also have emotional and behavioral disabilities natal factors were controlled for, there was a par-
described previously. In addition, similar to the adoxical reduced risk of CP in Black children,
larger population of CSHCN, children with CP indicating the influence of these factors on CP
also have overlapping disparity groups (e.g., low and their independent association in pregnant
income/poverty, Black, Hispanic, and non-English Black females (Durkin et al. 2015). Alternatively,
proficiency) (Fig. 3). Asians have been shown to have a decreased risk
for cerebral palsy compared to Whites within East
Racial Variance Within Cerebral Palsy Asian (Chinese, Japanese, Korean), southeast
Prevalence Asian (Cambodian, Laotian, Thai, Vietnamese),
Population-based studies have shown an increase Filipino, Indian, and Pacific Islander subgroups
in cerebral palsy prevalence in non-Hispanic even after adjusting for maternal age and educa-
Black infants (Van Naarden Braun et al. 2016; tion and birth weight (Lang et al. 2012). This
Kirby et al. 2011; Wu et al. 2011; Yeargin-Allsopp disparity remains unexplained.
et al. 2008). In an 8-year-old cohort of children More recently, Black children were not only
with cerebral palsy, Durkin et al. found Black found to have an overall increase in prevalence of
children to have a 52% higher risk of CP CP compared to White children, but this disparity
was found only in children with greater functional Oskoui was able to further analyze the effects
limitations (Maenner et al. 2012). In addition, the of socioeconomic status on functional status in CP
distribution percentage for severe functional limita- and found that both a decrease in maternal educa-
tions (GMFCS IV and V) was found to be 70% tion and neighborhood socioeconomic factors
higher in Black children. No difference in preva- were associated with greater motor functional
lence was found in the mild functional limitation limitations (Oskoui et al. 2016). Cerebral palsy
group (GMFCS I, II). Neither maternal nor birth children with mothers having lower than a high
characteristics were associated with motor severity school education had a three times higher risk of
since racial disparities persisted within both terms, being a GMFCS level 4 or 5. In those mothers with
very preterm, and within normal birth weight and higher educational levels, economically deprived
very low birth weight groupings. The authors neighborhoods were associated with a twofold
suggested unexplored contributions to the disparity higher likelihood of being non-ambulatory. Accord-
such as access to care, maternal age, or substance ingly, CP children with the greatest health burden,
abuse. those with greater functional motor limitations in
CP, appear to be impacted by social determinants
Socioeconomic Impact on Cerebral Palsy of health. Those social determinants that can be
Prevalence positively influenced at a population level may
Disentangling the socioeconomic impact on racial have an impact on decreasing cerebral palsy
disparities in cerebral palsy prevalence has been prevalence.
less explored. Several studies from developed
countries within the USA and Europe, however,
have shown the increase in cerebral palsy preva- Identifying Vulnerability Causing
lence with socioeconomic disadvantage. As Health and Healthcare Disparities
touched on earlier in the last section, Durkin in the Cerebral Palsy Population
et al. incorporated measures of socioeconomic
status which included maternal educational attain- Shi and Stevens describe vulnerable populations
ment into a large population-based assessment of as those “at substantially greater risk of poor
racial disparities of cerebral palsy prevalence physical, mental, and social or emotional health
(Durkin et al. 2015). Low versus high socioeco- and have much higher rates of morbidity and
nomic status was associated with a 67% increased mortality” (Shi and Stevens 2010a). In other
risk of developing overall CP and a 93% increased terms, vulnerable populations are those at risk
risk of spastic cerebral palsy. In their analysis, for health and healthcare disparities. Their model
after race and ethnicity were adjusted, the higher to study vulnerable populations (Fig. 4) is helpful
risk for spastic CP for children with low versus for identifying risk factors for vulnerability to
high socioeconomic status remained. Similarly, poor health, access to care, and quality of care as
once socioeconomic status was adjusted, the risk determined by the convergence of predisposing,
for CP remained higher in Black versus White enabling, and need factors at both the individual
children. In their study, adjustment for perinatal and ecological levels, each resulting in poor to
factors had little effect on socioeconomic factors good physical, mental, and social health outcomes
and CP risk, as opposed to the adjustment of these (Shi and Stevens 2010b). Predisposing factors
factors lowering the risk of CP in Black children. describe the propensity of individuals to use ser-
Therefore, socioeconomic factors appear to be vices according to factors such as age, sex, family
independent of perinatal risk factors in CP with size, and social structure variables such as race/
higher socioeconomic status having a protective ethnicity, education, occupation, and beliefs and
effect. Socioeconomic factors alone, however, did values about healthcare. Enabling factors are the
not fully explain the higher CP prevalence in resources that individuals have available for the
Blacks versus Whites, which also appears to be use of services such as income, insurance cover-
largely influenced by perinatal risk factors. age, and community/regional attributes and are
Risk Factors Health Outcomes

Ecological Individual Individual Population
Predisposing Predisposing
Physical Physical
Access to Care
Enabling Enabling Vulnerability Mental Mental
Quality of Care
Need Need Social Social
Fig. 4 Vulnerability framework model. (Adapted from Shi and Stevens)
more modifiable than predisposing characteris- also have greater medical complexity, requiring
tics. Individual need factors are specific self- both specialized orthopedic and primary medical
perceived or professionally evaluated illnesses or needs. They may also have greater difficulty
health needs that drive the need to seek healthcare obtaining medical access due to poor motor func-
and may be described by specific quality measures tion and expressing health needs due to poor oral-
of the disease and overall quality of life indicators. motor function and therefore communication. In
Shi and Stevens describe similar enabling, pre- addition, those individuals with CP who have
disposing, and need factors at both the individual intellectual disabilities may also have difficulty
and ecological (population) levels (Shi and Ste- with basic literacy and health literacy. Due to
vens 2010b). these factors, children with CP are generally
CSHCN and children with CP are populations dependent on family and/or caretakers for medical
defined by their specific health need factors. These access and care. As a result, children with CP
need factors often require greater coordinated and (as well as other CSHCN) typically take on the
specialized healthcare needs. Difficulty accessing predisposing and enabling risk factors of their
this degree of specialized care due to geographic parents or caretakers.
differences (Fulda et al. 2013), poor transporta- Predisposing, enabling, and need factors inter-
tion, lack of insurance coordination, or lack of act with one another at both the individual and
expertise within a geographic region, therefore, ecological levels to influence vulnerability, for
exposes them to greater vulnerability. Children example, a child who is an ethnic or racial minor-
and adults with CP have varying degrees of func- ity (two predisposing factors) with CP, GMFCS
tional disability, medical complexity, mental ill- 5, seizure disorder, G-tube fed, reactive airway
ness, and intellectual disability, resulting in disease, and severe scoliosis (medical and func-
multiple health need factors. Individuals with CP tional need factors) and whose family is socioeco-
who have greater functional disability generally nomically disadvantaged (an enabling factor
which is disproportionately represented among disparities indicators. Appropriate and adequate

racial/ethnic minorities). Add on lack of health measures are required to quantify these variances,
insurance (an enabling factor) and geographic/ identify causality, improve health, and ultimately
transportation barriers due to functional disability reduce health disparities. Basic estimates such as
(enabling factors) causing access barriers to spe- rate, percentage, ratio, mean, and proportion are
cialty healthcare (enabling factor), this child with used to measure disparities. However, accurate
functional, medical, and social complexity application of these estimates in quantifying
becomes extremely vulnerable to poor health out- within and between group or population differ-
comes, including orthopedic surgical outcomes. ences in health and health outcomes requires some
Over a lifetime, the child’s poor health status basic knowledge of a comparison matrix mainly
(need factor) may become a financial (enabling the domain and referent group or point. The
factor) burden to the family, missing work due to domain reflects a specific population or group
the many hospitalizations and accumulating med- with subpopulations clearly defined, with mem-
ical bills of the child (Zan and Scharff 2015). For bership in one subpopulation affecting member-
the child with CP, time in the hospital reduces ship in the other subpopulation. For example, as
educational time (U.S. Department of Health and noted earlier, CP or CSHCN may be characterized
Human Services, Health Resources and Services as a health disparity domain, with race subgroups:
Administration, Maternal and Child Health White, Black, Asia/Pacific Islander, American
Bureau 2013a) (enabling factor) in school and Indian and Alaska Native, and Hawaiian Native.
eventually lowers employment status and income Disparities should be quantified in absolute and
potential (enabling factor) as an adult. These risk relative terms, with absolute terms reflecting the
factors for the family and eventually the adult with percent or prevalence difference, expressed, and
CP lead to a cycle of vulnerability (Fig. 5). mere mathematical difference (population A
percent–population B percent) (Holmes Jr 2013).
The Measurement of Healthcare The rate or risk ratio (RR), a widely used
Disparities in Cerebral Palsy epidemiologic measure of association, remains
The identification of many predisposing and an appropriate measure of health disparities and
enabling factors involves the collection of race, is estimated by the rate in the exposed (Re)/rate in
ethnicity, and language (REAL) data, disability the unexposed (Ru) (Holmes Jr 2013). As a health
and other need factor data, and social determi- disparity measure, implying a relative measure,
nants data (Tan-McGrory et al. 2018; Institute of this quantity is interpreted as the rate in the pop-
Medicine of the National Academies 2014). ulation of interest (R1) divided by the rate in the
While some of these data collection methods are reference population termed the reference point or
standardized for adults, many have not been well group (R2) or RR = R1/R2. In practice, the refer-
defined for the pediatric population or for children ent population, R2, is the advantaged or the pop-
with special healthcare needs (Tan-McGrory et al. ulation with the best/better rate (e.g., for race R2 is
2018). often Caucasians, while R1 is the disadvantaged
Health disparities reflect within-group and population, e.g., Blacks or Hispanics). In the con-
between-group variations in vulnerability to dis- text of CP, the ratio may compare the subpopula-
ease due to (a) biologic and genetic, (b) social, tions: Black CP children/Caucasian CP children.
(c) psychosocial, (d) behavioral, (e) political, and Recommendations for measuring health dis-
(e) environmental factors and conditions. In parities are as follows: (1) provision of reference
effect, health disparities research is complex and point and the rationale for selecting such referent
embraces genetic susceptibility; individual behav- to be explained in health disparities studies for CP
ior; the social, political, and physical environ- (Council on Community Pediatrics and Commit-
ment; disease prevention; and access to tee on Native American Child Health 2010) and
healthcare, diagnosis, and treatment interventions (2) use of reasonable and meaningful comparison
that result in the observed differences by health across different indicators, with all of the
Children w/ CP have
greater barriers to
good health/
healthcare/health
resources
Untreated problems Greater time in

create further hospital leads to
barriers to missed time
healthcare, education, child's school
employment /parental work
Without
adequate access
parental
to primary and
unemployment/low
specialty care,
wage jobs in
ancillary services
adulthood less
and equipment,
likely to offer
health problems
Lack of or poor health insurance
remain untreated
health insurance
reduces access to
primary care,
specialty care and
ancillary
services/equipment
Fig. 5 Risk factors and the cycle of vulnerability in children/families with CP (and other CSHCN with physical
disability and medical complexity)
indicators requiring expression in either desirable express the precision of the parameter or point
or adverse event. Additionally, we suggest the estimate in disparity measures (Drum et al.
application of the undesirable or adverse event, 2009). Where necessary, prospective designs are
since the disparity involves either absolute or rel- preferable in avoiding reverse causation inference
ative measures. This suggestion is meaningful, in causal association studies.
given the goal of a disparity measure is to improve
health by identifying and monitoring the
unwanted health outcomes, thus achieving health Strategies to Resolve Healthcare
equity (Krahn et al. 2015). Both relative and abso- Disparities in the Cerebral Palsy
lute measures should be applied to express health Population
disparities (Oreskovich and Zimmerman 2012).
Where necessary, random error quantification Recently, the National Quality Forum identified a
such as confidence interval should be used to roadmap for promoting health equity and
eliminating health disparities within populations propensity of individuals to use services, includ-
(National Quality Forum 2017). The roadmap ing healthcare. Most individuals have minimal
involves four actions: (1) Identify and prioritize influence over these factors, which are often a
the reduction of disparities, (2) implement result of individual and institutional discrimina-
evidence-based interventions to address the dis- tion and unconscious bias. Institutional education
parity, (3) invest in the development and use of at the healthcare organization level, cultural com-
health equity performance measures, and petence training, and unconscious bias training
(4) incentivize the reduction of health disparities are helpful to slowly move these factors in a
and achievement of health equity. The prioritiza- positive direction (Dabney et al. 2015; Krause
tion of intervention measures to reduce disparities et al. 2010). Also important is the creation of
is a challenge for most healthcare organizations at national, state, and organizational structures, pol-
all levels. Consideration of the size, impact, as icies, and resources that institutionalize values
well as the feasibility (ease of implementation, promoting equity in these populations.
cost and utilization of other resources) of Enabling factors which influence the resources
implementing measures to reduce vulnerability that individuals have available for services such as
risk factors must all be considered before deter- socioeconomic status, health insurance, income
mining the priority of short-, medium-, and long- level, and language concordance (e.g., English
term interventions. Evidence-based interventions proficiency) may be positively influenced by pub-
are best to adopt; however, many intervention lic insurance access, transportation, interpretation
areas are unexplored within the CP population services, improving health literacy, higher educa-
and the pediatric population as a whole. tion access, and job advocacy which can all be
Measures to address each predisposing, influenced by policies and procedures at the level
enabling, and need factors should be considered of the individual healthcare organization, local,
at the patient/provider, healthcare system, and state, and federal government. Examples are inter-
population levels. pretation policies, policies to set literacy levels for
Health equity quality measures must be care- patient health information.
fully monitored, preferably utilizing a dashboard
over specified time intervals. Each measure Need Factor Interventions Within the CP
should be stratified by those risk factors, which Population
influence disparities in order to make sure that the Children with CP have need factors related to
interventions implemented are successful within (1) mobility barriers which can limit accessibility
all CP subpopulations (e.g., by race, socioeco- to healthcare due to the severity of their motor/
nomic status, language, etc.) When developing musculoskeletal involvement (spasticity/tone, skel-
strategies to decrease health and healthcare dis- etal deformity, and low bone density), (2) communi-
parities in the CP population and other cation challenges due to oral-motor involvement
populations of CSHCN, it is helpful to develop a affecting their ability to express their healthcare
logic model in order to identify vulnerability (pre- needs, (3) intellectual/developmental disability
disposing, enabling, and need) factors at all levels causing difficulty advocating for their healthcare
and then develop strategies to improve them preferences, and (4) medical need factors due to
(Fig. 6). Further research will be necessary to medical comorbidities.
identify the comparative effectiveness of each In children with ambulatory potential, need fac-
intervention to decrease disparities within the CP tor interventions to minimize mobility barriers
population. include a combination of orthotics, mobility aides,
and surgical interventions to improve lower extrem-
Predisposing and Enabling Factor ity alignment, lever arm function, and restore the
Disparity Interventions prerequisites needed for a normal gait. Spasticity
Predisposing factors such as demographics, cul- control to improve energy efficiency during gait is
tural beliefs, and social status often describe the also important to improve mobility. Single-event
Health Need Factors Interventions

Cerebral Palsy Specific
Attributes 1) Access to mobility aides,
1)Self-perceived or professionally therapy, spasticity and
evaluated health status 1) Motor/Mobility Needs
surgical management
2) Communication Needs
to improve mobility.
2)Quality of life indicators 3) Nutritional Needs
2) Communication Devices
4) Medical Needs
3) GI specialty/nutritionist
3) Subpopulation defined by 5)Mental/Behavioral/
access
high health risks includes Developmental Needs
4) Care Coordination/
physical health (chronic 6) Caretaker Status
Primary Care/Specialty
illness, disabled), mental Co-management
health, and social well-being 5) Early Intervention; Integrated
Mental Health/Behavioral
6) Caretake/respite support
Predisposing Factors Cerebral Palsy Specific

Interventions
Attributes
Reflects risk factors for access 1) Increased prevalence of CP
to care, quality of care, and 1) Cultural competency and
in African American population unconscious bias training;
health status such as: leading to decrease in: access to
1) Demographics associated improvement of access to
healthcare, health status, and primary/specialty care,
with variations in health quality of care (decrease access
status ancillary services for CP
to primary/specialty care with children in minority
2)Cultural and health beliefs CP expertise.
3)Social structure variables communities.
2) Initial poorer health status 2) Coordinated care for
associated with status and of child and family members
resource access such as family members of children
3) Increased chance of provider with CP with poor health
race/ethnicity/gender bias
Cerebral Palsy Specific Attributes Interventions

Enabling Factors
1) Increased prevalence 1) Improve: local public
transportation access to
Factors associated with the use of CP in low SES
services; satellite and
of healthcare services such as population leading to a community services
SES, health insurance, decrease in: access to 2) Education of providers on
transportation, language quality CP healthcare communication; care
concordance/low English services, literacy and coordination; community
proficiency, low literacy/health health literacy health workers.
literacy.
2) Difficulty communicating 3) Policy measures to provide
health needs due to public insurance access to
decreased health literacy all CSNCN
3) Decrease in private insurance 4) Home health support,
4) Increased financial and time Educational and job
burden in CP family and child. support for CP adult
Fig. 6 Logic model for individual level: health need, predisposing, and enabling factors specific to cerebral palsy
multilevel lower extremity surgery in ambulatory use of motorized wheelchairs, building accessibility
CP children with the goal of improving walking through ramps and handrails, lightweight orthotics,
function may help improve future mobility and and other mobility aids.
therefore assist future healthcare, educational, and Communication need factors due to poor oral-
job access for older CP children as they approach motor function can be improved through the use
adulthood. For CP children and adults with greater of augmentative communication devices in chil-
motor involvement, access is improved through the dren with adequate cognition. Medical staff
training to teach staff how individual patients with complex population of CSHCN, the Maternal
CP prefer to communicate and encourage them to and Child Health Bureau recommends that
take the extra time to communicate is also CSHCN receive ongoing comprehensive care
important. within a medical home, defined as a model of
Intellectual and developmental need factors family-centered, community-based care for
require the integration of mental and behavioral CSHCN (American Academy of Pediatrics Med-
health providers as well as special education pro- ical Home Initiatives for Children With Special
fessionals in order to develop appropriate individ- Needs Project Advisory Committee 2004). A sys-
ual educational profiles (IEPs) for the child, as tematic review by Homer et al. of 30 studies was
well as develop adequate education training to performed which provided moderate support that
maximize the chance of the child gaining mean- the medical home concept improved health-
ingful employment and income as an adult. related quality outcomes for CSHCN compared
The presence or absence of predisposing and/or to nonmedical home care settings (Homer et al.
enabling risk factors may positively or negatively 2008). The greatest impact was in the areas of
influence impact access to services such as primary family-centeredness, effectiveness, timeliness
and specialty care, educational services, therapy (of access), health/functional status, and family
services, orthotic and wheelchair services, etc. function; however, positive effects were found in
These services may directly affect outcomes of all outcomes which also included efficiency and
need factors, all of which may increase or decrease cost. More recently, the American Academy of
the risk of disparities in surgical and/or nonsurgical Pediatrics published a clinical report to guide the
outcomes that improve mobility. For this reason, an clinician providing a primary care medical home
integrated and coordinated care approach is neces- for children and youth with CP (Liptak and Mur-
sary to help mitigate poor access to services and phy 2011). They stressed ongoing collaboration
improve communication between those providers between parents, primary and specialty care pro-
who provide CP care. viders, dentists, and community agencies (recrea-
tional, educational, and parent groups).
The Medical Home and Care Coordination The US Department of Health and Human
CP children with multiple healthcare need factors Services in their Healthy People 2010 called for
(musculoskeletal, medical, intellectual, mental, all CSHCN to receive coordinated, ongoing, com-
etc.), often termed medically complex, require prehensive care as a fundamental part of a “med-
integration and coordination of primary care ical home” which includes children with CP,
with multiple specialty care providers, ancillary especially those with associated medical com-
services, and community resources. Typically, plexity (Department of Health and Human Ser-
children with greater motor dysfunction need fac- vices 2000). Care coordination is a process that
tors (motor involvement) also have greater com- facilitates the linkage of children and their fami-
munication, intellectual/developmental, and lies with appropriate services and resources
medical need factors. In addition, CP children (American Academy of Pediatrics Council on
with greater motor involvement and medical com- Children with Disabilities 2005). Recommended
plexity frequently have greater predisposing and characteristics include:
enabling risk factors (socioeconomic and cultural
complexity) (An 2016; Maenner et al. 2012). In a (1) A plan of care developed by the primary care
community-based survey of the CSHCN of chil- physician, practice care coordinator, child and
dren ages 2–17, there was an increased likelihood family, other providers, and agencies and
of Blacks relative to Whites of having organizations involved in the child’s care.
comorbidities such as a seizure disorders, devel- (2) A centralized confidential record/database of
opmental delay, and speech impairment (Dabney all of the child’s outpatient and inpatient care.
et al. 2018). In order to better coordinate and (3) Information which is shared among the child
integrate care in this socially and medically and family, appropriate medical and surgical
specialists, and behavioral/developmental deformity affecting ambulation, hip subluxation,

health professionals. and scoliosis. Of course, the CP neuromuscular
(4) Families are linked to support groups and specialist must stay current and should be
other family resources. involved with multidisciplinary organizations
(5) The care coordination physician assists the that focus on the care of the CP child such as the
child/family with understanding clinical American Academy of Cerebral Palsy and Devel-
issues being managed by subspecialists/ opmental Medicine (AACPDM).
consultants. Recent models of care coordination have also
(6) The medical home physician interprets spe- included telehealth technology as a means to
cialists’ recommendations and implements incorporate specialty collaborative care, one of
those appropriate for the child. which also included a full-time advanced practice
(7) A plan of care is coordinated with the educa- nurse added to an existing medical home to
tional and community organizations to ensure improve nursing support time through increasing
that the special healthcare needs of the child are family-centered care with telehealth support when
addressed (American Academy of Pediatrics necessary (Cady et al. 2015). Supporters of tele-
Council on Children with Disabilities 2005). health claim improved access to care, especially
for rural areas, as well as a decrease in financial
In the community, the educational system and burden to families (Hooshmand and Yao 2017).
the home care coordination may require written The neuromuscular pediatric orthopedist
individual family plans, individual educational or should be an integral part of a care coordination
504 plans, and/or home nursing/therapy services. collaborative framework for the child with CP and
Benefits to care coordination have included: a should include evidence-based treatment recom-
reduction in hospital admissions, length of stay, mendations for orthopedic interventions to
and charges; a reduction in emergency room improve gait, hip dislocations, spinal deformity,
visits, and improved patient satisfaction and qual- strengthening, tone management, etc. Other col-
ity outcomes (American Academy of Pediatrics laborative specialists may be necessary to assist
Council on Children with Disabilities 2005). with guidance on nutrition and growth, seizure
However, numerous barriers to care coordination control, cortical visual impairment, hearing,
exist and may include lack of patient access; lack bone health, and family support, especially in the
of knowledge about CP; poor communication CP child with medical complexity. Another model
between care providers and entities caring for of care coordination more formally utilized a col-
the child; lack of clearly defined roles within the laborative primary care medical home team/spe-
care coordination team, which includes the fam- cialty care coordination team model, specifically
ily; inadequate acknowledgment and reimburse- for CSHCN and medical complexity, including
ment for care coordination; a poorly organized children with CP (Cady et al. 2015). The model
care coordination system; and language/cultural, coordinated care between the child’s/family’s
educational, and socioeconomic barriers (Ameri- existing medical homes and specialty care sites
can Academy of Pediatrics Council on Children within an integrated pediatric specialty healthcare
with Disabilities 2005). Within the structure of system. The specialty care coordination team
care coordination, it is important for the neuro- consisted of a registered nurse, social worker,
muscular orthopedic surgeon and pediatric reha- and an appointment coordinator, supporting a
bilitation medicine physician to be integrated with shared plan of care and communication between
the medical home by educating the medical home primary care and specialty care providers.
primary care physician and team and being avail-
able for consultation to address important muscu- Disparities in the Transition into Adult
loskeletal issues that can negatively impact Healthcare
quality of life and mobility in the CP child such One of the most vulnerable time periods for chil-
as muscle contractures, spasticity, and boney dren with CP and other CSHCN is those
transitioning from youth into adulthood. This received transition into an adult medical home;
transition occurs over multiple areas including however, disparities persisted when comparing
changes in medical care, insurance coverage, transition rates to an adult medical home of
development of self-care skills, and education non-Hispanic Whites (59%) to those of
and job planning (Lotstein et al. 2010). As a result, non-Hispanic Blacks (45.5%) and non-Hispanic
the provision of healthcare and social services for other races (41.9%) (which combined Asians,
the CP child becomes fragmented into adulthood. Pacific Islanders, Native Americans/Eskimo) and
Stevenson et al. showed that the usage of health Hispanics (44.6%) in transition (Richmond et al.
and social services decreased in CP youth after 2012). Characteristics which predicted medical
school age (Stevenson et al. 1997). The medical home transition in both Hispanic and
home in combination with care coordination can non-Hispanic included a household member with
assist with the transition from pediatric to adult more than a high school education and adequate
healthcare providers and access to adult commu- insurance, while being >200% of the federal pov-
nity resources and social activities. The transition erty level positively predicted medical home tran-
discussion should begin early, no greater than sition within the Hispanic population of CSHCN.
12 years old, to allow some overlap while the No characteristics were positively predictive of
youth is transitioning providers. Formal transition medical home transition within the non-Hispanic
should occur between 18 and 21 years old (Young Black population. The authors recommended a
2007; Cooley and Sagerman 2011). Examination more culturally tailored intervention which incor-
of the 2001 and 2005 National Surveys of Chil- porates quality improvement approaches to pro-
dren with Special Health Care Needs gress medical home transition, especially for the
(NS-CSHCN) showed only 15.3% and 41.2%, Black population. In addition, policy measures
respectively, of CSHCN to have achieved positive which improve transition service reimbursements
transition performance outcome criteria indicating and improve health literacy and communication
one possible reason for a decrease in usage of style may further increase transition rates.
healthcare in this population (Strickland et al.
2009). This gap was greater for minority Transition of Orthopedic Services in the CP
CSHCN. Poor transition of services leads to dis- Population
parities in access to healthcare for CSHCN. The Over 90% of children with CP will survive
2005 NS-CSHCN demonstrated an even lower beyond their 18th birthday (Strauss et al. 2008).
transition performance outcome than the 2001 After the transition of the CP adolescent to adult
survey, with only 28.7% of non-Hispanic Blacks care, it may be very difficult to find access to an
and 26.3% of Hispanic youth achieving the out- adult orthopedic surgeon experienced in neuro-
come measure compared to the 41.2% overall muscular surgical care. It is important to anticipate
CSHCN population (Lotstein et al. 2009). After this and to recommend most major surgical care
a multivariate analysis, comparing non-Hispanic (e.g., spinal fusion, multilevel surgeries, hip
White CSHCN with non-Hispanic Black youth reconstructions, etc.) while the child with CP
and Hispanic CSHCN, the latter had 1.5 and still has access to an experienced pediatric CP
1.43 times higher odds, respectively, of not surgeon. This may also be true for other pediatric
achieving the transition outcome measure. After specialists. In the future, it will be important for
controlling for race and ethnicity, those who did adult specialty societies to provide more expertise
not speak English had a 2.45 odd of not achieving in the care of cerebral palsy adults during resi-
the transition outcome. Richmond et al. found dency training so that adult specialty providers
racial disparities in the transition to adult will be adequately prepared to provide care for
healthcare in a cohort of youth with special this population, therefore becoming less of an
healthcare needs despite being a part of a pediatric access issue.
medical home. In their study, approximately 57% The orthopedic needs upon transition will dif-
of overall youth with special healthcare needs fer depending on the motor involvement and
current functional status and deformities of the industrialized nations, but especially true through
young person with CP. Parents and young adults the health equity lens (Davis et al. 2014;
with CP often report an increase in burden of care, Schneider et al. 2017). Coupling this paradox
a decrease in provider communication for what is with the fact that the USA leads the world in
often a very different subculture between pediatric healthcare expenditures, with healthcare spending
and adult-oriented medical and orthopedic care. reaching approximately 17% of our gross domes-
As an example, the adult CP patient may find tic product, has caused us to face the harsh reality
herself seeing several orthopedists, given the of how we can deliver a higher quality of
fields’ many narrow areas of sub-specialization healthcare for equal or lower cost (Adverse health
(spine, hip, upper extremity, foot/ankle) that may conditions and health risk behaviors associated
be required. Burns et al. recommend clear com- with intimate partner violence—United States,
munication and documentation from the pediatric 2005 2008).
to the adult orthopedic CP provider which they The value proposition, defined by the value
term “the minimum clinical data set,” a transition equation, is simply put as quality in the numer-
document that accurately summarizes some of the ator and cost in the denominator, but may prove
medical record, corrects inconsistent information, to be difficult to define, depending on whose
and focuses on the musculoskeletal history and prospective quality and cost comes from
active/ongoing problems (Stevenson et al. 1997). (Bachman et al. 2017; Moriates et al. 2015).
The document may include patient information From the patient and family’s prospective, qual-
regarding spasticity management, muscle contrac- ity equates to what benefits the patient and fam-
tures, bone health/fracture management, pain ily, while the denominator cost equates to the
management, hip dysplasia/degenerative arthritis, financial impact on the family (e.g., out-of-
spinal deformity, torsional malalignments, need pocket costs, family financial burden, days mis-
for orthotics and other mobility aides, etc. sed from work/school, cost of family member
(Burns et al. 2014). This document should be providing care, etc.). The definition varies when
reviewed in detail with the patient and family. the perspective moves to the payor or the pro-
The motor classification of the patient should vider with the cost side equating to healthcare
also be clearly documented. Spine and hip radio- expenditures or cost to the payor or provider,
graphs should be performed prior to transition. In while quality relates more directly to medical
addition, health-related quality of life metrics are outcome measures and the patient experience
helpful to document outcome measures in order to within the healthcare system.
manage specific treatable issues which may
impact need factors causing vulnerability to qual-
ity of life, therefore becoming a health disparity to Value for CSHCN, CMC, and Children
the CP adult compared to his or her peers. with CP: The Patient and Family
Perspective
Quality, Cost, and Value: Their Impact The financial impact on families of CSHCN is
and Importance on Disparities substantial. Children from low-income families
in Children with Disabilities have higher financial barriers to healthcare and
pay a higher proportion of out-of-pocket income
A global comparison of healthcare shows that (Wong et al. 2005). Newacheck reported that
while the USA is one of the most technologically CSHCN pay two times the out-of-pocket
advanced, it is ironically has one of the worse healthcare needs compared to those without spe-
delivery systems among technologically cial healthcare needs (Newacheck and Kim 2005).
advanced countries. This is the case when com- According to the 2001 National Survey of
pared using several quality measures with other CSHCN, greater than 80% of families reported
having annual out-of-pocket healthcare expendi- Services, Health Resources and Services Adminis-
tures averaging $752 (Porterfield and DeRigne tration, Maternal and Child Health Bureau 2013c).
2011). The 2009–2010 National Survey of Time burden spent providing care to the
CSHCN has shown annual out-of-pocket pay- CSHCN is another potential burden to the family.
ments for greater than 50% of children to be This includes time giving medications and thera-
greater than $250, with 22% of families spending pies, arranging or coordinating care providers,
greater than $1000 of out-of-pocket costs (U.S. providing transportation to medical appointments,
Department of Health and Human Services, etc. This time burden was reported higher in
Health Resources and Services Administration, low-income families with 20% of poor families
Maternal and Child Health Bureau 2013b). Out- reporting spending 11 h or more per week provid-
of-pocket costs for low-income families had a ing care compared to only 6% in families with
higher likelihood of being covered compared to incomes of 400% above the poverty level (U.S.
the 2000 survey. This is likely due to the current Department of Health and Human Services,
coverage by Medicaid and SCHIP, which limit Health Resources and Services Administration,
copays to families. Non-Hispanic White families Maternal and Child Health Bureau 2013d). Simi-
are most likely to pay > $1000 out-of-pocket lar to financial burden, time burden was more
expenses which are likely due to the lower public common in families of children with greater func-
insurance status in this population. The survey, tional disability (29.3%) (U.S. Department of
however, did not address relative out-of-pocket Health and Human Services, Health Resources
expenses (out-of-pocket cost as a proportion of and Services Administration, Maternal and Child
family income) as previously reported by Wong Health Bureau 2013d). Romley et al. did a cost
et al. (2005) or financial burden reported by Lindley analysis on family-provided care from the
and Mark (2010), both of whom reported higher 2009–2010 CSHCN survey finding that 5.6 mil-
levels of relative out-of-pocket income and financial lion CSHCN received 1.5 billion hours of care
burden, respectively, for lower-income children. annually (Romley et al. 2017). This equates to
This was validated in the 2009–2010 survey, an estimated annual home health aide cost of
which did ask families whether the child’s condition $35.7 billion, or $6500 per child per year. Alter-
or need caused a financial problem for the family natively, it equates to an annual minimum wage of
(U.S. Department of Health and Human Services, $11.6 billion or $2100 per child per year. Addi-
Health Resources and Services Administration, tionally, annual forgone earnings were estimated
Maternal and Child Health Bureau 2013c). While at $17.6 billion. The greatest amount of family-
children from lower-income families with CSHCN provided care lived below the poverty level were
had lower out-of-pocket costs, they reported higher Hispanic, were parents/guardians without a high
financial problems caused by the child’s condition school diploma, and had CSHCN with severe
compared to higher-income families (U.S. conditions. Of CSHCN listed, families of children
Department of Health and Human Services, Health with CP had the highest number of family-
Resources and Services Administration, Maternal provided care hours per week with an estimated
and Child Health Bureau 2013c). The highest per- 14.4 care hours per week per child given (Romley
centage of families reporting financial problems due et al. 2017). Socioeconomic disparities also exist
to the child’s condition were those who were according to the impact of CSHCN on parent
uninsured (47.6%). Public insurance appears to par- employment with the percentage of parents of
tially mitigate this burden (21%) compared to those CSHCN cutting back or stopping their employ-
with private insurance (19%). Those families with ment which increased according to the level of
children who have conditions affecting daily activ- poverty (33% in those below the poverty line
ities the most (i.e., severe physical disabilities) versus only 18% in those families greater than
have the highest reported financial problems 400% above the poverty line). This effect on
(38.5%) (U.S. Department of Health and Human employment was found to be highest among
children with greater disability and medical child, per year) than children without CP ($1674
complexity. per Medicaid-enrolled child, per year), while
those children with both CP and an intellectual
Value of CSHCN, CMC, and Children disability had a cost that was 26 times higher (per
with CP: The Provider and Payor Medicaid-enrolled child, per year $41,664)
Perspectives (Autism and Development Disabilities Monitor-
Delivering high-value healthcare to vulnerable ing (ADDM) Cerebral Palsy Network 2013).
populations such as CSHCN with disabilities, Considering the high medical cost and family
CMC, and children with CP is also important from burden per year of CSHCN, CSHCN with medical
the payor and provider perspective since they carry complexity, and children with CP coupled with
such a heavy cost burden. Healthcare expenditures the many poor-quality measures already stated,
related to the entire disabled population (children the value equation from the payors, healthcare
and adults) have been estimated at 400 billion dol- organizations, and the family perspective leaves
lars annually, with a majority spent on public pro- much room for improvement. In order to improve
grams (Anderson et al. 2010). While CSHCN value for these vulnerable pediatric populations,
represent a small percentage (15–18%) of the pedi- including children with CP, innovative healthcare
atric population, they account for approximately delivery and payment models will be crucial. In
42% of total pediatric medical costs, 33.6% of addition, these models must create equitable out-
total healthcare costs of pediatric healthcare spend- comes within their respective subpopulations
ing, and 52% of children’s hospital days according (e.g., by socioeconomic status, race, ethnicity,
to 2000 Medical Expenditures Panel Survey language, etc.).
(Strauss et al. 2008). Ultimately, improvement in value for CSHCN,
CSHCN with medical complexity represent a CMC, and children with CP will depend on
smaller subgroup of CSHCN of only 0.4–0.7% of improving or creating healthcare delivery models
US children, but with higher expenditures per child that decrease expenditures and decrease the time
and account for 15–33% of all children’s healthcare and cost burden to families while improving both
spending, approximately $50–$110 billion annu- the quality of medical care and quality of life for
ally. These patients often have high inhospital, emer- these pediatric populations and their caretakers.
gency department visits, pharmacy charges, and On the payor/provider side, alternative payment
homecare costs and represented 71% of unplanned models will need to incentivize and hold providers
30-day readmissions (Berry et al. 2014). These accountable for meeting cost and quality targets.
authors proposed a business case of how cost sav- Finally, state and federal policies will need to
ings in each of these areas could provide a greater protect patient’s interest by regulating a balance
investment into outpatient and community care of between payors and providers to keep the patient’s
these children. The same study showed children and family’s needs at the center. Since children
with neurologic or neuromuscular conditions with CP are a subgroup of CSHCN, CMC, and
represented approximately 25% of CSHCN with children with disabilities, the examples and prin-
medical complexity. Many children with cerebral ciples that follow are largely applicable to the CP
palsy fall within this subgroup, especially those population as well.
who are GMFCS levels 3, 4, and 5.
In the case of children with CP, the CDC esti- Value and Healthcare Delivery Models
mated that the lifetime costs of children born with in CSHCN, CMC, and Children with CP
cerebral palsy in the year 2000 would total Most models of healthcare delivery for CMC and
approximately 11.5 billion dollars (Autism and CSHCN heavily emphasize enhanced care coor-
Development Disabilities Monitoring (ADDM) dination as well as the importance of integrating
Cerebral Palsy Network 2013). Medicaid- primary, subspecialty, and community care, each
enrolled children with CP had a cost that was of which is critical to address the need, pre-
10 times higher ($15,047 per Medicaid-enrolled disposing, and enabling factors within vulnerable
populations described earlier and which are nec- becoming involved in the care of the patient
essary to eliminate the health outcome disparities until the problem has become too advanced (e.g.,
within the CP, CMC, and CSHCN subpopula- hip dislocation and advanced scoliosis in the CP
tions. In their review of care for CMC, Pordes child) if the primary care physician is the sole
and colleagues describe three categories of care gatekeeper to specialty care. There is also a risk
delivery models for children with medical com- for diffusion of responsibility of coordination and
plexity: primary care-centered, co-management- integration of care with other specialties and
centered, and episode-based models (Pordes community-based services (i.e., “no captain of
et al. 2018). Each category has separate implica- the ship”), which can result in lack of care
tions for quality and cost for CMC. accountability to the patient and family. Also,
The primary care-centered model is defined by enrollment criteria within many collaborative
the patient-centered medical home, described ear- care models may leave some subsets of children
lier in this chapter. Its advantage is that it is typi- with unmet medical and technology needs.
cally geographically closer in proximity to the Episode-based models are most effective when
family’s home and therefore results in easier acute medical management is required such as the
travel, access, and less time and financial burden need for around-the-clock bedside management
to the family. In addition, their knowledge and and primarily occurs within an inpatient facility.
access to community resources is often better The greatest advantage is the ability to treat the
than the other models of care. On the other hand, child during their most vulnerable clinical status
resources and infrastructure may be lacking for with caretakers who have a high degree of famil-
care coordination, and adequate medical record iarity with the specific condition of the child. In
sharing across systems and/or an adequate knowl- the more involved CP child, this is often the case
edge/skill level to take care of condition-specific post-surgery or for an acute medical episode.
problems such as CP may be minimal. The latter While there is also the advantage that the burden
may negatively impact cost, quality, and clinical of care provision is removed from the family
decision-making. In addition, the evidence for the during this acute episode, time and financial bur-
cost-effectiveness of the medical home for den is often highest for the family due to missed
CSHCN is mixed with one study supporting time from work and time with other children dur-
decreased inpatient expenditures, especially in ing the acute medical episode of care. In addition,
those with physical limitations (Romaire et al. episode-based care has a high-cost tag, despite
2012). There is also some evidence that a hybrid often being associated with strict discharge stan-
community-based primary care-centered model dardizations. Finally, this model of care is most
linked to a tertiary care center for CMC may associated with poor care continuity and coordi-
decrease healthcare system costs as well as parent nation with the child’s primary medical provider
out-of-pocket costs while improving quality of and educational and community care teams.
life domains like comfort, emotions, and social CSHCN and CMC are at especially high risk
within the child’s quality of life (Cohen et al. for hospitalization and may require weeks to
2012). months for the recovery of overall health and
Co-management models are usually connected function. In addition to the comprehensive care
with a tertiary care center such as children’s hos- models described above, home healthcare and/or
pitals which often have a higher service delivery post-acute facility care may help to reduce the
cost, but may also have dedicated resources for overall cost of care to the healthcare system and
the start-up cost of care coordination and elec- out-of-pocket cost and burden to the parents of
tronic medical record systems compared to a pri- prolonged acute care hospitalizations in the case
mary care-centered model, leading to better care of home healthcare. In addition, lengthy stays in
coordination and integration. This model is often an acute care facility increase the risk in CMC for
consultative and also provides greater expertise, inhospital nosocomial infections. In a national
but also stands the risk of the specialist not study by Berry et al., discharge of children to
home healthcare and post-acute facilities was Accordingly, ACOs are also focused on coordi-
much less common than for adults and was more nated care in order to avoid unnecessary duplica-
common in children with four or more chronic tion of services while encouraging quality
conditions (CMC) and with neuromuscular com- outcomes. Finally, bundled or episodic payments
plex chronic conditions (Berry et al. 2016). create a single payment for a single service or an
Racial/ethnic disparities were found with a lower episode of care such as a surgical episode. For
percentage of Hispanic children discharged to example, in the case of the child with cerebral
both home healthcare and to post-acute care facil- palsy, a bundled payment may include a preoper-
ities. On the other hand, a higher percentage of ative gait analysis and a single-event multilevel
non-Hispanic Black children were discharged to surgery, plus the postoperative rehabilitation/ther-
post-acute care facilities. It is unclear why these apy services as one episodic payment. The pro-
racial/demographic disparities exist. Further study vider therefore assumes the full financial risk for
is necessary to ascertain the role and outcomes of the entire episode, including any preventable sur-
post-acute care and home healthcare post-hospital gical complications, and various bonus payments
admission in CMC and their success in different for achieving performance measures.
racial, ethnic, and socioeconomic groups. Whether the impact of alternative payment
models will be positive or negative is currently
Value and Alternative Payment Models largely unknown. Incentives under alternative
in CSHCN, CMC, and Children payment models allow investment into care coor-
with Cerebral Palsy dination, community health workers, and care
Currently, an increasing interest in improving management, typically not reimbursed in most
overall value in healthcare is evolving by improv- fee-for-service models. In the child with cerebral
ing cost-effectiveness through the use of alterna- palsy, value-based purchasing strategies will
tive payment models or so-called value-based require knowledge of the lifetime cost per child
purchasing strategies. This shift from fee-for-ser- with cerebral palsy according to their motor and
vice to value has primarily been used in adult intellectual involvement, as well as the lifetime
healthcare systems, with value-based purchasing cost per CP child according to coexisting medical
slowly being incorporated into pediatric morbidities. Further complicating this is the added
healthcare and will likely have a significant cost of social complexity found in the overlying
impact on the care of all CSHCN (Bachman socioeconomic and racial disparities that fre-
et al. 2017). Alternative payment models vary quently occur in the CP population. In addition,
from pay-for-performance features to full-risk while the pay-for-performance features of value-
models that pay providers a capitated fee for the based purchasing strategies theoretically incentiv-
care of a specified population (Langer et al. 2018). ize and improve the quality side of the value
Those which have pay-for-performance features equation, there currently are no consistently
pay bonuses for improved high-quality perfor- agreed upon quality outcome metrics that impact
mance through incentivizing payments for value CSHCN or children with cerebral palsy. Also,
and health outcomes such as patient-centered financial penalties in alternative payment models
care, care coordination, improving social determi- may bias providers into the selection of caring for
nants of health, integrating behavioral health and less medically and socially complex patients
community-based organizations, and clinic sys- (Joynt Maddox 2018) which may further increase
tem integration. In addition to rewarding high socioeconomic and/or racial and ethnic disparities
quality, other types of alternative payment within the CSHCN, CMC, and cerebral palsy
models, such as accountable care organizations populations. Adequate risk adjustment will there-
(ACOs), are penalized for poor outcomes. ACOs fore be necessary to incentivize providers to care
are formed by groups of physicians and typically for complex pediatric patients. Predictive model-
receive a risk-adjusted global budget for a popu- ing of high-cost patients using parent-reported
lation (capitation) and must manage total costs. measures which include sociodemographic
characteristics has been shown to be helpful in place to assist with the musculoskeletal needs of
predicting the risk of high health costs in the child, including assistance with therapy,
CSHCN (Leininger et al. 2015). Regardless of equipment needs, and community resources.
the delivery or payment model, care management Care coordinators rotate between their care coor-
for the delivery of care to CSHCN, especially dination role, seeing patients in the outpatient
within integrated systems such as state Medicaid clinic and being a part of the inpatient team during
systems, is critical for controlling cost through the episodes of inpatient care.
reduction of duplicative services, internal incen- The need for orthopedic surgery is common for
tives for cost reductions, and improvements for the child with CP. In our model upon anticipation of
the coordination of care and decreasing adminis- a surgical episode, the musculoskeletal care coordi-
trative costs in the processing of claims (Marcu nator begins to prepare the child and family for
et al. 2016). Through the combination of innova- surgery. This first step involves educating the family
tive care delivery systems, alternative payment and child (age appropriate) about the surgical proce-
models, and care management, high-value care dure and the postoperative course, including assis-
for all CSHCN, especially those CMC, and chil- tance with any medical and community resources
dren with CP can hopefully be achieved. that will be needed to support the family and child
postoperatively. The goal is to minimize inhospital
A High-Value Musculoskeletal Model acute care and time/financial burden to the family,
of Care Delivery for the CP Child expedite the rehabilitation process, and assimilate the
Within our own healthcare organization, a large child and family back into their home and commu-
cerebral palsy center, an integrated primary/spe- nity. Families with a diverse race/ethnic background,
cialty musculoskeletal care collaborative model a more rural geography, a community of lower
exists with medical care coordination occurring socioeconomic background, a limited English profi-
in tandem with orthopedic care coordination. A ciency, and an immigrant status often have increased
team of primary care physicians rotate, caring for barriers to the necessary resources to provide the
the more medically complex surgical CP patients proper postoperative equipment, support, and reha-
during their preoperative work-up and their inpa- bilitation services (Parish et al. 2012; Eneriz-Wiemer
tient surgical episode. Patients who are close geo- et al. 2014; Kan et al. 2016). In such cases, the child
graphic proximity are also a part of the medical may benefit from inpatient or intensive outpatient
home. In this model, there is also an integrated rehabilitation in a hospital or post-acute care setting
team of neuromuscular orthopedic surgeons and in order to mitigate these barriers and achieve opti-
rehabilitation medicine specialists who see the mal and equitable surgical outcomes.
child as an outpatient every 6 months. A team of Using this care delivery model allows each
nurse practitioners and physician assistants share member of the team to familiarize themselves with
the role as neuromuscular care coordinator and each child and their family. In addition, this model
communicate with the family prior to their first allows the patient to move between primary care-
visit to ascertain the family’s needs and then centered, collaborative care-centered, and episode-
develop a preliminary plan of care which includes based care models when necessary while preserving
the possible need for orthotic services, therapy patient-/family-centered care coordinators who
services, wheelchair or other assistive devices, have developed a relationship with the patient.
augmentative communication, bone health, gait
analysis, primary care, mental/behavioral health
services, and/or specialty care (including orthope- Health Policy to Prevent Health
dic surgery). Next, a coordinated visit is set up and Healthcare Disparities in CSHCN
between the necessary specialty care providers
and the family and child. Ongoing communica- In addition to the creation of innovative healthcare
tion between the musculoskeletal care coordina- delivery and alternate payment models aimed to
tor, primary care provider, and the family takes mitigate disparities in health need factors in
pediatric vulnerable populations such as children independent living, etc. (Field and Jette 2007).
with CP, health programs and policies at both the An early focus on long-term planning for a
state and federal levels are put in place to help child’s transition into adult life can help families
regulate and protect CSHCN with disabilities, identify and ameliorate potential concerns.
CMC, and children with CP at a population health There is increasing pressure on our national
level. For example, the Rehabilitation Act of healthcare and public health sectors to suffi-
1973, Section 504, protects the rights of individ- ciently address the existing and future health
uals with disabilities who are involved in pro- needs of children with disabilities across their
grams or activities that receive federal financial lifespan (Krahn et al. 2015).
assistance from the Department of Education (The Even with better access to insurance, the Amer-
Rehabilitation Act 2017). Additionally, the Amer- ican health system is not well designed to meet the
icans with Disabilities Act of 1990, Title II needs of people with serious long-term health con-
(ADA), prohibits discrimination based on disabil- ditions or disabilities. CSHCN and disabilities are
ity and guarantees equal opportunity for those more likely than other children to have health insur-
with disabilities in employment, public accommo- ance and are somewhat more likely to have public
dations, telecommunications, and state and local insurance compared to other children (Field and
governments (Americans with Disabilities Act Jette 2007). As mentioned previously, this popula-
(ADA) 2015). tion also utilizes more healthcare services than other
Furthermore, there are available programs children (Bachman et al. 2017). Medicaid, along
and policies that are aimed to help children with other public insurance options, covers 44% of
with healthcare needs and disabilities to CSHCN, serving as the primary source of coverage
smoothly transition into adulthood. Some exam- for more than one-third of this population (Schubel
ples of health-related public programs that are and House 2017). Medicaid is considered the gold
being implemented are Title V of the Social standard for insurance coverage of CSHCN and
Security Act and the Individuals with Disabil- disabilities because states are required to provide
ities Education Act (IDEA) (Field and Jette the Early and Periodic Screening, Diagnostic and
2007). The former allows the Maternal and Treatment (EPSDT) benefit, which guarantees indi-
Child Health Bureau (MCHB) to direct a major viduals under the age of 21 access to comprehen-
program of state block grants that offer support sive and preventive health services (Schubel and
services for mothers, children, and infants. House 2017). These services include regular well-
Additionally, it offers specialized national pro- child visits; hearing, vision, and dental screenings;
grams that are catered toward children with spe- and treatments for physical, mental, and develop-
cial healthcare needs or disabilities. IDEA mental diseases and disabilities, as well as long-
mandates that children with disabilities who term services and supports.
require special education and associated ser- Even with the availability of public insurance,
vices receive free appropriate public education. however, there is instability across Medicare,
Federal policies also require that school districts Medicaid, and State Child Health Insurance Pro-
pay for certain services and assistive technolo- gram (SCHIP). For example, children are often
gies for children who require special education disenrolled and reenrolled in different program
and associated services. IDEA also mandates options due to strict program requirements,
that transition planning into adulthood should changes in family income, or characteristics of
begin no later than age 16. This transition is the child that determine whether they are eligible
intended to be results-oriented and dedicated to for Medicaid, other public coverage, or no cover-
helping the child reach their highest functional age (Field and Jette 2007). This is especially
and academic potential and facilitates fluid concerning for CMC. In 2015, Advancing Care
movement between the different aspects of for Kids Act was introduced as a bill to congress,
their life, from school to post-school activities, which would give states the option of providing
community involvement, employment, services to CMC under the Medicaid and SCHIP
programs through a Medicaid Children’s Care performance features. Additionally, financial

Coordination Program (Langer et al. 2018). The incentives should be explicitly guarded not to
Act helps to account for the inability of typical bias providers from selecting complex cases. In
policy measures which are focused on access, addition, increased funding and reimbursements
cost, and quality in the general population and are needed for both home- and community-
adult chronic conditions and are unable to take based services that are currently underfunded.
into account the nuances of delivery systems for Further measures are also necessary to mitigate
CMC (Langer et al. 2018). family hardship burdens.
In the future, policy makers will need to CSHCN, with and without disabilities, and
address a number of policy issues to achieve CMC are particularly at risk for marginalization
optimum care in CMC (Bachman et al. 2017; and health inequity. Risk adjustments for poor func-
Langer et al. 2018). First, providers, payors, tional status should be considered in pay-for-perfor-
and policy makers will need to reach a definitive mance alternative payment models along with
consensus definition of CMC in order to better medical complexity. Finally, vulnerable pediatric
understand the true number of patients within populations also have an increase in both racial
the CMC population to ascertain better accuracy and ethnic and socioeconomic disparities, all of
of the number of CMC for resource allocation, which will require consideration in value-based
quality, cost, and reimbursement for this medi- purchasing and alternative payment models.
cally complex population. There also needs to be
consensus on broadly measured quality mea-
sures for CSHCN and CMC in order to establish Cases
viable quality metrics for alternative payment
models. This will help enable adequate risk Case 1 (Pre-care Coordination) (Fig. 7)
complexity adjustment to prevent providers
who care for increased numbers of CSHCN, This is a 14-year-old young lady with diagnoses
especially CMC, from being disadvantaged by that include quadriplegic CP with microcephaly,
alternative payment models with pay-for- seizure disorder, a need for gastrostomy tube
Fig. 7 (Left) The patient’s AP radiograph immediately postoperatively after her spinal fusion. (Right) A decubitus ulcer
that the patient developed due to poor nutrition 2 months postop
feedings with dysmotility and FTT, global devel- multiple decubitus ulcers (medial malleolus,
opmental delay, and severe intellectual disability over prominent pelvic fixation, and ischium (see
(GMFCS V, nonverbal). figures below)). The patient required a 1-month
The child was initially seen at age 3 (2006) by hospitalization for wound care, rotational skin
orthopedics and rehabilitation medicine. She is flap, and antibiotic treatment. Opportunities for
seen by multiple providers including develop- improvement included care coordination to
mental pediatrics, gastroenterology, general sur- improve communication between specialty pro-
gery nephrology, neurology, ophthalmology, and viders and work on improving the child’s nutrition
urology. status prior to surgery as well as improve educa-
Socially, the child lives with parents and four tion about the surgery with the family.
siblings. They live approximately 2 h, drive from
hospital, and attend special needs school. The
child attends a special needs school 1 h. away. Case 2 (Fig. 8)
The family has no home nursing.
Most recently, the child was noted to have a This child is a 13-year-old male with a history of
progressive scoliosis (see figure below), and a quadriplegic pattern CP (GMFCS 5), severe spas-
posterior spinal fusion with instrumentation was ticity, communication disorder requiring commu-
recommended; however, the family was reluctant nication device, poor oral intake due to
to have surgery until 1 year later. Preoperatively, swallowing disorder, gastroesophageal reflux,
the child was seen by pulmonology, neurology, mild reactive airway disease, mild sleep apnea,
and pediatrics for clearance. The child was below and chronic nutritional deprivation with
the tenth percentile weight for height ratio with BMI < fifth percentile. The child had previous
intermittent nutritional problems due to social hip procedures, a femoral head resection, and
issues. valgus osteotomy for hip pain and continues to
The surgery was without complications; how- have chronic pain requiring chronic opioids. The
ever, postoperatively after discharge, the patient family called to request a second opinion due to
developed a fever, wound breakdown, and the child’s continued chronic hip pain.
Fig. 8 (Left) An AP radiograph of this 13-year-old male left hip replacement to treat the failed left femoral head
with CP, quadriplegia who had previous left femoral head resection, and a right femoral varus derotational osteotomy
resection and valgus osteotomy to treat left hip pain. with and right peri-acetabular pelvic osteotomy. Now with
(Right) Development of a right hip dislocation and also improved care coordination, the patient had improved out-
right hip pain with recurrent left hip pain. This shows the comes and is pain free
final postop radiograph of this patient after treatment with a
Socially, the child lives with his grandmother system and/or improve the health of all children. Pedi-
and aunt in a rural community with poor access to atrics 113:1545–1547
Americans with Disabilities Act (ADA). 2015 Oct
services and is greater than 2 h away from the 15 [cited 21 Jan 2018]; Available from: https://www2.
hospital. ed.gov/about/offices/list/ocr/docs/hq9805.html
Our care coordinator called the family prior to An R (2016) Unmet mental health care needs in U.S.
their visit and did a telephone intake history and children with medical complexity, 2005–2010.
J Psychosom Res 82:1–3
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bilitation medicine, our pediatrics complex medi- (2010) Estimates of state-level health-care expendi-
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Part IV
Pathology
Neuroimaging Pathology in
Cerebral Palsy 13
Rahul M. Nikam, Arabinda K. Choudhary, Vinay Kandula, and
Lauren Averill
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 178
Fetal Neuroimaging Techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 179
Hypoxic-Ischemic Brain Injury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 180
Preterm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181
Term Infants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 186
Congenital Infections of the Central Nervous System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189
Cytomegalovirus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191
Toxoplasmosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193
Lymphocytic Choriomeningitis Virus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193
Congenital Malformations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 195
Lissencephaly (The Agyria-Pachygyria Complex) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 196
Microcephaly with Simplified Gyral Pattern (MSG) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 197
Schizencephaly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 197
Megalencephaly-Postaxial Polydactyly-Polymicrogyria-Hydrocephalus Syndrome
(MPPH) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199
Septo-Optic Dysplasia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200
18q-Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 202
Syntelencephaly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203
Joubert Syndrome and Related Disorders (Molar Tooth Malformations) . . . . . . . . . . . . . . 203
Rhombencephalosynapsis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 206
Aicardi Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209
Hydranencephaly . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211
R. M. Nikam (*) · A. K. Choudhary (*) · V. Kandula ·

L. Averill
Nemours A I duPont Hospital for Children,
Wilmington, DE, USA
e-mail: Rahul.Nikam@nemours.org;
arabinda.choudhary@nemours.org;
vinay.kandula@nemours.org; lauren.averill@nemours.org

https://doi.org/10.1007/978-3-319-74558-9_10
178 R. M. Nikam et al.
Miscellaneous . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211
Kernicterus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 211
Abstract interval (CI) 1.98–2.25). Although neuroimaging is

Neuroimaging in cerebral palsy, although not a not a prerequisite for the diagnosis of CP, neuroim-
prerequisite for diagnosis, provides vital aging findings are abnormal in more than 80% of
insights in elucidating the etiopathogenesis children with CP (Himmelmann et al. 2017;
and has widespread implications in treatment, Korzeniewski et al. 2008; Krägeloh-Mann and
prognosis, and planning early interventions Horber 2007). Also, neuroimaging provides vital
to curtail complications. Neuroimaging is insights into etiology, pathogenesis, and prognosis
abnormal in a majority of children with cerebral and has implications for prevention and interven-
palsy. Magnetic resonance imaging, due to its tional strategies. Accurate determination of the etio-
superior soft tissue differentiation, multiplanar logy of CP has specific implications regarding
capabilities, and prospect for functional imag- treatment, prognosis, and ongoing medical manage-
ing, is uniquely qualified for assessment of fetal ment of associated conditions (Ashwal et al. 2004).
and postnatal brain. Cranial ultrasound and Neuroimaging is frequently obtained if there
computed tomography, although inferior in is history of perinatal complications, prematurity,
soft tissue resolution, have a potential role in or when neonatal examination is positive
emergent situations. Hypoxic-ischemic enceph- for neurologic symptoms or signs. The array of
alopathy is one of the commonly identified imaging techniques available for evaluation of
causes of cerebral palsy with other etiologies neonatal brain includes ultrasonography (US), com-
being congenital infections of central nervous puted tomography (CT), and magnetic resonance
system such as Cytomegalovirus (CMV) and imaging (MRI). At times, the risks of obtaining a
toxoplasmosis and congenital malformations. neuroimaging study in an affected neonate may
potentially outweigh the benefits of further defining
Keywords the etiology, which is predominately related to
Cerebral palsy · Magnetic resonance imaging · transportation of the neonate out of the intensive
Hypoxic-ischemic brain injury · Congenital care unit and possible need for sedation.
infections of CNS Cranial ultrasound (US) is the preferred initial
investigation, particularly in high-risk and unstable
premature infants due to its portability, widespread
Introduction availability, low cost, speed, and lack of ionizing
radiation. Cranial US is most useful for detection
Cerebral palsy (CP) is a clinical diagnosis and and follow-up of hydrocephalus, intracranial hem-
is defined as “a group of disorders of development orrhage, and periventricular leukomalacia (PVL).
of movement and posture, causing activity limita- The major limitations met with cranial US include
tion, that are attributed to non-progressive distur- operator dependence, image quality reliant on
bances that occurred in developing fetal or infant acoustic window, and suboptimal evaluation of
brain” (Bax et al. 2005). According to the systematic the posterior fossa and myelination. Also, diffuse
review and meta-analysis of 49 population-based white matter injury, as can be seen in preterm
studies on the prevalence of CP conducted by infants, is not well evaluated by cranial US.
Oskoui et al. 2013, the pooled overall prevalence Computed tomography (CT), based on the
of CP was 2.11 per 1000 live births (95% confidence principle of X-ray attenuation, produces high-
13 Neuroimaging Pathology in Cerebral Palsy 179
resolution images of the brain and provides exqui- imaging (DWI) exploits the random Brownian
site osseous details. It is the least sensitive modal- motion of protons within the voxel of tissue
ity for evaluation of neonatal hypoxic-ischemic and is useful in evaluation of acute infarction,
encephalopathy (HIE), because high water con- hypoxic-ischemic insult, grading of gliomas,
tent of the neonatal brain results in poor paren- differentiation of epidermoid from arachnoid
chymal contrast resolution. However, CT offers cyst, encephalitides, demyelinating diseases, and
a comparatively rapid investigative tool in emer- leukoencephalopathies such as adrenoleukodys-
gent situations and has a role in evaluation trophy. Susceptibility-weighted imaging (SWI)
of intracranial hemorrhage, hydrocephalus, and is exquisitely sensitive for blood products and
parenchymal calcifications. calcium and is of paramount importance in eval-
The superior soft tissue resolution and multi- uation of hemorrhagic transformation of infarc-
planar capabilities of magnetic resonance imaging tion, HIE, and perinatal infections. Proton
(MRI) make it uniquely qualified for the assess- magnetic resonance spectroscopy (HMRS) is
ment of the brain. MRI utilizes a strong static a noninvasive diagnostic method of analyzing
magnetic field and radiofrequency waves to gen- tissue metabolism, yields chemical data reflec-
erate images and has no known potential harmful ting tissue composition, and plays a vital role
effects in biologic tissues within clinically pre- as an adjunct to conventional imaging in diagno-
scribed parameters. Compared to CT, MRI does sis of mitochondrial and metabolic disorders,
not use ionizing radiation. MRI, however, poses leukoencephalopathies, and grading of gliomas.
several limitations such as longer scan times and
need for sedation and is precluded in patients with
certain implanted ferrous instrumentation, cardiac Fetal Neuroimaging Techniques
pacemakers, and neurostimulators. The various
imaging sequences acquired for evaluation of the Evaluation of the fetal brain is performed as part
brain include sagittal 3D T1 weighted, sagittal 3D of routine second trimester fetal ultrasound,
T2 weighted, axial and coronal fluid-attenuated providing information about fetal growth param-
inversion recovery (FLAIR), diffusion weighted eters, brain morphology, and ventricular size.
(DWI), and susceptibility weighted (SWI). Addi- When a brain abnormality is suspected with ultra-
tional imaging sequences such as MR spectros- sound, fetal MRI is often performed to confirm the
copy (MRS), MR perfusion, and MR angiography suspected abnormality, detect additional abnor-
(MRA) can be acquired as per the clinical malities, or elucidate inconclusive sonographic
concern. Sagittal T1-weighted images are vital findings. A recent meta-analysis of 27 studies
for assessment of midline structures including including 1184 fetuses showed that in 23% of
the corpus callosum, pituitary gland, hypothala- cases, fetal MRI demonstrated additional or dif-
mus, and cerebellar vermis and hemispheric ferent pathology than detected with ultrasound
convexities such as perisylvian regions. Also, (van Doorn et al. 2016). In an additional 8% of
myelination is best evaluated by T1-weighted sonographically suspected brain abnormalities,
images from birth to 6 months of age. Axial MRI was normal. On follow-up, fetal MRI had
or sagittal T2-weighted images are important 80% complete agreement with the postnatal
for evaluation of parenchymal pathologies includ- assessment, while neurosonography agreed in
ing structural abnormalities, hypoxic-ischemic 54% of cases. In another meta-analysis, fetal
insult, leukoencephalopathies, and neoplasms. brain MRI changed the clinical management of
From 6 to 8 months of age until approximately the pregnancy in 30% of cases (Rossi and
24 months, myelination is better assessed with Prefumo 2014). Although providing detailed
T2-weighted images. FLAIR-weighted sequence anatomic information, fetal MRI is considered
suppresses free fluid within the ventricular a problem-solving tool supplementary to ultra-
and subarachnoid space, increasing conspicuity sound due to higher cost, longer scan time, and
of parenchymal pathologies. Diffusion-weighted lower accessibility.
Fetal MRI is typically performed in the second Table 1 Etiology of cerebral palsy
and third trimesters at 1.5 T, although recently Hypoxic-ischemic insult
reports of highly detailed brain MRI at 3 T are White matter injury of immaturity
also emerging (Victoria et al. 2014). There Basal ganglia/thalamic damage
are theoretical risks to the fetus from radio- Focal infarct
frequency energy deposition, magnetic field expo- Cortical/subcortical damage
sure, and acoustic noise. Nonetheless, fetal MRI Infections
is a highly useful tool with no adverse outcomes CMV
reported (Bouyssi-Kobar et al. 2015; Strizek et al. Toxoplasmosis
2015). Fetuses as young as 18 weeks’ gestation can LCMV
be evaluated with MRI, although greater informa- Rubella (German measles)
Varicella (chicken pox)
tion can be obtained later in gestation as the
Herpes
sulcation pattern of the brain matures. The most
Syphilis
commonly employed fetal MRI techniques are
Zika
routine motion-insensitive sequences available
Congenital malformations
from all manufacturers, performed at 3–5 mm Bilirubin encephalopathy
slice thickness. Gyral anatomy, cortical develop- CNS injury in multiple pregnancies
ment, and white matter signal intensity are best Birth trauma
assessed with T2-weighted single-shot fast spin Neonatal hypoglycemia
echo and steady-state free precession sequences, Genetic abnormalities
while the presence of hemorrhage, calcification, Coagulopathies causing stroke
or fat is evaluated with gradient echo T1-weighted
and T2-weighted echoplanar sequences (Lyons
et al. 2015; Manganaro et al. 2017). Advanced Table 2 The harmonized classification of magnetic reso-
nance imaging based on pathogenic pattern
imaging techniques including diffusion-weighted
imaging and diffusion tensor imaging can also be A. Maldevelopments
employed for evaluation of ischemia and fiber A1. Disorder of cortical formation (proliferation
and/or migration and/or organization)
tracking, respectively.
A2. Miscellaneous (e.g., holoprosencephaly, Dandy-
Table 1 enumerates the most common known Walker malformation, agenesis of corpus callosum,
etiologies associated with cerebral palsy. cerebellar hypoplasia)
The harmonized classification of magnetic B. Predominant white matter injury
resonance imaging based on pathogenic patterns B1. PVL: mild, severe
(MRI classification system) was proposed by B2. Sequelae of IVH or periventricular hemorrhagic
the Surveillance of Cerebral Palsy in Europe infarction
(SCPE) network and is described in Table 2 B3. Combination of PVL and IVH sequelae
C. Predominant gray matter injury
(Himmelmann 2016).
C1. Basal ganglia/thalamus (mild/moderate/severe)
C2. Cortico-subcortical lesions only (watershed
lesions in parasagittal distribution/multicystic
Hypoxic-Ischemic Brain Injury encephalomalacia)
C3. Arterial infarctions
The incidence of hypoxic-ischemic encephalopa- D. Miscellaneous: Hypomyelination, cerebellar atrophy,
thy (HIE) is 2–9 per 1000 live births and is cerebral atrophy
one of the most common identified causes of E. Normal
cerebral palsy (Chao et al. 2006). The underlying
pathophysiology of HIE is complex and not and decreased systemic blood pressure
completely understood. Perinatal asphyxia is the (Barkovich 2012). There is resultant loss of nor-
most important cause of HIE (Chao et al. 2006) mal vascular autoregulation of the term neonate,
and results in hypoxemia, hypercarbia, acidosis, described as “passive pressure flow” (Barkovich
2012; Del Toro et al. 1991; Boylan et al. 2000). metabolic activity. The visual cortex becomes
Furthermore, preterm infants and infants with increasing more metabolically active by
neurologic impairment and seizures demonstrate 44 weeks post-conceptional age. After third/
an absent autoregulatory response (Boylan et al. fourth postnatal months, the remainder of the
2000). Thus, the decreased systemic blood pres- cerebral cortex and basal ganglia become
sure and “passive pressure flow” contribute to increasingly metabolically active and most vul-
the majority of hypoxic-ischemic brain injury. nerable to hypoxic-ischemic insult (Barkovich
Intrauterine asphyxia occurs when placental 1992, 2012).
blood flow and gas exchange is interrupted
and can be caused by fetal factors (fetomaternal
hemorrhage, fetal thrombosis, and fetal bradycar- Preterm
dia), inadequate placental perfusion (maternal
hypotension, preeclampsia, chronic vascular White Matter Injury of Prematurity or
disease, abruptio placenta), impaired maternal Periventricular Leukomalacia (Mild
oxygenation (asthma, pulmonary embolism, to Moderate Hypoperfusion)
pneumonia, carbon monoxide poisoning, severe The most common pattern of injury of the pre-
anemia), or disrupted umbilical circulation (tight mature brain is periventricular leukomalacia.
nuchal cord, cord prolapse). Postnatal asphyxia Screening cranial US may demonstrate hyper-
results from underlying severe hyaline membrane echoic periventricular flare adjacent to trigones
disease, pneumonia, meconium aspiration, or and frontal horns in focal and more generalized
congenital heart anomalies that cause neonatal increased echogenicity in diffuse white matter
pulmonary failure or hypotension (Chao et al. injury. Neonatal cranial US has significant lim-
2006). itations in demonstrating non-cystic white mat-
The various patterns of brain injury are ter injury with low sensitivity (26%) and low
a result of three primary factors: maturity of the positive predictive value (36%). However, US
brain, severity of hypotension, and duration demonstrates high reliability in the detection of
of the hypoperfusion event (Chao et al. 2006; cystic white matter injury (Inder et al. 2003).
Barkovich 1992, 2012; Okereafor et al. 2008). Three different types of white matter injury have
A premature infant with mild to moderate hypo- been described and can be categorized with mag-
perfusion will sustain insult to the peri- netic resonance imaging (MRI). These include dif-
ventricular and deep white matter (“white fuse white matter injury, with mildest clinical
matter injury of prematurity” or “periventricular manifestations; focal/multifocal non-cavitary
leukomalacia”), which are the regions at highest white matter injury, with intermediate severity;
risk due to their state of immaturity and vascular and focal/multifocal cavitary white matter injury,
supply, with sparing of subcortical white matter with severe clinical manifestations (Volpe 2008a).
and cerebral cortex (Barkovich 2012). With mat- Early MRI findings include small T1
uration of the brain and its vascular system, the hyperintense foci in periventricular white matter
pattern of injury begins to change between 34th and diffuse T2 hyperintense white matter signal
and 38th post-conceptional weeks. In term abnormality. Diffusion-weighted imaging may
infants, a similar degree of mild to moderate demonstrate foci of restricted diffusion in peri-
hypoperfusion leads to injury of watershed por- ventricular white matter and may be negative before
tions of the cerebral cortex and underlying sub- 24 h or after 5 days. Subacute findings include
cortical and periventricular white matter cavitary changes in periventricular white matter,
(Li et al. 2009). The thalami and brainstem are and chronic findings include loss of periventricular
most metabolically active in early third trimes- white matter volume, angular ventricular morphol-
ter. From mid-third trimester to 40 weeks of ogy with “squared off” trigones, cortical ribbon
gestation, the brainstem, thalami, basal ganglia, extending to the ventricular margins, and focal thin-
and peri-Rolandic regions have the highest ning of body of corpus callosum (Figs. 1 and 2).
Fig. 1 14-month-old female, born at 32 weeks of gesta- periventricular and subcortical white matter. Of note,
tion, with spastic diplegic cerebral palsy. Axial FLAIR- there is enlargement of both lateral ventricles with cortical
weighted images through the centrum semiovale (a) and sulci reaching up to the ventricular margins with resultant
basal ganglia (b) demonstrate abnormal hyperintense sig- undulating ventricular contour (white arrow), related to
nal within the periventricular and subcortical white matter white matter volume loss. Midline sagittal T1-weighted
(black stars and white arrows, respectively), with associ- image (d) demonstrates thinning of the corpus callosum
ated enlargement of the lateral ventricles secondary (white arrowhead), secondary to transcallosal axonal
to white matter volume loss. Coronal T2-weighted degeneration. Findings are characteristic of periventricular
image (c) at the level of the atria of lateral ventricles leukomalacia
further depicts abnormal hyperintense signal within the
Profound Hypotension in Preterm Infants findings in preterm infants with profound hypo-
In preterm infants, the thalami, brainstem, and tension include hyperechogenic parenchyma
cerebellum are most susceptible to severe on US and restricted diffusion, T1 hyper-
hypotension. There may be coexisting white intense, and variable T2 signal abnormality on
matter injury and germinal matrix hemorrhage MRI, in the aforementioned distribution
(Barkovich and Sargent 1995). The imaging (Fig. 3).
Fig. 2 16-year-old female, born at 31 weeks of gestation, loss. The white matter volume loss is best appreciated on
with spastic quadriplegic cerebral palsy. Axial FLAIR- axial (b) and coronal (c) T2-weighted images as evidenced
weighted image (a) through the superior aspects of lateral by enlargement of lateral ventricles, cortical sulci reaching
ventricles demonstrates confluent abnormal hyperintense up to the ventricular margins, and undulating ventricular
signal involving bilateral periventricular white matter contour (white arrows). Findings are characteristic of peri-
(white arrows) with associated severe white matter volume ventricular leukomalacia
Germinal Matrix and Intraventricular 32 weeks of gestational age and below 1500 gm
Hemorrhage weight and is unusual after 34 weeks of gestation
The incidence of germinal matrix and intraven- (Volpe 2008b; Greisen 1992). Hemodynamic insta-
tricular hemorrhage (GMH/IVH) among preterm bility associated with birth is presumably related
neonates is 45%, and it is inversely related to to these germinal matrix hemorrhages, as 40%
gestational age and weight at birth (Kadri et al. have their onset within 5 h of birth and 90% within
2006). GMH is most common in infants less than the first 4 days (Volpe 2008b). The most frequent
Fig. 3 1-day-old baby, born at 35 weeks of gestation putamina (black open arrow), amygdalae (black arrow-
with unresponsiveness and in utero trauma. Sagittal head), and midbrain (black arrow). Axial diffusion-
T1-weighted image (a) shows hyperintensity in the dor- weighted image (d) shows reduced diffusivity in the
sal brainstem (white arrow). Axial T1-weighted images bilateral ventrolateral thalami (white arrows). Features
(b and c) show hyperintensity in the bilateral thalami are in keeping with profound hypotensive injury
(black stars), Globi pallidi (white arrow), lateral
area of GMH is near the posterior aspect of cau- approximately 19% in premature neonates
date head, the ganglionic eminence portion of (Steggerda et al. 2009). Risk factors for cere-
germinal matrix. Within the cerebellum, the bellar hemorrhage include birth weight less
external granular layer represents the germinal than 750 gm, emergent Cesarean section, patent
zone (Barkovich 2012; Rakic and Sidman ductus arteriosus, and low 5 days’ minimum
1970), and hemorrhages within this area are pH. GMH has been divided into four grades –
not uncommon with prevalence of grade I, GMH at the caudothalamic groove;
Fig. 4 2 1/2-year-old male with spastic quadriplegic bilateral cerebellar hemispheres and vermis (black
cerebral palsy, born preterm at 25 weeks of gestation arrows) and corpus callosum (white arrowhead).
with obstetric history significant for premature rupture Susceptibility-weighted images (d and e) demonstrate
of membranes. Axial T2-weighted image (a) through the old blood products within the lateral ventricles, left
lateral ventricles demonstrates severe white matter vol- caudothalamic groove, and residual cerebellum (white
ume loss involving the bilateral cerebral hemispheres, arrows). These findings are compatible with sequela of
more pronounced on the right, with undulation of ven- prior grade IV intraventricular hemorrhage and cerebellar
tricular margins (white arrow). Axial (b) and sagittal (c) germinal matrix hemorrhage
T2-weighted images depict severe atrophy of the
grade II, GMH with IVH; grade III, GMH with represents the underlying etiology for congenital
IVH and ventriculomegaly; and grade IV: hem- porencephalic cysts. The acquired variety may
orrhagic periventricular venous infarction result following trauma, surgery, vascular insult,
(Fig. 4). or infection. Familial porencephaly is a rare auto-
somal dominant condition characterized by
Porencephalic Cyst mutation of the gene encoding procollagen type
Porencephaly is defined as a congenital or IV A1 (chromosome 13q, COL4A1), essential for
acquired CSF-filled parenchymal cavity that basement membrane stability (Breedveld et al.
usually communicates with the ventricular 2006), with resultant increase in risk of intracere-
system and/or subarachnoid space and is lined bral hemorrhage. Inherited thrombophilia, most
by reactive gliosis/astrocytic proliferation. In often secondary to heterozygosity for factor V
utero encephaloclastic process caused by cerebral Leiden mutation (gene F5), also predisposes to
vascular insult or infectious injury (CMV) porencephalic cysts (Fig. 5).
Fig. 5 10-year-old female, born preterm at 24 weeks (white arrows) (distinct from gray matter-lined open-lip
of gestation with obstetric history significant for placen- schizencephaly). Postcontrast sagittal T1-weighted
tal abruption. Axial (a) and coronal (b) T2-weighted and image (d) demonstrates gracile corpus callosum. Find-
axial FLAIR-weighted (c) images demonstrate a large ings are most consistent with a porencephalic cyst, typ-
fluid-filled cyst in the left cerebral hemisphere, in the ically due to encephaloclastic insult (e.g., intrauterine
frontoparietal region corresponding to the left middle infections or ischemia)
cerebral artery territory. This cyst is lined by white matter
Term Infants ischemic insult in term infants with prolonged

partial hypoxia, and injury manifests as
Watershed Predominant Pattern restricted diffusion in watershed territories,
of Injury involving both the cortex and subcortical white
The watershed zones between anterior and mid- matter. Children with the watershed predominant
dle cerebral arteries and middle and posterior pattern of injury may develop symptomatic
cerebral arteries are most predisposed to parieto-occipital epilepsy in late childhood, low
Fig. 6 9-year-old male with diplegic cerebral palsy. hyperintense signal is visualized in the periventricular
History of hypoxic-ischemic insult at 3 years of age sec- white matter of both occipital lobes, extending to the left
ondary to atypical refractory Kawasaki’s disease. Axial T2 occipital pole (white arrow). Additionally, there is signal
(a and b) and axial FLAIR (c and d) images through the abnormality involving the cerebellar cortex (arrowhead).
lateral ventricles and posterior fossa demonstrate general- Findings are most consistent with sequela of profound
ized cerebral and cerebellar atrophy. Abnormal T2/FLAIR hypoxic-ischemic insult
IQ, and visuospatial cognitive dysfunction prolapsed cord (Okereafor et al. 2008; Oguni
(Oguni et al. 2008) (Figs. 6 and 7). et al. 2008). Children with the basal ganglia/
thalamic pattern of injury tend to be severely
Basal Ganglia/Thalamus Pattern disabled due to dyskinetic cerebral palsy
This pattern is also referred to as a pattern fol- (de Vries and Groenendaal 2010). In extremely
lowing acute near total asphyxia and is most severe profound hypoxic-ischemic injury, all of
often seen ensuing an acute sentinel event such the supratentorial structures may be affected
as uterine rupture, placental abruption, or a (Fig. 8).
Fig. 7 10-year-old male with incontinentia pigmenti and the right cerebral white matter (white arrow), thalamus and
spastic hemiplegic cerebral palsy. Coronal T2 (a) and T1 posterior limb of internal capsule (axial FLAIR-weighted
(b) weighted images demonstrate right-sided cerebral vol- images, c and d). There are additional areas of abnormal
ume loss as demonstrated by prominence of cerebral con- hyperintense signal in the left frontal and parietal white
vexity sulci and lateral ventricle (black star). Also, there is matter (white arrowhead). These findings are most com-
diffuse abnormal T2/FLAIR hyperintense signal involving patible with sequela of remote hypoxic-ischemic insult
Perinatal Stroke et al. 2015). In the newborn, unlike the older

Ischemic perinatal stroke is defined as “a group child or adult, there are no clinical signs that
of heterogeneous conditions in which there is permit even a presumptive diagnosis of perinatal
a focal disruption of cerebral blood flow second- stroke; diagnosis rests on neuroimaging (Nelson
ary to arterial or cerebral venous thrombosis, or 2007). Neonates and young infants usually pre-
embolization between 20 weeks of fetal life sent with encephalopathy and/or seizures. Perina-
through 28th postnatal day, confirmed by neuro- tal stroke is the commonest cause of hemiplegic
imaging or neuropathologic studies” (Machado cerebral palsy (Basu 2014) and has a prevalence
Fig. 8 7-year-old female, born at 32 weeks of gestation hyperintense signal in the bilateral posterior putamina
with mixed spastic and dystonia cerebral palsy, secondary and thalami (white arrows), with associated volume loss
to perinatal hypoxic-ischemic insult related to fetal in keeping with sequela of profound hypoxic-ischemic
hydrops. Obstetric history was significant for preeclamp- insult. Of note is subtle hyperintense signal in the peri-
sia. Axial T2-weighted (a), axial FLAIR-weighted (b), and ventricular white matter with mild white matter
coronal T2-weighted (c) images demonstrate abnormal volume loss
of 1 in 2300 to 5000 live births (Barkovich 2012),

often leading to long-term neurological disability, Congenital Infections of the Central
including congenital hemiplegia, seizure, and Nervous System
cognitive disorders, and has an extremely variable
presentation depending upon the age, cause, and Transplacental infection of the fetus during
involved vascular territory (Lanni et al. 2011) development can lead to a wide spectrum of
(Figs. 9 and 10). insults to the brain. The most important set of
Fig. 9 11-month-old female, born by Cesarean section at image (c) shows corresponding T1 hypointense signal
38 weeks of gestation for failure of progression of labor (white arrow). Additional signal abnormality is visualized
and preeclampsia, with left-sided hemiplegic cerebral in the right posterior putamen and lateral thalamus (d,
palsy. Axial FLAIR-weighted images (a and b) demon- coronal T2-weighted image, white arrow). Findings are
strate abnormal hyperintense signal compatible with compatible with remote infarction in right middle cerebral
gliosis with a small area of encephalomalacia (white artery territory. Of note is mild ex vacuo enlargement of
arrows) within the right corona radiata extending along right lateral ventricle
the posterior limb of internal capsule. Axial T1-weighted
these infections are represented by the TORCH parvovirus B19, and recently Zika virus (Ribeiro
acronym, denoting Toxoplasma gondii, rubella, et al. 2017). Although the different infectious
Cytomegalovirus, herpesviruses, and syphilis agents can produce specific clinical and imaging
(Hedlund et al. 2012). This list has been features, the most important factor in the type
expanded to also include lymphocytic and degree of brain injury is the fetal gestational
choriomeningitis virus, varicella zoster, age at the time of infection. Infections during the
first and second trimester typically cause devel- postnatal MRI and postnatal CT offer greater
opmental brain abnormalities due to disruption detail of brain involvement.
of neuronal migration, while infections in the
third trimester may cause focal destructive
lesions or only minor problems such as hearing Cytomegalovirus
impairment. Fetal ultrasound is the first line of
imaging in congenital CNS infections and may Cytomegalovirus (CMV) is an endemic herpesvi-
provide the first evidence of infection. Fetal and rus spread by close human-to-human contact with
Fig. 10 (continued)
Fig. 10 5-year-old male with spastic quadriplegic cere- demonstrating restricted diffusion have evolved into exten-
bral palsy, hemophagocytic lymphohistiocytosis, and juve- sive areas of cystic encephalomalacia in the bilateral cere-
nile xanthogranuloma. Postnatal history was significant for bral hemispheres (g and h, axial FLAIR-weighted images,
respiratory distress, anemia, thrombocytopenia, and direct i, parasagittal T2-weighted image). There are multiple foci
hyperbilirubinemia. Serial imaging demonstrates evolu- of hyperintense signal on T1-weighted (j) and hypointense
tion of hypoxic-ischemic insult. Initial imaging at 6 days signal on susceptibility-weighted (k) imaging, compatible
of age: Axial diffusion-weighted (a, b) and apparent diffu- with remote blood products. The regions of
sion coefficient (c, d) images through the centrum semi- encephalomalacia appear T1 hypointense. Imaging at
ovale and basal ganglia depict extensive restricted 18 months of age: Further evolution of regions of cystic
diffusion in the bilateral cerebral hemispheres, basal encephalomalacia, including progressive confluence of
ganglia, and thalami. Axial T2-weighted image (e) dem- encephalomalacia in the right frontal lobe, with volume
onstrates corresponding abnormal hyperintense signal in loss of the bilateral cerebral hemispheres (l, axial FLAIR-
the regions of restricted diffusion. There is gyriform T1 weighted and m, axial T2-weighted images). Again, visu-
hyperintense signal in the bilateral frontoparietal lobes alized are multiple foci of hypointense signal on
(f, axial T1-weighted image, white arrows). Findings are susceptibility-weighted imaging (n) in the bilateral
most consistent with severe prolonged hypoxic-ischemic parieto-occipital regions in keeping with remote blood
insult. Follow-up imaging at 5 weeks of age: The regions products
bodily fluids and can be identified in 0.6 to 0.7% who acquire a primary infection during preg-
of all live births (Colugnati et al. 2007). CMV is nancy. There is a wide range of outcomes with
spread to the fetus transplacentally and poses congenital CMV infection, with most children
the greatest risk to a developing fetus in the first asymptomatic at birth. However, congenital
or second trimester, especially in mothers CMV infection can cause sensorineural hearing
loss, visual impairment, developmental delay, 1985; Jeong et al. 2015). Chorioretinitis is the
cognitive impairment, seizures, and cerebral most consistent feature of symptomatic congenital
palsy (Malm and Engman 2007). toxoplasmosis and can manifest at birth or years
Neuroimaging, both pre- and postnatally, later (Safadi et al. 2003).
provides important diagnostic and prog- The hallmark calcifications of toxoplasmosis
nostic information in congenital CMV infection. are depicted well with pre- and postnatal ultra-
Ventriculomegaly, microcephaly, or peri- sound as well as CT and susceptibility-weighted
ventricular calcifications detected on prenatal MRI, usually involving the basal ganglia,
ultrasound may be the first indication of infection. periventricular and subcortical white matter,
Fetal MRI provides greater detail of brain and cortex, occasionally taking on a tram track
involvement, allowing increased sensitivity and appearance (Surendrababu et al. 2006).
positive predictive value of long-term compli- These calcifications can decrease or resolve
cations (Doneda et al. 2010). Anterior temporal with treatment, corresponding to clinical
polar cysts, intraventricular septa, cerebellar improvement (Patel et al. 1996). Prenatal ultra-
hypoplasia or dysplasia, cortical migration sound may show macrocephaly due to hydroceph-
anomalies, and white matter abnormalities are alus, although microcephaly is also seen. The
features well depicted with fetal MRI (Averill combined sonographic features of hydrocephalus
et al. 2015). In fact, the characteristic but non- and parenchymal calcifications are a poor prog-
specific anterior temporal lesions and intraventric- nostic sign (Malinger et al. 2011). Extensive brain
ular septations are often more pronounced in the parenchymal destruction with porencephaly or
fetus compared to older children. These features hydranencephaly can be seen in severe cases
should be specifically evaluated with MRI in of congenital toxoplasmosis, but abnormalities
a child with unexplained developmental delay of cortical migration are atypical, in contrast
and hearing loss. Likewise, these areas should to congenital CMV (Hedlund et al. 2012)
be given special scrutiny in an MRI scan of (Fig. 12).
a child showing polymicrogyria, as the diagnosis
of congenital CMV infection may curtail unnec-
essary lengthy and expensive genetic testing. Lymphocytic Choriomeningitis Virus
Ultrasound and CT more easily depict the classic
periventricular calcifications seen in approxi- Lymphocytic choriomeningitis virus (LCMV) is an
mately half of the cases (Fink et al. 2010) arenavirus endemic in wild mice and can also be
(Fig. 11). harbored in pet mice, guinea pigs, and hamsters
(Bonthius 2012). The virus can be passed to
humans coming in contact with rodent secretions,
Toxoplasmosis urine, feces, and their bedding causing a flu-like
illness and transmitted through the placenta to the
Toxoplasmosis, caused by the parasite developing fetus. The gestational age at infection
Toxoplasma gondii, is the second most common dictates the severity of brain abnormalities, with
congenital infection after CMV (Hedlund et al. earlier infection causing more profound injury
2012). T. gondii infects birds and mammals, (Bonthius et al. 2007a). Long-term morbidity
with domestic cats implicated as the major source including cerebral palsy, cognitive impairment, sei-
of human infection. Although most infections are zures, and visual impairment is common, although
asymptomatic, transplacental infection, especially the true spectrum of disease is not known (Bonthius
before 20 weeks’ gestation, can cause severe et al. 2007b). Congenital LCMV infection is
neurological complications including microceph- thought to be uncommon but also under recognized
aly, hydrocephalus, quadriplegia or diplegia, cog- (Delaine et al. 2017; Schulte et al. 2006). It should
nitive impairment, and seizures (Diebler et al. be suspected in infants with chorioretinitis in
Fig. 11 Fetus at 37 weeks’ gestation with congenital of age demonstrates polymicrogyria in the bilateral frontal
cytomegalovirus (CMV) infection. Fetal brain MRI was (black arrows) and perisylvian regions more easily seen
performed for possible arachnoid cyst seen on prenatal than on the fetal MRI. Also note white matter hyper-
ultrasound. Parasagittal T2 MR image (a) shows cystic intensity involving the bilateral frontal lobes (dashed
dilation of the occipital and temporal horns (white arrows) black arrows). An axial T2-weighted image (d) through
of the lateral ventricles with a thin septation (curved white the posterior fossa additionally shows mild cerebellar dys-
arrow). Axial T2-weighted image (b) shows bilateral ante- plasia (open arrows), well depicted postnatally but only
rior temporal lobe cysts with T2 hyperintensity in the subtly visible prenatally (b). The constellation of above
surrounding white matter (dashed white arrow), near features is highly suggestive of early in utero timing of
completely resolved by 7 months of age (image d). Post- CMV infection
natal axial T2-weighted image (c) performed at 7 months
association with hydrocephalus or microcephaly, LCMV has strong tropism for neuroblasts, lead-
who test negative for the more commonly ing to periventricular calcifications, periventricular
encountered CMV and toxoplasmosis infections cysts, and neuronal migration abnormalities similar
(Hedlund et al. 2012, Anderson et al. 2014). to congenital CMV infection (Wright 1997;
Fig. 12 Premature infant born at 33 weeks gestation with Subcortical cysts are noted on ultrasound, a few of them
increasing head circumference, hyperbilirubinemia, and hyperechoic (curved white arrows), and MR shows hypo-
metabolic acidosis. Coronal (a) and sagittal (b) ultrasound, intensity within the cysts (black arrow) likely representing
sagittal fast imaging employing steady-state acquisition calcification/hemorrhage. Diffuse hyperintense T2 signal
(FIESTA) MRI (c and d) performed in the newborn period, within the cerebral white matter, likely representing cere-
and axial T2-weighted MRI (e) performed at 6 months of bral edema and delayed myelination (dashed arrow).
age. Imaging shows moderate hydrocephalus including Abnormally shaped globes bilaterally with retinal detach-
lateral ventricles and the third ventricle (*), but no signif- ment, secondary to chorioretinitis (open arrow). Signifi-
icant enlargement of the fourth ventricle. FIESTA images cant progression of white matter volume loss and atrophy
demonstrate obstruction at the level of the aqueduct of is seen on MRI performed at 6 months of age (e). Serology
Sylvius (white arrow) likely secondary to ependymitis. testing was positive for toxoplasma
Bonthius 2012; Anderson et al. 2014). Cerebellar

hypoplasia and porencephalic cysts can also be seen Congenital Malformations
(Bonthius et al. 2007b). Communicating hydro-
cephalus, similar to toxoplasmosis, is seen in more The prevalence of congenital anomalies in chil-
than 50% of affected neonates (Hedlund et al. 2012; dren with CP is higher than in the general
Bonthius et al. 2007b). Those without hydrocepha- population, with majority being malforma-
lus often have microcephaly due to poor brain tions of cerebrum such as microcephaly, hydro-
development (Delaine et al. 2017). Different from cephaly, and schizencephaly (Garne et al. 2008;
other TORCH infections, though, LCMV typically MacLennan et al. 2015). Also, there is increased
has few systemic effects in the rest of the body prevalence of noncerebral malformations such as
(Fig. 13). cardiac, musculoskeletal, and renal (MacLennan
Fig. 13 4-day-old infant with microcephaly and sensori- regions (curved arrows) with underlying polymicrogyria.
neural hearing loss. Coronal ultrasound (a), axial CT (b), There is also diffuse white matter volume loss (black
axial (c), and coronal (d) T2-weighted MR images dem- arrows). Imaging studies of neonates and infants with
onstrate moderate hydrocephalus (*) secondary to lymphocytic choriomeningitis virus (LCMV) are nearly
aqueductal obstruction likely from necrotizing identical to those of congenital CMV and toxoplasmosis.
ependymitis. Periventricular calcifications are shown on Diagnosis of LCMV was made by serologic studies in this
CT and ultrasound (straight arrows). MRI demonstrates child
abnormal sulcation of the posterior frontal and perisylvian
et al. 2015). According to the data from 11 CP Lissencephaly (The Agyria-Pachygyria

registries contributing to the European Cerebral Complex)
Palsy Database, 11.9% of children with CP were
reported to have a congenital malformation, Lissencephaly encompasses malformations
with majority (8.6%) were diagnosed with a cere- caused by arrested neuronal migration, resulting
bral malformation (Garne et al. 2008). in thick four-layer cortex and smooth brain
surface. Both agyria and pachygyria are likely Inheritance is typically autosomal recessive.
caused by abnormal regulation of microtubule Various gene mutations are implicated in
activities. A variety of gene alterations are impli- the MSG pattern including MCPH1 (8p23,
cated in the pathogenesis such as the LIS1 microcephalin), ASPM (1q31, spindle-like
(17p13.3) responsible for regulating microtubule microcephaly protein), ARFGEF (20q13.13),
motor protein cytoplasmic dynein (Toba et al. CDK5RAP2 (9q34, CDK5 regulatory subunit-
2012); DCX (Xq22.3–q23) encoding for associated protein 2), CENPJ (13q12.2,
doublecortin, a neuronal microtubule-associated centromeric protein J), SLC25A19 (17q25.3,
protein involved in cell division and/or cell migra- mitochondrial deoxy-nucleotide carrier), EIF2AK3
tion (Bahi-Buisson et al. 2013); RELN (7q22) (2p12, eIF2 alpha kinase 3), and PKNP
encoding for reelin, an extracellular matrix protein (19q13.33, polynucleotide kinase 30 phosphatase)
that regulates neuronal migration and synaptic and affect pathways involving neurogenesis
plasticity; ARX (Xp21.1, homeobox-containing (Barkovich 2012). Nijmegen breakage syndrome
gene); and TUBA1A (12q12–q14.3) encoding is an autosomal recessive disorder related to DNA
for microtubule constituent protein (Okumura repair disorders and is characterized by MSG,
et al. 2013). Microcephaly is seen in lissencephaly intrauterine growth retardation, short stature,
associated with ARX, RELN, and TUBA1A recurrent sinopulmonary infections, an increased
mutations. risk of cancer, and premature ovarian failure
Miller-Dieker syndrome results from large (Varon et al. 1999; Lammens et al. 2003).
LIS1 deletions and includes, in addition to classic MSG has been classified into six genetic
lissencephaly, craniofacial, cardiac, and renal classes and accordingly can be associated
anomalies and omphalocele (Chih-Ping Chen with various anomalies such as agenesis/dys-
and Shu-Chin Chien 2010). genesis of the corpus callosum, periventricular
Characteristic imaging findings of nodular heterotopia, cortical dysgenesis, and
lissencephaly include absence or diminished cerebellar hypoplasia (Barkovich 2012)
number of cortical sulci throughout the cerebral (Figs. 15 and 16).
hemisphere with thick cortex, hourglass or figure
of 8 shape of cerebral hemispheres, and truncated
arborization of white matter. T2-weighted imag- Schizencephaly
ing in neonates may demonstrate three discrete
layers of the cortex, including relatively thin Schizencephaly is a rare congenital malformation
and smooth, outer cellular layer, deeper with a population prevalence of 1.54/100,000 and
thick layer of arrested neurons mimicking band is characterized by gray matter-lined clefts of the
heterotopia, and intervening cell-sparse layer cerebral mantle extending from the cortical sur-
(Barkovich et al. 1991) (Fig. 14). face to the lateral ventricles – pia to ependyma
(Curry et al. 2005). Associated CNS abnormali-
ties include septo-optic dysplasia, absent septum
Microcephaly with Simplified Gyral pellucidum, frontal lobe dysplasia, hippocampal
Pattern (MSG) and callosal anomalies, contralateral poly-
microgyria, and periventricular heterotopias.
Microcephaly with simplified gyral pattern There is an associated non-CNS abnormality in
(MSG) describes malformations associated with one third of cases, over half of which could be
microcephaly (head circumference of 3 or more classified as secondary to vascular disruption,
standard deviations below the mean) and too few including gastroschisis, bowel atresia, and amni-
and abnormally shallow sulci (<1/2 the depth of otic band disruption sequence (Curry et al. 2005).
normal sulci) (Barkovich 2012; Dobyns and Mutations of COL4A1 and COL4A2 have been
Barkovich 1999). found to be associated with schizencephaly with
Fig. 14 4-month-old male with developmental delay, thick with a thicker inner layer (open white arrow), a cell-
hypotonia, and absent visual following. Sagittal sparse zone (black dashed arrow), and a very thin outer
T1-weighted image (a) shows abnormally broad midline cortical layer (dashed white arrow). The Sylvian fissures
gyri with few midline sulci (white arrow). The midbrain, are vertically oriented and shallow (black open arrow).
pons, and medulla appear mildly hypoplastic (curved white Additionally, on the coronal T2-weighted image (c), there
arrow); however the corpus callosum, cerebellum, and is diffuse prominence of the extra-axial CSF spaces. The
vermis are normal. Axial T2-weighted image (b) demon- lateral ventricles are mildly prominent (*). Features are
strates pachygyria (black arrow) in the frontal and anterior highly consistent with classic lissencephaly. Gene defect
temporal regions bilaterally, while there is complete agyria was identified at 17p13.3 (gene encoding PAFAH1B1) in
involving the parietal, occipital, and posterior temporal this child
regions. In the posterior aspect of the brain, the cortex is
the underlying mechanism being disturbed vascu- prognosis (Barkovich and Kjos 1992; Barkovich
lar supply (Yoneda et al. 2013). 1992). Imaging studies of schizencephaly show a
Schizencephaly is classified as closed lip trans-mantle CSF-lined cleft lined by gray matter
(15–20%) or open lip and can be unilateral with a bumpy outer surface and an irregular gray-
(60%) or bilateral. The size and location of white matter junction. Pathologically, the gray
clefts are very important in determination matter lining the schizencephalic cleft is dysmor-
of patients’ prognosis, with patients having bilat- phic with absence of normal cortical lamination.
eral schizencephaly and large or medium Closed-lip schizencephaly may be confused for
unilateral schizencephaly bearing very poor trans-mantle heterotopia if the walls of the cleft
Fig. 15 1-year-old male with microcephaly and quadri- diminished supratentorial gyral formation with shallow
plegic cerebral palsy. Sagittal T1-weighted image (a) dem- sulci. The cortical thickness, however, is normal for the
onstrates marked microcephaly as evidenced by decrease patient’s age. No gray matter heterotopia was identified.
in craniofacial ratio. Axial (b) and coronal (c) T2-weighted Findings are consistent with microcephaly with simplified
and axial T1-weighted (d) images show diffusely gyral pattern (MSG) type 1
are closely apposed, and a dimple in the wall of malformations such as bilateral perisylvian
the adjacent lateral ventricle may suggest the diag- polymicrogyria and variable degree of ventricu-
nosis (Fig. 17). lomegaly (Mirzaa et al. 2004; Colombani et al.
2006). MPPH syndrome is inherited as autoso-
mal dominant. The molecular diagnosis of
Megalencephaly-Postaxial Polydactyly- MPPH syndrome is established in a proband
Polymicrogyria-Hydrocephalus with suggestive clinical and imaging features
Syndrome (MPPH) and the identification of a heterozygous patho-
genic variant in one of three genes: AKT3,
MPPH syndrome is a developmental brain dis- CCND2, or PIK3R2 (Colombani et al. 2006).
order, first described in 2004 and is character- Neurologic manifestations reported include
ized by megalencephaly with cortical congenital or early postnatal megalencephaly
Fig. 16 2-year-old male with spastic quadriplegic cere- supratentorial gyral formation with shallow sulci. Of
bral palsy. Sagittal T1-weighted image (a) demonstrates note, there is normal cortical thickness for the patient’s
marked microcephaly as evidenced by decrease in cranio- age. Also, there are multiple foci of subependymal gray
facial ratio. The rostrum and splenium of the corpus matter nodular heterotopia. These findings are consistent
callosum appear hypoplastic. Axial (b) and coronal (c) with microcephaly with simplified gyral pattern (MSG)
T2-weighted images show diffusely diminished type 3
(occipital frontal circumference at birth ranges Septo-Optic Dysplasia

from normal to 6 SD above the mean), oromotor
dysfunction, epilepsy, hypotonia, and intellectual Septo-optic dysplasia (SOD) or de Morsier’s
disability (Mirzaa 2016). Imaging findings syndrome is defined as an association of
of MPPH include cortical malformations, partic- optic nerve hypoplasia and midline brain
ularly bilateral perisylvian polymicrogyria, pro- malformations with/without hypopituitarism
gressive ventriculomegaly leading to (Cemeroglu et al. 2015). The majority of cases are
hydrocephalus, cerebellar tonsillar ectopia or sporadic. However, in a number of familial cases,
Chiari malformations, and thick corpus callosum identification of mutations in the key developmen-
(Mirzaa 2016) (Fig. 18). tal gene, HEX1 suggests that a genetic causation is
Fig. 17 Fetus at 37 weeks gestation with suspicious of the lateral ventricles to the cortex. The clefts are lined by
arachnoid cyst on prenatal ultrasound. Axial image of dysplastic gray matter (dashed white arrow). Note absence
fetal ultrasound (a) shows abnormal shape of the lateral of the septum pellucidum. Features are in keeping with
ventricles with suspicious cystic structure (*). Note lack of bilateral frontal lobe open-lip schizencephaly. On the cor-
definition of surrounding cerebral cortex. Axial onal T2-weighted image of the fetal brain (c), within the
T2-weighted image (b) of the fetal brain demonstrates left parietal lobe, there is thinning of the cortex (black
bilateral clefts (curved white arrows) involving the poste- arrow) and beaking from the lateral ventricle with dysplas-
rior frontal lobes. The clefts are extending through the tic gray matter (open white arrow) representing additional
entire hemisphere from the ependymal lining of the body closed-lip schizencephaly
Fig. 18 3-year-old female with postaxial polydactyly cerebral hemispheres (dashed white arrows) and enlarged
affecting upper and lower extremities and macrocephaly. subarachnoid spaces (black arrows). Note, cerebellum is
She also has spasticity, seizure disorder, and severe devel- morphologically completely normal. Sagittal T2-weighted
opmental delay. Axial T2-weighted image (a) shows dif- image (c) performed after shunt placement demonstrates
fuse polymicrogyria (white arrows) as well as vertical relatively normal size of the ventricular system, and the
orientation of the Sylvian fissures bilaterally (curved corpus callosum (open arrow) appears normal. Features are
black arrows). Coronal T2-weighted image (b) shows in keeping with megalencephaly-polymicrogyria-polydac-
enlargement of the lateral ventricles and third ventricle tyly-hydrocephalus (MPPH) syndrome
(*). There is diffuse white matter volume loss in the
also likely in the more common sporadic cases plus” is a term coined for cases with additional brain
(Kelberman and Dattani 2007). Additionally, dupli- malformations and may simply reflect the associa-
cation of SOX3 and mutations of both SOX2 and tion of optic nerve hypoplasia, endocrine dysfunc-
SOX3 have been implicated in the etiology of var- tion, and developmental delay with complex brain
iants of SOD (Kelberman and Dattani 2007). “SOD malformations (Miller et al. 2000) (Fig. 19).
Fig. 19 4-month-old female with diabetes insipidus and T2-weighted image (b) at a lower level demonstrates bilat-
in utero diagnosis of bilateral schizencephaly. Axial eral temporal lobe polymicrogyria (dashed white arrows).
T2-weighted MR image (a) shows bilateral clefts (curved Sagittal midline T1-weighted image (c) demonstrating the
black arrows) involving bilateral posterior frontal lobes. ectopic neurohypophysis in the hypothalamic region. The
The clefts extend through the entire hemisphere from the pituitary stalk is also hypoplastic. There is also diffuse
ependymal lining of the body of the lateral ventricles to the thinning of the corpus callosum (white arrow). Coronal
cortex and are lined by dysplastic gray matter (white thin section orbital T2 image (d) demonstrates hypoplasia
arrows). Note the absence of the septum pellucidum. Fea- of bilateral optic nerves (white arrowheads) and the chiasm
tures are in keeping with bilateral frontal lobe open-lip (not shown). The constellation of above findings is in
schizencephaly, larger on the left than the right. Axial keeping with “septo-optic dysplasia plus” syndrome
18q-Syndrome delay, ocular movement disorders, seizures,

craniofacial dysmorphism (midface hypoplasia,
The 18q- syndrome, first reported by De Grouchy frontal bossing, carp like mouth), limb anomalies,
et al. in 1964, is caused by partial deletion of genital hypoplasia, and decreased growth
the distal long arm of chromosome 18 (18q) and (Loevner et al. 1996).
consists of a wide range of phenotypic variation Children with 18q- can be missing up to 30 Mb
including mental retardation and developmental of DNA, a region encompassing approximately
100 known genes, including a 2-Mb region of ventricular cavity. In majority of patients (86%),
18q23. This region contains seven known genes, the Sylvian fissures are abnormally connected
one of which encodes for myelin basic protein across the midline over the vertex (Simon et al.
(MBP) (Lancaster et al. 2005). 2002). Gray matter heterotopia and cortical dys-
The dysmyelination characteristics of the 18q- plasia are also seen including abnormal thicken-
group include delayed onset, a slower rate of pro- ing of cortex lining the anterior interhemispheric
gression, and a lower level of myelin at equilibrium fissure (Simon et al. 2002). Reduced sulcation
(Lancaster et al. 2005). The most common pattern (absent internal frontal sulci) is seen in approxi-
on MRI studies is diffuse, bilaterally symmetric mately 71% of patients (Simon et al. 2002).
deep white matter T2 hyperintensity, most pro- Incomplete separation of thalami can be seen in
nounced in posterior periventricular regions 1/3 of patients, whereas caudate nuclei are incom-
(Loevner et al. 1996; Miller et al. 1990). Involve- pletely separated in approximately 11% patients.
ment of subcortical white matter, depicted by poor - There is dysgenesis of the corpus callosum and an
gray-white matter differentiation or abnormal azygous anterior cerebral artery. Other associated
T2-hyperintense signal, is also visualized (Loevner anomalies include cephalocele (10%, overlying
et al. 1996). In addition to diffuse disease, super- the bridge of unseparated parenchyma) and pos-
imposed focal deep white matter lesions can be seen terior fossa abnormalities (19%) including Chiari
in approximately 1/4 of cases (Loevner et al. 1996). I and II malformations, cerebellar hypoplasia, and
Hypoplasia of the anterior pituitary has also been hypogenesis of the inferior vermis (Fig. 21).
reported with 18q- syndrome (Bekiesinska-
Figatowska and Walecki 2001) (Fig. 20).
Joubert Syndrome and Related
Disorders (Molar Tooth Malformations)
Syntelencephaly
Joubert syndrome (JS) is an autosomal recessive
The middle interhemispheric variant of disorder presenting with hypotonia, ataxia, devel-
holoprosencephaly, also referred to as syn- opmental delay, mental retardation, irregular
telencephaly, consists of an abnormal midline con- breathing in the neonatal period, and ocular
nection between the cerebral hemispheres motor apraxia (Poretti et al. 2007; Boltshauser
in posterior frontal and parietal regions with normal and Isler 1977; Joubert et al. 1969). Associated
interhemispheric fissure separating the basal fore- abnormalities include juvenile nephronophthisis,
brain, anterior frontal lobes, and occipital regions multicystic dysplastic kidneys, ocular anomalies
(Takanashi et al. 2003; Simon et al. 2002) and is a (retinal dysplasia and coloboma), hepatic fibrosis,
result of failure/reduction of induction and patterning heart disease, and polydactyly (Poretti et al. 2007;
of the rostral neural tube (Takanashi et al. 2003). Satran et al. 1999; Saraiva and Baraitser 1992).
Mutation of ZIC2 (13q32), a dorsalizing gene impor- JS-related disorders have been recently divided
tant in neural tube closure and differentiation of the into four separate disorders: JS, COACH (cere-
roof plate, has been described with the middle bellar vermis hypoplasia, oligophrenia, ataxia,
interhemispheric variant of holoprosencephaly; ocular coloboma, hepatic fibrosis) syndrome,
a mutation of this gene can also cause classic CORS (cerebro-oculo-renal syndrome), and
holoprosencephaly (Brown et al. 2001). Interest- oculo-facial-digital syndrome type VI (OFD-VI
ingly, due to ZIC2 control of neural tube closure, syndrome).
mutation may also result in cephalocele, JS is predominantly inherited in an autosomal
myelomeningocele, or Chiari II malformation and recessive manner. To date, pathogenic variants
can be seen associated with syntelencephaly in 34 genes are known to cause JS; 33 of
(Simon et al. 2002). these are autosomal and 1 is X-linked, and molec-
Imaging studies depict midline continuity ular diagnosis can be established in 62–94%
of the posterior frontal/parietal cortex with normal of individuals with JS (Parisi and Glass 2003).
separation of the frontal pole and a single Nine genetic loci associated with JS-related
Fig. 20 5-year-old male with cerebral palsy, conductive myelination in a 1.5-year-old child. Diffusion-weighted
hearing loss, bilateral nystagmus, and decreased vision. image (d) shows higher diffusivity (curved arrow) than
Axial T1-weighted image (a) appears normal, but the age-matched controls. Genetic testing revealed chromo-
axial T2-weighted (b) and axial FLAIR (c) images show some anomaly 18q-. Chromosomal deletions at 18q- can
indistinct separation of gray matter and white matter (white affect the gene for myelin basic protein; hence children
arrows) due to hypomyelination of the white matter. This with this chromosomal abnormality will often have
appearance on FLAIR would be more typical of normal delayed or diminished myelination
disorders have been identified at chromosomes TMEM67), 16q12 (JBTS7, RPGRIP1L), 3q11.2
9q34.3 (JBTS1, INPP5E), 11p11.2–q12.3 (JBTS8, ARL13B), and 4p15.3 (JBTS9, CC2D2A)
(JBTS2, TMEM216), 6q23 (JBTS3, AHI1, (234,916–918,920,921) (Barkovich 2012). Most
encoding Jouberin), 2q13 (JBTS4, NPHP1), of these genes encode ciliary proteins, which
12q21 (JBTS5, CEP290), 8q22 (JBTS6, are important in a wide range of functions,
Fig. 21 3-year-old female with chief complaints of devel- image (c) demonstrates clear cleavage of the hypothala-
opmental delay. Upper extremities were hypotonic, and mus, thalami, lentiform nuclei, and caudate nuclei (dashed
lower extremities were hypertonic. Coronal T2-weighted arrows). The lateral ventricles have a rudimentary shape,
MR images (a and b) show failure of cleavage of the and the septum pellucidum is absent (black arrow). Sagittal
posterior frontal and anterior parietal regions of the brain T1-weighted image (d) shows the corpus callosum is sep-
across the midline. There is a thin sling of normal- arated into two distinct anterior (genu) and posterior
appearing cortex bridging the midline just below the (splenium) portions with hypoplastic body (partial inter-
callosomarginal sulcus (white arrows). There is an azygous mediate agenesis) (white arrow heads). Constellation of
anterior cerebral artery (curved arrow). Axial T2-weighted above features is in keeping with syntelencephaly
including ciliogenesis, body axis formation, renal superior cerebellar peduncles, and abnormally
function, brain development, and ocular develop- deep interpeduncular fossa (Poretti et al. 2007;
ment (Barkovich 2012; Louie and Gleeson 2005). Maria et al. 1997). The cerebellar vermis is dysplas-
The key imaging findings in JS include tic and small with midline clefting. Also, the roof of
cerebellar vermis hypoplasia in combination with the fourth ventricle is dysplastic with lost fastigial
the “molar tooth sign,” a complex midbrain malfor- point. On diffusion tensor imaging and
mation characterized by thickened and elongated tractography, there is absence of decussation of the
Fig. 22 2-year-old male with hypotonic cerebral palsy. and triangular fourth ventricle. Also, the quadrigeminal
There is deepening of the interpeduncular fossa with thick, plate and prepontine cisterns are enlarged. The cerebellar
straight, and long superior cerebellar peduncles (a, axial hemispheres appose in the midline without fusion (d, cor-
T2-weighted image) classically described as the “molar onal T2-weighted image). No supratentorial anomaly was
tooth sign.” Sagittal T2- (b) and T1- (c) weighted images identified in this patient. This constellation of findings is
demonstrate vermian dysgenesis with resultant capacious characteristic of Joubert syndrome
superior cerebellar peduncle and more lateral local- hemispheres (Patel and Barkovich 2002),
ization of deep cerebellar nuclei. Additionally, there with midline continuity of the cerebellar hemi-
is absence of decussation of corticospinal tracts spheres, deep cerebellar nuclei, and superior
(Poretti et al. 2007) (Fig. 22). cerebellar peduncles. Gómez-López-Hernández
syndrome (GLHS) is a rare neurocutaneous syn-
drome characterized by the triad of rhombence-
Rhombencephalosynapsis phalosynapsis, trigeminal anesthesia, and bilateral
parieto-occipital alopecia (Kobayashi et al. 2015).
Rhombencephalosynapsis is an uncommon Associated abnormalities include VACTREL-H
cerebellar malformation, defined by vermian association (vertebral, anal, cardiac, tracheoe-
agenesis/hypoplasia and fusion of the cerebellar sophageal, renal, and limb anomalies, with
Fig. 23 10-year-old female with macrocephaly, growth septum pellucidum (black arrow). Coronal T1-weighted
retardation, and developmental delay. Sagittal image (c) shows associated mildly hypoplastic optic chi-
T2-weighted MR image (a) shows partial agenesis of the asm (open arrow). Axial diffusion tractography imaging
corpus callosum (white arrow) in a child with complete (DTI) in a different patient demonstrates transverse fibers
rhombencephalosynapsis. Primary fissure (dashed white across the cerebellar hemispheres (white arrowhead). Fea-
arrow) and prepyramidal fissure (curved white arrow) are tures are in keeping with complete rhombencephalo-
absent. Axial T2-weighted image (b) shows absence of the synapsis with associated septo-optic dysplasia
hydrocephalus) (Pasquier et al. 2009), autosomal 57 affected patients analyzed by array compara-
dominant polycystic kidney disease type I (Elliott tive genomic hybridization, microrearrangements
and Harter 2008), and septo-optic dysplasia. were detected in 7% of the rhombencephalo-
The embryologic and genetic mechanisms synapsis cases. The microarray analysis did not
involved are still unknown, and to date, no animal identify recurrent rearrangements or deletions
models are available. In a large series of of regions encompassing genes known to be
Fig. 24 7-year-old female with infantile quadriplegic (white arrowhead). Also note enlargement of both the
cerebral palsy. Postnatal history was significant for lateral ventricles, left greater than right. Axial (d) and
infantile spasms and neonatal seizures. Sagittal sagittal (e) T2-weighted images through the orbits dem-
T2-weighted image through the midline (a) demonstrates onstrate bilateral optic nerve sheath coloboma. This con-
absent corpus callosum (white arrow). Axial (b) and stellation of findings is characteristic of Aicardi
coronal (c) T2-weighted images depict extensive syndrome, with the typical clinical presentation of infan-
migrational anomalies including gray matter hetero- tile spasms
topias (white arrow) and pachygyria/polymicrogyria
Fig. 25 13-month-old female with spastic quadriplegic projection images (d and e) demonstrate diminutive
cerebral palsy. Sagittal T1-weighted (a) and axial bilateral internal cerebral arteries with small caliber M1
T2-weighted (b) images demonstrate absence of the segments. Bilateral anterior cerebral arteries and remain-
majority of the cerebrum with fluid-filled cranial vault. der of the distal middle cerebral arteries are not visual-
On a more inferior T2-weighted image (c), there is resid- ized. The posterior circulation, however, is preserved.
ual neuroparenchyma of bilateral occipital and anterior These findings characterize hydranencephaly. Probable
inferior temporal lobes, and posterior fossa structures etiologies include in utero vascular occlusion, infection,
including the brainstem and cerebellum are preserved. or trauma after the first trimester
Time-of-flight MR angiography maximum intensity
involved in embryogenesis of the cerebellum inferred from the amiculum and are medially
(Démurger et al. 2013). located in rhombencephalosynapsis (Widjaja
Imaging findings include abnormal cerebellar et al. 2006) (Fig. 23).
morphology with a single-lobed cerebellum,
horizontally oriented folia crossing midline,
and absent vermis. Multiple other intracranial Aicardi Syndrome
findings are described such as hydrocephalus
(50%), dysgenesis/agenesis of the corpus Aicardi syndrome is characterized by triad
callosum (71%), absent septum pellucidum of callosal agenesis, infantile spasms, and
(62%), pontine hypoplasia (24%), cortical dyspla- chorioretinal lacunae (Aicardi 2005) and
sia (17%), and holoprosencephaly (7%) (Pasquier results from an X-linked genetic defect that
et al. 2009). Color fractional anisotropy maps may is fatal in males and hence manifests only in
demonstrate vertically oriented fibers in the mid- females, although a few cases have been
portion of the cerebellum (Widjaja et al. 2006). reported in 47 XXY males (Shetty et al.
The location of deep cerebellar nuclei can be 2014).
Fig. 26 22-month-old female with hyperbilirubinemia FLAIR (c) images show abnormal hyperintensity and atro-
during the newborn period caused by maternal-infant phy of the globi pallidi (white dashed arrows), hippocampi
blood group incompatibility. The patient presented with (curved white arrows), and right subthalamic nucleus
seizures, developmental delay, loss of milestones, hyper- (open white arrows). Also, there is diffuse cerebral white
tonicity, and agitation. Axial FLAIR image (a) demon- matter volume loss with prominent sulci. Features are
strates hyperintensity and atrophy of the bilateral globi consistent with the chronic phase of kernicterus injury
pallidi (white arrow). Coronal T2-weighted (b) and
Neuroimaging manifestations of Aicardi colpocephaly (78%), ventriculomegaly (78%), cere-

syndrome include dysgenesis of the corpus bral asymmetry (100%), cysts (midline, 81%; intra-
callosum (complete, 70%; partial, 30%), hetero- ventricular, 29%), cerebellar anomalies (95%), and
topias (periventricular, 100%; subcortical, 30%), miscellaneous (opercular abnormalities, increased
frontal/frontoparietal polymicrogyria (100%), tectal size) (Hopkins et al. 2008) (Fig. 24).
Hydranencephaly resulting in kernicterus (Parashari et al. 2009).

Clinically, chronic kernicterus is characterized
The characteristic features of hydranencephaly by well-described clinical tetrad of abnormal
include absence of the cerebral hemispheres with motor control, movement and muscle tone, an
intact thalamus, brainstem, cerebellum, and skull/ auditory processing disturbance with or without
meninges. The space for the cerebral hemispheres hearing loss, oculomotor impairments particu-
is filled with CSF, creating the so-called water bag larly impairment of upward vertical gaze, and dys-
brain (Cecchetto et al. 2013). The plasia of enamel of deciduous teeth (Shapiro 2010)
etiopathogenesis of hydranencephaly is still (Fig. 26).
unknown; however the most widely accepted
hypothesis suggests brain insult secondary to
early occlusion of the internal carotid artery Conclusion
(ICA) as demonstrated by anatomic distribution
respecting the ICA territory and angiographic Neuroimaging substantiates our understanding
findings of aplastic or hypoplastic ICAs (Pavone of neuroanatomical basis of functional impair-
et al. 2014). Also, postulated molecular dysfunc- ment. Imaging plays an important role in manag-
tions include COL4A1 (Meuwissen et al. 2011) ing cerebral palsy; in elucidating etiology,
and PI3K-Akt3-mTOR (Poduri et al. 2012) muta- for prognostication; and in planning therapeutic
tions. The prognosis of hydranencephaly is usu- interventions.
ally quite poor. Affected patients mostly die in
utero, and live-born survivors usually succumb
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▶ Genetic Abnormalities and Congenital
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Current Imaging: PET Scan Use in
Cerebral Palsy 14
Sreenath Thati Ganganna and Harry T. Chugani
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 218
Cranial Ultrasonogram . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 218
Magnetic Resonance Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 219
Positron Emission Tomography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 221
Diffusion Tensor Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 223
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 224
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 224
Abstract commonly have the spastic diplegic type of

Cerebral palsy (CP) is a heterogeneous group CP. When one hemisphere is affected, spastic
of disorders of movement and posture due to a hemiplegic CP may occur. There have been
defect, injury, or lesion of the immature brain radical changes in our understanding of the
during the antenatal, natal, or early postnatal etiology of CP over the past several decades
period. The major types of cerebral palsy due to rapid advances in neurogenetics and the
include spastic, extrapyramidal, and mixed advent of neuroimaging tools including cranial
cerebral palsy. Prematurely born babies most ultrasound, computed tomography (CT), mag-
netic resonance imaging (MRI), positron emis-
sion tomography (PET), and newer advanced
imaging modalities such as diffusion tensor
S. T. Ganganna (*) imaging (DTI). The use of MRI has revolution-
Nemours/Alfred I. duPont Hospital for Children, Nemours ized the capacity of clinicians to obtain detailed
Neuroscience Center, Wilmington, DE, USA
e-mail: Sreenath.ThatiGanganna@nemours.org
images of the brain neonatally (even prena-
tally) and in the investigation of CP. Used in
H. T. Chugani
NYU Comprehensive Epilepsy Center, Department of
Neurology, NYU School of Medicine, New York, NY,
USA
e-mail: hchugani@pet.wayne.edu;
Harry.Chugani@nyulangone.org

https://doi.org/10.1007/978-3-319-74558-9_11
218 S. T. Ganganna and H. T. Chugani
combination with history and clinical exami- Cranial Ultrasonogram

nation, the neuroimaging studies play a pivotal
role in elucidating the etiology and pathogen- Ultrasound is a highly useful and readily available
esis of CP. imaging technique that uses high-frequency
sound waves to produce images with good clarity.
Keywords The anterior fontanelle is the most commonly
Cerebral palsy · Neuroimaging · MRI · PET · used acoustic window. More recently, the poste-
Diffusion tensor tractography rior fontanelle and the mastoid window have been
used to achieve better visualization of the occipital
part of the ventricles, the occipital white matter,
Introduction and posterior fossa (Correa et al. 2004;
Limperopolous et al. 2005). Cranial ultrasound
Cerebral palsy is an umbrella term encompassing can be serially performed with minimal perturba-
a group of nonprogressive, but often changing tion of the neonate, making it the study of choice
motor impairment syndromes secondary to in high-risk preterm infants (Ment et al. 2002).
lesions or anomalies of the brain arising in the Major intracranial lesions, such as large intraven-
early stages of development (Mutch et al. 1992). tricular hemorrhage (IVH grade III) and paren-
The prevalence of CP has changed very little over chymal hemorrhage (grade IV) or cystic
the past several decades, in spite of many techno- periventricular leukomalacia, can be detected
logical advances that have decreased mortality in with cranial ultrasound using a high-resolution
compromised preterm and full-term infants. The transducer with a wide range of insonation
prevalence rate has been estimated to be approx- (de Vries et al. 2011) (Fig. 1).
imately 2 per 1000 live births (Himmelmann et al. All major intracranial lesions mentioned above
2005). Cerebral palsy often brings with it many are predictive of CP and to a lesser degree cogni-
associated problems with learning, language, and tive impairment, depending upon the size and site
epilepsy, as well as hearing and vision impairment of the lesion. Per the results of the EPIPAGE
(Bax et al. 2005). cohort study (Ancel et al. 2006), on the basis of
Traditionally, CP is classified based on the ultrasound findings in the neonatal period, about
pattern of motor impairment: spastic CP (diplegia, 17% of infants with isolated grade III IVH and
quadriplegia, monoplegia, triplegia), extrapyra- 25% of infants with white matter damage (i.e.,
midal CP (dyskinetic, choreoathetoid, ataxic), ventricular dilation, persistent echodensities, or
and mixed CP (Cans 2000). In general, children cystic periventricular leukomalacia) had CP, com-
with spastic CP often show white matter injury, pared to 4% of infants with normal ultrasound
whereas extrapyramidal syndromes frequently scans. Kuban et al. (2009) reported the utility of
have basal ganglia abnormalities on imaging. cranial ultrasound in detecting brain lesions in
Neuroimaging studies can play a very important 40–50% of the infants who subsequently were
role in the diagnosis of CP, distinguishing the diagnosed with CP. A more recent study by de
pathological lesions of various types of CP. Vries et al. (2011) reported detection of major
When combined with history and neurological cranial ultrasound abnormalities in the majority
examination, the neuroimaging studies can pro- of preterm infants (83%) who developed CP;
vide insights into the etiology and pathogenesis, these investigators used high-resolution, sequen-
expand treatment options, and provide prognostic tial cranial ultrasound during the first 4–6 postna-
information. Currently, there is a wide array of tal weeks and again between 36 and 40 weeks
imaging techniques to evaluate brain structure postmenstrual age. According to the recommen-
and function: cranial ultrasound, computed dations for neuroimaging given by the Quality
tomography (CT), magnetic resonance imaging Standards Subcommittee of the American Acad-
(MRI), diffusion tensor imaging (DTI), and posi- emy of Neurology and the Practice Committee of
tron emission tomography (PET). the Child Neurology Society (Ment et al. 2002),
14 Current Imaging: PET Scan Use in Cerebral Palsy 219
Fig. 1 Head ultrasound of

an infant showing left
hemispheric porencephalic
cyst
all infants with a gestational age of 30 weeks or useful for determination of normal anatomy as
less should have cranial ultrasound examination at well as structural abnormalities. T2 weighting
7–14 days of age, and this optimally should be refers to transverse relaxation time. Cerebrospinal
repeated at 36–40 weeks postmenstrual age. How- fluid is bright on T2-weighted images and mature
ever, cranial ultrasonography has shortcomings in white matter is dark. Fluid attenuation inversion
terms of negative predictive value as demon- recovery (FLAIR) images are useful in visualiz-
strated in a study of 1749 very low birth weight ing brain lesions located in the parenchyma close
survivors with a normal head ultrasound. Nearly to the ventricles and CSF pia which frequently are
30% of these infants had either CP or a Bayley obscured by the bright CSF signal in T2-weighted
Mental Developmental Index score less than 70 at images.
18–22 months corrected age (Laptook et al. 2005) Magnetic resonance imaging has several
advantages over computed tomography (CT)
including higher tissue contrast resolution, lack
Magnetic Resonance Imaging of radiation exposure, and absence of bone arti-
fact. However, MRI is more expensive than CT
Magnetic resonance imaging (MRI) is an exten- and often requires to be performed under sedation
sively used imaging modality in the realm of in young children because of the high sensitivity
pediatric neurology. The detailed physics of to patient movement (Accardo et al. 2004).
MRI is beyond the scope of this section. How- Brain MRI is increasingly used in the evalua-
ever, briefly, MRI uses the intrinsic magnetic tion of CP. Seventy to 90% of children with CP
properties of protons to produce gray-scale have abnormalities on brain MRI (Candy et al.
images in multiple planes (Wehrli et al. 1984). 1993). In the European Cerebral Palsy Study
In this technique, the protons in the biological (Bax et al. 2006), the most common MRI brain
tissue are placed in a static magnetic field and abnormality in patients with CP was peri-
then subjected to a pulse of magnetic energy. ventricular leukomalacia (42.5%), followed by
Three properties of tissues determine the intensity basal ganglia lesions (12.8%), cortical/subcorti-
of MRI signals – proton density, T1 relaxation cal lesions (9.4%), malformations (9.1%), focal
time, and T2 relaxation time. T1 weighting refers infarcts (7.4%), and miscellaneous lesions (7.1%)
to longitudinal relaxation time. On T1-weighted (Figs. 2, 3, 4, and 5). Normal MRI findings were
images, mature white matter, which has a short present in only 11.7%.
T1, appears bright, gray matter appears gray, and Not only do brain MRI scans help reveal the
cerebrospinal fluid appears dark. T1 images are pathological basis of CP, but also, the MRI
findings have strong correlation with the clinical

findings. The clinical and brain MRI correlates in
CP were extensively studied in the European
Cerebral Palsy Study (Bax et al. 2006).
White matter damage of prematurity including
periventricular leukomalacia was found in 71.3%
of the children with diplegia, 34.1% of those
with hemiplegia, and 35.1% of those with quadri-
plegia. Among children with bilateral spastic
CP, those with posterior or middle white matter
injury in MRI scan were found to have spastic
diplegia. These children were often able to walk
and had some communication skills. However,
children with spastic quadriplegia had extensive
damage across all areas of the brain, and virtually
all these children were non-ambulatory and had
severe cognitive impairment. Basal ganglia and
thalamic damage was mainly associated with
dystonic CP and was occasionally seen in chil-
dren with spastic quadriplegia. There were no
children with hemiplegia that had basal ganglia
Fig. 2 Periventricular leukomalacia. Axial FLAIR image
shows volume loss and increased signal in periventricular or thalamic lesion. Focal cortical infarcts were
white matter almost exclusively related to the clinical
Fig. 3 MRI brain of a

patient with dystonic CP
showing basal ganglia
injury secondary to
neonatal
hyperbilirubinemia
malformations including lissencephaly, poly-

microgyria, schizencephaly, and cortical dyspla-
sia were mostly associated with the diagnosis of
hemiplegic CP but were found across all sub-
types of CP. Children with normal MRI results
were distributed across all clinical subtypes of
CP, although they constituted more than half the
group with ataxic CP.
Different patterns of brain abnormalities result
from different time periods of compromise or
injury during brain development. By identifying
the specific brain lesions, brain MRI scans help us
understand the timing of CP origin (Okumura
et al. 1997). Brain MRI can be used to understand
the relationship of prenatal, perinatal, and postna-
tal events to CP (Truwitz et al. 1992). Brain MRI
scans of patients born prematurely usually reveal
findings of periventricular white matter damage
Fig. 4 MRI of a child with spastic quadriplegic CP show- and multicystic encephalomalacia, indicative of
ing bilateral cystic encephalomalacia hypoxic-ischemic brain injury, the chronology of
which is usually difficult to determine. On the
other hand, the MRI of patients born at term
usually reveal one of three major patterns: gyral
anomalies (polymicrogyria) consistent with
mid-second trimester injury; isolated peri-
ventricular leukomalacia reflecting late second
trimester or early third trimester injury; and water-
shed cortical or deep gray nuclear damage consis-
tent with late third trimester, perinatal, or postnatal
injury.
MRI brain patterns can also help provide infor-
mation about the type of hypoxic-ischemic insult
sustained by the developing brain. Cerebral palsy
patients who had prolonged or repeated partial
asphyxia commonly have a “watershed distribution”
of damage along the borders of the major cerebral
arteries, while the patients that had acute profound
hypoxia tend to demonstrate prominent lesions in
the basal ganglia and thalami (Sie et al. 2000).
Fig. 5 MRI brain of a patient with hemiplegic CP show-

ing schizencephaly on the left side Positron Emission Tomography
diagnosis of hemiplegic CP. MRI findings of Positron emission tomography (PET) is a diag-
multicystic encephalomalacia was found in all nostic imaging tool that can detect and map abnor-
subtypes of CP patients except ataxic CP. Brain malities in various organs related to glucose
metabolism, blood flow and receptor binding, The clinical phenotype of CP that later
oxygen utilization, protein synthesis, neurotrans- emerges may be predicted in the newborn by
mitter synthesis, release, and transport (Kannan the patterns of hypometabolism noted on
and Chugani 2010). This is achieved using com- FDG-PET scans. Bilateral thalamic hypo-
pounds labeled with positron-emitting isotopes metabolism (especially lateral thalamic nuclei)
generated by a cyclotron; the radiotracers are predicts the spastic diplegic type of
injected intravenously, and their distribution and CP. Furthermore, focal areas of hypometabolism
fate are detected by a positron camera. in the cerebral cortex (connected to the sites of
Although MRI of the brain has been exten- white matter injury) may predict the type of
sively used to reveal macrostructural brain cognitive impairment in these children. New-
abnormalities in children with CP, such as peri- borns that show a predominantly unilateral pat-
ventricular leukomalacia, ventricular dilatation, tern of hypometabolism on FDG-PET are likely
porencephalic cysts, and cerebral atrophy, con- to develop infantile hemiplegic type of CP
ventional MRI is unable to detect micropathology (Kerrigan et al. 1991). Transient hyper-
or functional activity in children with CP. MRI metabolism followed by severe hypometabolism
detectable lesions are absent in about 17% of the in the thalami and basal ganglia appears to be
patients with CP (Juhasz et al. 2000). On the other related to the development of dystonic/
hand, PET imaging may be helpful in detecting choreoathetoid CP (Batista et al. 2007). With
metabolic abnormalities and changes in regional partial prolonged hypoxic-ischemic brain injury
blood flow and receptor expression at a much in the perinatal period, the clinical type of CP is
earlier stage, before the development of structural usually spastic quadriplegia, which on MRI is
or morphological abnormalities (Volpe et al. seen as multifocal cystic encephalomalacia and
1983, 1985) (Fig. 6). PET scans can also help on FDG-PET as multifocal hypometabolism. In
estimate the actual extent of injury because the the most severe cases with severe extensive
abnormalities in glucose metabolism, using brain injury, glucose metabolism remains only
2-deoxy-2(18F)fluoro-D-glucose (FDG), often in the basal ganglia, brain stem, and cerebellum
extend beyond the site of structural lesion seen (Kerrigan et al. 1991).
in the MRI scan (Kerrigan et al. 1991). In recent years, PET imaging is being recog-
nized as a potential tool to understand the
neuroinflammatory response in the pathogenesis
of periventricular leukomalacia. There have been
in vitro and in vivo studies that implicated a
neuroinflammatory response mediated by acti-
vated microglial cells in the development of peri-
ventricular leukomalacia and CP (Bell and
Hallenbeck 2002; Li et al. 2005; Block et al.
2007). The excitotoxic metabolites and pro-
inflammatory cytokines produced by the activated
microglial cells may cause cytotoxic injury to
oligodendrocytes. The presence of activated
microglia in neuronal tissue has been demon-
strated in animal studies by PET imaging using
carbon-11 labeled PK11195 isoquinoline ligand
(Banati 2002; Gerhard et al. 2003, 2006). There-
fore, PET imaging with [11C]PK 11195 can poten-
tially be an effective tool in the early detection of
Fig. 6 PET scan of a patient with athetoid CP showing PVL in the neonate even before structural changes
hypometabolism of basal ganglia occur (Kannan and Chugani 2010).
Diffusion Tensor Imaging brain in a group of children with chronic bilateral

spastic CP and periventricular leukomalacia. The
Diffusion tensor imaging (DTI) is a recently intro- study demonstrated highly significant modifica-
duced technique that allows the integrities of tions of DTI measurements in these patients at
white matter tracts to be estimated by virtue of several levels involving not only motor but also
its ability to visualize the diffusion characteristics nonmotor regions: cerebellar peduncles,
of water (Neil et al. 2002). The technique is based corticospinal tracts and posterior thalamic radia-
on nuclear magnetic resonance methodology tions, posterior corpus callosum, external capsule,
that is sensitive to Brownian motion of water anterior thalamic radiation, superior longitudinal
molecules. It is based on the measurement of the fasciculi, corona radiata, optic nerves, and optic
variability in the direction of water diffusion chiasm. Statistically significant correlations were
(anisotropy) as well as the rate of water diffusion. found between clinical motor impairment and
Diffusion tensor tractography (DTT) is a 3D visu- fractional anisotropy in corticospinal tracts and
alized version of DTI and thus provides concrete commissural and associative tracts of the supra-
descriptions of the architecture and integrity of the tentorial brain.
white matter tracts (Mori and Zhang 2006) The study by Thomas et al. (2005) highlighted
(Fig. 7). Although this was primarily a research the usefulness of quantitative diffusion tensor
modality, it is finding increasing clinical applica- imaging (DTI) and fiber tracking in delineating
bility (Feldman et al. 2010). Several studies have the primary and secondary degenerative changes
demonstrated that DTI provides a powerful means in cerebral white matter and deep gray matter in
of detecting white matter lesions and evaluating patients with spastic CP due to periventricular
the states of neural tracts in patients with CP. white matter injury. There was a significant reduc-
Arrigoni et al. (2016) studied the pattern of tion in DTI fiber count on the lesional side involv-
DTI white matter abnormalities of the whole ing the corticospinal tract, corticobulbar tract, and
Fig. 7 Diffusion tensor

tractography showing
corticospinal tract and white
matter fascicles
superior thalamic radiation in the patient group needed before DTI can be used routinely for clin-
compared with controls. The corticospinal tract ical purposes.
in the brain stem, the body of corpus callosum,
and the head of caudate and lentiform nuclei
showed features of secondary degeneration on Conclusion
the affected side. Also, evidence suggesting the
reorganization of sensorimotor tracts in the unaf- Cerebral palsy is primarily a clinical diagnosis
fected side of spastic hemiparetic patients was based on the presence of abnormalities of tone,
noted. posture, and movement secondary to a non-
Variability of white matter tract injuries was progressive lesion of the developing brain. The
evaluated using DTI by Nagae et al. (2007), in role of neuroimaging has taken on increasing
children with CP associated with PVL. The importance in the diagnosis and management of
study concluded that there was marked variabil- children with CP. Among all children diagnosed
ity in white matter injury pattern in patients with with CP, 70–90% will have abnormal MRI
PVL, with the most frequent injury to the findings. With the advent of newer neuroimaging
retrolenticular part of the internal capsule, pos- modalities including DTI and PET, detection of
terior thalamic radiation, superior corona complex structural as well as functional brain
radiata, and commissural fibers. The great vari- abnormalities has become possible. These neuro-
ability of white matter lesions in CP is thought to imaging studies not only improve our understand-
be one of the reasons why response to therapies ing of pathogenesis of CP but also help us
is so variable in these patients. The tract-specific determine the prognosis and can enable targeted
evaluation revealed a family of tracts that are management of these patients. Since these images
highly susceptible in PVL, important informa- are not static, these modalities can be used objec-
tion that can potentially be used to tailor treat- tively to monitor the effectiveness of various
ment options in the future. interventions.
DTI methods have been used to link features
of white matter maturation to cognitive function.
In a whole-brain analysis of the subjects using Cross-References
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Neuromuscular Junction Changes in
Spastic Cerebral Palsy 15
Karyn G. Robinson and Robert E. Akins
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 228
Structure and Action of the NMJ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 228
NMJ Formation during Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 230
Postsynaptic Maturation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 230
Presynaptic Maturation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 231
NMJ Microanatomic Organization in CP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 232
NMJ Ultrastructure in CP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 234
NMJ Gene Expression in CP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235
Medications That Target NMJs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 237
Abstract motor nerves and muscle fibers. The coordina-

Spastic cerebral palsy (CP) is associated with tion of NMJ structure and function and the
deficits in the central nervous system; however, colocalization of junctional components in
the major symptoms of CP involve movement, NMJs are highly controlled, and the develop-
movement control, and musculoskeletal ment of the NMJ requires signaling between
changes indicating that patients with CP motor neurons, skeletal muscle fibers, and peri-
have disruptions in the peripheral neuromotor synaptic Schwann cells.
system as well. The neuromuscular junction Patients with CP demonstrate sensitivity to
(NMJ) is the site of communication between depolarizing neuromuscular blocking agents
and resistance to nondepolarizing neuromus-
cular blocking agents which target the NMJ;
K. G. Robinson · R. E. Akins (*) therefore, knowledge of NMJ organization in
Nemours Biomedical Research, Nemours – Alfred CP is critical to assure safe management of
I. duPont Hospital for Children, Wilmington, DE, USA patients. Additionally, individuals with CP
e-mail: karyn.robinson@nemours.org;
demonstrate alterations in the localization of
robert.akins@nemours.org

https://doi.org/10.1007/978-3-319-74558-9_12
228 K. G. Robinson and R. E. Akins
NMJ proteins, increased primary postsynaptic Anesthesiologists recognize that the doses of
fold length, increased distance between synap- neuromuscular blocking agents needed in surgical
tic folds, reduction in mitochondrial load in the patients with CP are quite different from those
nerve terminal, and increased expression of the needed in non-CP populations. For example,
COL4A3, LAMB2, and KCNN3 genes. These patients with CP are resistant to vecuronium and
defects appear to be distinct from those due to rocuronium (Hepaguslar et al. 1999; Moorthy
immaturity, denervation, or other pathologic et al. 1991; Na et al. 2010; Suzuki et al. 2000).
conditions. Knowledge of the NMJ deficits Vecuronium and rocuronium are aminosteroids
and abnormal neuromotor function in CP is that act as nondepolarizing neuromuscular
critical to understand the pathways contribut- blocking agents by competitively inhibiting
ing to disordered movement in CP. nicotinic acetylcholine receptors (nAChR) in
NMJs. The result of this inhibition is skeletal
Keywords muscle relaxation and temporary paralysis,
Cerebral palsy · Neuromuscular junction · which are needed to allow surgery to proceed.
Skeletal muscle Resistance to neuromuscular blocking agents
like vecuronium and rocuronium is associated
with altered expression, density, or distribution
Introduction of nAChR at NMJs, and NMJs are exclusively in
the PNS.
Much of our understanding of spastic cerebral The resistance to neuromotor blockade in CP is
palsy (CP) stems from the concept that CP arises not expected, and understanding NMJs and their
from a static encephalopathy involving the motor components in CP may be an important factor in
cortex of the brain, and significant research has understanding a patient’s condition. Disruption of
focused on the genesis and nature of brain and the expression or localization of proteins in NMJs
central nervous system (CNS) deficits in has been associated with other neuromuscular
CP. There is also accumulating evidence that CP conditions. These conditions are hereditary or
is associated with effects in the peripheral nervous have acquired autoimmune origins and include
system (PNS) as well. In this chapter, we review myasthenia gravis, Lambert-Eaton myasthenic
evidence and concepts surrounding PNS involve- syndrome, neuromyotonia (Isaacs’ syndrome),
ment in CP with a specific focus on neuromotor and congenital myasthenic syndromes (Hirsch
innervation. 2007), as well as Escobar syndrome (Robinson
The idea that individuals with CP have et al. 2013b) and Duchenne muscular dystrophy
altered neuromotor innervation in their PNS (Theroux et al. 2008). Awareness of the pathways
originates from observations made during sur- leading to PNS disruption and disordered move-
gery. Almost all patients with CP require surgi- ment is likely to improve our understanding of
cal intervention; in fact, most require multiple neuromotor function in CP and may improve our
surgeries over their lifetimes. Anesthetics used ability to diagnose, track, and support individuals
at the time of surgery act to assure the patient is with CP and CP-like conditions.
relaxed, doesn’t feel pain, is unconscious, and
doesn’t move around. Some of the compounds
used for anesthesia can have broad effects in Structure and Action of the NMJ
these regards, but the neuromuscular blocking
agents used to inhibit movement work at highly The NMJ is a chemical synapse formed between
specialized sites in the PNS where individual an α-motoneuron and a skeletal muscle fiber
α-motor neurons interact with muscle fibers: (Nishimune and Shigemoto 2018; Wu et al.
neuromuscular junctions (NMJs). 2010). As illustrated in Fig. 1, NMJ structure
15 Neuromuscular Junction Changes in Spastic Cerebral Palsy 229
Fig. 1 Neuromuscular junction structure and function are the receptor which allows Na+ ions to enter and depolarize
tightly aligned. Depolarization of the motor nerve terminal the muscle cell membrane. The action potential is propa-
activates voltage-gated calcium channels, causing an influx gated across the surface of the muscle, activating a cascade
of calcium ions which trigger synaptic vesicles containing that results in muscle contraction. Acetylcholinesterase in
acetylcholine to fuse with the plasma membrane. Postsyn- the synaptic cleft quickly degrades available synaptic ACh
aptically, nAChRs at the crests of junctional folds in the to prevent prolonged contraction. Signals between moto-
sarcolemma bind ACh, causing a conformational change in neurons, skeletal muscle fibers, and perisynaptic Schwann
and function are tightly aligned. Functionally, and protein organization (Darabid et al. 2014;
depolarization of the motoneuron activates Jessen and Mirsky 2005; Sanes and Lichtman
voltage-gated calcium channels, causing an influx 1999). Thus, in many cases of CP, which
of calcium. Calcium ions bind to proteins on syn- often arise in utero between 24 weeks
aptic vesicles in the nerve terminal, triggering gestation and birth (Hadders-Algra 2014),
them to fuse with the plasma membrane at NMJs are specified prior to the onset of the
active zones, releasing the neurotransmitter ace- condition but are maturing as CP sets in.
tylcholine (ACh) into the synaptic cleft. On the
muscle fiber, nAChRs at the crests of junctional
folds in the sarcolemma bind ACh, causing Postsynaptic Maturation
depolarization of the muscle fiber and activating
a cascade that leads to calcium release within NMJs are indispensable for survival, and highly
the muscle and the actin-myosin interaction efficient and well organized NMJs are found
that results in muscle contraction (Rogers and across mammalian species. Not surprisingly,
Nishimune 2017). Acetylcholinesterase (AChE) then, the coordination of NMJ structure and func-
in the synaptic cleft degrades synaptic ACh tion and the colocalization of junctional compo-
very rapidly, thereby preventing prolonged nents in NMJs are highly controlled and regulated
contraction. (Darabid et al. 2014; Kummer et al. 2004; Lin
et al. 2001). The development and maintenance
of NMJ organization in mammals has been well
NMJ Formation during Development studied and requires signaling between motoneu-
rons, skeletal muscle fibers, and perisynaptic
In development, muscle formation and innerva- Schwann cells (Darabid et al. 2014; Legay and
tion are tightly coupled events (Darabid et al. Mei 2017; Wu et al. 2010). Early in development,
2014; Jessen and Mirsky 2005; Sanes and muscle fibers produce primitive acetylcholine
Lichtman 1999). Mononucleated muscle progen- receptors (nAChR), which generally accumulate
itor cells migrate into position and fuse to form in the central region of muscle fibers in a nerve-
multinucleated myotubes and then myofibers. independent process called prepatterning (Lin
NMJs form on these muscle cell syncytia as the et al. 2001; Yang et al. 2001). Prepatterning can
terminus of the motor axon and its attendant serve to provide a target on the muscle sarco-
Schwann cells approach and interact with the lemma for the approaching α-motor axon terminal
nascent muscle. In human quadriceps femoris, in early synapse formation (Shi et al. 2012).
primitive NMJs appear in the ninth week Once the axon terminal contacts the muscle,
of fetal life with NMJs developing by week pre- and postsynaptic elements are induced to
20 (Fidzianska 1980; Kelly and Zacks 1969). differentiate to form a localized synapse (Legay
During the remainder of gestation and into and Mei 2017). Muscle membrane depolarization
postnatal motor development, subsequent triggered by ACh released from the axon terminal
alterations in NMJs occur. These principally results in negative regulation of nAChR clusters
involve elimination of polyinnervation, so that away from the nerve terminal by suppressing
each muscle fiber is innervated by only one nAChR subunit gene transcription, increasing
nerve ending, and maturation of NMJ structure nAChR degradation (Salpeter et al. 1986), and
Fig. 1 (continued) cells are necessary for the proper postsynaptic b1 integrin to regulate presynaptic maturation
development of the NMJ. Additionally, the basal lamina and postsynaptic nAChR clustering. Illustration used with
plays an important role in NMJ development with synaptic the permission of Steven Cook, MD
laminin b2 binding to presynaptic calcium channels and
inhibiting nAChR clustering through pathways at the NMJ, and the transcription of genes
involving the serine/threonine kinases cyclin- encoding the synaptic proteins forming the mus-
dependent kinase 5 (Cdk5) and Ca2+/calmodu- cle side of the NMJ is active exclusively in syn-
lin-dependent kinase II (CaMKII) (Wu et al. aptic myonuclei (Merlie and Sanes 1985).
2010). Motoneuron-derived positive signals like
the protein agrin counteract this effect in the area
of the muscle that is immediately across from Presynaptic Maturation
the axon terminal (Wu et al. 2010), ultimately
leading to a high density of nAChRs and other As the NMJ matures, muscle fibers with more
components at the maturing NMJ with little or no than one innervating nerve ending eliminate
nAChR found away from the nerve. supernumerary sites leading to a one-to-one cor-
Agrin, a proteoglycan (Legay and Mei 2017), respondence between nerve and muscle with a
induces nAChR clustering by binding LRP4, a single innervation site on each muscle fiber
member of the low-density lipoprotein receptor- (Sanes and Lichtman 2001). In addition, there
related protein family (Shi et al. 2012), on the are changes in the distribution and types of cal-
muscle surface. Through LRP4’s interaction with cium channels expressed, and there is an increase
muscle-specific kinase (MuSK), an intracellular in the number of active zones (Darabid et al.
cascade is initiated that results in nAChR 2014). These specialized regions of presynaptic
clustering (Kim et al. 2008; Zhang et al. 2008). membrane where secretory vesicles dock align
Once MuSK is phosphorylated, it signals via directly with the postsynaptic folds of the sarco-
WNT (Darabid et al. 2014; Henriquez and lemma (Sanes and Lichtman 2001). The signals
Salinas 2012), a muscle-specific adapter protein responsible for these events are secreted by the
(downstream-of-tyrosine-kinase 7; Dok7), and a muscle fiber and present in the basal lamina (BL),
membrane-bound cytoplasmic molecule (rapsyn) an ordered extracellular matrix (ECM) structure in
to activate nAChR clustering (Legay and Mei the synaptic cleft.
2017; Okada et al. 2006). Rapsyn then acts as a The BL plays an important role in NMJ devel-
scaffold protein, bridging the nAChRs to the cyto- opment. Studies have shown that following the
skeleton and clustering them (Ramarao et al. destruction of both the motoneuron and muscle
2001). This agrin-induced clustering of nAChRs fiber, the muscle regenerates and there is
is a hallmark of the maturing synapse (Huh and reinnervation at the original synaptic site, indicat-
Fuhrer 2002; Witzemann et al. 1991). ing that the BL contains essential components for
In addition to clustering, nAChR subunit com- synaptic localization and differentiation (Letinsky
position is altered, with the fetal ααβγδ penta- et al. 1976; Marshall et al. 1977; Sanes et al.
meric nAChR channels changing to the adult 1978). The principal components of the BL are
ααβεδ type when the γ-subunit is replaced by the agrin, laminin, collagen IV, collagen XIII, the
ε-subunit late in gestation (Sunesen and ColQ-bound form of AChE, perlecan, tenascin,
Changeux 2003). This subunit switch alters chan- fibronectin, and entactin/nidogen (Singhal and
nel gating properties and conductance, allowing Martin 2011; Yurchenco et al. 2004; Yurchenco
the nerve to excite the muscle fiber to membrane and O’Rear 1994). The two major BL proteins,
potentials above those required to elicit contrac- laminin and collagen IV, both have different syn-
tion (Mishina et al. 1986). The regulation of tran- aptic and extrasynaptic isoforms (Singhal and
scription of nAChR-encoding genes is controlled Martin 2011).
at least in part by neuregulin-1. Neuregulin-1, Laminins are glycoproteins that guide cell dif-
secreted by motoneurons, muscle fibers, and ferentiation, migration, and adhesion (Patton et al.
Schwann cells, binds to the tyrosine kinase recep- 1997) and are important regulators of presynaptic
tors of the ERBB family to promote the synthesis terminal maturation (Darabid et al. 2014).
of nAChR and its associated proteins (Darabid Laminins associate into heterotrimers comprised
et al. 2014). nAChR mRNA is therefore enriched of three different chains: α, β, and γ. In humans,
19 laminin trimers have been identified from Several growth factors may also be involved
the combination of five different α chains, three in vesicle clustering and presynaptic differentia-
different β chains, and three different γ chains tion, including certain fibroblast growth factors
(Rogers and Nishimune 2017). In skeletal muscle, (FGFs), brain-derived neurotrophic factor
laminin-211 (α2β1γ1) predominates through- (BDNF), glial-cell-derived neurotrophic factor
out the extrasynaptic BL, while laminin-421 (GDNF), and transforming growth factor-β
(α4β2γ1), laminin-521 (α5β2γ1), and laminin- (TGF-β) (Darabid et al. 2014). Both GDNF and
221 (α2β2γ1) are exclusively present at the syn- TGF-β are expressed by Schwann cells, which are
aptic cleft (Patton et al. 1997). The laminin β2 believed to play critical roles in NMJ develop-
chain is confined to the synapse and plays a role ment, particularly in guiding motoneuron growth
in active zone formation and organization, and cones, engulfing and cleaning up axons that
in changing the composition of voltage-gated become fragmented during synapse elimination,
calcium channel (VGCC) types at the NMJ and motoneuron survival (Feng and Ko 2008;
(Nishimune et al. 2004). It has been demonstrated Hayworth et al. 2006; Reddy et al. 2003;
that laminin β2 binds directly to P/Q- and N-type Trachtenberg and Thompson 1996). Schwann
VGCCs but not other VGCC types expressed in cell maturation is in turn modulated by both pre-
motoneurons, and clusters them to flank active and postsynaptic molecules, including adenosine
zones (Nishimune et al. 2004). Laminin β2 also triphosphate (ATP), laminin, and neuregulin-1
activates the β1 integrin receptor, and this interac- (Darabid et al. 2014).
tion has been shown to be crucial for presynaptic
development (Schwander et al. 2004). Laminin β2
may also have a role in postsynaptic development NMJ Microanatomic Organization
as it can bind β1 integrin, α7 integrin, and in CP
dystroglycan on the muscle surface. The binding
to dystroglycan appears to anchor the laminin The formation of a reliable and highly efficient
chain to the intracellular cytoskeleton through NMJ relies on complex molecular interactions
the dystrophin, utrophin, the syntrophins, and between presynaptic, postsynaptic, and synaptic
dystrobrevin (Barresi and Campbell 2006). Like components, and precise organization is critical.
laminin β2, the laminin α4 and α5 chains appear to Several studies have demonstrated a disorganiza-
play roles in aligning presynaptic active zones tion of NMJ components in pediatric patients with
with postsynaptic components (Nishimune et al. CP. Theroux et al. immunofluorescently labeled
2008; Patton et al. 2001; Patton et al. 1997). AChE and nAChR in erector spinae biopsies from
Synaptic vesicle clustering is also promoted by 59 pediatric participants (39 with spastic CP and
collagen IV. There are six collagen IV chains (α1- 20 controls). When blinded investigators evalu-
α6). In skeletal muscle, collagen IV (α1)2(α2) is ated the photographs for the presence of abnormal
the major form in the extrasynaptic BL, while nAChR distributions, they found that samples
collagen IV (α3, α4, α5) and collagen IV from 11 out of 39 participants with spastic CP
(α5)2(α6) are expressed specifically at the synapse had significant nAChR staining present outside
(Fox et al. 2007; Miner and Sanes 1994; Sanes AChE. In comparison, 0 out of 20 samples from
et al. 1990). The α2 chain appears to promote control participants with idiopathic scoliosis had
vesicle clustering during the embryonic stage, extrajunctional nAChR (Theroux et al. 2002).
while α3 and α6 play that role during postnatal In a follow-up study, the distribution of
development (Fox et al. 2007). Another collagen- nAChR relative to AChE was quantified in biopsy
like molecule, ColQ, is exclusively localized to samples using imaging software and a customized
the NMJ, binds to perlecan and AChE, and is software macro. The “extra-AChE spread” (EAS)
essential for the localization of AChE to the of nAChR in each NMJ was calculated as the
NMJ (Feng et al. 1999; Rotundo 2003; Sanes fraction of all AChR stained pixels in digitized
and Hall 1979). images exhibiting nAChR but no AChE
immunofluorescence. EAS was found to be sig- proteins were appropriately localized in CP; how-
nificantly higher in samples from children with ever, samples from participants with spastic CP
spastic CP (0.28 0.04; n = 7) than in samples had significantly more AChE present outside
from children with idiopathic scoliosis nAChR, AChE present outside laminin β2,
(0.07 0.04; n = 26) (Theroux et al. 2005). nAChR present outside laminin β2, AChE present
When this method was applied to 59 biopsies outside SV2, and significantly less laminin β2
obtained from gracilis, vastus lateralis, and gas- present outside AChE than samples from control
trocnemius of participants with spastic CP, EAS participants (Fig. 2). Comparison of data from
values indicated no significant differences each study participant with spastic CP against
between the three muscle types. However, non- the pooled data from all the control samples
ambulatory participants with spastic CP were indicated that 84% of the participants with spastic
determined to have significantly higher EAS CP had evidence of significantly altered NMJs
values (0.23 0.14; n = 38) than ambulatory relative to control with the most frequent differ-
participants with spastic CP (0.16 0.08; ence being increased AChE outside laminin
n = 21) (Theroux et al. 2005). While there was β2. Consistent with this result, when median
no correlation between EAS and Modified colocalization scores were calculated in pair-
Ashworth Scale (MAS) score, there was a signif- wise comparisons for each sample, AChE present
icant correlation between EAS values and Gross outside laminin β2 was statistically higher in par-
Motor Function Measure (GMFM) Section D ticipants with spastic CP. A logistic regression
scores (Theroux et al. 2005). These results indi- analysis also determined that AChE outside of
cated that decreased colocalization of nAChR laminin β2 was the best predictor of a diagnosis
versus AChE was more likely to be found in of spastic CP (Robinson et al. 2013a). The fact
highly affected individuals and that the organiza- that the comparison that was most common, most
tion of these key NMJ components may be asso- significant, and most likely to be associated with a
ciated with voluntary muscle control and GMFM diagnosis of spastic CP was AChE outside lami-
Section D scores but independent of reflex muscle nin β2 suggests that the NMJ disorganization seen
control and, therefore, unrelated to MAS. in spastic CP is associated with disruptions of
Although these early studies established that proteins located in the synaptic cleft. While lam-
NMJs were disorganized in at least some children inin β2 mRNA levels have been shown to be
with spastic CP, they did not distinguish whether elevated in spastic CP muscle relative to normal
AChE, nAChR, or both were inappropriately controls (Smith et al. 2009), additional studies
localized at NMJs, which are defined by nerve- are needed to resolve the distribution of AChE,
muscle interactions. To address this issue, Robin- laminin β2, and additional synaptic components
son et al. investigated the relative distribution of and to determine the mechanisms at the root of
presynaptic, synaptic, and postsynaptic compo- the molecular dysfunction leading to NMJ
nents and examined the ultrastructure of NMJs disorganization.
in muscle from pediatric participants with CP Examples of the non-colocalization of NMJ
(see next section). The distributions of nAChR components are found in the literature including
and AChE relative to each other, synaptic vesicle in cases involving immobility due to disuse, pro-
protein 2 (SV2), and laminin β2 were compared in longed exposure to NMBAs, or casting as well as
erector spinae samples from 25 participants with in cases of hereditary dystroglycanopathy disease
spastic quadriplegic CP and 28 samples from con- (Taniguchi et al. 2006). Disorganization of NMJ
trol participants with idiopathic scoliosis (Robin- components is also seen during neuromotor mat-
son et al. 2013a). When data from all the NMJs uration (Deschenes et al. 2001; Sanes and
from the control group (n = 1899) and the spastic Lichtman 1999; Yanez and Martyn 1996) and
CP group (n = 1589) were pooled and compared, after rounds of α-motor nerve degeneration/regen-
both groups had well match SV2 and nAChR, eration (Levitt-Gilmour and Salpeter 1986;
indicating that presynaptic and postsynaptic Nishizawa et al. 2003). Of these possibilities,
Fig. 2 Compared to samples from control subjects with present outside AChE. Both groups had well matched
idiopathic scoliosis, triple stained samples from subjects SV2 and nAChR, indicating that the pre- and postsynaptic
with spastic CP had significantly more AChE (blue) out- components may be well aligned, but there is dysmorphism
side nAChR (red), AChE present outside laminin β2 related to components within the synaptic cleft (Robinson
(green), nAChR present outside laminin β2, AChE present et al. 2013a)
outside SV2 (green), and significantly less laminin β2
repeated cycles of regeneration seem most possi- occurs in conjunction with continuing NMJ acti-
ble in CP, but studies of telomere length, which is vation, which is in contrast to the reduced NMJ
an indicator of regeneration cycling in muscle, in activation that is generally associated with other
biopsy samples from individuals with spastic CP causes of immobility. These observations indicate
demonstrated that cycles of degeneration/regener- that the mechanisms responsible for the NMJ
ation were similar in spastic CP and control disorganization in CP may be distinct from those
groups, indicating that recurrent rounds of muscle seen in other conditions.
regeneration did not account for the differences in
NMJ organization (Robinson et al. 2013a). Anal-
ysis of muscle fiber types and myosin heavy chain NMJ Ultrastructure in CP
isoforms demonstrated that surgical samples from
children with CP had the appearance of mature The structural disorganization of NMJs in chil-
muscle (Robinson et al. 2013a). There is no dren with CP can also be seen using transmission
known linkage between CP and the dystroglyca- electron microscopy for ultrastructural analysis.
nopathies, and while individuals with spastic CP In a study of NMJs in erector spinae samples
exhibit lack of mobility due to weakness, spastic- collected from participants undergoing posterior
ity, and loss of motor control, this immobility spinal fusion surgery with a diagnosis of spastic
CP (n = 25) or idiopathic scoliosis (n = 25), the carpi ulnaris muscle and extensor carpi radialis
general ultrastructure of NMJs was similar brevis muscle biopsies from participants with
with both exhibiting close apposition of the moto- spastic CP (n = 6) and control participants
neuron and muscle fiber, absence of poly- (n = 2), the genes encoding the subunits of the
innervation, and distinct postsynaptic folds nAChR were not significantly altered in spastic
(Fig. 3). In samples from participants with spastic CP. However, the genes encoding the extracellular
CP, however, there was a significant increase in matrix proteins collagen IV α3 (COL4A3) and
the length of primary postsynaptic folds, a signif- laminin β2 (LAMB2) and the small-conductance
icantly greater distance between synaptic folds, calcium-activated potassium channel (KCNN3)
and a significant reduction of mitochondrial load were significantly upregulated in muscle from
in the nerve terminal (Robinson et al. 2013a). The individuals with spastic CP compared to controls
difference in postsynaptic fold length may reflect (Smith et al. 2009). These studies provide
functional differences in the efficiency or duration supporting evidence that patients with spastic
of neuromotor transmission, as the folds are rich CP have inherent abnormalities in their NMJs
in Na+ channels necessary for muscle depolariza- and that these abnormalities differ from those
tion. Postsynaptic membrane folding can be com- found during development or other pathologic
plex, but synaptic fold length is very consistent conditions.
(Slater et al. 1992), and altered fold length in
conditions like limb-girdle myasthenia are associ-
ated with altered synaptic transmission efficiency Medications That Target NMJs
(Slater et al. 2006). Decreased mitochondrial load
may also be associated with compromised neuro- It is important to consider the potential NMJ
transmission as high levels of mitochondria are dysfunction in patients with CP when determin-
necessary to support neurotransmitter filling of ing appropriate medications. Clinical research
synaptic vesicles, neurotransmitter release, nerve has indicated that children with CP have
terminal function, and ATP release by the nerve increased sensitivity to the depolarizing agent
(Kann and Kovacs 2007; Lee and Peng 2006; Lee succinylcholine (Theroux et al. 1994) and
and Peng 2008; Nelson et al. 1993; Todd and decreased sensitivity to the nondepolarizing mus-
Robitaille 2006). Overall, ultrastructural observa- cle relaxants vecuronium (Moorthy et al. 1991)
tions support pharmacologic and light micro- and rocuronium (Na et al. 2010). Depolarizing
scopic data indicating that NMJs have altered agents act as nAChR agonists by binding to the
organization and function in spastic CP. nAChR and generating an action potential.
Because they are not metabolized by AChE, the
binding of drug to the receptor is prolonged,
NMJ Gene Expression in CP resulting in an extended depolarization of
the muscle and preventing repolarization. Non-
Several studies have examined the transcriptional depolarizing agents, on the other hand, act
profile of muscles from individuals with CP, as competitive antagonists. They bind to the
including components of the NMJ. While imma- nAChR but are unable to induce ion channel
ture or denervated muscles express the γ-subunit openings; however, by competing for ACh bind-
of nAChR (Sanes and Lichtman 1999) and mus- ing, they prevent depolarization of the muscle.
cles from other pathologic conditions express the The anomalous responses of surgical patients
α7-subunit of nAChR (Nizri et al. 2007), quanti- with spastic CP to these agents suggest some
tative PCR studies have failed to detect either the degree of NMJ abnormality, including the possi-
γ-subunit or the α7-subunit in erector spinae sam- bility of extrajunctional nAChRs, and are impor-
ples from participants with spastic CP (Robinson tant to note as there is the potential for potassium
et al. 2013a; Theroux et al. 2002). Similarly, when to be released into the extracellular fluid when
Affymetrix microarrays were performed on flexor depolarizing neuromuscular blocking agents are
Fig. 3 Electron micrographs of NMJs from control sub- spastic CP demonstrated a significant increase in the length
jects with idiopathic scoliosis (a) and subjects with spastic of primary postsynaptic folds, a significantly greater dis-
CP (b) both exhibit close apposition of motoneuron and tance between synaptic folds, and a significant reduction of
muscle fiber, an absence of polyinnervation, and distinct mitochondrial load in the nerve terminal (Robinson et al.
postsynaptic folds; however, samples from subjects with 2013a)
used during anesthesia (Gronert and Theye 1975; reasons disrupted NMJs are seen in CP remain
Martyn and Richtsfeld 2006). unclear, but there are three compelling schools
Magnesium sulfate is often used as an adjuvant of thought (Robinson et al. 2013a). The disorga-
during general anesthesia. Magnesium sulfate nization and altered function of NMJs seen in CP
demonstrates anesthestic, analgesic, and muscle may be an adaptive response to years of altered
relaxation effects (Gupta et al. 2006) due to its activity and weakness; PNS effects like those at
action as both an N-methyl-D-aspartate (NMDA) NMJs may be a primary result of the same inci-
receptor antagonist and an inhibitor of ACh dent, inflammatory event, or infection that caused
release (Na et al. 2010). Its inhibitory effect the CNS injury; differences in NMJs may arise
on ACh release leads to reduced excitability of because of altered molecular signaling from lower
the muscle fiber, potentiating the neuromuscular motor neurons during recovery from the CNS
blockade produced by nondepolarizing NMBAs. injury suffered during neuromotor maturation.
In one study, individuals with spastic CP Regardless of the mechanisms, the NMJ disorga-
receiving magnesium sulfate in conjunction nization seen in CP is an important finding as
with rocuronium (n = 30) had a diminished neurotransmission and responses to medications
rocuronium requirement compared to individuals targeting the NMJ may be altered. Knowledge of
with spastic CP receiving rocuronium alone NMJ dysfunction in CP is therefore necessary to
(n = 30); however, both groups required more assure safe and effective management of patients
rocuronium than the recommended pediatric and to further our understanding of the peripheral
dose (Na et al. 2010). and systemic manifestations of CP.
Botulinum toxin type A, which may be used
to treat spasticity in patients with CP, targets
presynaptic components the NMJ. The light
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Muscle Changes at the Cellular-Fiber
Level in Cerebral Palsy 16
Sudarshan Dayanidhi and Richard L. Lieber
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 242
Muscle Growth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243
Longitudinal Growth and Sarcomere Addition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243
Postnatal Development . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 243
Sarcomere Adaptation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 244
Sarcomeres in Children with CP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 245
Extracellular Matrix . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246
Changes in ECM Content . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 246
Passive Mechanical Properties of Muscle Fibers and Bundles . . . . . . . . . . . . . . . . . . . . . . . . . 246
Muscle Stem Cells, Postnatal Development, and Contractures . . . . . . . . . . . . . . . . . . . . 247
Satellite Cells (Muscle Stem Cells) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247
Function of Satellite Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 248
Satellite Cells in Children with Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 250
Abstract in parallel and series. Myofibers in turn are

Muscle changes are routinely observed in chil- made up of basic contractile proteins actin
dren with cerebral palsy. The natural progres- and myosin that interact to form sarcomeres.
sion of gait leads to a reduction in passive Sarcomere length and force production are
range of motion and muscle contractures. intricately associated such that at very long
Here we discuss the physiological properties and short sarcomere lengths, there is a reduc-
of skeletal muscle tissue and recent advances in tion in force-generating capacity. During typi-
the biological basis of contractures. Skeletal cal postnatal development, longitudinal
muscles are highly organized structures com- skeletal muscle growth occurs by addition of
posed of muscle cells, i.e., myofibers, arranged sarcomeres secondary to stretch induced by
bone growth. In children with cerebral palsy,
sarcomere lengths are overstretched, and serial
S. Dayanidhi · R. L. Lieber (*)
sarcomere number is lower, associated with a
Shirley Ryan AbilityLab, Chicago, IL, USA limitation in joint range of motion, suggesting
e-mail: sdayanidhi@sralab.org; rlieber@sralab.org

https://doi.org/10.1007/978-3-319-74558-9_13
242 S. Dayanidhi and R. L. Lieber
reduced ability for muscle growth and weak-

ness. Increase in muscle extracellular matrix
content and increase in passive mechanical
stiffness of fibers and fiber bundles are also
observed in contractured muscles. Satellite
cells are resident stem cells indispensable for
postnatal development, repair, and regenera-
tion of skeletal muscles. The satellite cell pop-
ulation is dramatically reduced in contractured
muscles. Overall these findings suggest that
impaired muscle growth and contractures in
children with cerebral palsy are related to a
reduced muscle stem cell number.
Keywords
Contracture · Skeletal muscle · Cerebral palsy ·
Muscle stem cell · Satellite cell · Sarcomere
Introduction Fig. 1 Contractures in gait impairments. Equinus and

crouch gait are common gait patterns seen in children with
Cerebral palsy (CP) is the most common devel- CP, which are associated with muscular contractures of the
plantar flexors, hamstrings, and hip flexors. The contrac-
opmental movement disorder and affects 2–4
tures limit the available excursion at the hip, knee, and
children per 1000 live births (Hirtz et al. 2007; ankle joints
Durkin et al. 2016). Spasticity is the largest sub-
category, and 70–80% children with CP have
spasticity either unilaterally or bilaterally (Van with age when they become static with limited
Naarden Braun et al. 2016). Although the pri- range of motion permissible at the joints.
mary neurological injury in these children is Broadly speaking, population-based studies
nonprogressive, significant secondary impair- have shown that spasticity increases in children
ments develop in the musculoskeletal systems. with age till the age of 4, after which there is a
Specifically, muscle weakness and contractures steady decline in muscle tone (Hagglund and
are seen in the upper and lower extremities that Wagner 2008) and older children show limita-
limit the available range of motion at the joints tions in range of motion presumably more asso-
(Graham et al. 2016). Common walking patterns ciated with change in properties of skeletal
in children with spasticity are equinus gait asso- muscles (Nordmark et al. 2009). Even in younger
ciated with contractures of the plantar flexors that children, spasticity does not appear to be the only
limit ankle dorsiflexion and crouch gait associ- contributor to contractures, and changes are
ated with knee flexion and hip flexion contrac- observed in passive mechanical properties, i.e.,
tures that limit knee extension and hip extension passive joint torque (Willerslev-Olsen et al.
(Rodda et al. 2004) (Fig.1). Similarly, elbow 2013). Importantly, while spasticity is a contrib-
flexion and wrist flexion contractures are seen uting factor, elimination of spasticity by selective
in the upper extremity, associated with limita- surgical dorsal rhizotomy does not in of itself
tions in elbow extension and wrist extension prevent contracture development (Tedroff et al.
(Leafblad and Van Heest 2015; Bunata and 2011). In their 10-year follow-up, these investi-
Icenogle 2014). gators observed that surgical dorsal rhizotomies
Contractures may be dynamic initially, i.e., reduced spasticity and improved passive range of
accompanied by spasticity, but this changes motion in the short-term but did not prevent
16 Muscle Changes at the Cellular-Fiber Level in Cerebral Palsy 243
development of contractures in the long-term. Muscle Growth

Similarly, in children undergoing botulinum
toxin injections for local reduction of spasticity, Longitudinal Growth and Sarcomere
there were short-term gains in range of motion Addition
and spasticity reduction, but long-term follow-up
1–3 years later showed a decline in range of Skeletal muscles are structurally-hierarchically
motion (Tedroff et al. 2009). These studies sug- organized tissues composed of bundles of fascicles,
gest that development of contractures is not sim- which in turn are bundles of muscle cells, i.e.,
ply caused by the presence of spasticity. myofibers, which are made up of myofibrils, com-
The natural progression of walking in chil- posed of a collection of sarcomeres (Lieber 1986).
dren with cerebral palsy over a 2–4-year period, Sarcomeres are the basic functional units of mus-
without surgical intervention, leads to a gradual cles composed of contractile proteins, actin and
reduction in permissible joint excursion and a myosin, whose interaction via the cross-bridge
crouch gait pattern (Bell et al. 2002; Johnson cycle is responsible for force generation. Sarco-
et al. 1997). Correspondingly, lower limb pas- meres are organized in series to provide length
sive range of motion decreases from early child- and in parallel to provide cross-sectional area to
hood to adolescence (Nordmark et al. 2009), the myofibers. The force-length relationship is an
suggesting an inability to align muscle growth important predictor of active force generation such
with bone growth (discussed more in the section that increased or decreased sarcomere length rela-
on “Longitudinal Growth and Sarcomere Addi- tive to optimum leads to reduced force, while an
tion”). Muscle growth and volume in children optimal sarcomere length, reflecting a maximal
with cerebral palsy are significantly lower than overlap between the actin and myosin filaments,
in children with typical development produces maximal force (Gordon et al. 1966).
(TD) (Barber et al. 2011, 2016, Handsfield
et al. 2016; Noble et al. 2014) even in children
15 months of age (Herskind et al. 2016). Longi- Postnatal Development
tudinal bone growth is also reduced in children
with CP (Oeffinger et al. 2010). Specifically, Postnatal muscle development is characterized by
tibial length is reduced in ambulatory children both longitudinal and cross-sectional myofiber
with CP compared to children with TD and is growth (Gokhin et al. 2008b). Longitudinal
lower in children who are more severely growth increases the range over which a muscle
affected. In addition, abnormal torsion along functions, while cross-sectional growth increases
the femur and tibia are reported, either due to muscle contractile force (Lieber and Friden 2000).
failure for typical postnatal developmental It is important to note that during postnatal devel-
changes such as in femoral anteversion or is opment, in mammalian muscles, the number of
acquired due to muscle force abnormalities myofibers does not increase (Enesco and Puddy
(Graham et al. 2016; Rethlefsen et al. 2006; 1964; Montgomery 1962). In a series of seminal
Bobroff et al. 1999). Consequently, most clinical murine studies (Griffin et al. 1971; Williams and
treatments for children with CP are focused Goldspink 1971, 1973; Goldspink 1970), Wil-
toward promoting appropriate muscle and bone liams and Goldspink studied the role of sarcomere
growth and preventing muscular contracture length and sarcomere number on myofiber longi-
(Graham et al. 2016; Graham and Selber 2003; tudinal and cross-sectional development. They
Thomason et al. 2012). reported increased myofiber cross-sectional area
In recent years, progress has been made to by addition of myofibrils (Goldspink 1970). We
understand the biology of muscle growth and recently showed (Gokhin et al. 2008b) that
contractures from human studies utilizing biop- between postnatal day 1 and day 28, there was
sies from children and animal studies, which we an almost twofold increase in myofibrillar pack-
review here. ing, a sevenfold increase in myofiber cross-
Fig. 2 Muscle growth and contractures. During post- length and decreased sarcomere number (right) along with
natal development as a young child’s muscle (left) grows, a reduced increase in number of myonuclei. This results in
in typical development (middle), there is an increase in the a decreased capacity for muscle excursion leading to
myofiber length associated with an increase in the serial reduced range of motion and contractures (bottom). The
sarcomere (distance between the black bands) number and distance between black bands of a myofiber represents a
myonuclei (blue). This allows for maintenance of range of sarcomere, and the serial sarcomere is the number of sar-
motion (bottom). In the case of children with CP, there is an comeres along the length of the myofiber. Note the differ-
increase in myofiber length with an increase in sarcomere ences between the child with TD and CP
sectional area, and a fourfold increase in muscle sarcomere number increase with bone growth
mass (Gokhin et al. 2008b). (Boakes et al. 2007). In this case, with a twofold
Longitudinal myofiber length increases by the increase in fiber length, there was a similar
addition of sarcomeres in series such that the increase in sarcomere number showing that the
force-length relationship is maintained (Fig. 2). increase in fiber length was not purely just a case
This increase using mouse models has shown of stretching existing fibers and creating fibers
that there is a fivefold increase in sarcomere num- with increased sarcomere length (Fig. 2).
ber during the postnatal period (Gokhin et al.
2008b; Griffin et al. 1971; Williams and
Goldspink 1971). Sarcomere addition is difficult Sarcomere Adaptation
to measure directly in humans, but a clinical case
has shown, in a child undergoing distraction oste- Serial sarcomere number is a dynamic property
ogenesis, that there was a corresponding even in mature adults. This can be seen by
addition and subtraction of sarcomeres in range of motion such that the children who have
response to maintaining a muscle in a lengthened the worst contractures also have the longest sar-
and shortened position of immobilization, comere lengths (Pontén et al. 2007). Sarcomere
respectively. When a muscle is maintained in a lengths of the antagonistic extensor, extensor
stretched position for 2–4 weeks, it will stretch carpi radialis brevis, are also increased but not
the myofiber and increase its length. Initially the correlated with the degree of maximal range of
existing sarcomeres are in a lengthened position motion, consistent with the idea that the imbal-
but, over the course of several weeks, will add ance between the larger flexors and smaller
new sarcomeres such that sarcomere lengths extensors drives the adaptation.
return to optimal (Williams and Goldspink Sarcomere length measured in contractures in
1973). Similarly, if a muscle is maintained in a lower limb muscles (gracilis, semitendinosus,
shortened position, myofiber length will reduce and soleus) was also increased by 20–50%
over several weeks and will lose sarcomeres such (Smith et al. 2011; Mathewson et al. 2015). The
that the sarcomeres are no longer in a shortened popliteal angle, measuring degree of hamstring
position (Williams and Goldspink 1973). If a contracture, is negatively correlated with sarco-
growing muscle is prevented from increasing in mere length. Similar to the finding in wrist flex-
length by maintaining a shortened position for ion contractures, sarcomere lengths were longest
3 months from a few days after birth, it does not in children who had the more severe contractures
increase serial sarcomere number. However, if it (Smith et al. 2011). This suggests an inability in
is then allowed to recover (Williams and the ability of the growing contractured muscle to
Goldspink 1971, 1973) by removing the immo- add sarcomeres in series to increase the length of
bilization, subsequent stretch and growth would the muscle fiber and an over-lengthening of the
result in rapid serial sarcomere number increase existing sarcomeres. Consistent with this logic,
similar to the contralateral side. These experi- we see that when serial sarcomere number of
ments demonstrate that the postnatal period is contractured muscle is calculated, it is approxi-
particularly plastic for adaptation and serial sar- mately 40% lower compared to typically devel-
comere addition. This finding leads to the idea of oping children (Mathewson et al. 2015). In
using serial casting in children with CP to children with TD, the bone grows and stretches
increase the range of motion and muscle length, myofibers which respond by addition of new
presumably by the addition of sarcomeres sarcomeres to maintain the capacity for excur-
(McNee et al. 2007). sion of the fiber and consequently range of
motion (Fig. 2). In contrast, it is our hypothesis
that, in the case of children with CP, with muscle
Sarcomeres in Children with CP stretch there is an increase in myofiber length
without concomitant increase in sarcomere num-
Sarcomere length measured in vivo during sur- ber that is reflected by similar fiber length with
gical correction of wrist contractures in children overstretched sarcomeres (Fig. 2) and develop-
with CP revealed an interesting pattern. These ment of contracture (Fig. 1). Transcriptional
muscles showed seemingly contradictory pat- studies from both upper and lower limb muscle
terns of over-lengthened sarcomeres although contractures show a significant upregulation of
the joints were in static contractures, i.e., have genes related to embryonic and perinatal myosin
markedly reduced range of motion at the joint. heavy chain isoforms (Smith et al. 2009, 2012),
The sarcomere length of the flexor carpi ulnaris routinely not seen during later postnatal devel-
was ~45% increased compared to opment (Schiaffino et al. 2015; Gokhin et al.
non-contractured muscles in control subjects 2008a). This implies either a reduction in overall
(Lieber and Fridén 2002). Intraoperative sarco- muscle development and/or impaired muscle
mere length is highly correlated with the degree regeneration that could be related to contracture
of contracture, i.e., maximal permissible passive development.
Extracellular Matrix marked qualitative increase compared to muscles

from children with TD (Smith et al. 2011) (Fig. 3).
Changes in ECM Content Quantitative analyses for collagen using hydroxy-
proline assays also showed a significant increase in
Extracellular matrix (ECM) is the connective tissue extracellular matrix content in contractured mus-
that surrounds the muscle fiber, fiber bundles, and cles (Smith et al. 2011). However, histological
the whole muscle and connects to the tendon. Tra- evaluation, which might not have the resolution
ditionally, it is described as having an endomysium to detect differences have not shown such changes
(surrounding individual myofibers), perimysium in intramuscular connective tissue in contractured
(surrounding fiber bundles), and epimysium (sur- muscles of the upper extremity (de Bruin et al.
rounding the whole muscle), which, while conve- 2014). Interestingly, there is some evidence to sug-
nient, may not be very helpful to understand the true gest that children with moderate-severe spasticity
organization and how force interaction and trans- have a greater collagen content (Booth et al. 2001).
mission occur from the contractile proteins to the At the level of transcription, contractured muscles
tendon and bone (Gillies and Lieber 2011). The of both the lower and upper extremity demonstrate
microstructure and function of normal ECM are an increased gene expression related to the ECM,
complex, and we only discuss some aspects rele- specifically in collagens and laminin (Smith et al.
vant to what is known in children with CP. Readers 2009, 2012). In addition, there is increased expres-
seeking more detailed information are referred to sion of some genes related to the breakdown and
reviews (Patel and Lieber 1997; Gillies and Lieber maintenance of the ECM, such as meta-
2011). Briefly, collagen is the major protein of lloproteinases, its inhibitors, and other associated
the ECM with Type I and III being the major glycoproteins, suggesting dysregulation in the
components although other types such as Type IV, microenvironment of the ECM.
glycoproteins, and proteoglycans also play a
significant role.
Children with CP have a significant increase in Passive Mechanical Properties
ECM material around myofibers seen by immuno- of Muscle Fibers and Bundles
histochemical evaluation of sections of
contractured muscles. Labeling for collagen I and One way to test the stiffness of skeletal muscles is
laminin (component of the basal lamina) shows a to dissect fiber bundles (~20 fibers) or single fibers
Fig. 3 Extracellular matrix is qualitatively increased. Note that the scale bars indicate 150 μm in both images
Representative images showing Laminin labeling for the showing markedly reduced myofiber areas as well in the
basal lamina from semitendinosus muscle section in a child child with CP. (Data from Zogby et al. 2017)
with typical development (left) and cerebral palsy (right).
from biopsies, secure them with a force transducer muscles, but no differences were observed in the
on one end and a stable base on the other side, fiber bundles. The mass of the titin was greater in
stretch them to various sarcomere lengths, and children with CP, contradictory to what would be
measure the development of passive stiffness expected with greater stiffness since it would sug-
(Meyer and Lieber 2011). The use of single fibers gest more compliant fibers. Interestingly titin
and fiber bundles helps observe if any observed molecular mass was not correlated with the
differences in stiffness compared to controls are observed fiber stiffness. All of these studies
due to a change in the ECM material or due to using passive mechanical properties and extracel-
properties inherent to single fibers (e.g., intracellular matrix measurements show that, while it is
lular large protein titin, which secures the myosin clear there are differences in children with CP
filament to the Z-disk of the sarcomere). Increased compared to children with TD, it is not clear
passive stiffness could contribute to development how they related to contractures. As mentioned,
of contractures and any increase in stiffness in the previous section, even in healthy muscles,
observed during clinical evaluations of passive there is a poor understanding of how all these
range of motion such as popliteal angle components create passive force transmission
measurement. from the muscle to the tendon as well as overall
The stiffness of single fibers of various muscle excursion capabilities.
contractured muscles from the upper extremity
combined together was slightly higher than control
muscles (Lieber et al. 2003). However the control Muscle Stem Cells, Postnatal
muscle bundles had dramatically greater stiffness Development, and Contractures
than the bundles from muscle contractures. Impor-
tantly, qualitatively the amount of ECM observed Satellite Cells (Muscle Stem Cells)
was much greater in the bundles compared to con-
trols. This suggested that although the spastic Satellite cells are the primary resident muscle
contractured muscles in the upper extremity had stem cells responsible for muscle development,
greater ECM content, they generated much less repair, and regeneration throughout the life span
stiffness under conditions of stretch, i.e., their (Yin et al. 2013). Satellite cells were so named
material was not organized in the same way as based on their peripheral location in the myofiber,
control muscles. Passive stiffness was measured sandwiched between the sarcolemma and basal
in fibers and bundles from specific medial ham- lamina (Mauro 1961) (Fig. 4). In contrast, multi-
string muscles rather than combining different ple myonuclei of myofibers are present within the
types of muscles (Smith et al. 2011). This revealed sarcolemma. During postnatal development, there
that, in both gracilis and semitendinosus muscles, is an increase in myonuclear number (Enesco and
there was a significant increase in bundle stiffness Puddy 1964). However adult (mature) myonuclei
but not in single fibers compared to controls and no are terminally differentiated, i.e., unable to divide,
difference seen in mass of the intracellular protein proliferate, or regenerate. Consequently there
titin. This supports the idea that increased ECM must be other myogenic tissue-specific stem
content, mentioned in the previous section, was cells that can make the skeletal muscle. Indeed,
associated with the increased stiffness of the bun- the source for postnatal increase in myonuclei
dles rather than any change in intracellular stiff- comes from proliferation, differentiation, and
ness. Interestingly, gracilis passive stiffness was far fusion of mononucleated satellite cells to existing
greater than of the semitendinosus although they myofibers (Macconnachie et al. 1964; Moss and
were both different from control muscles, illustrat- Leblond 1971). By definition, an adult tissue stem
ing the idea of variability between different mus- cell has two properties – the ability to differentiate
cles with contractures. to create new tissue and the ability to self-renew
In the case of gastrocnemius and soleus mus- (Weissman 2000). The ability to self-renew is a
cles, fiber stiffness was greater than control critical feature that allows all stem cells to
Fig. 4 Muscle stem cells and contractures. Satellite satellite cell population is lower by 60–70% compared to
cells are muscle stem cells located in their niche between children with TD demonstrated using two different
the basal lamina of the extracellular matrix and the sarco- methods (flow cytometry and immunohistochemistry) in
lemma of the myofibers. They are the source for myonuclei two different cohorts of children. (Modified from Smith
and are indispensable for growth and regeneration through- et al. (2013), Dayanidhi and Lieber (2014), and Dayanidhi
out life. In contractured muscles in children with CP, the et al. (2015))
maintain their presence and functionality through- which are important in the postnatal period during
out life, without which their population would be bone-mediated muscle growth. Postnatal muscle
depleted as they are used over time. Satellite cells development is critically dependent on satellite
were visually identified back in the 1960s, but it cells (Lepper et al. 2009; Oustanina et al. 2004).
was not until the 2000s, after new molecular Pax7 null mice demonstrate a dramatic reduction
markers such as the Pax7 transcription factor in both myofiber size and in satellite cell number
were identified (Seale et al. 2000), that it was during the postnatal period. Using a transgenic
convincingly shown that the satellite cells are mouse that conditionally inactivates Pax7, Lepper
indeed the primary muscle stem cell capable of et al. show that myoblasts from Pax7 lineage fuse
self-renewal and differentiation (Collins et al. into myofibers and are indispensable during the
2005; Zammit et al. 2004; Halevy et al. 2004). postnatal period. Conditional satellite cell inacti-
vation during the postnatal period results in
severely compromised muscle regeneration after
Function of Satellite Cells injury. A number of studies (von Maltzahn et al.
2013; Lepper et al. 2011; Sambasivan et al. 2011;
Satellite cells are normally quiescent but become Günther et al. 2013) conclusively show that Pax7-
activated during growth or, in case of repair, pro- expressing satellite cells are critical for long-term
ceed down the so-called myogenic pathway, i.e., muscle repair capability even in adult muscle.
proliferate, differentiate, and create new myo- Satellite cells have similarly been show to con-
blasts that fuse with the existing myofibers. Satel- tribute to routine maintenance in uninjured fibers
lite cells have a large number of activation factors during adulthood and aging (Keefe et al. 2015;
(Kuang et al. 2008) including mechanical stretch, Pawlikowski et al. 2015).
Satellite Cells in Children after injury (Murphy et al. 2011). More recently,
with Cerebral Palsy Fry et al. showed that activated satellite cells are
important regulators of ECM changes in response
It is clear that muscle in children with CP has to muscle overload (Fry et al. 2014). Similarly,
reduced capacity for longitudinal and cross- with age, lack of satellite cells leads to increased
sectional growth during the postnatal period. ECM content and fibrosis (Fry et al. 2015). One
In light of the discussion above where we pre- proposed mechanism is that satellite cell activa-
sented evidence that satellite cells play a signif- tion is associated with upregulation of interstitial
icant role in muscle growth, we speculate that collagenases, which allow ECM remodeling and
contracture formation may, in part, be due to satellite cell migration (Pallafacchina et al. 2010;
satellite cell dysfunction. Using flow cytometry Nishimura et al. 2008).
of muscle biopsies from children with CP As previously discussed, compared with chil-
(Smith et al. 2013), we showed that, compared dren with typical development, muscles of chil-
to typically developing children, children with dren with cerebral palsy have increased collagen
CP had a significantly reduced (~60%) satellite content, increased bundle passive stiffness, and
cell population (Fig. 4). However, as noted, qualitatively increased levels of ECM – consis-
children with CP have extracellular matrix tent with muscle fibrosis (Smith et al. 2011).
(ECM) abnormalities that may systematically These contractured muscles also have signifi-
bias flow cytometry results in that it may be cantly reduced satellite cell number (Smith
more difficult to extract satellite cells from CP et al. 2013; Dayanidhi et al. 2015), providing
muscle. To test this idea, we used the much more support for the idea that increased ECM might
labor-intensive in situ immunohistochemistry be related to decreased satellite cell number.
method to quantify satellite cells (Dayanidhi With reduced satellite cell number, it appears
et al. 2015) using antibodies for satellite cells as though this process of ECM regulation could
(anti-Pax7), the basal lamina (anti-Laminin), fail and result in the development of muscle
and a nuclear stain (DAPI). By systematically contractures. Recently, we showed that under
sampling large volumes of tissue, we quantified conditions of stretch, limited sarcomere addition
satellite cell number in situ without significant can occur in satellite cell-specific transgenic
tissue manipulation. The satellite cell number mouse models in the presence of a reduced num-
quantified from these sections, as number per ber of satellite cell, but there is also considerable
100 myofibers, similarly showed a 70% proliferation of the ECM and fibrotic changes
decrease compared to age-appropriate controls (Kinney et al. 2016).
(Fig. 4). These two studies using different
methods and different human subjects, demon-
strate that it is highly likely that there are sig- Summary
nificant changes in the satellite cell population
in children with CP and suggest possible future Children with CP have poor longitudinal muscle
avenues for therapeutic intervention using growth and develop contractures. This is associ-
regenerative medicine. ated with increased sarcomere length, decreased
Satellite cells are primary muscle stem cells, serial sarcomere number, and changes in the
but they do not act independent of other mononu- extracellular matrix. The number of muscle
clear cell types such as fibroblasts, macrophages, stem cells, responsible for postnatal develop-
etc. (Bentzinger et al. 2013). Recent evidence ment, repair, and regeneration, is significantly
from animal studies suggest that satellite cells reduced in contractured muscles. Future avenues
negatively regulate the extracellular matrix will utilize regenerative medicine to provide
(ECM). Murphy et al. demonstrated that interac- novel therapeutics for improving the muscle
tion between satellite cells and fibroblasts is stem cell function to prevent development of
important for appropriate muscle regeneration contractures.
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Muscle Size, Composition,
and Architecture in Cerebral Palsy 17
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 254
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 254
Muscle Anatomy and Typical Muscle Growth and Development . . . . . . . . . . . . . . . . . . . . . 254
Skeletal Muscle Size and Architecture in Typically Developing Children . . . . . . . . . . . . 254
Skeletal Muscle Size, Composition, and Architecture in Children with CP . . . . . . . . . . . 256
Assessing Muscle in Children with CP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 260
Factors Contributing to Atypical Muscle Growth and Development
in Children with CP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 261
Physical Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 261
Muscle Spasticity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 262
Medications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 262
Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 262
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 263
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 264
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 265
Abstract with cerebral palsy (CP) have smaller muscles

There is tremendous growth and development that contain less contractile tissue and more fat,
of skeletal muscle during childhood and ado- both of which interfere with force generation.
lescence. Increase in cross-sectional area and These muscle deficits are linked to the
length and change in architecture allow mus- impaired movement, low physical activity,
cles to generate greater forces needed to and the higher risk of chronic diseases in indi-
accommodate increase in body size that occurs viduals with CP. In this chapter, we will review
during the first two decades of life. Children how the muscles differ in children with CP
compared to typically developing children.
We will also review factors that contribute to
C. M. Modlesky (*) · C. Zhang the poor muscle growth and development in
Department of Kinesiology, University of Georgia,
children and adolescents with CP, methods of
Athens, GA, USA
e-mail: christopher.modlesky@uga.edu

https://doi.org/10.1007/978-3-319-74558-9_14
254 C. M. Modlesky and C. Zhang
muscle assessment, and potential treatment specific connective tissue that surrounds the mus-
strategies. cle belly, or the whole muscle, and attaches the
muscle belly to the tendons. The muscle belly is
Keywords composed of many muscle fascicles, which are
Cerebral palsy · Muscle morphology · Muscle long bundles of 10–100 muscle fibers encased in
quality · Muscle architecture · Muscle strength their own connective tissue called perimysium.
Muscle fibers are individual muscle cells, which
are composed of many thread-like myofibrils.
Introduction Each myofibril is composed of multiple adjoining
sarcomeres, which are units made up of thin
Cerebral palsy is a disorder associated with pro- actin and thick myosin protein filaments that are
found muscle weakness (Elder et al. 2003). The anchored together by noncontractile proteins
low force production is associated with muscles called Z disks.
that are smaller (Elder et al. 2003; Johnson et al. Force is generated by skeletal muscle with
2009; Modlesky et al. 2010), have abnormal fibers arranged in a longitudinal or pennate fash-
architecture (Mohagheghi et al. 2008; Shortland ion (Fig. 2). Muscle fibers arranged in a pennate
et al. 2002), and have a higher concentration of fat fashion are generally at a 0–30 angle relative to
(Johnson et al. 2009; Noble et al. 2014a; Whitney the force generation axis. Most muscles are con-
et al. 2017) and collagen (Booth et al. 2001) than sidered multipennate because their fibers are
expected with typical development. The restricted arranged at different angles relative to the force-
muscle growth and development during child- generating axis (Lieber 2002; Wickiewicz et al.
hood and adolescence likely reflects the muscle, 1983). Muscle fibers arranged in a longitudinal
movement, and physical activity profile in adult- fashion run parallel to the force generating axis
hoods with CP and increases the risk of develop- (Wickiewicz et al. 1983).
ing chronic diseases (Peterson et al. 2012). In this
chapter, we will review: (1) typical muscle growth
and development; (2) muscle growth and devel- Skeletal Muscle Size and Architecture
opment in children with CP compared to typically in Typically Developing Children
developing children; (3) muscle assessment tech-
niques; (4) factors that contribute to the muscle Clearly, muscle size increases during childhood
growth and development deficits in children and and adolescence (Xu et al. 2009). Positive rela-
adolescents with CP; (5) potential treatment strat- tionships with age suggest that anatomical muscle
egies; and (6) future directions for research. cross-sectional area (CSA) (Kanehisa et al. 1995),
physiological CSA (pCSA) (O’Brien et al. 2010a, b),
thickness (Maurits et al. 2004), type I and II fiber
Natural History CSA (Lexell et al. 1992; Verdijk et al. 2014),
proportion of type II fibers (Lexell et al. 1992),
Muscle Anatomy and Typical Muscle and number of fibers per fascicle (Sjostrom et al.
Growth and Development 1992) all increase during childhood and adoles-
cence. There is also evidence that some of the
Skeletal muscle is the force producing tissue that architectural properties of muscle also change
attaches to bone via tendons and is necessary for during childhood and adolescence. Compared to
physical movement. A summary of skeletal mus- adults, children have shorter muscle fascicles
cle and its components is presented in Fig. 1. (Shortland et al. 2002). However, change in
Skeletal muscle, like some other tissues, is other aspects of muscle architecture during child-
surrounded by dense connective tissue referred hood and adolescence, such as muscle fascicle
to as deep fascia. The epimysium is a muscle- angle, is less certain. There is evidence that
17 Muscle Size, Composition, and Architecture in Cerebral Palsy 255
Fig. 1 Overview of skeletal muscle morphology and include the deep fascia, epimysium, muscle belly, muscle
architectural features. The plantar flexor skeletal muscles, fascicles, perimysium, muscle fibers, myofibrils, sarco-
their tendons, and a breakdown of their components in the meres actin, myosin, and z-disks. (Figure created by Karlee
gastrocnemius are highlighted. The primary components Diane Rogers)
Fig. 2 A review of the

different arrangements of
skeletal muscle fibers.
Skeletal muscles fibers can
be arranged in a pennate
(a) or longitudinal
(b) fashion. In the pennate
arrangement, the fibers and
fascicles attach to the
aponeurosis at an angle (α)
ranging from 0 to 30 . In the
longitudinal arrangement,
the fibers and their
associated fascicles run
along the length of the
muscle
muscle fascicle angle in the gastrocnemius muscles remains constant from childhood through
increases with age from childhood to adulthood adulthood.
and thereafter it is constant (Binzoni et al. 2001). There is evidence that differences in muscle
However, the degree to which the angle increases between boys and girls become apparent during
during the growing years is debatable and the puberty. For example, there is no apparent sex
consistency of the increase is unclear. Some stud- difference in muscle CSA in children 7–12 years
ies suggest that gastrocnemius muscle fascicle of age. However, between 13 and 15 years of age,
angle does not change (Benard et al. 2011) or boys begin to gain muscle at a greater rate than
increases minimally (Legerlotz et al. 2010) during girls, which continues throughout adolescence
4–12 years of age. It is also plausible that changes (Kanehisa et al. 1995). Whether there is a
in muscle fascicle angle are joint angle dependent sex-effect in other aspects of muscle, and when
(Shortland et al. 2002). One study found a signif- they may emerge, requires further investigation.
icantly ( p < 0.05) smaller muscle fascicle angle in
the gastrocnemius of children compared to adults
at an ankle joint angle of 30 of plantar flexion Skeletal Muscle Size, Composition, and
(Shortland et al. 2002). Although muscle fascicle Architecture in Children with CP
angle was smaller at all other joint angle ranges
studied (ranged from maximum plantar flexion to Most of our understanding about the effect of CP
maximum dorsiflexion) in the children, the differ- on muscle size, composition, and architecture is
ences were not statistically significant. The lack of via cross-sectional comparison studies between
statistical significance at other joint angles may be children and adolescents with CP and their typi-
the result of the very small sample sizes included cally developing peers. In addition to inherent
in the study (n = 5/group). Studies by O’Brien limitations associated with cross-sectional stud-
et al. (2010a, b) observed no differences in fasci- ies, many of the studies examining muscle prop-
cle angle for any of the quadriceps muscles in erties in children with CP had very small sample
males vs. females or adults vs. children. There- sizes. Furthermore, many of the studies did not
fore, it is possible that fascicle angle for some necessarily match children with CP with typically
developing control children. This likely contrib- the control leg, and that the posterior compart-
utes to the inconsistency in some study results. ment muscle volume for the same leg was about
Nonetheless, the available studies demonstrate 72% of the control leg. Bandholm et al. (2009)
remarkable deficits in many aspects of muscle in reported 32% lower CSA of the dorsiflexor mus-
individuals with CP. cles in the hemiplegic leg vs. the unaffected (or
Most studies examining muscle size in chil- less affected) leg of children with
dren with CP have focused on the lower extrem- hemiplegic CP.
ities. When compared to typically developing Pitcher et al. (2018) found 30–40% lower
children, children with CP have smaller muscles medial gastrocnemius, lateral gastrocnemius,
as reflected by lower CSA, volume, mass, and soleus, and triceps surae muscle CSA and
belly length. It has been reported that mid-thigh 26–55% lower gastrocnemius, soleus, triceps
muscle mass is approximately 50% lower in chil- surae, and tibialis anterior muscle volume in a
dren with quadriplegic CP who are unable to small sample of ambulatory children with spastic
ambulate (i.e., Gross Motor Function Classifica- diplegic CP and level II on the GMFCS scale
tion Scale, GMFCS IV-V) or only able to ambu- (n = 7; 5–12 years) when compared to typically
late with assistance (i.e., GMFCS III) than developing children (n = 19). Although a similar
typically developing children (Modlesky et al. pattern was observed in children with CP at level I
2010). Similarly, it has been shown that on the GMFCS scale (n = 10), none of the differ-
mid-thigh muscle CSA is approximately 50% ences in CSA were statistically significant. More-
lower in children with quadriplegic CP (GMFCS over, the magnitude of the difference in muscle
III-V) than in typically developing children volume was generally smaller, and only the
matched to children with CP for age, sex, and soleus, tibialis anterior, and triceps surae differ-
sexual maturity and not different from the 50th ences were statistically significant ( p < 0.05).
age- and sex-based percentiles for height and It is not clear if there is a size deficit in the
body mass (Johnson et al. 2009). muscles of the unaffected (or less affected) side in
The effect of CP on muscle size is not limited children with hemiplegic CP. Using magnetic res-
to nonambulatory children with CP. Ambulatory onance imaging (MRI), Elder et al. (2003) found
children with CP also have notable muscle-size no significant difference in the volume or CSA of
deficits. For example, a recent study (Whitney the anterior or posterior compartment and CSA of
et al. 2017) reported 39% lower mid-leg muscle the soleus in the unaffected leg of hemiplegic
volume in ambulatory (GMFCS I-II) children children with CP compared to typically develop-
with spastic CP compared to typically developing children. In a study of children with spastic
ing children (n = 12/group) matched to children hemiplegic CP compared to typically developing
with CP and not different from the 50th age- and children, Malaiya et al. (2007) reported no differ-
sex-based percentiles for height, body mass, and ences in gastrocnemius muscle volume between
body mass index. There is evidence that the the unaffected leg in children with hemiplegic CP
muscle size deficit is greater in the affected (or and the leg of typically developing children. A
more affected) side in children with hemiplegic third study (Obst et al. 2017) also found that
CP than in children with diplegic CP (Barber absolute volume of the gastrocnemius was not
et al. 2011). Lower muscle CSA (Bandholm different in the unaffected leg of ambulatory
et al. 2009; Elder et al. 2003) and muscle vol- (GMFCS I and II) children with hemiplegic CP
ume (Elder et al. 2003; Fry et al. 2007; Malaiya compared to controls. However, the children with
et al. 2007) have also been reported in the ante- CP tended to be older (average 1.4 years;
rior and posterior compartments of the leg in p = 0.065). When the muscle volume was nor-
mildly-to-moderately affected children with malized for height and body mass, the gastrocne-
hemiplegic or diplegic CP. Elder et al. (2003) mius volume was smaller in the unaffected leg of
reported that the anterior compartment muscle children with hemiplegic CP compared to
volume in the hemiplegic leg was about 73% of controls.
Most studies suggest that compared to typi- anterior muscle belly, children with spastic diplegic
cally developing children, the muscles in children CP and GMFCS level II also had shorter medial and
with CP are not as thick. When compared to the lateral gastrocnemius muscle bellies (12 and 15%,
unaffected leg, it has been reported that muscle p < 0.05).
thickness is ~20% lower in the gastrocnemius The deficits in muscle size are greater distally
(Mohagheghi et al. 2007) and the dorsiflexor mus- than proximally. For example, in one study muscle
cles (Bandholm et al. 2009) in the affected leg of volume of the hemiplegic side was 72% of the
children with hemiplegic CP. Studies have unaffected side at the leg compared to 84% at the
reported 30% lower muscle thickness of the rectus thigh in a study of adolescents and young adults
femoris and vastus lateralis in children and young with hemiplegic CP (Lampe et al. 2006). Similarly,
adults (7–19 years) with spastic CP and GMFCS another study reported greater side-to-side muscle
I-IV compared to a typically developing compar- volume deficits in the dorsiflexors and plantar
ison group (Moreau et al. 2012, 2009). The deficit flexors than in the quadriceps and hamstring mus-
in muscle thickness is linked to the severity of cles in adolescents and young adults with spastic
CP. For example, a 27% thinner quadriceps hemiplegic CP (Riad et al. 2012). This is consis-
femoris has been reported in children with severe tent with the finding of Noble et al. (2014b), who
forms of CP (GMFCS V) compared to children reported average muscle deficits of ~28% in nine
with moderate-to-severe forms (GMFCS III-IV) major lower extremity muscles of 10–24-year-old
(Ohata et al. 2009). Furthermore, annual assess- individuals with diplegic CP compared to non-CP
ments for three consecutive years suggest that the controls, with the average deficit greater in the leg
increase in muscle thickness is more restricted in muscles than in the thigh muscles. Moreover, the
children with severe than moderate-to-severe largest deficit was in the medial gastrocnemius
forms of CP (Ohata et al. 2009). This notion is (38% lower) and the smallest deficit was in the
supported by a recent study (Kruse et al. 2018) that vastus intermedius + vastus lateralis (8% lower).
attributed the lack of difference in gastrocnemius In addition, a study of children with hemipelgic
muscle thickness between a small group of ambu- and diplegic CP compared to typically developing
latory children with spastic diplegic CP (GMFCS children suggests that there is considerable hetero-
I-II; n = 10) and a small group of controls to the geneity in the muscle volume deficits of children
mild form of the disorder in the children with CP with CP with the gluteus minimus, quadratus
they studied. femoris, iliacus semitendinosus, and vastus
Muscle belly length is poorly studied in children lateralis being the most heterogeneous muscles
with more severe forms of CP. However, there is (Handsfield et al. 2016).
consistent evidence that children with hemiplegic In addition to their small muscle size, children
(Malaiya et al. 2007) and diplegic (Fry et al. 2007; with CP also have a high concentration of non-
Kruse et al. 2018; Pitcher et al. 2018) CP have a contractile tissue. A two to threefold higher concen-
shorter muscle belly length than typically develop- tration of intermuscular fat has been observed in the
ing children. It has been found that medial gastroc- thigh of children with quadriplegic CP (Johnson
nemius muscle belly length normalized to fibular et al. 2009) (Fig. 3). Higher concentrations of intra-
length is 12–19% shorter in children with spastic muscular and intermuscular fat have also been
diplegic CP than typically developing children (Fry reported in the leg muscles of ambulatory children
et al. 2007; Kruse et al. 2018). There is also evi- with spastic CP (Whitney et al. 2017). Moreover,
dence that the degree of muscle belly shortness is higher intermuscular fat in the leg muscles has been
dependent on the level of involvement in observed in young adults with spastic CP. Of the
CP. Specifically, Pitcher et al. (2018) reported that five lower limb muscles studied (i.e., medial and
the tibialis anterior muscle belly was shorter in lateral gastrocnemius, soleus, tibialis posterior, and
children with spastic diplegic CP and GMFCS tibialis anterior), the most pronounced infiltration of
level I compared to typically developing children. fat was in the soleus (Noble et al. 2014a). There may
However, in addition to having a shorter tibialis also be a higher concentration of collagen in the
Fig. 3 Magnetic resonance images of the mid-thigh dem- (i.e., subcutaneous, subfascial, and intermuscular); b and
onstrate the high degree of adipose tissue infiltration of e contain only subfascial and intermuscular adipose tissue;
muscle in the mid-thigh of a prepubertal girl with quadri- and c and f only contain intermuscular adipose tissue
plegic CP (a-c) compared to a typically developing prepu- (Johnson et al. 2009)
bertal girl (d-f). A and D contain all layers of adipose tissue
muscle of children with spastic CP. A positive rela- Studies that have examined the effect of CP
tionship between hydroxyproline concentration in on measures of muscle architecture have yielded
the vastus lateralis and measures of spasticity and inconsistent results. Most of these studies have
balance in children with mild to moderate forms of focused on the gastrocnemius. No difference in
CP has been reported (Booth et al. 2001). The (Barber et al. 2011; Malaiya et al. 2007; Shortland
collagen concentration seems to be high in the et al. 2004, 2002), lower (Kruse et al. 2018), and
endomysium around the myofibers near the basal higher fascicle length and no difference in (Barber
lamina. et al. 2011; Malaiya et al. 2007; Shortland et al.
The compositional differences in the muscles of 2002), lower, and higher (Kruse et al. 2018) fasci-
children with CP may not be limited to the muscles cle angle have been reported in children with CP
that are primarily affected. For example, higher and compared to typically developing children. It has
more heterogeneous echo intensity has been been suggested that the inconsistency in studies
observed in the gastrocnemius of the affected and may be related to the joint angle at which muscle
unaffected limbs in children with hemiplegic CP fascicle length and angle were measured. For
(Obst et al. 2017). In addition, there is evidence of example, some studies assessed muscle fascicle
fewer satellite cells in the muscles of children with length and angle while the ankle joint was in a
CP and contractures compared to the muscles of resting position. This may be problematic because
typically developing children (Smith et al. 2013). the ankle joint tends to be more plantar flexed in
These findings of atypical muscle composition in children with CP than in typically developing chil-
children with CP may help explain the decreased dren. Muscle fascicle angle increases and muscle
longitudinal growth of the muscles in children with fascicle length decreases as the degree of plantar
CP and the development of uncontrolled muscle flexion increases (Barber et al. 2011). This idea is
contractures. supported by a study of a combined sample of 2–5-
year-old children with hemiplegic and diplegic For example, the physiological CSA of the plantar
spastic CP in which fascicle angle and fascicle flexors and dorsiflexors are strongly related to
length of the medial gastrocnemius were not dif- muscle force (Fukunaga et al. 1996). In addition,
ferent when compared to typically developing chil- a higher concentration of intramuscular fat is asso-
dren with the ankle at the resting angle. On the ciated with lower muscle strength (Goodpaster
other hand, children with CP had a smaller fascicle et al. 2001). Although muscle properties, such as
angle and a greater fascicle length with the ankle at size, are not as predictive of muscle strength in
the maximal plantar flexion position (Barber et al. children with CP as they are in typically develop-
2011). However, inconsistency is also present ing children (Reid 2015), they are reasonable pre-
when muscle fascicle length and angle are assessed dictors, and assessment is still important. The
at a set ankle joint angle suggesting that there are following techniques can be used to assess muscle
other, unexplained, underlying issues. size, composition, and architecture in vivo.
It is also possible that the presence or absence Magnetic resonance imaging is a gold standard
of a muscle architecture difference between indi- method for providing measures of muscle size, such
viduals with and without CP is muscle dependent. as muscle CSA, volume, and mass (Mitsiopoulos
One study reported no differences in fascicle et al. 1998). A major advantage of MRI is it does
angles in the rectus femoris of children with CP not involve exposure to ionizing radiation, as
compared to typically developing children when does computed tomography, another method
rested in supine position (Moreau et al. 2009). that provides accurate estimates of muscle size.
However, the same study also found that the aver- As a result, there is less concern about scanning
age fascicle angle for the vastus lateralis muscle multiple sites of the body. Other muscle measures
was 3 lower in children with CP than in typically that can be acquired with MRI include muscle
developing children. Other potential reasons for belly length, intermuscular and subfascial adi-
the inconsistency in studies of muscle architecture pose tissue CSA, volume and mass (Johnson
in individuals with CP include the heterogenetic et al. 2009; Whitney et al. 2017), intramuscular
levels of gross motor function of the children fat concentration (Noble et al. 2014a; Whitney
within each study and the poor matching of chil- et al. 2017), muscle stiffness (Dresner et al. 2001),
dren with CP to typically developing children. For and muscle fiber CSA, number and type (Damon
example, in the studies that reported no difference et al. 2002; Noehren et al. 2015; Scheel et al.
in fascicle length between children with CP and 2013). The main disadvantages associated with
typically developing children, children with CP MRI are the high expense, the technical expertise
tended to be older (average ~ 10 years of age vs. required, the small space within which the MRI
~ 8 years of age; though not statistically signifi- images are acquired, the noisy environment, and
cant) (Malaiya et al. 2007; Shortland et al. 2004, the potential involuntary movement associated
2002). The age difference may have masked the with spasticity and behavior issues. To minimize
shorter fascicle lengths in children with CP movement, sedation (Englander et al. 2015) and
because muscle fascicle length increases with immobilization using restraining straps (Bandholm
age (Benard et al. 2011; Binzoni et al. 2001). et al. 2009), bracing (Elder et al. 2003), or vacuum
The small number of children with and without pressure (Johnson et al. 2009; Modlesky et al.
CP in studies of muscle architecture may also 2008, 2009, 2015; Whitney et al. 2017) have
contribute to inconsistent results. been used.
Computed tomography, like MRI, provides
accurate estimates of muscle size, such as muscle
Assessing Muscle in Children with CP CSA and volume (Mitsiopoulos et al. 1998). It
also provides estimates of the fat concentration of
Measures of muscle size, composition, and archi- muscle (Goodpaster et al. 2000). The main disad-
tecture provide useful information about the force vantage associated with computed tomography is
generating capacity and function of the muscle. that it involves exposure to ionizing radiation. The
concern can be minimized by collecting single Fortunately, recent evidence suggests DXA can
images at a single site. However, a single image provide accurate estimates of muscle mass if algo-
provides limited information about the entire mus- rithms developed using children with CP are
cle. Furthermore, the use of computed tomogra- applied (Zhang et al. 2018). It can also be difficult
phy in the assessment of muscle architecture has to collect DXA scans in children with CP due to
not been demonstrated. excessive movement. Movement artifact can lead
Ultrasound can be used to assess muscle CSA to unpredictable estimates of fat-free soft tissue
(Noorkoiv et al. 2010), volume (Macgillivray mass (Koo et al. 1995). Assistance from an expe-
et al. 2009), and thickness (Ohata et al. 2008). It rienced DXA operator or the use of a vacuum
can also provide measures of muscle belly length pressure system can also minimize movement
(Fry et al. 2004), muscle fascicle length during DXA scans in children with CP (Modlesky
(Shortland et al. 2002), and muscle fascicle et al. 2010; Whitney et al. 2019) without
angle (Shortland et al. 2002), as well as muscle impacting fat-free soft tissue measurements
stiffness (Brandenburg et al. 2014). There is some (Rawal et al. 2011).
evidence that ultrasound may provide estimates of
the fat concentration within muscle (Young et al.
2015). The primary advantage of ultrasound is Factors Contributing to Atypical
that images can be acquired without exposure to Muscle Growth and Development in
ionizing radiation or without enclosure in a small Children with CP
space. One disadvantage of ultrasound is that the
measurements are operator dependent, which has A number of factors associated with the level of
led some to question its reliability. However, very muscle deficit in children with CP, such as gross
good reliability has been demonstrated for the motor function, ambulatory status and type of CP
assessment of muscle using ultrasound (Kwah (i.e., hemiplegic vs. diplegic vs. quadriplegic),
et al. 2013). have already been discussed. Several additional
Dual-energy X-ray absorptiometry (DXA) can factors may also be associated with the muscle
be used to estimate muscle mass from fat-free soft deficits of children with CP.
tissue or lean tissue mass in the total body, and at
appendicular and nonappendicular sites. The
advantages of DXA are that scans of the entire Physical Activity
body are fast and assessment of the total body and
specific regions is not complicated. Dual-energy An obvious factor associated with the muscle
X-ray absorptiometry has been used to show that deficits in children with CP is low participation
fat-free mass, the body component within which in physical activity. Children with CP have
muscle mass is housed, is lower at all GMFCS 40–80% lower physical activity counts than typ-
levels in children with CP than in typically devel- ically developing children (Johnson et al. 2009;
oping children (Oftedal et al. 2017; Whitney et al. Whitney et al. 2017). Children with CP who are
2019). Disadvantages of DXA include the inabil- independent ambulators (GMFCS I-II) or who
ity to assess individual muscles, intramuscular fat, ambulate with assistance (GMFCS III) take ~
or muscle architecture. Another disadvantage of 40% fewer steps than typically developing chil-
using DXA to assess muscle mass is that fat-free dren (Bjornson et al. 2007). There is evidence
soft tissue mass, not muscle mass, is estimated. that lower participation in physical activity is
This can lead to overestimates of muscle mass if associated with lower muscle quality in children
algorithms developed using typically developing with CP. Specifically, the amount of
children are applied to children with CP because intermuscular fat CSA relative to muscle CSA
children with CP compared to typically develop- in the thigh is greater children with CP who
ing children have a low concentration of muscle in participate in less physical activity (Fig. 4)
the fat-free soft tissue (Modlesky et al. 2010). (Johnson et al. 2009).
0.2 SNARE complex, facilitating the transport of ace-

CP (n = 12) tylcholine through the neuronal membrane and into
IMAT CSA/Muscle CSA
Controls (n = 12)
the neuromuscular junction. Without acetylcholine,
muscle contraction is inhibited. Despite its wide-
0.1 spread use, there is some concern that botulinum
toxin A causes a decline in the volume (Warner
et al. 2006) and architectural properties (Booth
et al. 2001; Fortuna et al. 2013) of muscle. For
0 example, C57BL/6 mice injected with botulinum
0 200 400 600 800 1000 toxin A vs. saline had a 47% and 60% reduction in
Physical Activity (counts sqrt) quadriceps and calf muscle mass, respectively, after
21 days (both p < 0.001) (Warner et al. 2006). In a
Fig. 4 Scatter plot of transformed total physical activity
counts from an activity monitor worn on the hip vs. the study of ambulatory children with CP (GMFCS
ratio of intermuscular adipose tissue (IMAT) cross- I-II), a 4.5% loss in the gastrocnemius muscle vol-
sectional area (CSA) to muscle CSA in the mid-thigh of ume but a 4% rise in soleus muscle volume was
children with quadriplegic cerebral palsy (r = 0.76,
observed 6 months after bilateral botulinum toxin
p < 0.01) and typically developing children (r = 0.19,
p = 0.56). (Modified from Johnson et al. (2009)) A treatment of the gastrocnemius (Williams et al.
2013b). A similar pattern of muscle volume change
Muscle Spasticity following botulinum toxin treatment has been
reported by others (Alexander et al. 2018; Barber
Muscle spasticity is another factor that may sup- et al. 2013). Animal studies suggest that botulinum
press muscle growth in children with CP. Using a toxin A may also cause a decrease in contractile
mouse model, it was suggested that muscle and protein and an increase fat infiltration of the treated
tendon size in CP model develop at a much slower muscle (Fortuna et al. 2013). There is evidence that
rate for spastic muscles when compared to controls the muscle decline may be offset when botulinum
(Ziv et al. 1984). Interestingly, it has been shown toxin A is combined with strength training (Wil-
that spastic muscle fibers are not only shorter but liams et al. 2013a), but more research is needed.
also stiffer than normal cells as determined by
mechanical testing (Friden and Lieber 2003).
This is consistent with the finding that spasticity Surgery
is associated with increased collagen content accu-
mulation (Booth et al. 2001) and stiffer extracellu- It is possible that surgical recession of the gastroc-
lar matrix (Smith et al. 2011). A reduced satellite nemius (Fig. 5) suppresses muscle growth in chil-
cell population has also been found in spastic mus- dren with CP. One study (Fry et al. 2007) reported
cles in children with CP (Smith et al. 2013). Over- that medial gastrocnemius muscle volume was
all, it seems that spasticity is associated with lower and belly length was shorter in children
stunted muscle growth, reduced muscle plasticity, with diplegic CP than in typically developing chil-
and less potential for muscle development. dren before surgery.
Recession of the gastrocnemius led to a slight
decrease in muscle volume ( p = 0.052) and belly
Medications length ( p = 0.026) approximately 7 weeks after
surgery. By 12 months postsurgery, muscle vol-
Botulinum toxin A, which is obtained from anaer- ume increased beyond the presurgical measure-
obic, gram negative bacteria called Clostridium ment but muscle belly length did not change.
botulinum, is widely used as a treatment for spas- Muscle belly length relative to fibular length
ticity in patients with CP (Jefferson 2004). The drug decreased, however, suggesting there may have
is typically injected into the affected muscle where been a suppression of expected growth in muscle
it cleaves SNAP-25, a protein that is part of the length. Results from another study of ambulant
Fig. 5 The leg muscles

before (a) and after (b) a
gastrocnemius recession
children with CP suggest that surgical recession children with CP is strongly encouraged
may also lead to a decrease in muscle fascicle (Damiano 2006). Current studies provide prelim-
length, the degree of which is variable, ranging inary evidence that muscle morphology and archi-
from essentially none to more than 40% tecture adapt to resistance training in children and
(Shortland et al. 2004). Considering the small adolescents with CP. For example, a randomized
sample sizes in these two studies (Fry et al. 2007 controlled trial examined the effect of functional
and Shortland et al. 2004; 10/group), additional resistance training on muscle architecture in chil-
studies are needed to confirm the effect of surgical dren with CP and a GMFCS I–III. Six weeks of
recession on muscle and the potential long-term functional training (3 d/wk for 30 min/day) that
consequences in children with CP. included loaded (5% of body weight, followed by
progressive increases) sit-to-stand, lateral step-up,
and half knee rise led to increases in quadriceps
Treatment femoris muscle thickness, rectus femoris muscle
CSA, and medial gastrocnemius fascicle angle
A number of treatments could potentially aid in (Lee et al. 2015). A review of the literature
the growth and development of muscle in children found that resistance training leads to muscle
with CP. The adoption of resistance training and hypertrophy in children and adolescents with
intense physical activity in therapy programs for CP; however, studies examining the effect of
resistance training and intense physical training Compromised nutrition has been linked to
on muscle composition and architecture are stunted growth in children with CP (Stallings
lacking. Furthermore, low methodological study et al. 1993, 1995; Stevenson et al. 1994). There-
quality (i.e., lacking randomized controlled trials), fore, nutritional interventions may also aid in
heterogeneity of the training programs, inconsis- addressing muscle deficits in children with CP
tent outcome measures, and a lack of appropriate (Verschuren et al. 2018). Nutritional interventions
control groups makes interpretation of the current that offer the greatest promise include protein,
studies difficult (Gillett et al. 2016). As a result, it essential amino acids, and vitamin D, especially
was concluded that caution needs to be taken when if combined with resistance training or physical
interpreting the relative results. More high quality activity (Verschuren et al. 2018); however, future
research studies are needed before definitive conclu- studies are needed to assess their effectiveness.
sions can be drawn and specific recommendations
can be made.
Vibration has recently emerged as a potential Summary
treatment for muscle deficits in children with
CP. Some studies of groups without CP suggest In summary, when compared to typically devel-
that vibration treatment improves muscle mass oping children, children with CP have smaller
(Gilsanz et al. 2006), strength (Leung et al. muscles that are infiltrated with fat and collagen,
2014; Reyes et al. 2011), and coordination which contribute to significant muscle weakness.
(Leung et al. 2014). While vibration treatment The deficit is greatest in children with more
may be beneficial to muscle in other involved forms of the disorder, but it is present
populations, few studies have specifically even in milder forms. The more distal muscles are
looked at its effect on muscle in children with particularly small. There is also considerable het-
CP. Among the available studies, Wren et al. erogeneity in muscle size deficits suggesting that
(2010) randomized children with CP (GMFCS each child with CP has a unique muscle profile
I-IV) to either stand on a plate that emits a high- that is more difficult to predict than the profile of
frequency, low-magnitude vibration (30 Hz, typically developing children. Whether muscle
0.3 g) or on the floor at home 10 min/day for fascicle angle and length are altered in children
6 months. Children then swapped their condition with CP is unclear. The controversy may be
for another 6 months (i.e., children who stood on related to methodological differences between
the vibration plate now stood on the floor and studies, joint angles at which the muscles were
vice versa). There were no significant increases evaluated, and small sample sizes. Therefore,
in leg muscle area in the children in the standing additional studies with designs that take these
or standing + vibration conditions. On the other factors into consideration are needed. In vivo
hand, another randomized controlled trial that techniques can be used to assess muscle size,
included a higher magnitude stimulus, a lower composition, and architecture in children with
frequency (range = 5–25 Hz), and multiple CP, and all have strengths and weaknesses. Ultra-
3 min bouts of treatment reported significantly sound may offer the greatest promise because it
greater increases in thickness of the tibialis ante- has wide availability, it does not pose significant
rior (31 vs. 2%, p = 0.001) and soleus (40 vs. safety issues, it can be used in a comfortable
2%, p = 0.001), but not the gastrocnemius, in setting, and it is very flexible. Specifically, it can
children with CP treated with vibration + con- be used to assess muscle size, composition, and
ventional physical therapy vs. children who only architecture. Potential contributors to the muscle
received conventional physical therapy (Lee and deficits in children with CP include ambulatory
Chon 2013). Further studies are needed to con- status, type of CP, physical inactivity, muscle
firm the findings from these studies and to deter- spasticity, medications, such as botulinum toxin
mine if continued vibration treatment is needed A, and surgical procedures, such as surgical reces-
to maintain the positive changes in muscle. sion of the gastrocnemius. More research is
needed to determine some of their specific contri- Barber L, Hastings-Ison T, Baker R, Barrett R, Lichtwark
butions. Treatment strategies that include resis- G (2011) Medial gastrocnemius muscle volume and
fascicle length in children aged 2 to 5 years with cere-
tance training, vibration, and nutrition bral palsy. Dev Med Child Neurol 53(6):543–548
intervention may be effective; at improving the Barber L, Hastings-Ison T, Baker R, Kerr Graham H,
size, composition, and architectural properties of Barrett R, Lichtwark G (2013) The effects of botulinum
muscle in children with CP however, additional toxin injection frequency on calf muscle growth in young
children with spastic cerebral palsy: a 12-month prospec-
studies are needed before specific recommenda- tive study. J Child Orthop 7(5):425–433
tions can be made. Benard MR, Harlaar J, Becher JG, Huijing PA, Jaspers RT
(2011) Effects of growth on geometry of gastrocnemius
muscle in children: a three-dimensional ultrasound
analysis. J Anat 219(3):388–402
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Bone Size, Architecture, and Strength
Deficits in Cerebral Palsy 18
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 270
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 270
Bone Anatomy and Typical Bone Growth and Development . . . . . . . . . . . . . . . . . . . . . . . . . . 270
Bone Growth and Development in Children with CP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 272
High Rate of Fragility Fractures in Children with CP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 274
Assessing Bone in Children with CP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 274
Factors Contributing to Atypical Bone Growth and Development in Children
with CP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275
Gross Motor Function and Physical Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275
Muscle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 275
Nutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 276
Medications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 276
Bone Health in Adults with CP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 277
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 279
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 280
Abstract strains on the skeleton due to the increasing

Childhood and adolescence are the most weight of the growing body and the increasing
important periods of bone development. The muscle forces produced during physical activ-
bones experience an increase in size, an accre- ity. Children with cerebral palsy (CP) tend to
tion of mineral, a change in architecture, and an have smaller bones, lower areal bone mineral
increase in strength that accommodate greater density, and less developed bone architecture
compared to typically developing children,
which contributes to their much weaker bones
C. M. Modlesky (*) · C. Zhang and higher risk for fracture. In this chapter, we
Department of Kinesiology, University of Georgia, will review how deficits in bone that emerge
Athens, GA, USA
during the growth and development of children
e-mail: christopher.modlesky@uga.edu

https://doi.org/10.1007/978-3-319-74558-9_15
with CP contribute to their high rate of fragility techniques, fractures in children with CP, factors
fractures. We will also review methods of bone that contribute to atypical bone growth and devel-
assessment, factors that contribute to the poor opment in children with CP, bone health in adults
bone development in children and adolescents with CP, and potential treatment strategies.
with CP, bone health in adults with CP, and
potential treatment strategies.
Natural History
Keywords
Cerebral palsy · Bone structure · Bone Bone Anatomy and Typical Bone
strength · Fracture · Unloading Growth and Development
We will focus on long bone anatomy and typical

Introduction bone growth and development in this section
(Fig. 1). A long bone, such as the femur, consists
During childhood and adolescence, there is a tre- of wide extremities at the proximal and distal ends
mendous growth and development of the bones of the bone (epiphyses), a cylindrical tube in the
that comprise the skeleton (Heaney et al. 2000; middle (diaphyses), and developmental regions
Modlesky and Lewis 2002). It has been proposed between them (metaphyses). The metaphyses
that environmental factors have a considerable and epiphyses are separated by the epiphyseal
influence on the bone changes that occur during (i.e., growth) plates which are responsible for the
this early period of life (Parfitt 1994). For exam- longitudinal growth of bone. Bone is encased by
ple, regular mechanical loading and adequate the periosteum, which consists of an inner layer of
nutritional intake are necessary to facilitate the bone cells and an outer fibrous layer of membrane
expected increases in mass and the changes in that lines the bone’s external surface via perforat-
composition and architecture of bone during the ing (Sharpley’s) fibers. It is at the external surface
first two decades of life (Heaney et al. 2000; where bone tissue is added to increase the width of
Modlesky and Lewis 2002). Because of their the bone. This ability to increase its width allows
issues with movement and posture, children with the bone to accommodate larger loading that pro-
cerebral palsy (CP) do not have the same level of gressively occurs during growth. The endosteum
mechanical loading as typically developing chil- is similar to the periosteum except it lines the
dren (Bjornson et al. 2007; Johnson et al. 2009; medullary cavity, which is the internal surface of
Modlesky et al. 2009). Furthermore, some chil- the bone’s diaphysis. In between the periosteum
dren with CP do not receive the same nutritional and endosteum is densely packed compact
intake (Henderson et al. 1995, 2002a). As a result, (or cortical) bone tissue on the periosteal side
atypical bone growth and development are com- and a thin layer of spongy (or trabecular) bone
mon (Binkley et al. 2005; Henderson et al. 2002a; on the endosteal side. Cortical bone consists of
Modlesky et al. 2008, 2009, 2015; Whitney et al. osteons (Haversian systems), which are made up
2017) and the incidence of fragility, or low-energy, of concentric layers of lamellae through which
fractures is increased, especially in the lower blood vessels and nerve fibers run. Trabecular
extremity bones of children with CP who are non- bone, which is composed of a network of small
ambulatory (McIvor and Samilson 1966; Presedo trabecular structures (i.e., trabeculae), is much
et al. 2007). Poor bone growth and development more porous and metabolically active than corti-
during childhood likely carries through adulthood cal bone. In addition to lining the medullary cavity
and increases the risk of fractures later in life (Hea- in the diaphysis, trabecular bone is also highly
ney et al. 2000; Modlesky and Lewis 2002; Wren concentrated in the epiphysis and metaphysis
et al. 2014). In this chapter, we will review typical (Marks and Odgren 2002). Cortical and trabecular
bone growth and development, bone growth and bone contain osteocytes, which are former osteo-
development in children with CP, bone assessment blasts that become trapped within the bone during
18
Bone Size, Architecture, and Strength Deficits in Cerebral Palsy
Fig. 1 Overview of the anatomy of the femur, which is a long bone. The bone contains in the epiphyses and metaphyses. Cortical bone consists of osteons (Harversian sys-
an epiphysis at each end, a diaphisis in the middle and metaphyses between them. The tems), which are concentric layers of lamellae through which blood vessels and nerve
epiphyses and metaphyses are separated by the epiphyseal (growth) plate. The perios- fibers pass. Trabecular bone is composed of a network of small trabecular structures
teum lines the outer portion of the bone and the endosteum lines the medullary cavity. (i.e., trabeculae). Osteocytes are former osteoblasts that reside in lacunae within cortical
Between the periostem and endosteum are cortical (compact) and trabecular (spongy) and trabecular bone and communicate with other osteocytes via canaliculi.
bone. In addition to lining the medullary cavity, trabecular bone is highly concentrated Figure created by Karlee Diane Rogers
271
bone formation and repair and act as mechanore- Bone Growth and Development
ceptors that respond to strain. The osteocytes reside in Children with CP
in lacunae and communicate with other osteocytes
via projections called canaliculi (Cowin et al. 1995; There is a restriction in the growth and develop-
Martin et al. 2015; Weinbaum et al. 1994). ment of bone in children with CP. Bone length is
Bone modeling is the primary process that stunted as reflected by the 16% shorter bones
facilitates the growth and development of bone and 13% shorter height observed in children
during infancy, childhood, and adolescence with CP who are unable to ambulate (i.e.,
(Parfitt 1994). The activity of bone modeling is Gross Motor Function Classification,
carried out by chondrocytes, osteoblasts, and oste- GMFCS = IV-V) or are only able to ambulate
oclasts. The chondrocytes in the epiphyseal with assistance (i.e., GMFCS = III) compared to
(growth) plate develop and expand. The children with typical development (Krick et al.
chondrocytes that are close to the diaphysis attract 1996; Modlesky et al. 2009) and the >2 SD
osteoblasts and lead to the production of new shorter height than normative values in infants
bone. The activities of the chondrocytes and oste- with CP (Krick et al. 1996). In addition to
oblasts facilitate the elongation of bone until the shorter bones, children with CP have much
body matures and the epiphyseal plates fuse and lower areal bone mineral density (aBMD) and
stop producing new chondrocytes. During the bone mineral content in the distal femur (Hen-
modeling process, osteoclasts are also involved, derson et al. 2002a; King et al. 2003; Modlesky
but they are not necessarily coupled with the oste- et al. 2008), as assessed by dual-energy X-ray
oblasts. For example, as osteoblasts are working absorptiometry (DXA). Low aBMD has also
with chondrocytes to elongate the bone and to add been reported in the lumbar spine, though the
bone on the periosteal surface to increase the width discrepancy is not as marked. In children with
of the bone diaphysis, there is osteoclast activity CP and a GMFCS III-V, aBMD z-scores of 3.1
on the endosteal surface leading to an expansion of in the distal femur and 1.8 in the lumbar spine
the medullary cavity (Marks and Odgren 2002). have been reported (Henderson et al. 2002a).
Overall, there is greater osteoblast activity than The compromise was the largest in children
osteoclast activity during modeling, which leads who had the most severe motor deficits
to an increase in the thickness of the cortical walls (GMFCS V) and the smallest in the children
and the thickness of the trabeculae (Kirmani et al. with the least severe motor deficits (GMFCS
2009), as well as the size of the bones and the III) (Henderson et al. 2002a).
overall skeleton. Peak bone mass is reached during When the composition of bone in children with
the third decade of life (Heaney et al. 2000). CP is evaluated, it is clear that trabecular and
Bone remodeling, a secondary process during cortical bone are both compromised. Fewer tra-
growth and development, plays a much larger role beculae have been observed in the distal femur of
in the mature skeleton (Parfitt 1994). During bone children with CP and GMFCS III-V compared to
remodeling, osteoclasts and osteoblasts work typically developing children matched to children
closely together to replace old bone tissue with with CP for age, sex, and race (Modlesky et al.
new bone tissue (Langdahl et al. 2016). Osteo- 2008). Specifically, children with CP had 30%
cytes, although not directly involved in bone tis- lower trabecular bone volume, approximately
sue formation or resorption, play an important role 20% fewer trabeculae and 12% thinner trabeculae
in translating mechanical loading into biochemi- (Fig. 2). The underdevelopment of trabecular
cal signaling and thus help regulate the modeling bone becomes more pronounced with increasing
and remodeling processes (Bonewald and John- distance from the epiphyseal plate (Modlesky
son 2008). Throughout the growth period, bones et al. 2015).
change in size and shape to accommodate the Children with CP also have a much thinner
mechanical stimulation created by gravitational cortical shell in the shaft of the femur and tibia
forces and increased muscle action on bone. (Modlesky et al. 2009; Whitney et al. 2017;
18 Bone Size, Architecture, and Strength Deficits in Cerebral Palsy 273
Fig. 2 Magnetic resonance images taken immediately (b). Trabecular bone microarchitecture was evaluated on the
above the epiphyseal plate from the distal femur of a non- left side of each image (darker gray), which is the lateral
ambulatory 10-year-old boy with CP (a) and a typically aspect of the distal femur. Binarized images show that
developing boy of the same age and at approximately the trabecular bone microarchitecture was markedly underdevel-
50th age- and sex-based percentiles for height and body mass oped in the child with CP (c) relative to the control child (d)
Binkley et al. 2005). In a study of 8-to-12 year old There is evidence that there is no compromise
children with CP and GMFCS III-V, the femoral in the material density of bone in children with CP
shaft was almost 30% thinner compared to typi- and it may even be higher in children with CP than
cally developing children matched to children in typically developing children at greater cortical
with CP for age, sex, and race and were not widths (Binkley et al. 2005). However, aBMD
different from the 50th percentile for height and assessed by DXA is lower in children with CP
body mass index (Modlesky et al. 2009) Children than in children with typical development (Hen-
with CP also had 50–60% lower total and cortical derson et al. 2002a; Modlesky et al. 2008). The
bone volume (Fig. 3) and 60–70% lower bone lower aBMD is a reflection of the smaller bones in
strength in the midfemur than the typically devel- children with CP. Interestingly, children with CP
oping children. Although the deficit is not as also have a higher concentration of fat in their
pronounced, another study found that ambulatory bone marrow (Whitney et al. 2017), which may
(GMFCS I-II) children with CP also have lower indicate a greater propensity of mesenchymal
cortical bone volume and bone width in the tibial stem cells to form adipocytes rather than osteo-
shaft, which results in 30–40% lower bone blasts due to the limited mechanical loading asso-
strength (Whitney et al. 2017). ciated with CP (Luu et al. 2009).
Fig. 3 Magnetic resonance images of the midsection of mass index (b). The black ring in the middle of each
the femoral shaft from a nonambulatory 9-year old boy image (see arrow) represents the cortical bone. Notice
with quadriplegic CP (a) and a typically developing boy of that the bone is much thinner and smaller in the child
the same age and at approximately the 50th age and with CP
sex-based percentiles for height, body mass, and body
High Rate of Fragility Fractures in Assessing Bone in Children with CP

Children with CP
Areal bone mineral density assessed by DXA is
Due to the atypical growth and development of the single best measure used to assess fracture risk
bone in children and adolescents with CP, fra- that is widely available (Genant et al. 1996) and it
gility fractures are a significant complication. has been shown to predict fracture in the distal
Fractures are most common in children with femur of children and adolescents with CP and a
CP who have the most limited mobility; they GMFCS III-V (Henderson et al. 2010). On the
occur in approximately one quarter of children other hand, aBMD is an imperfect surrogate of
with CP with a GMFCS III-V and >10 years of bone strength and fracture risk, especially in chil-
age (Henderson et al. 2002a). Repeat fractures dren. Moreover, there is a significant overlap in
are often experienced later in life (Henderson aBMD from DXA in those who do and do not
1997; Lee and Lyne 1990; McIvor and Samilson fracture (Ciarelli et al. 2000; Kleerekoper et al.
1966). Most fractures in children with CP occur 1985; Majumdar et al. 1999; Ott 1993). Up to
in the lower extremities (McIvor and Samilson 50% of the variance in bone strength is explained
1966, Presedo et al. 2007). The femur is the most by other features of the skeleton (Ciarelli et al.
commonly fractured bone, and the distal femur 2000; Dempster 2000; Link et al. 1998; Majumdar
is the most common fracture site (McIvor and et al. 1999; Parfitt 1987). Furthermore, because it
Samilson 1966, Presedo et al. 2007). While is affected by bone size, using aBMD alone to
femur fractures represent only 2% of all frac- make clinical decisions in children has been
tures in children without physical disabilities questioned (Klein et al. 2005; Lewiecki et al.
(Worlock and Stower 1986), they represent half 2004). Bone mineral content controlled for body
or more of all fractures in nonambulatory chil- size is viewed as a more appropriate measure to
dren with CP (Henderson 1997; McIvor and assess fracture risk in children (Heaney 2004; Pren-
Samilson 1966; Presedo et al. 2007). tice et al. 1994). However, it also has limitations.
One key feature that should be considered Moreover, studies evaluating the distal femur, the
when evaluating bone status in children (and most common fracture site in children with CP
adults) is bone architecture, which is also referred (McIvor and Samilson 1966; Presedo et al. 2007),
to as bone structure (Ciarelli et al. 2000; Dempster are lacking.
2000; Kleerekoper et al. 1985; Link et al. 1998;
Majumdar et al. 1999; Parfitt 1987). This notion is
supported by strong evidence that bone architec- Factors Contributing to Atypical Bone
ture can discriminate between those who do and Growth and Development in Children
do not fracture (Ciarelli et al. 2000; Dempster with CP
2000; Jamal et al. 2006; Kleerekoper et al. 1985;
Link et al. 1998; Majumdar et al. 1999; Parfitt Gross Motor Function and Physical
1987; Sornay-Rendu et al. 2007). Furthermore, Activity
there is an improvement in the prediction of
strength and fracture when measures of bone The most obvious and dominant factors that con-
mass are combined with measures of trabecular tribute to the bone mass and bone architectural
bone microarchitecture, such as trabecular bone deficits and high fracture risk in children with the
volume to total volume, trabecular number, tra- most severe forms of CP are limited weight bearing
becular thickness and trabecular separation and poor motor function (Henderson et al. 2002a).
(Majumdar et al. 1999; Siffert et al. 1996), or While, on average, aBMD is 1.8 SD below the
measures of cortical bone architecture (Augat norm in children with CP who can ambulate with
and Schorlemmer 2006; Bousson et al. 2006; assistance (GMFCS III), it is 3.8 SD below the
Laib et al. 2001; Sell et al. 2005). norm in children with CP who are nonambulatory
Magnetic resonance imaging (MRI) and com- (GMFCS IV-V) (Henderson et al. 2002a). Progres-
puted tomography provide accurate estimates of sively, lower aBMD in the distal femur of children
bone architecture in humans (Boutroy et al. 2005; with CP is associated with lower levels of mobility
Majumdar et al. 1998; Woodhead et al. 2001). (Henderson et al. 2002a).
Magnetic resonance imaging is particularly attrac- Children with CP usually exhibit functional
tive when working with children with CP because impairments such as spasticity, lack of dexterity,
there is no ionizing radiation. The main challenges and a restricted range of motion, which may all
associated with the widespread use of MRI contribute to their limited participation in daily
include the high expense, the limited available physical activity (Bjornson et al. 2007). Com-
technological expertise and the potential involun- pared to their typically developing peers, children
tary movement of some individuals with CP due with CP not only have a significantly lower phys-
to spasticity and behavior issues. To minimize ical activity but also a lower percentage of
movement, sedation (Englander et al. 2015) and medium and high levels of activity (Bjornson
immobilization using restraining straps et al. 2007; Johnson et al. 2009; Modlesky et al.
(Bandholm et al. 2009), bracing (Elder et al. 2009). Moreover, the physical activity perfor-
2003), or vacuum pressure (Johnson et al. 2009; mance decreases as motor function decreases.
Modlesky et al. 2008, 2009, 2015; Whitney et al. Children with CP and a GMFCS III-V have phys-
2017) have been used. Dual-energy X-ray absorp- ical activity that is 70–80% lower than typically
tiometry has also been used to assess bone archi- developing children (Johnson et al. 2009,
tecture (Beck 2007). Currently, cortical bone Modlesky et al. 2009).
architecture can be estimated in the proximal
femur (Petit et al. 2002) and trabecular bone
microarchitecture can be estimated in the lumbar Muscle
spine (Bousson et al. 2012). However, because
DXA is a two-dimensional technology, the accu- Muscle plays a very important role in bone
racy of its bone architecture estimates is limited. growth. It has been proposed that forces generated
during muscle contraction have a greater impact Nutrition

on bone than the loading provided by the gravita-
tional force associated with weight bearing (Burr Better nutritional status, as reflected by markers of
1997; Frost 1997; Lu et al. 1997). Several studies growth such as height, weight, and skinfold thick-
have established a positive relationship between ness, is viewed as one of the strongest predictors
muscle and bone in adults and children (Bajaj of aBMD in children with CP (Henderson et al.
et al. 2015; Lebrasseur et al. 2012; Schoenau 1995). Better nutritional status is associated with
et al. 2000; Snow-Harter et al. 1990). A significant higher aBMD (Henderson et al. 2002a) and
positive relationship between thigh muscle vol- greater increases in aBMD in individuals with
ume and femur bone strength, but not between CP during childhood and adolescence (Henderson
leg muscle volume and tibia bone strength, has et al. 2005). In addition, calcium is the primary
been observed in 10–23 year-old individuals with mineral stored in bone and contributes to the
bilateral spastic CP (Noble et al. 2014). In addi- overall strength of bone. Vitamin D is important
tion to the obvious biomechanical coupling of in facilitating the absorption of dietary calcium via
muscle and bone, muscle also acts as an endocrine the intestines (Bronner 2009). Due to oral-motor
organ that helps regulate bone metabolism. Mus- dysfunction, medication use and absorption issues
cle can produce several cytokines, including associated with medication use in some children
insulin-like growth factor 1 and osteonectin with CP, inadequate intake of calcium, vitamin D,
(Cianferotti and Brandi 2014), which have essen- and other nutrients important for bone growth and
tial anabolic function in bone growth and repair. It mineralization may occur (Henderson et al.
has been demonstrated that children with CP have 2002a). Some studies suggest that calcium and
smaller muscles (Elder et al. 2003; Johnson et al. vitamin D supplementation can increase lumbar
2009; Modlesky et al. 2010; Shortland et al. 2002; spine aBMD in children with severe CP (Jekovec-
Whitney et al. 2017), greater fat infiltration within Vrhovsek et al. 2000). Whereas, other studies
their muscles (Johnson et al. 2009; Whitney et al. suggest that calcium intake and serum
2017), as well as a lower capacity to generate 25-hydroxyvitamin D are not correlated with
muscular force (Elder et al. 2003). Such compro- aBMD (Finbraten et al. 2015; Henderson et al.
mise in muscle quality, coupled with the observed 2002a) or fracture (Henderson et al. 2010) in this
lower physical activity level in children with CP, population. Furthermore, there is no difference in
suggest not only a lack of mechanical loading but aBMD in children with CP who consume low
also a potentially hormonal dysregulation on bone vs. high amounts of calcium or who have low
growth in this population. vs. normal levels of serum 25-hydroxyvitamin D
In addition to the direct and indirect influence (Henderson et al. 2002a). If the effect of calcium
that muscles have on bone, stronger muscles can and vitamin D on bone is limited, it may be that
also provide mechanical advantages in fall and there is insufficient mechanical stimulation to
fracture prevention. In older adults, lower effectively use these nutrients (Duncan and Turner
extremity muscle weakness is associated with a 1995), especially in nonambulatory children with
higher fall risk (Moreland et al. 2004). There is CP. Without mechanical coupling as the first step,
evidence that individuals with CP have a higher further steps in bone mechanotransduction may not
risk of falling than the general population occur. More studies are needed to determine the
(Ferdjallah et al. 2002; Hsue et al. 2009), effect of nutrition on bone health in children
which is consistent with their underdeveloped with CP.
musculature and poor neuromuscular control.
Increased fall risk combined with the lower
aBMD, underdeveloped bone architecture and Medications
low bone strength could at least partly explain
the high fracture rate in children with CP at Medication use may also contribute to low bone
atypical fracture sites. mass and poor bone development in children
with CP. In particular, there is evidence that Bone Health in Adults with CP
antiepileptic drugs have a negative effect on
bone in children with CP (Henderson et al. As the medical care system has improved, the life
2002a). Because epilepsy is more common in expectancy of individuals with CP has increased
children with CP than in the general population (Brooks et al. 2014). However, the age-related
of children (Wallace 2001), the use of anti- problems associated with a longer life span may
epileptic drugs, such as phenobarbitol and include greater fracture risk for adults with CP. It
diphenylhydantoin, may be a significant prob- is also possible that the problem in adults with CP
lem. The proposed negative effect of some anti- may exceed the problem in children with CP
epileptic drugs on bone is attributed to increased (Sheridan 2009). Unfortunately, research studies
induction of expression of cyp24, a member of involving bone rarely focus solely on adults with
the cytochrome p450 superfamily, which may CP. One longitudinal study that included young
lead to greater inactivation of vitamin D (Pack adults with CP found a wide range of annual
2011). Research examining the effect of anti- aBMD change with both increases and decreases
epileptic drugs on bone in children are observed over time (Grossberg et al. 2015). A
conflicting. In a review of the literature that cross-sectional study found that unlike in chil-
included cross-sectional, cohort, case-control, dren, Z-scores were not related to age in adults
and randomized controlled trials, it was con- with CP 18 to 50 years of age (Fowler et al. 2015).
cluded that carbamazepine and valproate were The findings suggest that the discrepancy in
associated with a limited decrease in aBMD aBMD between adults with and without CP does
(Vestergaard 2015). The effect of antiepileptic not widen with age. On the other hand, there is
drugs may be related to the type of medication evidence that the prevalence of osteoporosis in
use. Polytherapy with antiepileptic drugs has adults with CP is increased. In addition to the
been associated with a larger decrease in limited number of studies that have directly
aBMD than monotherapy (Vestergaard 2015) compared the aBMD between adults with and
Furthermore, some studies suggest that newer without CP, studies examining bone architecture,
antiepileptic drugs may not have a detectable bone strength and fracture patterns in adults with
effect on bone (Vohora and Anwar 2013). CP are lacking. One investigation reported that
It is possible that the effects of antiepileptic adults with spastic CP have lower femur trochan-
drugs on bone health in children with CP depends teric aBMD than adults with dyskinetic CP (Kim
on the level of involvement of the disorder. For et al. 2015) suggesting that the type of CP should
example, an epidemiological retrospective study also be considered when evaluating bone health.
that looked at the risk factors associated with Overall, the sparse literature suggests that more
fractures in children with CP suggested that attention needs to be given to adults with CP to
there was a two-fold fracture risk increase associ- help us better understand their bone health and
ated with antiepileptic drug therapy for those with fracture risk.
a GMFCS IV-V, whereas a similar relationship
was not detected for those with a milder form
with CP (Wort et al. 2013). However, caution is Treatment
needed when interpreting observation studies that
involve children with severe forms of CP, as hav- Childhood and adolescence are critical periods of
ing limited mobility itself can be associated with overall growth and development. Therefore, an
other issues, such as increased seizure and absence or a restriction of environmental factors
gastrostomy, which may have an intrinsic link to that facilitate normal change during these periods
low bone mass and increased fracture risks (Hen- may have a devastating effect on any tissue. For
derson 2013). Therefore, the effect of antiepileptic example, limited mechanical loading, as experi-
medications on bone in children with CP remains enced by children with CP, clearly abates the
uncertain. accretion of bone mineral (Henderson et al.
2002a; King et al. 2003; Modlesky and Lewis activity group compared to controls demonstrated
2002; Modlesky et al. 2008) and the development a notable increase in femoral neck bone mineral
of bone architecture (Binkley et al. 2005; content (9.6% vs. -5.8%, p < 0.05) and volumetric
Modlesky et al. 2008, 2009, 2015; Whitney et al. BMD (5.6% vs. -6.3%, p <0.05). For non-
2017). Thus, it is likely that peak skeletal mass ambulatory children with CP, even standing for a
does not reach its genetic potential in individuals longer period of time may be beneficial. A ran-
with CP. This idea is supported by the low aBMD domized controlled trial reported that non-
reported in adults with CP (Nakano et al. 2003; ambulatory prepubertal children with CP who
Sheridan 2009) and the slower and less consistent stood 50% longer than their normal standing
rate of change in distal femur aBMD observed in time for 9 months increased their trabecular volu-
children and young adults with CP than expected metric BMD in the spine by 6% compared to
(Grossberg et al. 2015; Henderson et al. 2005). controls. However, a significant change was not
Furthermore, the discrepancy in aBMD between found in their proximal tibia (Caulton et al. 2004).
children with and without CP becomes progres- High-frequency, low-magnitude vibration also
sively worse with age (Henderson et al. 2010). shows promise as an intervention strategy for
Therefore, in theory, an effective treatment initi- children with CP. Some studies suggest it
ated during childhood or adolescence should improves muscle mass (Gilsanz et al. 2006),
facilitate growth and development of bone that is strength (Leung et al. 2014; Reyes et al. 2011),
closer to that experienced by typically developing and coordination (Leung et al. 2014). While low-
children (Fig. 4). magnitude mechanical loading is osteogenic in
A number of intervention studies suggest that theory (Gilsanz et al. 2006; Leung et al. 2009;
regular exposure to mechanical loading can Rubin et al. 2001, 2004, Xie et al. 2006), few
enhance the accretion of bone mineral during studies have specifically looked at its effects on
growth (Fuchs et al. 2001; Laing et al. 2005; bone in children with CP. Among the available
Petit et al. 2002). In one of the few intervention studies, Wren et al. (2010) randomized children
studies focused on physical activity and bone in with CP (GMFCS I-IV) to either stand on a plate
children with CP (Chad et al. 1999), a small group that emits a high-frequency, low-magnitude vibra-
of children with spastic CP were randomly tion (30 Hz, 0.3 g), or on the floor at home 10 min/
assigned to participate in a weight-bearing physi- d for 6 months. Children then swapped their con-
cal activity program or no intervention for dition for another 6 months (i.e., children who
8 months (n = 9/group). Children in the physical stood on the vibration plate now stood on the
Fig. 4 The theoretical

pattern of bone accretion in
children with CP compared
to typically developing
children and the potential
change in bone mass
(or bone architecture or
bone strength), if an
appropriate intervention is
employed. (Modified from
Modlesky and Lewis 2002)
floor and vice versa). The vibration condition led percentage of fractures in children with CP
to increases in cortical bone properties (i.e., corti- dropped from 31% to 13% per year after
cal bone area and estimates of bone strength) in 13.6 months of pamidrotate treatment (Bachrach
the tibial midshaft that were approximately double et al. 2010). However, due to the limited number
the increases observed during the floor-standing of studies available, a recent review concluded
period (average increase of 16% vs. 8%). No that there was only “possible” evidence that
significant changes were detected in the meta- bisphosphonates are effective at reducing fragility
physis of the proximal tibia or in the lumbar fractures in children with CP (Ozel et al. 2016). To
spine, which are highly concentrated in trabecular date, more definitive studies examining the effect
bone. Although studies examining the potential of bisphosphonates on fragility fractures are
effect of standing, weight-bearing physical activ- needed. Studies are also needed to determine if
ity and mild vibration are encouraging, recent the potential effect of bisphosphonates on bone
reviews of the literature (Fehlings et al. 2012; fragility fractures in children with CP is mediated,
Ozel et al. 2016) concluded that there is insuffi- at least in part, by changes in bone architecture
cient evidence to support the recommendation of and increases in bone strength.
weight-bearing activities as effective interven- Poor feeding and undernutrition is common in
tions to improve low aBMD or to decrease fragil- children with CP (Fung et al. 2002; Kim et al.
ity fractures. Intervention studies that assess larger 2018). Recent reviews of the literature concluded
samples sizes for a longer period of time are that there is “possible” evidence for calcium and
needed to make more definitive recommendations vitamin D to improve low aBMD in children with
regarding weight bearing and bone health in chil- CP (Fehlings et al. 2012, Ozel et al. 2016). How-
dren with CP. ever, there is inadequate evidence to support the
Pharmacologically, bisphosphonates have use of calcium and vitamin D supplementation to
shown excellent promise as a treatment for low decrease fragility fractures in children with
aBMD in children with CP. In a randomized con- CP. Due to the possible effectiveness of calcium
trolled trial, nonambulatory children with CP who and vitamin D, their good safety record, and their
received pamidronate injection showed a two- to existing recommendation for children, an
ten-fold increase in aBMD at the distal femur and approach that includes vitamin D supplementa-
a two-fold increase in aBMD at the lumbar spine tion and adequate calcium intake through the
relative to placebo controls 6 months after treat- diet is viewed as good clinical practice (Fehlings
ment (Henderson et al. 2002b). In another study et al. 2012). However, further research is neces-
that involved 23 nonambulatory children with sary (Ozel et al. 2016).
spastic CP, low-dose pamidronate was given intra-
venously. The 12-month intervention yielded a
significant increase in aBMD in both the lumbar Summary
spine and femoral neck (Plotkin 2006). A recent
investigation also found that orally administering Children with CP have significant deficits in bone
alendronate (1 mg/kg/week) increased lumbar health, as demonstrated by low aBMD, low bone
spine aBMD in children with quadriplegic CP mineral content, less developed bone architecture,
without inducing side effects (Paksu et al. 2012). and very low bone strength. Although the degree
Based on the available published studies, a recent of the deficits are greatest in nonambulatory chil-
review concluded that there was “probable” evi- dren with the most severe forms of CP, significant
dence that bisphosphonates are effective at deficits are present even in ambulatory children
improving low aBMD in children with CP (Ozel with milder forms of CP. The limited data avail-
et al. 2016). able suggest that bone health is also compromised
Bisphosphonates also show promise in the in adults. However, the extent of the deficit
reduction of fragility fractures in children with and whether it deteriorates at a greater rate than
CP. For example, one study reported that the observed with typical aging is unknown. Treatment
strategies that include standing, weight-bearing, related to trabecular and cortical bone architecture in
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Part V
Diagnosis
When and How to Evaluate the Child
with Possible Cerebral Palsy 19
Sonika Agarwal
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 288
Etiology and Pathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 288
Congenital (Antenatal) Etiologies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 289
Neonatal and Perinatal Etiologies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 289
Postnatal Etiologies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 290
Classification of Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 290
Diagnosis of Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 290
Clinical Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 291
Neuroimaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 292
Metabolic and Genetic Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 292
Coagulopathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293
Diagnostic Evaluations for Associated Conditions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 294
Abstract and by a seizure disorder. CP may be caused

Cerebral palsy is a neurodevelopmental disor- by several different etiologies causing insults
der with lifelong consequences. It includes a to the developing brain at different stages of
group of disorders of movement and posture, development. CP is a clinical diagnosis based
attributed to nonprogressive disturbances that on a thorough history (prenatal, perinatal, and
occurred in the developing fetal or infant brain. postnatal), review of developmental mile-
The motor disorders of cerebral palsy are often stones, and neurologic examination. The
associated with disturbances of sensation, cog- work-up may include neuroimaging, metabolic
nition, communication, perception, behavior, or genetic testing, and testing for specific dis-
orders. Also, the work-up may include testing
for the associated conditions and complica-
S. Agarwal (*) tions: intellectual disability (52%), epilepsy
Division of Neurology, Perelman School of Medicine at
University of Pennsylvania/Children’s Hospital of
(45%), speech and language disorders (38%),
Philadelphia, Philadelphia, PA, USA
e-mail: agarwals2@email.chop.edu

https://doi.org/10.1007/978-3-319-74558-9_16
288 S. Agarwal
vision defects (28%), and hearing impairments in all specialties and to facilitate research into this
(12%). These children often need long-term condition.
multidisciplinary care and therapies and sup- As per this workshop: “CP describes a group of
ports for educational and social functioning disorders of development of movement and pos-
to optimize the outcome. The disorder ture, causing activity limitations that are attributed
may exhibit a wide spectrum of functioning. to non-progressive disturbances that occurred in
Although the approach to treatment and reha- the developing fetal or infant brain. The motor
bilitation may be similar for most children with disorders of cerebral palsy are often accompanied
CP, a description of the condition based on by disturbances of sensation, cognition, commu-
neuroimaging, and metabolic or genetic test- nication, perception, and/or behavior, and/or by a
ing, may help individualize treatment and also seizure disorder” (Bax et al. 2005).
help better predict the associated morbidity and CP itself is a nonprogressive neurodeve-
what to expect for a particular child. lopmental disorder, not as a result of a recognized
progressive or degenerative brain disease (Nelson
Keywords and Ellenberg 1978). The description always
Cerebral palsy · Neurodevelopment · involves a motor deficit, usually presenting to
Developmental delay · Neuroimaging · the physician with varying degrees of delay in
Genetic · Delayed milestones · Perinatal brain the attainment of motor milestones at the appro-
injury priate chronological age. In most cases a thorough
history (prenatal, perinatal, and postnatal) estab-
lishes the nonprogressive nature of the condition,
Introduction and a detailed neurologic examination will show
signs of cerebral abnormality or an upper motor
Cerebral palsy (CP) is a well-recognized neuron involvement. The majority of children
neurodevelopmental disorder beginning in early with CP present with symptoms of delayed
infancy and with lifelong consequences. CP was neurodevelopment as infants or toddlers, and the
originally reported by Little in 1861 and labeled as diagnosis is made before the age of 2 years,
“cerebral paresis.” CP is the most common motor though some may present at a later age. The
disability in childhood. Population-based studies timing of the insult or the onset of symptoms
from around the world report prevalence estimates may be variable, and there is no consensus to
of approximately 1.5–4 per 1000 live births include these factors in the definition or classifi-
(Arneson et al. 2009; Bhasin et al. 2006; Paneth cation (Ashwal et al. 2004). The diagnosis of CP
et al. 2006). and its classification is important for identifying
Over the last few decades, there have been the needs for multidisciplinary care, rehabilita-
several modifications of the definition and tion, education, and social services.
description of this condition. An International
Workshop on Definition and Classification of
Cerebral Palsy was held in Bethesda, Maryland Etiology and Pathology
(2004), to revisit and update the definition and
classification of CP, taking into consideration the The developing brain may be exposed to insult or
emerging research on developmental neurobiol- injury during the prenatal, perinatal, or postnatal
ogy, newer diagnostic techniques (especially neu- period, and these may lead to a diverse etiologic
roimaging and genetic testing), and the concept and pathologic basis for CP. Although the
of functionality to describe the impairment. The approach to treatment and rehabilitation may be
new definition took into account the advances in similar for most children with CP, a description
pathology and physiology of neurodevelopment, of the condition based on neuroimaging, and met-
with the idea of maintaining a standard classifica- abolic or genetic testing, may help individualize
tion to facilitate communication among clinicians treatment and also help better predict the
19 When and How to Evaluate the Child with Possible Cerebral Palsy 289
associated morbidity (such as seizures, intellec- chorioamnionitis is associated with an increased

tual disability, etc.). risk of CP in term infants (Grether and Nelson
1997; Wu et al. 2003). Perinatal infection appears
to play a key role in the pathogenesis of PVL and
Congenital (Antenatal) Etiologies subsequent CP in preterm infants (O’Shea 2002).
Cytomegalovirus leads to intellectual disability
Congenital developmental malformations: This and hearing loss in up to 90% of infected infants,
group comprises the structural central nervous but only about 50% develop motor deficits.
system anomalies, which have been reported in Genetic abnormalities: Genetic disorders were
14% of the children with CP compared to 1% in historically thought to be uncommon causes of
controls (Croen et al. 2001). These abnormalities CP, noted in 0 to 4% of patients. However in the
may result from changes affecting cell prolifera- genomic era, the role of genetic variants and their
tion, migration, differentiation, survival, or syn- diagnostic testing is increasingly recognized in
aptogenesis. Though the exact neurobiology is the etiology of CP (Schaefer 2008; Moreno-De-
sometimes unknown, these disorders have been Luca et al. 2012).
associated with exposure to radiation, toxins, or
infectious agents during a critical period of gesta-
tion or with genetic alterations. Disorders may Neonatal and Perinatal Etiologies
follow Mendelian inheritance (schizencephaly)
or be associated with chromosomal abnormalities Neonatal and perinatal causes of CP are mainly
(holoprosencephaly associated with both trisomy related to prematurity and obstetric complications.
13 and 18). These malformations may cause min- The immature and developing brain has specific
imal disability to very severe quadriplegic presen- patterns of injury and evolution and is character-
tation, usually with spasticity and intellectual ized by neuroplasticity, and the outcome is mod-
disability. ifiable by early intervention.
A child with brain malformation may present at Prematurity-related brain injury: The most
any age or be diagnosed prenatally, due to increas- common cause of brain injury in the premature
ing use of fetal MRI for neuroimaging in preg- fetus or infant is the hemorrhage arising from the
nancy. They often go undiagnosed and present germinal matrix, intraventricular hemorrhage
later. (IVH), and periventricular leukomalacia (PVL).
Case #1: A 9-month-old boy presents with The general trend is a worse outcome with greater
increased tone, delayed developmental mile- grade of hemorrhage and when it involves the
stones, and abnormal movements consistent with brain parenchyma. CP risk was reported to be
seizures. Due to global developmental delay, 9% in grade I, 11% in grade II, 36% in grade III,
spastic quadriplegia, hyperreflexia, and tone and 76% in grade IV IVH (de Vries et al. 1993).
abnormalities, an MRI of the brain is done. MRI Case #2: An infant presents at 9 months with
confirms the brain malformation (lissencephaly inability to roll over or sit, with history of pro-
in this case), and EEG detects abnormal back- longed hospitalization in the neonatal intensive
ground waves, rhythmic alpha/beta/delta waves, care, and is found to have hypertonicity and spas-
and absence of sleep-wake differentiation. These ticity of lower extremities with persistence of
infants usually have moderate to severe global primitive reflexes. Exam confirms spastic diplegia
developmental delay and medically refractory with low axial tone, and MRI of the brain shows
epilepsy. periventricular leukomalacia and ex-vacuo dila-
Intrauterine infection: Congenital infections tion of ventricles, which are the characteristic
with organisms such as cytomegalovirus, syphilis, pattern of injury in prematurity.
Zika virus, varicella virus, and toxoplasmosis are Perinatal hypoxic-ischemic injury: Perinatal
associated with an increased risk of CP. Bacterial hypoxia and/or ischemia also is associated with a
infections are also associated with CP. Maternal risk for CP, various studies reporting rates of 3 to
290 S. Agarwal
50% of proportion of infants with CP having birth (lower extremities involvement and spasticity).
asphyxia as a precursor (Ellenberg and Nelson CP is also classified based on the type of neuro-
2013). On magnetic resonance imaging (MRI), muscular deficit: spastic (with spasticity), dyski-
characteristic injuries may include basal ganglia/ netic (choreoathetoid and dystonic), ataxic,
thalamic lesions predominantly or a watershed hypotonic, or mixed type (Zhou et al. 2017).
pattern (Executive summary, Obstet Gynecol
The Gross Motor Function Classification System
2014). Infants with CP caused by an acute
(GMFCS) is widely used to classify the gross
intrapartum hypoxic-ischemic event are more motor function of children with CP both for clinical
likely to have spastic quadriparesis or dyskinetic and research purpose (Morris and Bartlett 2004;
CP, rather than other subtypes of CP. McCormick et al. 2007; Palisano et al. 2006). The
GMFCS is a five-level pattern recognition system
Perinatal and neonatal stroke: Stroke in the
(level I represents the best and level V the least
perinatal period contributes to CP, especially spas- gross motor function).
tic hemiparesis. The infant may present with a
seizure in the neonatal period or later when early
hand preference is noted. Some infants present in
later infancy with hemiparesis or seizures. Diagnosis of Cerebral Palsy
There is no standard agreed upon criterion to

Postnatal Etiologies make the diagnosis of CP in a child. Usually
parents will seek medical attention when a child
There is an overlap with the prenatal and neonatal is not meeting developmental milestones, has
causes of CP. Postnatal trauma (falls, motor vehi- persistent primitive reflexes, or has significant
cle accidents), metabolic encephalopathy, infec- abnormalities in motor function or tone. A
tion, abusive head trauma, and toxicities also detailed history exploring the antenatal, perinatal,
cause CP. Various studies report 10 to 25% of and postnatal period, along with a family history,
CP cases having a postnatal cause. Neonatal bac- will demonstrate the nonprogressive nature of the
terial meningitis also has severe sequelae, and CP lesion and that it is not inherited. Developmental
is seen in up to 30–50% of the survivors (Miller delay is the term to diagnose milder or marginal
and Clark 1998). Metabolic encephalopathies abnormalities in the neurodevelopmental mile-
are also a diverse group of rare disorders pre- stones, implying that these children may catch
senting with varying degrees of impact on up with time. The diagnosis of CP is important
neurodevelopment. from the family’s perspective to help them under-
stand the developmental differences in their child,
what caused them, and to individualize therapy.
Classification of Cerebral Palsy CP is a clinical diagnosis based on a thorough
history (prenatal, perinatal, and postnatal), review
The definition of CP includes children with a wide of developmental milestones, and neurologic
range of clinical presentations and activity limita- examination. The work-up and diagnostic testing
tion; therefore it is helpful to classify the condition are based on the course of development and history
into classes or groups based on description (nature since the early life of the infant. Early diagnostic
and severity of the problem), prediction (for cur- work-up may be indicated by the presence of hand
rent and future services), comparison (for inclu- preference at a younger age than normal, promi-
sion in research), and evaluation of change nent fisting, abnormalities of tone (spasticity, hypo-
(clinical course) (Rosenbaum et al. 2007). tonia, or mixed tone of variable distribution),
Historically, CP has been classified according persistence of abnormal neonatal reflexes, delay
to the anatomic location: quadriplegia (involving in emergence of protective and postural reflexes,
all four limbs), hemiplegia (unilateral paresis with asymmetric crawl, hyperreflexia, or clonus.
upper limbs more affected than lower), or diplegia Repeated examinations and observation may be
required over a period of time before a definite stiffness. Usually, hyperreflexia is part of this syn-
diagnosis can be made. Abnormal quality or total drome and may present with exaggerated reflexes,
absence of fidgety movements was found to be a clonus, or crossed adductor signs. The opposite end
simple and valid predictor of later neurologic out- of spasticity is hypotonia, which means decreased
come, much before the changes in tone appear muscle tension when the joint is moved.
(Prechtl et al. 1997). Persistence of primitive reflexes is an impor-
Historically, CP could not be identified accu- tant sign on examination which reflects the abnor-
rately before the age of 12–24 months, and this malities in tone, posture, and movement and their
was considered as the silent period. However, in control in the central nervous system. Most prim-
recent years sophisticated neuroimaging tech- itive reflexes are normally integrated within the
niques have led to earlier prediction of an infant first 4 to 8 months, but in children with CP, they
at risk (Novak et al. 2017). Diagnostic testing may persist into later years. Persistence of these
should be highly sensitive to determine the eligi- reflexes interferes with the development of volun-
bility for effective early intervention for an infant tary motor movements by causing alterations in
at risk, though it does not need to be highly spe- tone and posture of the limbs. These reflexes
cific, so as to avoid errors of exclusion. Specific include asymmetric tonic neck reflex, tonic laby-
diagnosis is required for inclusion in clinical trials rinthine reflex, Moro’s reflex, plantar and palmar
or for newer tailored treatments. The American grasp, stepping reflex, and parachute reflex.
Academy of Neurology (AAN) and the Practice History and physical examination: The evalu-
Committee of the Child Neurology Society (CNS) ation of children with suspected CP begins with a
have developed practice parameters for diagnostic detailed history and physical examination, which
assessment of a child with CP based on available should include the following elements:
evidence which is discussed in the following sec-
tions (Ashwal et al. 2004). • History: review of prenatal and birth history
and the neonatal period, to identify risk factors
for CP
Clinical Diagnosis • Newborn screening results
• Review of the family history – first-degree rela-
Neurologic maturity in infants in the first year of tives with any of the following should raise sus-
life develops from proximal to distal. Developing picion for a genetic cause of CP: intellectual
infants first gain head control, then ability to bear disability/developmental disabilities, seizures,
weight on arms, followed by truncal control and CP, neuromotor/movement disorders,
ability to sit, and then crawling, cruising, and neurobehavioral disorders, joint contractures/
walking. The proximal to distal maturation stiffness, thromboses/vascular accidents, congen-
includes development of motor skills. An early ital anomalies, recurrent miscarriages/stillborns,
sign of CP may be preferential use of one arm and adult-onset neurodegenerative conditions
for reaching or weight bearing, tone differences in • Assessment of growth and of motor
extremities or axial tone, or delayed attainment of development
motor milestones. Differences in neurologic mile- • Evaluation of motor tone
stones are usually the first signs of CP, though • Assessment of age-appropriate motor control
consideration should be given to the range of • Assessment of posture
ages of attainment for each milestone. • Evaluation of coordination
Motor tone abnormalities are the most common • Screening for accompanying impairments
motor abnormalities that occur in children with (vision or hearing impairment, attention,
CP. Infants may present with hypertonia or hypoto- behavioral, communicative, and/or cognitive
nia which may be generalized or localized to certain deficits)
extremities. Spasticity is a velocity-dependent • Evaluation of any limitations in functional
increase in resistance to motion or clasp-knife activities
292 S. Agarwal
The goals of examination are to diagnose and such as hemorrhage, arteriovenous malfor-
to classify the type of CP, which provides clues as mations, or hydrocephalus. MRI is more sensitive
to the underlying etiology and pathology. It is also than US for global or focal hypoxic-ischemic
important to determine the static or progressive injury or structural malformations. Neuroimaging
nature of the condition, and this may have impli- is also usually recommended in an infant or child
cations regarding the likelihood of associated con- presenting with developmental delay, motor defi-
ditions. Although the lesion in CP is static, clinical cit, or abnormal neurologic exam later in life.
signs evolve and the examination findings change Recent data on 1426 children who underwent
as the nervous system matures, requiring serial neuroimaging indicated an abnormality in
examinations and a close follow-up. 62–100%: mean for CT 77% and mean for MRI
Case #3: A 14-month-old infant presents 89% (Ashwal et al. 2004). Both CT and MRI may
with decreased use of right arm and leg and early help diagnose prenatal or postnatal causes such as
left handedness. Exam shows discrepancy in the intrauterine infections, stroke, hypoxic-ischemic
size of limbs, right hemiplegic, and spastic encephalopathy, trauma, or hydrocephalus. MRI
CP. MRI brain is done and confirms left perinatal better evaluates the structural malformations,
stroke with characteristic cortical involvement, brain parenchyma, delayed myelination, and
ex-vacuo dilation of ventricles, and gliosis in sur- abnormalities of cortical development (details
rounding tissues. Such an infant may benefit from in chapter: Neuroimaging Brain Pathology in
earlier intervention with constraint-based physical Cerebral Palsy). MRI is also more sensitive
and occupational therapy and is at risk of symp- in detecting periventricular leukomalacia and
tomatic localization-related epilepsy in later life. congenital anomalies of brain development
The characteristic features that raise the possi- (lissencephaly, schizencephaly, pachygyria, poly-
bility of a diagnosis other than CP, such as a microgyria). Scan abnormalities may occasionally
neurodegenerative disease or metabolic disorder, (5 to 22%) (Razek et al. 2009) identify conditions
are absence of a known risk factor for CP, family such as cortical dysplasia, suggesting an increased
history of the neurologic condition, regression of risk for intellectual disability and epilepsy. Such
developmental milestones, ataxia, involuntary children could possibly benefit from epilepsy sur-
movements, oculomotor abnormalities, muscle gery evaluation. Other conditions treatable by
atrophy, sensory loss, hypotonia associated with surgery may be identified which may benefit
weakness, rapid deterioration of neurologic signs, from surgery: hydrocephalus, porencephaly, arte-
and worsening during periods of catabolism riovenous malformation, subdural hematomas,
(fasting or illness). and hygromas.
Based on the practice parameters, neuroimag-
ing is recommended in evaluation of a child with
Neuroimaging CP if the etiology has not been established by
earlier perinatal imaging, and MRI is preferred
The role of neuroimaging has been studied and to CT scan because of a higher yield in determin-
summarized in the practice parameters of the ing the etiology and timing of insult causing CP
Child Neurology Society and American Academy (Ashwal et al. 2004; Msall et al. 2009).
of Neurology (Ashwal et al. 2004). Neuroimaging
(ultrasound, CT, or MRI) is frequently obtained
when there are perinatal complications, prematu- Metabolic and Genetic Testing
rity, or abnormalities in neurologic examination at
birth. Head ultrasound (US) is the first step imag- The incidence of metabolic disorders was found to
ing study in a newborn due to ease of availability be about 4% and genetic disorders 2% in the
and cost. Head US is important for rapid initial various studies included in the development of
assessment of a sick neonate or premature infant practice parameters (AAN and CNS) for diagnosis
and helps rule out large space-occupying lesions of CP (Ashwal et al. 2004), though some studies
excluded infants with diagnosed metabolic prob- pallidus, severe symptoms in absence of a history
lems. Metabolic or genetic disorders may mas- of perinatal injury, a pattern of disease inheritance
querade as CP and may present at variable ages or consanguinity, neurodevelopmental regression
in early infancy. Some recent studies have or progressive worsening, isolated muscular
reported the diagnostic yield of metabolic testing hypotonia, rigidity, or paraplegia.
in CP to be up to 20% (Whitehouse 2011).
Metabolic or genetic testing is not routinely indi-
cated in evaluation of CP due to the low yield. Coagulopathies
However, if clinical history or examination or
imaging indicates a specific metabolic or genetic Cerebral infarction due to pre- or perinatal cere-
cause or neuroimaging does not determine the brovascular occlusion is reported in 13 to 37% of
etiology, or if there are additional atypical clinical children with hemiplegic CP and has been linked
features, the diagnosis of these disorders should to coagulation disorders, congenital heart disease,
be considered. or infectious process as the cause of stroke
Case #4: A 2-year-old presenting with global (Ashwal et al. 2004). However, the evidence has
developmental delay, uneventful perinatal period, been insufficient to recommend diagnostic testing
and exam significant for spasticity, seizures, and for coagulation disorder for all other types of CP.
vision changes may require a more detailed work-
up with a stepwise approach, starting with MRI of
the brain. If the MRI fails to show a cause of the Diagnostic Evaluations for Associated
clinical picture, then the next step is the metabolic Conditions
and genetic work-up, as the differential is broad.
In a study using whole exome sequencing in Children with CP may need further diagnostic
183 patients with CP, 14 percent had a potentially testing based on the associated risk for intellectual
disease-causing gene variant, de novo or inherited disability (52%), epilepsy (45%), speech and lan-
(McMichael et al. 2015). In a study of 52 children guage disorders (38%), vision defects (28%), and
with CP without an identified etiology, genomic hearing impairments (12%) (Ashwal et al. 2004).
testing with chromosomal microarray analysis EEG is not usually useful in determining the eti-
identified clinically significant copy number var- ology of CP, and evidence does not suggest
iations in 31% (Segel et al. 2015). recommending EEG if the child with CP does
Recent advances in molecular genetics such not have seizures. The guidelines do recommend
as chromosomal microarray and next-generation EEG for a child with CP if there are features of
sequencing have further revolutionized the epilepsy or an epileptic syndrome. The practice
detailed characterization of the etiology of parameters also recommend screening for intel-
CP. Genetic testing can guide therapy and is lectual disability (neuropsychological testing),
highly significant for providing answers on prog- ophthalmological impairments, and audiological
nosis and genetic counseling. Early diagnosis of testing for all children with CP. Nutrition, growth,
neurogenetic disorders masquerading as CP and and swallowing dysfunction may also need
presenting with a phenotype similar to CP is monitoring.
important to determine the specific etiology and
prognosis and to help guide genetic counseling for
the families. A recent study highlights the step- Conclusion
wise approach for diagnostic evaluation of the
individuals presenting with a CP phenotype (Lee It is important to recognize the diverse nature of
et al. 2014) and identifies the clinical and imaging CP in both etiology and diagnostic work-up and
red flags in patients with suspected CP indicating consider an individualized approach. Each child
further genetic work-up. These include normal needs a careful clinical evaluation to classify the
MRI, imaging abnormalities isolated to the globus condition, have a differential for the etiology, and
294 S. Agarwal
then consider a stepwise approach to confirm the Program, 1996 and 2000. MMWR Surveill Summ 55
diagnosis and specific disease process. Also, it is (1):1–9
Croen LA, Grether JK, Curry CJ, Nelson KB (2001)
important to take the families’ perspective into Congenital abnormalities among children with cerebral
consideration for knowledge about the causative palsy: more evidence for prenatal antecedents. J Pediatr
factors and for long-term rehabilitation of these 138:804
children. The support and care for this diverse de Vries LS, Eken P, Groenendaal F, van Haastert IC,
Meiners LC (1993) Correlation between the degree of
neurologic disorder is multidisciplinary, involv- periventricular leukomalacia diagnosed using cranial
ing a team of specialists who work together to ultrasound and MRI later in infancy in children with
optimize the outcome. cerebral palsy. Neuropediatrics 24:263–268
Ellenberg JH, Nelson KB (2013) The association of cere-
bral palsy with birth asphyxia: a definitional quagmire.
Dev Med Child Neurol 55:210
Cross-References Executive summary: neonatal encephalopathy and neuro-
logic outcome, second edition. Report of the American
▶ Classification Terminology in Cerebral Palsy College of Obstetricians and Gynecologists’ task force
on neonatal encephalopathy. (2014) Obstet Gynecol
▶ Current Imaging: PET Scan Use in Cerebral 123:896
Palsy Grether JK, Nelson KB (1997) Maternal infection and
▶ Genetic Abnormalities and Congenital cerebral palsy in infants of normal birth weight.
Malformations as a Cause of Cerebral Palsy JAMA 278:207
Lee RW, Poretti A, Cohen JS, Levey E, Gwynn H,
▶ Infectious Etiologies of Cerebral Palsy Johnston MV, Hoon AH (2014) Fatemi . A diagnostic
▶ Neuroimaging Pathology in Cerebral Palsy approach for cerebral palsy in the genomic era.
▶ Perinatal Stroke as an Etiology of Cerebral NeuroMolecular Med 16(4):821–844
Palsy McCormick A, Brien M, Plourde J, Wood E, Rosenbaum P,
McLean J (2007) Stability of the gross motor function
▶ Postnatal Causes of Cerebral Palsy classification system in adults with cerebral palsy. Dev
▶ Problems During Delivery as an Etiology of Med Child Neurol 49:265–269
Cerebral Palsy in Full-Term Infants McMichael G, Bainbridge MN, Haan E et al (2015)
Whole-exome sequencing points to considerable
genetic heterogeneity of cerebral palsy. Mol Psychiatry
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Dan B, Jacobsson B, Damiano D (2005) Proposed Darrah J, Eliasson AC, de Vries LS, Einspieler C,
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Cerebral Palsy Prognosis Based on the
Physical and Neurologic Examination 20
S. Charles Bean
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 298
Making the Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 298
Early Diagnostic Uncertainty Complicates Early Prognosis . . . . . . . . . . . . . . . . . . . . . . . . . . . 299
Developing a Prognosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 299
Prognosis: Comorbidities and Life Expectancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 301
The Challenge of Masqueraders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 301
Early Neurologic Examination Predicting Specific CP Syndromes . . . . . . . . . . . . . . . . 302
Specific Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 304
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 307
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 307
Abstract slowly changing and presumably static condi-

Cerebral palsy (CP) is a static disorder of tion for masqueraders of CP, particularly pro-
movement and posture due to injury, genetic, gressive, degenerative, treatable, or specific
and/or developmental abnormality of the genetic disorders.
maturing fetal, neonatal, or early infant central The neurologist and pediatrician have an
nervous system. The early neurodeve- important role to help families understand the
lopmental exam, although helpful, cannot reli- uncertainty and complexity of a diagnosis of
ably prognosticate the severity and type of CP, which should never be a final diagnosis
CP. The diagnosis needs to be secure. With without a modifier of what risk factors or spe-
the advent of neuroimaging, metabolic studies, cific causative etiology may exist. CP is a
and explosion of genomic studies, the physi- starting point, not an end in itself.
cian must be more vigilant to not confuse this Discussion with the family of the potential
for motor dysfunction and neurologic injury
should be addressed as early as possible, even
S. C. Bean (*) before a clear diagnosis of CP is established.
Emeritus Professor of Pediatric Neurology, Nemours AI Developmental therapies should be initiated
duPont Hospital, Wilmington, USA early. The physician should clearly emphasize
e-mail: cbean216@verizon.net

https://doi.org/10.1007/978-3-319-74558-9_17
298 S. C. Bean
that predicting severity is often impossible exceeded expectations and 60% reported exceed-
from the infant examination. Hopeful, positive, ing expectation when prognosis was based on
and guarded expectations should be provided. medical imaging (Guttmann et al. 2018). Earlier
Additionally, serial follow-up for monitoring diagnosis of neurologic injury generally correlates
the progression of symptoms and preparing the with the most severe injury, with the child having
family for the comorbidities that may accom- greater functional limitations (Guttmann et al.
pany the CP motor disability is important. 2018). For the child diagnosed later, there is
It is essential for the neurologist, pediatri- more nuance, often with less severe neurologic
cian, and developmental team to be vigilant for abnormality. Families often feel communication
uncovering the myriad of CP masquerading is “fragmented, chaotic, and contradictory”, espe-
conditions. They should also provide ongoing cially in the acute illness setting, such as the
support and therapeutic guidance while neonatal intensive care unit (NICU), with neuro-
respecting the integrity of the family facing logic diagnosis such as neonatal encephalopathy,
the challenges of CP. hypoxic ischemic encephalopathy, ischemic
events, or intraventricular hemorrhage (Lemmon
Keywords et al. 2016). Parents feel there can be too long a
Cerebral palsy · Cerebral palsy masqueraders · delay in making the diagnosis. On the other hand,
Cerebral palsy comorbidities · Cerebral palsy parents often perceive a positive influence of
neurologic examination · Cerebral palsy receiving a diagnosis and then starting therapeutic
diagnosis · Cerebral palsy prognosis interventions. Even in the more subacute and
chronic situations with developmental delays or
asymmetric motor function, the same challenges
Introduction exist to properly inform families about the non-
homogeneous nature of the cerebral palsy as a
The diagnosis or suspicion of cerebral palsy congenital motor dysfunction and not a single
(CP) has a cataclysmic effect on family dynamics definitive diagnosis in itself. Static and non-
and escalates family stress. Dashing the hopes of a progressive, early findings do not clarify severity
“normal” parenthood and the expectations of a or associated comorbidities. The neurodeve-
“normal” child’s future promptly leads to ques- lopmental examination alone usually does not
tions of prognosis. What is the predicted course of clarify etiology, except if dysmorphic features
the condition? What outcomes are to be expected? lead to a specific genetic diagnosis such as Tri-
What therapy choices will help? These are diffi- somy 21 or Miller-Dieker Syndrome.
cult issues for the physician, as children with CP
are not a homogeneous population. The initial
presentation is often in the first 6–24 months of Making the Diagnosis
life, when the child presents either because of
unexpected motor delay or because prenatal In 2006, the International Consensus Panel defined
and/or neonatal risk factors have alerted the fam- cerebral palsy as “a group of permanent disorders
ily to follow a child closely because of potential of the development of movement and posture caus-
higher risk for the development of CP and neuro- ing activity limitations that are attributed to
logic abnormality. The diagnosis is usually made non-progressive disturbances that occurred in the
between 12 and 24 months of age, although it can developing infant or fetal brain. The motor disor-
often be later. ders are often accompanied by the disturbances of
The physician is presenting the diagnosis and sensation, perception, cognition, communication
prognosis before the infant’s nervous system has and behavior, by epilepsy, and by secondary mus-
fully developed. It is understandable that families culoskeletal problems” (Rosenbaum et al. 2007,
remember prognostic discussion about their p. 11.) Although nonprogressive, CP is changeable,
child’s functioning: 46% reported their child as its symptoms are often nonspecific initially,
20 Cerebral Palsy Prognosis Based on the Physical and Neurologic Examination 299
and then unfold into clearly recognized patterns On the other hand, children with a clear diag-
as the child’s cortical and subcortical control nosis of cerebral palsy can improve and clear their
begins to influence brainstem and spinal reflex motor symptoms and be free of motor disability at
patterns. The earliest pathological findings based school age (Nelson and Ellenberg 1982;
on neonatal and postural reflexes and neurologic Korzeniewski et al. 2016). However, these chil-
examination do not consistently predict the type dren are at higher risk to develop disorders of
of motor dysfunction or the severity of motor cognition, speech, and epilepsy. Many more
dysfunction in the older child. Therefore, there infants show transient neurologic signs and devel-
is a continued tension between the difficulty opmental variability but clear without progression
of making an exact diagnosis and the need to (Mink 2013). Premature infants with self-limited
inform the family so appropriate therapeutic transient dystonia of the lower limbs can show
measures can be initiated. Most children with CP improved tone under observation and develop
have a well-established stable pattern of motor normally. This is difficult to predict but should
dysfunction by 7 or 8 years of age, but some con- be considered on giving prognosis in young
ditions may unfold at a later time. Between infants. There are other full-term infants, under
2 and 4 years of age, the basic pattern of motor 12 months, that can develop a transient dystonia
dysfunction is often clear, but particularly hyperki- of upper or lower limbs that clears (Willemse
netic/dystonic symptoms often show a delayed 1986; Calado et al. 2011; Angelini et al. 1988).
presentation. There is still much to learn about the reparative
processes at different developmental stages in the
fetus, newborn, and older child, which amelio-
Early Diagnostic Uncertainty rates the neurologic dysfunction from acquired
Complicates Early Prognosis illness like trauma or hypoxia as well as dysmor-
phic and genetic etiologies of brain development
Severity of CP judged by the Gross Motor Func- like schizencephaly and lissencephaly. Brain plas-
tional Classification System (GMFCS) often ticity and reparative success is complex and not
needs to be adjusted after 2 years of age, as the significantly elucidated. There are likely some
nervous system matures and functional abnormal- similar, universal mechanisms, and other different
ities are more clearly observed (Palisano et al. unique mechanisms for specific etiologies. Plas-
2008; Hanna et al. 2009). Often, the earlier func- ticity, or successful brain function repair, for the
tional category noted is more severe. Although the individuals with CP is difficult to predict (Giza
GMFCS category system with five levels of sever- et al. 2009; Johnston et al. 2009).
ity is excellent in predicting motor development, it
does not give a picture of other important aspects
of development like cognition. The GMFCS can Developing a Prognosis
be difficult for families to understand. I have
found parents understand a three-tiered descrip- When reviewing literature about prognosis, cer-
tion more easily. tain important questions need to be considered
(Hansebout et al. 2009). Was the specific literature
Mild: Abnormal movements, posture, and tone review a homogeneous and representative sample
but can function in all tasks without significant similar to your patient?
aides (corresponds to GMFCS I)
Moderate: Abnormal movement, posture, and tone 1. Were the literature subjects at a similar stage in
and may need aides to complete daily functional the disease (timing of insult) or developmental
tasks (corresponds to GMFCS II–III) process?
Severe: Abnormal movements posture and tone 2. Were adjustments made for significant prognos-
and cannot complete daily tasks even with tic factors and clinically relevant subgroups?
aides (corresponds to GMFCS IV–V) 3. Was follow-up sufficiently long and complete?
300 S. C. Bean
The American Academy of Neurology’s Prac- initial insult till the static neurologic picture is
tice Parameter: Diagnostic assessment of the appreciated. It also does not address potential
child with cerebral palsy (Ashwal et al. 2004) confounding issues of secondary injury like sei-
does a wonderful job in reviewing the literature. zures, and the deterioration due to orthopedic
Nevertheless, the prognostication to families is issues and pain. RD Lund in Development and
faced with nonhomogeneous etiologies and risk Plasticity of the Brain (Lund 1978) correctly
factors, different patterns of unfolding gross notes “that neurons and specific patterns of
motor function, and different timing of the their connections are not the product of a single
onset of dysfunction. These limitations increase event but are the result of continued interaction
the difficulty of predicting what is most impor- throughout all stages of development between
tant for the quality of life of persons with CP and the neuron and its environment. Even as we
their families. Cognitive function, communica- mature the neuron is still subject to the vicissi-
tion, and behavior disturbances are the most sig- tudes of its surroundings.” This applies in my
nificant issues affecting quality of life in older opinion to the microscopic and neurochemical
children, teenagers, and adults, and their fami- environment as well as the macroscopic envi-
lies. From the families’ point of view, motor ronment in which the individual person with CP
challenges are important, but it is only the most and his family reside.
severe motor dysfunction that significantly With these issues unresolved, it is understand-
impacts quality of life, especially nonambulatory able that often physicians are hesitant to declare
dystonic-hyperkinetic CP and nonambulatory the diagnosis too early. Families are concerned
spastic quadriplegic CP. This is not to deny the often by what they perceive as a late diagnosis
lifelong challenges with milder motor dysfunc- which could delay beginning active therapy
tion. Teenagers more than younger children and (Guttmann et al. 2018).
their parents find even mild motoric disability This problem can be alleviated by careful his-
very impactful on their quality of life. tory and serial neurodevelopmental examinations.
It is remarkably difficult to answer the ques- Attention to details of maternal gestation, labor
tions that make ultimate prognosis more accurate and delivery, and the neonatal period are impor-
for an individual‘s specific etiology and risk factant. A good family history is also essential. One
tors. This is especially true under 2 years of age. does not have to wait to provide early intervention
The exception to this is in the most severely with family-based physical therapy (PT) and/or
motorically affected children. Even that is not occupational therapy (OT) until a formal diagno-
certain. I have cared for a nonambulatory high sis of CP is made. When early tone and abnormal
school senior with a severe spastic triplegia with postural reflexes raise suspicion of potential motor
dystonia and poorly understandable speech due to dysfunction, prompt beginning of early interven-
oral buccal spastic dyspraxia who was one of the tion strategies is essential. Discussion with the
top academic performers of his class and was family of the potential for motor dysfunction and
sought after as a preferred science project partner. neurologic injury should be addressed but with
He is presently in college. The American Acad- clear emphasis on the difficulty in predicting
emy of Neurology’s Practice Parameter (Ashwal severity which is often impossible from the infant
et al. 2004) called for future research to enhance examination. The physician should provide hope-
strategies to uncover cost-effective diagnostic ful positive and guarded expectation. Addition-
evaluations for discovering CP etiology, quality ally, serial follow-up consultations for observing
of life issues related to education, social support, specific associated conditions and preparing the
and to discover the mechanisms related to meta- family for the comorbidities that may accompany
bolic and genetic conditions. the CP motor disability is important. It is essential
Although CP is considered static, its slowly for the physician and developmental team to be
unfolding nature does not address what mecha- vigilant for the myriad of CP masquerading
nisms of injury and repair are occurring from the conditions.
Prognosis: Comorbidities and Life 0.35% over the next 20 years. The heterogeneity
Expectancy of these populations has to be considered when
applied to an individual child.
Quality of life and functional mastery of life’s chal- When families ask “How long will my child
lenges are not just determined by motor function. live?”, they are not wanting to know mean or
The comorbidities associated with CP, particularly median survival. They want to know how to plan
intellectual deficits, poor communications skills, for the long term for their child. Of course no one
and behavior disorders are extremely important has a crystal ball, but in most children, except the
(Fig. 1). Epilepsy can affect 20–40% of individuals most severely involved, a normal life expectancy
with CP and presents significant challenges. These is predicted. During the last 40 years, I have
comorbidities particularly are overrepresented in followed children into adulthood. I observed that
individuals with the most severe motor limitations. if the most impaired individuals survive to age
Most children with CP live to adulthood. In a 6, families need to be prepared for them to live
Swedish study, 60% of the most severely motori- to at least 30 years of age. Of course many die
cally limited (GMFCS V) individuals were alive before this, but it is important for family planning
at 20 years (Westbom et al. 2011). to be aware of the most likely possibilities.
A California study (Strauss et al. 1998) noted
that children with the most severe limitations,
(who were immobile, could not lift their heads The Challenge of Masqueraders
when prone and were tube fed) had a limited life
expectancy. They often died by 5 years of age. Not only are the unfolding, changing signs, sever-
Only 20% of these severely affected individuals ity, and type of CP difficult to prognosticate, the
with multiple handicaps survived to 10.9 years in diagnosis needs to be secure and not confused for
1983. Survival improved to 17.1 years in 2010 masqueraders of CP. With the advent of neuroim-
(Brooks et al. 2014) strongly suggesting that the aging (especially MRI), metabolic testing, and the
quality of supportive care is important. E. Blair explosion of genomic studies (microarray and
(Blair et al. 2001) noted mortality above 1% per whole genome), the physician needs to be more
year for the first 5 years and then dropping to vigilant to diagnose progressive conditions. CP
80% COMORBIDITIES
70%
60%
50%
40%
30%
20%
10%
0%
Fig. 1 Comorbidities associated with cerebral palsy diag- who will have these most common comorbidities. Num-
nosis. This figure represents the percent of patients in a bers are abstracted from the reported literature. (Hanna
population of children with a diagnosis of cerebral palsy et al. 2009; Ashwal et al. 2004)
302 S. C. Bean
should not progressively worsen but subacute Even noncentral nervous system diseases can
slowly evolving conditions that have specific neu- masquerade as CP. I have seen a 5-year-old child
rosurgical treatment could be missed such as sub- diagnosed with CP, when her prominent muscle
dural hematomas or slowly progressive bulk, fluctuating increased tone, and stiffness
hydrocephalus. Consideration for spinal cord dis- decreasing after “warming up exercises” was
orders should be thought of with paraplegias. found to be due to myotonia congenita. This rein-
An increasing number of specific genetic and forces the danger of CP being a final diagnosis and
metabolic diseases of the central nervous system not keeping an open mind. This child has been
can be diagnosed. Some of these diagnoses have significantly helped with carbamazepine.
specific treatments or unfavorable prognoses Each of the CP syndromes (spastic hemiplegia,
because they are degenerative. Without the spastic diplegia, spastic quadriplegia, Hyperkinetic-
appropriate diagnosis, it is impossible to have dystonic, ataxic, and hypotonic) has masqueraders.
the opportunity for genetic counselling, providing The high percentage of specific and progressive
appropriate prognosis, specific treatments to disorders presenting and persisting as hypotonic
improve or ameliorate the condition, appropriate and ataxic CP makes me very cautious to even
medication adjustment, and more appropriate include them in the CP rubric. A search for specific
informed disease monitoring (Lee et al. 2014). etiologies needs to be particularly complete with
Many neurogenetic disorders can be subtle in these syndrome complexes before attempting to
their presentation. Leukodystrophies such as give prognostic guidance to families.
metachromatic leukodystrophy, Pelizaeus- The diagnostic process can be difficult. The
Merzbacher disease, and Retts syndrome can be kernicterus story is a good example. Hemolytic
challenging to separate from the slowly unfolding disease of the newborn from RH incompatibility
and changing neurologic symptoms of CP which can lead to a newborn picture of an acute bilirubin
are due to static, nondegenerative, time limited encephalopathy with stupor, hypotonia, poor
insults like intraventricular hemorrhage, peri- suck, and seizures in the first days. By
ventricular leukomalacia, focal ischemic stroke, mid-week, hypertonia, opisthotonus, and
watershed ischemia of hypoxia and ischemia, retrocollis occurs, only to be followed in the next
and deep basal ganglionic injury from near total 12 months by apparent improvement with
asphyxia. The paper by R. W. Lee et al. is a diminishing tone, abnormal asymmetric tonic
particularly good review of these masqueraders neck reflex, and brisk DTRs. There is delay in
and should be referred to for further in depth motor milestones and then development of abnor-
reading (Lee et al. 2014). mal up gaze, and sometimes years later variable
The clinical RED FLAGS, which should alert chorea and athetoid movements becomes appar-
one to consider these CP-like conditions and ent. There are partial and milder presentations
explore further evaluation, are as follows: with normal appearing children with high tone
deafness and mild very late chorea. Kernicterus
1. A history not consistent with pre- or perinatal is presumably a static insult in the early newborn
and neonatal risks. period. If the newborn and early childhood history
2. Normal MRI or MRI only showing globus was unavailable, this changing, slowly unfolding
pallidus abnormalities or disease specific disorder could be misconstrued as a degenerative
abnormality. hyperkinetic disorder.
3. Consanguinity or a suspect inheritance pattern.
4. Neurologic regression or clear deterioration
and loss of milestones. Early Neurologic Examination
5. Hypotonia as the prominent symptom. Predicting Specific CP Syndromes
6. Rigidity rather than spasticity as a prominent
symptom. I like to separate CP types into syndromes of
7. Paraplegia alone. motor dysfunction: spastic hemiparesis, spastic
8. Ataxia as the predominant symptom. diplegia, spastic quadriplegia, hyperkinetic-
dystonic, ataxic, and hypotonic CP. These syn- late development of reflexes and postures signal
dromes correlate to the neuropathological locali- risks of CP.
zation of dysfunction. I recognize that there are Delayed motor milestones corrected for gesta-
frequently mixed and overlapping syndromes, but tional age such as not sitting by 8 months, not
when fully established, the prominent syndrome walking by 18 months, and asymmetry of hand
does lend therapeutic and prognostic guidance. function before 18 months are useful early indi-
The newborn and early infancy neurodeve- cators. Serial examination of appropriate appear-
lopmental examination is less specific for ance and disappearance of neurodevelopmental
uncovering the specific etiology and neuropatho- reflexes and milestones is very helpful in alerting
logical localization of a specific CP syndrome. to the possibility of CP. I have found that using
The general examination can be more revealing many of the techniques from the Brazelton Neo-
of CP etiology. Attention to growth, height, natal Assessment Scale (Brazelton 1978; Als et al.
weight, and head circumference is important. 1977), especially visual and social interaction, are
Neurocutaneous stigmata and facial dysmorphism very helpful in alerting parents to neurologic sta-
often predict central nervous system abnormality. tus of their infant in ways that help them under-
Hypotelorism and hypertelorism can suggest mid- stand their infant’s behaviors and reactions.
line defects. Inspection of the skull noting cranial The reader is encouraged to review the work
sutures and fontanels, asymmetry, macrocephaly, of Bronson Crothers (1951a, b) and Richman
microcephaly, and dolichocephaly is important. Paine (1962), Amiel-Tison (1978; Amiel-Tison
Ocular abnormalities, such as colobomas and cat- and Stewart 1989), Barry Brazelton (1978), and
aracts, as well as organomegaly, limb deformities Arnold Capute (Allen and Capute 1989), and
and asymmetries, and midline spine defects others who have added significant insight into
should be sought. These help to delineate the this evaluation which requires careful observation
specific CP etiology and help clarify and clinical skill; checklists usually miss the
prognostication. essence. In the clinical interaction performed
The neonatal neurodevelopmental examina- with kindness and sensitivity, a bond is made
tion relies on tone, neonatal/infant and postural with parents that sets the stage for supportive
reflexes, alertness, and attentiveness. The dys- care of the child in a family context. The serial
function causing abnormalities in these parame- examination sets the stage for a helpful prognos-
ters is most indicative of acute central nervous tication and therapeutic alliance. Abnormality on
system stress. Except for visual tracking, visual the sequential newborn examination can be a sig-
following, optokinetic nystagmus, and possibly nificant risk factor for the development of CP.
the ocular spinning response (initiating ipsilateral Many who will develop CP will display vary-
deviation of the eyes and reverse nystagmus from ing periods that I call “pseudo-normalcy” before
spin direction), the neonatal tests uncover func- unfolding persistent signs of CP. They seem to
tion below the diencephalon in the brainstem and reestablish more normal neonatal reflexes and
spinal cord. The Moro, suck and root, non- improved alertness, but sometimes show
obligatory tonic neck, righting response, traction extremely subtle decrease in normal adventitious
and head lag, foot placement and step, newborn movements, often with more stereotypic character
reflex walking, vertical and horizontal suspen- without the normal alternating ballet like smooth
sion, parachute, Landau, supported standing with alternating movements. This more normal period
feet on a flat surface, “flying on air sign” (placing can be falsely reassuring as the infant may pro-
feet on flat surface causing legs to flex and with- ceed to show motor abnormalities when older.
draw), and visual and tactile habituation, all give This emphasizes the need for serial examination
the examiner a sense of the homeostatic function of the child while providing family-centered
and organization of the infant with relative insen- support.
sitivity of cortical function. Only visual function Only the most severely affected infants do not
and social interactive awareness give more corti- show improvement of their neonatal and early
cal clues to development. Excessive persistence or infancy symptoms. They remain hypotonic,
304 S. C. Bean
apathetic with blunted visual responses, have a neonatal stereotypic foot placement), and an
paucity of stiff, “cramped” movement, disordered absent or asymmetrical parachute response.
suck and swallow, depressed reflexes, or abnor- 3. At 12 months, a strong stereotypic extensor
mally persistent reflexes like the Moro, automatic trunk and leg thrusting is noted in the vertical
stepping, neck hypertonia, and asymmetrical position (Bleck 1979; Aicardi and Bax 1992).
obligatory tonic neck responses, and abnormal
parachute. Deep tendon reflexes are usually Prediction of the motor progress and walking
increased. These infants progress to severe dys- does not always predict cognitive status and
tonic and/or severe spastic quadriplegia without a comorbidities.
period of pseudo-normalcy or a very short period
in which they appear to be improving.
Remarkably, despite a grim presentation, some Specific Syndromes
neonates with newborn encephalopathy
completely resolve. A case example is an infant Spastic Hemiplegia – These children generally
born full term with a diagnosis of hypo- have hemispheric injury often by ischemia in the
xic–ischemic encephalopathy with Apgars of middle cerebral artery distribution or injury to the
0/0/0/1. He displayed profound hypotonia, deep periventricular white mater. The former are
suppressed ocular-vestibular reflexes, poor suck, more often seen in full-term infants. Most often
apathy, poor visual responses, and fragmentary the children are normal at birth but the family
multifocal seizures for the first few days of life. notes the infant has subtle disinclination to use
He gradually improved over the next weeks, one hand, usually noted by 4–9 months of age
appearing vigorous on discharge from the NICU. (normal handedness 18 months). Examination
He was a perfectly normal child at 4 years of age. reveals stiffness and clasp knife spasticity and
This is a case emphasizing the prognostic diffi- decreased reaching or grasping with the distal
culty from the early life examination. Crothers hand, which is stiffly fisted with the thumb flexed
and Paine (1959, 1988) appropriately cautioned into the palm (cortical thumb). The arm has a
“over optimism is as dangerous as unjustified flexed, abducted posture. Pincer grasp does not
pessimism.” develop. The ipsilateral leg has more extensor
Some infants may have no hint of neonatal tone and less movement. This is more obvious
encephalopathy and unexpectedly begin to show with attempts to crawl, cruise, stand, and walk.
delayed milestones and motor abnormality. The Clonus, brisk deep tendon reflexes, and toe walk-
severity outcome is difficult to predict in these ing is seen on the affected side. There is rarely
situations, especially when there seems to be significant facial asymmetry. Remarkably 98% of
early resolution of abnormal signs. The most these children walk and some before 18 months,
severely affected infants with persistently severe albeit with a hemiplegic gait with a flexed upper
findings of apathy and hypotonia, transitioning limb and circumducted extended spastic
into spasticity, rigidity, and dystonia, predictably lower limb.
do not do well. If an ipsilateral visual field defect can be
The prognosis for walking, which is a frequent uncovered, the lesion is usually large, involving
early question from parents, will likely be signif- the frontal, parietal, and occipital lobes. Bringing
icantly delayed if: a colored tape measure or small red ball dangling
on a string from behind the child’s head slowly
1. After 6 months (corrected age), the Moro reflex into his visual field, one can discern unilateral
persists, there is strong obligatory and asym- visual inattention as early as 6 months. Children
metrical tonic neck reflex, and a strong oblig- with a visual field defect have more motor
atory neck righting response. disability, more cognitive dysfunction and higher
2. After 12 months, there is absence of visual and percentage of symptomatic epilepsy. Children
tactile foot placement reaction (not the with deep white matter lesions often function
much better than those with cortical insults At 5–6 months, movement from horizontal to
in regard to cognition and epilepsy. Seizures vertical suspension causes bilateral tonic stiff,
are frequent in this group. Older children demon- spastic leg scissoring, and pointed toes. The legs
strate parietal sensory neglect, astereognosis, and have prominent hyperreflexia and clonus. There is
agraphesthesia. Parietal and occipital dysfunction usually much milder spasticity of the upper limbs,
can impact cognition, education, and employ- with hyperreflexia, abnormal posturing, and poor
ment. Dyskinesia may also develop, particularly hand grasp. Sitting position is unique with a stiff
in older children and teenagers. Growth of the lower lumbar sacral spine and a more flexible
affected limbs is blunted in length and girth. Com- forward bending upper spine. Paraspinal muscle
paring front view of thumb sizes picks up early palpation easily demonstrates the tight lumbar
growth disparity. Contractures are common. sacral area and softer cervical thoracic region.
Spastic Diplegia – These children are predom- This correlates with the white matter tracts to the
inantly premature and have periventricular lumbar sacral area layering in close proximity to
leukomalacia, with or without germinal matrix the leg fibers, as there is more extensively injured
hemorrhages. In more severe cases, they may white matter at the ventricular external angle by
have unilateral venous infarction of the central periventricular leukomalacia. This pathologic
cerebral vein. Ultrasound shows cystic cavitation white matter injury can unfold more slowly in
in the periventricular area, but this may clear even milder cases, with symptoms noted first between
in the neonatal period. Bilateral and often asym- 12 and 18 months of age. When attempting to
metrical ventricular irregular curvilinear enlarge- walk, these children are on tip toes with flexed
ment is seen on imaging. The deep white matter knees and hips, and with a positive Babinski sign
tracts curve around the lateral edge of the ventri- (more difficult to demonstrate under 1 year of age)
cle, with leg areas closest to the ventricle surface, and hyperreflexia. Ambulation without a wheel-
followed by trunk, arms, and face fibers. The optic chair is successful in 98% of these children, Epi-
radiations in the posterior lateral ventricle can be lepsy is less frequent and cognitive and learning
involved. These areas are the arterial end zones in challenges are generally less severe.
the premature brain vasculature and sustain the Spastic Quadriplegia – These children have
most injury from ischemia (Volpe 2018). severe bilateral cortical and brainstem pathology
Children with diplegia have bilateral and fre- with variable involvement of the basal ganglion.
quently asymmetrical spasticity of the lower Many different pre- and perinatal and occasion-
legs, with hand and arm spastic involvement ally postnatal encephaloclastic insults can cause
being relatively less severe. The premature this pattern of CP. Many genetic and dysmorphic
infants may show early low tone, feeding diffi- etiologies, and CP masqueraders also are associ-
culty, and blunted alertness for a few months, ated with spastic quadriplegia. Multicystic
but often have a benign appearing course, encephalomalacia, bilateral watershed infarction,
“pseudo-normalcy,” until the higher cortical selective neuronal necrosis, hydranencephaly, as
input exerts its controlling effects on spinal well as major migrational abnormalities are fre-
and brainstem reflexes. As with other CP quent with this form of CP.
types, prolongation of the disappearance of the These infants initially have profound hypoto-
Moro reflex, automatic stepping, involuntary nia. There are delayed milestones and decreased
plantar and palmar grasp, a strong obligatory spontaneous movement without the normal
asymmetric tonic neck reflex and neck righting infant’s stretching and dance like alternating
reflex, abnormal Landau, abnormal parachute, smooth spontaneous movement. Oral motor con-
and subtle more “cramped” less alternating and trol is abnormal with feeding difficulties and
smooth leg kicking can be seen. These abnor- abnormal suck and swallow. Oculocephalic
malities are often absent or not as prominent as reflexes initially are abnormal. Tracking and
in severe spastic quadriplegic or dystonic- visual following are poor and often there is a
hyperkinetic CP. bland facial appearance with blunted visual
306 S. C. Bean
reactivity. Flaccid tone with brisk or normal deep unremitting dystonia and chorea movements and
tendon reflexes eventually evolves into increased unintelligible speech, who was frustrated with the
tone and tightness, with subsequent development lack of therapeutic gains. She researched deep
of severe spasticity in all limbs. There is a persis- brain stimulation and presented the supportive
tent Moro response, abnormal obligatory asym- articles on her computer to the medical team.
metrical tonic neck and righting responses, flying Abnormalities seen in the thalamus and poste-
on air sign (withdrawal of legs when attempting to rior putamina in the basal ganglion are the hall-
place feet on surface), and asymmetrical or mark of this type of CP. Often there are coexisting
delayed parachute reaction. Visual and interactive cortical and brainstem abnormalities.
responsiveness is often blunted. Hypotonic/Ataxic CP – This group is the most
The prognosis for ambulation without signifi- worrisome to assign a CP label, as the masquer-
cant aides is poor; with only 24% (GMFCS III–V) aders are legion that can present with this clinical
walking. Cognition is very frequently affected. picture. There are a great number of global cere-
Seizures are frequent. There remains a gradation bral abnormalities in addition to cerebellar and
of injury and severity of symptoms with milder brainstem circuit dysfunctions which impair coor-
cases showing less severe early signs and more dination of movement. The pathology and etiol-
rapid improvement. ogy are the most heterogeneous and this CP group
Dystonic-Hyperkinetic CP – The development has a high percentage of genetic disorders and
of hyperkinetic-dystonic symptoms (dystonia, cho- fewer acquired encephaloclastic disorders. For
rea, athetosis) are often superimposed on the spas- example, cerebellar hemorrhages rarely dominate
ticity of hemiplegia and spastic quadriplegia even the clinical picture in premature infants, and
years after the insult. At times, the successful ame- symptomatically are overshadowed by pyramidal
lioration of spasticity by dorsal rhizotomy or with dysfunction, so those infants are usually classified
the intrathecal baclofen pump in teenagers brings as spastic CP although there is a significant under-
out the hyperkinetic- dystonic movements that were lying ataxic component.
not previously appreciated. Likely the severe abnor- Early and prolonged periods of hypotonia and
mality of pyramidal tract spasticity hides the extra- failure to meet milestones eventually develop into
pyramidal symptoms. Although there are mild recognizable ataxia, dysmetria, tremor, and
cases not appearing until after 10 years of age titubation first noted at 1 year or later when there
even after normal early milestones, most hyperki- are attempts at sitting, which is often difficult even
netic and dystonic symptoms develop after with support. Although 23% of this group even-
1–3 years of age and often progress in severity tually walks, it is often very late and frequently
over the next few years. These symptoms often associated with cognitive abnormalities, seizures,
lead to torsional movement disorders and worsen- and hearing and speech disorders. Giving a prog-
ing motor severity scores. nosis here is fraught with danger unless a specific
The early infant examination can show auto- etiology can be uncovered with imaging and
matic and stereotypic mouth opening and signifi- genetic studies. Typical rare disorders that often
cant opisthotonos, prominent asymmetrical tonic present initially as hypotonic CP include Jouberts,
neck reflexes, and retrocollis. Feeding dysfunc- mitochondrial disorders, Dandy-Walker malfor-
tion is prominent. Only 25% develop some level mation, peroxisome disorders, Vanishing white
of ambulation. The difficulty with dyspraxic matter disease, PKU, rhombencephalosynapsis,
speech is that it often leads to an underestimation 4-H syndrome, etc. The more persistent the hypo-
of the intelligence of the child, although they do tonia or ataxia, the more vigilant one must be in
have variable cognitive issues. making a diagnosis before a prognosis is
A case example is a 16-year-old non- entertained (Lee et al. 2014). The purely hypo-
ambulatory woman with severe painful tonic cases also have significant cortical
dysfunction but particular attention to non-CNS early brain injury. Prognosis offered to families
etiologies such as muscle and anterior cell disor- should be offered with some optimism.
ders should be considered. I do not think these
children are served by a CP diagnosis.
Cross-References
Conclusion ▶ Cerebral Palsy and the Relationship to
Prematurity
The diagnosis of CP is not an ending point. CP is a
▶ Infectious Etiologies of Cerebral Palsy
beginning point requiring a search for risk associ-
▶ Perinatal Stroke as an Etiology of Cerebral Palsy
ations and specific etiologies. Making the diagno-
▶ Problems During Delivery as an Etiology of
sis of CP in the young infant is usually very
difficult due to the unpredictable effects of brain
maturation. It is also very important to always
consider the many masqueraders of CP especially
when the initial workup does not lead to a defin-
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99260
Classification Terminology
in Cerebral Palsy 21
Katherine B. Bevans and Carole A. Tucker
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 310
Goals and Environment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 310
Technique . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 311
Type and Topography of Neuromotor Impairment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 311
Neuroanatomical Classifications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 314
Gait Pattern Classifications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 315
Functional Classification Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 316
Evidence of Effectiveness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 320
Cross-Reference . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 320
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 320
Abstract participants. Classification systems categorize

Classification systems are intended to reduce people with cerebral palsy (CP) on the basis of
the complexity of heterogeneous conditions by type and topography of neuromotor impair-
grouping people with similar clinical manifes- ment, neuroanatomical disturbances, gait pat-
tations together. Classifications are intended terns, and functioning. The systems differ in
to improve communication among clinicians, their coverage of body structure, body func-
researchers, patients, and caregivers. They may tion, and activity levels as specified in the
guide clinical diagnosis, prediction of prog- International Classification of Functioning,
noses, goal setting, treatment decisions, and Disability, and Health framework. This chapter
determinations for service eligibility. They reviews commonly used classification systems
are used for population surveillance and for for people with CP, including their reliability,
identifying and/or describing research validity, and utility for specific uses.
Keywords
K. B. Bevans (*) · C. A. Tucker Classification · Type · Topography ·
Department of Health and Rehabilitation Sciences, College Functioning · Reliability
of Public Health, Temple University, Philadelphia, PA,
USA
e-mail: katherine.bevans@temple.edu;
carole.tucker@temple.edu; tuckerc@temple.edu

https://doi.org/10.1007/978-3-319-74558-9_20
310 K. B. Bevans and C. A. Tucker
Introduction an account of the severity of the condition and

how it is likely to evolve over time, for which
Cerebral palsy (CP) encompasses a group of functional and prognostic classification are neces-
permanent neurodevelopmental disorders of sary (Wood and Rosenbaum 2000; Rosenbaum
movement and posture caused by an insult to the et al. 2006). Healthcare systems may use classifi-
developing fetal or infant brain. Characteristic cations to predict service needs and utilization
signs of spasticity, movement disorder, muscle rates. Epidemiologists and outcomes researchers
weakness, ataxia, and rigidity range from subtle use classifications to estimate the population
localized impairment to severe whole-body prevalence of CP subtypes, conduct etiological
involvement. Beyond motor symptoms, people research, and study intervention effectiveness.
with CP are at increased risk for sensory, percep- In this chapter, we describe and evaluate classifi-
tual, cognitive, communicative, and behavioral cation schemes that are most commonly applied to
deficits, epilepsy, and secondary musculoskeletal people with CP. We review evidence of each
problems. Symptoms and comorbidities lead to a method’s reliability, validity, and utility for vari-
range of activity limitations, participation restric- ous applications.
tions, and reduced quality of life. There are numerous types of classification
The term CP is applicable to people with a schemes for people with CP. Each categorizes peo-
wide range of symptoms and functional capaci- ple according to a unique set of health or disability
ties. Given its heterogeneity, a CP diagnosis factors. The World Health Organization’s (WHO)
(in the absence of additional information) says International Classification of Functioning, Dis-
little about the condition’s manifestation, severity, ability, and Health (ICF) provides a useful frame-
or impact on a person’s participation and quality work for analyzing the degree to which
of life (Rosenbaum et al. 2014). Moreover, CP classification schemes consider body structure
definitions and diagnostic criteria are increasingly (anatomical), body function (physiological and
critiqued for their inattention to the occurrence psychological), or activities (execution of a task
and impact of nonmotor symptoms such as sei- or action) and participation (involvement in life
zures and learning and behavioral challenges. situations) (Rosenbaum et al. 2014; Jeevanantham
Alternatives to the predominance of motor deficits and Bartlett 2017). The ICF expands the traditional
in CP definitions reflect the need for an individu- medical model, which focuses on “fixing” primary
alized multidimensional approach to each affected bodily impairments by placing equal value on
person’s functional status and needs (Rosenbaum functional activities and participation in all aspects
et al. 2006). Broadening the conceptualization of of life. The prevailing classifications of CP used
CP reinforces the need for meaningful classifica- in rehabilitation can be broadly divided into four
tion of affected individuals. categories, each of which categorizes people
according to their body structures, body functions,
or activities (Table 1). These include type and
Goals and Environment topography of neuromotor impairment, neuroana-
tomic disturbances, gait patterns, and functioning.
Classification schemes are intended to reduce There are several important defining
the complexity of heterogeneous conditions features of classification systems. First, classifica-
by grouping people with similar clinical manifes- tions within a single system are meant to be
tations together. Classifications are intended mutually exclusive and collectively exhaustive
to improve communication among clinicians, (Rosenbaum et al. 2014). Second, classification
researchers, patients, and caregivers. They may systems are not tests, outcome measures, or diag-
guide clinical diagnosis, prediction of prognoses, nostic tool. However, it is important to consider
goal setting, treatment decisions, and determina- the psychometric properties of the tools used to
tions for service eligibility (Jeevanantham and classify people as well as the properties of the
Bartlett 2017). Parents and families wish to have classification system itself. Third, classifications
21 Classification Terminology in Cerebral Palsy 311
Table 1 Types of classification systems for people with CP

ICF
System type Description levels Example classification(s): categories
Type and Tonal and movement abnormalities Body Type: spastic, dyskinetic (dystonia and
topography of and distributional pattern of structure choreoathetosis), ataxic, hypotonic
neuromotor neuromotor impairment Topography: monoplegia, hemiplegia,
impairment diplegia, triplegia, and quadriplegia;
unilateral, bilateral
Neuroanatomic Location and presumed timing of Body MRI classification system (MRICS):a
brain injury structure maldevelopments, predominant white
matter injury, predominant grey matter
injury, and “miscellaneous” injuries
Gait pattern Gait deviations based on kinematic, Body Winters, Gage, and Hicks classification:b
classifications kinetic, temporal–spatial, and/or function four progressively more involved gait
electromyographic (EMG) data patterns based on sagittal plane kinematics
of the ankle, knee, hip, and pelvis
Functioning Classifications based on functional Activities Gross motor: Gross Motor Function
performance in everyday life (what Classification System (GMFCS)c
people can do) Manual ability: Manual Ability
Classification System (MACS);d Bimanual
Fine Motor Function Classification System
(BFMF)e
Communication: Viking Speech Scale
(VSS);f Functional Communication
Classification System (FCCS);g
Communication Function Classification
System (CFCS)h
Notes: aHimmelmann et al. 2017; bWinters et al. 1987; cPalisano et al. 1997, 2008; dEliasson et al. 2006; eElvrum
et al. 2016; fPennington et al. 2013; gBarty et al. 2016; hHidecker et al. 2011
serve many purposes and the utility of each sys- important outcomes (e.g., response to therapy).
tem varies across different applications (Gorter The validity of a classification system rests
et al. 2004). End-users should consider the fol- essentially on the usefulness of its categories.
lowing features of classification systems when For example, do the categories enable people
assessing their value for a specific use: to make meaningful distinctions between the
subgroups?
• Reliability: the consistency or repeatability of • Utility: Usefulness of the classification system
the classification. This includes the likelihood for a particular setting. The training, proce-
that different examiners will assign any given dures, and time required to accurately apply a
individual to the same class (interobserver reli- classification influence its utility.
ability) and that an individual will be assigned
to the same class at different times by the same
examiner (intraobserver reliability). No classi- Technique
fication system is useful unless it is reliable.
It is, therefore, not enough to specify the char- Type and Topography of Neuromotor
acteristics to be used in classification; they Impairment
must be operationally defined to enable exam-
iners to apply the system in a reliable manner. Conventional classifications group people with CP
• Validity: the likelihood that the clinical defini- according to the type of tone or movement abnor-
tion is important and meaningful to the person mality and the distributional pattern of affected
(content validity), associated with criterion limbs. Spasticity, predominates for 70–75% of peo-
(gold standard) measurements, and predicts ple with CP, followed by dyskinesia (10–15%),
ataxia (<5%), and hypotonia (2%) (Sankar and whether one (unilateral) or both (bilateral) sides
Mundkur 2005). Neuromotor types are differenti- of their bodies are affected (SCPE 2000). Among
ated according to whether positive or negative people with CP for whom spasticity predominates,
motor signs predominate (Sanger et al. 2003, 31–39% are classified as unilaterally affected and
2006, 2010). Positive signs include increased fre- 61–69% as bilateral affected (Novak et al. 2017).
quency or magnitude of muscle activity, movement, The CP classification systems used for popula-
or movement patterns (Sanger et al. 2003, 2010), tion surveillance of CP in Europe, Australia, and
whereas negative signs stem from insufficient mus- North America use different topographical spas-
cle activity or control (Sanger et al. 2006). ticity categories (Goldsmith et al. 2016). Within
spastic CP subtypes, Australian CP Registries
Spasticity use conventional limb distribution categories
Spasticity is defined as velocity-dependent (diplegia, triplegia, quadriplegia, hemiplegia).
increase in tonic stretch reflexes (muscle tone) European registries differentiate unilateral and
with exaggerated tendon jerks, resulting from bilateral spasticity and most North American pro-
hyperexcitability of the stretch reflex. Spasticity grams use both systems.
differs from other types of hypertonia (e.g., dys-
tonia) in that resistance to externally imposed Dyskinesia
movement have a speed or angle threshold that Like spasticity, dyskinesia is a symptom of
results in a “spastic catch,” the sudden appearance increased muscle activation and movement
of increased muscle tone (Sanger et al. 2003; Love (Sanger et al. 2010). Whereas spasticity is obser-
et al. 2016). Spasticity subtypes are differentiated ved in response to externally imposed (passive)
according to the number and location of affected movement, dyskinetic activity and movements are
limbs. The following prefixes are combined with performed by the affected person (Sanger et al.
the root word “plegia” (meaning paralyzed) to 2003, 2010). Dyskinetic CP is dominated by
specify how limbs are affected by spasticity: abnormal patterns of posture and movement
and/or involuntary, uncontrolled, recurring, and
• Monoplegia (<1%): one limp is affected; sometimes stereotyped movements (Sanger et al.
sometimes considered a form of hemiplegia 2010). Muscle tone is varying (Cans et al. 2007).
where one limb is more significantly impaired Abnormal postures are due to sustained muscle
than the other contractions including slow rotation, extension,
• Diplegia (29–36%): two limbs affected; usu- and flexion of body parts (Cans et al. 2007). The
ally indicates the legs are more affected than classification system used in most European coun-
the arms tries (Surveillance of Cerebral Palsy in Europe
• Hemiplegia (29–39%): the arm and leg on one [SCPE]) differentiates two dyskinesia subtypes:
side of the body are affected dystonia and choreoathetosis (Cans 2000). Dys-
• Triplegia (2%): three limbs are affected (e.g., tonic cases present with abnormal postures that
both arms and a leg, both legs and arm) or are repeatedly superimposed upon or substitute
could mean one upper and one lower extremity for voluntary movements. Increased tone is easily
and the face elicited. Although dystonic postures differ
• Quadriplegia (23–33%): all four limbs are between individuals, foot inversion, wrist ulnar
involved. Maybe be further specified as tetra- deviation, and lordotic trunk are common (Sanger
plegia (all four limbs are affected equally) or et al. 2010). Dystonic postures are often triggered
double hemiplegia (all four limbs are involved, by attempts at specific voluntary movements and
but one side of the body is more affected than they are sustained for variable lengths of time
the other). (Sanger et al. 2010). Choreoathetosis involves
sequences of involuntary movements or move-
An alternative topographical classification ment fragments that may flow continuously or
scheme groups people with CP according to comprise multiple discernable (jerky)
submovements. People with choreoathetosis often bilateral spastic CP by operationally defining

appear to be in constant motion. limb distribution categories (e.g., “four limb
dominated” means that arms are equally or more
Ataxia affected than legs) and specifying a dyskinetic-
Ataxia is the inability to generate a normal volun- spastic subtype (when lower limb spasticity is
tary movement pattern, such that movements present, but dyskinetic posturing is a dominant
are performed with abnormal force, rhythm, and feature). These standardized class definitions
accuracy (Sanger et al. 2006; Cans et al. 2007). resulted in close prevalence rates of bilateral spas-
Trunk and gait ataxia results in disturbed balance. tic CP subtypes across geographic regions
People with ataxic CP often over- or under-shoot (Krägeloh-Mann et al. 2008).
goal directed movements. Other prominent fea- SCPE, a network of CP registries maintained
tures include slow tremor and low tone (Cans by 14 centers in 8 European countries, developed
et al. 2007). hierarchical algorithms for determining whether
cases meet CP inclusion/exclusion criteria and for
Hypotonia classifying cases according to neuromotor deficit
Hypotonic CP is characterized by diminished tone type and limb distribution (Cans 2000; Cans et al.
and decreased resistance of muscles in the limbs, 2007). By this system, predominance of increased
trunk, or craniofacial skeletal to passive stretching muscle tone in one or more limb indicates spas-
(Lisi and Cohn 2011). The major CP Registry in ticity, a category that is further differentiated
Australia and North America classify children based on the number of affected limbs and
with predominant hypotonic impairment. whether involvement is unilateral or bilateral.
Despite their abundant use, most classification Dyskinesia is characterized by involuntary,
systems based on type and topography of neuro- uncontrolled, recurring, and sometimes stereo-
motor deficits have poor inter- and intra-rater reli- typed movements. This category includes dys-
ability (Flamand et al. 2013; Gainsborough et al. tonic and choreoathetotic subclasses. Ataxic CP
2008). Early work estimated agreement among cases lack orderly muscular coordination such
trained clinicians to be about 50% for topograph- that movements are performed with abnormal
ical classifications and 40% for motor disorder force, rhythm, or accuracy and disrupted balance.
type (Blair and Stanley 1985). Inconsistencies in The SCPE classification groups children with
classifications based on neuromotor deficit type mixed CP form (e.g., spasticity and ataxia)
and topography arise from variable and imprecise according to their dominant clinical features.
category definitions (Gorter et al. 2004). For Initially, CP registries applied the SCPE
example, ambiguities exist regarding the level of classification algorithms with fair interobserver
upper extremity impairment required to indicate agreement about case inclusion/exclusion
quadriplegia (rather than diplegia). Determining (weighted kappa [Kw] = 0.59, mean agreement
the relative severity of arm and leg involvement 89.3%), but significant discrepancies in the clas-
can be challenging because upper and lower sification of CP subtypes (Gainsborough et al.,
extremities have such unique functions. 2008). Classification reliability was poor in two
Unreliable categorization of CP cases pre- areas: differentiating between spastic versus dys-
cludes data aggregation, which is necessary to kinetic type and judging distribution of spastic
amass sufficient numbers of people with CP for involvement (unilateral verses bilateral). An eval-
population surveillance and to analyze subgroups uation of intraobserver reliability (5 months later)
of people with CP, particularly over time (Cans revealed wide variation in raters’ determinations
2000; Cans et al. 2007). In response to this chal- about case inclusion over a 5-month interval
lenge, several research networks have attempted (Kw = 0.25 to 1.0). For CP subtype, mean
to standardize CP case identification and classifi- intraobserver agreement was 74.4% among raters
cation methods. Krägeloh-Mann and colleagues who classified cases as meeting CP inclusion
improved classification precision for people with criteria at both time points. Altered responses
showed relatively poor repeatability of both limb Poor reliability may impede validity of
distribution categories (e.g., changing from spas- neuromotor type and topography classification
tic bilateral to spastic unilateral) and neuromotor systems (Gorter et al. 2004). Multiple studies
deficit subtypes (e.g., changing from dystonic to demonstrate that these classifications fail to dif-
choreoathetotic) (Gainsborough et al. 2008). ferentiate functional levels or predict functional
In response of these initial challenges, SCPE development in CP (e.g., mobility) (Ross and
developed standardized data collection forms and Engsberg 2007; Alriksson-Schmidt et al. 2017).
reference and training material to improve consis- Moreover, type and topographical classifications
tency with which the algorithms were applied have not met their promise in aiding diagnosis
across registries. A subsequent study tested phy- or therapy. Because brain dysfunction has
sician rater agreement for their classifications diffuse manifestations in childhood, knowledge of
based on primary (video) observations of children neuromotor type and distribution is insufficient for
with CP and review of clinical information identifying therapeutically important disorders or
presented in case vignettes (Sellier et al. 2012). for selecting treatment approaches (Shapiro 2004).
Reliability was excellent in assessing whether or
not a child had CP based on primary observation
(Kw = 1.00) and substantial for vignettes Neuroanatomical Classifications
(Kw = 0.73). Agreement on neuromotor subtype
was substantial for both primary observations Neuro-anatomical classifications have evolved
(Kw = 0.85) and vignettes (Kw = 0.78), indicating in recent years and continue to progress as cere-
that training and standardized tools help profes- bral imaging techniques improve (▶ Chap. 13,
sionals classify children with CP more reliably. “Neuroimaging Pathology in Cerebral Palsy”).
Nonetheless, physician raters continued to dis- Use of neuroimaging modalities such as mag-
agree on the predominance of a single motor netic resonance imaging (MRI) show that over
deficit type for cases with multiple types of 80% of children with CP have neuroanatomical
motor impairment signs, especially when clinical abnormalities and reveal pathogenic patterns
information was abstracted from case vignettes that may underlie CP signs and symptoms
(Sellier et al. 2012). Rosenbaum et al. (Korzeniewski et al. 2008; Himmelmann et al.
recommended classifying both dominant and 2017). The human brain undergoes complex
secondary tone or movement abnormalities when organizational changes during both intra- and
multiple impairment types are present in the same extrauterine development. Thus, lesions or abnor-
individual (Rosenbaum et al. 2006). Consistent malities observed through neuroimaging reveal the
with these recommendations, the CP classification developmental stage when the insult took place.
system used by the Autism and Developmental For example, if an insult takes place during the
Disabilities Monitoring (ADDM) Network first or second trimesters, during which most corti-
includes multiple “mixed” impairment categories: cal neurogenesis takes place, maldevelopments
spastic-dyskinetic, spastic-ataxic, and dyskinetic- such as lissencephaly, pachygyria, or poly-
ataxic classes (Yeargin-Allsopp et al. 2008). microgyria may occur. CP may result if these
Classification systems are only as reliable of the maldevelopments affect the motor cortex. Distur-
measurement tools used to assess categorization bances to brain development that occur during the
criteria. Several systematic reviews of spasticity third trimester, when neuronal differentiation
assessment tools (e.g., Modified Ashworth Scale, events predominate (e.g., axon, dendrite, synapse
Modified Tardieu Scales) reveal wide variation in formation; myelination), mainly result in clastic
the reliability of these measures (Scholtes et al. lesions. White matter is especially affected early
2006). Similarly, measures of dystonia (e.g., Barry- in the third trimester. Lesions that occur in the
Albright Dystonia Scales, Burke–Fahn–Marsden central motor domains during the third trimester
Dystonia movement Scale, Unified Dystonia Rating generally affect the cortical grey matter, basal
Scale) have limited sensitivity when applied to chil- ganglia, and thalamus (Himmelmann et al. 2017).
dren with CP (Elze et al. 2016). Thus, certain pathological patterns are
characteristic of disturbances or insults that take Palsy Gait Pathology”). They are intended for
place at specific time periods during early brain diagnostic use, to streamline communication
development (Korzeniewski et al. 2008). among clinicians, and to facilitate clinical
Numerous neuroanatomical classification decision-making (Dobson et al. 2007). In a sys-
systems were devised to enable research on tematic review of existing gait classification sys-
the etiology, pathology, and timing of insults that tems, Dobson and colleagues identified 18 studies
cause CP and to characterize brain structure- that described methods for classifying children
function relationship (Korzeniewski et al. 2008; with CP based on gait impairments or deviations.
Himmelmann and Uvebrant 2011; Reid et al. Most classifications used kinematic data. Some
2014). The SCPE developed the MRI clas- systems used kinetic information to supplement
sification system (MRICS) by harmonizing kinematics. Fewer systems used EMG and
multiple neuroanatomical classifications for CP temporal–spatial information. About half of the
(Himmelmann et al. 2017). MRICS differentiates gait classification systems were created using
maldevelopments, predominant white misspelled quantitative statistical construction techniques,
injury, predominant grey matter injury, and mainly cluster analysis. Remaining classifications
“miscellaneous” injuries (e.g., cerebellar atrophy, were qualitatively constructed. For most qualita-
cerebral atrophy, delayed myelination). tively constructed classifications, the process used
Interrater reliability of the MRICS was found to to identify and define categories was poorly
be weak (Kw = 0.57) for clinicians’ classification described and justified. Although efficient walk-
of images, but strong (Kw = 0.81) for ratings of ing relies upon the appropriate alignment of the
reports of images (Himmelmann et al. 2017). lower limbs in all three of the sagittal, coronal, and
Although raters tended to agree on the classification transverse planes, two-thirds of gait classification
of predominant white matter, maldevelopments, systems identified by Dobson et al. (2007) relied
and predominant grey matter injuries, they identi- solely on data from the sagittal plane. Only a
fied “miscellaneous” injuries with less consistency. single system considered variables in all three
Further, no clear approach was established for clas- planes of motion. This limitation reduces the clin-
sifying cases with multiple lesions. It is difficult to ical utility of gait classification systems, such as
determine which abnormality causes the CP signs for informing clinical decisions related to invasive
and symptoms. Methodological differences in neu- surgical interventions that rely heavily on gait
roanatomical classification resulted in varied esti- information in the transverse plane (e.g.,
mates of class prevalence across studies. Although osteotomies of the femur and tibia). Finally,
variation in the distribution of motor function levels none of the gait classification systems had com-
across neuroanatomical classes indicates that neu- plete and adequate reliability evidence.
roanatomic classification systems may have some Winters, Gage, and Hicks (1987) (WGH)
clinical validity (Himmelmann and Uvebrant developed the most commonly used and cited
2011), the principle contribution of these classifi- gait classification system. It matches children
cation systems has been to advance understanding with unilateral spastic CP to four progressively
of CP etiology and pathogenesis (Shapiro 2004; more involved gait patterns based on sagittal
Korzeniewski et al. 2008). plane kinematics of the ankle, knee, hip, and
pelvis. Interrater reliability of the WGH classifi-
cations was assessed among 16 experienced clini-
Gait Pattern Classifications cians who reviewed kinematic reports and videos
of 34 children with spastic hemiplegia (Dobson
Multiple classification systems have been pro- et al. 2006). Overall, interrater reliability was sub-
posed for grouping people with CP based on gait stantial for both clinical reports (Kw = 0.77) and
deviations. Gait classification systems categorize videos (Kw = 0.62), but exact agreement was
people into like classes based on kinematic, unacceptable for some gait patterns (65%, range
kinetic, temporal–spatial, and/or electromyo- 32–74% for reports and mean 53%, range
graphic (EMG) data (▶ Chap. 90, “Cerebral 35–94% for videos). In a separate study,
McDowell et al. (2008) found that 42% of chil- movement and use of assistive devices (walkers,
dren with hemiplegic CP were “not classified” crutches, canes, wheelchairs) for mobility during
according to the WGH criteria. The WGH classi- a person’s usual activity. It was initially developed
fication system may lack sensitivity for gait devi- for 2- to 12-year-old children based on empirical
ations exhibited by children with milder motor examination of Gross Motor Function Measure
impairment, especially when motor deviations (GMFM) scores and thereafter, refined based on
are best detected by coronal and transverse plane nominal group process and Delphi survey con-
kinematics. Although WGH and other gait sensus methods involving physical therapists,
classification systems are useful for facilitating occupational therapists, and developmental pedi-
communication among clinicians, they are a sim- atricians (Palisano et al. 1997). The GMFCS was
plification of reality. A continuum of gait devia- later revised and expanded to include descriptions
tions exist between classes and some gait of adolescent (>12 to 18 years) gross motor func-
deviations are not described by existing classifi- tion and to improve differentiation between levels
cation systems (Dobson et al. 2007). Moreover, while taking in to account children’s ages and
gait kinematic parameters (in isolation or in com- normative developmental milestones (Palisano
bination) are only weakly associated with overall et al. 2008). The GMFCS expanded and revised
physical functioning and perceived health status (E&R) version is used to classify self-initiated
in children with CP (Abel et al. 2003). movements, in sitting and walking, according to
5 levels of function from level 1 (independent
movement) to level 5 (complete assistance).
Functional Classification Systems Each level of the GMFC-E&R provides func-
tional descriptions for five age groups: 1–2, 2–4,
Functional classification systems categorize peo- 4–6, 6–12, and 12–18.
ple with CP according to their performance of GMFCS interrater reliability is strong when
functions that meaningfully impact daily life. classification is based on review of written clinical
Functional classification systems describe what reports (Wood and Rosenbaum 2000), viewing
people can do without regard to the way the func- video recordings of children (Ko et al. 2011),
tion is achieved, and without traditional emphasis and abstraction of information from medical
on “normal” function (Rosenbaum et al. 2014). records (Benedict et al. 2011). To be useful as
Classification systems for gross motor function a classification system, the GMCFS should be
[Gross Motor Function Classification System relatively stable over time, even as children
(GMFCS)], fine manual function [Manual Ability change with age and development (Paulson and
Classification System (MACS); Bimanual Fine Vargus-Adams 2017). Overall, studies suggest
Motor Function Classification System (BFMF)], that GMFCS levels remain relatively stable over
and communication [Viking Speech Scale (VSS); time, although classification levels are less stable
Functional Communication Classification System in infants compared to older children and adoles-
(FCCS); Communication Function Classification cents (Wood and Rosenbaum 2000; Palisano et al.
System (CFCS)] are now frequently used in 2006; Alriksson-Schmidt et al. 2017). Among
surveillance registers, enabling the severity of 610 children with CP who were assigned between
impairments to be compared across time and 2 and 7 GMFCS ratings (mean = 4.3) over an
regions (Virella et al. 2016). Commonly used average of 33.5 months (SD = 10.3), weighted
classification systems are summarized in Table 2. kappa coefficients between the first and last rat-
ings were 0.84 for children under <6 years of age
Gross Motor Function and 0.89 for children 6 of age. About 1 in 4
The Gross Motor Function Classification System children remained in the same GMFCS category
(GMFCS) is the most established and commonly for all ratings (Palisano et al. 2006). Children
used functional classifications in CP. The GMFCS initially classified as levels I and V are the least
five-level classification describes self-initiated likely to be reclassified over time (Palisano
Table 2 Summary of functional classification levels

Classification Level I Level II Level III Level IV Level V
GMFCSa Can walk without Walk with Walk with assistive Walking ability Transported by
limitations limitations mobility device severely limited manual wheelchair
even with assistive
device; use of
power wheelchair
MACSb Handles objects Handles most Handles objects Handles a limited Does not handle
easily and objects but with with difficulty; selection of easily objects; has
successfully somewhat reduced needs help to managed objects severely limited
quality and/or prepare and/or in adapted ability to perform
speed modify activities situations even simple
actions
BFMFc One hand: (a) One hand: (a) One hand: (a) Both hands: Both hands: only
manipulates manipulates manipulates only ability to ability to hold or
without without without restrictions. grasp, (b) one worse
restrictions. The restrictions. The The other hand no hand: only ability
other hand: other hand: only functional ability, to grasp. The other
manipulates ability to grasp or
(b) one hand: hand: only ability
without hold, (b) both limitations in more to hold or worse
restrictions or hands: limitationsadvanced fine
limitations in more in more advanced motor skills. The
advanced fine fine motor skills other hand: only
motor skills ability to grasp or
worse
VSSd Speech not Speech is Speech is unclear No understandable N/A
affected by motor imprecise but and not usually speech
disorder usually understandable to
understandable to unfamiliar listeners
unfamiliar out of context;
listeners out of difficulties
context; loudness controlling
adequate for one to breathing for
one conversation; speech, harsh
articulation is sounding voice,
imprecise; most sudden change in
consonants are pitch; very small
produced range of consonants
FCCSe Effective Effective Effective Assistance Communicates
communicator in communicator in communicator in required in most unintentionally
most situation; can most situations, most situations; can situations; with others using
independently but needs some communicate a communicates movement and
communicate help; small range of routine needs/ behavior; routine
wide variety of communicates messages to most wants with needs/wants
messages to wide variety of familiar people; familiar people interpreted by
familiar and messages to requires assistance and accepts or familiar people
unfamiliar people familiar people; with unfamiliar rejects offered who observe
in most difficulties with people, topics, and choices with body individual’s
environments unfamiliar people, environments; may movements, facial emotions, body
topics, and use conventional expressions, or movements, and
environments gestures vocalizations behavior
CFCSf Effective sender Effective but Effective sender Sometimes Seldom effective
and receiver with slower paced and receiver with effective sender sender and
unfamiliar and sender and/or familiar partners and receiver with receiver with
familiar partners receiver with familiar partners familiar partners
unfamiliar and
familiar partners
Notes: aPalisano et al. 1997, 2008; bEliasson et al. 2006; cElvrum et al. 2016;dPennington et al. 2013; eBarty et al. 2016;
f
Hidecker et al. 2011
et al. 2006; Alriksson-Schmidt et al. 2017). absolute agreement) (Imms et al. 2010; Öhrvall
Caregiver-determined GMFCS classifications are et al. 2014) and over 3–5 years (Kw = 0.96, 78%
also relatively stable over time (Morris et al. 2004; agreement) (Öhrvall et al. 2014). The classifica-
Imms et al. 2010). Several studies provide evi- tion’s construct validity has been demonstrated by
dence of the GMFCS’s validity. GMFCS levels observed associations between MACS levels and
are strongly associated with mobility measures, scores on measures of hand function (Box and
including the Pediatric Evaluation of Disability Block Test, ABILHAND-Kids) and performance
Inventory (PEDI) mobility domain (Ko et al. of self-care activities at home (self-care domain of
2011) and expert-rated locomotion stages (Sanz the PEDI Caregiver Assistance Scale) (Öhrvall
Mengibar et al. 2016). After the age of 2 years, et al. 2013). MACS interrater reliability and con-
GMFCS level predicts walking function at age vergent validity have also been demonstrated for
12 with a positive predictive validity of 0.74 and young adults with CP (mean age = 20 years) (van
a negative predictive validity of 0.90 (Wood and Meeteren et al. 2010).
Rosenbaum 2000). Predictive validity of GMFCS Recently, Eliasson et al. (2017) developed the
classification systems was firmly established in Mini-MACS, a modified version of MACS for
longitudinal study of motor development curves children ages 1–4 years. With expert therapist
(Rosenbaum et al. 2002). and parent input, the MACS category descrip-
tions were adjusted to be more relevant for youn-
Manual Ability ger children. For example, both the MACS and
Manual Ability Classification System (MACS). Mini-MACS level I descriptions refers to slight
The MACS describes how children handle limitations in the performance of manual tasks.
objects in daily life irrespective of differences But given normative developmental differences,
in function between the two hands (Eliasson et al. the level I descriptions differ in their reference to
2006). It focuses on children’s typical performance adult assistance. Whereas children classified as
of relevant and age appropriate activities. The level I on the MACS are not restricted from inde-
MACS emphasizes handling of objects in an indi- pendence in daily activities, those at the same
vidual’s personal space (the space immediately level on the Mini-MACS may require more adult
close to one’s body) to minimize the potential assistance when handling objects compared with
confounding influence of gross motor limitations other children of the same age (Eliasson et al.
(Eliasson et al. 2006). The MACS five-level clas- 2017). Such age-related adjustments improved
sification is analogous and complementary to the the tool’s interrater reliability and the percentage
GMFCS (Paulson and Vargus-Adams 2017). The of absolute agreement between raters compared
levels are determined by a parent or caregiver with earlier attempts to use the original MACS
who regularly observes the child’s functions in with younger children (Plasschaert et al. 2009).
daily life, in collaboration with a health care Interrater reliability of the Mini-MACS was good
professional. between the parents and therapists (Kw = 0.90) as
Expert clinicians and parents of children with well as between the therapists (0.97) (Eliasson
CP were engaged in development of the MACS, et al. 2017).
thereby enhancing the system’s meaningfulness Bimanual Fine Motor Function (BFMF). The
and understandability (content validity) (Eliasson BFMF is a five-level system for classifying chil-
et al. 2006; Öhrvall et al. 2014). For children dren’s ability to use both hands together to manipu-
aged 4–18 years, the MACS has moderate to late objects (Beckung and Hagberg 2007). Levels
strong interrater reliability between clinicians differ in the severity of functional impairment and
(Kw = 0.66–0.97) and between clinicians and contain one or two sets of criteria for rating whether
parents (Kw = 0.73–0.96) (Eliasson et al. 2006; the impairment is predominantly unilateral/symmet-
Morris et al. 2006). MACS levels are highly stable ric or bilateral (Beckung and Hagberg 2007; Randall
over 12 months (Kw = 0.92–0.97, 67–82% et al. 2013). The BFMF differs from the MACS in
that it classifies hand function solely according to Viking Speech Scale (VSS). The VSS is a
the child’s fine motor function. The MACS 4-level system for classifying the extent to which
describes the child’s typical manual performance motor symptoms influence how speech is pro-
in daily life which is influenced by personal and duced in daily life to communicate information.
environmental factors in addition to the motor func- Interrater reliability of the VSS was found to be
tion. Moreover, the BFMF describes fine motor moderate-to-strong across parent and clinician
function for each hand separately, whereas the raters (Kw = 0.58–0.81). Test-retest reliability
MACS classifies manual performance irrespective (after 2–4 weeks) was moderate-to-strong for
of differences between the two hand (Eliasson et al. clinicians who classified children based on direct
2006; Beckung and Hagberg 2007; Elvrum et al. observations (Kw = 0.68–0.97) and case note
2016). A preliminary evaluation of BFMF interrater review (Kw = 0.92). Over 90% of raters consid-
reliability found that two pediatric therapists ered the VSS easy to use (Pennington et al. 2013).
strongly agreed on BFMF classification for 20 chil- Given its feasibility and reliability, the SCPE
dren aged 4–11 years with CP and periventricular recommended use of the VSS to classify chil-
white matter injury was strong (Kw = 0.98; 90% dren’s motor speech abilities for epidemiological
agreement) (Randall et al. 2013). A substantial cor- surveillance (Virella et al. 2016). The VSS has
relation between BFMF and MACS levels among been translated into multiple languages following
539 children with CP (rho = 0.89) provides validity international guidelines for this purpose
evidence, but children with milder mobility limita- (Pennington et al. 2013).
tions (GMFCS level I) were over represented in Functional Communication Classification
these analyses (49.5%) (Elvrum et al. 2016). Addi- System (FCCS). The FCCS was designed to clas-
tional research on the psychometric properties of the sify functional everyday communication produc-
BFMF is warranted. tion among children with CP ages 4 and 5 years
(Barty et al. 2016). The system was later evaluated
Communication for use with older individuals (up 18 years of age)
Between 31% and 88% of people with CP are (Virella et al. 2016; Caynes et al. 2019). The five
estimated to have a communication disorder classification levels describe children’s typical
(Virella et al. 2016). Motor disorders of CP can verbal and nonverbal expressive communication
impair the production of speech and gestures and during daily activities and considers variation in
limitations in sensations and cognition can affect the types of communication messages or topics,
both expressive and receptive communication. familiarity with communication partners, and use
Differentiation between motor speech and com- of augmentative and alternative communication
munication impairments is critical for facilitating technology (Barty et al. 2016). The FCCS has
tailored treatment and management approaches strong interrater reliability for 4- to 5-year-olds
for people with CP (Barty et al. 2016). Multiple overall (Kw = 0.97), with better agreement
classification systems that describe speech and/or between professionals (Kw = 0.94) than between
other modes of communication have been devel- parents and professionals (Kw = 0.59). Almost
oped and/or applied for people with CP (Virella perfect interrater agreement was demonstrated
et al. 2016). Three communication classifications, between speech language pathologists (SLPs)
VSS, FCCS, and CFCS, were recently reviewed and parent FCCS ratings (Kw = 0.96) for youth
for population-based implementation by SCPE with CP ages 5–18 years (Caynes et al. 2019). For
(Virella et al. 2016). All three systems were both age groups, FCCS levels were positively
found to have adequate psychometric properties. correlated with GMFCS (rs = 0.71–0.72) and
They differ in focus on motor speech and commu- MACS (rs = 0.71–0.74) levels, indicating that
nication impairments, coverage of expressive and as functional motor performance decreases, func-
receptive communication, and ease of use (Virella tional communication also tends to decrease
et al. 2016; Barty et al. 2016). (Barty et al. 2016; Caynes et al. 2019).
Communication Function Classification same type/topography category, these classifications

System (CFCS). The CFCS is a five-level clas- have limited prognostic value and they have not
sification system designed to parallel and com- aided therapy (Shapiro 2004; Paulson and Vargus-
plement the GMFCS and MACS (Hidecker et al. Adams 2017). Neuroanatomical classifications have
2011). Raters consider all modes of receptive and some diagnostic value (e.g., to rule out genetic or
expressive communication (e.g., vocalizations, progressive conditions), but their primary contribu-
signs, eye gaze, pictures, speech generating tion has been to research on the etiology and path-
devices) with familiar and unfamiliar communi- ogenesis of CP (Korzeniewski et al. 2008). Despite
cation partners when selecting a class. The CFCS increasing evidence that treatment planning with
was developed through a consensus development 3-dimensional gait analysis improves patient out-
process involving a person with CP, a parent of comes, gait analysis classifications are somewhat
a child with CP, and a multidisciplinary group unreliable, lack sensitivity to certain gait deviations,
of experienced clinicians, thus ensuring the tool’s and fail to predict functional outcomes (Dobson
clarity and usefulness (Hidecker et al. 2011). et al. 2007; McDowell et al. 2008). Lastly, growth
CFCS interrater reliability was found to be mod- in the number and breadth of functional classifica-
erate (Kw = 0.66) between professionals and fair tion systems for children with CP reflects increasing
(Kw = 0.49) between parents and professionals. dissatisfaction with the medical model’s traditional
Professional interrater reliability was better for promotion of “normal” or typical developmental
classification of children above 4 years of age pattern. Instead these classifications place greater
(Kw = 0.77). Test-retest reliability of profes- emphasis on finding solutions through training and
sionals’ CFCS ratings was strong (Kw = 0.82) adaptation to enable children to autonomously
over a 2 week span (Hidecker et al. 2011). CFCS engage in age appropriate and meaningful activities,
levels are moderately correlated with GMFCS even in the face of significant limitations of body
(rs = 0.47) and MACS (rs = 0.54) levels structure or function (Paulson and Vargus-Adams
(Hidecker et al. 2012). A knowledge translation 2017). Moderate associations between gross motor,
intervention involving an online training and manual ability, and communication levels indicate
CFCS decision flow chart improved SLPs’ abil- that multiple (existing and new) functional classifi-
ities to correctly classify children using the cation systems are needed to comprehensively char-
CFCS (Cunningham et al. 2016). acterize children’s performance of meaningful
activities in their everyday lives (Hidecker et al.
2012; Compagnone et al. 2014).
Evidence of Effectiveness
Classification systems are commonly used to reduce Cross-Reference

heterogeneity within subgroups of people with
CP. This chapter describes four of the most com- ▶ Motor Control and Muscle Tone Problems in
monly used types of CP classification systems. The Cerebral Palsy
systems differ in their coverage of the ICF’s body ▶ Spasticity Assessment in Cerebral Palsy
structure, body function, and activity levels, as well ▶ Spinal Deformity in Children with Cerebral
as in their utility for specific applications Palsy: An Overview
(Rosenbaum et al. 2014; Jeevanantham and Bartlett
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Measuring Outcomes in Children
with Cerebral Palsy 22
Colyn J. Watkins, Rachel L. DiFazio, and Benjamin J. Shore
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 326
Generic Versus Disease-Specific Measures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327
Self-Report Versus Parent Proxy Reporting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327
International Classification of Functioning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 328
Functional Outcome Measures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 329
Pediatric Outcomes Data Collection Instrument (PODCI) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 329
Gillette Functional Assessment Questionnaire (FAQ) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331
Shriner’s Hospital Upper Extremity Evaluation (SHUEE) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331
Pediatric Evaluation of Disability Inventory (PEDI) and Pediatric Evaluation of
Disability Inventory Computer-Adaptive Test (PEDI-CAT) . . . . . . . . . . . . . . . . . . . . . . . . . . . 331
Quality of Life/Health-Related Quality of Life Measures . . . . . . . . . . . . . . . . . . . . . . . . . . 332
Cerebral Palsy Quality of Life Questionnaire (CP-QOL-Child) . . . . . . . . . . . . . . . . . . . . . . . 333
Cerebral Palsy Quality of Life Questionnaire (CP-QOL-Teen) . . . . . . . . . . . . . . . . . . . . . . . . 333
Caregivers Priorities and Child Health Index of Life with
Disabilities (CPCHILD) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 333
Pediatric Quality of Life Inventory (PedsQL) 3.0 Cerebral Palsy (CP) Module . . . . . . . 335
DISABKIDS-CP Module (CPM) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 335
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 336
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 337
Abstract
Cerebral palsy (CP) defines a group of condi-
tions, arising from an injury to the developing
C. J. Watkins · R. L. DiFazio · B. J. Shore (*) brain. This injury results in disturbances of
Orthopedic Center, Boston Children’s Hospital, movement and posture, affecting balance,
Boston, MA, USA gait, and communication. Reduced activity
e-mail: Colyn.watkins@childrens.harvard.edu;
Rachel.Difazio@childrens.harvard.edu; levels and participation restrictions due to the
Benjamin.Shore@childrens.harvard.edu above impairments may lead to decreased
https://doi.org/10.1007/978-3-319-74558-9_21
326 C. J. Watkins et al.
health-related quality of life (HRQOL), com- Pediatric outcomes research, including

pared to unaffected peers. Increasingly, research in the area of CP, has historically focused
research and clinical practice is focused on on survival rates and treatment outcomes rather
interventions not only to improve biomechan- than on morbidity, health status, and the psycho-
ical alignment or functional outcomes for chil- logical and social consequences of medical and
dren with CP but also to improve HRQOL. surgical treatment (Theunissen et al. 1998). Out-
Clinicians need to utilize outcome measures come measurement is a systematic and objective
that accurately assess HRQOL in children procedure designed to determine the success and
with CP to provide evidence that their inter- impact of a treatment program (Ottenbacher et al.
ventions and management strategies are posi- 1997). Health-related quality of life has been
tively influencing HRQOL, activity and defined as referring to “the physical, psychologi-
participation. Outcome measures must be cal, and social domains of health, seen as distinct
valid, reliable, and responsive to change. No areas that are influenced by a person’s experi-
single measure covers all domains relevant to ences, beliefs, expectations, and perceptions
children with CP; therefore, a range of mea- (Testa and Simonson 1996). These tools objec-
sures is required to assess a child with CP tively quantify some aspect of a person’s health
comprehensively. Each outcome tool has spe- (physical, mental or emotional, or others). Com-
cific performance characteristics, some of prehensive measurement in children with CP is
which are better suited for clinical use and complex due to the wide variation in severity as
others for research. The purpose of this chapter well as physical and developmental limitations
is to review the most common functional and and co-morbidities. Outcome tools should be
HRQOL outcomes measures for children with valid, reliable, and responsive to change. Validity
CP to aid providers in their daily practice. is the degree to which a scale measures what it is
intended to measure. Reliability is the extent to
Keywords which a measure yields consistent values over
Cerebral palsy · Outcome measures · Self- time when no change has occurred and yields
report · Parent proxy · Health-related quality of consistent values between examiners. Respon-
life · Functional outcomes siveness establishes a tool’s ability to detect
change when a change has occurred (Oeffinger
et al. 2009).
Introduction Until recently, most clinical studies have only
assessed outcomes that reflect the level of patient
Children and youths with Cerebral Palsy (CP) are impairment. The primary focus has been the lim-
subjected to a number of interventions and thera- itation of joint range of motion measured on phys-
pies (bracing, Botulinum toxin injections, and ical exam and radiographic hip stability and spinal
orthopedic surgery) to address their musculoskel- deformity. Unfortunately, these objective mea-
etal deformities (fixed joint contractures, hip surements are less important to the patients and
instability, and spinal deformities) that develop their caregivers than HRQOL and functional
as a result of growth in the setting of unrelenting activity outcomes (Porter 2010). As a result of
spasticity. These interventions share the common increased survival, there has been a recent shift
goals of relieving or preventing pain; improving in focus from mortality to morbidity, which has
locomotion; facilitating feeding, toileting, and led to a dramatic increase in the development and
hygiene; as well as improving the health-related use of pediatric instruments designed to evaluate
quality of life (HRQOL) of these children. Many the impact of an illness and its treatment on the
of these interventions are resource intensive and daily functioning and overall well-being of chil-
costly. Surprisingly, there is little objective evi- dren (Varni and Limbers 2009). Pediatric mea-
dence that these interventions are effective in sures are much less well developed than those
achieving improved function and/or HRQOL. used in adult outcomes research and a limited
22 Measuring Outcomes in Children with Cerebral Palsy 327
number of psychometrically robust instruments diabetes, asthma, or CP (e.g., CPCHILD). These

exist to measure outcomes in children with CP. instruments focus on the specific disease and its
CP affects almost all aspects of an individual’s treatment and may be more sensitive to specific
life; therefore, a multidimensional approach is clinical changes in children with the disease in
required to assess problems, select appropriate question and cannot be applied to a healthy indi-
therapies, and evaluate change following inter- vidual (Wiebe et al. 2003). The disadvantage of
ventions. Great consideration must go into using these instruments is that it is impossible to
selecting the appropriate outcome measures that compare results across diseases or healthy
accurately capture a child’s abilities, overall populations (Varni et al. 2005). Although signifi-
health, and well-being. Over the last 20 years, cant progress has been made in the development
several comprehensive health status instruments of data collection instruments and in the examina-
have been developed for patients with chronic tion of the validity and reliability of these instru-
disability. However, despite this influx of new ments; we do not routinely collect and report data
instruments, there has yet to be one universally on these instruments (Dawson and Carr 2001).
accepted physical disability instrument applicable Both generic and disease-specific instruments
to all children and youths with CP. Patients with can be beneficial in outcomes measurement in
CP demonstrate a broad range of physical and children with CP. The use of both of these types
cognitive impairments, making the reliability of of measures will allow for a more comprehensive
any one functional assessment tool challenging. evaluation of the child (Varni and Limbers 2009).
Several things must be considered when selecting A disease-specific instrument would focus on the
outcome measures. Enhanced patient-centered impact of the disability, functional level, and emo-
outcomes monitoring should help in the identifi- tional well-being, while a generic measure would
cation of evidence-based clinical pathways that focus on the child’s overall well-being. Evaluating
result in improved service delivery for children the results of both of these types of measures will
and youths with neuromuscular disabilities. provide clinicians and researchers with a more
holistic view of the child.
Generic Versus Disease-Specific

Measures Self-Report Versus Parent Proxy
Reporting
Outcome measurement tools can either be generic
(used to collect information on healthy or sick There has been great debate in the pediatric out-
children to compare across other diseases) or dis- comes literature regarding who is the most appro-
ease-specific (used to collect information on priate person to assess a child’s outcomes. Some
symptoms or disease-specific health problems researchers believe that the child should be asked
from more specific populations) (Shore et al. directly, while others prefer to rely on the parents
2015). A generic instrument incorporates a com- as proxy respondents. Some have even advocated
prehensive array of domains of well-being which for obtaining both the child’s and the parents’
allows for screening in healthy populations, com- perspective whenever feasible (Eiser and Morse
parisons across pediatric populations with chronic 2001). Each method has advantages and disad-
health conditions, and benchmarking with healthy vantages. Some researchers believe that children
populations (e.g., Pediatric Quality of Life Inven- lack the cognitive and language skills necessary
tory) (Varni et al. 2005). The disadvantage of for self-report (Upton et al. 2008). However, there
generic measures is that they are not likely to be is now growing evidence that children can self-
responsive to changes in disease-specific symp- report reliably as long as their emotional level,
toms (Guyatt et al. 1993). cognitive ability, and reading level are considered
Disease-specific instruments are used to assess (Riley 2004). Pediatric self-report is quickly
characteristics of a specific condition such as becoming the gold standard for measuring
outcomes. However, there are certain groups of 2000; Ostensjo et al. 2003; Majnemer and Mazer
children who are unable to accurately self-report 2004). The ICF reflects a paradigm shift from a
due to their young age, severe intellectual impair- purely medical model to an integrated model of
ment, medically unstable condition, or significant human functioning and disability and evaluates
communication disorders. In these cases, the only the impact of a health condition, such as CP, on
way to obtain outcomes data is by using parent human functioning. The ICF guidelines have
proxy measures (Varni and Limbers 2009). The important implications for outcomes measure-
primary concern that researchers have about rely- ment. The ICF identified three different domains/
ing on parent proxy reports is that they may be levels of functioning that should be evaluated:
negatively influenced by the burden of caregiving, (1) body functions/structure, (2) activities, and
stress, and the parent’s own mental, physical, and (3) participation (Fig. 1). These domains are clas-
economic status (Eiser and Morse 2001). In addi- sified with contextual factors including personal
tion, research has found that there exists a lack of and environmental. The ICF focuses on the indi-
agreement between respondents when obtaining vidual’s level of health rather than on the individ-
parent proxy measures (Bates et al. 1998); with ual’s disabilities and acknowledges that every
some studies reporting high parent-child agree- human being, regardless of age, race, gender, or
ment (Guyatt et al. 1993; Upton et al. 2008), and nationality can experience disability. Therefore,
others reporting low parent-child agreement the ICF can be used across all people within all
(Vogels et al. 1998; Eiser and Morse 2001; societies (WHO 2001). Quality of life is not for-
Jokovic et al. 2004). mally included in the ICF framework and is
defined as “what people feel about their health
condition or its consequences” (WHO 2001).
International Classification One of the challenges in pediatric orthopedics is
of Functioning that the majority of the commonly used outcome
tools only measure ICF dimensions of body func-
In 2001, the World Health Organization (WHO) tions/structures and activities/participation, ignor-
released the International Classification of Func- ing other important domains such as domains
tioning, Disability, and Health (ICF) Framework related to a patient’s environment and personal
(WHO 2001). The ICF provides a comprehensive factors.
framework to approach outcome measurement in Each of the components within the ICF frame-
children with disabilities (Beckung and Hagberg work are linked to one another by multi-
Fig. 1 WHO ICF

framework for disability.
(Adapted from WHO ICF
2001)
directional arrows indicating nonlinear relation- environmental factors (Wright and Majnemer
ships between all of the aspects of functioning 2014). Nonetheless, given the physical impair-
(Fig. 1) (Rosenbaum and Stewart 2004). The ments of children with CP, functional outcome
term disability is not a component of the frame- measurements remain a cornerstone of prognosis
work, but rather an umbrella term that describes and treatment. In many conditions, such as CP, for
the outcomes of the interactions between health which there is no cure, maintaining or improving
conditions (diseases, disorders, and injuries) and function is the long-standing goal of interven-
contextual factors (environmental and personal tions. In the following section, we will review
factors). The first level, body functions/structure, the most common functional outcome assess-
is the physiological and psychological functions ments applied to children with CP. Please refer
of the body system. The second level, activity, to Table 1 for a summary of these instruments.
represents functioning at the level of the whole
person. The third level, participation, represents
the person’s functioning in his/her complete envi- Pediatric Outcomes Data Collection
ronment. The contextual factors that influence Instrument (PODCI)
disability and function include both environmen-
tal factors and personal factors. The environmen- The Pediatric Outcomes Data Collection Instru-
tal factors include family, social aspects, and ment (PODCI) is an instrument designed to assess
culture. The personal factors include gender, age, patients in the domains of upper and lower
education, coping styles, and social background. extremity motor function, relief of pain, and res-
Outcomes are based on the interaction between toration of activity (Daltroy et al. 1998). The
the health condition and the contextual factors instrument was developed collaboratively by the
(Organization 2010). The ICF recognizes disabil- American Academy of the Orthopaedic Surgeons
ity as a universal human experience and views it (AAOS) and the Pediatric Orthopaedic Society of
holistically. North America (POSNA) to assess children and
adolescents aged 2–18 years with a broad assort-
ment of musculoskeletal disorders (Daltroy et al.
Functional Outcome Measures 1998).
The instrument itself is a questionnaire that
Accurate measurement of functional outcomes is seeks to evaluate five domains of health: upper
critical to determine the appropriate treatment extremity and physical function, transfers and
option for a child with CP. Broadly speaking, mobility, sports and physical function, pain/com-
measures of function seek to measure a child’s fort, and happiness (Klepper 2011). For adoles-
ability to complete a given task (Wilson and cents, there is a patient self-report questionnaire
Cleary 1995). consisting of 83 items and a co-administered par-
Functional status is defined as the ability of an ent questionnaire consisting of 86 items. For chil-
individual to perform activities of daily living in dren less than 10 years of age or for those children
numerous aspects of life including physical, psy- that cannot self-report, there is an 86-item instru-
chological, social, spiritual, intellectual, and role ment. On average, it takes 10–12 min for an
functioning (Wang 2004). In CP, these functional adolescent to complete the instrument and
outcomes most frequently measure the ability to 15–18 min for a parent to complete (Daltroy
participate in, or complete, activities of daily liv- et al. 1998). PODCI scores are on a scale of
ing, mobility, and communication (Shore et al. 0–100. Lower values represent more disability
2017). Functional status, however, is only a com- and higher values represent higher function.
ponent of a child’s health and does not fully There is also a Spanish language version of the
describe the child’s overall health status. Addi- questionnaire (Wren et al. 2007).
tionally, functional status is affected both posi- The PODCI has been validated as a measure of
tively and negatively by psychosocial and functional health status in children with CP
Table 1 Functional outcome measures
330
Country
Measure of origin Age range Respondent Domains # Items Reliability Validity
Pediatric United 2–18 years Self-report 5 domains 83 Adolescent Good to excellent test- Validated for CP (Daltroy
Outcomes Data States and/or Upper extremity 86 Parent retest reliability et al. 1998; Wren et al. 2007;
Collection parent proxy and physical Parent: 5/5 domains McCarthy et al. 2002)
Instrument function with Internal reliability
(PODCI) (Daltroy Transfers and coefficient > 0.80
et al. 1998) mobility Adolescent: 4/5
Sports and domains with internal
physical function reliability
Pain/comfort coefficient > 0.80
Happiness (Daltroy et al. 1998)
Gillette United 3–19 years Self-report or 2 domains Ten level classification Good test/retest Validated for CP (Novacheck
Functional States parent proxy Ambulation system and 22 higher reliability in parents et al. 2000)
Assessment Higher level level functional Good inter-rater
Questionnaire functional activity activity rating reliability coefficients
(FAQ) between parents and other
(Novacheck et al. caregivers (>0.80)
2000) (Novacheck et al. 2000)
Shriner’s United 3–18 Video based, 1 domain 15 min video Excellent intra and inter Validated for CP (Davids
Hospital Upper States therapist Upper extremity administration observer reliability et al. 2006)
Extremity administered function and range (Davids et al. 2006)
Evaluation and of motion
(SHUEE) evaluated
Pediatric United PEDI parent proxy 3 Domains >200 questions, Excellent reliability, Validated for CP (McCarthy
Evaluation of States 6 months – Self-care /daily 30–60 min internal reliability et al. 2002)
Disability 7 years activities administration time coefficient > 0.90
Inventory (PEDI) Mobility (McCarthy et al. 2002)
Social function
Pediatric United Birth – Parent proxy 4 Domains Computer adaptive High test-retest reliability Validated in CP, good to
Evaluation of States 21 years Self-care /daily test estimates (Dumas and excellent validity across four
Disability activities “Precision CAT” Fragala-Pinkham 2012; domains (Dumas and
Inventory Mobility version 40–60 Haley et al. 2010). Fragala-Pinkham 2012;
Computer- Social function questions Haley et al. 2010; Shore et al.
Adaptive Test Responsibility Comprehensive 2017).
(PEDI-CAT) CAT version
120 questions
C. J. Watkins et al.
(McCarthy et al. 2002; Wren et al. 2007). Impor- Shriner’s Hospital Upper Extremity
tantly, it is also used as an instrument to evaluate Evaluation (SHUEE)
the effectiveness of surgical interventions
(McCarthy et al. 2002). Compared to other similar The SHUEE is a validated instrument for evalua-
instruments, the PODCI assesses more advanced tion of upper extremity function in children with
functions such as sports and outdoor play CP (Davids et al. 2006; Smitherman et al. 2011).
(Damiano et al. 2005). It is, therefore, a good The SHUEE differs from other functional mea-
instrument for orthopedic interventions, as these sures in that it is a video-based instrument. It is
interventions typically seek to improve higher- performed by an occupational therapist with a
level motor function but demonstrates floor and standardized set of tasks and standardized camera
ceiling effects in children with CP who demon- position. The study has duration of 15 min and
strate greater functional deficits (Vitale et al. requires administration and scoring by a qualified
2001). However, because it does include satisfac- occupational therapist.
tion and expectations as part of the assessment, Unlike many other functional outcome mea-
the PODCI is not a purely functional outcome sures, the SHUEE does not rely solely on patient
assessment. The instrument, therefore, seeks to or parent recall but rather real-time functional per-
assess a child and parent’s overall satisfaction formance. While there is a history-based assess-
with their treatment, not simply motor functional ment of the child’s ability to perform activities of
assessment. daily living, a significant component of the instru-
ment is direct observation of how the child uses the
involved extremity. The instrument measures the
Gillette Functional Assessment active and passive range of motion from the shoul-
Questionnaire (FAQ) der to the fingers. It also evaluates the spontaneous
use of the extremity while performing specific
The Gillette Functional Assessment Question- tasks on demand. Finally, the instrument measures
naire (FAQ) is a child or parent reported question- the patient’s ability to grasp and release the digits
naire that assesses functional ability in ambulatory with the wrist held in flexion, neutral, and exten-
children with CP (GMFCS I-III). The instrument sion (Davids et al. 2006). The video recorded com-
includes a ten-level classification of ambulatory ponent of the assessment can be a useful part of the
ability coupled with 22 other higher level func- medical record, particularly when comparing pre-
tional activities rated on a five-point Likert scale and postintervention function.
(Gorton et al. 2011). The FAQ is validated for
patients with CP, describes ambulatory function,
and can monitor change after intervention Pediatric Evaluation of Disability
(Oeffinger et al. 2007; Stout et al. 2008). Impor- Inventory (PEDI) and Pediatric
tantly, the FAQ only assesses the domain of func- Evaluation of Disability Inventory
tional ability, without evaluation of happiness, Computer-Adaptive Test (PEDI-CAT)
pain, or expectations (Novacheck et al. 2000).
The FAQ seeks to assess the child’s commu- The PEDI functional outcome instrument evaluates
nity ambulatory status, which is often difficult to three functional domains including Self-care (Daily
assess in the clinical setting. Clinic and gait lab Activities), Mobility, and Social Function. It is
environments often have a simple, even terrain, meant for children with disabilities between the
allowing providers to see the child at their “best.” ages of 6 months to 7 years. With more than
This may not be reflective of the child’s function 200 items, it requires 30–60 min to administer. It
in their community. The FAQ provides insight is meant to be completed by a proxy, such as a
into the child’s function in the community, with parent or therapist (Feldman et al. 1990; McCarthy
all of its challenges of uneven ground, crowds, et al. 2002). Items on the PEDI are generally easier
tight quarters, and obstacles. in content, and while good for evaluation of children
with moderate or severe disability, the instrument and social well-being. The physical domain
demonstrates a ceiling effect with children who includes the impact of illness on functioning, the
demonstrate higher function (Shore et al. 2017). psychological domain includes coping and adap-
Released in 2012, the PEDI-CAT is an update tation, and the social domain incorporates the
of the PEDI instrument for children from birth to individual’s relationship with family and friends
21 years of age. The PEDI-CAT is a computer- (Berzon 1998; Cooley 1998; Taylor et al. 2008).
adaptive test (CAT) that requires no special equip- HRQOL and quality of life (QOL) are terms that
ment other than software installed on a computer are sometimes used interchangeably. However,
or tablet. It requires no physical testing. The QOL is a much broader construct that includes
PEDI-CAT evaluates ability in the same three aspects of life that are not easily changed by health
functional areas as the PEDI (Daily Activities, care services, such as social interactions with
Mobility, and Social/Cognitive) but also has a peers and family relationships (Varni and Limbers
fourth Responsibility domain that reports the 2009). In children with CP, HRQOL measure-
child’s participation and amount of responsibility ments can be used to track changes over time
assumed for activities of daily living. and/or determine the effects of specific interven-
The CAT platform of the PEDI-CAT was built tions on a child’s HRQOL. Improvements in
with a set of 218 coordinated items (item banks) HRQOL should be considered one of the primary
based on functional ability of children with CP and goals in the management and treatment of chil-
seeks to describe the unique ability of the individual dren with CP.
child. Parents are first asked a question, which rep- Measuring HRQOL in children with CP is
resents a task from the middle of an ability range, particularly challenging since these children dem-
and then further questions are directed according to onstrate a wide range of functional and cognitive
how the parents answer this first question according abilities (Vitale et al. 2005). A limited number of
to their child’s ability level. Parents are asked to HRQOL instruments exist to measure outcomes
answer questions about their child’s functional abil- in children with CP and a gold standard does not
ity on a four-point rating scale (unable, hard, a little exist. The Pediatric outcomes data collection
hard, and easy) (Haley et al. 2010). instrument (PODCI) (Daltroy et al. 1998) and
Both the PEDI and PEDI-CAT are validated in the Child Health Questionnaire (McCullough
children with CP. The PEDI has demonstrated and Parkes 2008) were designed to measure func-
good concurrent validity when compared to tional status which does not capture the multi-
other functional instruments (McCarthy et al. dimensionality of the HRQOL. Early researchers
2002; Han et al. 2011). Similarly, the PEDI-CAT believed that physical functioning played a major
correlates well with previously validated instru- role in the child’s HRQOL and therefore this
ments in patients with CP and is able to differen- became the primary focus of early outcomes stud-
tiate across both fine and gross motor functional ies in children with CP. This idea has since proven
levels (Dumas and Fragala-Pinkham 2012; to be inaccurate in that adolescents perception of
Dumas et al. 2015, 2017; Shore et al. 2017). The their life is not solely based on their physical
PEDI-CAT is a useful outcome instrument that functioning; therefore, studies using the PODCI
can be used for any school age child with a wide and CHQ are not good indicators of HRQOL
spectrum of disability. (Rosenbaum et al. 2007; Shelly et al. 2008).
HRQOL has remained largely unmeasured due
to limitations in measurement. Four disease-
Quality of Life/Health-Related Quality specific, psychometrically sound, and validated
of Life Measures instruments have been identified to measure the
impact of having CP on HRQOL in children and
Health related quality of life (HRQOL) is a multi- adolescents: Cerebral Palsy Quality of Life Ques-
dimensional theoretical construct consisting of tionnaire (CP-QOL-Child and -Teen) (Waters
three broad domains: physical, psychological, et al. 2007), Caregivers Priorities and Child
Health Index of Life with Disabilities (CPCHILD) administered pre- and postoperatively. High qual-
(Narayanan et al. 2006), Pediatric Quality of Life ity of life scores were reported by the children
Inventory 3.0 Cerebral Palsy Module (PedsQL- following SEMLS, which were significantly
CP) (Varni et al. 2006), and the DISABKIDS higher than their parent’s scores ( p < 0.05). Sig-
(Mueller-Godeffroy et al. 2016). Please refer to nificant differences ( p < 0.05) between GMFCS
Table 2 for a summary of these instruments. level III and levels IV–V were identified in the
functional-related domains. No significant
changes were noted in the socioemotional
Cerebral Palsy Quality of Life domains (Himpens et al. 2013).
Questionnaire (CP-QOL-Child)
The Cerebral Palsy Quality of Life Questionnaire Cerebral Palsy Quality of Life
(CP-QOL-Child) (Waters et al. 2007) was Questionnaire (CP-QOL-Teen)
designed to assess quality of life changes in chil-
dren with CP with a focus on well-being rather The CP-QOL-Teen is a measure of QOL designed
than illness. The CP-QOL-Child has child self- for teens with CP. It consists of adolescent self-
report for children ages 9–12 years and parent report and parent proxy measures. The self-report
proxy-report for children ages 4–12 years. The measure has 72 items and the parent proxy mea-
self-report measure has 55 items while the parent sure has 17 additional items related to access to
proxy report has 66 items. Items related to service services and caregiver health for a total of
access and primary caregiver health are only 89 items. The questionnaire has seven domains:
included in the parent proxy measure. This mea- (1) General Well-Being and Participation
sure assesses seven aspects of quality of life: (21 items); (2) Feelings about Functioning
(1) Social Well-Being and acceptance (11 items); (5 items); (3) Communication and Physical
(2) Functioning (12 items); (3) Participation and Health (16 items); (4) School Well-being
Well-being (6 items); (4) Emotional Well-Being (7 items); (5) Access to Services (9 items);
(6 items); (5) Access to Services (5 items); (6) Social Well-being (7 items); (7) Family Health
(6) Pain and Impact of Disability (8 items); and and Well-being (4 items). Each of the items is
(7) Family Health (4 items). The measure was worded the same as the CP-QOL-Child question-
developed based on the International Classifica- naire. Reponses are on a 9-point rating scale rang-
tion of Function (ICF) (WHO 2001) and the def- ing from 1 = very happy to 9 = very unhappy.
inition of quality of life. The questions ask how Total scores can range from 0 to 100 with
the child feels about his/her life and how the 100 representing a higher HRQOL (Davis et al.
parent proxy feels about their child’s life in 2013). At the time of publication of this book,
terms of family, friends, health, and school. The no published outcomes studies utilizing the
vast majority of the questions begin with: “How CP-QOL-Teen measure could be identified.
do you think your child feels about. . ..” or “How
do you feel about. . ..” Therefore, the focus of the
questions is on how the child feels and not what Caregivers Priorities and Child Health
they can do. Reponses are on a 9-point rating scale Index of Life with Disabilities
ranging from 1 = very happy to 9 = very (CPCHILD)
unhappy. Total scores can range from 0 to
100 with 100 representing a higher HRQOL The CPCHILD was designed to measure HRQOL
(Waters et al. 2007). in children with severe nonambulatory CP
The CP-QOL-Child has been used to measure (Narayanan et al. 2006). It was developed specif-
quality of life in children with cerebral palsy after ically to measure the effectiveness of interven-
single-event multilevel surgery. Both self-report tions in children with GMFCS level IV–V
and parent proxy CP-QOL-Child measures were CP. The CPCHILD has parent proxy and child
334
Table 2 Disease-specific quality of life/health-related quality of life measures

Country of Age #
Measure origin range Respondent Domains Items Reliability Validity
Cerebral Palsy Quality of Life United 9–12 Self-report 4: physical well-being, social 52 Self-report: Self-report:
Questionnaire Kingdom 4–12 Parent proxy well-being, emotional well- Not not completed
(CP QOL-Child) (Waters et al. being, acceptance by others completed Parent proxy:
2007) Parent moderately correlated with the
Proxy: KIDSCREEN (r = 0.30–0.57)
Cronbach Moderately correlated with
Alpha the Global QOL
0.74–0.89 (r = 0.18–0.58) and global
Test-Re-test health (r = 0.21–0.56)
(0.76–0.89)
DISABKIDS (Baars et al. International 4–16 Self-report 6: Medication, limitation, 37 Internal
2005) Australia, 4–16 Parent proxy emotion, independence, social consistency
France, inclusion, social exclusion with
Germany, acceptable
Greece, results
Holland,
Sweden
Caregiver Priorities and Child Canada 2–18 Parent proxy 6: personal care, positioning, 36 Parent Parent proxy: correlated with
Health Index of Life with Questionnaire transfers and mobility, proxy: related instruments
Disabilities (CPCHILD) used only in communication and social internal
(Narayanan et al. 2006) children with interaction, comfort, emotions consistency
severe CP and behavior, health and overall (0.7 or > in
(GMFCS IV-V) QOL all domains)
Test-retest
(0.88–0.96)
Pediatric QOL Inventory Australia 5–18 Self-report 7: daily activities, school 35 Self-report: Parent-proxy:
(PedsQL) CP Module (Varni 2–18 Parent proxy activities, movement and internal correlations between the CP
et al. 2006) balance, pain and hurt, fatigue, consistency module and generic core scale
eating activities, speech and (0.63–0.93) were varied ranging from
communication Parent- weak (0.14–0.23) to moderate
proxy: (0.40–0.43) and significant
internal (90.52–0.84)
consistency
(0.88–0.96)
C. J. Watkins et al.
self-report measures for children and youths ages for both groups (DiFazio et al. 2016). This rela-
3–18 years. The measure consists of 37 items, tionship continued throughout the follow-up
which are categorized into seven different period. Difazio et al. (2017) demonstrated that
domains: (1) Activities of daily living (9 items); following spinal fusion, there was a significant
(2) Positioning, transferring, and mobility improvement in CPCHILD scores 1 year after
(8 items); (3) Comfort and emotions (9 items); surgical intervention; however, at 2 years, those
(4) Communication and social interaction scores returned to the baseline.
(7 items); (5) Health (3 items); and (6) Overall
quality of life (1 item). The last domain, #7,
examines the importance of each item to the Pediatric Quality of Life Inventory
child’s quality of life (36 items). The caregivers (PedsQL) 3.0 Cerebral Palsy
are asked to rate how difficult each of the listed (CP) Module
activities were in the past 2 weeks. Activities
included such things as toileting, getting in and The PedsQL is an instrument designed to measure
out of bed, and sitting in a wheelchair. In addition, HRQOL in children and adolescents with CP
caregivers are asked to choose the level of assis- (Varni et al. 2006). It has child self-report for
tance that was required to help their child perform children ages 5–18 years and parent proxy-report
these activities. Items are rated on a 6-point ordinal for children ages 2–18 years. The PedsQL is self-
scale. For items related to activities, a “level of administered for children ages 8–18 years and is
assistance” modifier is included, a 4-point ordinal interviewer-administered for children ages
scale from independent (0) to total assistance (3). 5–7 years. It has 35 items encompassing 7 scales:
For items related to symptoms, a 3-point ordinal (1) Daily Activities (9 items); (2) School Activi-
“level of intensity” scale was added with (0) being ties (4 items); (3) Movement and Balance
severe and (3) being none. Scores are reported for (5 items); (4) Pain and Hurt (4 items); (5) Fatigue
each domain and in total with 0 being the worst and (4 items); (6) Eating Activities (5 items); and
100 being the best (Narayanan et al. 2006). The (7) Speech and Communication (4 items). The
CPCHILD has demonstrated the ability to detect instructions ask the parent or child to report how
changes in HRQOL in children with severe cere- much of a problem each of the items has been
bral palsy who received oral modafinil for spastic- during the past month. A 5-point Likert scale is
ity reduction (Murphy et al. 2008) and following a used with responses ranging from 0 = never a
spinal fusion (Narayanan et al. 2011). The English problem to 4 = almost always a problem. The
version has been translated into: Bahasa Malay- response options are simplified for the young
sian, Brazilian Portuguese, Canadian French, Dan- child self-report (ages 5–7 years) and include
ish, Dutch, Farsi, German, Hebrew, Korean, only three options. Scores can range from 0 to
Norwegian, Spanish, and Swedish. 100 with a higher score indicating a better
The CPCHILD has been used to demonstrate HRQOL (Varni et al. 2006). There is no data
change after spinal and hip surgery in non- published on responsiveness to change following
ambulant children with CP. In a prospective lon- an intervention. In addition, there is an over-
gitudinal study, the CPCHILD was found to relate emphasis on the functional domains, which may
to the preoperative migration percentage. A neg- limit its ability to measure all aspects of quality of
ative correlation was detected between the preop- life. The instrument has been translated into
erative migration percentage and the preoperative numerous languages.
CPCHILD score (r = 0.50; p = 0.002). The
preoperative CPCHILD total scores differed
between the migration-percentile groups (mean DISABKIDS-CP Module (CPM)
difference = 13 points; 95% confidence inter-
val = 3.3 to 22.8; p = 0.01). However, after hip The DISABKIDS CP module was designed to
surgery, the CPCHILD score improved similarly measure HRQOL in children and youths who
suffer from chronic health conditions such as CP construct/theoretical underpinnings that the
(Baars et al. 2005; Mueller-Godeffroy et al. 2016). instrument measures, age of children, and patient
The instruments are available as self- or proxy versus parent proxy versions to name a few. No
report in children between the ages of single instrument can be used to measure all of the
4–16 years. The CP module was intended to be components of the ICF. Therefore, multiple mea-
used in conjunction with the 37-item sures may be the most appropriate. The goal mov-
DISABKIDS chronic generic module (DCGM- ing forward is to demonstrate responsiveness of
37), which assesses 6 domains: (1) Independence; the outcome measures we use so that we accu-
(2) Physical limitations; (3) Emotion; (4) Social rately assess change after interventions in children
inclusion; (5) Social exclusion; and (6) Treatment with CP.
(Simeoni et al. 2007). The DISABKIDS CP mod- Outcomes measurement is complex in children
ule has two specific domains: (1) Impact of the with CP. Ideally, therapists, researchers, and
condition (8 Items) and (2) Communication orthopedic surgeons hoping to assess HRQOL in
(2 items). The impact domain asks questions children with CP should have a choice of valid,
about difficulty with walking or other physical reliable, easy to administer, low-cost instruments,
activities such as swimming, getting dressed, suited to the cultural and societal background of
sports, and climbing stairs. The communication the children involved. Outcome measurement
domain asks questions about the impact of the allows providers to measure a child’s abilities
condition on the child’s ability to communicate before and after treatments and track changes
with others. Responses are in a Likert-scale for- over time. When applied to clinical practice, the
mat. Scores can range from 0 to 100 with higher collection of outcome instruments can be thought
scores indicating better adjustment to CP of as a toolbox that contains the tools (the mea-
(Mueller-Godeffroy et al. 2016, translated into sures that reflect the core set items) that the clini-
Dutch, English, French, German, Greek, Swedish, cian can use to evaluate the effect of the task
and Norwegian). at hand.
All of these measures have both self-report and
parent proxy versions. Each measure focuses
on different aspects of the child’s physical and
psychological well-being. Evaluation of these Cross-References
instruments demonstrates sound psychometric
properties with acceptable reliability and validity ▶ Epidemiology of Cerebral Palsy
and responsiveness to change. ▶ Family Stress Associated with Cerebral Palsy
▶ Foot Deformities in Children with Cerebral
Palsy: An Overview
Conclusion ▶ Functional ADL Training for Children and
Youth with Cerebral Palsy
An increasing demand for evidence-based deci- ▶ Health and Healthcare Disparities in Children
sion-making has challenged the medical commu- with Cerebral Palsy
nity to clearly demonstrate which treatments ▶ Hip Problems in Children with Cerebral Palsy:
translate to functional and clinical improvements An Overview
in a patient’s environment. Outcome tools are ▶ Muscle Performance in Children and Youth
designed to measure functional performance, as with Cerebral Palsy: Implications for Resis-
a baseline descriptive assessment, select treatment tance Training
goals, and to evaluate treatment. Selecting the ▶ Musculoskeletal Physiology Impacting Cere-
appropriate outcome instrument depends on bral Palsy Gait
many factors including: the specific research ▶ Overview of Knee Problems in Cerebral Palsy
question, type of intervention to be evaluated, ▶ Spinal Deformity in Children with Cerebral
the instrument’s psychometric properties, the Palsy: An Overview
▶ Therapy Management of the Child with Cere- Dumas HM et al (2015) Pediatric Evaluation of Disability
bral Palsy: an Overview Inventory Computer Adaptive Test (PEDI-CAT) and
Alberta Infant Motor Scale (AIMS): validity and
▶ The Upper Extremity in Cerebral Palsy: An responsiveness. Phys Ther 95(11):1559–1568
Overview Dumas HM et al (2017) Construct validity of the Pediatric
Evaluation of Disability Inventory Computer Adaptive
Test (PEDI-CAT) in children with medical complexity.
Disabil Rehabil 39(23):2446–2451
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Biomarker Blood Tests for
Cerebral Palsy 23
Robert E. Akins and Karyn G. Robinson
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 339
Types and Classes of Biomarkers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 340
Basics of Diagnostic Biomarker Test Performance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 340
Circulating Biomarkers in the Blood . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 341
Epigenetic Biomarkers and DNA Methylation in Blood Cells . . . . . . . . . . . . . . . . . . . . . 342
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 345
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 345
Abstract preferably collected at the time of birth, may

Together, the multiple types of cerebral palsy allow for earlier diagnosis, intervention, and the
(CP) represent the most common physical dis- development of novel therapeutics. Biomarkers
ability in childhood with the spastic type that identify CP patients are needed, and multi-
accounting for ~77% of cases. CP arises with a ple efforts to identify useful biomarkers in blood
disturbance in the brain, which in most cases samples are underway. It is important to under-
occurs between 24 weeks gestation and birth. stand the nature of diagnostic biomarkers and
Early intervention is desirable, but early diag- the types of blood biomarkers being investi-
nosis is very challenging, and diagnosis is often gated in individuals with CP.
delayed for several months or even years. No
current molecular biomarker platform readily Keywords
identifies individuals with CP, but screening Cerebral palsy · Biomarker · Blood test
assays that could measure blood biomarkers,
Introduction
R. E. Akins (*) · K. G. Robinson
Nemours Biomedical Research, Nemours – Alfred Cerebral palsy (CP) arises from a disruption of
I. duPont Hospital for Children, Wilmington, DE, USA brain development. In most cases, this disruption
e-mail: robert.akins@nemours.org; occurs during fetal life, and many children are
karyn.robinson@nemours.org

https://doi.org/10.1007/978-3-319-74558-9_211
340 R. E. Akins and K. G. Robinson
born with CP (Hadders-Algra 2014; Nelson and 3. Monitoring: Used over time to assess the pres-
Ellenberg 1986). Clinical intervention at an early ence, status, or extent of a disease, medical
stage is highly desirable in CP; (Hadders-Algra condition, or the effects of a treatment.
2014; Spittle et al. 2015) unfortunately, it can 4. Pharmacodynamic/response: Shows that a bio-
take several years for a child to be diagnosed logical response has occurred after exposure to
(Hubermann et al. 2016). Even with babies a specific agent.
who are highly affected at birth, the diagnosis of 5. Predictive: Identifies individuals who are
CP doesn’t occur until months or sometimes years likely to experience a known effect.
later (Hubermann et al. 2016; Maitre et al. 2013). 6. Safety: Indicates the likelihood, presence, or
Thus, although most individuals with CP are born extent of toxicity after an exposure.
with it, diagnostic challenges can delay therapy 7. Susceptibility/risk: Indicates the potential for
and services until after important therapeutic developing a disease or condition.
opportunities may have already been missed.
Improving the ability to detect CP, especially at In the context of CP, there are several types
an early age so that interventions may begin ear- of biomarkers that are used or that may be useful,
lier, would be a tremendous benefit to the personal including brain imaging and movement assess-
health of individuals with CP as well as to their ments. Given the challenges associated with iden-
families and to the healthcare systems that provide tifying individuals with CP early in life, potential
their care. Among several strategies to help iden- diagnostic biomarkers have received significant
tify individuals with CP, significant effort has attention.
been exerted to find molecules in the blood that
can serve as biomarkers. In this chapter, we dis-
cuss work toward the development of screening Basics of Diagnostic Biomarker Test
assays for CP based on blood biomarkers. Performance
The utility of a diagnostic test depends on how

Types and Classes of Biomarkers well it identifies individuals with a condition from
others who do not have the condition. The perfor-
Broadly defined, biomarkers are personal charac- mance of a diagnostic test can be quantified using
teristics that can be measured and evaluated. some basic characteristics, including:
Biomarkers can indicate physiological or patho-
logical processes or a response to a therapeutic 1. Accuracy: How often the diagnostic test gives
intervention. They may indicate things that are the correct answer; often given as a percent.
happening currently in an individual or may indi- 2. Sensitivity: How often the diagnostic test gives
cate things that happened in the past. Gene expres- a positive result when the individual has the
sion patterns, levels of a protein or metabolite in condition.
the blood or urine, blood pressure, and changes in 3. Specificity: How often the diagnostic test gives
brain activity seen by imaging are all examples of a negative result when the individual does not
biomarkers. have the condition.
A working group of the US National Institutes 4. Positive Predictive Value (PPV): The propor-
of Health and Food and Drug Administration rection of individuals with a positive test result
ognized seven classes of biomarkers based on who have the condition.
usage (Group F-NBW 2016): 5. Negative Predictive Value (NPV): The propor-
tion of individuals with a negative test result
1. Diagnostic: Detects or confirms a disease or who do not have the condition.
condition or a subtype of a disease.
2. Prognostic: Indicates the likelihood that a If a perfect diagnostic biomarker test were
disease-related event or condition will occur. available, all patients with a condition would be
23 Biomarker Blood Tests for Cerebral Palsy 341
Table 1 Example of results for a mock diagnostic bio- Table 2 Illustrative comparisons between study and clin-
marker study ical performance data for a fictitious diagnostic test
Individual Individual does not Study Expected clinical
has condition have condition Total characteristics characteristics
Number of 100 200 300 # Tests performed 300 10,000
participants # True positive 99 19.8
Positive 99 True 4 False positives 103 # False negative 1 0.2
biomarker positives (FP) # True negative 96 9780.4
test (TP)
# False positive 4 199.6
Negative 1 False 196 True negatives 197
Accuracy 98.3% 98.0%
biomarker negative (TN)
test (FN) Sensitivity 99.0% 99.0%
Specificity 98.0% 98.0%
Positive predictive 0.961 0.09025
detected and no patients without the disease value (PPV)
would be diagnosed. In practice, however, perfect Negative predictive 0.995 0.99998
biomarker tests are difficult to achieve, and under- value (NPV)
standing a test’s performance characteristics is
critical. To evaluate a biomarker test, a reference
diagnosis is needed for comparison. As shown in Circulating Biomarkers in the Blood
Table 1, comparison to a reference diagnosis
allows the calculation of the true and false positive The idea that factors circulating in umbilical cord
as well as true and false negative determinations blood may be associated with CP is an intriguing
by the biomarker test. possibility that has been investigated by several
The information from Table 1 allows calcula- groups (Costantine et al. 2011; Palatnik et al.
tion of performance characteristics for the mock 2015; Varner et al. 2015; Sorokin et al. 2014).
validation study involving 300 participants. These In short, molecules that become elevated in the
characteristics also allow an estimation of how blood as a result of inflammation, infection, brain
the test might perform if it were used in a clinical or neural injury, hypoxia, asphyxia, or ischemia,
setting. For example, if the imaginary test were which are associated with the onset of CP, may be
a diagnostic for a condition that occurs with elevated in the cord blood of newborns at high
the birth prevalence of CP (about 1 in 500 chil- risk of developing CP. Researchers have investi-
dren) (Data and Statistics 2017; Key Findings gated the relationships between conditions like
2017) and was applied to a group of 10,000, the these and elevated blood levels of specific pro-
expected results would be as shown in Table 2. teins. For example, one study looked at levels of
Importantly, this example shows how the preva- S100 calcium binding protein B (S100B),
lence of the condition being assessed has a dra- neuron-specific enolase (NSE), and the soluble
matic effect on the relative number of false receptor for advanced glycation end-products
positive results and on the predictive value of (sRAGE) (Costantine et al. 2011); a study mea-
the diagnostic test. sured serum magnesium (Palatnik et al. 2015);
Also of importance, the specific conditions another study examined the inflammatory cyto-
under which the diagnostic test can be employed kines interleukin-8 (IL-8), interleukin-1 beta
are extremely crucial and can dramatically affect (IL-1 β), and tumor necrosis factor alpha
test performance. In addition, the cost, complexity, (TNF-α) (Varner et al. 2015); another looked at
and reliability of the test are all important. Clear interleukin-6 (IL-6), C-reactive protein (CRP),
conditions for when the test is used, low cost, and myeloperoxidase (MPO) (Sorokin et al.
straightforward interpretation, and minimal vari- 2014). Unfortunately, despite the strong
ance when the test is performed at different times suspected relationships between the markers
or clinical sites would all be expected to increase measured in these studies and CP, the levels of
the usefulness of any diagnostic biomarker test. serum analytes measured did not yield significant
associations with CP or with poor neurodeve- to verify whether miRNA is a useful diagnostic
lopmental outcomes. biomarker for CP.
Despite the lack of strong correlation with CP DNA methylation describes the addition of
in the studies involving circulating biomarkers a methyl group (-CH3) to a specific carbon on
from cord blood so far, the possibility that such cytosine bases. DNA methylation is essential for
biomarkers can be developed is still being normal growth and development, and the process
researched. The timing, levels, and patterns of of DNA methylation has been extensively studied
circulating biomarker levels are very complex, (Ziller et al. 2013; Smith and Meissner 2013).
and additional analytic work to resolve the Studies have shown that significant stresses in
possibility of using such levels in cord blood fetal or early life can alter DNA methylation pro-
to identify newborns at high risk for developing files in a variety of tissues, including blood cells.
CP is needed. Importantly, the cascades that are suspected
of leading to CP involve hypoxia, infection,
inflammation, and growth restriction, (Adams
Epigenetic Biomarkers and DNA Waldorf and McAdams 2013; McIntyre et al.
Methylation in Blood Cells 2013; MacLennan et al. 2015) and studies show
that DNA methylation is altered by hypoxia,
Recent studies have examined the possibility bacterial infection, inflammation, intra-uterine
that epigenetic biomarkers may be present in growth restriction, and trauma or stress (Blaze
CP. Epigenetics refers to mechanisms that and Roth 2015; Hartley et al. 2013; Pacis et al.
alter gene expression without affecting the pri- 2015; Xiao et al. 2016; Houtepen et al. 2016;
mary sequence of the coding DNA. The three Labonte et al. 2012; Rask-Andersen et al. 2016;
primary epigenetic alterations include DNA Stirzaker et al. 2015; Joubert et al. 2016).
methylation, post-translational modification of Alterations in the methylation of DNA in
histones, and effects mediated by small or micro- blood cells of individuals with CP have been
RNAs (miRNA) (Epigenetics and Public Health assessed in studies from our group (Crowgey
2014). Both DNA methylation in blood cells et al. 2018) and others (Mohandas et al. 2018;
(Crowgey et al. 2018; Mohandas et al. 2018; Jiao et al. 2017). In a small study examining
Yuan 2017) and circulating, cell-free miRNA blood from four pairs of monozygotic twins in
(Chapman et al. 2018) have been investigated as which one developed CP while the other did
potential biomarkers in CP. not, Jiao and co-workers found differences in
MicroRNAs are small (about 22 nucleotides), DNA methylation in 190 genes including genes
nearly ubiquitous, and under tight biosynthetic that were hypo-methylated (153) and others that
control (Treiber et al. 2018; Gebert and MacRae were hyper-methylated (37) (Jiao et al. 2017).
2018). They perform critical regulatory functions Mohandas, et al. also looked at monozygotic
under a variety of physiologic and pathologic twins that were discordant for CP, but they
conditions and can be found circulating in the evaluated DNA methylation in dried blood
blood either within exosomes or as free nucleic spots from 15 twin pairs obtained during new-
acids (Gebert and MacRae 2018). Changes in born screening. Their group identified 33 sites
circulating miRNA have been associated with with altered methylation and two larger regions
a variety of pathologies, and miRNAs may be that were differentially methylated in CP; a sig-
useful diagnostic biomarkers in conditions rang- nificant number of the sites they found were
ing from breast cancer (Bahrami et al. 2018) to indicative of inflammatory signaling, cytokine
traumatic brain injury (Toffolo et al. 2018). secretions, and cellular immunity (Mohandas
A recent report discusses the possibility that et al. 2018).
miRNA regulation of gene expression subsequent Our team at the Alfred I. duPont Hospital has
to preterm brain injury may be important in also investigated DNA methylation in blood
the development of motor dysfunction in CP cells in the hope that CP arising gestationally
(Chapman et al. 2018). Additional work is needed might be diagnosed using epigenetic biomarkers
in blood cells (Crowgey et al. 2018). Since meth- was used to find sets that had 40 or fewer sites. In
ylation patterns that have been altered in brief, this approach involved the following steps.
utero can be sustained long term, (Joubert et al.
2016) we hypothesized that children with discrete 1. Filter the 61,278 potentially informative sites
types of CP have specific methylation patterns that based on a false-discovery-rate (FDR) adjusted
are sustained later in life. Using a whole genome p value <0.05. This step left 2,809 hypo-
approach that took advantage of methylation- methylated and 3,779 hyper-methylated sites
sensitive-restriction-enzyme digestion, next- in the CP cohort relative to controls.
generation DNA sequencing, a computational 2. Consider the top 200 ranked sites with the
pipeline to reassemble and analyze methylation lowest FDR-adjusted p values.
patterns, and machine learning algorithms to iden- 3. Computer randomly selects between 15 and
tify sets of potentially diagnostic methylation sites, 40 of these 200 sites.
our group was able to develop an approach that (a) From the 32 sets of participant data, com-
identified a group of spastic di- and quadriplegic puter randomly selects 8 CP cases and
CP patients from controls. 8 controls for training of the computer
In brief, the AIDHC study involved analysis regarding the differences between CP and
of methylation patterns in 32 genomic DNA sam- control at the 15–40 sites.
ples from peripheral blood mononuclear cells, (b) The computer uses information from 3a to
16 from subjects with spastic CP with an average evaluate the remaining 16 sets of data
age of 14.7 3.3 years and 16 from control sub- using linear discriminant analysis (LDA).
jects with an average age of 15.0 2.2 years. (c) Repeat 3a and 3b 20 times.
All study participants were surgical patients 4. If sensitivity >98% and specificity >90%
scheduled for spinal fusion surgery at the hospital across all 20 replicates, the set of methylation
and all provided informed consent for the sites was scored as a “good.”
IRB-approved study. A total of 1.47 million 5. Repeat all of step 3 again with any sites con-
potential methylation sites were identified across sidered “good” in step 4 given a slightly higher
all 32 study participants; of these, 61,278 individ- chance of being included in subsequent
ual sites had at least 10% variability between the models.
CP and control cohorts. To assess the ability to 6. After 6.8 million LDAs, 252 models based
discriminate between the CP and control groups on <40 CpG sites with near perfect accu-
based on DNA methylation patterns, a clustering racy were found.
analysis was performed on the 61,278 sites. The
clustering analysis collapses complex, multi- The results of this bootstrap approach clearly
dimensional datasets into a small number of com- support the notion that DNA methylation patterns
ponents that cluster the differential relationships in blood cells can discriminate between scoliosis
within the original data, effectively isolating the surgery patient with spastic CP and those without
patterns that are conserved within each group that CP. The DNA samples analyzed in the models,
were also divergent between the two groups however, came from participants who were
(CP vs. control). There was a strong separation approximately 15 years old. To test whether the
of the two groups (see Fig. 1). 252 models developed with the ~15 year olds
The results of the clustering analysis strongly could identify CP in much younger patients,
indicated that there were substantial differences a pilot validation test was done using data from
in the methylation patterns of the study partici- 11 subjects who had donated blood when they
pants with CP and the controls. However, 62 k is were approximately 4 years old. Amazingly,
a large number of methylation sites to evaluate even though DNA methylation changes with age
for a potential diagnostic test. To determine (Jones et al. 2015) and the test was based on a
whether there were significantly smaller sets of small number of methylation sites and was not
methylation sites that would also discriminate the developed to account for the more than 10 years
two groups, a guided, machine-learning approach of age difference in the cohorts, a distinct
Fig. 1 Non-metric multidimensional scaling clustergram tion of the cohorts in this way indicates that the DNA
based on cytosine methylation patterns between CP and methylation patterns were fundamentally different.
control cohorts. Each point represents a single subject and CP = orange points; control = green. This figure appears
is positioned based on all potentially informative methyl- in Crowgey et al., BMC Bioinformatics, 2018, and is used
ation sites (n = 61,278). Boundaries represent the 90% here under a Creative Commons Attribution License:
confidence intervals. Axes are dimensionless representa- https://creativecommons.org/licenses/by/4.0/, https://creat
tions of the relative similarity between points. The separa- ivecommons.org/publicdomain/zero/1.0/
classification signal persisted. The performance Table 3 Results of a pilot validation using models based
characteristics of the pilot validation test are on training data from ~15 year old subjects to determine the
diagnosis of blinded samples from ~4 year olds
shown in Table 3.
Although far from perfect, the results of the Pilot validation test performance
pilot validation and the overall results of the study # Spastic CP cases 6
strongly support the notion that discriminating # Controls 5
DNA methylation patterns exist. Further refine- # True positive 6
# False negative 0
ment of the DNA methylation pattern analysis
# True negative 2
approach to include data from more study partic-
# False positive 3
ipants, to evaluate more combinations of methyl-
Accuracy 73%
ation sites, and to account for changes in
Sensitivity 100%
methylation with age is expected to improve the Specificity 40%
specificity and the diagnostic capability of the test.
Conclusion FDA-NIH Biomarker Working Group: BEST (Biomarkers,

EndpointS, and other Tools) Resource. (2016) https://
www.ncbi.nlm.nih.gov/books/NBK326791/
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Part VI
General Medical Concerns
General Nutrition for Children
Nicole Fragale, Natalie Navarre, and Jaclyn Rogers
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 350
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 350
Etiology of Impaired Growth in Children with Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . 350
Evaluating Growth in the Child with Non-ambulatory Cerebral Palsy . . . . . . . . . . . . . . . . 351
Evaluating for Nutritional Deficiencies in the Child with Cerebral Palsy . . . . . . . . . . . . . 351
Role of Diet in Bone Health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 352
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 352
Nutritional Requirements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 352
Nutrition Interventions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 353
Oral Nutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 353
Enteral Nutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 354
Bone Health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355
Follow-Up . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355
Complications of the Treatment and Disease Process . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 356
Complications of Calorie Boosting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 356
Complications of Enteral Tube Feedings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 356
Complications of Mineral Supplementation for Bone Health . . . . . . . . . . . . . . . . . . . . . . . . . . 357
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 357
Abstract indicated in this patient population and include

Children with cerebral palsy can have unique attention to growth charts, physical exam, eval-
nutritional requirements due to poor growth, uation of food diaries, and laboratory monitor-
inadequate oral intake of food or fluids, depen- ing. Interventions may include diet fortification
dence on tube feedings, and micronutrient defi- using oral supplements, calorie-boosting tech-
ciencies. Nutrition assessments are often niques, tube feeding adjustments, and vitamin
and mineral supplementation. Optimizing the
nutritional status of the child with cerebral
N. Fragale (*) · N. Navarre · J. Rogers
Clinical Nutrition, Nemours/AI duPont Hospital for
palsy should be a priority for all clinicians
Children, Wilmington, DE, USA caring for these patients.
e-mail: Nicole.fragale@nemours.org; Natalie.
navarre@nemours.org; Jaclyn.Rogers@nemours.org

https://doi.org/10.1007/978-3-319-74558-9_23
350 N. Fragale et al.
Keywords Physical derangements such as compromi-

Nutrition · Growth · Diet · Food · Bone sed oral motor skills may lead to difficulty or
a complete inability to chew and swallow. Tooth
pain as a result of poor mouth care may lead to
Introduction difficulty chewing. Those who struggle to chew
and swallow often require feeding tubes, which
Nutrition is a very important topic for the disabled places them at nutritional risk because they will
child with cerebral palsy. Children with cerebral require close monitoring and adjustments to calo-
palsy should have a nutrition assessment com- ries and fluids as they age. Physical disabilities
pleted by a dietitian at least once per year. leading to inability to bear weight and walk can
Children who are at high risk for nutritional defi- also lead to decreased bone growth (Samson-Fang
ciencies and impaired growth may see a dietitian and Stevenson 1998).
more frequently. A nutrition assessment is a mul- Altered metabolic requirements are common,
tifaceted approach used to assess growth, body either hypermetabolism or hypometabolism.
composition, dietary intake, use of dietary supple- A child’s muscle tone will often dictate their calo-
ments, and evaluation of nutrition-related labs. ric requirements. For example, the spastic quadri-
Nutrition status has a direct impact on brain devel- plegic child with athetoid muscle spasms will
opment and bone health. often have elevated caloric requirements due to
increased energy expenditure. Hypermetabolic
patients are often underweight or require high-
calorie diets to sustain growth. On the contrary,
Natural History the child with hypotonia and limited movement of
extremities will have decreased caloric require-
Etiology of Impaired Growth ments as a result of decreased energy expenditure.
in Children with Cerebral Palsy Hypometabolic patients are at risk for becoming
overweight or obese.
Children with cerebral palsy are at risk for having It is important to understand that energy
poor growth and nutritional deficits for a variety requirements for children change often. In chil-
of reasons. These reasons often are related to the dren with cerebral palsy, changes to medications,
nature of the child’s cerebral palsy. For example, new therapies, and increasing age can result in
a child with cerebral palsy who was born with abrupt changes to calorie expenditure. Many med-
very low birth weight (VLBW) or small for ges- ications are accompanied by side effects that
tational age (SGA) is inherently at risk for short may impact a child’s weight. Antiepileptic drugs
stature and impaired growth during early child- such as valproic acid may lead to weight gain
hood (Trebar et al. 2007; Itabashi et al. 2007). (Dinesen et al. 1984), whereas topiramate may
Some children may have a deficiency in growth lead to weight loss (Antel and Hebebrand 2012).
hormone as a result of the insulting brain injury Baclofen, a medication used to treat spasticity, is
that led to the cerebral palsy. A deficiency in often associated with weight gain due to its effect
growth hormone will lead to impaired longitudi- on decreasing muscle tone and therefore redu-
nal growth (Hamza et al. 2011). Precocious cing energy expenditure (McCoy et al. 2006).
puberty is often seen as a result of hormonal A child who is starting puberty may also experi-
imbalances related to the cerebral palsy and can ence an increase in caloric requirements, followed
also lead to short stature. Also, behavioral prob- by a decrease in calorie requirements as longitudi-
lems associated with cognitive delays may con- nal growth tapers off (Dietary Guidelines for
tribute to a limited diet that may be deficient in Americans. 2010). Close monitoring of weight sta-
calories, protein, and crucial vitamins such as tus is indicated in these situations. Weight mainte-
iron, calcium, or vitamin D. nance is often the goal after puberty has concluded.
24 General Nutrition for Children with Cerebral Palsy 351
Evaluating Growth in the Child a height measurement that was initially an esti-
with Non-ambulatory Cerebral Palsy mate of the patient’s height. BMI also does not
take into the account the altered body composition
Ambulatory children with hemiplegic cerebral of the child with cerebral palsy and should there-
palsy should have their growth monitored and fore be used cautiously (Samson-Fang and Ste-
assessed the same way as a child without cerebral venson 2000). No matter what the method,
palsy. Recommendations for the best way to eval- consistency is the key when monitoring length
uate the growth of a child with non-ambulatory or height over time.
cerebral palsy(GMFCS 4-5) are limited. Potential A patient’s overall body composition may be
for errors in weight and height measurements better evaluated via the use of triceps skinfold
are common due to difficulties moving a child and mid-upper arm circumference measurements
who is disabled and who may have contractures to measure fat stores. Repeated measurements
in their legs. Weight measurements are often over time are more meaningful than a single
straightforward as long as the patient is weighed measurement.
using a consistent method. Different methods of Use of cerebral palsy growth charts should be
weighing a disabled patient include using a wheel- limited due to the limited sample size that was
chair scale or a sling scale. Careful attention must utilized to create these growth charts. Also, the
be paid to the equipment that is also being sample of patients used to create these charts was
weighed in these situations. For example, a patient not necessarily a well-nourished population and
who is weighed in a wheelchair will need to be therefore should not be used as a standard for all
removed from the wheelchair in order to have children with cerebral palsy. Instead, the use of the
the weight of the wheelchair subtracted from the WHO growth charts for children 0–2 years of age
total weight measurement initially taken. Alterna- and the CDC growth chart for children 2–19 years
tively, a parent may hold their child while being of age should be encouraged (Department of
weighed, and then the weight of the parent may be Health and Human Services 2002). Many children
subtracted from the weight of both the child and with cerebral palsy will be below the fifth percen-
the parent together. Errors in mathematics via tile for weight and length/height on these growth
these methods can result in large discrepancies charts, and the parent should be educated that this
and inappropriate nutrition intervention. To does not necessarily mean that their child is mal-
avoid error in these methods that utilize mathe- nourished. Gradual increases in weight and
matics, one can “zero” the scale after the parent or length/height indicate that a patient is receiving
the wheelchair has been placed on the scale. This adequate nutrition, even if the percentile is less
will ensure that the weight reading will be that of than the fifth. Z-scores may be used to identify
the child only, when he or she is added to the more acute changes in weight and height. A stable
parent or wheelchair already on the scale. or increasing z-score would indicate a child that is
Methods for obtaining an accurate height on gaining weight appropriately. As mentioned ear-
a patient who is wheelchair bound and who has lier, measurement of fat stores on the arm will also
contractures may vary. A standing height is the help to determine adequacy of caloric intake.
most accurate and preferred method but, however,
is not always feasible. Height estimations from
a knee height or ulnar measurement may be used Evaluating for Nutritional Deficiencies
(Samson-Fang and Bell 2013). A segmental in the Child with Cerebral Palsy
recumbent length may be done by a trained pro-
fessional who consistently uses this method to When conducting a nutrition assessment in the
measure the patient. BMI should be used cau- child with cerebral palsy, it is important to be
tiously when evaluating patients with cerebral aware of signs and symptoms of nutritional defi-
palsy due to the magnified error of squaring ciencies. Kalra et al. (2015) showed that children
with cerebral palsy have lower serum levels of and take into account the child’s mobility, muscle
iron, copper, and magnesium when compared to tone, activity level, altered metabolism, and
age-matched controls of similar weight status. growth. It can be difficult to estimate the energy
These results indicate that vitamin and mineral needs of a child with neurological impairments due
supplementation may be warranted. Close atten- to the heterogeneity of the population, altered body
tion must be paid to the child’s hair, eyes, skin, composition, and reduced physical activity levels.
and nails when assessing for micronutrient defi- Various methods have been proposed, but no one
ciencies. Thinning hair may be a result of inade- accepted method has been identified (Bell and
quate intake of protein or iron. The hair that is dull Samson-Fang 2013). Table 2 outlines a few
or dry could be a result of inadequate protein
intake or an essential fatty acid deficiency. Pale
Table 1 Dietary Reference Intakes (DRIs): recommended
conjunctiva may be indicative of a deficiency in
dietary allowances of adequate intakes, vitamins, and
folate, vitamin B12, iron, or copper. A sore, red elements
mouth may be a result of riboflavin deficiency or
Calcium Phosphorus Vitamin D
another B vitamin. Unusually dry skin may be Age (mg) (mg) (IU)
a result of essential fatty acid deficiency or inad- 1–3 700 460 600
equate intake of vitamin A. Spoon-shaped, con- years
cave nails may be a sign of inadequate intake of 4–8 1,000 500 600
protein or iron. Labwork is often helpful in years
confirming deficiencies, but physical exam is usu- 9–18 1,300 1,250 600
years
ally the first step to identifying them (Mordarkis
19–30 1,000 700 600
and Wollf 2015). years
Food and Nutrition Board, Institute of Medicine, National
Academies, 2011
Role of Diet in Bone Health
Table 2 Methods for estimating energy requirements
Calcium and vitamin D play a vital role in bone
Krick et al. 1992 Calories per day = Resting energy
development and maintenance. Children with expenditure muscle tone
cerebral palsy who are wheelchair bound are at factor activity factor + growth
an increased risk for low bone density factor(s)
(osteopenia) and therefore fractures (Stevenson Resting energy expenditure:
Utilizing the WHO equations
et al. 2006). Measures that should be taken to specific to age and gender
address this issue include assurance that the Muscle tone factor:
child is consuming a diet that contains enough Add 10% for high tone
calcium and vitamin D to meet the RDAs for age Subtract 10% for low tone
No adjustment for normal tone
(see Table 1). Serum levels of vitamin D should be Activity factor:
checked at least once yearly to assure sufficient Add 15% for bedridden state
levels. Additional supplementation may be indi- Add 20% for wheelchair
cated should the vitamin D 25 OH level be below dependent
Add 30% for ambulatory
32 ng/mL. Growth factor(s):
Add 5 kcal/gram of expected
or desired catch-up growth per
Treatment day
Height-based 14.7 kcal/cm in children without
method motor dysfunction
Nutritional Requirements (Culley and 13.9 kcal/cm in ambulatory
Middleton 1969) patients with motor dysfunction
Prior to implementing nutrition interventions, 11.1 kcal/cm in non-ambulatory
nutritional requirements need to be established. patients
Energy requirements should be individualized Pediatric Nutrition Care Manual (2018)
proposed methods for estimating energy require- requirement of 800–1,000 international units
ments for this population. Of note, equations should be considered (Penagini et al. 2015).
involving the length or height should only be
used when an accurate measurement has been
obtained. Nutrition Interventions
It is well recognized that energy needs to vary
throughout the CP population, ranging from The route of nutrition intervention depends upon
hypocaloric to hypercaloric needs. Many children the nutritional status of the child, the child’s
and adolescents with CP have decreased energy oral motor/swallowing function, and the risk
requirements when compared to typically devel- for aspiration (Bell and Samson-Fang 2013). In
oping children. This difference can be attributed addition, sensory impairments, fine and gross
to decreased basal metabolic rate and decreased motor limitations, neurological impairments,
physical activity. There are multiple factors and communication difficulties must also be con-
that contribute to fluctuations in energy needs. sidered when developing individualized nutrition
As previously mentioned, altered metabolism, interventions (Arvedson 2013).
muscle tone, physical activity, medications, age, A detailed assessment of feeding history,
and pubertal status can all play a role in altering physical examination, anthropometric parame-
energy requirements. It is important to keep in ters, and laboratory tests will facilitate the devel-
mind that estimations of nutritional requirements opment of the nutrition intervention. Assessment
are intended as a starting point only. Ongoing of feeding history should assess for diet consis-
monitoring and reassessments are essential to pre- tency (type, texture, viscosity), quantity and
vent over- or under-feeding. Objective measures quality of intake, feeding route, length/frequency
of improving nutrition status, such as adequate of meals, self-feeding abilities, and where
weight gain, growth, and improving skinfolds, meals take place. The physical examination
should be used in conjunction with reports of should assess for signs of protein-calorie malnu-
dietary intake when assessing whether or not trition and micronutrient deficiencies. Anthropo-
a child is meeting his/her nutritional needs (Bell metric parameters assessed should include at
and Samson-Fang 2013). least weight, height, mid-upper arm circumfer-
In regard to specific nutrient requirements, ence, and triceps skinfold thickness. Laboratory
there are no evidence-based recommendations tests should be assessed for nutrition-related
specific to children with cerebral palsy. In addi- labs which may include, but are not
tion, there is no evidence to support increased limited to, complete blood count, comprehensive
or decreased protein, vitamin, and mineral metabolic panel, prealbumin, iron assay,
needs in this population. However, if a child is 25-hydroxyvitamin D, phosphorus, and magne-
severely malnourished, it is suggested that protein sium (Penagini et al. 2015).
intake of 2 gm/kg/day and an increase in calories In children where adequate nutrition is lacking,
by 15–20% may be sufficient to promote the provision of optimized nutrition may achieve
improved weight gain and growth (Kuperminc linear growth restoration, weight normalization,
et al. 2013). Many children with cerebral palsy decreased spasticity and irritability, improved
may undergo multiple orthopedic surgeries wound healing, decreased frequency of hospitali-
that may temporarily impair nutritional status zations, and improved quality of life (Penagini
and increase energy demands (Krick and Miller et al. 2015).
2013). During the postoperative period, there is an
increased need for calories and protein to support
wound healing. The Dietary Reference Intakes Oral Nutrition
(DRIs) for vitamins and minerals are appropriate
to use, with the exception of vitamin D. Due to First-line interventions should promote oral nutri-
increased risk for vitamin D deficiency in this tion when possible. When developing nutrition
population, it is recommended that a higher daily interventions for a child with CP, it can be very
helpful to work with the therapists involved in the additional calories and protein, as well as micro-
child’s care to ensure that a feasible, achievable, nutrients (Bell and Samson-Fang 2013).
and safe plan is being established. Appropriate
positioning and physical support during meal-
times may assist in optimizing intake and Enteral Nutrition
ensure safe swallowing. The use of adaptive feed-
ing equipment may encourage self-feeding and Enteral tube feedings are indicated in children
independence at meal times. Speech-language with CP with a functional GI tract who are unable
pathologists (SLP) specialized in feeding therapy to meet nutritional needs orally, despite oral sup-
play a critical role in determining the most appro- plementation. Other indicators warranting the use
priate diet type for the child with CP. Due to oral of enteral tube feeds include severe malnutrition
motor dysfunction and/or dysphagia, altered food and feeding/swallowing dysfunction resulting in
textures and/or fluid consistencies may be indi- risk for aspiration. Depending on the individual-
cated. Nutrition recommendations must take these ized needs of the child, enteral tube feeds may be
food/fluid modifications into account when devel- used as a sole source of nutrition or as a supple-
oping interventions. ment to oral intake.
Calorie boosting techniques can be used for The topic of initiating enteral tube feedings
children who are able to eat by mouth, but who often evokes an emotional response from the care-
have difficulty consuming enough volume to giver(s) of the child. It is important to take a
meet their calorie needs. The purpose of calorie sensitive approach when discussing the initiation
boosting is to increase the caloric density of each of tube feeds with caregivers. The risks and ben-
bite of food the child consumes without having to efits of tube feeds should be discussed, as well as
increase the volume. This is often done with the reassurance of how tube feeding will fit into day-
use of high-fat items since fats contain the most to-day life.
calories per gram compared to carbohydrates and The route of tube feeds varies depending on a
protein. Oils and butters may be added to foods variety of factors. Nasogastric tube feeds are com-
during preparation or cooking. Dairy-based bev- monly used for short-term use since they are less
erages and foods may be fortified with the addi- invasive. For anticipated long-term feeding,
tion of dry milk powder, heavy cream, and/or ice gastrostomy tube feeds are most often used.
cream. High-fat spreads such as nut butters, gua- There are instances where post-pyloric feeds
camole, and cream cheese may be added to crack- with either a naso-jejunal tube or jejunostomy
ers and sandwiches. Commercially available tube may be indicated. Indications for post-
calorie modulars in the form of carbohydrates, pyloric feeds will be discussed further in the fol-
protein, and/or fat can also be utilized. There lowing section.
are a variety of ways in which calorie-boosting Tube feeding regimens are individualized and
techniques can be incorporated into a daily diet influenced by route of access, tolerance of feeds,
regimen in an effort to increase calorie intake oral intake, and family schedule. Bolus feeding
orally. regimens are often used to provide a more physi-
If there is no improvement in nutrition status ological feeding schedule that mimics meals.
from the use of calorie boosters alone, commer- Bolus feedings are larger volume feedings admin-
cially available oral supplements should be con- istered in 1 h or less. This type of regimen can
sidered. There are a variety of oral nutrition encourage oral intake by offering meals by mouth
supplements available. Depending on the child’s before administering the formula bolus. The
preference, there are both milk-based and juice- timing of bolus feeds should be far enough apart
based options. The standard oral supplement pro- so that the child is able to develop a sense of
vides 1 cal/mL. There are also more calorically hunger before oral meals are presented. Some-
dense formulas available that provide 1.5 cal/mL times, daytime boluses with continuous overnight
and 2 cal/mL. Oral supplementation provides feedings are indicated if it is not feasible to
provide the goal formula volume during the day. products such as milk and cereals. Dietary intake
Continuous feeding regimens may be indicated of vitamin D, calcium, and phosphorus should be
for children with gastrostomy feeds due to diffi- assessed at each visit. Please reference the first
culty in tolerating large volumes in short periods section for Recommended Dietary Allowances
of time. For post-pyloric access, a continuous (RDA) of these nutrients. Supplementation should
feeding regimen must be used to avoid intoler- be considered if the RDA is not being met.
ance, diarrhea, and dumping. Time off of the Vitamin D levels are determined by assessing
feeding pump should be allotted if possible. levels of serum circulating 25-hydroxyvitamin D
There is a wide variety of commercially pre- [25(OH)D]. Vitamin D deficiency is defined by
pared formulas available. The type of formula a level below 20 ng/ml (50 nmol/L). Vitamin D
used depends on the individualized needs of the insufficiency is defined by a serum level of
patient. Formulas are categorized into polymeric, 21–29 ng/ml (52.5–72.5 nmol/L). Vitamin D
semi-elemental, and elemental. Standard poly- levels are considered sufficient at 30 ng/ml
meric formulations at 1 cal/1 mL are most com- (75 nmol/L) and above (Holick et al. 2011).
monly used unless otherwise indicated. For Supplementation with vitamin D3 is preferable
children with volume intolerance, a 1.5 cal/1 mL in the treatment and prevention of vitamin D defi-
formulation may be beneficial. For children with ciency (Tripkovic et al. 2012). For infants (0–1
lower energy needs, there are hypocaloric formu- years of age), treatment of 2,000 IU/day or
las (0.6 cal/1 mL) available that allow for ade- 50,000 IU once weekly for 6 weeks is suggested
quate provision of micronutrients, protein, and to achieve a serum vitamin D level greater than
fluid while minimizing calorie intake (Bell and 30 ng/ml, followed by maintenance therapy of
Samson-Fang 2013). Some indicators for use of 400–1,000 IU/day. For children and adolescents
semi-elemental or elemental formulations may (1–18 years of age), treatment of 2,000 IU/day or
include, but are not limited to, intolerance of 50,000 IU once weekly for at least 6 weeks is
feeds, delayed gastric emptying, diarrhea, and suggested to achieve a serum vitamin D level
multiple food allergies. greater than 30 ng/ml, followed by maintenance
therapy of 600–1,000 IU/day (Holick et al. 2011).
Higher oral doses of 8,000 to 10,000 IU/day
Bone Health of vitamin D may be used for more severe
deficiencies.
As mentioned in the previous section, children
with cerebral palsy are at an increased risk for
low bone mineral density (BMD). Contributing Follow-Up
factors include inadequate dietary intake of cal-
cium, phosphorus, and vitamin D, minimal The purpose of nutrition follow-up and monitor-
sunlight exposure, muscular weakness, limited ing is to ensure nutrition status is adequate or
mobility, poor weight bearing, and use of anti- improving, managing enteral/oral feedings, and
epileptic medications (Penagini et al. 2015). weaning enteral tube feeds as appropriate.
Vitamin D, calcium, and phosphorus are key As previously mentioned, using equations for
nutrients in bone health. Optimizing intake of estimating nutrient needs are only a starting
these nutrients is important in preventing and point. Adequacy of weight gain and improve-
treating low bone density. Calcium and phospho- ments in anthropometrics is a more sensitive indi-
rus are minerals that support bone structure and cator of improving nutrition status. The frequency
function. Foods high in calcium include milk, of nutrition follow-up depends on the child’s
cheese, and yogurt. Phosphorus is found in clinical picture and nutrition status. For children
dairy, fish, eggs, poultry, nuts, and grains. Vitamin at risk for or presenting with malnutrition for
D helps the body to absorb calcium. Food sources which nutrition recommendations are being
of vitamin D include salmon, tuna, and fortified made, a follow-up within 4–12 weeks would be
appropriate. If on an established nutrition plan and or high-calorie milkshakes and smoothies should
demonstrating positive outcomes, a follow-up be tolerated better than solid foods. Also, encour-
every 6–12 months has been suggested (Bell and age smaller-volume meals more frequently
Samson-Fang 2013). throughout the day (i.e., 4–6 smaller meals instead
of three large meals). Medium-chain triglyceride
(MCT) oil may also be added to the diet, which is
Complications of the Treatment a type of fat that is readily absorbed. MCT oil in
and Disease Process appropriate doses is well tolerated and adds extra
calories without slowing down gastric emptying.
Complications may arise with calorie boosting,
enteral feedings, or mineral supplementation for
bone health. Complications with feeding interven- Complications of Enteral Tube
tions are often due to gastrointestinal problems Feedings
including gastroesophageal reflux, gastroparesis,
vomiting, constipation, and diarrhea. Other com- Similarly, the complications seen with calorie
plications may include weight gain, refeeding boosting may also occur with enteral tube feeds.
syndrome, and nutrient-nutrient or drug-nutrient A patient with reflux, gastroparesis, diarrhea, and
interactions. See below for possible issues that constipation may have trouble tolerating his or her
may occur with each nutrition intervention and tube feeding. If the patient is severely malnour-
how to manage those obstacles when they arise. ished, he or she may experience feeding intoler-
ance when enteral feeds are first introduced. Signs
of tube feeding intolerance may include abdomi-
Complications of Calorie Boosting nal pain, retching, vomiting, and diarrhea.
For those with reflux, gastroparesis, and/or
Calorie boosting involves adding energy-dense vomiting who do not tolerate gastric feedings,
foods to the patient’s diet to optimize calorie there are several interventions to try. For one,
intake and help him or her gain weight. Foods try a formula that contains hydrolyzed protein
that are highest in calories are also highest in fat and a higher percentage of fat from MCT oil,
such as oil, butter, nut butters, whole milk, and such as Peptamen. In more severe cases, an ele-
heavy whipping cream. Patients who have gastro- mental formula may be warranted. Some patients
esophageal reflux, gastroparesis, and/or vomiting are sensitive to volume. Using a higher calorie
may not tolerate a diet high in fat. This is because formula can help cut back on volume and improve
fat slows down gastric emptying, allowing food to tolerance. When using higher calorie formulas,
sit longer in the stomach and exacerbate those make sure the patient’s fluid needs are still being
gastrointestinal issues. Patients with diarrhea met. Another intervention is adjusting the feed-
may or may not tolerate a diet high in fat. Patients ing regimen to decrease the amount of volume
with constipation often have decreased intake and given at one time. Some patients do not tolerate
early satiety leading to poor weight gain. While it bolus feeds and may need to run via pump at
is important to optimize calorie intake in these a continuous rate.
patients, resolving the constipation first will help If a patient continues with gastric feeding intol-
the patient tolerate his or her diet better and there- erance despite a trial of the above interventions, he
fore improve nutrition intake. Making sure the or she may need post-pyloric feeds. When feeding
patient is getting adequate intake of fiber and fluid to the small intestine, choose a formula with
is important in the management of constipation. a lower osmolality if possible. Formulas concen-
To manage complications with calorie boos- trated above 30 cal/oz. will have a higher osmo-
ting due to reflux, gastroparesis, and/or vomiting, lality and may cause diarrhea. Elemental formulas
encourage fat in liquid form rather than solid. also have a higher osmolality. Consult with
Supplemental beverages such as Boost or Ensure a dietitian to choose the most appropriate formula.
Patients who are severely malnourished and same time as vitamin D to optimize absorption.
are starting enteral feeds for the first time may be Calcium carbonate interferes with the absorption
at risk for refeeding syndrome. Refeeding syn- of iron, so it should not be taken at the same time
drome is a term to describe metabolic and func- as an iron supplement. Calcium citrate does not
tional complications that can occur when nutrition interfere with the absorption of supplemental iron
is given after a period of starvation. When carbo- (Nelms et al. 2007).
hydrates are reintroduced, hypophosphatemia, Be cautious when using any vitamin or mineral
hypokalemia, and hypomagnesemia may occur supplement with other medications, as there may
as well as issues with sodium and fluid balance be drug-drug interactions. Provide supplemental
and thiamine deficiency. Those at risk for calcium and phosphorus as needed to meet the
refeeding syndrome should be monitored closely RDA for the patient’s age. There is no benefit to
as nutrition is introduced and advanced gradually exceeding the RDA. Excessive amounts of cal-
(Corkins and Balint 2015). cium and phosphorus can be harmful. The goal is
to optimize nutrition and bone health without
causing adverse side effects.
Complications of Mineral
Supplementation for Bone Health
Cross-References
There are a few things to keep in mind when
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optimize intake and bone health. Phosphorus sup- Palsy
plementation may have a mild laxative effect that ▶ Gastroesophageal Reflux in the Child with
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(Goldman et al. 2011). Cerebral Palsy
Adverse gastrointestinal side effects with cal- ▶ Managing the Child with Cerebral Palsy Who
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gas, bloating, and constipation when compared to in Patients with Cerebral Palsy
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Managing the Child with Cerebral
Palsy Who Has Medical Complexity 25
Dennis Z. Kuo, Sara R. Slovin, and Amy E. Renwick
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 360
Role of Primary Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 360
Care Coordination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 361
Practice Transformation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 362
Models of Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363
Medical Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 364
Transition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 366
Payments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 367
Cases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 367
Case 1: Agitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 367
Case 2: Fever . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 368
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 369
Abstract caregiver demands and costs. Care for the

Children with cerebral palsy often have medi- child with cerebral palsy who has medical
cal complexity, defined as requiring multiple complexity encompasses social determinants
specialists, frequently requiring medical tech- of health and psychosocial aspects of care.
nology, and incurring significant family Addressing medical complexity in the primary
care setting is best supported in the medical
home through a team-based approach with
D. Z. Kuo practice transformation, family-centered care,
Department of Pediatrics, University at Buffalo, Buffalo,
care coordination, clinical guidelines, and pay-
NY, USA
e-mail: dkuo@upa.chob.edu ment support. Frameworks of care and practi-
cal tips presented in this chapter aim to enable
S. R. Slovin (*) · A. E. Renwick
Nemours Alfred I. duPont Hospital for Children, the primary care physician to collaborate with
Wilmington, DE, USA families in managing the health of children at
e-mail: Sara.Slovin@nemours.org; Amy. highest risk for adverse outcomes.
Renwick@nemours.org

https://doi.org/10.1007/978-3-319-74558-9_24
360 D. Z. Kuo et al.
Keywords (IDEA) and the Americans with Disabilities Act

Cerebral palsy · Medical complexity · Medical (ADA). The care of a child with medical complex-
home · Care coordination · Transition ity involves coordinating many different providers
and services, and the financial and caregiving stress
on the family is considerable. In addition, care of
Introduction the CMC is typically very expensive due to hospi-
talizations, emergency room use, frequent outpa-
Cerebral palsy (CP) is often accompanied by tient encounters, and an increasingly recognized
numerous and wide-ranging healthcare needs, need for mental and behavioral health services.
whether caused directly by the CP or by All CMC are entitled to the same promotion of
comorbidities. The abnormal neurologic develop- healthy growth and development as any other child.
ment or insult that results in the characteristic Their medical care needs often entail consideration
motor findings of cerebral palsy may also be asso- of feeding and nutrition, respiratory issues, and
ciated with impairments of other body systems neurodevelopmental and behavioral disorders. Like
such as orthopedic, pulmonary, and gastrointesti- all children, CMC are impacted by social determi-
nal (GI). Psychosocial and mental health impacts nants of health and may be more adversely impacted
of cerebral palsy are also common (Mattson et al. due to the extensive service needs. Nonetheless, the
2019). The presence of numerous chronic condi- primary care provider (PCP) is crucial to maintaining
tions requiring an array of providers and support the health and wellness of CMC. This chapter will
services is increasingly described as “medically describe the foundational aspects of primary care of
complex,” and such children are recognized as children with cerebral palsy who have medical com-
“children with medical complexity” (CMC). plexity, as well as the medical considerations for
As a group, CMC are characterized by their promoting health and wellness in such children.
high rate of healthcare use, high cost, and exten-
sive family support needs (Cohen et al. 2011). An
example of a child with medical complexity is a Role of Primary Care
child with a genetic syndrome and prematurity
who has cerebral palsy, neurodevelopmental dis- It is critical to understand the role of primary care
ability, asthma, and feeding intolerance, is depen- for all children, but particularly for the child with
dent on supplemental oxygen and a feeding tube, cerebral palsy who has medical complexity. Two
and needs care from a pulmonologist, gastroen- definitions are helpful:
terologist, surgeon, and a developmental-
behavioral pediatrician, in addition to a primary • Starfield defines primary care as the “level of
care physician. This child would also require an a health service system that provides entry into
array of community-based services including the system for all new needs and problems,
schools, therapies, pharmacies, medical supply provides person-focused (not disease-oriented)
companies, and home nursing, as well as exten- care over time, provides care for all but very
sive support services for the caregivers. uncommon or unusual conditions, and coordi-
CMC are increasingly recognized simply nates or integrates care provided elsewhere by
because there are more of them today. Many others” (Starfield 1998).
CMC are alive because of advances in medical • Bright Futures (Hagan et al. 2017) defines
technology, particularly in the neonatal intensive children’s health as “The extent to which
care unit, over the last 30 years. Many CMC are individual children or groups of children are
living at home and attending school in their com- able or enabled to (a) develop and realize their
munities, supported by laws and programs that potential, (b) satisfy their needs, and
recognize and support the child’s right to live in (c) develop the capacities that allow them to
the community. Examples of relevant laws include interact successfully with their biological,
the Individuals with Disabilities Education Act physical and social environment.”
25 Managing the Child with Cerebral Palsy Who Has Medical Complexity 361
Primary care can support the continuum of chil- of care under categories such as education, legal,
dren’s health by being based in the community social, and medical. Often there are dozens of care
where the child resides. Many families know pri- components under multiple groups. Each group,
mary care as the first contact for illness and preven- in turn, may be governed by different laws, regu-
tive care for their children. These expectations lations, and training standards. In the middle are
should apply equally for CMC. The PCP often is the child and family, who are faced with the task
the medical provider who has a longitudinal rela- of navigating the extremely fragmented system.
tionship with the family and may best know and Care coordination is defined by the American
understand the accompanying social determinants Academy of Pediatrics as an activity that is
of health as well as supporting services in the com- “patient and family-centered, assessment-driven,
munity. Thus, the PCP is the ideal person to support team-based activity designed to meet the needs of
the continuum of health and wellness of CMC and children and youth while enhancing the caregiv-
their families. Even if specific expertise is lacking ing capabilities of families. Care coordination
for a medical condition, the PCP can act as the addresses interrelated medical, social, develop-
conduit to tertiary care services by acting as the mental, behavioral, educational and financial
“eyes” and “ears” for a specialist. Primary care is needs to achieve optimal health and wellness out-
thus uniquely positioned to integrate all healthcare come.” Care coordination addresses the “in-
and support health and wellness for CMC. between” of services, including scheduling, refer-
The potential challenges for PCPs include rals, information transfer, and feedback, ensuring
inadequate time, payments, expertise, staffing, that the overall care received by the child and
and facilities. PCPs faced with the time pressures family is seamless and supportive of health and
and inadequate face-to-face encounter payments wellness. Notable terms include:
in fee-for-service environments may be better
supported under value-based payment systems • Patient- and family-centered. The care must
that may provide dedicated payments for care be centered on the needs of the child and fam-
coordination and management. Medical expertise ily, including the range of social determinants
for the care of CMC can be addressed by use of of health.
available medical guidelines and collaboration • Assessment-driven. An array of structured
with appropriate subspecialists and tertiary care assessments is utilized.
systems. Staffing and facilities that accommodate • Team-based. Different tasks require different
the needs of CMC are addressed by deliberate skills and training, so it is important that care
investments in practice transformation that are coordination is viewed as a team-based activ-
similarly supported under value-based payment ity, even if it is directed by one or two people.
systems. With the percentage of children with • Enhance the caregiving capabilities of fam-
chronic conditions rising, practices will need to ilies. The child and family are at the center of
support investments in chronic care capabilities in the care map, and care is best performed in the
order to meet patient needs and remain viable. community setting where the child and family
reside. All care coordination activities should
be viewed as supporting family needs and self-
Care Coordination management.
Care coordination is essential to the practice of Common questions that may arise when plan-
caring for the child with medical complexity. A ning care coordination for CMC include who does
care map demonstrates the components of care the care coordination, where the care coordination
that are necessary for caring for CMC. With a staff are located, and what kind of training is
care map, the family lists all components of care typically needed. A designated point of contact
and groups them by service category. The care at a primary care practice is typically ideal for
map in Fig. 1 (Kuo et al. 2018) shows examples CMC. Practices that are of sufficient size may
Fig. 1 Care map reflecting the multitude of relationships and professionals involved in the care of a child with medical
complexity. (Reproduced with permission from the American Academy of Pediatrics. July 15, 2019)
have a designated staff person who is called a care

coordinator and acts as that point of contact. Nurs- Practice Transformation
ing background tends to be helpful for a care
coordinator for CMC, specifically because man- Practice transformation is also essential to the
agement issues often necessitate medical exper- practice of caring for the child with medical com-
tise. In some cases, designated care coordinators plexity. Under practice transformation, the prac-
may reside in an accountable care organization or tice utilizes a team-based, population health
a complex care service that works with a primary strategy instead of one that is based on volume
care practice. It is still important for a primary care and illness. Practice transformation may also be
practice to have a designated point of contact that referred to as medical home, patient-centered
works with that practice, as the primary care prac- medical home (PCMH), advanced primary care,
tice remains the first point of contact for medical or team-based care. Regardless of the term, prac-
issues, durable medical equipment needs, and tice transformation supports the medical home
home health aide or skilled nursing support. concept as defined by the American Academy of
Pediatrics: care that is patient and family centered, • Team-based care. Many providers are involved
accessible, continuous, comprehensive, coordi- with the healthcare of a child with medical
nated, compassionate, and culturally effective complexity. Care is best delivered as a team,
(American Academy of Pediatrics 2002). The pri- with defined roles and lines of communication.
mary care provider leads the medical home team. While an identified point of contact in a prac-
The teams develop longitudinal relationships with tice is important for CMC, additional team
the patients and families, identify shared goals of roles may also reside within the primary care
care, and utilize these to facilitate the CMC’s care practice. Examples include care coordinator,
with specialists and therapeutic, educational, or educator, navigator, social worker, counselor,
community services the CMC needs. Partnerships or dietician. Such staff may reside within the
among families, healthcare providers, and com- practice or be identified outside of the practice,
munity agencies are critical to high-quality but all team members should function as a
healthcare delivery for CMC (Liptak et al. 2011). high-performing team.
Medical home certification may be available in • Quality improvement. Under quality improve-
certain states or locations and may make the prac- ment (QI), data is utilized to set performance
tice eligible for enhanced payments that support targets and practice changes. CMC, as noted
additional staff. above, may be excluded from QI initiatives
Under practice transformation, a practice uti- because they are seen as outliers. However,
lizes specific tools and processes that support care CMC are often cost and utilization drivers,
of the child with cerebral palsy who has medical and it is important to identify and manage the
complexity. They include: outliers under a QI framework.
• Population management. Put simply, popula-

tion management means care is provided Models of Care
regardless of whether the child is in the office
or not. Data are used to oversee care of the Three general approaches to models of care have
population, including CMC that is within the arisen for children with complexity. Each has its
attributed population. Internal data from the own staffing and training requirements and may
electronic medical record (EMR) may be used be adapted depending on resources.
for quality improvement purposes. External
data from payers may be used for performance • Primary care centered. In this model, the pri-
review. Children with cerebral palsy, particu- mary care physician addresses many of the
larly those that have medical complexity, are aspects of care for CMC, including preventive
often seen as the “outliers” from a cost and care, care coordination, and medical manage-
utilization perspective. As such, they are some- ment. This model typically requires dedicated
times excluded from a population management staff with defined care coordination roles and
strategy, but a practice should identify and may be more suitable for large practices with a
address outliers nonetheless. larger number of CMC.
• Registry with risk stratification. Practices • Co-management. In this model, the primary
maintain a registry of patients with CMC that care physician and consulting specialty care
is used for surveillance, tracking, and quality services may manage different aspects of care
improvement. Patients may be identified with agreements on what roles each will play.
through risk stratification algorithms or by For example, the primary care physician may
clinical review. Many risk stratification algo- focus more on feeding and swallowing, while
rithms are not optimized for pediatrics, so clin- the tertiary care-based specialist may address
ical review of a patient registry remains technology management that requires exper-
important to ensure the right patients are in tise not found in the primary care setting.
the correct stratum. Co-management works well with agreed-
upon roles, care protocols, and direct support Preventive care is important for all CMC. Rou-
by the specialist. Dedicated staff contacts tine well visits, preferably with continuity with the
should exist at both the primary care and ter- same provider over time, and timely immuniza-
tiary care sites. tions are standard of care. In addition to standard
• Tertiary care centered. Some tertiary care cen- well care, it is important to establish a partnership
ters may have complex care services that pro- with families, and introduce other members of the
vide multidisciplinary care and a level of team – including a care coordinator, if available –
expertise not available in the primary care set- and provide specific contact information for any
ting. In this model, the primary care physician and all questions. Pre-visit planning can be inte-
may defer the majority of clinical decision- grated into the routine of well visits, which entails
making to the tertiary care center, including the care coordinator contacting and collecting his-
feeding, respiratory, and behavior management. tory and parent goals prior to the in-person visit.
The PCP, however, continues to provide Pre-visit planning saves time and encourages
community-based care, preventive care, immu- team-based care, as assessments from additional
nizations, and first point of contact for illnesses. team members (including nursing and social
work) give a fuller picture of the needs of the
A fourth model has more recently arisen. Large family. Following the visit, scheduled follow-ups
organizations such as accountable care organiza- to monitor areas of concerns, such as growth,
tions may have care coordinators that work with breathing, feeding, spasticity, and behavior, may
primary care physicians, community-based ser- be warranted, every 1–3 months initially and then
vices, and tertiary care centers, thus expanding spacing out as needed. Regardless of need, it is
the care network to an outside entity. The potential often helpful to monitor CMC and manage
advantage is that an externally located coordinator chronic issues at least every 6 months. The PCP
may be based in the community and therefore should be aware that frequent sick visits may lead
would be able to focus on social determinants of to unintentionally missed routine preventive care
health and cross-sector collaborations. It is impor- appointments. A care coordinator that monitors a
tant, however, for a primary care physician to patient registry can help mitigate this
continue to identify CMC proactively and have a phenomenon.
clinical staff member work with the externally Risk stratification and a registry of CMC may
located coordinator. proactively identify families that will require extra
time during visits. It is important to update the
problem list and reconcile medications at every
Medical Care visit. Growth can be monitored by the primary
care physician; signs of feeding dysfunction,
Bright Futures (Hagan et al. 2017) guidelines recurrent coughing, or constipation are also com-
emphasize health and wellness through a family- mon and can be assessed by the PCP. The PCP can
centered, life course approach. This approach sup- assess the medical technology that may be
ports growth and development and understands needed, including oxygen, feeding tube, baclofen
that children should be provided with opportunity pump, augmentative communication devices, and
to achieve their potential. The life course ventriculoperitoneal shunts, and coordinate and
approach applies for the child with cerebral refer as needed. The PCP should also determine
palsy who has medical complexity. Building resil- if other durable medical equipment such as
iency within families and mitigating adverse MAFOs (molded ankle-foot orthoses), standers,
childhood experiences are important goals for bath chairs, patient lifts, walkers, or wheelchairs
the child, family, and PCP to aim for. Proactive can enhance strength, mobility, and activities of
screening for psychosocial needs, appropriate daily living. Whether medical daycare, home
referrals, and follow-ups are critical to support health aides, or skilled nursing may support care-
CMC. givers in the care of CMC or allow for respite care
during times of additional stress should also be • Growth and nutrition. CMC may have diffi-
discussed. culty with feeding and swallowing. GI dys-
A Shared Plan of Care can be implemented for function, including constipation, is common
all children with medical complexity (McAllister and may result in feeding intolerance and
2014). The Shared Plan of Care is jointly devel- reflux. Some CMC may be dependent on feed-
oped by the provider and family and includes a ing tubes due to dysphagia or oral feeding
medical summary and negotiated action steps. aversion. Follow growth closely, be aware of
The care plan should include goals of care, sub- signs of reflux such as vomiting and coughing,
specialist contact information, and required tech- and consider collaborating with GI, speech,
nology or recommended interventions. Under the and/or nutrition.
Shared Plan of Care, action steps are discussed • Respiratory. Many children with CMC have
and prepared proactively and then monitored con- chronic respiratory issues, whether a primary
tinuously. For example, the provider and family etiology or secondary to conditions resulting in
may discuss mobility and nutrition goals, address chronic aspiration. A history of coughing, con-
resources and system navigation needed to carry gestion, or difficulty breathing is important,
out these goals, and document goals for follow-up and it is important to mitigate potential causes
at subsequent visits. Tools exist to guide monitor- or exacerbation such as chronic reflux. Good
ing of medical conditions and activity level in growth with aggressive nutrition is important
children with cerebral palsy (Liptak et al. 2011). to address lung growth. Co-management with
CMC have a higher likelihood of being hospi- pulmonology may be helpful.
talized and visiting the emergency room. Com- • Musculoskeletal. Children with cerebral palsy
mon reasons are respiratory illnesses, seizures, have different levels of mobility related to their
and medical technology dysfunction. Emergency gross motor function classification and may
care planning is important, including instructions experience secondary effects on joints. Physi-
on warning signs of distress and contact informa- cal therapy and co-management with physical
tion for emergencies. Written emergency care medicine and rehabilitation may be needed.
plans can be helpful when the family seeks Pay close attention to joint range of motion,
emergency care. particularly extremities and hips, and monitor
Common medical issues for CMC include: for signs of scoliosis. Monitoring for hip sub-
luxation needs periodic x-rays, as physical
• Neurodevelopmental. CMC have a higher like- signs only develop late with frank dislocation.
lihood of neurodevelopmental disability. As Spasticity can impact function and quality of
such, referral to early intervention is typically life. Bone health should also be assessed. Peri-
warranted for children under 3 years of age. odically evaluate serum 25-OH vitamin D
Attention should also be paid to comorbidities levels, and determine if the child’s diet is meet-
that can develop with neurodevelopmental dis- ing their calcium and phosphorus needs.
abilities, including seizure, respiratory, feed- Encourage weight-bearing when tolerated,
ing, musculoskeletal, gastrointestinal, which sometimes requires utilization of
genitourinary, and behavioral disorders. standers or other mobility supports. Non-
Neurodevelopmental disability may limit hear- traumatic fractures are an indication of low
ing and vision screening obtained in the pri- bone density, and further investigation (such
mary care setting. Engage ophthalmology and as DXA scan) will be helpful.
audiology to conduct indicated screening, Neurologic. Seizure disorders may occur in
when needed, which may require special tech- some CMC. Inquire about jerking motions,
niques beyond the routines used in primary staring spells, periods of apnea, or other poten-
care (such as brainstem auditory evoked tial signs of a seizure disorder. Uncontrolled
response (BAER) and/or visual evoked poten- seizures or a progressive or unstable neuro-
tial (VEP) testing). logic condition is a precaution for the pertussis
component of DTaP (CDC 2019); the decision planning, ideally starting no later than 14 years
on timing of the pertussis-containing vaccine is of age (White et al. 2018). Templates and
often made in consultation with neurology. resources exist to facilitate assessment of transi-
• Behavioral. Medical comorbidities in conjunction tion readiness, goal setting, and information trans-
with speech and motor impairments experienced fer. For medical care, the upper age limit of all
by children with cerebral palsy can negatively pediatric providers should be ascertained and may
affect mental health. Children with cerebral be as early as 18 years of age. Appointments with
palsy have a higher prevalence of depression, new adult providers should occur before the pedi-
anxiety, ADHD, and behavior/conduct problems atric age limit is reached, so there is no gap in care.
compared to their non-affected peers (Whitney It is ideal, though not always possible, to choose
et al. 2019). Assess for bullying, victimization, adult providers who are all in the same health
and mental health concerns. All adolescents system. For patients who frequently use emer-
should receive routine annual depression screen- gency medical services, the system affiliation of
ing beginning at age 12. Clinicians should be the nearest emergency room may be a deciding
aware of the social and emotional support factor when choosing among health systems.
resources available to children with cerebral palsy. Other factors to consider when selecting adult
• Condition-specific issues. In addition to rou- providers include insurance participation, avail-
tine vaccination, remember vaccines for spe- ability of a patient portal, transportation options,
cific populations such as PPSV23 for patients and office accessibility. Concise medical summa-
with cochlear implant or meningococcal B for ries – one from each specialist – and/or a compre-
children with functional asplenia. Give hensive document from the medical home given
palivizumab to infants with significant prema- to patients can facilitate information sharing with
turity and cardiac, respiratory, or musculoskel- new providers and give patients and families use-
etal disease that meet criteria to receive ful insight into the medical history and current
it. Review health supervision and management status.
guidelines available for special populations Self-management skills should be encouraged
that may have medical complexity such as in CMC at all ages in preparation for maximal
Down syndrome (Bull et al. 2011) or Noonan adult independence. Even young children may
syndrome (Ramano et al. 2010). be able to give some medication information,
ask and answer questions about their health, and
Families of CMC often have to shoulder tre- participate in developing the care plan. Parents of
mendous caregiving burden, between direct med- teens should be encouraged, to the extent that it is
ical care, care coordination and navigation, and reasonable, to gradually transfer to the teen
behavior management. It is important to address responsibility for tasks such as medication man-
the home environment, impact on caregiver agement, making appointments, and describing
employment, and the impact on siblings. A care their health during visits. Supervision and
coordinator can address the home environment coaching will likely be needed in the early stages,
and partner with families to address such issues. and parents should keep in mind that the use of
Tools such as care mapping and the Shared Plan of apps, patient portals, and other technology may be
Care can help with needs assessment, care plan- more acceptable to teens, and more accessible,
ning, goal setting, and organization of services. than the ways parents are accustomed to doing
things.
Complex medical conditions affect many
Transition aspects of adult life. Guidance may be needed
regarding residential options, college navigation,
As children with cerebral palsy grow older, care vocational training, transportation, and financial
coordination includes planning for transition to arrangements. Financial and parents’ estate plan-
the adult system of healthcare. Healthcare transi- ning should address what resources will be avail-
tion is a process that requires preparation and able when the parents are no longer there; care
should be taken to maintain eligibility for poten- Cases

tially applicable government programs. Informa-
tion on healthy sexuality and family planning Children with medical complexity, especially
should be offered. Patients who use an augmenta- those with communication impairments, can be
tive communication device, even if primarily at particularly challenging to evaluate when
school, need to have a device that they own and experiencing concerning symptoms. It is helpful
can program, so they can communicate after grad- to include in the medical record baseline vitals and
uation. In some situations parents are told they findings, how discomfort is typically expressed,
must obtain legal guardianship of their young and what signs accompanied prior presentations
adult children. However, guardianship is the of illness. CMC often have additional risks related
most restrictive option for support, and full guard- to implants or devices or their underlying medical
ianship may not be needed. Other less restrictive problems. Two cases are presented here with a
options may include a healthcare power of attor- systematic approach to illustrate special consider-
ney or a health decision surrogate. Options differ ations when evaluating the medically complex
between states. child. (To demonstrate the broad approach often
needed, the physical exam is omitted intention-
ally, as these findings would naturally narrow
Payments etiologies to consider.)
CMC are typically high resource utilizers, and

their medical care often requires investments in Case 1: Agitation
resources and staff training. Under fee-for-service
payment models, it is important to adequately Julia is a 16-year-old female with spastic diplegic
document and bill for time and complexity. cerebral palsy and severe intellectual disability,
In-person and face-to-face encounters are reim- impaired expressive and receptive language, and
bursed under fee-for-service, and the billing mild intermittent asthma, who presents with agi-
codes must reflect the diagnostic and management tation and refusal to walk. She has had a posterior
complexity. Care management and care plan over- spinal fusion due to scoliosis. Her medications
sight codes are potentially available to address include albuterol, Tylenol, and ibuprofen. She is
non-face-to-face time as well. able to eat purees by mouth with assistance. She
Under value-based payment, additional primarily uses a wheelchair but is able to transfer
methods of payment that support care for CMC and walk short distances with assistance, utilizing
may become available. Examples of additional MAFOs. Parents report that Julia has had inter-
payment sources may be care coordination pay- mittent agitation that lasts for a few days every
ments, per-member-per-month population-based few months, which they have associated with her
payments, or bonus payments for meeting qual- menstrual cycle. However, over the past month,
ity metrics. “PCMH” certification may be avail- she has seemed agitated or uncomfortable more
able in certain states or locations and may make frequently, and in the past week she has refused to
the practice eligible for upfront or bonus pay- ambulate independently.
ments that can support additional staff. Risk There are many possible etiologies to consider
stratification may be important to adequately when evaluating a child with cerebral palsy, med-
adjust for medical complexity and lead to addi- ical complexity, and new onset of agitation. For
tional payments as well. It is important to clini- this patient, a musculoskeletal issue may be con-
cally verify the appropriateness of any risk sidered. Are there concerns that her wheelchair,
stratification methods that may be used. Finally, walker, MAFOs, or other mobility equipment do
it is important to ensure that any payments that not fit appropriately, whether from outgrowing
come under population health and care coordina- them or due to obtaining new equipment that
tion are tracked and directed to support such needs adjustment? Has Julia experienced changes
activities. in the frequency or goals of physical therapy that
could affect mobility? Is she demonstrating signs A broad team-based history and physical,
of increased muscle tightness or spasticity? Poten- aided by continuity, is warranted in this situation.
tial causative injuries include occult fracture, hip Additional history and physical exam findings
dislocation, or complications related to her spinal may guide a focused evaluation, but sometimes
fusion or non-accidental trauma. While osteomy- broader laboratory and imaging studies are
elitis may explain Julia’s symptoms, other infec- needed in complex patients with limited commu-
tions such as UTI, cellulitis, and acute otitis media nication ability to express what they are
should also be considered in a child with agitation. experiencing. Primary care clinicians may need
Julia requires a thorough evaluation of her skin to obtain observations and assessments from
integrity as a decubitus ulcer could present in this other members of the child’s care team (school/
manner. She may merit a rheumatologic evalua- home nurse, physical therapist, occupational ther-
tion depending on other signs or symptoms dis- apist, speech language pathologist) while coordi-
covered during the visit. nating evaluation and management with
Other etiologies may independently contribute subspecialty providers. Consultation and coordi-
to agitation or irritability such as a mood disorder. nation with the specialists may also be warranted.
Medications such as albuterol could cause agita-
tion, particularly if temporally related to adminis-
tration, although we would not expect significant Case 2: Fever
impact on mobility. Arrhythmia may lead to agi-
tation as well, and clinicians should be thoughtful Robert is a 3-year-old ex 25-week preterm male
about medications or medication interactions that with epilepsy, ventilator-dependent chronic respi-
may predispose to this. A patient’s underlying ratory failure, hydrocephalus that is VP shunt
cardiac disease may cause his or her symptoms dependent, spastic quadriplegic cerebral palsy,
through chest pain or activity intolerance. and GERD with profound intellectual disability
Neurologic etiologies of agitation include sei- who requires a G-tube for enteral nutrition. Rob-
zures and headaches. Children with ventriculo- ert’s parents have brought him into the office for
peritoneal shunts or vagal nerve stimulators may evaluation since he has had 3 days of fever and
need these devices evaluated. Sleep problems are increased seizure frequency.
common; screen for obstructive sleep apnea, fre- While self-limiting viral infections are a com-
quent coughing, or disrupted sleep cycles. Aller- mon etiology of fever, the clinical course can be
gic rhinitis with sinus congestion may also cause particularly severe in CMC, whether due to
facial discomfort that presents as agitation when impaired airway clearance, immunocompromise,
the child is unable to verbally express the symp- or technology dependence. These higher-risk chil-
toms they are experiencing. Dental problems are dren currently qualify for treatment or prophylaxis
another source of agitation to consider. in the setting of active influenza infection or expo-
Constipation and gastroesophageal reflux are sure to influenza (Fiore et al. 2011) and may
common and if not well controlled can lead to require higher levels of supportive care during
discomfort and agitation. Screen and treat for con- illness. Bacterial tracheitis and ventilator-
stipation aggressively. Polypharmacy may contrib- associated pneumonia should be considered
ute to dyspepsia. Feeding intolerance should also when evaluating Robert’s fever. He should also
be considered, especially in children with feeding be evaluated for acute suppurative otitis media,
tubes or whose agitation appears to coincide with while urinary tract infection and group A strep
receiving nutrition. Kidney stones or other etiolo- pharyngitis may also need to be contemplated.
gies leading to obstructive uropathy can present Guided by history and physical exam, consider
with agitation. It may be more challenging for additional sources of bacterial infection in tech-
caregivers to identify changes to urinary frequency nology- and device-dependent children such
and related symptoms in children without bladder as VP shunt infection, bacteremia in patients
control unless hematuria is present. with indwelling lines, or infection at the site of
implanted hardware. Potential secondary compli- ▶ Health and Healthcare Disparities in Children
cations should be mitigated as well. Examples with Cerebral Palsy
include increased airway clearance such as bron- ▶ Life Care Planning for the Child with Cerebral
chodilators and chest physiotherapy. The Palsy
co-managing specialist(s) should be notified for ▶ Outpatient-Based Therapy Services for Chil-
additional support. dren and Youth with Cerebral Palsy
Prevention is even more critical in this popula- ▶ School-Based Therapy Services for Youth with
tion. Nutrition, growth, function, and quality of Cerebral Palsy
life should be optimized to increase both physical ▶ The Child, the Parent, and the Goal in Treating
and psychosocial resiliency; the child whose feed- Cerebral Palsy
ing is optimized and airway is protected will be
less likely to develop recurrent aspiration pneu-
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Managing Bone Fragility in the Child
Heidi H. Kecskemethy and Steven Bachrach
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 372
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 372
Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 372
Medical Effects of CP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 373
Bone Basics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 373
Gross Motor Function Classification System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 374
Relationship of BMD and Fracture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 374
Pathophysiology/Etiology of Compromised Bone Health . . . . . . . . . . . . . . . . . . . . . . . . . . . 375
Malnutrition/Suboptimal Nutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 375
Puberty . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 376
Weight Bearing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 376
Medications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 376
Treatment and Complications: Identification and Prevention . . . . . . . . . . . . . . . . . . . . . 377
Identification of Risk Factors and Prevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 377
Review Medical Risk Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 377
Medication Selection/Consideration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 377
Weight Bearing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 378
Assessment of Bone Density . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 379
Handling/Mechanics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 381
Education of Care Providers (School, Nurses/Aides, Families) . . . . . . . . . . . . . . . . . . . . . . . . 381
H. H. Kecskemethy (*)
Departments of Biomedical Research and Medical
Imaging, Nemours/Alfred I. duPont Hospital for Children,
Wilmington, DE, USA
e-mail: Heidi.kecskemethy@nemours.org
S. Bachrach
Department of Pediatrics, Nemours/Alfred I. duPont
Hospital for Children, Wilmington, USA
e-mail: Steven.bachrach@nemours.org

https://doi.org/10.1007/978-3-319-74558-9_26
372 H. H. Kecskemethy and S. Bachrach
Pharmacologic Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 382

Bisphosphonates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 382
Other . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 384
Summary/Wrap Up . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 384
Case Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 384
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 390
Abstract complications (Shevell et al. 2009). These mani-

Skeletal health during the childhood years has festations have a direct effect on bone health
a direct effect on lifetime risk of osteoporosis (as well as on the ability to evaluate bone density).
and bone fragility. Children with cerebral palsy While heritability is well-accepted as a major
(CP) frequently have comorbidities that influ- determinant of bone health, environmental factors
ence bone development and health. With – weight bearing, nutritional status and intake, and
increased severity of the CP, there are greater ingestion of medications that affect bone density
systemic effects on body systems and com- and accrual – clearly affect the attainment of
mensurate deleterious effects on bone. These genetic potential (Schoenau and Fricke 2008).
comorbidities may include nutritional deficien- Load bearing has a direct effect on bone because
cies, limited or no weight bearing, use of var- bones adapt, changing internal architecture and
ious medications that affect bone, and lack shape, based on need (Frost 1987). Thus, the
of exposure to sunlight. The presence of these children with CP who are classified as GMFCS
comorbidities has a direct effect on bone 3–5 have the highest risk of developing low bone
health, which results in decreased bone mineral density and osteoporosis, due to their very limited
density and puts many of these children at risk (or no) ambulation and their high risks for poor
for fragility fractures. In this chapter, we will nutrition and multiple medication intake. In this
review the natural history of CP and the basics chapter, we will review the natural history of CP
of bone formation, discuss assessment of bone and the basics of bone formation, discuss assess-
health for children with CP including measurement of bone health for children with CP includ-
ment of bone density, and present current treating measurement of bone density, and present
ment practices for children with compromised current treatment practices for children with
bone health. compromised bone health. We will also present a
number of case histories, which help illustrate the
Keywords decision points involved in treatment.
Bisphosphonate · Bone density · Fragility
fracture · Non-weight bearing · Nutrition
Natural History
Introduction Cerebral Palsy
Cerebral palsy is a static encephalopathy that The term cerebral palsy (CP) “describes a group
results in disorders of movement and posture. of permanent disorders of the development of
The range of impairment is well described by the movement and posture, causing activity limita-
categories of the Gross Motor Function Classifi- tion, that are attributed to non-progressive distur-
cation System (GMFCS) (Palisano et al. 1997). bances that occurred in the developing fetal
With increased severity of involvement, there or infant brain. The motor disorders of CP are
is an increased risk of secondary medical often accompanied by disturbances of sensation,
26 Managing Bone Fragility in the Child with Cerebral Palsy 373
perception, cognition, communication, and can result from neurologic effects to the head
behavior, by epilepsy, and by secondary muscu- and neck. The presence of these secondary effects,
loskeletal problems” (Rosenbaum et al. 2007). and the degree and severity of the effects, is
The manifestations are alterations in tone and governed by the location and effect of the damage
motor control and can involve spasticity, to the brain.
athetosis, hypotonia, or a combination of the The effect of CP on body systems can result in
three. Motor function impairment can involve a cascade of sequelae that further affect body
from one to all four limbs and the head and functions, resulting in secondary medical effects
neck. This range of impairment is well described (Table 2). For example, severe scoliosis (curva-
by the categories of the Gross Motor Function ture of the spine) directly affects functions of the
Classification System (GMFCS) (Palisano et al. pulmonary (the ability to breathe by compression
1997). With increased severity of involvement, of the chest) and the gastrointestinal (reflux due
increased risk of secondary medical complica- to compression of the stomach and intestines)
tions follows (Shevell et al. 2009). These mani- systems (Banta et al. 1998).
festations have a direct effect on bone health as
well as the ability to evaluate bone density.
Bone Basics
Medical Effects of CP Bones begin to form in utero and at birth are

composed of a combination of mineralized bone
Primary Effects and cartilage. As a child ages and grows, cartilage
Because CP results from damage to the brain, is ossified to become mineralized bone, which
many children with CP have other brain functions increases in size and density throughout child-
affected in addition to the motor dysfunction that hood and adolescence. By the third decade of
is the hallmark of CP (Table 1). One or all of these life, approximately 90% of peak bone mass is
effects may be present, to varying degrees, and are
determined by the location and severity of the Table 2 Common secondary medical effects of cerebral
palsy
brain lesion.
Aspiration pneumonia
Secondary Medical Problems Bladder dysfunction
Compromised nutrition
Because of the chronic tone abnormalities caused
Constipation
by CP, many children have secondary complica-
Dental caries
tions that affect their musculoskeletal, pulmonary,
Depression
and gastrointestinal systems. The abnormality of
Excessive drooling
muscle tone that is characteristic of CP can affect Fragile bones
the head and neck area, which causes problems Frequent fractures
with the ability to eat, swallow, and speak; upper Gastroesophageal reflux
airway obstruction or aspiration of food or saliva Gum hypertrophy
Hip dislocation
Table 1 Neurologic effects commonly seen with cerebral Joint contractures
palsy Leg-length discrepancies
Motor dysfunction Motility problems
Cognitive and learning impairments Obstructive sleep apnea
Communication disorder Poor growth
Seizure disorder/epilepsy Poor mouth/lip closure
Sensory impairments – vision and learning Scoliosis/kyphosis
Speech impairment Tooth decay/gum disease
Swallowing difficulties Upper airway obstruction
achieved (Bonjour et al. 1991; Heaney et al. Gross Motor Function Classification
2000). Modeling and remodeling of bone occur System
throughout life at varying rates, as determined
by genetics, forces on the bones, hormonal The Gross Motor Function Classification System
milieu, sex, and availability of vitamin and min- (GMFCS) is an assessment tool that is used to
eral substrate. While heritability is well-accepted describe the functional abilities and limitations of
as a major determinant of bone health, environ- children with CP. The five-level classification sys-
mental factors – weight bearing, nutritional status tem is based on an evaluation of the child’s gross
and intake, and the presence of substances that motor skills and abilities of self-initiated move-
affect bone density and accrual – clearly affect ment. The original GMFCS classification system
the attainment of genetic potential (Schoenau was for children aged 2–12 years (Palisano et al.
and Fricke 2008). Load bearing has a direct 1997). Since its introduction, Palisano and col-
effect on bone because bones adapt, changing leagues have refined and revised the tool, known
internal architecture and shape, based on need as the GMFCS-E&R, to include an age band for
(Frost 1987). 12- to 18-year-olds and emphasize the concepts in
The modeling and remodeling of bone during the World Health Organization’s International Clas-
childhood provide for the increases in bone size, sification of Functioning, Disability, and Health
bone mineral content, and density that occur dur- (IFH). The GMFCS is useful to families and clini-
ing growth. Bone remodeling throughout life cians because it provides a prediction of equipment
allows for repair and healing of bone and liberates and mobility aids that the child may need in the
calcium and phosphorus for other body functions. future. Beyond the age of 5 years, a child will likely
Throughout life, bone modeling and remodel- not improve his or her GMFCS level.
ing occur at different rates. During childhood, A child’s GMFCS level is indicative of his or
bones are amassed at a greater rate than her ability to ambulate, among other things, and,
remodeling (resulting in growth); during adult because weight bearing greatly affects bone forma-
years, bone mass is typically maintained, and, tion and density, GMFCS level is directly related to
by the fifth decade of life, the rate of remodel- bone development. Children with GMFCS levels
ing exceeds the rate of deposition (resulting in of 1 and 2 are generally able to fully bear weight all
bone loss and sometimes later osteoporosis). of the time. Children with GMFCS level 3 are
There is greater risk for fracture and osteoporosis usually partial weight bearers, and children with
later in life if attainment of peak bone mass is GMFCS levels 4 and 5 seldom bear weight unless
compromised during childhood (Hui et al. 1990; done via passive standing. The GMFCS level is
Melton et al. 1989). directly related to bone mineral density (BMD)
In children with CP, differences in bone growth and fracture history (Henderson et al. 2010).
and development can be seen. Compared with For additional information about GMFCS,
typically developing, healthy children, the rate of see ▶ Chap. 21, “Classification Terminology in
bone accrual is lower in children with complex CP Cerebral Palsy.”
(Henderson et al. 2005). If the child is unable to
bear weight and has atypical muscle tone, struc-
tural differences are seen, and periosteal expan- Relationship of BMD and Fracture
sion is negatively affected. Lower leg bones of
non-ambulatory children with CP have been The most common site of fracture in healthy chil-
shown to be smaller and thinner than those of dren is the forearm, and trauma from a fall is the
typical children (Binkley et al. 2005), and, most common mechanism of fracture (Goulding
among children with CP, those who were unable et al. 2005). Half of all healthy boys and nearly
to walk had lower tibial cross-sectional area and one-third of girls will experience at least one bro-
cortical bone area than those who could walk ken bone during childhood and adolescence, with
(Wren et al. 2011). most occurring in an upper limb (Jones et al. 2002).
Once a child has experienced a fracture, they are resulting in poor bone density and fragility frac-
more likely to sustain another fracture later in life, tures (Kecskemethy and Harcke 2014). These risk
even into adulthood (Farr et al. 2014). After sus- factors include the following.
taining one fracture, the odds that a child will have
another fracture are 1.9 times higher than for those
who never had a fracture and are 3.04 times higher Malnutrition/Suboptimal Nutrition
after the second fracture (Goulding et al. 2005).
As with normally developing children, children Feeding problems in children with severe CP are
with CP who experience fracture are more likely to common and are associated with poor health sta-
sustain additional fractures (Henderson et al. tus and compromised growth (Fung et al. 2002).
2002a; Stevenson et al. 2006). For children with Feeding problems result in poor nutritional status.
CP who are GMFCS 1–3, fracture rate, location, Compromised nutritional status is directly related
and mechanism of fracture have been reported to to compromised bone health in children with CP
be similar to those of their typically developing (Henderson 1997; Henderson et al. 2002a, 2004).
peers (Uddenfeldt Wort et al. 2013). However, The feeding disorder that children with CP, espe-
fracture rate of children who are GMFCS 4 or 5 is cially (but not exclusively) those with quadriple-
higher (Uddenfeldt Wort et al. 2013) and the frac- gic CP, can experience is caused by lack of
tures experienced by non-weight-bearing children coordination of the muscles of the mouth and
with CP are notably different from those experi- throat, which affects their ability to chew and
enced by typically developing, healthy children: swallow food and their own saliva (Jones 1989;
the most common site of fracture is the lower Waterman et al. 1992). These children are at risk
extremity, and the mechanism is low or minimal for aspiration, resulting in frequent respiratory
trauma (Henderson 1997; Lee and Lyne 1990; symptoms and infections. A history of coughing
Mughal 2014). Of lower extremity fractures, and choking during meals or of recurrent respira-
60–70% occur at the distal femur (Bachrach et al. tory infections, or both, will point to a child who
2010; Henderson et al. 2002a; Presedo et al. 2007). may be aspirating. Feeding and swallowing dys-
While the relationship between BMD and frac- function due to tongue thrust, tonic bite reflex,
ture is clearly described in adults, this relationship is poor lip closure, gum hypertrophy, and poor
not as rigorously proven in pediatrics. The predic- tongue lateralization causes significant challenges
tive value of BMD for fracture in healthy, typically with food ingestion and can result in prolonged
developing children has not been demonstrated. meal times (sometimes up to 6 h per day) (Jones
Yet, in children with chronic illness, particularly 1989). Periodic review of a child’s growth chart as
conditions affecting weight bearing or ambulation well as a diet history will identify the child who is
such as CP, Duchenne muscular dystrophy, and malnourished because of the inability to take in
spina bifida, both low BMD and fracture are enough food by mouth. See ▶ Chaps. 49, “Over-
observed in the lower extremities (Haas et al. view of Feeding and Growth in the Child with
2012; Harcke et al. 2006; Henderson et al. 2004). Cerebral Palsy” and ▶ 24, “General Nutrition for
A strong correlation between fracture history and Children with Cerebral Palsy” for more informa-
BMD Z-scores in the distal femur in children with tion about growth and nutrition.
CP has been demonstrated (Henderson et al. 2010). Inadequate intake of food results in inadequate
intake of macro- and micronutrients including the
primary nutrients of concern for bone: calcium,
Pathophysiology/Etiology phosphorus, and vitamin D. Most children, and
of Compromised Bone Health especially adolescents, take in insufficient
amounts of calcium because of low milk con-
The secondary medical problems commonly seen sumption (Black et al. 2002). While some children
in children with CP can result in higher than with CP have a true milk allergy, it is not uncom-
average risk for compromised bone health mon for parents/care providers to eliminate milk
from their child’s diet because of their perception from their healthy, typically developing peers,
that dairy makes their child congested. with an earlier onset and a prolonged duration
Vitamin D is obtained via ingestion or by sun (Worley et al. 2002). The timing of onset of
exposure. For people who are able to be outdoors, puberty is inversely related to BMD in typically
sun exposure during the summer months can pro- developing children: early onset results in higher
vide adequate vitamin D. For children who are adult BMD, and delayed onset of puberty results
intolerant to heat, who are taking medications in low adult BMD (Cattran et al. 2015; Finkelstein
where sun exposure is contraindicated, or who et al. 1992). It is unknown how the altered onset
are covering their skin with clothing or sun and duration of puberty are commonly seen in the
block, exposure to the sun is limited, limiting CP population affects BMD.
formation of vitamin D. These children need to
obtain vitamin D from dietary sources. The Food
and Nutrition Board of the Institute of Medicine Weight Bearing
(IOM), National Academy of Sciences, recom-
mends that all children take a supplement of As described above, weight bearing has a positive
600 IU of vitamin D daily, but there is a high effect on bone formation, growth, and density.
percentage of children, even in the general popu- Lack of weight bearing results in long, thin
lation, with vitamin D deficiency (Pettifor 2014). bones that are more apt to fracture with minimal
Disagreement currently exists regarding the defi- to no trauma. Children who are GMFCS 2 or
nition of vitamin D deficiency. According to the 3, who are able to walk, are generally not running
Endocrine Society guidelines, deficiency is a level and jumping as much as their typical counterparts
below 20 ng/mL, insufficiency a level between (and often not at all), giving them some risk as
20 and 30 ng/L, and adequate levels are 30 ng/ well for low BMD and possible fractures. Some of
mL or higher (Holick et al. 2011). According to these children may be so discouraged because
the IOM, deficiency is a level below 12 ng/mL, they cannot keep up physically with their peers
insufficiency is 12–20 ng/mL, and an adequate that they are not doing even the physical activities
level is 20 ng/mL or higher (Institute of Medicine of which they are capable. Children who are
2010). There is, thus, controversy whether to treat GMFCS 4 or 5 are unable to bear weight on
levels between 20 and 30 ng/mL in a healthy their own, placing them at greatest risk for
population. The evidence shows that levels in poor bone density and risk for fracture (Bachrach
the deficient and insufficient range are common et al. 2010; Chad et al. 1999; Henderson 1997;
in children (Manios et al. 2017) and adults Henderson et al. 2002a, 2004).
(Chapuy et al. 1997), especially in the winter
and in northern latitudes. Since the CP population
is at high risk for low BMD and fractures (espe- Medications
cially those in GMFCS 3–5), it is prudent to use
the Endocrine Society recommendations and to Medications can have a negative or positive effect
treat levels below 30 ng/mL with supplemental on BMD through a variety of mechanisms. Mech-
vitamin D. anisms include changes in bone metabolism, vita-
min D metabolism, or nutrient absorption.
Chronic steroid use is clearly associated with
Puberty low BMD in adults and children. There are
conflicting reports that certain anticonvulsants
Puberty is the time during which the greatest (phenobarbital, phenytoin, and valproic acid) neg-
amount of bone accrual occurs during life, atively affect vitamin D metabolism (Dhillon
resulting in rapid linear growth, bone accretion, 2011; Beerhorst et al. 2013). Prolonged use of
and gains in BMD. The pattern of puberty in proton pump inhibitors has been associated with
children with moderate to severe CP is different nutrient malabsorption and fractures (Ito and
Jensen 2010), and aluminum-containing antacids patient is very important. Specifics about prior
bind with phosphorus in the gut, affecting nutrient fracture(s), the location of the fracture(s), and
absorption. High levels of thyroid hormone cause circumstances that led to it should be obtained, if
excretion of calcium and phosphorus, resulting in possible. Low-energy fractures (those that occur
loss of mineral in bone. Depot medroxypro- with little to no trauma) of the leg bones are
gesterone (Depo-Provera, Pfizer, New York, NY), common in non-ambulatory children with CP,
aromatase inhibitors, and gonadotropin-releasing and, once a child has sustained a fracture, they
hormone agonists (GnRH) decrease estrogen are more likely to sustain additional fractures
levels, resulting in a reduction in bone formation (Henderson et al. 2002). Because smoking and
and an increase in bone resorption (Davidge Pitts consumption of large quantities of soda can
and Kearns 2011; Rahman and Berenson 2010). adversely affect bone density (Dorn et al. 2013;
An increased risk of fracture has been reported with Tucker et al. 2006), questions about these two
tricyclic antidepressant (CTA) and selective sero- practices should be asked. Family history of
tonin uptake inhibitor (SSRI) use (Rabenda et al. osteoporosis should be reviewed, specifically
2013). Immunomodulating drugs methotrexate ascertaining if there is a history of multiple frac-
(MTX) and 6-mercaptopurine (6-MP) are associ- tures or non-traumatic fractures in other family
ated with low BMD in children (Semeao et al. members at a young age. While this is an
1999; Wasilewski-Masker et al. 2008). Use of stim- unmodifiable risk factor, it is useful information
ulants for attention-deficit/hyperactivity disorder for the overall consideration of risk.
(ADHD), which activate the sympathetic nervous
system, has been shown to negatively affect BMD
in children (Feuer et al. 2016). Many of these Medication Selection/Consideration
medications are used to manage medical concerns
in children with CP. Medication use should be reviewed, particularly if
there is a history (current or prior) of prolonged
use of steroids, anticonvulsants, antidepressants,
Treatment and Complications: or depot- medroxyprogesterone. Sometimes an
Identification and Prevention alternative medication that is not as deleterious
to the child’s bone density can be offered (such
Identification of Risk Factors as substituting a long-acting reversible contracep-
and Prevention tion for depot- medroxyprogesterone). At other
times, the family or physicians may be reluctant
Identification of risk factors present in a patient to change a medication because it has been effec-
will help to inform medical decision making and tive (e.g., an effective anticonvulsant). Discussion
planning to help decrease risk for fractures and should occur with both the family and other phy-
compromised bone health. sicians about the risk of a change in medication
versus the risk of continuing it but worsening the
bone density. The Endocrine Society recommends
Review Medical Risk Factors two to three times more vitamin D for their age
group for children and adults who are taking anti-
The first step in evaluating a child with CP for convulsant medications, glucocorticoids, antifun-
possible low bone density is to review the medical gals such as ketoconazole, and medications for
history and identify risk factors, modifying those AIDS to satisfy their body’s vitamin D require-
that are amenable to change. A thorough medical ment (Holick et al. 2011).
history (including birth history) will often identify
a child at increased risk, whether because of a Nutrition Assessment
history of prematurity, feeding problems, or diffi- Nutrition: evaluation of intake, laboratory assess-
culty ambulating. History of any fracture in the ment, and correction of deficiency.
Growth is a gauge of the adequacy of nutri- evaluation. Serum 25-OH-vitamin D level should
tional intake. A weight indicates acute nutritional be checked annually thereafter. Vitamin D defi-
status, and height indicates chronic nutritional ciency is the most common nutritional problem
status. Assessment of the child’s growth pattern identified in children with CP. The Endocrine
over time will reveal chronic problems. Nutri- Society recommendation for patients identified
tional assessment of dietary intake (3- to 5-day as deficient or insufficient is as follows: vitamin
food records) should be performed and evaluated supplements of 2000 IUs of vitamin D2 or D3
for meal timing, volume and variety of foods and once daily or 50,000 IU once a week for at least
beverages, and adequacy of macro- and micro- 6 weeks. If the repeat vitamin D level is above
nutrients. Once nutrient analysis is completed 30 ng/ml, a maintenance dose of 800–1200 IU
and assessed, it is common practice in the United daily may be enough to maintain adequate
States to provide dietary nutrient supplements to a levels, though, in some patients, a higher mainte-
patient for any vitamin or mineral that is less than nance dose will be needed (Holick et al. 2011).
75% of the recommended intake. Internationally, Some clinicians argue for higher levels of 25-OH-
nutrient recommendations vary, and supplemen- vitamin D in these vulnerable patients, but there is
tation practices differ globally. Dietary reference no evidence for any benefit from levels above
intake requirements for the US population can be 30 ng/mL.
found at https://www.nal.usda.gov/sites/default/
files/fnic_uploads/recommended_intakes_individ
uals.pdf. Evaluation of diet should also include Weight Bearing
review of cola soda intake, which both displaces
more nutritional, calcium-containing beverages Standing
and has a high phosphorus content, which can As noted earlier in this chapter, bone formation is
have a direct deleterious effect on bone density sensitive to mechanical stress, and the lack of
(Tucker et al. 2006). A pediatric dietitian can weight bearing negatively affects normal bone
assess the adequacy of the diet as described growth and development. This puts children at
above as well as examine mealtime practices, GMFCS levels 4 and 5, who are not walking, at
including time required for feeding, use of feeding the greatest risk for low bone density and sec-
supports (therapeutic feeding utensils and cups), ondary fragility fractures. Children at GMFCS
and timing of meals and snacks. The dietitian can levels 2 and 3, who are walking, are generally not
provide counseling/education to the child and running and jumping as much as their typical
their family/care providers and make recommen- counterparts (and often not at all); therefore,
dations for supplementation if required. Referral they also have some risk for low bone density
to an occupational therapist or speech therapist, or and possible fractures. Weight-bearing activities
both, may be indicated for assistance with thera- have been suggested as a way to increase BMD
peutic feeding and feeding supports. For addi- in children, but the evidence is not clear because
tional information about growth and nutrition, of small sample sizes and short duration in the
see ▶ Chaps. 49, “Overview of Feeding and Growth studies (Chad et al. 1999; Ozel et al. 2016). A
in the Child with Cerebral Palsy” and ▶ 24, “Gen- systematic review looking at interventions for
eral Nutrition for Children with Cerebral Palsy.” children with CP and low BMD concluded that
weight-bearing activities and administration of
Laboratory Evaluation bisphosphonates yield positive results on BMD
Blood tests are helpful as part of the evaluation and fracture prevention (Hough et al. 2010). For
of bone health. Basic chemistries should be some children, weight-bearing opportunities
performed to rule out kidney and liver problems, occur by walking in a gait trainer; for others,
which can negatively affect bone. Serum levels of passive standing may be the most they can
calcium, phosphorus, alkaline phosphatase, and do. Children with CP should begin physical ther-
25-OH-vitamin D should be acquired at the first apy as early as possible. A physical therapist can
evaluate a child’s abilities and make recommen- modalities are available for assessing bone in
dations on type and kind of stander, walker, or children, the techniques are limited to research
gait trainer that is best suited to the child. Chil- use. Recommended body sites to measure in
dren who are ambulatory but limited in their children are the whole/total body less head and
ability to walk rapidly or run (GMFCS 2–3) lumbar spine, and, for children with neuromuscular
should be encouraged to do as much as they conditions, the lateral distal femur (LDF) is an
can, such as walking on a track on a daily basis. alternative site to measure (Crabtree et al. 2014).
Some of these children may be discouraged The LDF DXA was developed for those chil-
because they cannot keep up physically with dren who are unable to be safely and comfortably
their peers and may not be doing much physical positioned because of contractures and move-
activity. These children need to understand the ment disorders or who have nonremovable
importance of continuing to remain physically indwelling artifacts (metallic rods, pins, clips,
active for their overall health and especially to and screws and shunt or feeding tubes and but-
continue weight-bearing activities for their bones. tons) that affect BMD results (Harcke et al. 1998;
Henderson et al. 2002b). Figure 1 shows the LDF
Vibration DXA positioning, and Fig. 2 shows the scan
Low-magnitude mechanical stimuli (LMMS) image (Figs. 1 and 2). The LDF DXA is the
have been shown to be anabolic to bone in a most clinically relevant site to measure for non-
variety of animal and human models. Experi- weight-bearing children, because this is the body
ments in animals have demonstrated that high- site most likely to fracture. The LDF DXA is a
frequency (10–90 Hz), extremely low-magnitude nonstandard exam on bone density machines,
(less than 100 microstrain) stimuli are anabolic to and DXA technologists must be trained on how
trabecular bone (Rubin et al. 2001). Brief expo- to correctly acquire and analyze the scan. Addi-
sures (10–20 min daily) to these low-level sig- tional information about the LDF DXA can be
nals have been shown to inhibit disuse found at www.lateraldistalfemur.org. Normative
osteoporosis in these animal models. There are values are available only for Hologic machines
several LMMS devices available with differing (Hologic, Inc., Marlborough, MA) (Zemel et al.
properties and technical details. When applied 2009).
to children with CP, the results on bone density Pediatric bone presents unique challenges for
have been variable. For instance, one study densitometry because of growing bones. Repro-
using 31 children with CP in GMFCS 1–4 ducibility in DXA is extremely important for
showed improved bone density only in the corti- accurate serial results, and growing bone changes
cal bone of the appendicular skeleton (Wren et al. over time. Measuring the bones of children with
2010), whereas another study published the same CP is even more challenging because of changes
year and in a similar population showed no effect in contractures, worsening scoliosis, development
on bone density, though the children had improved of fractures, or the addition or removal of indwell-
average walking speed (Ruck et al. 2010). Another ing artifacts that affect results. Scan times are
study in children who were GMFCS level 2 or quick, ranging from 30 s to 6 min, depending on
3 showed improvement in BMD, muscle mass, body site scanned and type of scanner. However,
and mobility (Gusso et al. 2016). movement during the scan yields invalid results.
Sometimes sedation is used for DXA, but the risk
of sedation versus the benefit of the information
Assessment of Bone Density must be considered when deciding to use seda-
tion. Certain body sites are more easily obtained
Dual-energy x-ray absorptiometry (DXA) is in children with CP because of scan time, position,
the most readily available, widely used, and and comfort. The whole body scan takes the lon-
recommended technique for assessing BMD gest time to acquire (3–6 min), requires that the
in children and adults. While other imaging body lie flat on the table, and is particularly
Fig. 1 The position for

lateral distal femur, dual-
energy absorptiometry
scan acquisition is side-
lying, with the knee
positioned for a true
lateral view. Positioning
aids ensure comfort and
stability, minimizing
movement; the position is
generally well-tolerated
susceptible to movement; it is the most difficult to

acquire on children with CP and is the most likely
to contain artifacts that affect results. Lumbar
spine DXA is quick (<60 s) but is only valid if
there are no artifacts present (metal, pumps, tubes,
buttons) on the scan. The LDF DXA has a scan
time of less than 2 min and is acquired in a side-
lying position that is usually comfortable for
patients and is therefore well-tolerated. A DXA
technologist who is familiar with the scan can
usually acquire a successful LDF DXA on a
child with CP without sedation.
Ordering physicians should identify which
imaging center will be able to successfully scan
children with CP before referring patients.
Ascertaining the following information will help
the clinician to identify an imaging center that can
accommodate children with CP:
• Familiarity with measuring children

• Ability to accommodate wheelchairs or beds in
the DXA room
• Scanning techniques that they offer (LDF)
• Pediatric software and normative values on the
Fig. 2 The lateral distal femur dual-energy x-ray absorp-
bone density machine
tiometry image is analyzed with three regions of interest • Availability to lift patient
(R1 – R3). Each region of interest provides different infor- • Familiarity with pediatric DXA interpretation
mation about the bone. R1 is adjacent to the growth plate
and contains primarily trabecular bone; R2 is meta-
To get the best bone density study results – a
diaphyseal and is comprised of trabecular and cortical
bone; and R3 is diaphyseal and contains primarily successful scan and interpretation – it is important
cortical bone to provide the following information about your
patient to the imaging center: ambulatory status, normative values, each patient can serve as his or
indication for scan, history of bisphosphonate her own control with serial scans.
use, Tanner score, fracture history, and presence Normal growth over time results in stable
of nonremovable artifacts. This information will (unchanging) Z-scores. Negative Z-scores getting
guide which body sites are scanned and will help closer to zero over time indicate improvement in
with scan interpretation. BMD greater than expected with normal growth.
The DXA study results are reported as BMD Bisphosphonates affect trabecular bone more
values (gm/cm2) and the corresponding Z-scores. markedly than cortical bone; areas high in trabec-
Some centers will also report bone mineral con- ular bone (the end of long bones and spine) are
tent (BMC) (gm) and the corresponding Z-score. affected by bisphosphonates during growth.
Z-scores indicate how the patient’s result com- Z-scores further deviating from the mean over
pares with the average result for a healthy child time indicate lack of bone accrual or, if the
of the same age, race, and sex. Z-scores of 2.0 or BMD is less than in the prior scan, bone loss.
below are considered “low or below normal.” The Repeat DXA scans should be performed when
term “osteopenia” based on BMD results is not meaningful change might occur. In the growing
recommended in pediatrics. Currently, the term skeleton, this is usually annually. However, clini-
“osteoporosis” in pediatrics is used based on cal treatments, presence and type of risk factors,
either (1) the presence of one or more vertebral and age may indicate a different timeframe for
compression fractures in the absence of disease or repeat scans.
high-energy trauma or (2) both low bone density
(DXA Z-score of 2.0) and the presence of one
or more of the following: (a) two or more long Handling/Mechanics
bone fractures by age 10 years and (b) three or
more long bone fractures at any age up to age The GMFCS level of the child is a good indicator
19 years (Crabtree et al. 2014). Children with of risk for fracture, as described earlier in this
severe CP frequently have low BMD. Consider- chapter, largely because of weight-bearing status.
ation of risk factors can help with interpretation of Little to no weight bearing compounded by the
results. Size adjustments to BMD are presence of other risk factors to bone health results
recommended, but the type of adjustment used in fractures, frequently with little or no identified
varies by both scanner and body part scanned. trauma. Children who are GMFCS 4 or 5 require
Furthermore, one of the size adjustments is assistance with activities of daily living, including
based on height, which is often very difficult to toileting and transfers into and out of their chair.
accurately obtain on children with complex CP. How transfers are managed vary, whether via a
Scans obtained on different manufacturers’ mechanical lift, stand-pivot transfer, or single- or
machines are not comparable because the two-person lift. During transfers, body mechanics
machines use dissimilar energy sources and tech- should be considered to minimize the possibility of
nologies. Normative values are machine specific. trauma and low-energy fractures. Care should be
The first scan acquired on a patient will serve taken to minimize motions that overstretch, twist,
as the baseline or comparison scan. It is important or have the potential to create a lever arm situation
to measure as many body sites as possible with the long bones of the legs.
because, over time, body sites may become inva-
lid because of the addition of metallic hardware,
fractures, or surgeries involving the bone. Repro- Education of Care Providers (School,
ducibility (of positioning and analysis) is impor- Nurses/Aides, Families)
tant in DXA with serial scans. It might not be
possible to position a child with CP in the It is important to educate both children and mem-
recommended position for a scan. When there bers of their care community about the importance
are technical concerns that invalidate the use of of bone health and risk of fracture. Optimizing
nutrition, increasing weight-bearing opportunities children, the intravenous medication pamidronate

(walking, gait trainers, use of stander), and aware- is by far the best-studied and most widely used
ness of decreasing risks all represent ways to bisphosphonate. Though the treatment regimen
contribute to a child’s bone health. Including can vary, it is typically given 3 days in a row,
aspects of bone health in the therapeutic goals every 3–4 months, in a dose of 1 mg/kg/day.
within the individualized education plan (IEP) at Typical side effects include fever, chills, muscle
the child’s school can ensure that plans are aches, nausea, vomiting, hypocalcemia, and
followed. Telling all care providers (including hypophosphatemia. Fever and chills are most
nurses, aides, therapists, family) about fracture commonly seen with the first course of treatment,
history is paramount, because the risk for second may be seen to a lesser degree with the second
fracture is great. course, and then usually are no longer experi-
enced. Other side effects are less common but
can occur with any of the treatment courses; there-
Pharmacologic Treatment fore, serum calcium and phosphorus should be
checked before the first day and after the third
Many of the medications used to treat day of each treatment course. A more severe but
osteoporosis in adults are also used in children. less common side effect is osteonecrosis of the
These medications increase bone density by jaw (ONJ). ONJ from bisphosphonate use has
increasing osteoblastic or decreasing osteoclastic never been reported in a pediatric patient.
activity. Antiresorptive medications work by Among adults, when ONJ occurs, it is typically
inhibiting normal bone breakdown that occurs seen in those receiving both bisphosphonate
during remodeling (e.g., bisphosphonates, anti- and chemotherapy for cancer treatment, but
RANKL) (Genant et al. 2013; Russell et al. it has been seen in some adults receiving
2008). Other medications increase bone formation only bisphosphonates (Woo et al. 2006).
by stimulating osteoblastic activity similar to Atypical femur fracture (AFF) is another side
parathyroid hormone (e.g., teriparatide) (Jiang effect reported in the adult literature associated
et al. 2003). While these medications are with bisphosphonate use. In pediatrics, several
approved for use in adults, use in pediatrics is case studies report AFF with long-term
new, and data on their safety, efficacy, dosing, bisphosphonate use in children with osteogenesis
and long-term effects in children are limited. imperfect (OI) (Carpintero et al. 2015; Vasanwala
When to initiate pharmacologic treatment in et al. 2016; van de Laarschot and Zillikens 2016;
children with CP is not well established, and prac- Boyce et al. 2017). However, Trejo et al. deter-
tices vary. Some clinicians will treat only after a mined that the atypical femur fractures observed
second fragility fracture, while others will begin in 90 patients seemed to be related to the severity
treatment after a first fracture if other risk factors of OI rather than to bisphosphonate treatment
have been addressed. Still other clinicians will history (Trejo et al. 2017). The duration of treat-
start bisphosphonate treatment based on a very ment with bisphosphonate in children with OI is
low BMD by DXA, even if no fracture has yet long, starting at weeks of life and extending
occurred. The approach to treatment needs to be through puberty. For children with OI, current
individualized to the patient and the family clinical practice is to continue treatment once
because there is currently a lack of evidence as started through puberty because of reported
to which practice is best. resumption of fractures after treatment cessation
(Ward et al. 2007).
There is no clear evidence about optimal
Bisphosphonates duration of bisphosphonate treatment in children
with CP. The long-term use of bisphosphonates
These medications act by blocking the osteoclas- throughout childhood, as seen with children
tic activity of bone and have been used to treat with OI, is not the current practice for children
osteoporosis in both adults and children. In with CP. Drug holidays are recommended
in adults receiving bisphosphonate; however, the “pamidronate lines” (zones of dense bone seen
growing bone is different. In children with CP in those treated with intravenous pamidronate)
who received a 1-year treatment regimen of (Fig. 4). This suggested that these areas might be
pamidronate, BMD decreased after treatment more susceptible to fracture because of the “stress
was stopped, but the fracture rate remained riser” created by the newly treated bone next to the
lower than before treatment 2 years after treat- less dense bone that was laid down after treatment
ment stopped (Bachrach et al. 2006). It is ended (Harcke et al. 2012). Our group’s practice is
common practice to treat children with CP with to now decrease the first three doses by half and to
bisphosphonate for 1–3 years and then stop the taper the last three courses gradually, so that the
therapy. In the small percentage who sustain quality of the pamidronate-treated bone might not
another fracture after the drug is discontinued, differ as abruptly from its neighboring bone. Pre-
treatment can be resumed for another period of liminary results show that this may be effective in
time to stop fractures (Bachrach et al. 2010). deceasing the fracture rate after treatment has
A dental exam should occur prior to initiation ended, though further study is required.
of bisphosphonate treatment, and any dental work Other bisphosphonates besides pamidronate
that is needed (especially teeth extraction or root are used in children. Both alendronate and
canal treatment) should be completed before zoledronate offer different conveniences and
bisphosphonates are started. While much of the risks than pamidronate. Alendronate is administered
published data on pamidronate in pediatrics is in orally once a week and is most commonly used in
children with OI, there are publications specifi- adults. A well-known side effect of alendronate is
cally addressing its use in children with CP. The gastrointestinal upset and worsening of reflux.
only randomized, placebo-controlled, double- Because many children with CP experience gastro-
blind study of pamidronate in children with CP esophageal reflux, alendronate may not be tolerated
involved six matched pairs of children with CP or the best choice for those with significant gastro-
who were treated with pamidronate for 1 year intestinal issues. Zoledronate is given intravenously
(3 doses every 3 months for a total of 15 doses) once every 6 months, which is more convenient for
(Henderson et al. 2002c). Bone mineral density families than the more frequent 3-day, every
dramatically increased in the children who 3–4 month administration of pamidronate.
received pamidronate, with the greatest increase Zoledronate is a newer drug than pamidronate
in BMD seen in region 1 of the distal femur. and is increasingly used with children, but
Z-score improvement was also greatest in region there are fewer reports on tolerability, safety, and
1 of the femur, increasing from an average of efficacy (Simms et al. 2011). In studies comparing
4.0 0.6 to 1.8 1.0. A follow-up study the effects of pamidronate versus zoledronate in
of these patients (Bachrach et al. 2006) showed children with OI, effects on BMD and fracture
that many of the gains in BMD were not rate appeared to be similar (DiMeglio and Pea-
sustained, and the Z-scores returned to pre- cock 2006; Saraff et al. 2018). In a retrospective
treatment values within 2–3 years after treatment chart review of 81 patients who received
ended. However, fractures were not experienced zoledronate for a variety of conditions, including
during this time period. A later study (Bachrach osteoporosis and OI, the most common side
et al. 2010) looked at 25 children with CP effects were hypophosphatemia in 25%, acute
(GMFCS 4–5) treated with a similar regimen of phase reactions in 19%, and hypocalcemia in
15 doses of 1 mg/kg over an average of 16% of infusions. Though these reactions were
13.6 months. This group had a high fracture rate described as mild, two episodes of symptomatic
(average of 30% per year) prior to treatment that hypocalcemia resulted in the need for intravenous
fell significantly following the initiation of calcium (George et al. 2015). Most pediatric prac-
pamidronate. The fracture rate, including those titioners start zoledronate at ½ dose for the first
that occurred during treatment, fell to an average administration due to concerns about side effects
of 13% per year. It was noted that these post- of hypocalcemia and hypophosphatemia. While
treatment fractures often occurred at the border of there is less information on the efficacy and safety
of zoledronate (or alendronate) specifically in weight bearing, nutritional compromise, and med-
children with CP, it is likely to be similar to that ication use that can negatively affect bone density.
seen in children with OI. Identification of risk factors for low BMD and
anticipatory actions to improve bone health
can mitigate low BMD and current and future
Other risk for fracture. Assessment of BMD can be
challenging in children with CP, but techniques
There are other medications used for osteoporosis assessing BMD by DXA are available, most com-
in adults that have seen minimal to no use in monly at centers familiar with pediatric bone
children because of concern about development assessment. Current treatments for low BMD
of tumors. There is a statistically significant include maximizing nutrition, weight bearing,
increase in the risk of the development of cancer and bisphosphonates.
in calcitonin-treated adult patients (compared A summary of current evidence about
with bisphosphonates) (Hsiao and Hsu 2017), osteoporosis in children with CP can be found at
and therefore it has not been used in children. https://www.aacpdm.org/publications/care-pathw
Similarly, both PTH analogue teriparatide and ays/osteoporosis.
recombinant human PTH (rhPTH) have a black
box warning from the FDA regarding osteosar-
coma, which developed in 45% of the rats that Case Studies
were treated at the highest doses. Post-marketing
surveillance has found only a few cases of osteo- The following case studies are actual patient expe-
sarcoma in treated adults (Subbiah et al. 2010), riences; each case study is presented to highlight
and there are case reports of its safe use in children different aspects of the management and treatment
with hypoparathyroidism (Fox and Gilbert 2016; of bone problems in children with CP.
Saraff et al. 2017), but it is not being used for Case 1 Summary: This case presents a clear
disuse osteoporosis given the safety concerns. diagnosis of osteoporosis, and a clear indica-
Denosumab is a monoclonal antibody with tion for treatment, which was uncomplicated
affinity for RANK-L. RANK-L activates osteo- and successful.
clast precursors and subsequent osteolysis.
Denosumab binds to RANK-L and prevents oste- Case #1: Case 1 is a 12-year-old boy with spastic
oclast formation, leading to decreased bone quadriplegic CP, GMFCS V. He has been
resorption and increased bone mass in osteoporo- followed since 2 years of age by an orthopedist
sis. Denosumab has been tested in children with and his primary care physician. He eats a regular
OI, and preliminary results show improved BMD diet by mouth, including three servings of dairy
with no severe side effects (Hoyer-Kuhn et al. (milk, cheese, yogurt) daily, and stands three to
2016). It may eventually become an alternative four times a week in a stander at school. His only
to bisphosphonates in children. Atypical femur medication is valproic acid. He has a history of
fractures and osteonecrosis of the jaw have been four non-traumatic fractures over the previous
reported in adults receiving denosumab. 4 years, all involving his lower extremities.
Work-up 2 years ago showed normal serum
calcium, phosphorus, and vitamin D levels,
Summary/Wrap Up with a mildly elevated alkaline phosphatase of
380 (normal: 146–333). Bone mineral density of
Children with CP are at increased risk for the lumbar spine (LS) showed a Z-score of 3.6,
compromised bone health. Those children who as measured by DXA. Whole-body scan could
are more medically involved have even greater not be obtained because of excessive movement.
risk for low BMD and fracture because of limited Lateral distal femur DXA results were as follows:
R1 Z-score = 3.2, R2 Z-score = 4.2, and R3 results showed Z-scores of 2.0 at the LS and
Z-score = 3.8 for the right distal femur –2.2, –2.1, and –2.9 at regions 1, 2, and 3, respec-
R1 Z-score = 3.3, R2 Z-score = 4.0, and R3 tively, of the left distal femur. Three years after
Z-score = 3.7 for the left distal femur. treatment ended, his LS bone density results were
just above baseline, average left distal femur results
Now, at age 12 years, he has undergone a right for R1 were back to baseline, and results for
hip osteotomy for a hip subluxation and has been regions 2 and 3 were slightly better than baseline.
non-weight bearing for 6–8 weeks. After At 5 and 8 years from treatment discontinuation,
returning to school, the school’s physical therapist bone density results were only slightly better than
was instructed to begin gentle range of motion baseline, but he had no further fractures. A 1-year
(ROM) exercises. On the first day of physical course of pamidronate resulted in no additional
therapy, Case 1 began to cry during gentle ROM fractures in the 10 years following treatment.
exercises. He was immediately referred to his
orthopedic surgeon, who obtained a radiograph Case 2 Summary: This case represents a
that showed a small chip fracture of the right distal common occurrence, whereby a patient sus-
femur. He was placed in a soft bulky cast, and all tains a non-traumatic fracture and the decision
weight bearing was stopped. Over the next is made to first try non-pharmacologic treat-
6 months, he suffered two more right distal ment for bone disease rather than
femur fractures and a left proximal tibia fracture, bisphosphonate. This case illustrates the nutri-
each time while being transferred. After the last of tional measures that were instituted. When the
these fractures, he was referred to the Bone Health patient sustained a fracture a second time
Clinic for evaluation. 2 years later, bisphosphonate treatment was
Fanconi’s syndrome (which can be caused by then initiated. This case also shows common
valproic acid use) was ruled out with normal uri- side effects of bisphosphonates and how treat-
nary phosphorus. Serum calcium, phosphorus, ment might differ for a young adult.
magnesium, BUN, creatinine, and electrolyte
levels were normal, as were PTH and vitamin D Case #2: NF is a 10 year old-old girl, Tanner
levels. Alkaline phosphatase was mildly elevated 1, who has spastic quadriplegia and is GMFCS
at 492. Urinary N-teleopeptide, a marker of bone level 4. She uses a gait trainer in school for 30 min
resorption, was markedly elevated. Bone densi- at a time, twice a week. She is fed via gastrostomy
tometry was performed. The DXA results showed tube and eats small amounts of food by mouth.
Z-scores of 4.8 at the LS and –5.0, 4.8, She was referred to her orthopedist because she
and 4.3 at regions 1, 2, and 3, respectively, of began to cry while being transferred from her
the left distal femur. Bone mineral density mea- wheelchair, and she seemed to have pain when
surement of the right distal femur was her right leg was touched or moved. On plain
contraindicated because of the healing fractures. radiographs, she had a displaced fracture of the
This young man meets the current definition of RDF (Fig. 3), and her leg was placed in a soft cast
osteoporosis (see definition above). Treatment for 6 weeks. Follow-up radiographs at 6 weeks
with intravenous pamidronate was initiated at showed good bone healing and some callus for-
1 mg/kg/day for 3 consecutive days every mation at the site of fracture. The cast was
3 months, for 1 year (total of five courses). removed, and she was referred to the Bone Health
After treatment was discontinued, DXA results Clinic for evaluation. A bone density exam was
showed Z-scores of 2.0 at the LS and 1.9, performed. Results showed Z-scores of 2.5 for
2.3, and 2.5 at regions 1, 2, and 3, respectively, her LS; 2.7 for the whole body less head
of the left distal femur. Healing callus precluded (WBLH); 2.2, 2.6, and 2.2 for regions 1–3,
accurate interpretation of BMD for the right distal respectively, of the right distal femur; and 5.0,
femur. One year later, follow-up bone density 5.7, and 5.1 for regions 1–3, respectively, of
Fig. 3 Acute displaced

right distal femur fracture
in 10-year-old girl with
cerebral palsy. Note
osteopenia of proximal
tibia and both femora
the left distal femur. Her LDF results were deemed developing peers. The Z-scores of her right and
by the radiologist to be more accurate on the left left distal femur were now similar to each other
than on the right because of the healing callus (the callus had remodeled), and were now similar
present in the right femur DXA. to the results in the left distal femur from the
Her diet was evaluated, and her parents previous year (right distal femur Z-scores were
reported that her oral intake was negligible. Her R1 = 5.5, R2 = 5.0, and R3 = 5.5; left distal
primary source of nutrition came from her femur Z-scores were R1 = 5.0, R2 = 5.0, and
gastrostomy tube feeds of three cans (750 mL) R3 = 5.3).
per day of a pediatric tube feeding formula. This Her serum vitamin D level was 35 ng/mL, and
gave her 900 mg of calcium and 630 mg of phos- she had been taking daily calcium, phosphorus,
phorus daily, which meant she was not meeting and vitamin D supplements as prescribed. She had
the dietary reference intake (DRI) for her age for been walking in her gait trainer for an hour daily
calcium (1300 mg) and phosphorus (1250 mg). when in school but not on weekends or vacations
Nutrient supplements were started: 400 mg of when she was home.
calcium and 600 mg of phosphorus to meet (but At age 12 years (2 years after her first fracture),
not exceed) the DRI for these two minerals. Her NF came home from school and seemed fussy,
serum 25-OH-vitamin D level was 20 ng/ml, and, over the next 24–48 h, her apparent discom-
so she was also started on vitamin D, 2,000 IU fort increased. School personnel knew of no his-
daily, plus a multivitamin. A prescription was tory of trauma. NF is nonverbal and does not
written for her time in the gait trainer to be communicate with a device. Her parents felt that
increased from twice a week to daily, as tolerated. her left leg was hurting her. A radiograph showed
Bisphosphonate treatment was not initiated at this a fragility fracture of the left distal femur, and a
time to see if the other treatment measures would soft bulky cast was again applied.
be sufficient to stabilize her bone density and Another DXA scan was done, which did not
perhaps avoid further fractures. A repeat level of include the left femur because her bulky cast was
serum vitamin D was 34 ng/mL after 8 weeks, and still present. The WBLH and LS DXA Z-scores
her dose was maintained at 2,000 IU daily. were 3.0, unchanged from those of the previous
One year later, she had no other fractures, and a year. The right distal femur Z-scores were slightly
repeat DXA showed worsening Z-scores of the LS lower than those of the previous year, with
and WBLH (both were 3.0), indicating that the Z-scores of 5.6, 5.2, and 5.6. However,
rate of her BMD accrual was less than that of her with this second episode of a fragility fracture,
age- and sex-matched healthy normally despite the nutritional measures and increased
standing, it was decided that she begin left distal femur: 1.8, 4.2, 4.7 (pretreatment
bisphosphonate therapy, despite the fact that she was 5.0, 5.0, 5.3)
does not meet the technical definition of osteopo-
rosis, as defined by the International Society for The dramatic improvement typically seen in
Clinical Densitometry. Before starting this treat- the R1 region of the LDF after treatment starts
ment, her parents were asked to take her to her occurs only in the growing bone and is described
dentist to screen for any dental pathology, espe- as “pamidronate or zebra lines.” These dense
cially the need for tooth extractions, because of metaphyseal bands form at the growth centers,
potential concerns of ONJ with bisphosphonate which are primarily trabecular bone, because of
use. osteoclast inhibition from the drug. Over time
Following dental clearance, she began treatment with continued growth, these lines migrate up
with three consecutive days of 1 mg/kg/dose of the femoral shaft, and, as bone remodeling occurs,
pamidronate. She received treatments in the outpa- they become less apparent and may eventually
tient infusion unit. Her parents were counseled disappear. As the bands migrate, commensurate
regarding potential side effects that commonly increases in BMD can be expected in regions
occur with the first course of bisphosphonate ther- 2 and 3 of the LDF. Bisphosphonate also improves
apy, such as fever, muscle aches, and vomiting. To cortical bone, and a less dramatic increase in
monitor for a drop in serum calcium or phosphorus BMD can be expected throughout all regions of
or both, her levels on day 1 and day 3 were the LDF as a result of treatment.
checked. Day 1 values were calcium = 9.0 mg/dl We followed NF for 7 years, repeating her bone
and phosphorus = 4.6 mg/dl. On day 3, calcium density test 2 and 5 years after treatment ended.
was 8.0 mg/dl and phosphorus was 3.2 mg/dl, She had a posterior spinal fusion done at age
neither enough of a drop to warrant any interven- 16 years, so the DXA could now only be done
tion (she continued on her usual supplements). for the distal femurs, as the metal rods in her spine
Sometimes prophylactic treatment of acetamino- will interfere with readings of both the LS and the
phen for fever or ondansetron for nausea is offered WBLH. Her LDF Z-scores are now close to her
to patients starting bisphosphonate therapy. She did pretreatment baseline. Annual 25-OH-vitamin D
not receive either. levels remained in the 35–40 ng/mL range, and
She had no side effects the first night, but, on she remained on 2,000 IU daily of vitamin D, as
the second night, she seemed uncomfortable at well as her calcium and phosphorus supplements.
home, and her mother gave her ibuprofen. This Seven years after treatment ended, at age 19 years
calmed her down and she went to sleep. On the (and now Tanner 5), she again fractured her left
3rd day, she had fever to 38.5 C during her femur while being lifted from her wheelchair into
infusion, and, before she went home, she was bed. At this age, the DRIs for calcium and phos-
treated with ibuprofen. Her fever lasted 24 h phorus decrease to 1000 mg of calcium and
then resolved. She had no vomiting. 700 mg of phosphorus. She was now on an adult
Three months later, NF returned for cycle tube feeding that had nutrient levels more appro-
#2. The same dose of 1 mg/kg/dose was given priate for her age. Adjustments were made to her
for 3 consecutive days. This time she had calcium and phosphorus supplements based on
no fevers or discomfort. She received three the new tube feeding and DRIs.
consecutive doses of 1 mg/kg/day every The options for treatment are now a bit
3–4 months for a total of five cycles. At the different:
end of this 14-month treatment with pamidronate,
her DXA Z-scores were as follows: 1. Continue to follow with yearly vitamin D
levels and DXA every 2–3 years.
WBLH: 2.0 (pretreatment was 3.0) 2. Treat again with intravenous bisphosphonate
LS: -2.2 (pretreatment was 3.0) (pamidronate or zoledronate) for 1–2 years.
right distal femur: 2.0, 4.5, 4.8 (pretreatment 3. Begin weekly alendronate at adult dose of
was 5.5, 5.0, 5.5) 70 mg once weekly for a maximum of 5 years.
Any of these options are reasonable. After Left distal femur Z-scores: R1 = 2.9, R2 = 4.6,
discussion with the family, NF was treated with and R3 = 3.9.
alendronate. To minimize the potential for esoph-
agitis, the main side effect of alendronate, it needs Two months later, he awoke one morning and
to be taken on an empty stomach, with 6–8 oz of indicated that his leg hurt. His right leg was swol-
water, and the patient must remain sitting upright len although there was no history of any trauma in
for at least 30 min after taking it. For NF, this was the preceding days. When these complaints
addressed by giving her the medication via her persisted over the next 24 h, his mother brought
gastrostomy tube first thing in the morning once a him to the emergency department, and a radio-
week, after she was sitting up in her wheelchair. graph was done that showed a buckle fracture of
Despite these measures, she showed significant the right proximal tibia. He was placed in a large
discomfort after each treatment with alendronate, soft bulky dressing and did not go to school
which was assumed to be due to esophagitis. For because of the concern that he had a long bus
this reason, her medication was switched to ride and might be jostled during the trip to and
zoledronate, to be given every 6 months. She from school. After 4 weeks, the radiographs
will continue to be monitored by her internist showed callus formation, and he was now free of
with a DXA scan every 2–3 years and a yearly pain. The bulky dressing was removed, and he
vitamin D level. was able to resume attending school and standing
in his gait trainer. A repeat vitamin D level was
Case 3 Summary: This case illustrates the again in the sufficient range, at 35 ng/mL.
bone disease that can occur in children with His mother questioned what could be done to
milder forms of CP and who walk to some prevent another fracture, given the significant pain
extent. It also illustrates an alternative sched- it caused him, as well as the disruption to his
ule for treating with pamidronate, using a school and her work attendance. While he did
tapering schedule, rather than abruptly stop- not fit the official diagnosis of osteoporosis, it
ping as was done in the first two cases. was felt that because of his worsening BMD and
fracture history, treatment with bisphosphonates
Case #3: Case 3 is a 9-year-old boy with spastic was justified. He was seen by his dentist, and no
quadriplegic CP, GMFCS level 4, and Tanner I. dental pathology was found. He was then started
He walks in a gait trainer at school, and his mother on intravenous pamidronate using a tapered dos-
has him stand for a half hour each day on the ing schedule. The treatment regimen involved
weekend. He consumes most of his nutrition by starting with 3 days of drug at 0.5 mg/kg/day,
mouth and gets supplemental gastrostomy tube followed every 3–4 months by 3-day courses of
feedings when he does not meet his caloric 1 mg/kg/day. After five courses, his dose was
needs orally. He was seen by the dietitian on the then tapered as follows: two 2-day courses of
bone health team, who assessed his nutritional 1 mg/kg/day, followed by a 1-day course of
intake. He is meeting the DRI for calcium 1 mg/kg/day (each separated by 3–4 months).
(1300 mg), phosphorus (1250 mg), and vitamin In total, he received 20 doses over 8 treatment
D (600 IU). His serum vitamin D level was 33 ng/ courses. He had DXA studies done 12 months
mL, and no further supplementation was needed. after starting treatment and at the end of treat-
He had a DXA done to have a baseline for future ment (Fig. 4). He has remained free of fractures
comparison and to assess what his BMD values in the 5 years since treatment ended.
were compared with those of his healthy, normally
developing peers. The DXA technicians were
unable to acquire a WB or LS scan because of Case 4 Summary: This case illustrates the
excessive movement, and right distal femur, due use of zoledronate for a patient with CP who
to presence of rod. Left distal femur was acquired, was not a good candidate for pamidronate
and his results were as follows: because of his co-diagnosis of autism.
Fig. 4 Serial change in lateral distal femur, dual-energy bands that formed from osteoclast inhibition with
absorptiometry scan of a 9-year-old boy treated with a bisphosphonate and migrated over time with bone growth
2-year course of pamidronate. Note dense metaphyseal
Case #4: Case 4 is an 11-year-old boy with spas- showed a non-displaced transverse fracture of the
tic CP, GMFCS level 3, and autistic spectrum dis- right distal tibia. He was placed in a hard cast with a
order (ASD) with no language skills, either verbal walking boot, but he refused to bear any weight and
or signing. He had been followed by the bone continued to show pain and discomfort for almost a
health clinic for a number of years, and his oral month after the fracture occurred. Bone densitom-
diet did not fully meet the DRI for minerals and etry was ordered, and his results were as follows:
vitamins; he received supplementation with cal-
cium 500 mg and phosphorus 500 mg daily. His WB Z-score = 5.0
serum 25-OH-vitamin D level was deficient at LS Z-score = 2.2
18 ng/mL, and he received supplementation with Right distal femur Z-scores: R1 = 4.0,
vitamin D, 2,000 IU daily. Repeat 25-OH-vitamin R2 = 5.1, R3 = 3.8
D level after 3 months showed his level in the Left distal femur Z-scores: R1 = 5.0,
insufficient range, at 25 ng/mL. His supplement R2 = 6.0, R3 = 4.2
was increased to 4,000 IU daily, and, thereafter,
his levels remained in the sufficient range, with The option of beginning bisphosphonate ther-
levels between 33 and 37 ng/mL, and the supple- apy was discussed with his family; they felt he
ment was continued at 4,000 IU daily. His ambu- could not possibly tolerate 3 days of infusions,
lation was limited, but he did walk at home while each lasting 4–5 h, which is typical for
his hand was being held, and he did some super- pamidronate. The alternatives were reviewed,
vised walking while in physical therapy at school. and it was decided to treat him with zoledronate,
He had a minor fall at home one evening, and the which is given intravenously for 30 min, once
next morning when his mother woke him for every 6 months. Before starting zoledronate, he
school, he would not bear weight. She had to was seen by a dentist for the first time in 2–3 years
carry him to the car, and she drove him to the and found to have a dental abscess and a number
orthopedist, who suspected a fracture. Radiograph of teeth with caries. His dental repairs were
performed, while he was under sedation. A month ▶ Managing Irritability and Nonoperative Pain in
after the dental work was completed, he was the Noncommunicative Child with Cerebral
started on zoledronate, at a dose of 0.025 mg/kg Palsy
for the first dose. This was tolerated well, with ▶ Mobility Supports in Educational Curriculum
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Managing Irritability
and Nonoperative Pain 27
in the Noncommunicative Child
with Cerebral Palsy
Tracy Hills and Steven Bachrach
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 396
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 397
Assessment of Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 398
Treatment and Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 399
Gastrointestinal Etiologies of Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 399
Constipation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 399
Gastroesophageal Reflux . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 400
Feeding Intolerance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 400
Visceral Hyperalgesia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 400
Musculoskeletal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 401
Spasticity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 401
Dystonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 404
CNS Shunt Malfunction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 405
Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 405
Surgical Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 405
Muscle Overuse Injuries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 408
Occult Fractures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 408
Treatment and Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 408
T. Hills (*)
Department of Pediatrics, Monroe Carell Junior Children’s
Hospital, Vanderbilt University, Nashville, TN, USA
e-mail: tracy.hills@vumc.org; Tracy.Hills@vanderbilt.edu
S. Bachrach
Department of pediatrics, Nemours/Alfred I. duPont
Hospital for Children, Wilmington, USA
e-mail: Steven.Bachrach@nemours.org

https://doi.org/10.1007/978-3-319-74558-9_27
396 T. Hills and S. Bachrach
Kidney Stones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 408

Paroxysmal Sympathetic Hyperactivity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 409
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 410
Cases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 410
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 410
Abstract received analgesia during their hospital stay.

Pain is defined as an unpleasant sensory and A comparable group of adults received multiple
emotional experience associated with actual or doses of pain medication. There was a belief that
potential tissue damage. Children with cerebral children did not experience pain, especially pre-
palsy (CP) have many reasons to experience mature infants, in whom PDA ligations were rou-
pain, including those that are common to all tinely done without analgesia until the classic
children (such as trauma, ear infection) and study by Anand and Hickey (1987) showed severe
many that are associated with their disability stress responses in these infants and a higher com-
(such as spasticity, hip dislocation, or fragility plication and mortality rate than in those who did
fractures). For children with CP who cannot receive analgesia. This lack of recognition may
communicate their experience of pain, the have been in large part because these young
challenge is great for those who care for them patients could not express their experience of
to recognize they are experiencing something pain to their physicians and nurses.
unpleasant and unusual and to evaluate what Though we have made progress in recognizing
the cause may be. In this chapter, we review and treating pain in our younger patients, children
many of the potential causes of pain and with CP present a special challenge, and many
discomfort in this population, the various of them continue to experience pain that is
ways to evaluate the severity of pain in a non- unrecognized and thus untreated. In addition to
communicative child, and various treatment all the reasons any child can experience pain,
measures. We also provide illustrative case such as an acute infection or traumatic injury,
histories to highlight the challenges these children with CP, especially those with complex
patients can present. disabilities, have many additional reasons to
experience discomfort and pain. Identifying pain
Keywords in nonverbal children with CP is difficult because
Cerebral palsy · Pain · Noncommunicative · of the communication challenges, as well as the
Discomfort potential for multiple pain etiologies. Children
with more severe cognitive impairments have a
higher risk of experiencing pain, because as com-
Introduction munication difficulties increase, the likelihood
their pain will go unrecognized or remain
Pain in children was not given much attention untreated also increases (Stallard et al. 2001).
until the last part of the twentieth century. In a Similarly, children with more severe levels of
study by Eland and Anderson (1977), it was noted physical disability with higher GMFCS (Gross
that only 12 of 25 children, aged 4–8 years, hav- Motor Function Classification System) levels
ing major surgical procedures (such as amputa- have more potential pain sources throughout
tion, nephrectomy, and heart surgery) had their bodies.
27 Managing Irritability and Nonoperative Pain in the Noncommunicative Child with Cerebral Palsy 397
Natural History pain, whereas 79% of nonambulatory children

with CP experienced pain (Svedberg et al. 2008).
Pain is described as “an unpleasant sensory and In children with a GMFCS level of 4 or 5, physi-
emotional experience associated with actual or cians identified the top causes of pain as hip dis-
potential tissue damage, or described in terms of location/subluxation (27%), dystonia (17%), and
such damage” (IASP 2018). Children with CP are constipation (15%) (Penner et al. 2013).
known to experience various types of pain, sec- Children with CP are at risk for both acute and
ondary to the physiological aspects associated chronic pain from a variety of sources. Acute pain
with CP, such as spasticity, gastrointestinal reflux is secondary to tissue damage or irritation, or both,
disease (GERD), rehabilitation therapies, and related to an injury, insult, surgery, or disease
the invasive medical and surgical procedures chil- expected to last a short duration of time. The
dren with CP undergo (McKearnan et al. 2004). symptoms of acute pain are expected to resolve
However, pain is frequently under recognized in once the etiology of pain is identified and treated.
children with disabilities, especially in those who Acute pain for children with CP can include mus-
cannot communicate, thus resulting in under treat- cle spasms/positional etiologies of pain, fractures,
ment, which can negatively influence quality of and common childhood diseases, such as otitis
life (Hauer et al. 2017; Penner et al. 2013; Stallard media and urinary tract infections (UTIs). Chronic
et al. 2001; Svedberg et al. 2008). A number of pain is pain that exists beyond the typical course
studies have examined pain in both verbal and of a disease or normal healing time for an injury.
nonverbal children with CP. One study of verbal Chronic pain can comprise of continuous pain as
children with CP found 70% experienced recur- well as recurrent/episodic pain, which may persist
rent chronic pain of moderate intensity on a daily in the absence of an identifiable etiology (Hauer
or weekly basis (Engel et al. 2005). In a study of et al. 2017). Chronic pain can be caused by etiol-
20 nonverbal children with CP, 67% of their par- ogies such as autonomic dysfunction or central
ents reported moderate to severe pain, but none of neuropathic pain, for which there are no tests
the children received pain treatment (Stallard et al. (Hauer 2018). Chronic pain is common in
2001). Similarly, in a study of 43 nonverbal chil- children with CP and can cause sleep distur-
dren with CP, 67% of parents reported observing bances, irritability, depression, fatigue, and anxi-
pain behaviors in their children over the last ety (Hauer et al. 2017; McKearnan et al. 2004).
month, with assisted stretching (93%), needle In one study, 90% of children had ongoing recur-
injection (40%), and range of motion manipula- rent pain for more than 1 year, but only half of
tion (58%) being the most frequently cited sources the children received treatment directed at pain
of pain (Hadden and von Baeyer 2002). (Svedberg et al. 2008).
Pain is a subjective experience with both bio- Nociceptive pain is pain associated with tissue
logical and psychosocial factors contributing injury or inflammation, such as fractures, GERD,
(McKearnan et al. 2004). Identifying pain in non- and spasticity (Hauer et al. 2017). Neuropathic
verbal children with CP is difficult secondary to pain is pain associated with injury or dysfunction
communication challenges, as well as the poten- of the central, peripheral, or autonomic nervous
tial for multiple pain etiologies. Children system. Features of neuropathic pain include
with more severe cognitive impairments and descriptions such as burning, tingling, electrical
communication difficulties have a higher risk of sensations, and shooting pains. When associated
experiencing pain that will go unrecognized or with the autonomic nervous system, features may
remain untreated (Stallard et al. 2001). Similarly, include mottling, increased sweating, and ery-
children with more severe levels of physical dis- thema (Hauer and O’Brien 2011). Visceral hyper-
ability with higher GMFCS levels have more algesia is an altered threshold to pain generation
potential pain sources. One study found that secondary to a stimulus in the gastrointestinal
48% of ambulatory children with CP experienced (GI) tract, where a normal stimulus, such as
gastric distension, can result in significant scales exist specifically for nonverbal children,
pain (Delgado-Aros and Camilleri 2005). Chil- including children with CP. These pain assess-
dren may have pain secondary to more than one ment tools include the Individualized Numeric
etiology, which makes treating the pain more Rating Scale (INRS), the Non-communicating
complex. Many of the etiologies of pain in chil- Children’s Pain Checklist – Postoperative Version
dren with CP, such as musculoskeletal sources, (NCCPC-PV), the Non-Communicating Chil-
have a natural progressive history, so as children dren’s Pain Checklist – Revised (NCCPC-R),
get older they may have an increased frequency or Pediatric Pain Profile (PPC), and revised Face,
severity of pain or both. Legs, Activity, Cry, and Consolability scale
(R-FLACC) (Breau et al. 2002a, b; Hunt et al.
2004; Malviya et al. 2006; Solodiuk et al. 2010).
Assessment of Pain The R-FLAAC and INRS allow families to indi-
cate specific pain behaviors for their child, thus
The inability to communicate verbally does not individualizing the pain scale to the child.
negate the possibility that an individual is
Common etiologies being common, acute pain
experiencing pain and is in need of appropriate
pain-relieving treatment. (IASP 2018) or discomfort can be a sign of common childhood
illnesses, such as otitis media, pharyngitis, sinus-
Identifying pain in normally developing children itis, and UTIs. However, in the nonverbal child,
can be challenging, but in nonverbal children with identifying the source of pain can be difficult,
limited or no ability to communicate, it can be particularly if the child does not exhibit any local-
especially challenging. Parents and caregivers izing physical symptoms. Children with CP are at
often know what behaviors are typical of their increased risk for gastroesophageal reflux, frac-
child at baseline and what behaviors indicate tures, and hip subluxation, all of which can cause
their child may be in pain. Such behaviors acute pain. Acute pancreatitis has been associated
can include crying, decreased activity, moaning, with children taking valproic acid and following a
decrease in sleep, irritability, discomfort with posterior spinal fusion (PSF) for scoliosis, while
feeds, inconsolability, facial grimacing, increased nephrolithiasis has been associated with immobil-
tone, and crying with movement (Hadden and von ity, taking topiramate, and a ketogenic diet (Hauer
Baeyer 2002; Penner et al. 2013). Some children et al. 2017). Choledocholithiasis is rare in infants
have less typical pain behaviors including and children but can sometimes occur in associa-
laughing, self-injurious behavior, drooling, red tion with hemolysis, chronic liver disease, and
cheeks, grunting, sticking out their tongue, and biliary tract malformations. In a review of
blunted facial expressions (Hadden and von 382 infants and children with gallstones, approx-
Baeyer 2002; Penner et al. 2013). When assessing imately half had recognized risk factors (Bogue
pain, it is helpful to keep track of the frequency et al. 2010). The most common risk factors iden-
and duration of pain episodes, as well as to track tified were sickle cell disease, parenteral nutrition,
responses to interventions. Sources of pain com- and cardiac surgery. The incidence of gallstones
mon in typically developing children can also be rises sharply in girls during puberty.
seen in children with CP, but during physical If the child is experiencing acute pain/discom-
assessment, it is helpful to pay special attention fort of an unclear etiology, prompt evaluation by a
to common sources of pain for children with CP pediatrician should occur to help determine if
such as hip subluxation/dislocation and dystonia. there is a treatable cause, such as an acute infec-
Numerous pain assessment scales exist, but the tion. A systematic history and physical exam may
majority of them are for children who are able to yield answers. The history for an adolescent
communicate. Pain assessment scales such as the female should include the timing of menstrual
Wong-Baker Faces Pain Scale are appropriate for periods and the relationship between pain epi-
children with a developmental age of 3 years or sodes and menstrual cycles. During the physical
greater (Tomlinson et al. 2010). Pain assessment exam, one needs to see if pain behaviors are
reproducible with palpation of different areas being considered for pain control, as many parents
(e.g., abdomen/hips) or with positioning/palpa- are concerned opioids will cause their child to
tion of extremities. If no clear source of pain is become addicted, may mask new pain, or may
identifiable on physical exam, diagnostic studies, cause other unwanted side effects such as consti-
such as blood work and urinalysis, to evaluate for pation or pruritus.
the etiology of pain may be beneficial. If there is
concern for a fracture, radiographic studies are
considered. Dental caries and abscesses can also Gastrointestinal Etiologies of Pain
be an occult source of pain. If there is any sugges-
tion of pain in the mouth, consider further evalu- Gastrointestinal (GI) etiologies such as constipa-
ation by a dentist. tion, GERD, vomiting, and feeding intolerance
are known etiologies of pain or discomfort, or
both, in children with CP (Del Giudice et al.
Treatment and Complications 1999; Erkin et al. 2010; Sullivan et al. 2000). In
one study of 58 children with CP, 92% had GI
A comprehensive evaluation is the initial step in symptoms including abdominal pain and GERD
the treatment of pain with an attempt to treat (Del Giudice et al. 1999). Children with CP who
identified etiologies of pain when possible. The have epilepsy, lack functional communication,
treatment of pain is individual to each child. The and lack functional hand use have a higher pre-
World Health Organization (WHO) developed disposition to GI symptoms than children with
a three-step ladder for pain control in 1986 higher levels of functioning (Erkin et al. 2010).
(WHO 2018). The three-step ladder was recently Various underlying issues, including delayed gas-
converted to a two-step ladder in children because tric emptying, immobilization, inadequate oral
the second step included codeine, a medication intake, and abnormal autonomic control of
no longer used in pediatrics secondary to gastrointestinal mobility (Krigger 2006), may
concerns about safety and efficacy related to cause constipation, GERD, and abdominal pain.
genetic variability with the metabolism of the Medications frequently used in the treatment of
drug (Ciskowski et al. 2009). The first step in the spasticity and seizures associated with CP have
ladder is for mild pain and consists of nonopioid side effects that can cause delayed gastrointestinal
analgesics such as acetaminophen and nonsteroi- motility. In addition, sudden cessation of medica-
dal anti-inflammatory drugs. The second step is tions used in children with CP, such as baclofen,
for moderate to severe pain and consists of opioid opioids, benzodiazepines, and tricyclic anti-
analgesics. Adjunct medications that can provide depressants (TCAs), can cause withdrawal symp-
relief of different types of pain, such as anticon- toms including gastrointestinal symptoms such as
vulsants and antidepressants for neuropathic pain, vomiting and diarrhea (Hauer et al. 2017).
can be used at either step. The other treatment
principles guided by WHO include “by the
clock,” “by the mouth,” and “by the child.” “By Constipation
the clock” indicates scheduled medications when
pain is frequent, with as needed doses of analge- Constipation is a common GI etiology of pain in
sics for breakthrough pain. “By the mouth” means children with CP, with different studies reporting
to administer medications by the least invasive 57–74% of children affected (Del Giudice et al.
route, including enteral, buccal, and transdermal 1999; Sullivan et al. 2000). The degree of
options. “By the child” refers to tailoring each constipation is frequently associated with the
pain plan to the child, as there is no standard severity of motor impairment. Lack of mobility,
approach to pain management in children with CP. uncoordinated muscle contractions, abnormal
It is also important to note potential barriers to autonomic control, inadequate fluid and fiber
the treatment of pain, especially when opioids are intake, and disordered rectal sphincter control
may all contribute to constipation (Erkin et al. However, a discussion of the benefits and burdens
2010). of each intervention with the family before pro-
Treatment of constipation frequently con- ceeding is recommended, as each intervention can
sists of both dietary changes and medications. affect quality of life. Children fed via their J tube
Some children may require more fluid intake require feeds over longer periods, and the J tube is
or fiber than other children. It is important to not replaceable at home. In some circumstances, a
work with a dietician to ensure the child is Nissen fundoplication significantly improves
receiving adequate fluid and caloric intake. GERD symptoms, but, in other circumstances, a
Medications for constipation include osmotic Nissen fundoplication can worsen other GI symp-
agents such as polyethylene glycol, lactulose, toms such as retching.
sorbitol, milk of magnesia, stool softeners
such as docusate, stimulants such as senokot,
promotility agents such as erythromycin or Feeding Intolerance
metoclopramide, as well as suppositories and
enemas. Children with CP frequently have feeding intoler-
ance secondary to delayed gastrointestinal motil-
ity. Symptoms of feeding intolerance include
Gastroesophageal Reflux abdominal pain, vomiting, and retching. Treat-
ment of feeding intolerance includes changing
Gastroesophageal reflux disease is very common formulas and limiting fluid intake. Medications
in children with CP and can be associated with a for feeding intolerance include promotility agents,
variety of etiologies. With delayed gastric empty- cyproheptadine, and gabapentinoids.
ing, the contents accumulate in the stomach,
which can increase the risk of reflux. Increased
intra-abdominal pressure secondary to spasticity Visceral Hyperalgesia
or constipation may overcome the barrier formed
by the lower esophageal sphincter and cause the The GI tract is a common source of recurrent pain
gastric contents to reflux into the esophagus for children with significant neurological impair-
(Erkin et al. 2010). Limited mobility, poor control ment, even after treatment of common etiologies
of orofacial musculature, scoliosis, seizures, and of pain such as GERD and constipation. This
impaired esophageal motility may also contribute recurrent pain is thought to be from visceral
to GERD (Del Giudice et al. 1999; Hall 2017). hyperalgesia, an altered threshold to pain gener-
Medications such as anticholinergics (commonly ated secondary to a stimulus in the GI tract
used for drooling) and sedatives can decrease the (Delgado-Aros and Camilleri 2005). A normal
lower esophageal sphincter tone, which in turns stimulus, such as distension or pressure in the GI
leads to an increased risk for reflux (Erkin et al. tract from constipation, can cause significant pain
2010). out of proportion to expectation. Symptoms sug-
If GERD is not appropriately treated, it could gestive of visceral hyperalgesia include pain asso-
result in recurrent pneumonia, recurrent esopha- ciated with gastrostomy or jejunostomy tube
gitis, cough, and wheeze. Treatment for GERD feedings, bowel gas, pain before a bowel move-
includes invasive and noninvasive interventions. ment, and pain relief after a bowel movement
Noninvasive interventions include medication (Hauer et al. 2017).
management, changes in formula, and changes In one study, visceral hyperalgesia was the
in positioning. Medications include H2 blockers source of GI symptoms in 12 out of 14 medically
and proton pump inhibitors, as well as promotility fragile children, the majority of whom had CP,
agents if delayed gastric emptying is a concern. were receiving treatment for GERD, and had a
Nonpharmacological interventions include con- Nissen fundoplication (Zangen et al. 2003). In
version to GJ tube and Nissen fundoplication. another study, 14 out of 22 children with severe
neurologic impairment and persistent pain had GI abnormality and another 5–10% with mixed CP,
symptoms despite receiving treatment for GERD with some amount of spasticity as secondary and
(Hauer and Solodiuk 2015). In both studies, athetosis, ataxia, or hypotonia as the primary
symptoms such as vomiting, retching, and feeding tone abnormality. Those patients with spasticity
intolerance improved after medications used to frequently experience chronic pain, and spastic-
treat visceral hyperalgesia and central neuropathic ity and pain can reinforce each other, causing an
pain, such as gabapentin, were initiated (Hauer escalating cycle of increased spasticity causing
and Solodiuk 2015; Zangen et al. 2003). pain causing more spasticity. This pain is most
Treatment of visceral hyperalgesia includes often reported to involve lower back and lower
pharmacologic and nonpharmacologic inter- extremities, including hips. For instance, in a
ventions. Medications include anticonvulsants survey of 83 adults with CP, at a mean age of
such as gabapentin and pregabalin (Hauer and 40.3 years, all of whom were able to communi-
Solodiuk 2015). Gabapentin is often the first med- cate (many via augmentative communication
ication used in the treatment of visceral hyper- devices), 63% reported experiencing chronic
algesia because of its low side effect profile. pain and rated their pain intensity over the past
Tricyclic antidepressants (TCAs), such as nortrip- week as 5.1 out of 10, on average. The most
tyline and amitriptyline, are second-line medica- common pain locations were the lower back,
tions for treatment of visceral hyperalgesia and hips, and legs. Physical interventions (e.g., phys-
require close monitoring because of the side effect ical therapy, strengthening) were the most com-
profile (Hauer et al. 2017). TCAs have anticholin- mon pain treatments reportedly used and were
ergic side effects, such as sedation, constipation, rated as moderately effective (Hirsh et al. 2011).
and urinary retention. TCAs can also cause pro- When dealing with children, the reports of pain
longed QT interval and cardiac dysrhythmia. often originate with their parents. For instance, in
Treatment of the underlying etiologies that a study by Penner et al. (2013), the primary
cause distension or irritation to the GI tract, such caregivers completed a questionnaire about the
as constipation, GERD, and GI dysmotility, is presence and characteristics of pain in their chil-
essential to help prevent pain secondary to dren aged 3–19 years. In addition, the treating
visceral hyperalgesia. Nonpharmacologic inter- physician was also asked to identify the presence
ventions including substituting feeds with of pain and provide a clinical diagnosis for the
electrolyte solutions or holding feeds, providing pain, if possible. Two hundred fifty-two children
intravenous hydration, venting the G-tube, having with a mean age of 9.5 years participated. Their
equipment to allow for venting during feeds, and motor abilities ranged across all five levels of the
decreasing the total volume of fluids by G-tube GMFCS. A total of 54.8% reported some pain,
can also help decrease discomfort (Hauer et al. and 24.4% reported pain significant enough to
2017). However, one must be cautious when affect their child’s activities. Of the 136 children
decreasing fluids, as many of these children do (54.0%) whose parents identified pain on the
not receive adequate fluids, contributing to con- pain location diagram, 82% of children had
stipation and chronic dehydration, which can lead pain in their lower extremities, 19% in their
to further discomfort. upper extremities, and 14% in their back.
Approximately half of the children were able to
report their own pain using the Wong-Baker
Musculoskeletal Faces Pain Scale. They were less physically
impaired, with GMFCS scores from 1 to 3, and
Spasticity 78% of them were ambulatory. Forty-seven per-
cent of them reported some pain, and the corre-
Spasticity is the most common tone abnormality lation between the children’s self-report and that
in children with CP, with 70–80% of patients of their parents was good. Physicians reported
with CP having spasticity as their primary tone pain in 38.7% of the participants, and the
correlation with parents was not as good, with Treatment and Complications
44 (17.4%) identified with pain by their caregiver Treatment is aimed at muscle relaxation and con-
but not by their physician. The most frequently sists of physical measures, such as massage,
identified cause of pain in those who were non- applying heat and stretching, and pharmacologic
ambulatory (GMFCS 4–5) was hip dislocation/ agents that can be taken orally, intramuscularly, or
subluxation (27%), followed by dystonia (17%). intrathecally. The physical measures for spasticity
Among those who were ambulatory (GMFCS are most helpful early in life before spasticity has
1–3), the most frequently identified causes were led to painful contractures. Massage, heat, range
focal muscle spasms (16%), muscle weakness/ of motion exercises, and stretching are all
overuse/fatigue (16%), and an abnormal gait pat- performed by physical therapists, with parents
tern (11%). Of the children, 66% were identified repeating these treatments at home after instruc-
as having one primary cause of pain, 26% had an tion. Bracing is also likely to be used to help
additional cause, and 8% had multiple sources of maintain range of motion. Progression of hip
pain. Frequency of pain also varied by GMFCS subluxation to dislocation is preventable by rou-
level, from 11.7% in GMFCS 1 to 38.6% in tine hip surveillance; hip radiographs every
GMFCS 5. Increasing age also correlated with a 6–12 months can detect subluxation, and mea-
higher frequency of pain experience, likely due sures can be taken to prevent full dislocation and
to the progression of musculoskeletal abnormal- the chronic pain associated with it. These mea-
ities, such as spasticity, leading to contractures, sures might include stretching, hip abduction
hip subluxation or hip dislocation with age. bracing, botulinum toxin, and orthopedic surgery
Other studies have reported similar findings, (Dobson et al. 2002).
though the percentages of those experiencing As children grow, their spasticity can become
pain varies, perhaps because of different meth- symptomatic, causing pain or interfering with
odologies for assessing pain. A cross-sectional daily function or both. This is when medications
study from Sweden looked at over 2700 children are usually added to the treatment regimen. Oral
with CP, aged 1 to 14 years, who were in a medications are used when a general antispasticity
national registry for CP. Of the children, 32.4% effect is the aim (Delgado et al. 2010). These may
reported pain, with significantly more girls than include benzodiazepines, though these are better
boys reporting pain and more children at used for acute management, such as for the spas-
GMFCS 3 and 5 than at GMFCS 1 reporting ticity and pain associated with acute injury or
pain. Pain frequency increased with age. Pain in surgery. Other commonly used oral agents include
the abdomen and hips was most frequent in those baclofen, tizanidine, clonidine, and dantrolene.
at GMFCS 5, knee pain in those at GMFCS Botulinum toxins A and B are neuromuscular
3, and foot pain in those at GMFCS 1 (Schmidt blocking agents, which are used to treat localized
and Hagglund 2016). In a study of parents’ per- spasticity, such as a specific limb or segment of
ception of their children’s pain related to health the body (Delgado et al. 2010). A study by Lundy
care procedures and daily living situations, et al. (2009) looked at the use of Botulinum toxin
43 parents completed a survey. Sixty-seven per- A in 26 children with spastic quadriplegic CP
cent of children were reported to have experi- (GMFCS class 5), ranging in age from 2 to
enced pain in the previous month. Assisted 19 years. Ten of the 26 had at least one hip
stretching was the activity of daily living most which was dislocated, and 3 had at least one hip
frequently identified as painful by parents (93% which was subluxed. They received Botox-A
of those reporting pain) and the one with the injections to the adductor, medial hamstrings,
highest pain intensity. Needle injection was the and iliopsoas muscle groups. Three months after
medical procedure most frequently identified as treatment, all showed significant decrease in their
painful (40%) and range of motion exercises the pain scores, and families reported an improve-
therapy most frequently associated with pain ment in quality of life, including improved sleep.
(58%) (Hadden and von Baeyer 2002). Another study looked at the effect of botulinum
toxin-A on 34 children (mean age 9 years) with symptoms are quite dramatic and call for atten-
CP, using a parent-proxy report of pain (Rivard tion. However, some patients have a slow leak that
et al. 2009). These were children whose parents may manifest much more subtly, such as with
had reported spasticity-related pain prior to enroll- headaches, a gradual increase in drowsiness, or a
ment. Parent ratings of their child’s pain were gradual increase in tone and increase in discom-
significantly reduced after injection with botuli- fort. Thus, any change in tone, behavior, or com-
num toxin A, with 62% of parents reporting the fort should trigger at least a question about the
absence of pain 1 month after injection, and 38% integrity of the pump.
reporting persistent pain. Medical cannabis has subjectively been
Common side effects of the oral medications reported to improve spasticity, dystonia, and
include drowsiness and sedation. In addition, pain in children with CP, but secondary to federal
dantrolene has GI side effects including vomiting regulations, few clinical trials exist to support the
and diarrhea. Intrathecal baclofen (ITB), also effects of medical cannabis on pain and symp-
known as the baclofen pump, and selective dorsal toms. In Israel, where research on medical canna-
rhizotomy (SDR) are aimed at generalized spas- bis is being conducted, a study without a control
ticity. In depth discussion of these two modalities group found medical cannabis improved spastic-
is beyond the scope of this chapter, as each has an ity and dystonia, sleep difficulties, and pain sever-
entire chapter in this book (see section “Cross- ity in children with complex motor disorders
References” below). Briefly, the baclofen pump (Libzon et al. 2018). In the USA, cannabis is
received FDA approval in 1996 for the treatment legal for medical purposes in about 50% of the
of spasticity of central nervous system etiology. states, but no cannabis products are approved
Since approval, it has been widely used, and ran- by the Food and Drug Administration (FDA)
domized placebo-controlled trials of its efficacy (Mead 2017).
have not been done. A recent study by Liew et al. The surgical procedure known as selective dor-
(2018) involved six pediatric ITB implant centers sal rhizotomy (SDR) is primarily used for children
across Australia. Twenty-five children who had with spastic diplegia where the spasticity is inter-
specified goals were included, of whom 19 had fering with gait. A review of published outcomes
CP, and 22 were at GMFCS 4 or 5. Strong evi- by Steinbok (2001) showed that SDR was shown
dence for an improvement in goal performance conclusively to decrease lower limb spasticity and
(2.33, 95% CI 1.70, 2.96, p <0.001) and perfor- increase lower limb range of motion. There is
mance satisfaction scores (3.08, 95% CI 2.28, strong, but not as conclusive, evidence that SDR
3.88, p <0.001) was demonstrated at 6 months, has a positive effect in the functional limitation
compared with baseline. The differences were dimension, with improvements in motor function,
clinically significant and were still present at and in particular the Gross Motor Function
12 months. The most commonly identified goals Assessment (GMFM). There was no comment
of parents of children treated with ITB therapy on pain in this study. In contrast, the study by
were improving ease of dressing, positioning, and Tedroff et al. (2015) looked at a cohort of
transfers. No assessment of pain was mentioned, 18 young adults who had SDR done 15–20 years
though if there is pain or discomfort with spastic- previously. They found that the best motor func-
ity, then the decrease in spasticity should result in tion (as measured by the GMFM) was 3 years
a decrease in pain. after the procedure, following which it gradually
Baclofen, when given orally or intrathecally, declined. SDR also did not prevent the develop-
must be tapered gradually before discontinuing, ment of contractures. Pain was present in 50% of
because an abrupt discontinuation (which can the individuals, and the pain in these individuals
happen with a malfunction of the pump or discon- was considered mild (as measured by median pain
nection of the tubing) can cause a sudden increase severity and interference). They concluded that
in spasticity, hallucinations, confusion, hyperther- the spasticity reducing effect of SDR can possibly
mia, and seizures (Verrotti et al. 2006). These reduce pain. However, a case control study by
Dauntner et al. (2017) which also looked at long- though clinically they all have been used
term follow-up of SDR (average 22 years after for treating the pain associated with dystonia.
surgery) found no decrease in pain or fatigue in Other medications, including levodopa, tri-
the SDR group, though they did have a lower hexyphenidyl, and botulinum toxin had some lim-
decline in gross motor function. Similarly, a ited data. For instance, there was one randomized
study by Munger et al. (2017) looked at 16–25- controlled trial of levodopa involving nine
year-old patients with CP who had undergone patients. They did not achieve improvement in
SDR as young children, and compared them to a upper extremity skills, and there was no assess-
matched cohort. There was no difference in the ment of pain. Two studies looked at the effect
pain scores of the two groups. of trihexyphenidyl on reduction of dystonia and
the conclusion was “probably ineffective,” but
there were inadequate data on pain to make any
Dystonia recommendation. A study of botulinum toxin
showed improved upper extremity function in an
Dyskinetic CP, which includes dystonia and arm-reaching task (Sanger et al. 2007) but, again,
athetosis, was described as the predominant type no evidence for reduction in pain.
of CP in 4.4% of children with CP in a large Two neurosurgical procedures have been used
registry from Australia. Another 9.1% had dyski- in recent years as a treatment for dystonia, intra-
nesia as the secondary motor type (with spasticity thecal baclofen (ITB), and deep brain stimulation
or ataxia as the primary type). These numbers (DBS). Intrathecal baclofen, discussed above as a
were similar to those of two large combined data treatment for spasticity, acts by binding GABA
sets that were used for comparison (Reid et al. receptors in the dorsal spinal cord. Its use as a
2011). Dystonia is described as “a movement treatment for dystonia may be due to a central
disorder in which involuntary sustained or inter- effect, though the exact mechanism is unclear.
mittent muscle contractions cause twisting and The evidence for ITB as a treatment for dystonia
repetitive movements, abnormal postures or was rated as possibly effective, with all studies but
both” (Sanger et al. 2003). Dystonia obviously one showing improvement in dystonia, and two
affects motor function and ease of care, but of the studies showing persistent dystonia reduc-
it also can be a source of pain and discomfort. tion over 12–24 months (Dachy and Dan 2004).
Dystonia was identified by the treating physicians However, there were inadequate data regarding
as the second most common cause of pain ITB improving pain and discomfort (as well as
(in 12%), following only hip dislocation/subluxa- improving motor control or ease of caregiving).
tion (in 16%) as a cause of pain among a group of The most common side effects were constipation,
252 children with CP ranging in age from 3 to decreased head control, and drowsiness. Intrathe-
19 years (Penner et al. 2013). cal baclofen certainly should be considered for
those patients with CP who have both spasticity
Treatment and Complications and dystonia.
Treating dystonia is a challenging and frustrating Deep brain stimulation has been used for a
endeavor for both patients and physicians, as no variety of adult movement disorders and is con-
treatment effectively and consistently ameliorates sidered the standard of care for Parkinson’s dis-
the pain associated with dystonia. In a recent ease (Krishnan et al. 2018). Studies of its efficacy
systematic review of both pharmacologic and for children with CP have shown mixed results.
neurosurgical treatments of dystonia (Fehlings Reduction of dystonia was reported in 6 of
et al. 2018), none of the treatments were found 12 studies, whereas 4 failed to show any reduction
to have evidence of effectiveness. There were no in dystonia, resulting in a conclusion that DBS
articles regarding the use of oral baclofen, benzo- could be possibly effective for reducing dystonia
diazepines, clonidine, and gabapentin that met the (Fehlings et al. 2018). Evidence for DBS improv-
inclusion criteria, and therefore no recommenda- ing motor function was conflicting, and the evi-
tions could be made regarding these agents, dence for reducing pain and discomfort was
inadequate, with two studies showing improve- shunt, 37% had CP, whereas with a shunt the
ment and two others failing to show any improve- incidence of CP was 80% (Adams-Chapman
ment in pain (Fehlings et al. 2018). Deep brain et al. 2008).
stimulation is used by clinicians in those patients
with generalized dystonia not well controlled
with oral medications or when pain and discom- Complications
fort are a major problem caused by the dystonia or
in both. Complications include infection, local The most common complications of a shunt (most
wound erosion, hardware malfunction, and local commonly VP or VA shunt) are infection and
hemorrhage. blockage of the shunt, both of which can cause
shunt malfunction. Shunt malfunction can present
with an abrupt onset of symptoms of increased
CNS Shunt Malfunction intracranial pressure (ICP), including headache,
vomiting without nausea, ocular palsies, and leth-
Although the percentage of preterm infants who argy. Not all of these symptoms are necessarily
suffer intraventricular hemorrhage (IVH) has present together, so that headache alone, espe-
decreased over the past decades, posthemorrhagic cially one that is persistent and more severe than
hydrocephalus (PHH) remains a serious problem typical for the patient, should raise the concern for
and is associated with a high rate of CP. For a blocked or infected shunt. Examination of the
instance, a study from England compared two eyes for the presence of papilledema and the vital
cohorts of infants with gestational age less than signs for Cushing’s triad (systolic hypertension,
27 weeks, one born in 1995 and the second born in widened pulse pressure, and bradycardia) can sup-
2006. While survival improved in the latter group, port or negate the concern of increased ICP. A CT
morbidity for most developmental outcomes did scan, especially when compared with a previous
not, including CP, which was found in 15% of scan, can confirm or rule out increased ICP. In
each cohort. In contrast, shunted hydrocephalus many children, however, the onset of symptoms
decreased from 5% in the 1995 cohort to 2% in the can be insidious rather than abrupt, as the block-
2006 cohort (Moore et al. 2012). A study of over age can be partial or intermittent. In this case,
7000 infants followed by the Neonatal Research symptoms can again include headache, but, rather
Network and born with birth weights between than vomiting and ocular palsies, the patients are
401 and 1000 grams during the years 1993–2002 more likely to present with a change in behavior
compared neurodevelopmental outcomes of those (including lethargy) and in school performance.
who required shunts with those who did not. A high index of suspicion for shunt malfunction
Among the 7693 children studied, 2530 (33%) should be maintained for any child with a shunt
had an IVH during their initial hospitalization, presenting with headache or behavior change or
and the IVH was severe (grade 3 or 4) for 13% both.
(998 of 7693). Three percent of infants (246 of
7693) had a shunt placed for PHH. These
246 infants represent 10% of the 2530 ELBW Surgical Complications
infants who had an IVH during the study period.
The risk for severe IVH was inversely related to The perioperative treatment of pain is discussed in
the gestational age of the infant. At follow-up, its own chapter and will not be discussed here.
40% of the 6161 children in the analysis groups However, there are some complications of surgery
had some type of neurodevelopmental impair- that can result in painful consequences and need to
ment at 18 to 22 months’ corrected age. CP was be considered, though the pain is not directly
diagnosed in 14%. Those with shunts were at a attributable to the surgery itself. For instance,
higher risk for CP. For instance, for those with scoliosis surgery in children who have a VP
grade 3 IVH but with no shunt, 23% had CP, while shunt can result in malfunctioning of the shunt,
with a shunt 57% had CP. For grade 4 IVH and no presumably due to mechanical injury or stress to
the shunt hardware resulting from correction of a pain team started her on a weaning program
severe curve (Lai et al. 2014). A common postop- of the clonidine, during which her nightly dose
erative complication of scoliosis surgery is pan- would decrease by 0.1 mg each night.
creatitis, reported to occur in 55% of a large series Emily was taken by her mother to the ED just a
(Abousamra et al. 2018), which causes severe few days later because of increased fussiness.
abdominal pain and vomiting. Following a poste- The GT was still leaking, and her mother
rior spinal fusion (PSF), one can see worsening of thought Emily was not getting her pain medi-
hip subluxation (Crawford et al. 2017), and there cation because of the leakage. In the ED, she
are cases of proximal fixation problems, which was given morphine 2 mg and diazepam 2 mg.
can lead to reoperation. We have also seen in our After admission, she received diazepam and
practice GE reflux develop or worsen in children ketorolac IV initially for pain control and
who have undergone PSF. All of these complica- then transitioned to diazepam PO, acetamino-
tions can cause pain in the postoperative period, phen, and hydrocodone-acetaminophen. She
which may be mistaken for pain due to the surgery had a gastric emptying scan, which showed
itself. One needs to consider a complicating event marked delay of gastric emptying. She then
when the pain lasts longer than is typical or underwent conversion of her GT to a GJ tube
develops after the child is out of the postoperative by interventional radiology (IR). She tolerated
period. If accompanied by fever, one must also her j-tube feeds well. Erythromycin was ini-
suspect an infection, though these are frequently tially started to help with gastroparesis. She
not painful and present with discharge or swelling developed diarrhea after erythromycin, so she
and redness at the site of the incision. was changed to metoclopramide. Her feeds
Case: The following case demonstrates some were changed to continuous. She was seen in
of the complexity of trying to understand what is the ER a week later for a clogged GJ tube that
causing pain in a nonverbal child with CP. While was thought to be secondary to clonidine tab-
it illustrates a postoperative complication, it also lets. She was switched to a compounded cloni-
shows how many confounding issues can be dine suspension.
involved. June: She was seen by her primary care pediatri-
cian (PCP) 3–4 weeks after surgery. She noted
Emily is a 13-year-old female who had a posterior that Emily had been more agitated since her
spinal fusion done for neuromuscular scoliosis posterior spinal fusion. She used to get around
secondary to CP. She is GMFCS class 4 with by scooting on her bottom, but now she is
kyphoscoliosis and chromosomal abnormality confined to a wheelchair. Prior to surgery,
and does not speak. She is exclusively on she never used a wheelchair and was able to
G-tube (GT) feedings and has had intermittent walk short distances holding people’s hands.
leaking from her GT. She also has a history of She is no longer taking hydrocodone for pain
constipation, which is well controlled on poly- but has been using diazepam more frequently
ethylene glycol. for both its relaxant properties as well as for
May: Her surgery went well and she was her behavior. She is currently on clonidine for
discharged home 7 days after surgery. sleep and fluoxetine for her behavior, which
Pain medication at the time of discharge was were prescribed well before surgery. On
hydrocodone-acetaminophen, as needed every exam, she was noted to be at a Tanner 2 stage
4 h, and diazepam 3 mg every 6 h as needed for of puberty (few pubic hairs). She was noted to
muscle spasms. She typically took 0.1 mg of have an impacted tooth and was referred to her
clonidine at bedtime, and this was increased to dentist.
0.5 mg. July: Two months after surgery, Emily is still
On the day after discharge, she was readmitted showing agitation. They have been using diaz-
because of leaking of her GT. Her GT was epam prn for increased agitation/head
changed to one with a smaller stoma. The banging. Emily was started on fluoxetine and
clonidine 4 years before for similar episodes, was given diphenhydramine. However, she
but doses have never been increased. She is continued to refuse to sit upright and had
currently on 12 mg of fluoxetine daily. It was increased agitation. Family was giving her
increased to 15 mg daily for 2 weeks, then to ibuprofen and diazepam intermittently. Ibupro-
20 mg daily. She was switched back from a GJ fen seems to help “somewhat” and diazepam
to a GT at this time. makes her sleepy and therefore less agitated,
September: Four months after surgery, Emily is but she continued to refuse to scoot around and
still having behavior issues and temper tan- displayed signs of pain when upright.
trums and hitting herself and others. She is January: Seen by orthopedics. There were no
also fighting sleep at night, sometimes for up signs of infection on clinical examination. An
to an hour and a half. Emily started at a new ESR and C-reactive protein test were ordered
school for children with special needs this and results were normal. A bone scan showed
month. Since school has started, Emily has increased signal intensity at the bottom of her
developed behavioral issues such as fighting fusion in the lumbar area, and so she had a CT
sleep, temper tantrums during the day, and scan done, which showed peri-implant halo
taking her clothes and diapers off at night in around her L3 pedicle screws bilaterally, sug-
bed. Mom felt that the increased dose of fluox- gestive of loosening of the screws. The CT
etine helped her behavior. She also takes diaz- also showed an incidental nonobstructing kid-
epam as needed for muscle spasms and ney stone. Urology subsequently evaluated her
agitation, but the diazepam is no longer help- and did not feel that the kidney stone was
ing. She currently takes clonidine at night causing pain. Reexamination by orthopedics
(0.1 mg). Clonidine dose has been the same showed that she was quite comfortable when
for 4 years. Clonidine dose was increased to lying on the exam table. There was no area of
0.15 mg daily (1.5 mL) to see if it might focal tenderness on deep palpation of her
improve her behavior. spine. However, any attempt to sit her up
October: Started on lorazepam. caused an extreme stress response with crying,
November: Seen by psychology. Entertained pos- screaming, and increase in random body
sible diagnosis of ASD. movements.
November: Swelling around impacted tooth, The initial plan by orthopedics was to place Emily
treated with clindamycin. Seen by dentist. in a rigid TLSO to see if this allowed her
December: Emily developed signs of significant symptoms to abate. The parents expressed
pain when sitting upright. Mom reports that some concerns over this plan, as she did not
Emily’s preferred position before this was to previously tolerate a brace for her scoliosis
be sitting upright and to be scooting around because of her tactile and sensory integration
the house on her bottom. However, she was issues. It was then decided to operate on her
refusing to do this and instead was “scooting” spine and revise the fusion. She underwent
around the house on her back. When her par- revision of the fusion, with screw exchange at
ents would sit her up, she would become very L3 and extension of the fusion to L4. She was
agitated and refuse to stay upright. She was discharged 3 days later, and the extreme agi-
ambulating previously but has refused to do tation has not re-appeared.
this as well. Also during this time, she was On follow up with her PCP in June, it was noted
diagnosed with possible flu (parents had it) that Emily had been doing well. Her behaviors
and was placed on oseltamivir. She then pre- had significantly improved since starting at a
sented to the ER because of concerns about different school that specializes in children
increased agitation and frequently throwing with behavioral problems. She remains on flu-
her head back. She was diagnosed with a pos- oxetine daily, but mom rarely needs to give
sible dystonic reaction. Oseltamivir and hydroxyzine or diazepam for agitation. She is
metoclopramide were discontinued, and she walking more with assistance, and her mom
feels like she is back to the “happy” Emily that not reveal a fracture, and a nuclear medicine bone
she was before her posterior spinal fusion. scan is needed to document the fracture. Though
the fractures may be hard to identify, the patients
experience significant pain, and opioid analgesics
Muscle Overuse Injuries are often required to help control the pain.
Overuse injuries are subtle and usually occur over

time, making them challenging to diagnose and Treatment and Complications
treat. They are the result of repetitive micro-
trauma to the tendons, bones, and joints that result Treatment for the fracture itself will involve the
in such injuries as tendinitis or a stress fracture. orthopedist, who may cast the extremity or, if the
They are commonly described in athletes and fracture is displaced, may need to operate and do
military personnel, two groups doing intensive an open reduction, which may involve placing a
activities repetitively (Hadid et al. 2018). Patients rod in the bone. In addition, treatment of the low
with CP may also develop such injuries, due to bone density to prevent or at least reduce the risk
repetitive use of one hand, for instance, in a child of future fractures is needed. This may include
with hemi- or diplegia using a power wheelchair nutritional supplements of calcium, phosphorus,
or communication device or putting stress on one and vitamin D; increased weight bearing after the
hip with an asymmetric gait due to hemiplegia. fracture has healed; and bisphosphonate treat-
ment, depending on how severe the osteoporosis
is and if this is the first fracture. (See ▶ Chap. 26,
Occult Fractures “Managing Bone Fragility in the Child with Cere-
bral Palsy” for more details.)
Children who are partially or totally non-
ambulatory are at risk for disuse osteoporosis
and fragility fractures. This risk is estimated at Kidney Stones
4% per year for children with moderate to severe
CP (GMFCS 3–5) and no previous fracture and Nephrolithiasis, also known as kidney stones, is a
7% if they have had a previous fragility fracture condition in which hard deposits of minerals,
(Stevenson et al. 2006). These fractures often most commonly calcium oxalate (in 45–65%),
occur without any obvious trauma and most calcium phosphate (in 14–30%), and struvite
often (70% of the time) involve the lower extrem- (13%), form within the urinary tract (Milliner
ities. Often, the child begins to express pain with- and Murphy 1993). The underlying risk factors
out any obvious preceding traumatic event. This include chronic infection, structural abnormalities
pain may be clearly associated with movement of of the GU tract, and metabolic abnormalities such
one particular limb or with swelling and tender- as hypercalciuria and hypocitrituria. The meta-
ness to palpation. However, at other times, none of bolic conditions for stone formation can be met
these signs may be present, and one has to remem- when the urine is highly concentrated, a situation
ber that an occult fracture is a possible cause of a common in many children with CP, whose oral
sudden onset of pain, especially in the child who intake of fluids may be quite limited because of a
is in a wheelchair. If the pain persists for a few swallowing disorder and are therefore chronically
hours and becomes localized on palpation or dehydrated. Nephrolithiasis has also been associ-
movement of one extremity, then a radiograph is ated with immobility, taking topiramate, and a
warranted. This needs to be reviewed by a radiol- ketogenic diet (Hauer et al. 2017), any of which
ogist or orthopedist who has experience with these may be seen in the patient with CP. Other drugs
types of fractures, as they are often quite subtle that can predispose a patient to nephrolithiasis
and difficult to see because of severe osteopenia. include furosemide, acetazolamide, and
There are occasions when a plain radiograph will allopurinol.
The incidence of nephrolithiasis has been entering her room, and physical touch would
rising in the USA for both children and adults often trigger episodes. Angela was treated with a
over the past 25 years (Dwyer et al. 2012). combination of methadone, baclofen, clonidine,
Most children present with acute flank or abdom- and gabapentin to control her symptoms. She
inal pain, though 15% to 20% are asymptomatic was trialed on propranolol twice, but each time
(usually in children under age 5 years), and the she became bradycardic, so propranolol was
stones are found on abdominal ultrasound done discontinued. For breakthrough episodes of irri-
for other reasons. Other presenting symptoms tability, she responded well to prn diazepam. Six
include gross hematuria, dysuria, nausea, and months post cardiac arrest, her episodes subsided
vomiting. The pain associated with kidney stones and medications were tapered slowly. She contin-
can vary from a mild ache to severe debilitating ued to have intermittent episodes primarily
pain. Nonverbal children with CP, as well as triggered by illness, but episodes overall were
young children, often are unable to articulate decreased in duration and intensity.
the location and severity of the pain. As a result, Paroxysmal sympathetic hyperactivity (PSH)
they are frequently evaluated for other causes is also known as autonomic dysfunction, auto-
of abdominal pain before the diagnosis of nomic storm, dysautonomia, thalamic storm, and
nephrolithiasis is made, often after an ultrasound sympathetic storm (Hall 2017; Hauer et al. 2017).
or CT scan of the abdomen. Paroxysmal sympathetic hyperactivity manifests
as extreme irritability with associated vital sign
changes, such as alterations in body temperature,
Treatment and Complications heart rate, and respiratory rate. The symptoms of
PSH are commonly confused with sepsis or severe
During the acute phase when the stone is being infection. This condition is frequently seen in
passed, management is focused on pain control children with severe neurological impairment,
and on facilitating passage or removal of the such as children with CP who have hypoxic ische-
stone. Initial treatment usually includes IV hydra- mic encephalopathy. Paroxysmal sympathetic
tion, a combination of opioids and NSAIDs for hyperactivity often occurs early after a neurologic
pain control, and assessment and treatment for injury, but, over time, the episodes often become
UTIs when suspected. After the acute episode, less frequent and less intense. The triggers for
management is aimed at prevention of recurrent PSH are individual to the child but typically relate
stone disease. This includes an evaluation to iden- to painful stimuli.
tify any underlying cause or risk factors for stone
formation that can be modified.
Treatment and Complications
Paroxysmal Sympathetic Treatment for PSH is individual to the child, with

Hyperactivity multiple medications frequently used. Many chil-
dren are on a combination of long-acting medica-
Case: Angela is a 3 year old with spina bifida tions to control on-going symptoms and short-
and bladder exstrophy who had a cardiac arrest acting medications for exacerbations. Gabapentin
postoperatively and subsequently developed is frequently one of the first medications used as a
severe hypoxic ischemic encephalopathy. Angela long-acting medication because of its excellent
is now nonverbal with global developmental safety profile. Additional medications include
delay and spastic quadriplegic CP. Angela had clonidine, baclofen, and beta blockers, such as
multiple episodes of extreme irritability in the propranolol. Short-acting medications include
6 months post cardiac arrest, which manifested opioids, benzodiazepines, and clonidine. The
as crying, fever, hypertension, tachypnea, tachy- symptoms the child presents with help determine
cardia, and muscle rigidity. Loud noises, people which medications to use. For example, if
hypertension and tachycardia are severe, propran-

olol and clonidine may provide greater benefit infection. On examination by the pediatri-
than medications without antihypertensive prop- cian, he had bilateral otitis media. He started
erties (Hall 2017). However, if the child has on antibiotics and his fussiness improved.
increased muscle spasms or muscle rigidity, bac-
lofen may provide a greater benefit than alterna-
tive medications. Some children benefit from
nonpharmalogical techniques’ such as swaddling, Cross-References
vibratory mats, and weighted blankets (Hauer
et al. 2017). ▶ Acupuncture and Traditional Chinese Medicine
Used to Treat Cerebral Palsy
▶ Deep Brain Stimulation for Pediatric Dystonia
Conclusion ▶ Focal Management of Spasticity in Cerebral
Palsy
Pain is a common symptom of many medical ▶ General Dentistry for Children with Cerebral
problems seen in children with CP. However, Palsy
because many children with the more severe ▶ Gynecological Issues in Girls and Young
forms of CP also have limited to no ability to Women with Cerebral Palsy
communicate, this pain often goes untreated, and ▶ Hip Problems in Children with Cerebral Palsy:
the underlying pathology may be missed for a An Overview
long period of time. While pain commonly pre- ▶ Hydrocephalus in the Child with Cerebral Palsy
sents with crying and irritability, it may present ▶ Intrathecal Baclofen Therapy: Assessment and
more subtly, with behavior changes such as sleep Medical Management
disturbances, irritability, depression, fatigue, or ▶ Kidney Stones: Risks, Prevention, and Man-
anxiety. While the typical causes of pain in chil- agement in Cerebral Palsy
dren, such as acute infections of the ears or ▶ Managing Bone Fragility in the Child with
sinuses, need to be considered in children with Cerebral Palsy
CP as well, there are a number of causes of ▶ Managing the Child with Cerebral Palsy Who
pain that are more common in these children Has Medical Complexity
than in typically developing children. Such causes ▶ Medical Management of Spasticity in Children
include fragility fractures, nephrolithiasis, post- with Cerebral Palsy
surgical problems such as pancreatitis, and CNS ▶ Palliative Care for Individuals with Cerebral
shunt malfunctions. Palsy
▶ Physical Therapy Elements in the Management
of the Child with Cerebral Palsy
Cases ▶ Postoperative Pain and Spasticity Management
in the Child with Cerebral Palsy
▶ Spasticity Assessment in Cerebral Palsy
Case 1 An Example of a Common Childhood
▶ Spasticity, Dystonia, and Athetosis Manage-
Illness Causing Pain in a Child with CP
ment in the Upper Extremity in Cerebral Palsy
Blaine is a 3-year-old nonverbal boy with
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Palliative Care for Individuals
Elissa Miller, Carly Levy, and Lindsay Ragsdale
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 414
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 414
Advance Care Planning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 415
Decision-Making Support . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 416
Pain and Symptom Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 419
Care Coordination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 419
Anticipatory Grief/Bereavement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 419
Family Support . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 419
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 420
Case Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 421
Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 421
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 422
Abstract pediatric patients with severe illness and their

Pediatric palliative care teams are interdisci- families. This chapter outlines a description of
plinary teams that focus on quality of life for palliative care teams and how they can assist
individuals with severe cerebral palsy and their
families along the journey of illness.
E. Miller (*) · C. Levy
Department of Pediatrics, Division of Palliative Medicine, Keywords
Nemours/AI duPont Hospital for Children, Wilmington, Cerebral palsy · Palliative care · Palliative
DE, USA
medicine · Advance care planning · Supportive
Sidney Kimmel Medical College Thomas Jefferson care · PPC · Pediatric palliative care · Quality
e-mail: Elissa.Miller@nemours.org;
of life · DNR
carly.levy@nemours.org
L. Ragsdale
Department of Pediatrics, Pediatric Palliative Care,
Kentucky Children’s Hospital, University of Kentucky,
Lexington, KY, USA
e-mail: lindsay.ragsdale@uky.edu

https://doi.org/10.1007/978-3-319-74558-9_25
414 E. Miller et al.
Introduction beliefs. For some, receiving a diagnosis of CP

might be the most difficult time in their lives.
The World Health Organization defines pediatric For others, coping with their child’s physical and
palliative care (PPC) as “the active total care of the functional limitations over the years ahead might
child’s body, mind and spirit, and also involves be the most challenging. PPC can help patients
giving support to the family. It begins when illness and families understand the diagnosis, build cop-
is diagnosed, and continues regardless of whether ing skills for times of stress, and anticipate and
or not a child receives treatment directed at the prepare for future challenges.
disease. Health providers must evaluate and alle- Recent data has shown an increase in hospital
viate a child’s physical, psychological, and social utilization and admissions at end of life for chil-
distress. Effective palliative care requires a broad dren with complex chronic conditions. Of these
multidisciplinary approach that includes the fam- children with three or more complex chronic con-
ily and makes use of available community ditions (cerebral palsy is considered a chronic
resources; it can be successfully implemented complex condition in this study), most children
even if resources are limited. It can be provided experienced at least four hospitalizations during
in tertiary care facilities, in community health the last year of life, and these admissions
centres and even in children’s homes” (World accounted for greater than 2 months of time
Health Organization 1998). With that definition (Ananth et al. 2015). Palliative care can assist
in mind, it is easy to see how individuals with families in setting goals and creating an advance
cerebral palsy, especially those who are severely care plan during this period of repeat admissions.
affected, may benefit from palliative care. PPC teams can start a conversation in conjunction
Palliative care focuses on the individual, pay- with primary and subspecialty providers about
ing close attention to quality of life while tailoring how we should care for a patient with cerebral
the patient’s treatment plan according to the palsy when they are declining. The psychosocial
patient/family’s goals of care. PPC uses an inter- providers on the team can provide grief and
disciplinary team to treat both the patient’s phys- bereavement support, assist with memory making
ical symptoms and the psychosocial, spiritual, and and funeral planning, and provide resources. PPC
emotional needs of the patient and family. The teams can serve the whole family including sib-
most common providers on a PPC team include lings, who can sometimes be overlooked
a physician, advanced practice nurse, registered (Lovgren et al. 2016, Gaab et al. 2014). The
nurse, social worker, and a chaplain. Teams have remaining part of this chapter is an in-depth dis-
an average of 2.33 full time equivalent dedicated cussion of the spectrum of care that PPC teams
practitioners per team (Feudtner et al. 2013) and can provide.
see patients in a consultative manner in the inpa-
tient, ambulatory, and home settings. PPC pro-
grams care for patients from diagnosis of their Natural History
serious illness, at any age, ranging from the pre-
natal period into adulthood. By providing conti- The natural history for individuals with severe
nuity of care across settings, PPC programs aim to cerebral palsy (Gross Motor Function Classifica-
better coordinate complex care and hopefully tion System levels 4 and 5) is predictable in some
avoid frequent hospital admissions and emer- ways and unpredictable in others. Though the
gency department visits for patients with brain injury that causes cerebral palsy is static,
end-stage illness (Kaye et al. 2015). progressive organ dysfunction develops in many
Palliative care can be helpful for patients at any of the most severely affected individuals. Organ
point along the disease trajectory from diagnosis systems involved include the respiratory, gastro-
to death (see Fig. 1). (Klick and Hauer 2010) Each intestinal, genitourinary, skin, musculoskeletal,
patient and family processes the new diagnosis of and autonomic nervous systems. Whether via
CP in the context of their prior experiences and upper motor neuron, autonomic nervous system,
28 Palliative Care for Individuals with Cerebral Palsy 415
100 2
Percent ideal health status

1
5
0
Time
Fig. 1 Figure description (figure and description modified from Current Problems in Pediatric and Adolescent Health
Care, July 2010): Point 1 represents the time of diagnosis and first hearing bad news. PPC teams can help with difficult
conversations and help the patient and family readjust hopes and expectations. Point 2 is another common point in time
where PPC teams can help families acclimate to their new normal and help process feelings of grief around the loss of their
prior functionality. Point 3 represents a time of significant illness or decompensation and unexpected recovery. These
moments can give space to talk about the “what if” questions and to create an advance care plan if this event were to
happen again. Point 4 depicts a downward trajectory in which patients can have a significant decrease in quality of life and
functionality. Many families are asked to decide about surgeries and additional technology in order to sustain the current
status. PPC teams can help families develop central goals, and these goals can help them make decisions as they arise.
Point 5 shows end of life in which the PPC team can provide end-of-life medical care at home or in the hospital with
meticulous symptom management
or enteric nervous system dysfunction, the com- risk of waiting until a medical crisis arises to
monality among the affected organ systems is the discuss ACP is potentially impulsive decision-
decline due to underlying abnormal neurologic making under significant stress, shock, and even
function. Affected organ systems typically decline desperation (Hammes et al. 2005). Clinician bar-
in a predictable manner, which can allow families riers to advance care planning include unrealistic
to engage in advance care planning. parent expectations, differences between clinician
and patient/parent understanding of prognosis,
and lack of parent readiness to have the discussion
Advance Care Planning (Durall et al. 2012). PC teams work closely with
primary providers to overcome these barriers.
PPC teams routinely talk with patient/families Typically, in severely ill children, ACP is done
about advance care planning (ACP) and assist in with the child’s surrogate decision-maker(s),
decision-making support. Advance care planning However, depending on the developmental stage
gives patients and families the chance to articulate and ability to comprehend, some children can
their preferences for future care, especially with participate in some part of ACP, such as helping
regard to additional medical technology aimed at craft preferences or wishes. For adult patients who
prolonging life, which could also decrease quality permanently lack decisional capacity, families or
of life. ACP empowers patients/families to have caregivers may obtain legal guardianship from the
some control over future interventions and court. In such cases, advance care planning would
encourages caregivers to plan ahead. ACP is ide- be completed with the court-approved surrogate
ally discussed and documented during a period of decision-maker(s). For adults with decisional
medical stability, as this allows time for clear capacity, palliative care teams often recommend
reflection on individual goals and values. The that ACP take place with family members present
to support the patient and ensure good communi- often express significant interest in the opportu-
cation, especially with a person’s designated nity to discuss their wishes for their loved ones’
healthcare agent, but this is not required. care (Liberman et al. 2014). Assisting in ACP is a
Advance care planning can take a variety of crucial role of PPC teams in the care of medically
forms. It can be as unassuming as a patient/family/ complex patients.
provider discussion that is documented in the
medical record or as complex as completing a
multipage ACP document. Living wills represent Decision-Making Support
one such ACP document and are a written record
of patient wishes, most often in a format that is The complexities of progressive organ system
legal in the patient’s area of residence. However, dysfunction in severe cerebral palsy are some-
written statements often do not capture the actual thing that no provider would expect patients or
circumstances of ones’ terminal illness. families to navigate alone. PPC teams can partner
Healthcare agent documents allow adults with with primary or subspecialty providers to give
decisional capacity to name a person or persons decision-making support to families at varying
to act as surrogate decision-maker(s) on their stages of the disease process (Feudtner 2007).
behalf in the event the patient is no longer able Palliative care is frequently asked to help fam-
to speak for him or herself. This person, called a ilies when patients and families are faced with a
healthcare agent or healthcare proxy, can help decision to pursue or decline a specific surgical or
make decisions on the person’s behalf based on medical intervention. A palliative care provider
knowledge of the person’s wishes combined with can often help caregivers better understand the
the details of a specific medical circumstance. different trajectories, identify goals of care, and
PPC teams often help teens and young adults ultimately facilitate decision-making. The follow-
discuss their wishes with their designated ing cases demonstrate how a palliative care team
healthcare decision-maker(s). can be helpful in the medical decision-making
For our most fragile patients for whom care- process.
givers and providers agree that resuscitation is
unlikely to be successful and would serve only Case 1: Dennis
to prolong their suffering and/or would do harm to Dennis is a 15-year-old male with cerebral palsy
them, many states now have specific out-of-hos- who is nonverbal and non-ambulatory with
pital advance directives known as medical orders chronic restrictive lung disease. He underwent
for life-sustaining treatment (MOLST) or physi- spinal fusion two years ago and is dependent on
cian orders for life-sustaining treatment (POLST) nighttime noninvasive positive pressure ventila-
forms. MOLST or POLST forms allow providers tion (NIPPV). He has had recurrent admissions for
to document resuscitation status including do not aspiration pneumonia with increasing frequency
intubate (DNI), do not resuscitate (DNR), and of admissions over the past year. His most recent
instructions to provide comfort care only. These admission included an intensive care unit (ICU)
advance directives constitute a physician’s order, course necessitating mechanical ventilation. He
and first responders are required to honor them if was ultimately discharged with a new baseline,
called to care for a sick or distressed patient (Insti- requiring positive pressure ventilation for
tute of Medicine 2015). They are employed most 8–10 hours during the day in addition to
commonly for patients living with serious illness overnight.
or frailty whose health practitioners “would not be Following discharge, he was seen by his Pul-
surprised if the patient died within the next year monologist in clinic, who expressed concern
(Delaware 2016).” about Dennis’ recent respiratory decline. He
Physicians worry that completing ACP will noted Dennis’ “lungs are sicker with each infec-
cause caregiver distress or undue burden to care- tion” and that eventually the doctors may be
givers. In reality, studies show that caregivers unable to extubate, necessitating tracheostomy
placement and long-term mechanical ventilation “We have known loving families whose goal
in order for him to live as long as possible.” The was to keep their child alive as long as possible,
pulmonologist acknowledges that the decision to even if that meant being dependent on machines
proceed with tracheostomy would be “the parents’ or even living in a facility and those families chose
choice,” and Dennis’ parents were appropriately to pursue tracheostomy; whereas other loving
tearful during this visit. They expressed grief families who would not want this quality of life
over the impending change in Dennis’ quality of for their child, chose to forgo tracheostomy,
life and also feared making the wrong decision. knowing their child’s life will be shorter but
The pulmonologist subsequently made a referral focused on quality and comfort.” Of note, it can
to the palliative care team to help identify the also be helpful to point out that some families
family’s goals of care and facilitate decision- choose to forgo tracheostomy or even intubation,
making. recognizing that for some it may be even harder
to “stop something that has already been started”
Assessing Medical Understanding (i.e., decannulation, terminal ventilator withdrawal).
During the first encounter, the palliative care pro- The palliative care provider respectfully
vider asked the parents “what have the doctors pointed out to Dennis’ parents how difficult this
told you about Dennis’ medical condition and decision is and that there is no right answer, only
what do you expect for his future,” as a way of what’s right for each individual child and family.
ascertaining their medical understanding of his The provider also informed the parents that no
clinical status and prognosis. Both parents reiter- matter what path they choose, the medical team
ated understanding that Dennis “was sicker” and will continue to support them.
they would ultimately have to make a decision
about whether or not they would want him End of Life Care
“hooked up to a machine all the time.” They also One year after the initial palliative care encounter,
articulated an accurate understanding of the Dennis was readmitted for acute on chronic respi-
advantages and disadvantages of a tracheostomy. ratory failure and intubated in the PICU, except
this time the team was unable to successfully
Goals of Care extubate him. Palliative care was consulted to
Recognizing both parents had a clear understand- readdress goals of care.
ing of Dennis’ current status and prognosis, the Both parents were still in agreement that they
palliative care provider explored their goals of did not want to pursue a tracheostomy, and thus
care by asking several questions: the palliative care provider engaged them in a
discussion around what things can still be done
• “Knowing what Dennis is up against, what is including a focus on keeping him comfortable,
most important to you? taking him home for a compassionate extubation
• “What are you most hopeful for?” (with hospice support) versus keeping him in the
• “What are you most worried about?” ICU for his end-of-life care. Child life involve-
ment was offered for legacy building (hand prints,
In response to these questions, Dennis’ parents hand molds, scrapbooking, and other craft activi-
noted they were most worried about his “suffer- ties to help families preserve physical reminders
ing,” which to them meant “living on machines.” of their child). Pastoral care and social work were
They were concerned about their ability to care for also following for spiritual and psychosocial sup-
him with a tracheostomy, even with home nursing port. His family chose to take him home and thus
support, and thus feared the potential need for the palliative care team coordinated the transport
facility placement. home and a hospice referral and directly managed
The palliative care provider helped frame the the end-of-life care in the home. He died peace-
decision by highlighting what other families have fully at home with his family and loved ones
chosen based on their respective goals of care: surrounding him.
Case Discussion if that meant “living on life support and poten-

Assessing Medical Understanding: Although tially being unable to go in the pool.”
providers do their best to present medical informa- For the family during a time of crisis, it was
tion clearly, patients and families do not always helpful to have had a pre-existing relationship
understand everything being communicated. This with the PPC team. After meeting with the family
communication breakdown is especially true after and readdressing their goals for her, it was clear
receiving bad news, such as news of a clinical they wanted her to live as long as possible and thus
decline. Having a third party like a palliative care agreed about moving forward with a tracheostomy.
provider unpack what a family heard can be help- The palliative care team subsequently coordi-
ful, before moving forward with decision-making. nated a larger family meeting that included the
Making Recommendations: If the family’s ICU team, otolaryngology, pulmonology, her pedi-
medical understanding and goals of care are atrician, and the family to ensure their questions and
clear and appropriate, palliative care teams often concerns were addressed and they felt well-
offload the burden of decision-making by making supported. The family also understood that if
a recommendation that aligns with the families’ Melanie no longer had a good quality of life (recur-
respective goals of care. rent admissions, tracheostomy infections, etc.), they
For Dennis, the provider may say something could make a different decision in the future (i.e.,
akin to: “Knowing your goals for Dennis have decannulation) and the team would support them.
always been and continue to be focused on quality
of life, and you both agree that living on machines
is not a good quality of life, I would suggest Case Discussion
continuing to provide the current level of care. Care Coordination: Children with CP are often
When it comes time to make a decision about a followed closely by multiple subspecialists. Palli-
tracheostomy, I would not recommend this for ative care providers can help bridge communica-
him.” This approach, often called palliative pater- tion among the various subspecialties by
nalism, is discussed in more detail in the decision- coordinating and facilitating larger team and fam-
making section below. ily meetings. This could be particularly helpful
during major branch points in a child’s clinical
Case 2: Melanie course (Klick and Hauer 2010).
Melanie is a 12-year-old female with cerebral palsy Discontinuing Medical Technology: The deci-
experiencing recurrent aspiration pneumonias. She sion to decannulate in the scenario above repre-
makes eye contact and has a social smile but is sents one of many possible choices regarding life-
nonverbal and dependent on caregivers for all activ- sustaining technology that families of severely
ities of daily living. She has nocturnal NIPPV affected individuals with cerebral palsy may have
dependence and is well-known to the palliative to face. These decisions, such as decannulation in
care team, who follows her for chronic pain man- the setting of chronic respiratory failure and per-
agement. During an admission to the ICU, the team ceived poor quality of life, are often difficult for
was having difficulty extubating Melanie, and thus both providers and families, especially at times of
the palliative care team was consulted to readdress relative clinical stability. Involving a palliative care
goals of care and facilitate decision-making. team may help bridge communication among pro-
The family understood the decision they had to viders as well as with family members, especially
make. They had initially expressed some ambiva- when there is a lack of consensus.
lence about a tracheostomy, as it would potentially It is important to note that in the cases above,
preclude her from doing the things that she enjoys the families had the authority to decide whether or
“like floating in the pool.” Ultimately her family not to proceed with tracheostomy. However not
recognized that “she had too many other things to all medical decisions are optional. Families and
live for like school, her friends, and family,” even practitioners are bound by local laws as well as
cultural and ethical norms to provide care if it is
ethically obligatory. Treatment is ethically oblig- care. Achieving effective communication

atory if it clearly benefits the patient, such as a between those providers can be difficult. PPC
tracheostomy for a child who is injured in a motor teams frequently coordinate care plan meetings,
vehicle accident but is expected to recover fully team meetings, and family meetings. Because
and be decannulated before or shortly after hospi- PPC teams follow patients across settings, they
tal discharge. Treatment that is clearly futile commonly provide continuity of information and
should not be offered, such as extra corporeal relationships across care settings and throughout
membrane oxygenation (ECMO) for a patient the disease trajectory (Klick and Hauer 2010).
who is actively dying from heart failure who is
not a heart transplant candidate. The grey area of
uncertainty is the place where palliative care Anticipatory Grief/Bereavement
teams may be helpful. PPC teams along with
hospital ethics committees often help practitioners Families who have a loved one living with serious
decide if a patient’s family may or may not refuse illness often face significant grief and bereave-
a given treatment as in the cases in this chapter. ment. Grief can start at the time of diagnosis –
for example, with the birth of a very premature
infant. Parents grieve the loss of a normal birth
Pain and Symptom Management and newborn experience, the loss of first holidays
spent at home with family. And, for many prema-
Dyspnea due to respiratory failure, pain due to ture infants, grief reappears as the sequelae of
spasticity and musculoskeletal deformity, and dis- extreme prematurity begin to develop. With a
comfort due to autonomic dysfunction are all diagnosis of spastic, quadriplegic cerebral palsy,
examples of areas of focus for palliative care families grieve that their child will never walk,
teams. There is, of course, significant overlap may never live independently, and may not expe-
with the expertise of each of a patient’s sub- rience the adult romantic relationships that parents
specialty providers, and PPC teams work collab- often hope is in their child’s future. Finally, when
oratively with these providers to target symptoms. a patient with severe CP is dying from end-stage
An important component of palliative care’s role organ dysfunction, parents grieve the death of
in pain and symptom management is counseling their child. Anticipatory grief is feelings of loss
families if the medical team is approaching max- that precede the death of a loved one and stems
imal intervention for a particular symptom. For from knowing the death is coming, whether days,
example, in the case of a patient who is experienc- weeks, months, or years in the future. PPC teams,
ing pain due to progressive intestinal dysfunction, especially PPC social workers, are experts at
it is important to initiate conversations about goals supporting families who are experiencing antici-
of care and quality of life before a patient reaches patory grief. PPC teams also often provide
total intestinal failure and dependence on paren- bereavement support to parents and siblings after
teral nutrition. The same conversations are impor- the death of a pediatric patient (Klick and Hauer
tant for symptoms such as dyspnea due to 2010).
progressive respiratory system dysfunction, pain
due to seating difficulty from non-healing stage
IV pressure wounds, and other involved organ Family Support
systems (Hauer and Houtrow 2017).
Palliative care teams commonly describe them-
selves as providing an added layer of support.
Care Coordination This support can be medical, as described in detail
above, but also practical, emotional, or spiritual.
Medically complex children often have a large Practical support includes the support commonly
number of medical practitioners involved in their offered by hospital social workers – meal cards,
connections to community resources for finan- when discussing day-to-day healthcare deci-
cial support, help arranging leave from work due sions, such as antibiotic choice and length of
to family member illness, etc. Emotional and therapy for otitis media. However, DDM is
spiritual support, provided by a number of dif- more burdensome for providers when talking
ferent members of the palliative interdisciplinary about life-and-death decision such as
team, includes counseling services, prayer, and discontinuing a patient’s ventilator or other
medical play for siblings. PPC teams often pro- life-sustaining technology.
vide support to families across locations – inpa- 3. Palliative paternalism (PP) – Employed fol-
tient, ambulatory, and in the home setting. Some lowing goals of care discussions, palliative
teams also offer child life specialist services, art care clinicians frequently recommend the best
therapy, and other creative arts practitioners to medical path to achieve a patient or family’s
support patient and sibling coping. It is important goals. This takes the burden of medical
for practitioners to know about their local decision-making off the family, allowing the
resources and offer supportive care through patient and family to focus on what they are
their palliative care team as available (Klick aiming to achieve. When family goals of care
and Hauer 2010). are unattainable, PPC teams can provide assis-
tance by refocusing on attainable goals while
also recommending the necessary medical path.
Treatment
PPC providers often elicit from families how
Palliative treatment options include those that they want to receive medical information and how
focus on improved quality of life and/or those they make difficult medical decisions. For fami-
that help to meet an individual patient’s goals of lies who state clear preferences, PPC teams can
care. Some parents do not want their child to live a help all providers honor patient and family
life attached to machines, choosing quality of life wishes, even when that may be difficult for pro-
over quantity. For others, life-prolonging treat- viders, as in the case example below.
ment including long-term tracheostomy and ven-
tilator dependence would be valuable. For still Case 3: Jo
others, a palliative tracheostomy to help manage Jo is a 17-year-old female with cerebral palsy,
oral secretions provides symptomatic relief GMFCS level 4. She is dependent on caregivers
regardless of the need for mechanical ventilation. for all activities of daily living but is interactive
The treatment recommendation of palliative pro- and communicates via assistive technology. In
viders depends on the result of discussions with the recent months, she has had worsening abdominal
entire care team, including family care providers. pain and discomfort due to worsening intestinal
Palliative care teams make treatment recom- dysmotility. She is now receiving J-tube feeds
mendations using a variety of models: with oral tastes for enjoyment but develops severe
ileus requiring parenteral nutrition during periods
1. Shared decision-making (SDM) – Seen more of respiratory illness. During a recent hospitaliza-
and more as the gold standard for decision- tion, Jo’s gastroenterologist noted that her time to
making, SDM involves active participation by return to enteral feeds is increasing with each
providers and patients/families in treatment illness and mentions to Jo’s parents that “with
decisions. Information exchange, discussion one of these illnesses, we may not be able to get
of patient and family preferences, and a treat- her back to enteral feeds and she may require
ment plan that is developed jointly. at-home parenteral nutrition.” Jo’s parents imme-
2. Deferred decision-making (DDM) – Rarely diately ask “does this mean she will never eat by
requested by families, DDM is when patients mouth again? Because she loves eating more than
and families ask clinicians to “tell me what to anything.” After talking further and learning more
do and I will do it.” This is easy for providers about the family’s focus on Jo’s enjoyment, her
gastroenterologist recommends Jo’s family meet and focus on quality of life. Jo continued eating by
with the palliative care team to help establish mouth despite recurrent aspiration and died of
goals of care for Jo. respiratory failure at home with hospice support
When the palliative care team meets with Jo’s a few weeks later. Her gastroenterologist
family, it becomes clear that food is a centerpiece remained involved and supportive throughout
of the family’s social structure and eating, even the final days of Jo’s life.
small amounts, provides quality of life to Jo. Jo’s
parents verbalize that they “like to hear medical
information straight up. Don’t sugar coat it for Case Discussion
us.” When asked, they name Jo’s gastroenterolo-
gist and her pediatrician as trusted members of Decision-Making: Families wishing to engage in
Jo’s care team with whom they prefer shared shared decision-making may identify a trusted
decision-making. Together with her gastroenter- provider. The model of shared decision-making
ologist and the palliative care team, Jo’s family often works well in such circumstances. The
decides on the following: their goal for Jo is that breakdown in the case above occurred when the
she may always eat some food for comfort and provider’s medical recommendation conflicted
enjoyment, even if this becomes dangerous, such with the family’s wishes and goals of care. The
as aspiration, or painful to Jo. They do not mind PPC team was able to identify and navigate this
the idea of home parenteral nutrition so long as Jo breakdown, ultimately helping all members of the
remains able to eat tastes by mouth. They under- family and care team feel comfortable with the
stand that, if Jo’s abdominal pain became intrac- plan of care.
table, they would have the option to discontinue
artificial nutrition and hydration in the future, but
they “hope it doesn’t come to that.” With these Complications
goals in mind, the group discusses converting Jo’s
G-tube to a draining gastrostomy. This increases As patients with severe cerebral palsy experience
Jo’s daily care requirement, but would allow her progressive organ system dysfunction and
to eat by mouth for pleasure, then drain her gastric decline, complications relating to treatment
contents and possibly decrease her abdominal choices are likely to arise. Palliative care teams
pain while continuing J-tube feeds. Her parents are a resource to patients, families, and practi-
agree that this sounds like a reasonable option. tioners alike. Ultimately, for those who die from
Employing a draining gastrostomy, Jo is able disease decline, palliative care empowers families
to remain on J-tube feeds with decreased pain and to protect their loved ones from suffering at end of
continued eating by mouth for enjoyment for life and to focus on goals of care and quality of
many years. Ultimately, after a series of aspiration life. Grief and bereavement are as much a part of
pneumonias requiring intubation and mechanical living with chronic disease as they are a part of
ventilation, Jo’s gastroenterologist suggested that coping with the death of a loved one. Palliative
her family stop giving her food to eat by mouth. care teams often offer grief and bereavement ser-
Her family, consistent with prior wishes, declined vices to help families. It is important that pro-
to withhold this source of enjoyment from their viders know the palliative care resources in their
daughter. This caused her gastroenterologist sig- local area so they can refer families appropriately.
nificant distress, worried that the family was
harming Jo. With the help of the palliative care
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Aging with Cerebral Palsy: Adult
Musculoskeletal Issues 29
M. Wade Shrader
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 424
Spine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 425
Hip . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 427
Lower Extremity, Knee, and Foot . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 428
Rehabilitation Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 429
Health Care System Issues for the Adult . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 430
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 431
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 431
Abstract care that are not easily translated from the

The transition from a pediatric-based pediatric to the adult environment. This chap-
healthcare system to a more traditional adult- ter will discuss some of the reasons why an
based health model for adolescents and adults adult with CP will seek out orthopedic surgical
with cerebral palsy can be quite a daunting care and will highlight the most common sur-
challenge. Most fields of adult medicine are gical procedures that adults with cerebral palsy
not exposed to many patients with childhood- may require. The pathophysiology of spine,
onset disabilities. Although the technical hip, knee, lower extremity, and foot and ankle
aspects of orthopedic surgery do not differ will all be discussed in detail with particular
significantly from pediatric to adult care, the attention to the trajectory of musculoskeletal
judgment involved in the care of patients with issues from childhood to adulthood of patients
cerebral palsy and overall skill in treating them with CP. Specific surgical procedures will be
with respect and dignity are both aspects of discussed, as well as what particular providers
and what particular hospitals should perform
these procedures in this unique patient
M. W. Shrader (*) population.
Cerebral Palsy, Nemours A.I. duPont Hospital for
e-mail: wade.shrader@nemours.org

https://doi.org/10.1007/978-3-319-74558-9_231
424 M. W. Shrader
Keywords balance, weakness, and loss of sensation. The

Cerebral palsy · Adult · Transition · Cervical consequence of these primary problems combined
stenosis with the effects of growth, time, and developmen-
tal delays lead to progressive orthopedic issues
including dynamic muscle contractures, joint con-
Introduction tractures, instability, arthritis, and bony deformity
(Murphy 2010; Horstmann et al. 2009).
In the developed world, the annual incidence of It’s unclear about the effects of a longer time on
cerebral palsy (CP) is approximately 3–4 per 1000 any of these secondary impairments. Certainly the
live births. The annual incidence in the USA is lack of normal activities of daily living may lead to
estimated to be between 8,000 and 16,000 new progressive contractures. Increased tone, contrac-
cases of CP per year. The overall society preva- tures, and increased body mass index may lead to
lence is increasing due to increased survival of increased loads across joints with subsequent
premature infants and increase survivorship into arthritis and pain. There is very little in the medical
adulthood (Sellier 2018). literature regarding the outcomes of adults with
The exact number of patients with CP in the cerebral palsy. It is uncertain what surgical pro-
USA is unknown. However, it is estimated to be cedures may be needed. It is also unclear on who
between 700,000 and one million. As our society should perform the procedures and whether they
grows with more adults with CP, unique new should be done in pediatric or adult hospitals.
problems need to be addressed within the frame- Most adults with CP will have some subtle
work of our healthcare system. The concept of changes in their gait with decreased endurance.
“premature aging” is an important issue for these There is the concept of muscle wasting and
patients. The majority of adults with cerebral sarcopenia of aging. In nonambulatory patients,
palsy note chronic pain, and 25% of adults in poor soft tissue coverage can lead to skin ulcers
their 20s already have the early signs of arthritis and pressure injuries. It is important for clinicians
and degenerative joint disease. Figure 1 shows a to understand that aging complaints may be
typical adult population of patients with CP (Sellier disability specific. But it is equally important to
2018). The graph clearly shows that survivorship not ignore the typical problems of aging such as
of up to 80% can be expected out to age 40. hypertension, hypercholesterolemia, and physical
The primary impairments of cerebral palsy inactivity.
include abnormal muscle tone, loss of selected Up to 80% of adults will complain of chronic
muscle control, impaired coordination and pain (Murphy 2010). Pain management solutions
Fig. 1 Aging population of 1

adults with cerebral palsy
Proportion of survivors
0.9
0.8
0.7
0.6
0 5 10 15 20 25 30 35 40
Years of survival
Number at risk
3507 3394 2825 2229 1625 1132 714 347 29
29 Aging with Cerebral Palsy: Adult Musculoskeletal Issues 425
can be difficult to achieve in the setting of adult-

hood and CP. In addition to normal adult pain
management, the management of spasticity
including botulinum toxins and oral medications
such as baclofen and benzodiazepines can be
crucial in helping control pain in adults with
CP. Physical modalities such as massage, chiro-
practic care, or wheelchair modifications with fre-
quently changing positions are also very important.
Spine
Adults with cerebral palsy may have a variety of

issues with their spine (Murphy 2009). Scoliosis
is the most common spinal disorder that affects
adolescents with CP. These neuromuscular curves
may be progressive with significant issues affect-
ing seating and negatively affecting quality of life.
Often times, pelvic obliquity is associated with
cerebral palsy and scoliosis. Unlike idiopathic
scoliosis, a very high percentage of CP curves
progress over time, which makes this a very
relevant issue for our adult patient population.
Scoliosis in CP is more common in patients
with GMFCS IV and V level function. The initial
treatment is postural management with seating Fig. 2 Typical spine fusion for cerebral palsy
modifications of the wheelchair and possible brac-
ing. Once the curve is greater than 50 , most spine Spine fusion with cerebral palsy can have
deformities will tend to progress rapidly and spine a relatively high complication rate. Infection rates
fusion should be considered (Fig. 2). have been reported between 1% and 15% (Lonstein
Posterior spinal fusion should consist of a long et al. 2012). Perioperative mortality has been
fusion from the upper thoracic spine down to the reported to be as high as 1%. An international
lower lumbar spine often and usually includes study group for spine deformity has reported a com-
fusion to the pelvis (Fig. 3). This surgical proce- plication rate of 46% but show the complications
dure is often done in young adulthood. This may were not “correlated with quality-of-life scores were
occur in individuals who were recommended to consistent with.” They demonstrated that those
have surgery during adolescence, but their fami- scores increased personal care, positioning, and
lies were initially hesitant to proceed with the comfort domains over 5 years. The conclusion of
surgical procedure. this study was that the benefits of surgery in this
Literature shows that after spinal fusion fami- patient population certainly outweigh the risk of
lies of patients with cerebral palsy report complications (Miyanji et al. 2018).
increased quality-of-life scores. Approximately Adults with cerebral palsy can also have cervi-
90% of parents and caretakers recommend the cal stenosis. There is an approximately eight
surgery and report satisfaction. Disease-specific times increased risk of cervical stenosis, instabil-
instruments such as the CPCHILD quality-of-life ity, degenerative disk disease in patients with
instrument have been shown to increase after hyperkinetic cerebral palsy (Fig. 4) (Fuji et al.
spine fusion (Miyanji et al. 2018). 1987). This can lead to radicular pain myelopathy
426 M. W. Shrader
and progressive neurological deficits. Healthcare

providers should be wary of any patient
complaining of loss of function. Anecdotally,
this is blamed on the patients “cerebral palsy.” In
reality, the neurological lesion in CP is not pro-
gressive at all and any loss of function should be a
clue to look for cervical instability.
Treatment of any type of cervical dystonia
includes medical management of dystonia. Initial
treatment also includes seating and positional
modifications. Severe dystonia and hyperkinetic
movements may be treated by cervical intrathecal
baclofen pump placement or by deep brain stim-
ulation. Surgical decompression of the cervical
spine may be indicated for rapidly progressive
neurological deficits, failure of conservative treat-
ment, or progressive functional loss. Lumbar spi-
nal stenosis can also occur at higher levels in
patients in CP (Fig. 5).
Spondylolisthesis is another spine disorder
whose incidence is higher in the cerebral palsy
Fig. 4 Cervical stenosis in cerebral palsy
Fig. 3 Typical spinal deformity in cerebral palsy Fig. 5 Lumbar stenosis in cerebral palsy
population than in those typically developed However, once severe hip dysplasia hip arthri-
adults. The risk of a spondylosis is up to 20% of tis and pain are present, the treatment options are
patients with GMFCS I–III functional levels severely limited. This is where this issue becomes
(Hennrikus et al. 1993). That is compared to very prominent and pertinent in the adult popula-
only 5–6% of the general population. The risk of tion. Significant painful hip dysplasia in adults
a slip is theoretically higher after selective dorsal with cerebral palsy typically would be treated
rhizotomy (Harada et al. 1993). Low-grade slips with salvage surgery. One of the most common
should be responsive to conservative therapy types of hip salvage surgery would be a proximal
including physical therapy and activity modifica- femoral resection or a capsule interpositional
tion. Progression to high-grade spondylolisthesis arthroplasty (Castle and Schneider 1978). In this
may require an L4 to S1 posterior spinal fusion. case, the entire proximal femur is resected below
the level of the lesser trochanter and the muscula-
ture around the hip is interposed to provide pain
Hip relief (Fig. 6). Another common technique is the
McHale salvage procedure where the femoral
The biggest issue with children and adolescents neck is resected and the proximal femur is placed
with cerebral palsy in their hips is neuromuscular into a valgus position with an osteotomy (McHale
hip dysplasia. The incidence of dysplasia in et al. 1990; McCarthy et al. 1988). Salvage sur-
patients is extremely common up to 70–90% in geries in general are not as successful as recon-
patients with GMFCS IV and V functional level. struction and carry a high complication rate. Most
Treatment is recommended with either preventive complications include continual pain proximal
surgery or hip reconstruction when the migration migration and bony prominences and heterotopic
percentage reaches a critical value of 40% or ossification (Patel et al. 2015; Kolman et al.
more. The surgical procedure is often a varus 2015).
derotational osteotomy with soft tissue release Total hip arthroplasty can be performed in
and plus or minus pelvic osteotomy. This has select individuals; however, there are significant
quite a high success rate in the literature and out- risks of complications in the cerebral palsy
comes have been shown to be better with children
of advanced age, lower migration percentages at
the time of the hip surgery, and surgeon
experience.
Untreated hip dysplasia in patients with cere-
bral palsy can lead to frank dislocation over time.
Abnormal forces acting on the femoral head occur
from contact and rubbing of the pelvis and mus-
cles wearing across the cartilage surface
(Hodgkinson et al. 2001). This pathological
position of the femoral head leads to degenerative
joint disease and pain in a large percentage of
patients, and most centers with a large experience
of treating patients with cerebral palsy acknowl-
edged that the dislocated hip is likely to be more
painful than a reduced hip (Ramstad et al. 2017).
Knowing that salvage procedures are much less
predictive than reconstruction, this knowledge-
ably has led to formalized hip surveillance with
most patients being recommended to have more of Fig. 6 Proximal femoral resection for severe degenerative
a preventative strategy. hip disease
428 M. W. Shrader
population. Osteopenia and poor bone stock can significant knee flexion contracture in an adult
lead to loosening and peri-prosthetic fractures. with CP. For those patients who have lost a sig-
Medical issues place these patients at high risk for nificant functional ambulation potential, a distal
infection. Also muscle imbalance leads to a high femoral extension osteotomy with patellar tendon
rate of dislocation. However, there are some mod- shortening is the treatment of choice.
erate series which show the results of total hip Care should be taken to evaluate the
arthroplasty especially in some community patellofemoral joint for severe degenerative
ambulators to be quite promising (Schroeder et al. arthritis. Significant patellar cartilage loss is a
2010; Raphael et al. 2010; Houdek 2017). negative indicator for progressive ambulation in
the future. Patellofemoral arthroplasty can be con-
sidered in select cases. Also, these patients may
Lower Extremity, Knee, and Foot need tricompartmental arthroplasty, just like the
typically developed general population, and total
Most problems related to the knee in an adult with knee arthroplasty again may be utilized in select
cerebral palsy result from significant knee flexure populations (Houdek 2017a, b).
issues including the flexor contractures and lack Stiff knee gait is another common knee pathol-
of knee extension strength. The most common ogy that we see in adolescents with cerebral palsy
clinical scenario that we see in adults with cerebral and in adults. This typically results from rectus
palsy is a crouched gait. This can result from the femoris spasticity and limits the amount of knee
above-stated imbalance or can result from over flexion that we can get in swing phase and pushes
lengthening heel cords in childhood. Progressive the timing of peak knee flexion to later in the gait
crouched gait places the individual at a significant cycle. The patient presenting with isolated knee
mechanical disadvantage and walking with signif- stiffness that is limiting their ability to clear the
icant increases in energy expenditure. Progression foot in swing phase may benefit from a rectus
of the crouched position can lead to significant femoris resection.
anterior knee pain and patellofemoral arthritis. Patellar instability problems can also occur in
Progression of this overall clinical complex can the adult with cerebral palsy. Traditional, sports
lead some individuals to lose their walking ability type patellar realignment surgery such as lateral
(Fig. 7). releases and mid-medial patellofemoral ligament
As a general rule, in the lower extremity in reconstructions are not likely to be effective in the
adults with cerebral palsy, soft tissue lengthening setting of cerebral palsy. These procedures may
alone is not likely to provide meaningful func- need to be augmented with a tibial tubercle
tional improvements. Accordingly, a hamstring osteotomy a more significant lateral release more
lengthening alone is unlikely going to improve a significant medial reconstructions including
vastus medialis plications and possible Galeazzi
type reconstructions with tendon woven through
the patella.
Limb malalignment can occur in the adult with
cerebral palsy. This is typically from adolescence
to his malalignment in both femoral rotation
and/or tibial rotation was not addressed as an
adolescent. In adults with closed growth plates,
rotational procedures can be performed more per-
cutaneously with intramedullary nail fixation.
This can help facilitate the rehabilitation process
that otherwise is quite significant in adults with
CP. The rotational abnormalities can result in the
Fig. 7 Severe patella alta with inferior pole fragmentation classic lever arm dysfunction with external tibial
torsion, increased femoral anteversion, and pes through the joint would be required as well as a
planovalgus feet; this also needs to be recognized medial bony procedure with either a plantar-based
in a patient who presents with gait as the lever arm closing osteotomy of the midfoot and medial
malrotations affect the knee extension plantar cuneiforms or talonavicular fusion.
flexion couple and can be a causative factor for Significant deformities should be treated with
at least a portion of the patient’s increased knee either subtalar arthrodesis or triple arthrodesis
flexion (Putz 2016a, b). (Trehan et al. 2015). The treating physician
Probably the most common surgical proce- should not be hesitant to consider hindfoot fusion
dures performed by orthopedic surgeons in adults in the setting of adults with cerebral palsy. Less
with CP revolve around foot and ankle issues. definitive procedures are unlikely to make a sig-
These can be issues that were never addressed nificant difference for this patient population, and
during childhood and adolescence, or they can the rehabilitation is so significant that the best
be consequences of some of the negative aspects procedure that can be offered to most of these
of poorly designed treatment. The best example is patients would be a definitive one with a low
a calcaneus gait and foot deformity as a result of risk of recurrence.
overlengthened heel cords. This can cause signif- First ray deformities are also common in cere-
icant functional disability for the patient, and there bral palsy, and these typically include either a
is not an adequate surgical solution for this dorsal bunion or medial bunion. The dorsal
ill-advised procedure in childhood. The most bunon occurs primarily in nonambulatory patients
effective assistance that a provider can give the but hallux valgus occurs in both ambulatory and
patient in the situation is an excellent fitting nonambulatory patients. The most appropriate
orthosis. treatment for both of these foot deformities
Repeat Achilles tendon or plantar flexion would be a first metatarsophalangeal (MTP)
lengthening in the form of gastrocnemius reces- arthrodesis which is well tolerated by adults with
sions are probably the most commonly needed cerebral palsy and greatly appreciated with a sig-
foot and ankle procedure in adults with CP. This nificantly high patient satisfaction rate.
procedure alone is quite well tolerated and usually
allows the patient to significantly improve their
gait and requires a rehabilitation that is usually Rehabilitation Issues
quite well tolerated.
Patients will present with both varus and val- The concept of doing multiple surgical procedures
gus foot deformities. For the varus foot, an ante- and a single surgical setting is encompassed by the
rior or posterior tibial tendon transfer can improve term single stage multilevel surgery or SEMLS.
a flexible deformity. But as we mentioned previ- The idea is that all muscle lengthenings transfers
ously, a soft tissue procedure like this is unlikely and correction of all bony deformities would
to provide complete resolution of the deformity. occur in a single surgical session. The major
Bony reconstruction is likely necessary for most advantage of this is a single rehabilitative session
feet issues in adults with CP, and for the varus where the patient can truly concentrate on the
foot, that would include usually a calcaneal rehabilitation and have minimal other distractions
osteotomy and possibly a midfoot osteotomy in their schedule at this critical time of their lives
as well. (Putz 2016; Gannotti et al. 2010). It has been
Pes planovalgus foot deformities in people shown to have high patient satisfaction and possi-
with cerebral palsy are often treated with calca- bly improve function with the subsequent goals of
neal osteotomies and lateral column lengthenings. having minimal mobilization with the hopefully
This alone would be unlikely to be effective in decrease risk of recurrence of deformities. The
most adults that come and present with significant timing of any orthopedic surgery for an adult can
symptomatic pes planovalgus foot deformities. be more problematic to coordinate because of
More likely, a calcaneocuboid lengthening fusion differences in the calendar of life. Most adults
430 M. W. Shrader
are no longer students, many have jobs and Joint replacement can typically be performed
careers, and family obligations make a dedicated by arthroplasty surgeons and in fact this is an area
time to concentrate on rehabilitation more difficult where they would have considerably more exper-
to obtain and schedule. However, adults also typ- tise in the technical details of the surgery, when
ically have somewhat decreased endurance in compared to pediatric surgeons. Although in this
general for aerobic type exercise compared to particular procedure, the overall clinical judgment
adolescents, and even more simple surgical pro- and expertise in dealing with cerebral palsy may
cedures may take a significant amount of time to be lacking in the typical adult reconstruction prac-
recover and rehabilitate. Therefore, a social needs tice. Foot and ankle surgery is probably the area
assessment and very intentional and deliberate that translates most easily to adult and that most of
scheduling with a family-centered care approach the procedures that would be required for an adult
is crucial for the success of any orthopedic surgery with cerebral palsy are typical procedures that are
in adults with CP. performed in the adult foot and ankle practice.
The hospital location for where these proce-
dures should take place is also a complex issue.
Health Care System Issues Most pediatric hospitals are very comfortable
for the Adult taking care of older adolescents and young adults
with childhood-onset disabilities, especially those
The question comes up of who is the best surgeon that may have intellectual disabilities, and there-
to care for these adults with CP. Certainly an adult fore, it would make sense to have pediatric facil-
orthopedic surgeon who has some expertise in ities that could be open to treating some adults.
cerebral palsy is beneficial. However, subsequent However, this can become more problematic with
subspecialty training of adult orthopedic special- older adults who have more adult type medical
ties makes this type of surgeon a rare commodity. issues such as hypertension, diabetes, and coro-
In general, most of the surgical procedures that we nary artery disease. The medical subspecialty
have discussed in this chapter are not so techni- assistance in the form of internal medicine and
cally demanding that adult specialist are not famil- intensive care specialist may not be comfortable
iar with the techniques and are quite proficient in taking care of older adults. The operating room
them. The typical missing piece for adult pro- also has issues and that they may not regularly
viders is the clinical judgment that comes with stock certain instruments that might be needed
proper patient selection in the setting of cerebral especially in spine and arthroplasty surgery. Fur-
palsy and overall comfort for dealing with adults thermore, the OR personnel may not be accus-
with disabilities. tomed to those procedures, notwithstanding the
Hip salvage surgery procedures are really in surgeons experience.
the expertise of pediatric orthopedic surgeons and Conversely, many adult hospitals are not ses-
although adult hip surgeons do occasionally per- sile with treating adults with disabilities, espe-
form these, ideally the best scenario would be cially those with childhood-onset disability like
with a combined approach for pediatric and adult cerebral palsy. However, with the longevity of
specialist together. For young adults with spine these patients with neurodevelopmental disabil-
surgery, the pediatric orthopedic surgeon often is ities increasing and more children living into
called to treat them. This is probably appropriate adulthood, the burden on adult facilities will
up until the middle portion of adulthood. How- only increase.
ever, adult spine deformity surgery can involve The perioperative management of adults with
some specialized techniques including trans- cerebral palsy also may vary quite a bit from what
foraminal type decompression, anterior proce- is typically done in the pediatric hospital setting.
dures, and more decompression type surgery In particular, consideration of the ASA class in
where adult spine surgeons may be preferred for regards to cardiac risk may be important for cer-
their technical expertise. tain patients. And anticoagulation will need to be
considered for any lower extremity surgery in ▶ Planovalgus Foot Deformity in Cerebral Palsy
adults with cerebral palsy. That is typically not ▶ Surgical Treatment of Scoliosis Due to Cerebral
needed in pediatric orthopedic surgery in the set- Palsy
ting of CP as the literature demonstrates that the ▶ Tibial Torsion and Knee Instability in Cerebral
risk of thromboembolism is quite low in these Palsy
patients. However, in adults with CP, they are
much more at risk for deep venous thrombosis
and pulmonary embolism and prophylaxis has to
be considered at some level.
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Life Care Planning for the Child
Doreen Casuto, Andrea Nebel, and Haydee Piña
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 434
Definition of a Life Care Plan . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 434
Purpose of a Life Care Plan . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 434
Goals and Environment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 435
Healthcare Providers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 435
Treatment Interventions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 436
Diagnostics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 436
Medications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 436
Laboratory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 437
Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 437
Education . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 438
Assistive Technology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 439
Nursing/Attendant Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 440
Professional Services . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 440
Benefits/Resources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 441
Recreation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 442
Organizations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 442
Home Modifications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 442
Transportation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 442
Technique . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 443
Case History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 444
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 452
Abstract
This chapter outlines the purpose and develop-
D. Casuto (*) · A. Nebel ment of a life care plan (LCP) for an individual
Rehabilitation Care Coordination, American Association
of Nurse Life Care Planners, San Diego, CA, USA with cerebral palsy. Potential care needs and
e-mail: dcasuto@rehabcarecoord.com; their most common treatment options through-
anebel@rehabcarecoord.com out the life span are described. In addition, it
H. Piña explains how the LCP can serve as a guide for
Rehabilitation Care Coordination, San Diego, CA, USA families to access community resources and
e-mail: hpina@rehabcarecoord.com

https://doi.org/10.1007/978-3-319-74558-9_230
434 D. Casuto et al.
government benefits. The chapter presents the Once monies are awarded or designated, it is
implementation of an LCP by a nurse case essential that these dollars are used to meet the
manager working with a child with cerebral specific unique needs of the individual, rather than
palsy. those of the family. For this reason, these funds
will need to be protected in one of several ways:
Keywords
Cerebral palsy · Life care planning · Case • A special needs trust is created to ensure that
management · Benefits · Community the injured party has access to community,
state, and federal services which may be lim-
ited by existence of financial income or
Introduction resources. A special needs trust should be pre-
pared by an attorney specially trained to ensure
A life care plan is a dynamic living document that all benefits are protected. If the individual
outlining the plan of care for an individual’s is a minor or adult who lacks capacity, then a
needs throughout his/her life. It is most often court petition will be required to establish the
developed (sometimes as a result of litigation) trust.
for planning for long-term needs of patients with • Blocked account is a petition filed to allow the
injuries or chronic conditions requiring complex court to oversee the disbursement of funds
ongoing healthcare interventions and manage- on behalf of a minor or adult with a disability.
ment. The life care plan is considered a flexible If the funds are held in a blocked account,
document that should be modified with the growth they can be reached without a court order and
and development of the individual with cerebral are available to the minor once age 18 is
palsy (CP). reached.
• Minor’s compromise is a petition filed with
the court to ask the court to approve settlement
Definition of a Life Care Plan of a case in which the minor is the plaintiff. The
court has supervision over a settlement or com-
The life care plan is a dynamic document based promise and is generally held in Civil Court.
upon published standards of practice, comprehen- • Guardianship or conservatorship established
sive assessment, data analysis, and research, which
by an individual who has been identified to
provides an organized, concise plan for current and
future needs with associated costs for individuals serve as the guardian (for children under age
who have experienced catastrophic injury or have 18) or conservator (for an individual age 18 or
chronic health care needs. (International Associa- older) of the monies and is bonded to ensure
tion of Rehabilitation Professionals 2009)
protection of the money against abuse.
• ABLE accounts are tax-advantaged savings
Purpose of a Life Care Plan accounts for individuals with disabilities and
their families, with a maximum contribution of
The life care plan that is developed as a result of a $15,000 per year. The ABLE Act limits eligi-
lawsuit identifies monies available for future care bility to individuals with significant disabilities
needs, but it is intended to be used to augment with an age of onset of disability before turning
medical insurance and/or community, state or fed- 26 years of age. If the age criteria are met and
eral benefits, or resources. There are instances when the receiving benefits are already under SSI
the physician’s recommended treatment may not be and/or SSDI, the individual is automatically
authorized by the insurance company or payer eligible to establish an ABLE account.
source. The funds from a special needs trust set
aside by family or lawsuit can then be used to A life care plan serves different purposes for
provide out-of-network services and/or additional families with a child with CP. It can assist in the
evaluations, treatment, therapies, and interventions. application for a special needs trust. It can serve as
30 Life Care Planning for the Child with Cerebral Palsy 435
a guide for the family in identifying the types of A nurse case manager to coordinate the imple-
physicians, frequencies of therapies, services, and mentation and modification of the treatment
equipment that individuals will need at different plan while assisting in navigating the
stages of their lives. It can serve as a guideline for healthcare and school system, attendant and
the trustee or administrator in planning for current professional services, as well as state and fed-
and future care needs ensuring that resources are eral programs
available over the life span of the individual. An orthopedic surgeon to identify musculoskel-
Often the trustee will use the life care plan as the etal issues and treatment alternatives
foundation for the rationale of purchasing or A neurologist in treating seizure disorders
going outside of covered services provided by An orthotist for the manufacture or modification
a health plan or to identify appropriate trust of braces or supports
expenditures. A psychologist to work with the child/adult
and/or family to provide support and treatment
A dentist to provide additional treatment due to
Goals and Environment oral-motor impairment and medications
impacting dental hygiene, which may require
CP is a disorder of movement, muscle tone, or sedation or anesthesia in the hospital setting
posture; therefore signs and symptoms can vary
greatly. (For detailed ▶ Chap. 21, “Classification The following specialists may be needed in the
Terminology in Cerebral Palsy,” see Sect. 1.4 course of the lifetime of an individual with CP,
“Pathology and Diagnosis Overview: depending on secondary medical problems:
Diagnosis.”)
The life care plan can assist the family and An urologist to evaluate and treat underlying
healthcare providers as a guide for the care and pathology for urinary incontinence
treatment through the comprehensive array of A developmental pediatrician to identify growth
health services required, spanning all levels or and developmental delays with treatment
intensity of care and covering all stages of life. It recommendations using a biopsychosocial
includes recommendations for all functional perspective
tasks, such as mobility, gross and fine motor func- A neuropsychologist to assist the individual
tion, communication, etc. with CP and the family in determining educa-
tional and future life care needs based on
neurocognitive issues
Healthcare Providers A psychiatrist to evaluate and prescribe medica-
tion designed to treat hyperactivity, anxiety,
An interdisciplinary team of healthcare providers depression, or issues that impact functional
is required to meet the physical, emotional, and outcomes and independence
psychological needs and maximize function A gastroenterologist to treat gastrointestinal
while ensuring safety and improving the quality issues such as reflux and constipation
of outcomes of the child or adult with CP. The A nutritionist/dietician if oral-motor or cognitive
following providers are part of the core members dysfunction impacts nutritional balance
of the interdisciplinary team and coordinate treat- A sleep specialist to identify and treat disorders
ment for the individual with CP on a regular interfering with the sleep cycle
basis: An ophthalmologist/optometrist to provide
treatment for oculomotor abnormalities and
A physical medicine and rehabilitation physi- vision impairment
cian/physiatrist to oversee the treatment plan An otolaryngologist/audiologist to evaluate for
by facilitating therapy and medication manage- possible hearing impairments and identify
ment and referrals to specialists appropriate interventions
Treatment Interventions and wheelchair equipment with elevating foot-

rest will usually be required.
Typical growth and development patterns of A spinal fusion to align and/or stabilize the spine
a child with CP are altered, resulting in deformi- may necessitate home health aides during the
ties of bones, joints, tendons, and muscles. recovery period.
CP-specific growth charts are available through Tendon lengthening/release may require immo-
the CDC. Spasticity and/or pain may affect func- bilization for several weeks following the sur-
tion. At a young age, these issues can be managed gery. Adequate support for these care needs is
with noninvasive treatments, but as the child to be included in the life care plan. Splinting
develops, the deformity may result in impairments and/or bracing may still be indicated post-
or health conditions warranting surgical surgery and/or for long-term maintenance.
intervention. Tendon transfer may be considered for improved
With any treatment intervention, the goal is to function or hygiene.
optimize function while ensuring safety, fostering Selective dorsal rhizotomy for excessive muscle
self-care, and increasing or maximizing overall tone or tightness.
quality of life. Many of the interventions may
focus on reducing muscle tightness, preventing
or treating contractures, reducing pain, and iden- Diagnostics
tifying areas that may require assistance for activ-
ities of daily living, such as promoting cleanliness Periodic hip x-rays may be indicated especially if
and assisting with bathing areas difficult to access a child is not walking to determine if the hips
(i.e., palms of hands or perineal care). remain in the sockets. The American Academy
of CP and developmental medicine have hip
Common Nonsurgical Interventions screening guidelines based on the severity of the
A life care plan may include one or more of the CP. Yearly spine x-ray may be required until
following nonsurgical interventions which are growth is completed to determine need for bracing
discussed in detail in other chapters: or scoliosis surgery. EEG (electroencephalogra-
PT, OT, and speech therapy are often begun as phy) may be necessary if the individual with CP
part of an early intervention program and, for the has a seizure disorder. Hearing and vision
child with CP, are usually part of their treatment screening/testing might be needed throughout
throughout childhood. More intensive follow-up an individual’s lifetime to adjust the treatment
physical and/or occupational therapy must be plan. Urodynamic testing to assess function of
included in life care plan after serial casting, bot- bladder is helpful to determine a treatment plan if
ulinum toxin injections, or surgery. symptoms exist. Additional diagnostics such as
magnetic resonance imaging (MRI)/computed
Common Orthopedic Surgical tomography (CT), ultrasound, DXA/DEXA,
Interventions x-ray, etc. may be indicated with complications.
After nonsurgical treatment interventions
have been explored or implemented, surgical
intervention may be considered to maintain Medications
and/or improve alignment, mobility, and pain
relief and maximize gross and fine motor function. A variety of medications are available to treat the
The following examples are discussed in detail different symptoms and/or disorders for an indi-
throughout the chapters. The life care plan may vidual with CP. Detailed information about each
include: medication regimen and/or condition is available
throughout the textbook. Listed below are some of
An osteotomy to correct hip dislocation. In the the available treatments included in a life
post-op period, bowel and bladder management care plan.
Medication for Spasticity Medication for Depression/Anxiety

Several different medications are available to treat Selective serotonin reuptake inhibitors (SSRIs)
spasticity, relieve pain, and help achieve greater are some of the commonly prescribed
range of motion. Baclofen (Lioresal) can be medications.
administered by mouth (tablets) or via a pump
into the intrathecal space of the spine, allowing
for decreased dosage. The pump requires surgical Laboratory
trial, placement, and regular follow-up visits
every 2–6 months with physician for refill and All medications have potential side effects. It is
periodic surgical replacement of the battery, important to review the indications for periodic
device, and/or tubing. Diazepam (Valium), clo- laboratory monitoring with the prescribing
nazepam, cyclobenzaprine (Flexeril), dantrolene healthcare provider so that it can be incorporated
(Dantrium), and tizanidine (Zanaflex) are some into the treatment plan. This can include regular
alternative antispasticity medications. blood work and/or urinary tests.
Some of the antiseizure medications require
Antiepileptic Medication regular monitoring of the serum level to determine
Seizures may be controlled with medication, keto- a therapeutic drug concentration level in the body.
genic diet, a device called the vagal nerve stimu- If complications arise, such as pressure wounds,
lator, or epilepsy surgery and are discussed in infections, nutritional imbalance, etc., addi-
detail throughout the book. The following listed tional laboratory tests might be required to man-
medications represent some of the available age these.
medication treatment options to control seizure
activity: carbamazepine (Tegretol), levetiracetam
(Keppra), lamotrigine (Lamictal), gabapentin Therapy
(Neurontin), and phenytoin (Dilantin). A combi-
nation of two or sometimes even three antiepilep- Therapies promote, improve, and/or maximize
tics may be prescribed. Certain medications function while reducing pain and alleviating
require routine or periodic blood level monitoring, symptoms. This allows the patient to focus on
and electroencephalogram (EEG) may be improving abilities and independence at home
recommended for follow-up. and school and in the community. Most therapies
include evaluation and treatments prescribed at
Cognitive and Behavioral Medication different times over their lifespan. Therapists
Medications such as Adderall (amphetamine work collaboratively with physicians, nurses,
salt combo) and methylphenidate (Ritalin) are teachers, parents, caregivers, and other profes-
commonly prescribed for attention-deficit/ sionals involved in the care and treatment. Each
hyperactivity disorder (ADHD). Propranolol therapy available is discussed in detail in other
(Inderal) may be indicated to treat behavioral chapters throughout this book. Traditional, non-
issues. traditional, and mental health therapies may be
included in a life care plan.
Medication for Incontinence
Imipramine (Tofranil) or desmopressin-acetate Traditional Therapy
(DDAVP) nasal spray may be prescribed. Physical therapy for gross motor skills and
mobility; occupational therapy to address activ-
Medication for Acid Reflux ities of daily living and instrumental daily living
Proton pump inhibitors (PPI) such as omeprazole skills and oral-motor development; speech and
(Prilosec) or H2 blockers such as ranitidine language therapy to address oral-motor skills
(Zantac) may be beneficial in treating this and verbal communication and for identification
condition. and implementation of alternative communication
systems; sensory integration therapy for impairments, dyslexia, or cognitive problems,

sensory processing; recreational therapy; and assistive technology can help her function within
relaxation therapy are some of the therapies the classroom. These tools include any type of
available. equipment or device that helps students to com-
pensate for their learning disabilities. Each state is
Nontraditional Therapy different, and often the school system is the key to
The individualized life care plan will include non- accessing a variety of services. Knowledge of
traditional therapies such as music therapy to potential resources within the state may help the
improve cognitive function, motor skills, sensory family to maximize the benefits they receive for
skills, and social skills; equine therapy, also their child.
known as horse therapy; pet therapy; and After age 22, local state and county programs
aquatic therapy. can provide pre-employment or volunteer transi-
tion services or further education through local
Mental Health Therapy community colleges and universities.
Some mental health therapies available are as
follows: play therapy to help children express School
and communicate their feelings and develop rela- Some children with CP require special education
tionships; biofeedback to promote relaxation by programs that are offered at local public schools,
learning how to harness the power of the mind to providing an array of options for their special
gain control over body functions; behavioral needs. These children are entitled to participate
therapy to empower the individual and family to in educational programs from age 3 until they
control behavioral responses in social situations; either graduate from high school or receive a
and cognitive behavioral therapy to provide certificate of completion through their high
strategies to alter reactions to difficult situations school. If the special education program at
and emotions. the public school is unable to meet the individ-
ual’s needs, the school may be required to
place the child in a nonpublic/private school.
Education These schools may be responsible for providing
necessary accommodations to meet the child’s
The Individuals with Disabilities Education Act needs.
(IDEA) requires public schools to make available Schools are also required to provide resources
to all eligible children with disabilities free and for children with CP who require accommoda-
appropriate public education in the least restrictions, adaptive equipment, modifications, or one-
tive environment appropriate to their individual to-one aide for certain or all classes to meet their
needs. It also requires that the school system educational needs. Their education opportunities
develop individualized educational plans (IEP) should not be impacted by their physical, motor,
which delineate needs and services that the school or communication ability. This is often addressed
system will provide. It is important that the par- through an IEP to ensure appropriate education
ents and caregivers are knowledgeable about the services. Special education services during the
IEP process and how to advocate for their child’s school breaks, known as Extended School Year
needs. Their ability to do this may make the dif- (ESY), may be part of an IEP. These services are
ference in obtaining such benefits. Some of the individualized to maintain skills and continue pro-
benefits provided by the school district are one-to- gress toward set goals.
one or group therapy services (physical, occupa-
tional, speech, vision, and audiology therapy), an Educational Advocate
assigned aide during the school day, or supervised An educational advocate is a specially trained
bus transportation, as well as adaptive physical professional in education and disability law and
education (APE). If the student has physical is responsible to stay current with the regulations
that affect a child in an educational setting. An tech equipment. The following equipment items
educational advocate represents the best interest and/or devices might be considered:
of the child and works with the family, caregivers,
and the school personnel to assure that the child Activities of Daily Living Equipment
receives appropriate educational services in the Eating, bathing, dressing, grooming, and toileting
most appropriate educational environment under are all self-care activities which individuals with
the provisions of IDEA. CP may have difficulty performing independently
or with assistance. Equipment such as adaptation
Educational Therapist/Tutor for a toilet seat to compensate for the lack of motor
Educational therapists identify and assess student control, bath chairs, transfer boards, dressing aids,
learning needs, creating and implementing indi- and installed grab bars are all items enabling par-
vidual educational therapy plans specific to the ticipation and/or independence in self-care.
learning goals for each student. A tutor may
focus on specific subjects and review skills that Mobility Equipment
have already been taught in class. A physical therapist assesses the individual with
CP to determine which mobility equipment is
Vocational Rehabilitation Program most appropriate to achieve the highest level
This program enables individuals with functional, of independence. Walking sticks and canes,
psychological, and/or developmental impair- crutches, walkers, standers, lifts, wheelchairs,
ments to overcome barriers to access education and scooters are different types of mobility aides
and training for employment in appropriate occu- which can be modified and customized to fit the
pations. Services offered include educational individual’s needs. For some individuals, a chest
counseling, job training, apprenticeships, and support walker or reverse walker might be the best
non-paid work experiences after a comprehensive option, while for another child, a suspension
evaluation which determines abilities, skills, and walker is more appropriate. An installed ceiling
interests. lift might be a better option for one family, while a
Hoyer transfer lift is suitable for another. Regular
Day Program reassessment and modifications are needed, and
Adult day programs promote community inclu- maintenance of the equipment is required.
sion, life skills training, and continued develop-
ment of personal competencies. Programs are Assistive Technology for Cognition
typically offered 5 days per week, full or part Assistive technology for cognition aids such
days, and typically operate during normal busi- as computers or electrical assistive devices can
ness hours. Some programs offer additional days help with memory, attention, or other cognitive
or evenings. challenges and enables individuals to have greater
control over their own lives. Speech and commu-
nication devices, as well as memory aids,
Assistive Technology are available in many variations and customized
to the individual’s needs.
Due to the neuromuscular disorder associated
with CP, individuals may require adaptive equip- Orthotic Devices
ment and/or assistive devices offering support in The goals of orthotics, such as splints and braces,
completing activities of daily living, enhancing are to ensure the individual with CP maintains the
mobility and/or communication, and improving level of mobility by correcting physical issues that
and maintaining functional abilities. The devices interfere with function. Orthotics might be pre-
help achieve greater independence and self- fabricated or specially manufactured in specific
confidence in all areas of function. They can sizes and must be modified and replaced on a
include low-tech assistive devices and/or high- regular basis.
Nursing/Attendant Care provided through a care attendant at home, in a

healthcare facility, or at an adult day center.
Individuals with CP might need others to provide
care for them. The situation for each person is Life Skills Coach
unique, and their care needs vary in numbers of A life skills coach, also known as a life coach, is a
hours and frequency, depending on severity and mentor, coach, and teacher, helping individuals to
age of the care recipient. An individual might develop skills needed to integrate into the com-
need support/assistance for ADL’s (Activities of munity, pursue opportunities for employment, and
Daily Living which refers to self-care activities improve quality of life. Hours of training differ,
such as bathing, eating, etc.), IADL’s (Instrumen- depending on the individual’s functional and cog-
tal Activities of Daily Living which refers to nitive abilities and the goals set.
activities letting an individual live independently
in a community such as managing money, Care Facility
cleaning the house, etc.), cognition, or supervi- If the option of living at home with family mem-
sion. Providers who specialize in different areas bers and/or caregivers is not available for an indi-
are available, and their function and duties are vidual with CP, a residential facility, such as a
described below: board and care, assisted living or skilled nursing
facility or a group home, may have to be consid-
Care Attendant ered. This will often be the scenario later in life,
A care attendant is a person with a medical back- due to parents/family members no longer being
ground and/or specific training, aiding with daily able to care for their loved one.
tasks and chores. Some of their duties include
providing/assisting with a bath, preparing meals,
executing a home exercise program such as pas- Professional Services
sive range of motion, accompanying/driving to
appointments, and providing a safe environment Fiduciary/Trustee
for the care recipient to thrive in. A care attendant A fiduciary serving in the capacity of a trustee is
will provide care where the care recipient is an individual person, bank, or member of a board
located, which may be at home with family, dur- who has the control/powers of administration of
ing school, in a day program, during outings, or in assets for the benefit of a third party. They have
a residential facility/skilled nursing facility. the legal responsibility to carry out the terms of
Certain services such a complex wound care, the trust as stated in the trust document, which
tube feeding, intravenous therapy, injections, generally includes managing money that has been
pulmonary treatments, etc. can only be provided set aside in a trust, such as a special needs trust, for
by skilled care personnel, such as a registered the beneficiary. Some of their responsibilities
nurse (RN), licensed vocational nurse (LVN), or might include assisting the beneficiary in
licensed practical nurse (LPN). Nonmedical home maintaining eligibility for public benefits pro-
care may be considered to provide relief for family grams, bookkeeping and accounting of trust activ-
and/or caregivers and might allow an individual ities, appropriate investment of trust, and tax
with CP to continue to live in his/her current home reporting for the trust. To provide this service,
rather than having to move into a care facility. they must inquire into the needs and welfare of
the trust beneficiary, work with family members
Respite Care and care team, as well as consider both current and
In situations where the family members provide future needs of the beneficiary.
most care hours, respite care provides short-term
relief for primary caregivers. This can be arranged Attorney
for an afternoon, several days, weekends, or A special needs trust attorney can provide advice
weeks and on a regular basis. Care can be on public benefits issues and set up the special
needs trust. Once funds are deposited into the qualify for disability benefits depends on your age
trust, an attorney can provide guidance on making when you become disabled. Generally, you need
distributions in order to preserve the beneficiary’s 40 credits, 20 of which were earned in the last
public benefits. A special needs trust provides 10 years ending with the year you become dis-
financial support for the individual without jeop- abled. However, younger workers may qualify
ardizing government benefits. Leaving money in a with fewer credits. If you are under age 24, you
special needs trust allows for improved quality can earn 6 credits for 1.5 years of work, and if you
of life. are 24–30 years, you can earn 8–18 credits for
2–4.5 years of work. Individuals who have a med-
Conservatorship/Guardianship ical condition that prevents him/her from working
A guardianship/conservatorship is a legal rela- or is expected to prevent him/her from working
tionship created when a person or institution is for at least 12 months is eligible to receive bene-
named in a will or assigned by the court to take fits. If a parent is retired, is deceased, or has a
care of minor children or incompetent adults. A disability, a child or an adult may qualify.
guardianship is for a minor, and the minor remains
under court supervision until the child reaches Medi-Cal (California)/Medicaid (All Other
majority at 18. Conservatorship is a legal concept States)
whereby a court appoints a person to manage This program is funded by federal and states taxes
an incapacitated adult’s financial and personal and pays for a variety of medical, psychological,
affairs. The conservator’s duties include oversee- and dental services for children/adults with lim-
ing finances, establishing and monitoring the ited income and resources. There are income and
physical care of the conservatee, and managing resource restrictions, and the applicant must be a
living arrangements. resident of the state where the application is filed.
If an individual is eligible for SSI, he/she is
automatically eligible for Medi-Cal/Medicaid.
Benefits/Resources Medi-Cal/Medicaid Waiver Institutional Deeming
(ID) is a process to obtain full scope unrestricted
The goal of applying for benefits is to access funds Medi-Cal without a share of cost for disabled
from organizations that serve the needs of the individuals under age 18. Through ID, the indi-
disabled child/adult. Differences within each pro- vidual’s family income and resources are not
gram will vary from state to state. Social Security taken into consideration; the individual is
and Medi-Cal/Medicaid benefits are funded by the assessed on his/her own merit.
federal government, and the amount allocated for
each state will vary. Developmental Disability Services
This program provides services and supports to
Federal and State Benefit Programs individuals with developmental disabilities. The
following listed programs represent some of the
Social Security Benefits (All States) programs available in the United States. These
and Supplemental Security Income (SSI) programs are offered beginning from birth and
This program pays benefits to disabled children/ over the life span. Titles of these programs differ
adults who have limited income and resources. A in each state:
special needs trust (SNT) is not counted as a
resource. California – Regional Center
Utah – The Division of Services for People with
Social Security Disability Insurance (SSDI) Disabilities (DSPD)
This program pays benefits to individuals who Colorado – Regional Center Operations
have accumulated a designated number of work (DRCO)/Division for Developmental Disabil-
credits. The number of work credits you need to ities (DDD)
Other programs are offered from birth through specifically designed for their enjoyment. There are
age 21, with some examples below: camps available for specific disabilities, benefiting
participants with increased independence and self-
California – California Children Services (CCS) confidence and providing the opportunity to inter-
Arizona – The Children’s Rehabilitative Services act with other children, develop friendships, and
(CRS) build meaningful relationships. The following
Florida – Children’s Medical Services (CMS) website offers a list of summer camps designed to
New York – Children with Special Health Care accommodate individuals with CP throughout the
Needs Program (CYSHCN) USA: www.veryspecialcamps.com/summer/cere
Ohio – Bureau for Children with Medical Hand- bral-palsy-camps/.
icaps (BCMH)
Texas – Children with Special Health Care Needs
(CSHCN) Organizations
Department of Social Services Living with CP is different for each person
The program provides in-home support to disabled affected. Local or online support groups as well
individuals with limited income and who are Medi- as CP organizations can provide information,
Cal/Medicaid eligible to remain safely in their home. helpful resources, and support.
Eligibility varies by state; examples are below. Cerebralpalsy.org, Cerebralpalsygroup.com,
International CP Society, and MyChild at
California – In-Home-Support-Services/Home CerebralPalsy.org are some of the existing orga-
and Community-Based Services (HCBS) nizations. United Cerebral Palsy is an organiza-
Utah – Home and Community-Based Services tion that educates, advocates, and provides
(HCBS)/the Aging Waiver program support services to ensure a life without limits
Arizona – Arizona Long-Term Care System for individuals with CP and their families.
(ALTCS)
Georgia – Community Care Services Program
(CCSP) Home Modifications
New York – Managed Long-Term Care Program
(MLTC) Home modifications are changes made to the
Colorado – Consumer-Directed Attendant Sup- home to provide a barrier-free environment. It is
port Services (CDASS) crucial to eliminate barriers and allow accessibil-
Department of Rehabilitation ity to promote independence, improve the life of
The Department of Rehabilitation (DOR) is a the individual with CP, and prevent isolation and
state-funded program in all states that provides lack of participation. Those can be simple
services to individuals with a physical or mental changes, such as installed grab bars, lever handles
impairment that substantially impedes their ability on doors, or more involved projects such as
to secure employment and vocational rehabilita- adding a ramp, installing a lift for interior stairs,
tion services. Receiving social security benefits or or modifying a bathroom for accessibility.
possessing a valid ticket to work presumes eligi-
bility for DOR services.
Transportation
Recreation Transportation provides a lifeline for people with

disabilities to access community, medical, and non-
Camps medical appointments, education, employment, etc.
Summer camps function as a way for individuals The Americans with Disabilities Act (ADA) of
of all ages to spend time participating in activities 1990 requires accessibility for public transportation.
Despite ADA, transportation services are often not the care needs is collected. Accurate and compre-
accessible to individuals with disabilities as ade- hensive nursing diagnoses determine interven-
quate funding may not be provided to implement tions and outcomes and guide planning and
the policies. Alternative transportation options are implementation of care. Evidence-based nursing
available but vary greatly by state and city. The diagnoses are provided by the organization
purchase of a modified van equipped with a ramp NANDA International. The healthcare team
or lift to accommodate wheelchair-dependent indi- members follow the plan of care with the
viduals may be considered where public transporta- resources available, routinely evaluate and deter-
tion is limited or unavailable. mine if the expected outcomes were achieved, and
modify the care plan when necessary. The life care
plan fulfills the role of advocating for the individ-
Technique ual with CP and educating healthcare profes-
sionals to help plan for the future. Essential
Although a variety of professionals are qualified elements, such as individual and caregiver goals,
to create a life care plan, as nurses and authors of reasonable expectations, anticipated functional
this chapter, the technique for a nurse life care outcomes, and the means to achieve them, are
plan will be explained. addressed.
The American Association of Nurse Life Care Creating the life care plan, collaborating with
Planners claims that the American Nurses Asso- healthcare providers, using scientific evidence-
ciation (ANA) Scope and Standards of Practice is based guidelines, nursing research, and identify-
the defining conceptual base for nurse life care ing community resources and healthcare systems
planning. Nurse life care planners use critical are some of the functions of a nurse life care
thinking skills of the nursing process (Fig. 1) to planner. The cost associated with each care need
formulate a plan of care for an individual’s life- is outlined in the life care plan and obtained from
time, often involving decades of healthcare and providers, vendors, and other available reliable
other needs. The nurse life care planner applies the sources reflecting the value at the time
nursing process and then develops the plan, which researched. An economist determines the actuar-
includes the resources necessary to meet current ial figures.
and future medical and nonmedical needs and the
costs of these resources.
An assessment of the individual is performed,
and through appropriate methods, data relevant to
Assessment
Evaluation Diagnosis
Outcome
Implementation
Planning
Fig. 1 Critical thinking skills of the nursing process Picture 1 X at age 7

LIFE CARE PLAN PAGE 2
CARE NEED DESCRIPTION/ RATIONALE

NEUROLOGIST To monitor and treat seizures
Now 4-6X/year through age 18, then 2X/year
Pediatric follow up visit $90-$110
Adult initial evaluation $305
Adult follow up visit @ $90-$110
EEG @ $305-$325/time, every 2-3 years until age 18, then every 5-10
years
PHYSIATRIST To evaluate and make treatment recommendations
4-6X/year until age 18, then 2-4X/year
Initial evaluation $175-$275
Follow up visit $75-$95/time
ORTHOPEDIST To evaluate and make treatment recommendations
1-2X/year until age 18
Initial evaluation $187
Follow up visit $50-$110
Possible Heel Cord Lengthening For 1 leg
Surgeon and Anesthesia @ $680-$1628
Same day surgery or 1-day hospital stay @ $8277-$14586
Cast@ $203.50, 2X
GASTROENTEROLOGIST To monitor gastrointestinal issues, yearly until age 18
ENT To evaluate and make treatment recommendations
2-4X/year now through age 18, then 1-2X/year
Adult initial evaluation $100-$125
Adult follow up visit $65-$150
Audiogram $164, 1X
AUDIOLOGIST Every 6 months until age 7-8, then annually
Follow up visit @ $120-$150
Additional testing @$100-$300/time, 3-4X over life time
HEARING AIDES Currently X has bilateral hearing aides with molds @ $2690, replace
every 3 years until he receives his cochlear implant when he will only
need 1 hearing aide
Molds @ $50 per hearing aide, 2 needed until cochlear implant, replace 1
or 2 molds every 4 months until age 6, then every 6 months until age 16,
thereafter yearly
Batteries @ $3.25/month for 1 hearing aide, $6.55/month for 2 hearing
aides
Insurance for loss or damage of hearing aides - 1st year free of charge,
thereafter @ $120/year
Fig. 2 X’s life care plan
Case History cost, and advocacy while functioning as a crucial

guide for implementation of care by the family
The following described journey of X, who was and nurse case manager (Picture 1).
diagnosed with CP at age 2, demonstrates the X was born in 2000 and contracted pneumococ-
value and effectiveness of creating a life care cal meningitis at 5 months of age. As a result, he was
plan to outline future care needs, associated diagnosed with CP and developed a Lennox-

- Cochlear Implants Initial work up
Comprehensive Audiology evaluation @ $125, 1X
Acoustic Reflex @ $45, 1X
Tympanometry @ $55, 1X
Otoacoustic emission @ $100, 1X
Brain stem Evoked Response @$375, 1X
Cochlear Implant consultation @ $100, 1X
Psychological evaluation $250 (2 hours)
Test Assistant (under 6 years) @ $60,
Otological evaluation @ $90-$375, 1X
CT Scan @ $675, 1X
Surgery - every 10-20/years (first within next 1-3 years)

Surgeon $6360
Facial Nerve Monitoring @ $600-$900
Diagnostic Cochlear Implant Test Battery @ $100
Anesthesia fee @ $1500-$1600
Outpatient surgery suite and supplies @ $6000-$8000
Cochlear device @$18,000
Service contract on speech processor (external portion) has 3-year

warranty, additional warranty after 3 years @ $450 every 2 years
Service contract on head set (coil, microphone, magnet and cables) has 3-
year warranty with initial set up, additional warranty after 3 years @
$195 every 2 years
Insurance for loss or accidental damage of speech processor @ $195-year
(homeowners should cover theft)
COCHLEAR DEVICE FOLLOW Device set up @ $125/hour for 35 hours within 1 year, thereafter 3 hours
UP AFTER IMPLANTATION per year
Cochlear implant speech perception test @$60, 2-8 hours 2X/year for 2
years, then yearly
Mapping @ $125/hour, 2X/year for 2 years, then yearly
Cochlear Implant Check @ $60/time, 2X/year for 2 years, then yearly
Speech/Language Evaluation @ $360, 2X/year for 2 years, then yearly
Prosthetic Training $60 for 30 minutes, 2X/year for 2 years, then yearly
Test assistant @ $60, 2X/year for 2 years
ADDITIONAL SUPPLIES FOR Additional supplies
COCHLEAR IMPLANT Speech processor @ $6000, every 5 years
Padded pouch @$30, 2 per year
Lapel clips @ $12/=5, 2-5 packages per year
Dry pack @ $18, yearly
Magnet @ $36, 1 per year
Ear hook @ $9/#5, 2-5 packages every year
Signal checker @ $24, every 3 years
Lapel microphone @ $90 - $104 replace every 1-3 years
TV Hi-Fi cable @ $150, replace every 3-5 years, should be available for
use within the school district
Personal Audio cable - for use with computer, etc. @ $72, every 3 years
Telecoil @ $108, every 3 years
Telephone adapter @ $50, every 1-3 years
FM cable for community usage @ $90, every 3 years
Rechargeable Batteries @ $12 for #4, 2 packages every year, charger
every year @ $50/time


OPHTHALMOLOGIST Annual evaluation
Adult initial evaluation $200
Adult follow up visit $160/time
Glasses @ $100-$200/time, yearly
- Vision therapy 2-4X over life time
Initial evaluation @ $79
Vision therapy sessions @ $75/session, 8-24 sessions with MD follow up
in between at no additional charge
PEDIATRICIAN/ To provide treatment more than the typical child/adult
INTERNAL MEDICINE 3-4X/year until age 18, then 2X/year more
Pediatrician follow up visit @ $35/visit
Adult internal medicine follow up visit @ $43/visit
Flu @ $20/year
Pneumo vaccine @ $39, 1X
ADDITIONAL MEDICAL To provide treatment for additional care needs
SPECIALISTS 1-2X/year until age 18, then 2X/year
Evaluation @ $250-$250/time
DENTIST To provide treatment more than the typical child/adult
2X/year
Exam $25/time
Cleaning $25-$50/time
Sedation with cleaning at an additional $150 above cleaning price,
1X/year
PODIATRIST To deal with foot and nail issues related to disability
Now 1X/year until age 18, then 2-4X/year
Follow up visit $40
Ingrown nail treatment $115, 2-3X over life time
MEDICATIONS Currently on: Phenobarbital 7cc 2X/day
Future medications for seizures @ $120-$150/month
LAB WORK 2-3X/year
CBC @ $46.41-$88.20
BMP @ $102.67-$144
Seizure medication level @ $86.50-$131.04/time
DIAGNOSTIC STUDIES Spine films 4-5X @ $215-$375/time
Chest X-ray @ $150, 3-4X over life time
KUB $187.50, 3-4X over life time
Swallowing evaluation @ $315 and $75 for MD reading, 1X over life
time
EMERGENCY ROOM 1X/year
ER $500-$1000, MD @ $150-$250
HOSPITALIZATION 1 day per year
Hospitalization @ $2375 - $2988/day
MD @ $75-$150/day
NUTRITIONIST To monitor nutritional needs
Initially 4-6X/year for 1-2 years, then 2X/year for 2 years
Initial evaluation $80 (1.5 hours)
Follow up visit $40/hour


PHYSICAL THERAPY Now through age 6,3X/week
Age 7-10, 2X/week
Age 10-15, weekly
Age 15-21, monthly
Initial evaluation $210-S216
OCCUPATIONAL THERAPY Now through age 6, 3X/week
Age 7-10, 2X/week
Age 10-15, weekly
Age 15-21, monthly
SPEECH THERAPY In addition to services provided by school district
Now to age 6, 3-5X/week
Age 6-10, 3X/week
Age 10-18, 2X/week
Follow up visit $90-$199.50/session
REHABILITATION Starting at age 18, evaluation with 2 treatments annually for 5 years, then
RE-EVALUATION every 5 years
Physical therapy evaluation $210-$216
Physical therapy treatment $95-$207 /time
Occupational therapy evaluation $210-$216
Occupational therapy treatment $90-$207/time
Speech therapy evaluation $260-$320
Speech therapy treatment $90-$199.50/time
COUNSELING To assist X and his family with meeting his care needs
Weekly for 1 year now and 100 additional sessions over his life time
Follow up visit $120-$135/session
COMPUTER Cost of computer @ $1200-$2000, now and every 3 years
Enlarged screen @ $1000-$1399, with purchase of each computer
Set up $150
Initial programs @ $500
Yearly programs @ $100-$300
Training @ $95/hour, initially 10 hours, thereafter 3 hours per quarter
Maintenance @ $100-$200/year
Internet @ $21.95/month
AUGMENTATIVE To assist with communication
COMMUNICATION Parakeet 15 @ $550 cost, 2X
Accessories @ $200-$300
Maintenance @ $220/year
9-volt battery every month @ $2.59
Macaw II - $2500 cost, 1X
Accessories $200-$500
Maintenance @ $220/yr. after first year
Training @ $90-199.50/hour, initially 20-30 hours, then 5-10 hours
quarterly for 1 year, then 10 hours every 6 months
EDUCATIONAL ADVOCATE Now through age 21
Intake or evaluation fee @ $150-$500
5-10 hours for observation, attendance at IEP or additional meetings @
$75-$110/hour


ATTENDANT CARE Now until age 6 - 10 hours per day
Age 6 -21 - 6 hours per day for school days (180 day /year) and 10 hours
for non-school days
Agency @ $15.50-$17.50/hour or Agency Live-in $140-$150/day
OR
Private Placement fee $150-$350 (guarantee placement for 90 days) or
Placement fee $480 (guarantee placement for 1 year), 3X
Live in private rate @ $80-$100/day
Age 21- Options
1) Home with live in
Agency Live-in $140-$150/day
OR
Private live in @ $80-$100/day with placement fee of $150-$350 or
$480, 4-5X
2) Residential
Casa Colina @ @3900-$4500/month
Learning Services @ $295/day
RESPITE CARE To provide the parents and family time away or with additional assistance
during vacations with X
Monthly respite for 3 days until age 18 - 21 - Agency Live-in $140 -
$150/day
To enable X or participate in family vacation by providing live-in
attendant to go with family to provide for his care needs, 1 week per year
until age 18-21
Agency Live-in $140-$150/day or Private live-in @ $80-$100/day
CASE MANAGER To assist with accessing services and identifying resources
Now through age 6, 4 hours per month
Ages 7-15, 3 hours per month
Ages 15-18, 4 hours per month
thereafter 12-24 hours per year
Cost @ $80-$85/hour
FIDUCIARY To assist with bookkeeping and reporting to the courts
Fiduciary for 5-10 hours per month @ $75-$150/hour
Attorney cost for court reporting @ $500-$1000/year
HANDYMAN To maintain the safety of the environment
Starting at age 18, $15/hour for 2 hours 4X/year *
*needed if X is not residing in a residential placement
HOUSEKEEPING Starting at age 18, 2X/week for 4-6 hours per time
Initial visit @ $79 for 4 hours, thereafter @ $64-$95 for 4-6 hours per
time*
*needed if X is not residing in a residential placement
QUICKIE PEDIATRIC Now and replace every 3-5 years until age 18
(MANUAL) Cost of Zippie 2 Wheelchair @ $1550
WHEELCHAIR Lateral supports @ $200-$300
Solid back and seat @$500-$600
Tray table @ $200, with purchase of each wheelchair
QUICKIE ADULT Starting at age 18, purchase every 5-7 years
(MANUAL) Cost of Quickie 2 wheelchair @ $1850, maintenance @ $150-$250/year
WHEELCHAIR Tray table @ $200 with purchase of each wheelchair


POWER WHEELCHAIR Starting at age 8-10, replace every 7-10 years
Cost of Quickie @ $9475, Attendant control @ $795
Tray table @ $200 with purchase of each wheelchair
Batteries @ $310/pair, 2 needed yearly
WHEELCHAIR CUSHION Cushions to prevent skin breakdown or shearing
Cost of Roho @ $399-$439 or Jay @ $459.95, replace 1 cushion every 2-
3 years, replace cover every year @ $74.95/each
STANDER/ Cost of stander for child/young adult @ $1125-$2500, 2X starting now,
GRANDSTAND with maintenance @ $250 /year, tray table included
Purchase of Grandstand starting at age 18 and 1 additional time over life
time, cost @ $2595, includes tray table, maintenance @ $250-$500/year
POWER BED WITH Starting at age 10-13, purchase bed every 10 years
SIDE RAILS Cost of twin power bed @ $1178-$1378.95, Maintenance @ $50/year.
Replace mattress every 3 year @ $169-$399.99
ANKLE FOOT ORTHOSIS To assist with foot positioning, transfers and gait
Cost of AFO @ $300-$700/each, now and every 2-3 years until age 18,
then every 3 -5 years
WALKER Gait trainer 2X @ $254-$275, maintenance @ $25/year for 5-10 years
Rear walker 2X @ $279-$319.95, maintenance tips @ $7.99/pair and
wheels @ $39.95-$49.95/pair, yearly until age 18-21
Adult wheeled walker with brakes and seat (starting at age 16-18) @
$445,every 5 years, maintenance @ $20/year
ADL EQUIPMENT Handheld shower nozzle @ $44.95, now and every 2-3 years
Long-handled sponge @ $3.95, replace yearly after age 8-10
Folding shower chair with back @ $71, 2X, tips @ $15.80, every other
year
Cost of additional ADL equipment @ $300-$500 now and every 2 years
until age 21, then every 3-5 years
ADAPTIVE CLOTHING Cost @ $100-$200/yearly
TUB/SHOWER CHAIR To provide for bathing needs
Cost of shower/tub bench with back @ $98.60-$117. starting at age 5,
replace every 3-5 years, every 5 years after age 18
TOILET SEAT Adaptive toilet seat @ $493.95-$499.95, 2X
WIRELESS MONITOR Now and every 5-7 years @ $19.95-$59.95
Battery (9-volt) @ $3.00, every 1-2 months
MEDIC ALERT To identify issues related to X’s disability
Cost of bracelet/pendant @ $35. Cost to maintain information in national
file @ $15/year. Replacement of bracelet/pendant @ $25 every 2-3
year until age 18-21, then every 5 years
THERAPY/PLAY EQUIPMENT Initial equipment @ $500-$900, purchase of additional equipment @
$100-$200 every 2-3 years until age 18
ELECTRIC TOOTHBRUSH Cost of Oral B Kid’s Power Brush @$29.99, replace every 2 years until
age 16
Cost of Oral B Adult Power Brush @ $49.99 from age 16, replace every
2 years, replacement brushes @ $19.99 for 3 /pk, every 3 months


BOWEL AND BLADDER To provide for bowel and bladder management needs
MANAGEMENT Cost of small diapers @ $64.25 for #104, 5-6 per day
Cost of medium diapers @ $64.25 for #88, 3-4 per day
Cost of large diapers @ $64.25 for #72, 3-4 per day
Hygiene wipes @ $5.79 for # 46
Chux @ $39.95 for #90
Gloves @ $9.99 for #100
Skin shield spray @ $5.99/bottle
K-Y Jelly @ $1.99 4oz/tube
Magic Bullet @ $19.95/#12
EQUINE THERAPY To assist X with his balance and coordination
Cost of weekly session @ $100/month until age 8-10
AQUATICS AND FITNESS YMCA-Child enrollment @ $75/year
PROGRAM Adult (age 18 and up) enrollment @ $75/year with monthly fees @ $39
Trainer @ $35/hour, starting at age 18-21, monthly
Private swimming lessons @ $120 for 8 - 30 min sessions, 5 series per
year through age 6
Group swimming lessons @ $42 for 12 - 30 min sessions, 3 series per
year until age 18
24 Hour Fitness-
Enrollment @ $107 1X
Monthly fees @ $19
Trainer @ $50/hour
SUMMER CAMP 2 weeks per year
Camp Harmon @ $726-$847, 6-7-day camp, ages 8-40
Camp Eagle Lake @ $736-$920, 8-10-day camp, ages 10-25
Happy Adventure Day Camp @ Santa Barbara @ $90/week, 3-week
session, ages 5-18
VAN To assist X with transportation in the community now, and every 10
years or 60,000 miles
Van @ $20,000,-$30,000
Conversion @ $14,000-$17,000
EZ Lock @ $1295
AAA @ $64 first year, then $44/year thereafter
Cell phone @ $100-$200,every 3-5 years
Cellular phone service @ $19.99/month
HOME MODIFICATIONS To assist with care needs, entrance and exit into home, 1-2X over life
time
Cost of ramps @ $5,000-$10,000
Cost of wheelchair accessible bathroom @ $20,000-$30,000
ORGANIZATIONS To provide resources for the family and care givers regarding disabilities.
Epilepsy Foundation, Betty Clooney Foundation and Brain Injury
Association of America @ $100-$200/year
EDUCATION FOR PARENTS Abilities Expocon-entrance fee @ $5/per person, $50/person for room
and board 3 people/year
Additional conferences @ $500-$1000/year
Gastaut seizure disorder. As a result, there was a Money was awarded for X’s current and future
lawsuit and a life care plan prepared in 2002 (Figs. 2, care needs, and the family initially served as the
3, 4, 5, 6, 7, and 8) (Picture 2). guardians of the estate. A fiduciary and attorney
were later identified and appointed to oversee the make informed decisions regarding surgery or
expenditure of the money and to report to the placement of a vagal nerve stimulator were
court. The family used the life care plan to iden- important aspects of the case manager’s role.
tify the services and frequency that X would The family was often uncomfortable asking
need. The court and attorney used the life care questions or clarifying treatment options, but
plan as a guide for the appropriate expenditure of as the years passed, X’s mother assumed the
money and served as the basis for identifying and role as her son’s advocate. Due to X’s bilateral
funding services to meet X’s needs. Federal, cortical infarcts making him visually impaired,
state, and county resources were identified and advocating for his educational needs through
applied to augment X’s finances and meet his the IEP (Individualized Education Program)
needs. was another role that the case managers
Nurse case managers were involved in iden- assumed.
tifying and accessing physicians, therapy, sup- Currently X is 18 years old and living at home,
plies, equipment, and recreation programs and medically stable, participating in activities with
preparing justifications for home modifications family including swimming and community out-
and modified vans. The family relied on the ings, and attending school. The case manager’s
presence of the case managers at physician service hours have now been decreased, and
appointments, clinic evaluations, and educa- her function has changed to that of a resource
tional appointments and to assist them in navi- in planning for the next phase of X’s life as
gating the healthcare system. Educating the the family has learned to advocate for X’s needs
family about treatments and helping them to (Pictures 3 and 4).
Picture 2 X at age 7 Picture 3 X at age 14

▶ Surgical Treatment of Scoliosis Due to Cerebral

Palsy
▶ Upper Extremity Operative Procedures in Cere-
bral Palsy
▶ Classification Terminology in Cerebral Palsy
References
AANLCP, Nurse life care planning, scope and standards of
practice. Edition One
A Core Curriculum for Nurse Life Care Planning (2013)
American Association of Nurse Life Care Planners
Casuto D (2000) The influence of special needs trusts on
case management practice. Case Manag J 11(4):64–66.
TCM
Casuto D (2002) Pediatric life care planning. In: Guide to
injury management volume III, life care planning.
GeneralCologne Re, pp 14–17
Casuto D, Gumpel L (2003) A retrospective study of
Picture 4 X at age 18 pediatric life care plan outcomes. J Life Care Plan
(JLCP) 2(1):13–23. Elliott & Fitzpatrick, Inc.
Casuto D, Kendall S (2005) A quantitative reappraisal of
a qualitative survey to assess reliability and validity
of the life care planning process. J Life Care Plan
(JLCP) 4(2 & 3):75–98. Elliott & Fitzpatrick, Inc.
Cross-References Casuto D, McCollom P (2001) Life care planning.
In: O’Keefe M (ed) Nursing practice and the law.
▶ Epilepsy in the Child with Cerebral Palsy F.A. Davis, Philadelphia, pp 416–430
▶ Epilepsy Surgery for the Child with Cerebral IARP (2009) International Association of Rehabilitation
Professionals. International Academy of Life Care Plan-
Palsy
ners Standards of Practice
▶ Complementary and Alternative Medicine in Yudkof M (1998) Legal nurse consultants principles and
Cerebral Palsy practices. In: The life-care planning expert. p 657
▶ Gastroesophageal Reflux in the Child with Yudkof M (2003) Legal nurse consultants principles
and practices, 2nd edn. In: The life-care planning
Cerebral Palsy
expert. p 867
▶ Medical Management of Spasticity in Children
with Cerebral Palsy
▶ Intrathecal Baclofen Therapy: Assessment and Resources
Medical Management
The Internet offers. an incredible amount of information.
▶ Intrathecal Medication Administration in Cere- The following websites might be helpful for further
bral Palsy information and/or assistance in accessing benefits
▶ Dorsal Rhizotomy for Spasticity Management and services
in Cerebral Palsy https://archrespite.org/respitelocator
http://www.askearn.org/
▶ Psychiatric Disorders in Children with Cerebral https://www.benefits.gov/
Palsy http://www.cdss.ca.gov/
▶ Atlas of Foot and Ankle Procedures in Cerebral https://www.cerebralpalsy.org/
Palsy https://cerebralpalsygroup.com/
https://www.coveredca.com/
▶ Hip Reconstruction in Children with Cerebral https://www.dds.ca.gov/Rates/ReimbRates.cfm
Palsy http://dor.ca.gov/
▶ Surgical Atlas of Cerebral Palsy Hip http://www.cdss.ca.gov/In-home-supportive-services
Procedures https://www.inhomecare.com/
https://www.mybenefitscalwin.org/ http://ucp.org/
https://nasddds.org/ http://www.ucpmobile.org/ucp-programs/adult-services/
https://www.ssa.gov/ adult-day-program/
https://www.thearc.org/
Part VII
Central Neurologic Problems
Epilepsy in the Child with Cerebral
Palsy 31
Stephen Falchek
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 458
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 458
Seizures and Epileptogenesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 458
Clinical Features of Seizures and Epilepsy in a Child with Cerebral Palsy . . . . . . . . . . . . 459
Treatment Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 460
The Diagnosis of Epilepsy in the Cerebral Palsies and the Role of EEG . . . . . . . . . . . . . . 460
Treatment of Epilepsy Syndromes and Seizure Categories in Cerebral Palsy . . . . . . . . . 461
Specific Epilepsy Considerations and Syndromes in Cerebral Palsy . . . . . . . . . . . . . . . . . . 462
Epilepsy Remission in Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 465
Complications of Epilepsy and Its Treatment in Cerebral Palsy . . . . . . . . . . . . . . . . . . . 465
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 466
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 466
Abstract the assessment of likelihood of seizure recur-

Epilepsy is a significant comorbidity of cere- rence as the most important factor. The choice
bral palsy, occurring in 35–62% of affected of anticonvulsant medication is based upon
children. It is the leading cause of hospitaliza- seizure semiology, syndrome, and expected
tion in children with cerebral palsy. Most side effects. Specific epileptic syndromes,
patients with CP and epilepsy will experience most notably infantile spasms and Lennox-
their first seizures within their first year of Gastaut syndrome, are especially prevalent
life. The diagnosis of epilepsy is guided by in the cerebral palsy population. Although a
the clinical scenario and EEG findings, with serious problem, there is a high likelihood
of both seizure control and seizure remission
after 3 years of treatment, in the population
with cerebral palsy and epilepsy.
S. Falchek (*)
Division of Pediatric Neurology, Department of Pediatrics,
Wilmington, DE, USA
e-mail: Stephen.Falchek@nemours.org

https://doi.org/10.1007/978-3-319-74558-9_29
458 S. Falchek
Keywords perinatal hypoxic-ischemic injury, stroke, inborn

Epilepsy · Epileptogenesis · Lennox-Gastaut errors of metabolism, hydrocephalus, developmen-
syndrome · Infantile spasms · Stroke tal brain malformations, and intraventricular hem-
orrhage. This risk exists independent of the degree
of clinical features representing cerebral palsy.
Introduction However, the pattern and severity of brain injury
or involvement may loosely correlate with the like-
The terms epilepsy and cerebral palsy, commonly lihood of both seizures and cerebral palsy as late
used together, are frequently misunderstood, consequences. In published studies, children with
and their relationship misconstrued. They share hemiplegic and quadriplegic cerebral palsy are
common pathophysiology, i.e., they derive from most affected by epilepsy, with incidences up to
longstanding, disadvantageous rearrangements 70.6% and 66.1%, respectively (Ashwal et al.
of brain function. Consequently, they may involve 2004). However, partly due to the lack of consis-
an overlapping range of comorbidities, including tency in definitions of cerebral palsy subtypes,
intellectual disability, gross and fine motor some studies cite very high incidences of epilepsy
impairments, and medication side effects. These in other categories (Zafeiriou et al. 1999).
facts sometimes lead to the assumption that Of the many causes of cerebral palsy in chil-
the two diagnoses are mutually inclusive. How- dren, the most studied in relation to the risk
ever, epilepsy is a special consideration in the of subsequent epilepsy are stroke and hypoxic-
cerebral palsies, and its presence represents an ischemic encephalopathy. In one series, of 87
added dimension in diagnosis and management. children with arterial stroke in the perinatal or
According to the International League Against antenatal period, the 10-year cumulative inci-
Epilepsy (ILAE), a person has epilepsy if they have dence of a first remote seizure was 69%, and
either two unprovoked or reflexive seizures greater of active epilepsy was 54%. Acute symptomatic
than 24 h apart or one unprovoked or reflexive seizure in the neonatal period was the only
seizure and a greater than 60% risk of seizure recur- factor predictive of remote seizures across all
rence in the subsequent 10 years (Scheffer et al. statistical analyses (Fox et al. 2016).
2017). The prevalence of epilepsy in the pediatric Epilepsy accounts for a significant proportion
population varies among countries, but, in the of morbidity in patients with cerebral palsy. In
United States, is approximately 0.6%, or 6 in 1000 a retrospective analysis of hospital admissions
children (Zack and Kobau 2017; Russ et al. 2012). comprising 1064 children and young adults,
This is concordant with prevalence data from other epilepsy accounted for 12.8% of hospital admis-
developed countries (Aaberg et al. 2017). sions in children, and 7.5% of admissions in
Cerebral palsy is a broadly inclusive diagnosis, adults; it was the most common cause of hospital
representing a multiplicity of causes and clinical admission in children. Only acute pneumonia
scenarios. While there are many risk factors presented more frequently for hospital admission
identifiable at birth, the diagnosis typically becomes in adults with cerebral palsy (Young et al. 2011).
manifest later in infancy or childhood. Taken
together, these disorders eventually occur in approx-
imately 2–2.5 out of 1000 children (Colver et al. Natural History
2014). Of children with cerebral palsy, the incidence
of epilepsy ranges from 35% to 62% (Novak et al. Seizures and Epileptogenesis
2012; Singhi et al. 2003; Bruck et al. 2001; Ashwal
et al. 2004). Conversely, of children with seizures in Seizure events require the production of abnormal
the neonatal period, about 25% eventually will man- excitation in large networks of neurons, with a
ifest cerebral palsy (Ronen et al. 2007). propensity for sustained activity over a measurable
Many, if not all, causes of cerebral palsy also time. As such, epilepsy represents a gain-of-func-
convey a unique risk of epilepsy, including tion abnormality. This is due to factors that serve as
31 Epilepsy in the Child with Cerebral Palsy 459
direct neuronal irritants, e.g., regional gliosis, met- complex motor movements, pure sensory phe-
abolic derangements, altered synaptogenesis, and nomena, altered consciousness, myoclonic jerks,
toxic, excitatory compounds (as in some of the and autonomic changes. The specifics of seizure
inborn errors of metabolism). The loss of normal types (more than one may exist in one given
inhibition and the inhibitory neural networks, patient concomitantly or sequentially), the elec-
which serve as safeguards against seizures in the troencephalogram (EEG) characteristics, and
normally developing brain, are even more impor- the clinical scenario further delineate an epilepsy
tant factors. The injuries that cause cerebral palsy syndrome, and allow the assignment of descrip-
often damage these inhibitory networks in the brain tive categories.
as well, degrading the innate defenses against sei- Broadly speaking, epilepsy can be subdivided
zure activity. The incidence of epilepsy in patients into symptomatic (caused by a definable injury
with purely white matter injury on MRI imaging or physical change in the brain) or genetic.
demonstrates the importance of this last factor. In a Patients with cerebral palsy mostly fall into the
series of 166 patients with purely white matter symptomatic epilepsy category, although many
injuries resulting from either prenatal or perinatal epilepsy-provoking genetic abnormalities may
ischemia or hemorrhage, 41 (25%) had had at least also produce a cerebral palsy phenotype. A
one seizure after the neonatal period, i.e., outside of more useful categorization of epilepsy is the sei-
the immediate time of injury, and 15% satisfied zure classification scheme determined by the
criteria for a diagnosis of epilepsy. A clear majority ILAE (Scheffer et al. 2017) (Table 1). Of seizure
of seizures (30 children, or 18%) were focal sei- types, the focal epilepsies are by far the most
zures (Cooper et al. 2017). In the absence of gray numerous, both in the general population as
matter involvement, it would therefore appear that well as in patients with cerebral palsy. Children
the disruption of neuronal network connectivity, by with spastic quadriplegia or hemiplegia have a
disruption of white matter tracts, is itself sufficient higher incidence of epilepsy (50–94% in quadri-
to produce epilepsy in a substantial proportion of plegia and 30–70% in hemiplegia) than in
patients with cerebral palsy and epilepsy. diplegic or ataxic forms of cerebral palsy
Epilepsy presents a challenge to normal cere- (16–27%) (Ashwal et al. 2004; Ronen et al.
bral development, in that synaptogenesis is usage- 2007).
driven. Another complication is the phenomenon Children with epilepsy in the context of
of excitotoxicity, that is, over-stimulation of neu- cerebral palsy experience their first seizures
ral networks triggering the process of apoptosis, most commonly in the first years, with 61% to
or programmed cell death. Therefore, epilepsy 74% of patient experiencing their first seizure
can be destructive, in that it redirects networks within the first 12 months of life (Bruck et al.
from their normally assigned functions toward 2001; Ashwal et al. 2004; Zafeiriou et al. 1999).
the otherwise pointless task of seizure production, Most studies find that children with hemiplegic
and causes the untimely demise of some neurons or quadriplegic cerebral palsy suffer earlier
when there is repetitive overstimulation. When onset seizures than in other cerebral palsies.
sustained over time, this can result in increasingly As previously mentioned, a relationship between
treatment-resistant seizures and in the loss of severity of cerebral injury and epilepsy onset
remaining cerebral development potential. has thus been postulated (Bruck et al. 2001).
Also, the likelihood of treatment-resistant epi-
lepsy increases in cerebral palsy. In the model
Clinical Features of Seizures of arterial stroke, 33% of children with remote
and Epilepsy in a Child with Cerebral symptomatic epilepsy were poorly controlled
Palsy despite anticonvulsant therapy (monthly sei-
zures), and 29% were on treatment with more
There is a nearly infinite array of symptoms that than one anticonvulsant medication (Fox et al.
may herald the presence of a seizure, including 2016).
460 S. Falchek
Table 1 Current Seizure Classification “Reproduced from classification/ilae-classification-of-the-epilepsies-2017.

Epilepsia, a journal of the International League against https://creativecommons.org/licenses/by-sa/4.0/
Epilepsy” https://www.ilae.org/guidelines/definition-and-
ILAE 2017 Classification of Seizure Types Expanded Version1
Focal Onset Generalized Onset Unknown Onset
Aware
Impaired Motor Motor
Awareness tonic-clonic tonic-clonic
clonic epileptic spasms
Motor Onset tonic Non-Motor
automatisms myoclonic
behavior arrest
atonic2 myoclonic-tonic-clonic
clonic myoclonic-atonic
epileptic spasms2 atonic
hyperkinetic epileptic spasms2
Unclassified3
myoclonic Non-Motor (absence)
tonic
typical
Non-Motor Onset atypical
autonomic myoclonic
behavior arrest eyelid myoclonia
cognitive
emotional 1 Definitions, other seizure types and descriptors are listed in the
sensory accompanying paper and glossary of terms.
2 These could be focal or generalized, with or without alteration of awareness
focal to bilateral tonic-clonic 3
Due to inadequate information or inability to place in other categories
From Fisher et al. lnstruction manual for the ILAE 2017 operational
classification of seizure types. Epilepsia doi: 10.1111/epi.13671
is not necessary in all circumstances, and an EEG

Treatment Considerations manifesting significant, epileptiform abnormalities
may prompt the presumptive diagnosis of epilepsy.
The Diagnosis of Epilepsy However, the EEG also may show abnormality in
in the Cerebral Palsies and the Role 39.5% of patients with cerebral palsy and without
of EEG epilepsy (Senbil et al. 2002). In situations where
the diagnosis is ambiguous, prolonged EEG mon-
The investigation of suspected seizure activity itoring may increase study yield by capturing clin-
begins with efforts to exclude acute, correctable ical events or by increasing sampling time and
causes, such as medication effects, infection (men- documenting prevalence of epileptiform EEG
ingitis/encephalitis or shunt infection in the patient abnormalities.
with shunted hydrocephalus), intracranial hemor- Special considerations do apply to the
rhage, acute cerebral trauma, and electrolyte imbal- interpretation of EEG results in patients with
ance. Of equal importance is the distinction cerebral palsy. As stated above, the baseline EEG
between seizures and nonepileptic events, such as of patients with cerebral injury are often abnormal,
paroxysmal movement disorders, gastroesopha- confounding interpretations of an “abnormal” EEG
geal reflux, posturing, or medication intoxication, after an acute event. The presence of anatomic and
among many. Beyond clinical observation, the mechanical factors may create obfuscatory find-
most useful tool in supporting the diagnosis of ings. In cases of hydrocephalus, rhythmic frontal
epilepsy is the electroencephalogram (EEG). The 1–3 Hz activity, called Frontal Intermittent Rhyth-
diagnostic yield of EEG is greatest if a clinical mic Delta Activity (FIRDA), may be present and
event is captured during the study. However, this misinterpreted as an epileptic feature. In patients
with substantial losses of the neocortex, the In situations of proven medication resistance,
distance between the source of epileptic activity or poor tolerance across a spectrum of agents,
originating from surviving cortical tissue, remote alternative treatments are considered. These
from the scalp surface and the recording electrodes, include the ketogenic diet; vagus nerve stimula-
may obscure epileptiform features by volume dis- tion; epilepsy surgeries, including corpus
sipation of electrical signal (Van Rotterdam 2011). callosotomy, focal cortical resection, and
The chronic use of certain medications, such as hemispherectomies; and responsive neurosti-
phenytoin, causes thickening of the calvarium and mulation (RNS). While efficacy data for each
may also diminish EEG sensitivity by conduction of these strategies are readily available for the
losses. As a result, nonconfirmatory EEG results, general epilepsy population, results specific to
taken as a “negative” sign against a diagnosis of the cerebral palsy population are less well
epilepsy, may be misleading. Nonetheless, if we known (Jasega 2011). However, outcomes data
include nonspecific abnormalities, the EEG of suggest that, in cases of neurologic impairment
patients with both cerebral palsy and epilepsy dis- focused on learning disabilities, substantial sei-
plays abnormality in up to 90.3% of patients zure reduction (up to 56% with a > 75% reduction
(Senbil et al. 2002). in seizures, including seizure freedom) are still
the result of well-planned epilepsy surgeries.
Therefore, preexisting disabilities, such as those
Treatment of Epilepsy Syndromes encountered in cerebral palsy, should not be con-
and Seizure Categories in Cerebral sidered contraindications for epilepsy surgery
Palsy (Olsson et al. 2013).
In the past several years, there has also been a
Even in circumstances where a seizure has great deal of interest in cannabis-derived products
convincingly occurred, the decision to begin for the treatment of epilepsy, as an alternative to
treatment for epilepsy is predicated upon the conventional pharmacotherapy. The acknowledg-
estimated likelihood of seizure recurrence. The ment of efficacy in muscle spasms associated with
ILAE recommends a 60% or greater likelihood multiple sclerosis has heightened interest in myr-
of seizure recurrence as the deciding factor in iad applications for patients with cerebral palsy.
the decision to treat (Scheffer et al. 2017). By extrapolation, this reasoning has heightened
Upon recognition of the decision to treat, the interest in the potential anticonvulsant effects
entire armamentarium of current anticonvulsant of cannabinoids for this population. Cannabidiol,
medications may be applied to the treatment of the most studied of dozens of biologically active
children with cerebral palsy, with no categorical compounds derived from Cannabis sativa or
restrictions. For a given patient, seizure medica- Cannabis indica plants, has received the most
tion choice is predicated upon seizure type or attention as an anticonvulsant. In the United
epilepsy syndrome, anticipated side effect profile, States, both an FDA-approved, naturally derived
and interaction with other essential medications. purified cannabidiol, Epidiolex, and artisanal
When the first choice of anticonvulsant is either high-cannabidiol extracts of the cannabis plants
ineffective or poorly tolerated, it is necessary to are now in use in many states. The mechanism
convert therapy to a second drug. Medication- of action of cannabidiol in epilepsy remains to
resistant epilepsy is determined by the lack of be elucidated; it does not act primarily at endo-
seizure control after two, or at most three, trials cannabinoid receptors (Devinsky et al. 2014). The
of a well-chosen anticonvulsant, dosed well into most reliable data suggests that cannabidiol is
the therapeutic range. Medications withdrawn most applicable to patients with Dravet syndrome
at early stages of initiation due to allergy or lack (with many, but not all, cases caused by mutations
of tolerability, or titrated to suboptimal dosing in the SCN1A gene, one of thousands of genetic
for any reason, generally do not enter into the causes of epilepsy) and in patients with Lennox-
tally of medication failures. Gastaut syndrome in general. Epidiolex currently
462 S. Falchek
has FDA indication only for seizure types associ- The concept of an “epileptic encephalopathy”
ated with Dravet or Lennox-Gastaut syndromes. has particular relevance to children with cerebral
In patients with Dravet syndrome, seizure reduc- palsy. In these conditions, the burden of epilepti-
tion of 28.6–42.7% (for all types of seizures) have form abnormality has a deleterious effect on
been reported in controlled and open-label trials, functioning. While most of the affected patients
respectively (Devinsky et al. 2016, 2017). In will have observed clinical seizures, instances
patients with Lennox-Gastaut syndrome, open- of purely interictal findings, comprising an
label use of cannabidiol has produced up to excessive “spike burden,” are clearly recognized.
35.5% reduction across all seizure types. In One paradigm of this phenomenon is the diagno-
contrast, if all patients in the open-label trial sis of electrographic status epilepticus of sleep
with refractory epilepsy are considered in the (ESES), also known as continuous spikes and
denominator, the seizure reduction was 34.6% waves during slow wave sleep (CSWS). In these
across all seizure types. Few patients in either patients, epileptiform features partly obscure
the Dravet or Lennox-Gastaut category, though, the sleep portion of the recording, occupying
have shown true seizure freedom with 50% or more of the total time of sleep. Although
cannabidiol (3–5%) (Devinsky et al. 2016, the incidence of this phenomenon in patients
2017). Of note is the fact that cannabidiol with cerebral palsy is not known, it has been
significantly increases clobazam serum levels observed that cognitive functioning in nearly all
(Geffrey et al. 2015) and clobazam was a patients with ESES/CSWS worsens during the
coadministered drug in many of the responders period of active diagnosis, and up to 44% manifest
in the early cannabidiol trials (Devinsky et al. permanent cognitive impairment compared to
2016, 2017). At this point, there is no evidence prior baseline (Pera et al. 2013).
to suggest that cannabidiol differentially affects With the paradigm of ESES/CSWS in mind,
patients with cerebral palsy, and clarity is still some researchers have focused interest on the
lacking on many aspects of cannabidiol in the prevalence of interictal abnormalities in cerebral
full spectrum of epilepsy. palsy, and the prospect of clinical improvement
by means of their suppression (Jaseja 2007a, b).
However, at this time, the treatment of epilepti-
Specific Epilepsy Considerations form abnormalities in the absence of clinical
and Syndromes in Cerebral Palsy seizures or well-documented epileptic phenom-
ena like ESES/CSWS remains controversial.
The concepts of subclinical, or occult, seizure The American Academy of Neurology practice
activity and prevalence of interictal epileptiform parameters advises against routine EEG in chil-
features, or “spike burden,” are important consid- dren with cerebral palsy, in the absence of con-
erations in the patient with cerebral palsy. Sub- vincing concern for extant seizures or epilepsy
clinical seizures, which are events confirmable syndromes (Ronen et al. 2007).
only by EEG, have the same import in early life Infantile spasms are a specific epilepsy syn-
as clinical seizure events (Maartens et al. 2012). In drome of particular importance in cerebral palsy.
particular, a high seizure burden is significantly This is a malignant epilepsy of late infancy/
correlated with abnormal neurodevelopmental early childhood, with onset ranging from the first
outcomes, especially in neonates with hypoxic- days after birth to 6 years, but with a bimodal
ischemic cerebral injury (Kharoshankaya et al. distribution of greatest incidence between both
2016). Their impact on developmental potential 3 to 5 months and 6 to 8 months of age
is an important concern; for this reason, otherwise (Hadjipanayis et al. 1997). Of children with both
unexplained degradation of intellectual or physi- cerebral palsy and epilepsy, infantile spasms
cal performance is often investigated by means account for 6.5 to 22% of the incidence of epi-
of EEG, especially prolonged EEG monitoring. lepsy (Bruck et al. 2001; Ashwal et al. 2004;
Zafeiriou et al. 1999; Hadjipanayis et al. 1997). epilepsy of different semiologies (90%) and a
Most typically, infantile spasms present as clus- high proportion of cognitive impairment (80%)
ters of a brief, flexion motions of the torso and (Golomb et al. 2006).
upper extremities. These are often followed by Treatment options for infantile spasms are
a brief cry, and can be mistaken for physical limited, but efficacious in most cases. The
discomfort. Clusters may consist of only two to standard treatment is either adrenocorticotropic
three spams, or dozens. The EEG of a child with hormone (ACTH) or vigabatrin. The mechanism
infantile spasms manifests several hallmark of action of ACTH is unclear; it does have
clinical findings, namely a chaotic, disorganized strong affinity for melanocortin receptors
pattern with multifocal spikes, devoid of expressed on cortical neurons, but is relatively
most normal features, called hypsarrythmia, impermeable to the blood-brain barrier.
and brief periods of total signal suppression, Anti-inflammatory properties may be important,
called electrodecremental events (Fig. 1). When as evinced by the short-term efficacy of
these features are present, the eponymic label of high-dose systemic contricosteroids (Yeh et al.
West Syndrome is often used. However, a given 2017). Other potential mechanisms include
patient need not have persistent hypsarrythmia the production of neurosteroids like allo-
or electrodecremental events to qualify for a tetrahydrodeoxycorticosterone, from the adrenal
diagnosis of infantile spasms. Infantile spasms gland. These powerful modulators of γ-amino
will normally extinguish after several weeks to butyric acid (GABA-A) inhibitory receptors may
several months, but if untreated, infantile spasms also play an important role in its efficacy
have a very poor developmental prognosis. (Stafstrom et al. 2011). Vigabatrin is an irrevers-
According to data derived from neonatal stroke, ible inhibitor of GABA-transaminase, thereby
the majority of patients with infantile spasms increasing intra-synaptic GABA concentrations.
and cerebral palsy will manifest subsequent However, the relative lack of efficacy of other
Fig. 1 Hypsarrythmia. Note the relative flattening of signal (arrow) consistent with an electrodecremental event
464 S. Falchek
GABA-modulating agents in infantile spasms is either removed or isolated by disconnection

suggests other, perhaps yet unknown, mecha- of all main white matter pathways. Epilepsy sur-
nisms of action. gical interventions have produced good results
ACTH is given by tapering course of intramus- in up to 88% of cases of infantile spasms in one
cular injection over a 6-week course, beginning series of 65 patients (Chugani et al. 2015).
at 150 mg/M2/day. Vigabatrin is given at The Lennox-Gastaut syndrome (LGS) is a
50–150 mg/kg/day, usually titrated up to the persistent, often intractable, epilepsy syndrome
maximum dose within 1 week, for a longer, less marked by the occurrence of seizures of mixed
circumscribed period of time. Unlike ACTH, semiologies (atonic or “drop” seizures, tonic,
vigabatrin may be sustained indefinitely, and and atypical absence among the most common),
may be useful in managing subsequent seizure a characteristic EEG, and typically cognitive
categories. Patients who fail to respond to the delay or regression. The age of onset is typically
first course of treatment, or who relapse after its around 2 years, and ranges up to 8 years (Van
termination, may be given a second round of the Rijckevorsel 2008). This syndrome may often
same, or the alternate, treatment. Other anticon- result after a course of infantile spasms, but
vulsants are substantially less efficacious, but a spasms are not a prerequisite for the diagnosis
small corpus of literature supports the use of high- of LGS. The EEG of patients with LGS typically
dose topiramate, valproic acid, zonisamide, shows slow spike-and-wave activity in general-
levetiracetam, and benzodiazepines (Song et al. ized and multifocal distributions, often with a
2017) usually in isolated cases and small series. preponderance of activity frontally (Fig. 2). LGS
The ketogenic diet and modified Atkins diet is highly correlated with neurodevelopmental
have also demonstrated efficacy (Song et al. disabilities and chronic epilepsy. Of children
2017). Patients who fail to respond to the cardinal with LGS, up to 92.7% of them will have intel-
treatment strategies for infantile spasms may lectual disability, and 65.9% will have persistent
be good candidates for epilepsy surgery, in epilepsy (Kurokawa et al. 1980). When taken in
which the epileptogenic zone, or hemisphere, conjunction with a pre-existing diagnosis of
Fig. 2 The typical EEG of Lennox-Gastaut syndrome

cerebral palsy, the likelihood of intellectual (Zafeiriou et al. 1999). However, the definition
disability becomes virtually certain. of remission and the seizure-free time interval
Preferred treatment options for LGS include used as justification for a medication taper vary
valproic acid, clobazam, other benzodiazepines, from study to study. Most commonly, authors
topiramate, lamotrigine, felbamate, rufinamide, utilize a 3-year seizure-free interval as the mini-
and cannabidiol. Of these, rufinamide and mum requirement for consideration of a medica-
cannabidiol are the only anticonvulsants specifi- tion taper. Of note, the 5-year relapse rate of
cally developed and marketed for a specific 13.4% in the one series suggests that true remis-
epilepsy syndrome. Cannabidiol (Epidiolex) sion rates are lower than the first impression
most recently has received FDA approval for might suggest, especially if patients in such stud-
marketing in the United States. Response rates ies are followed for only limited periods of time
of all anticonvulsants in LGS are low, with many after medication withdrawal.
patients requiring polypharmacy and many resis-
tant to the use of two or more anticonvulsants.
In a trial of placebo, low- and high-dose cohorts, Complications of Epilepsy and Its
cannabidiol produced at high dose a median Treatment in Cerebral Palsy
reduction in drop seizures of 41.9% and all seizure
types of 38.4%. Only 7% or enrolled patients were As with any patient population, the patient with
free of drop seizures (but not necessarily other cerebral palsy is susceptible to side effects that
seizure types) in the maintenance phase of trial may render any given treatment regimen intolera-
(Devinsky et al. 2018). Many anticonvulsants ble, often by magnifying existing, concurrent
also have the drawback of worsening one health problems. Of many possible side effect
seizure type while improving another. This is concerns, sialorrhea, somnolence, weight distur-
especially true with the myoclonic and atonic bances, and osteoporosis disproportionately affect
seizures of LGS. Anticonvulsants that act on patients with cerebral palsy. Of these, the concern
sodium channels, such as phenytoin, lamotrigine, for osteoporosis as an enduring, and possibly
carbamazepine, and oxcarbazepine, especially irreversible, sequela of epilepsy treatment has
feature this problem (Van Rijckevorsel 2008). received particular attention. Older anticonvul-
sants, such as phenytoin and phenobarbital,
were considered definite risk factors for abnormal
Epilepsy Remission in Cerebral Palsy bone mineral density. In patients with cerebral
palsy and epilepsy, there is a significantly
Conventional wisdom dictates that children with higher risk of abnormal bone mineral density
cerebral palsy who develop remote symptomatic (as measured by z-scores) compared to patients
epilepsy have a low likelihood of seizure remis- with cerebral palsy alone – 70.2% vs 42.5%. This
sion, due to the enduring nature of the structural is especially significant when compared to
injury to their brains. Some studies, especially patients with epilepsy but not cerebral palsy,
from the developing world, seem to support this who have an 11.5% incidence of abnormal
notion (Bruck et al. 2001). However, data from z-scores (Coppola et al. 2012). While conven-
many studies show that 53–75% of patients with tional wisdom attributes this difference to the
epilepsy and cerebral palsy achieve seizure application of anticonvulsant therapies in the
freedom, many on monotherapy (Ashwal et al. setting of cerebral palsy, existing data appear
2004). Additionally, a high number (75.3%) to refute this argument. In patients without
discontinued anticonvulsants after 3 years of intellectual disability or cerebral palsy treated
seizure freedom in one large series of 178 patients. with anticonvulsants, three mainstream anticon-
Of these, 86% remained seizure free without vulsants (levetiracetam, carbamazepine, and
relapse in a mean follow-up period of 5.8 years, valproic acid) produced no statistically significant
thus yielding a long-term remission rate of 65.2% difference when compared to healthy controls
466 S. Falchek
(Serin et al. 2015). Therefore, it appears that the fairly good, seemingly over 50%, based upon
clinical scenario of cerebral palsy plus epilepsy medication withdrawal statistics. The entire
poses its own risk factor for abnormal bone armamentarium of anticonvulsant medications,
mineral density, independent of anticonvulsant and nonmedication strategies like the ketogenic
therapy. diet, and epilepsy surgeries, is appropriately
Of greater concern is the risk for sudden applied to patients with cerebral palsy and epi-
unexplained death in epilepsy (SUDEP). In the lepsy, depending upon the specifics of each
general epilepsy population, this risk ranges individual’s epilepsy syndrome.
widely, from 0.09 to 2.65 per 1,000 person-years
in community populations, to 6.0 to 9.3 in patients
treated with epilepsy surgery (Devinsky 2011). Cross-References
However, the relative risk of sudden death
events in the cerebral palsy population with ▶ Animal Models of Cerebral Palsy: What Can
epilepsy vs the cerebral palsy population in gen- We Learn About Cerebral Palsy in Humans
eral has never been rigorously determined. ▶ Current Imaging: PET Scan Use in Cerebral
An historical cohort study, of data from Danish Palsy
registries and death certificates for those age ▶ Epilepsy Surgery for the Child with Cerebral
1–35 years, determined an overall incidence of Palsy
definite and probable SUDEP to be 41.1 per ▶ Measuring Outcomes in Children with Cerebral
100,000 person-years (0.41 per 1,000 person- Palsy
years), but with a much higher incidence in ▶ Perinatal Stroke as an Etiology of Cerebral
the population over 24 years of age. The hazard Palsy
ratio after adjusting for factors including age,
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Epilepsy Surgery for the Child
Badal G. Jain and Harry T. Chugani
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 470
Impact . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 470
When Should Surgery Be Considered? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 470
Evaluation for Epilepsy Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 472
Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 472
Epilepsy Surgery Conference . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 474
Types of Epilepsy Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 474
Resective Surgeries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 475
Corpus Callosotomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 477
Neurostimulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 477
Minimally Invasive Epilepsy Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 479
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 479
Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 480
Abstract medications are the first line of therapy, a signif-

Epilepsy is a common comorbidity for children icant proportion of epilepsies in children with
with cerebral palsy. While antiepileptic cerebral palsy remain intractable. This can
cause significant morbidity and rarely mortality.
After having failed two or more appropriate
B. G. Jain (*)
medications, they should be evaluated for surgi-
Division of Neurology, Department of Pediatrics, cal candidacy. The consideration for epilepsy
Nemours/Alfred. I. duPont Hospital for Children, surgery requires a thorough and methodical con-
Wilmington, DE, USA sideration of clinical, electrodiagnostic, neuro-
e-mail: badal.jain@nemours.org
imaging, and neuropsychological information.
H. T. Chugani An array of imaging techniques are used with
Comprehensive Epilepsy Center, Department of
Neurology, NYU School of Medicine, New York, NY,
an attempt to fine-tune the surgical approach.
USA The approach for epilepsy surgery for chil-
e-mail: Harry.Chugani@nyulangone.org; dren with cerebral palsy is not dissimilar to the
hchugani@pet.wayne.edu

https://doi.org/10.1007/978-3-319-74558-9_32
470 B. G. Jain and H. T. Chugani
approach for children without cerebral palsy. referred to as secondary epileptogenicity from
This chapter provides the usual methodologi- intractable seizures.
cal approach in the evaluation for epilepsy (e) Subclinical interictal epileptiform discharges
surgery and describes the various types of sur- have been proposed to lead to transitory cog-
gical procedures and options available. These nitive impairment (Binnie 1996). It is pro-
include various curative and palliative surgeries posed that when the interictal spikes are
including multiple types of resective surgeries, highly frequent (referred to as high spike bur-
disconnective surgery, neurostimulation includ- den), the detrimental effects are compounded,
ing responsive neurostimulation, and minimally especially on a developing brain (Sánchez
invasive epilepsy surgery. Fernández et al. 2015).
Keywords
Epilepsy · Cerebral palsy · Epilepsy surgery · When Should Surgery Be Considered?
Vagal verve stimulator · Hemispherectomy
The response to adequate doses of the first appro-
priately chosen and well-tolerated antiepileptic
Introduction drug (AED) remains the best predictor of intrac-
tability. While the first line of therapy remains
Epilepsy is a common comorbidity in children pharmacological, there is an exponential decrease
with cerebral palsy. Among various studies, the in efficacy after attempting two appropriate and
incidence of coexisting epilepsy ranges from 35% well-tolerated antiepileptic medications.
to 41% (Novak et al. 2012; Christensen et al. In a pivotal study and multiple supporting stud-
2014). Epilepsy is often severe and more resistant ies since then, it has been shown that the likelihood
to antiepileptic medications when accompanied of seizure control is 47% with the first AED, 13%
by intellectual disability (Zafeiriou et al. 1999; with the second AED, and only 3% with the third
Singhi et al. 2003). AED. The likelihood of response progressively
decreases to 1% and less with further AEDs
(Kwan 2000; Pauli et al. 2017). The likelihood of
Impact medical intractability is higher with symptomatic
(i.e., associated with a known cause) epilepsy,
Intractable epilepsy negatively affects the child’s which is the commonest epilepsy type in children
quality of life in multiple ways. Apart from directly with cerebral palsy. The likelihood of success with a
increasing the likelihood of morbidity and occa- change in AED is greater if the change was carried
sional mortality from each individual seizure, there out because of intolerable side effects or allergic
are multiple other factors that influence the quality reaction, rather than lack of efficacy (Kwan 2000).
of life. These may include the following: Per the International League Against Epilepsy
(ILAE) consensus statement, the definition of drug-
(a) Increasing limitation of activities of daily liv- resistant epilepsy is failure of an adequate trial of
ing, with a lower likelihood for independent two well-tolerated, appropriately chosen first-line
living over time. AEDs (used as monotherapy or in combination) to
(b) Negative effect on learning, scholastic achieve sustained seizure freedom (Kwan et al.
achievement, and development. 2010). Sustained seizure freedom is usually
(c) Sedation from often multiple antiepileptic defined as no seizure for a period of 1 year or
medications, limiting participation in thera- three times the longest seizure-free interval (based
pies, learning, and social activities. on seizures in the past 1 year), whichever is longer.
(d) The process of kindling (whereby other
closely connected areas of the brain become (a) Role of newer AEDs. There has fortunately
more epileptogenic over time). This has been been a constant influx of newer AEDs brought
32 Epilepsy Surgery for the Child with Cerebral Palsy 471
into practice for use in pediatric epilepsy. can worsen the seizures. This phenomenon is,
Recent changes to the FDA approval process however, more likely with genetic (previously
will help accelerate this even further. Surpris- called idiopathic) epilepsies and less likely
ingly, the newer AEDs have not led to signif- with epilepsies associated with cerebral palsy
icant changes in long-term intractability (Mantoan and Walker 2011; Glauser et al.
(Chen et al. 2018). Using an additional 2006). A combination of AEDs with different
newer medication occasionally helps for a mechanisms of action and certain antiepileptic
brief period of time (commonly referred to as medication combinations are more likely to be
a “honeymoon period”), but relapses are not successful in controlling seizures (Abou-
uncommon soon after (Choi et al. 2008). Khalil 2017).
It is generally accepted that only complete It is equally vital to “achieve” optimal doses of
seizure freedom (and not a decrease in seizures), the AEDs. Suboptimal dosages, poor compliance,
treated medically or surgically, is associated with and poor absorption can all lead to a poor
an improvement in quality of life (Birbeck et al. response. Gastrointestinal factors such as blocked
2002; Pauli et al. 2017). However, there are situ- G tube, constipation, and diarrhea should also be
ations wherein the aim of the surgery is palliative taken into consideration, especially in children
and not always curative (see below). with cerebral palsy. It should be noted that
optimal-validated drug levels are established
(b) Appropriate diagnosis. While epilepsy and only for a few AEDs (Snodgrass et al. 2001).
cerebral palsy often coexist, it is important to Hence, obtaining blood levels of AED, while
ensure medical intractability of epilepsy before helpful, is not the gold standard for most AEDs.
considering epilepsy surgery. Children with Etiology is an important determinant of
cerebral palsy are more likely to have multiple pharmacoresistance in non-syndromic focal epi-
other paroxysmal events that masquerade as lepsy (Wirrell et al. 2014). Epilepsies associated
seizures. These may include a gastrointestinal with cerebral palsy (localization-related) are more
diagnosis that is more likely in cerebral palsy likely to be pharmacoresistant compared with gen-
(e.g., Sandifer’s syndrome), psychogenic eralized epilepsies (Brodie Glasgow story 2013).
non-epileptic events, spasticity-related tonic
posturing, ocular movement disorders, syn- (d) Age at surgery. There is no real lower limit of
cope, etc. (Bayram et al. 2016; Takasaki et al. age when evaluating for epilepsy surgery. It is
2016; Ito et al. 2017). These are more often vital to diagnose medical intractability early
diagnosed retrospectively as pseudorefractory in the course of treatment, more so for pedi-
or pseudoresistant epilepsy, since these do not atric patients. The reason for this is that, in
respond to AEDs and may even worsen with addition to psychosocial and medical con-
them (Viteva and Zahariev 2009). cerns, intractable epilepsy has detrimental
effects on normal brain development, includ-
The accurate identification of true seizures has ing over the uninvolved cortex. After epilepsy
improved with the use of video monitoring during surgery, the concept of “catch-up” develop-
EEGs, often overnight, preferably in hospital last- mental progress has been cited in various
ing 1 to 7 days. Note that more often than not, studies (Wyllie 1998; Loddenkemper et al.
children with cerebral palsy have a combination 2007). It has been increasingly recognized
of ongoing seizures and spasticity. that this is due to the reversal of adverse
effects of frequent seizures on normal brain
(c) Appropriate medication (or medications) maturation, while the brain still has consider-
and optimal dosage. It is well known that, able plasticity and capacity for recovery.
for certain epilepsy types, an inappropriate Hence, consideration for possible surgical
AED is not only unlikely to help but indeed candidacy should be made early, weighing
risks versus benefits. It should not take more from 2 to 6 months at most centers. This includes
than a year [>1–2, NIH consensus] to estab- routine procedures such as the following:
lish intractability of the seizures, and, A comprehensive history of epilepsy in the
although there is supposedly increased aware- child: this includes knowledge of seizure onset,
ness, it can still take years before surgery is different seizure semiologies, risk factors for epi-
considered. In a retrospective survey, most lepsy, AEDs used in the past, and the reason for
caregivers wished the surgery had been done stopping the medication. In addition, it helps to be
sooner (Shen et al. 2018). aware of any non-epileptic paroxysmal events in
the past, overall compliance, and socioeconomic
Formal neuropsychological testing in children status.
operated on under 36 months of age (range of 3 to A thorough exam should be performed, includ-
34 months) showed median improvement in DQ ing especially evaluation of the level of cognitive
overall for 71%. Those with surgery performed at a functioning, visual field defect, and motor defects
younger age and with better pre-surgical develop- among others. We have created a formatted refer-
ment had better outcome, presumably because the ral form for surgical patients, to prevent lapses in
seizures had a shorter time to negatively influence the transfer of information from prior providers to
brain development (Loddenkemper et al. 2007). the surgical team.
(e) Genetic diagnosis. With increasing recogni- • EEG: This includes the following:
tion of genetic mutations implicated in the path- – Prior routine EEG: reviewing prior EEGs
ogenesis of intractable epilepsy, it can be (including those performed at outside insti-
helpful to rule out an underlying genetic cause tutions), along with reviewing the actual
for the seizures. However, this is unlikely to be EEG tracings. These are to record the over-
the case in most children with cerebral palsy all background, asymmetry of background,
because it would imply two separate indepen- and interictal findings.
dent diagnoses in the same patient, although it is – Long-term monitoring: to record the above
still possible. Even then, an underlying genetic but also to record seizures. This is often
diagnosis does not always rule out a surgical performed over 3 to 7 days while inpatient
option for the seizures. Epilepsy surgery is more and usually involves AED taper, so as to
likely to be effective in children with genetic precipitate seizures. The video recording
mutation involving mTOR pathway and along with cognitive and motor testing
MRI-positive lesions, compared with those soon after seizure by trained nursing per-
with mutations in channel function and synaptic sonnel helps to know seizure semiology,
transmission with negative MRI results postictal deficits, electrographical charac-
(Stevelink et al. 2018). It is imperative in some teristics of seizure, and non-epileptic
epilepsies to identify some particular mutations events, if any.
(e.g., KCNT1 associated with migrating focal – Ambulatory EEG: performed over a few
epilepsy of infancy) where resective surgery is days while in the patient’s home. Although
never an option (Møller et al. 2015). it is more convenient and economical, it is
not the preferred EEG type for epilepsy
surgery evaluation because of movement
Evaluation for Epilepsy Surgery artifacts that often confound localization of
seizure onset.
Studies – HD-EEG: electric source imaging (ESI)
using 128 to 256 channel EEG (HD-EEG)
The following is a brief introduction of the various can help with localization of temporal and
tests that may be needed for surgical evaluation. extratemporal epilepsy and has been shown
The process of evaluation for surgery can take to correlate with the epileptogenic zone
identified by intracranial EEG (Megevand – Ictal SPECT: performed in the hospital with
et al. 2014; Staljanssens et al. 2017). concurrent EEG and requires intravenous
– MEG: magnetoencephalography (MEG) is injection of the radioactive tracer for cere-
a noninvasive, contactless, commonly bral blood flow within seconds of the sei-
interictal imaging modality that records zure onset.
magnetic fields generated by the cerebral – Functional MRI: to identify cortical areas
activity. It is often coregistered with struc- involved in eloquent functioning including
tural MRI (called magnetic source imaging motor-sensory and language and, to a much
[MSI]) and helps to localize seizure onset lesser extent, memory. Needs patient coop-
zone (Gallen et al. 1997; De Tiège et al. eration, remaining still, although light seda-
2008). MEG can also be used for localization can be used (Bernal et al. 2012).
tion or, more so, lateralization of “eloquent” – Combining different modalities like MRI,
cortex, for example, language and motor- PET, SPECT, fMRI, and MEG can give
sensory regions in the brain (Tamilia et al. complementary information, thereby help-
2019). ing in planning the epilepsy surgery.
• Neuroimaging • Other
– MRI: ideally performed with a 3 T magnet – Wada testing: unilateral intracarotid anes-
with thin cuts and good quality images thetic allows lateralization of language,
(under sedation, if needed). Under the age although its use has decreased over time
of 2 years, given incomplete myelination, with the use of fMRI and MEG. Determina-
special imaging techniques are needed. 3 T tion of memory is not as robust in pediatrics,
MRI confers advantages over 1.5 T MRI especially if the child has low full-scale IQ
and is preferred especially in “normal” or (Hamer et al. 2000).
equivocal findings (Phal et al. 2008). Neu- – Neuropsychological evaluation: formal
roradiologists often review MRI with neuropsychological testing provides insight
epileptologists to closely identify abnormal into the degree of cognitive and behavioral
areas, “incidental” findings, and the health dysfunction. It serves as a baseline to com-
of the hemisphere contralateral to the side of pare with postsurgical testing, character-
suspected seizure onset. A review of MRI izes strengths and deficits, contributes to
after other studies like PET/SPECT/MEG lateralization/localization of function, and
can identify (retrospectively) subtle but rel- helps with surgical planning (Jayakar et al.
evant abnormalities on the MRI (Salamon 2014).
et al. 2008).
– DTI tractography to identify white matter Invasive or Intracranial EEG Monitoring
tracts, predominantly motor-sensory, optic In a survey of 20 pediatric surgery programs about
radiation, and arcuate fasciculus (language their practice in 2004, 27% of patients overall
tract), among others. Correlation between underwent invasive monitoring (Harvey et al.
findings and postoperative language out- 2008). Given the increasing complexity of
comes has been studied particularly in tem- patients being considered for epilepsy surgery
poral lobe epilepsies (Powell et al. 2008; (including those with negative MRI findings),
Bonelli et al. 2012). the percentage needing invasive EEG monitoring
– Interictal FDG-PET: to identify areas of is likely to increase over time.
cerebral glucose hypometabolism, indica- Intracranial EEG monitoring is often needed
tive of potential epileptogenicity. The area when the data are divergent or the epileptogenic
identified is usually larger than the epilep- zone is suspected to be close to or involves elo-
togenic zone. Quantitative assessments quent cortex, and, although there is a reasonable
along with visual inspection can be helpful hypothesis of seizure onset, surgical margins need
(Mendes Coelho et al. 2017). to be defined.
Fig. 1 Example of a
subdural grid electrode
The primary aims of invasive EEG are the part of the evaluation and usually involves the
following: epileptologist, epilepsy neurosurgeons, neuroradiol-
ogist, neuropsychologist, social worker, neurology
1. To identify the epileptogenic zone that needs to and epilepsy fellows, and EEG lab technologists. In
be completely resected for seizure freedom and most academic children’s hospitals, these weekly
define the margins of resection needed. The epi- meetings involve adult and pediatric personnel, allo-
leptogenic zone often extends beyond the MRI wing diverse ideas and discussions.
findings, for example, in focal cortical dysplasia. After a comprehensive presentation of all
2. Identify the eloquent (language, sensory- information, including a review of EEG and neu-
motor) cortex, which should be spared to roimaging findings, the discussion is in an open
avoid a functional deficit. General anatomical format among all involved. While these are often
guidelines of eloquent areas do not always hold contentious, this allows for review of all available
true in patients with epilepsy because of func- information from all perspectives in an open
tional reorganization. format.
Based on a multidisciplinary review of clinical
Invasive EEG monitoring can include, among semiology, ictal and interictal EEG findings, and
other modalities, subdural grid and strip electrodes, structural and functional neuroimaging findings, a
depth electrodes, or stereotactic-guided EEG hypothesis of seizure onset and propagation based
(SEEG) (Fig. 1). Direct cortical stimulation (i.e., on consensus is generated for either additional
cortical mapping) is the gold standard for localiza- testing, proceeding with surgery and type of sur-
tion of eloquent areas. There are advantages and gery, holding off on surgery, or palliative proce-
disadvantages of each modality, and these are cho- dures. This is duly documented in detail in the
sen based on the etiology, planned epilepsy sur- medical chart for future reference.
gery, and the experience of each center.
Types of Epilepsy Surgery

Epilepsy Surgery Conference
Epilepsy surgeries include the following:
Once the primary epileptologist determines that the
child should undergo evaluation for epilepsy sur- • Resective surgeries
gery candidacy, the information gathered is – Hemispherectomy
discussed among peers in an interdepartmental – Lesionectomy and lobectomy
meeting. This multidisciplinary meeting is a vital – Multilobar resection
• Corpus callosotomy Martínez et al. 2005). The choice of the type of

• Neurostimulation surgery depends on various factors including
– VNS, RNS, and others etiology (e.g., in utero infarct vs. hemimega-
• Minimally invasive epilepsy surgery nencephaly, Sturge-Weber syndrome) and radiolog-
ical findings (e.g., presence of encephalomalacia
and size of ventricles).
Resective Surgeries
Selection
While adult epilepsy surgery often consists of The most ideal candidate for hemispherectomy
temporal lobe resection, pediatric epilepsies, has intractable seizures originating from the hemi-
especially when associated with cerebral palsy, sphere contralateral to the hemiparesis/hemiplegia
are more likely to be extratemporal. The resective with poor fine motor dexterity and hemianopsia
surgeries performed in children include hemi- and a healthy other hemisphere.
spherectomy but also focal resections such as The presence of generalized ictal or interictal
lobar resection and multilobar resection. A major- findings on scalp EEG should not be an absolute
ity of resective surgery in cerebral palsy consists contraindication for surgery. This is illustrated
of hemispherectomy in spastic hemiplegia. How- in a study (Wyllie et al. 2007) involving 50 chil-
ever, in situations where the lesion on MRI is dren and adolescents where 30% to 100% of
more localized, a more selected focal resection interictal epileptiform discharges were either
can be attempted. generalized or appeared to emanate from the
healthy hemisphere. All patients, however, had
Hemispherectomy a likely epileptogenic lesion on MRI. Some also
For appropriately selected children and adoles- had subtle MRI abnormalities on the contralat-
cents with hemiplegic cerebral palsy and medi- eral side that were overshadowed by the major
cally intractable seizures, hemispherectomy can abnormality on the targeted side. Etiology was
provide excellent clinical outcomes including sei- predominantly cortical malformation or cystic
zure freedom and improvements in cognition and encephalomalacia in 84% of the patients. Sur-
quality of life. Many children with hemiplegic gery was hemispherectomy in nearly two-thirds
cerebral palsy fulfill these criteria. of the patients, with lobar or multilobar resec-
While the earliest hemispherectomy procedure tion in the remaining. Seventy-two percent
for treating intractable epilepsy was in 1938 were seizure-free, and 16% had marked
(McKenzie 1938), over the years, there have improvement, with 12% showing no change
been multiple modifications and improvements after surgery.
made in surgical techniques. This has helped Even when surgery was targeted a priori to
decrease complications and improve clinical out- be more likely palliative, there was a fairly
come. These have included hemispherectomy, good outcome (Ilyas et al. 2014), wherein 44%
functional hemispherectomy, and modified func- achieved seizure freedom and an additional 17%
tional hemispherectomy among others (Adams had a more than 50% reduction in seizure
1983; Rasmussen 1983; Rasmussen and frequency.
Villemure 1989). There have been changes in the Evaluations such as interictal and ictal EEG
preferred surgical approaches. The aim of these recording, a careful review of MRI and other
modified techniques is to have complete discon- neuroimaging, PET scan (especially if bilateral),
nection of the epileptogenic zone of the brain fMRI, and intracarotid amytal injection (Wada
while leaving the disconnected hemisphere in test) in older patients, if needed, are very helpful.
situ and keeping blood supply intact. This is pri- A careful documentation of a thorough examina-
marily to avoid potential complications encoun- tion, neuropsychological baseline, and the aim of
tered previously in anatomical hemispherectomy, surgery (curative vs. palliative) should be made.
such as superficial cerebral hemosiderosis and The surgical outcome is usually presented as per
hydrocephalus (Kalkanis et al. 1996; González- the ILAE outcome scale.
Infancy of 6 years but can occur even at a later date, up to

Over the last couple of decades, epilepsy surgery adolescence. This was also confirmed with the
has been increasingly performed in selected transfer of language function as evident on fMRI
patients during infancy. In a study of 18 children (Hertz-Pannier et al. 2002). There is an innate
with a mean age of 1 year, 94% had more than ability of the right hemisphere to harbor language
90% decrease in seizures with 66% achieving function even at a later date. This has been studied
complete seizure freedom (González-Martínez in Rasmussen’s encephalitis (Boatman et al.
et al. 2005). Similar results were replicated in 1999). There is presumed more bilateral distribu-
other studies, with surgical results showing 60% tion of receptive than expressive language. Also,
seizure freedom in a series of children undergoing motor reorganization is less predictable compared
various epilepsy surgeries, with half of the with somatosensory function. For a patient under
patients younger than 1 year (Duchowny et al. evaluation for surgery, this can be studied nonin-
1998). The lower age limit is often of concern vasively with fMRI and diffusor tensor imaging.
because of potential medical complications from After surgery, parents often report accelerated
a major procedure, although these have decreased motor and cognitive milestones with improved
over time (Gröppel et al. 2018). behavior and socialization (Duchowny et al. 1998).
Outcome Complications
Across multiple studies, near or complete seizure Repeat surgical evaluation after a failed epilepsy
freedom is achieved in 65% to 80% of the surgery is not uncommon. It is needed in about
children undergoing epilepsy surgery (Moosa 20% to 54% of patients (Peacock et al. 1996;
et al. 2013; Peacock et al. 1996; de Palma et al. González-Martínez et al. 2005; Caraballo et al.
2019). In a study of 58 children undergoing hemi- 2011). This occurs usually when incomplete dis-
spherectomy at the mean age of 4.8 years, 60% connection or resection is made.
were seizure-free after 1 year, and another 28% Mortality ranges from 0% to 2% and is higher
had a more than 90% seizure reduction. In com- with younger age at time of surgery (Duchowny
parison with their pre-surgical motor functioning, et al. 1998; González-Martínez et al. 2005; Moosa
there was an improvement in 54%, unchanged in et al. 2013; de Palma et al. 2019; Peacock et al.
22%, and mixed results in 24% of the patients 1996). While shunt for hydrocephalus may be
(Peacock et al. 1996). required, this is more likely in anatomical hemi-
Earlier age at surgery has been associated with spherectomy, rather than functional hemispherec-
better developmental outcomes in multiple stud- tomy (Peacock et al. 1996; González-Martínez
ies, which have been replicated over time et al. 2005). Delayed development of superficial
(Tinuper et al. 1988; Peacock et al. 1996; Wiebe cerebral hemosiderosis is often a reason for
and Berg 2013; Lew 2014). This likely is from avoiding anatomical hemispherectomy (Kalkanis
prevention of harmful effects of intractable sei- et al. 1996; González-Martínez et al. 2005), but
zures on development and neuroplasticity at a anatomical hemispherectomy is sometimes pre-
younger age. ferred as in some brain malformations.
Since 95% of right-handed and 70% of left-
handed individuals have left hemispheric lan- Other Resective Surgical Techniques
guage dominance, early age for surgery is more Including Lesionectomy and Multilobar
important in left hemispheric epilepsy. When the and Lobar Resection
etiology for epilepsy has an onset before the age Apart from hemispherectomy, other types of
of language development (common in patients resective surgery include focal and multilobar
with cerebral palsy), the language often reorga- resection. Lesionectomy and focal resection can
nizes to the right hemisphere. The transfer of be performed successfully when the likely epilep-
language to the non-dominant side is more pre- togenic zone is suspected to be limited and there is
dictable when surgery is performed under the age no hemiparesis. When there is a clear congruency
between seizure semiology, MR imaging, and Adverse Effect

interictal and ictal scalp EEG, very few other In the pediatric age group, adverse effects are
additional tests may be needed (Jayakar et al. usually transient and rarely serious. Other than
2014). Multiple additional noninvasive testing those associated with the surgical procedure,
such as FDG-PET, SPECT, and MEG may be acute disconnection syndrome can occur in up to
needed when a discrepancy exists in pre-surgical 12.5% of complete callosotomy patients, which
testing. includes symptoms such as transient mutism and
Based on the location of the lesion, identifica- lethargy. This is more likely to occur in children
tion of eloquent areas may be needed with nonin- with intellectual disabilities and those above
vasive testing such as fMRI and MEG, although 12 years of age but almost never occurs in limited
direct cortical stimulation with subdural or depth anterior callosotomy. However, disconnection
electrodes is the gold standard. syndromes are usually transient and generally
nondisabling.
Corpus Callosotomy
Neurostimulation
Indication
This is a form of a palliative epilepsy surgery, Novel sites and methods of neurostimulation for
performed primarily with an intention to decrease optimal seizure control have been developed over
and often achieve seizure freedom from drop sei- the years. These include stimulation of the ante-
zures. These include atonic or tonic episodes lead- rior nucleus of the thalamus (SANTE trial
ing to a drop often resulting in facial and other Salanova et al. 2015), caudate nucleus, hypothal-
forms of trauma to the child (Graham et al. 2016). amus, and bilateral cerebellar stimulation (which
Over many decades, multiple studies, mostly may also decrease spasticity (Davis 2000), among
retrospective, have shown consistent improve- others. Varying results with moderate efficacy
ment in drop seizures following corpus have been reported. These devices, however,
callosotomy. In a recent series from Children’s stimulate the various sites at set parameters, and
Hospital of Michigan, Luat et al. reported that, the optimal settings continue to be refined.
with regard to drop seizures, 35% of patients A novel method of responsive neurosti-
achieved seizure freedom, 15% had a 76% to mulation (RNS, NeuroPace ®), which has an affer-
99% seizure reduction, and 50% had a 50% to ent arm along with an efferent arm, has been
75% reduction (Luat et al. 2017). A decrease in developed and is now FDA approved (Anderson
other seizure types was also noted, albeit to a et al. 2008) (Fig. 2). The efferent arm stimulates
smaller extent, and indeed no major improvement the epileptogenic area, but only when an early
in focal dyscognitive seizures was seen. seizure (pre-ictal EEG changes) is detected by
The exact mechanism of seizure amelioration the afferent arm of the device. Strip or depth
from corpus callosotomy is not completely under- electrodes are placed in one or more epileptogenic
stood, but likely extends beyond simply pre- areas and can help learn the patient’s epilepto-
venting the rapid spread of a seizure to the other genic pattern with an aim to optimize the respon-
hemisphere. sive stimulation. The patient is usually unaware of
For the pediatric age group (especially in chil- the stimulation. While approved solely in adults
dren less than 12 years of age), a much better until recently, there is increasing enthusiasm to
outcome is seen with complete callosotomy rather use RNS for intractable pediatric epilepsies
than the more limited anterior two-thirds (Kokoszka et al. 2018). This may become an
callosotomy (Graham et al. 2016). The surgery important tool in children with cerebral palsy
can be performed via open craniotomy but is who often have more than one epileptogenic
increasingly being performed endoscopically region and are not ideal candidates for resective
(Chandra et al. 2016). surgery.
VNS intractable epilepsy, including children with

Vagal nerve stimulation (VNS) provides program- Lennox-Gastaut syndrome (LGS) (Morris et al.
mable intermittent electrical current to the vagus 2013). Also, unlike most antiepileptic drugs, the
nerve (usually left) via a device placed in the efficacy of seizure reduction with VNS increases
subcutaneous region of the chest wall (Fig. 3). over time and persists (Arhan et al. 2010; Morris
There is proven efficacy in reducing seizure fre- et al. 2013). Apart from seizure frequency, there is
quency and severity and improving mood and, in an observed overall decrease in seizure severity,
general, quality of life. Most prospective studies recovery time after a seizure, and number of hos-
are, however, adult-based studies or retrospective pitalizations (Shahwan et al. 2009). The response
in nature, with the first prospective study in was even more favorable in the younger group
41 children only in 2012 (Klinkenberg et al. (<12 years at implantation) (Alexopoulos et al.
2012). 2006). Although there may be a lower efficacy in
While seizure freedom is seldom seen with children with intellectual disability (Mantel-
VNS, a seizure frequency reduction of more than Haenszel meta-analysis; p = 0.028, OR 0.18
50% was seen in about 55% of children with (CI 95% 0.039–0.84)), the known improvements
Fig. 2 Responsive
neurostimulation (RNS,
NeuroPace ®)
Fig. 3 Vagal nerve

stimulation (VNS) device
and its monitoring system
in quality of life measures and even some degree Minimally Invasive Epilepsy Surgery
of seizure reduction/severity favor the use of
VNS in children with epilepsy and intellectual With progressive improvements in neuroimaging
disabilities (Shahwan et al. 2009; Sourbron et al. coupled with robot-assisted stereotactic placement
2017). Additionally, by suppressing interictal of depth electrodes, minimally invasive surgical
epileptiform discharges, VNS implantation may techniques have increased over the last decade.
also favor improving neurocognitive develop- These include endoscopic corpus callosotomy
ment in children with cerebral palsy (Jaseja (Chandra et al. 2016), keyhole functional hemi-
2008, 2011). spherectomy (Schramm et al. 2001; Binder and
Improvement in mood is known to occur in Schramm 2006), MRI-guided stereotactic laser
adult patients but has not been adequately evalu- ablation (Curry et al. 2012), and stereotactic ther-
ated in children (Morris et al. 2013). A reduction mal ablation, among others. While limited to cer-
in dose or number of antiepileptic medications can tain etiologies of intractable epilepsy, these
be achieved at times (Shahwan et al. 2009) with a decrease duration of hospitalization, postoperative
resultant decrease in drug-related side effects and pain, and cosmetic consequences of surgery
increased alertness. (Reisch et al. 2013; Quigg and Harden 2014).
Because of the reasons cited above, there is
often an improvement in the quality of life and
parental satisfaction (Zamponi et al. 2008). More Conclusion
than two-thirds of caregivers opt to replace the
VNS battery, usually depleted after an average The basic concepts of epilepsy surgery in patients
period of 5 years. with cerebral palsy are similar to those in other
The surgery is usually an outpatient procedure children with intractable epilepsy. We have pro-
performed by a neurosurgeon via a single cervical vided the usual methodological approach in the
incision. The multiple programmable parameters evaluation for epilepsy surgery and described the
are then increased slowly, usually every 2 weeks, various types of procedures and options available.
by a neurologist using a wireless programming When appropriate, children with cerebral palsy
wand. Newer devices (Sentiva ®) can also be pro- should be considered for epilepsy surgery, and
grammed to auto-increase the parameters as per the presence of cerebral palsy should not be a
the desired schedule. A magnet (size of a watch) contraindication. However, children with cerebral
can be used to give a slightly higher current in palsy have additional confounding features, such
addition to the scheduled stimulation. This is used as the functional integrity of brain regions outside
as an abortive measure by the caregiver and can the epileptogenic area, and these have to be
help abort or shorten a seizure. It can also be used assessed since they are the substrates for reorga-
to temporarily switch off the device. nization following resection. The newer mini-
Side effects of VNS are generally acceptable. mally invasive devices and surgical procedures
Although infection is rare, it is more likely in are being increasingly considered in patients
children (Morris et al. 2013). Hoarseness of with cerebral palsy whose seizures are intractable.
voice, coughing, and tingling sensation are the
most common side effects and usually resolve
over time. A change in parameters (Chen et al. Cross-References
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Hydrocephalus in the Child
Jeffrey Campbell
Contents
Hydrocephalus in Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 483
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 483
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 484
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 489
Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 491
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 493
Abstract threat of new neurological injury from a

Approximately 15% of children with cerebral malfunctioning shunt.
palsy (CP) have concomitant hydrocephalus,
which can be both a cause of CP and a result of Keywords
disorders that independently lead to CP. While Hydrocephalus · Shunt · Endoscopic third
CP by definition is a static neurologic deficit, ventriculostomy · Ventricle · Cerebrospinal
hydrocephalus and its treatment is a dynamic fluid · Aqueductal stenosis · Dandy · Walker
process that can create new disability or even malformation · Intraventrentricular
death throughout the life span. It is vital for the hemorrhage of prematurity · Meningitis
provider to recognize hydrocephalus that ben-
efits from treatment and be able to offer the full
range of treatment options, including shunts Hydrocephalus in Cerebral Palsy
and endoscopic third ventriculostomies.
Unfortunately, even with the best of care, cur- Introduction
rent treatments of hydrocephalus are fallible,
and many patients live under the constant Hydrocephalus is both a cause and an effect of
cerebral palsy. Severe congenital hydrocephalus
can result in significant brain injury by the time
treatment is possible, resulting in varying degrees
J. Campbell (*)
of cerebral palsy (CP). Likewise, a variety of
Nemours/A.I. duPont Hospital for Children, Wilmington, developmental anomalies of the brain that cause
DE, USA CP, such as holoprosencephaly, includes a high
e-mail: jeffrey.campbell@nemours.org

https://doi.org/10.1007/978-3-319-74558-9_215
484 J. Campbell
likelihood of concomitant hydrocephalus. In addi- ventricular system, most commonly the aqueduct
tion, many acquired processes that create brain or the outlets from the fourth ventricle. Commu-
injury either prenatally or in the newborn, such nicating hydrocephalus occurs when CSF can exit
as an intraventricular hemorrhage of prematurity, the ventricular system but is not absorbed back
can cause hydrocephalus. into the bloodstream. In newborns, this results
from scarring of subarachnoid space from blood
or infection or increased venous sinus pressures
Natural History from congenital heart disease. By several months
of age, infants produce nearly as much CSF as
Anatomy and Physiology adults, averaging around 400 mL/day (Yasuda
The brain and spinal cord start embryonically as a et al. 2002). The amount of CSF produced in
tube, the center of which persists in the newborn preterm and newborn infants is less, although
as a series of ventricles within the brain that con- actual volumes are not well known.
tain cerebrospinal fluid (CSF). Most CSF is pro- It is important to distinguish between enlarged
duced within the ventricles, either by the choroid ventricles because of a pathological accumulation
plexus, which sits primarily within the lateral of CSF versus ex vacuo changes, where the ven-
ventricles, or within the brain tissue itself. CSF tricles are larger because of less brain paren-
travels from the two lateral ventricles, which are chyma. It is usually simple to distinguish
mirror images of each other, through the foramen between these states with simple observations on
of Monro into the single midline third ventricle. It physical exam, since children with ex vacuo
then passes through the aqueduct of Sylvius, a changes will not exhibit the signs and symptoms
1-mm-wide passageway that connects the third of increased intracranial pressure (ICP) described
and fourth ventricles. From the fourth ventricle, below and will have head sizes that are smaller
CSF leaves the ventricular system through the than average.
midline foramen of Magendie or the two lateral
foramen of Luschka and proceeds into the sub- Physical Findings
arachnoid spaces that surround the brain. CSF is Infants with hydrocephalus generally exhibit
absorbed into the bloodstream through the arach- symptoms and signs of increased intracranial
noid pacchionian granulations, which are small pressure. The symptoms of increased ICP in an
protrusions of arachnoid into the venous sinuses, infant include developmental delay, failure to
primarily along the sagittal sinus. CSF enters into thrive, lethargy, and feeding disturbances. Signs
the sinus through a pressure-mediated mechanism include rapid head growth, splitting of the sutures,
such that intracranial CSF pressure is higher than fullness of the anterior fontanel, dilation of scalp
the venous sinus pressure. Unlike any other veins, and sunsetting eyes, a manifestation of
venous structures in the body, the dural venous Parinaud’s syndrome. Older children develop
sinuses are held mechanically open and will go to more classic signs of increased ICP, including
negative pressures when the child is upright, since headache, nausea, vomiting, and lethargy. These
the head is well above the heart. The ICP follows symptoms are often worse in the early morning,
this pattern, so an infant will have a sunken fon- since intracranial pressure is highest when the
tanel when sitting up and more full when child is reclined for an extended period.
lying down.
The brain continuously produces CSF, so alter- Causes
ations in this circulation can cause it to accumu- There are various causes of congenital hydroceph-
late within the ventricles, thus creating alus. Some only involve the development of
hydrocephalus. In general, causes of hydrocepha- enlarged ventricles, while others involve other
lus are divided into two categories, obstructive central nervous system (CNS) malformations.
and communicating. The former occurs when Additionally, acquired CNS insults can cause
there is occlusion of passageways within the hydrocephalus in all patients including infants.
33 Hydrocephalus in the Child with Cerebral Palsy 485
A. Primary causes – Hydrocephalus by itself can have more mild intellectual disability and
be the cause of CP, especially when it develops adducted thumbs, but do not generally
prenatally to such an extent that CNS injury develop hydrocephalus. Other recognized
has occurred by the time of birth. Alternately, L1 syndromes associated with hydroceph-
some primary disorders of the brain that cause alus include X-linked complicated heredi-
CP can have associated hydrocephalus. tary spastic paraplegia type 1 and X-linked
a. Aqueductal stenosis – The most common agenesis of the corpus. These are associ-
form of primary hydrocephalus is obstruc- ated with more mild intellectual disability
tion of the aqueduct of Sylvius, accounting and the other named findings. In addition to
for approximately 30–40% of all cases of the X-linked forms of hydrocephalus, there
hydrocephalus in children (Hirsch et al. is an autosomal recessive form of
1986). This has a bimodal distribution of aqueductal stenosis with equal penetration
onset, with roughly half the cases pre- in males and females that has been reported
senting in newborns/infants and the other in a handful of children (Castro-Cago et al.
half acquired later, typically in adoles- 1996).
cence. There is a slight male preponder- c. Dandy-Walker malformation – The most
ance, likely secondary to X-linked prominent finding is aplasia or significant
hydrocephalus described below. When this hypoplasia of the cerebellar vermis,
develops prenatally, the severity of the resulting in what looks like an enlarged
hydrocephalus at birth can be impressive, fourth ventricle. There is usually atresia of
with head circumferences sometimes larger the foramens of Luschka and Magendie,
than the average adult circumference. Even resulting in obstructive hydrocephalus in
with adequate treatment of the hydroceph- roughly 80% of these children (Benda
alus, many of these children will have sig- 1954). A percentage of these children also
nificant developmental delay and develop have occlusion of the aqueduct resulting in
cerebral palsy. more complex hydrocephalus that requires
b. Inherited hydrocephalus – There are sev- treatment of both the fourth and lateral ven-
eral inherited forms of hydrocephalus, most tricles (Mohanty et al. 2006). Dandy-
of which are part of L1 syndrome, caused Walker malformations occur in roughly
by a mutation in the L1CAM gene and 1:30,000 births with a female preponder-
associated with the MASA syndrome: ance. While most of these cases occur spo-
mental retardation, aphasia, shuffling gait, radically, there is an association with
and adducted thumbs (Marin et al. 2015). various genetic disorders such as trisomy
The most common of these is known as 18, as well as an increased incidence with
X-linked or Bickers-Adams-Edwards syn- prenatal exposures such as warfarin and
drome (Edwards 1961), with an incidence maternal diabetes. Dandy-Walker
estimated at 1:33,000 births. It can be diag- malformations are also found in PHACE
nosed prenatally by the presence of syndrome – Posterior fossa brain
adducted thumbs in the first trimester malformations; Hemangioma on the skin
(Senat et al. 2001) and the impressive of the head or neck (greater than 5 cm);
hydrocephalus that typically develops in Arterial abnormalities in the neck or head;
the second trimester. These children have Cardiac abnormalities/aortic coarctation;
aqueductal stenosis, severe intellectual dis- and Eye abnormalities.
ability, adducted thumbs, and various brain d. Arachnoid cyst – The meninges of the brain
malformations in the corpus callosum, and spinal cord include the pia mater,
medulla, and cortex. These children may arachnoid, and dura. The pia is adherent
account for up to 25% of boys born with to the tissue, while the dura and arachnoid
aqueductal stenosis. Female carriers may form two large sacs that contain the brain
486 J. Campbell
and subarachnoid CSF that surrounds the create motor system findings that highly
brain. The inner sac, the arachnoid, is resemble more typical CP (Ozaras et al.
microscopically thin but watertight. The 2005). In particular, children who develop
space between the dura and arachnoid severe prenatal hydrocephalus may suffer
should be empty. Early in brain develop- sufficient brain injury prior to treatment to
ment, the arachnoid may curl on itself to have concomitant CP. In addition, symp-
form a separate pocket of CSF that is not in tomatic Chiari II malformations can create
continuity with the rest of the subarachnoid permanent brainstem and upper spinal cord
CSF. Approximately half of these form in injury with a resultant spastic quadriparesis
the anterior portion of the middle fossa, in addition to the flaccid paraparesis from
with the frontal convexity and posterior the myelomeningocele.
fossa the next most common locations. f. Holoprosencephaly – This disorder is
These represent 1% of intracranial lesions caused by failure of the prosencephalon to
and are more common in males. Even when divide into the two cerebral hemispheres,
these appear impressively large, they are resulting in a single-lobed brain structure.
most commonly incidental findings, since This occurs in roughly 1 in 8,000 live births,
a majority do not grow and cause symp- and the developmental consequences are
toms. The pathophysiology that allows variable, although most of these children
some of these to grow is unclear, but theo- develop CP as they get older (Raam et al.
ries include a CSF pressure gradient, uni- 2011). There is often midline fusion of the
directional ball-valve mechanism, and thalami and a dorsal cyst, which can create
oncotic gradient from increased proteins occlusion of the aqueduct, resulting in
in cyst or secretory cyst membranes obstructive hydrocephalus (Simon et al.
(Westermaier et al. 2012). The ones that 2001). This is common in the more severe
do grow usually do so in children under alobar form, where the brain makes little
the age of 4 (Al-Jolou et al. 2010). They attempt to divide into hemispheres (Hahn
can become massive and cause brain injury and Plawner 2004). Most cases appear spo-
or hydrocephalus, especially when they radically, although roughly 40% are associ-
enlarge prenatally. Hydrocephalus can ated with trisomy 13 and other genetic
develop when the cyst grows large enough disorders.
to distort midline structures and kink the B. Secondary causes – CP is frequently the result
aqueduct. of acquired CNS injury from prematurity,
e. Myelomeningocele – Failure of primary infection, trauma, and other insults to the
neurulation of the caudal neural tube brain prenatally or soon after birth. Many of
around 26 days postconception results in these acquired CNS injuries can secondarily
spina bifida cystica or myelomeningocele. cause hydrocephalus, which can increase the
The distal end of the cord does not form, brain injury and worsen the CP.
with resulting distal neurological dysfunc- a. Intraventricular hemorrhage of prematu-
tion such as a neurogenic bladder and vary- rity (IVH) – As viability has moved to
ing degrees of lower extremity flaccid younger gestational ages, the complications
paralysis, depending on the level. There associated with prematurity continue to
are a host of intracranial findings in most contribute to the development of cerebral
of these children including a Chiari II mal- palsy despite improvements in neonatal
formation and hydrocephalus. While the care. Bleeding into the germinal matrix
pattern of neurological dysfunction is typi- can cause both injury to the surrounding
cally distinct from children with cerebral brain and the development of hydrocepha-
palsy, some of these children will suffer lus as blood interferes with normal CSF
secondary brain or spinal cord injuries that circulation.
The germinal matrix is a periventricular Grade III: hemorrhage with extension into
region in the prenatal brain where early the ventricle with dilation of the
neurons reside before migrating along ventricle
radial glia to the hemispheric cortex. It is Grade IV: parenchymal hemorrhage
largest around 23 weeks gestation, halving
in size by 32 weeks, and largely The likelihood of death, disability, and
disappearing by 36 weeks (Duncan and hydrocephalus correlates with the grade of
Change 2008). The germinal matrix is IVH, with severe IVH an independent pre-
highly cellular and vascularized, with a cap- dictor of cerebral palsy (van Haastert et al.
illary bed that has a minimal collagen base- 2011). Approximately one third of very
ment membrane, paucity of pericytes, low-weight infants will suffer a germinal
fewer tight junctions, and diminished sup- matrix hemorrhage, with a higher incidence
port by surrounding astrocytes, resulting in and severity at younger gestational ages
vessels that are more fragile (Ballabh (Stoll et al. 2010). For each week of gesta-
2010). In addition, these vessels receive a tion prior to 28 weeks, there is a roughly 8%
disproportionate volume of cerebral blood absolute increase in incidence of IVH such
flow to support the high metabolic that two thirds of infants who survive 12 h
demands. These fragile vessels with at 22 weeks gestation will suffer a hemor-
impaired autoregulation are the site of ger- rhage. In addition, the average grade of
minal matrix hemorrhages and IVH. hemorrhage increases with early gestational
Bleeding into the germinal matrix is age such that infants born at 22 weeks are
often the consequence of respiratory or cir- tenfold more likely to suffer a grade IV
culatory fluctuations. Increased cerebral hemorrhage than an infant born at
perfusion pressure from hypertension can 28 weeks. Of infants who experience IVH,
rupture these vessels. Likewise, hypercap- roughly half do not develop hydrocephalus,
nia can dilate the cerebral vasculature, a quarter experience ventricular dilatation
increasing flow to these vessels. Hypoxia that stabilizes without intervention, and a
is thought to damage the endothelial lining quarter have progressive hydrocephalus
of the vessels leading to increased friability (Murphy et al. 2002). Of those with pro-
and hemorrhage. The incidence of germinal gressive hydrocephalus, 40% required per-
matrix hemorrhages in the very low-birth- manent treatment with a shunt, roughly
weight infant (<1500 g) fell in half during 10% of all infants with IVH.
the 1980s due to improved medical care but Hydrocephalus after IVH can develop
has remained around 20% since that time. for various reasons. Blood in the lateral
The incidence is higher in the extremely ventricles can produce a form of obstructive
low birth weight infant (<750 g) at around hydrocephalus by blocking the aqueduct
45% (Ballabh 2010). with clot. As CSF carries blood through its
While the source of bleeding is the ger- normal circulation, blood products can cre-
minal matrix, the hemorrhage often extends ate an inflammatory response in the outlets
into either the surrounding parenchyma of the fourth ventricle, creating a further site
and/or lateral ventricle. The most common of obstruction. Finally, blood will often cir-
grading scale divides IVH into: culate into the subarachnoid spaces and
create scarring that impedes CSF from
Grade I: hemorrhage confined to the sub- reaching the arachnoid granulation tissue.
ependymal layer Thus, the infants with persistent hydro-
Grade II: hemorrhage with extension into cephalus often have a mixed picture of
the ventricle without dilation of the obstructive and communicating hydroceph-
ventricle alus. They will also sometimes develop
488 J. Campbell
loculated hydrocephalus, where the fourth treatment, and some of these children will
ventricles do not communicate with either have dozens.
the subarachnoid space or the third ventri- c. Non-accidental trauma – The so-called
cle, complicating the treatment strategies. shaken baby syndrome can result in sig-
Severity of IVH correlates with nificant brain injury and cerebral palsy.
neurodevelopmental outcomes, with stud- These infants typically suffer high-
ies from the 1990s suggesting that IVH velocity cranial shaking and impacts that
severity was the primary determinant of create severe diffuse axonal injury and
cognition, motor function, and risk of epi- cerebral ischemia. While there are often
lepsy in survivors (Levy et al. 1997). As areas of subdural and subarachnoid hem-
will be discussed further in the section on orrhage, these rarely cause mass effect or
“Treatment”, a number of strategies have require acute surgical evacuation. Over
been explored to minimize the need for time as the blood in the subdural space is
shunting and lessen the long-term disabil- broken down, some of these children will
ity, none of which produced dramatic develop chronic subdural collections that
changes in the course of these children. may require drainage in the weeks after
b. Meningitis – While vaccines have signifi- the initial injury. Chronic subdurals result
cantly diminished the incidence of neo- from inflammatory membranes that form
natal meningitis, the infections that do around subdural hemorrhages that secrete
occur can result in significant brain injury fluid, as well as the increased osmotic
and cerebral palsy. The most common impact of digestion of red blood cells
pathogen causing spontaneous meningitis into smaller and more osmotically active
under a year of age is group B streptococ- components.
cus, with Escherichia coli and Listeria Treatment of chronic subdural collec-
monocytogenes as other common bacte- tions may include placement of a
ria. In the premature infants, secondary subdural-peritoneal shunt, since the fluid
meningitis from systemic infections is tends to recur after drainage, although
common. These children may develop within several months, most of these shunts
necrotizing enterocolitis with virulent are no longer necessary. A small number of
bowel pathogens such as E. coli, which these infants will develop hydrocephalus,
can create significant cortical injury if it most commonly communicating in nature,
spreads to the brain. from scarring of the subarachnoid spaces.
These bacteria create a significant These children will often require ventricu-
inflammatory response in the brain, includ- loperitoneal shunts for life.
ing in the walls of the ventricles and sub- d. Brain tumors – Congenital brain tumors
arachnoid spaces. As a result, many of tend to be large and aggressive. The most
these children develop hydrocephalus, common pathologies include germ cell
either because of obstruction within the tumors, choroid plexus carcinoma, atypical
ventricular system or communicating teratoid rhabdoid tumors, and primitive
hydrocephalus because CSF cannot reach neuroectodermal tumors. Many of these
the arachnoid granulations. Especially with form in a supratentorial midline location
E. coli infections, some of these children and cause obstructive hydrocephalus.
develop multiple sites of obstruction within Aggressive surgical resections are often
the ventricles or even multiple loculated both unwise and unhelpful, so surgical
cysts within the lateral ventricles. These treatment may be limited to tissue diagnosis
children with multiloculated hydrocepha- and treatment of hydrocephalus. Relatively
lus pose special challenges for treatment, few of these children survive more than a
since each loculated area requires year, but those that do often have
significant developmental delay and cere- with the invention of the shunt. This moves CSF
bral palsy. from the brain to somewhere else in the body
e. Congenital heart disease – Many forms of where the fluid reabsorbs back into the blood-
congenital heart disease result in high right stream. The first shunts drained CSF into the
atrial pressures and a resultant increase in ureter, although this sometimes resulted in elec-
systemic venous pressures. If the cerebral trolyte imbalances since CSF contains a signifi-
sinuses have increased venous pressures, cant amount of potassium and sodium. It was soon
less CSF will be absorbed since this process discovered that CSF could be drained directly into
is pressure mediated with ICP generally the bloodstream by putting the distal end into the
several Torr greater than sinus venous pres- right atrium. Soon thereafter, shunts were placed
sure. Many of these children will develop a into body cavities such as the peritoneal cavity,
mild form of communicating hydrocepha- where high volumes of fluid could be absorbed
lus, some of whom benefit from treatment into the walls of the organs.
of the hydrocephalus. There is an increased While shunts are effective treatments of hydro-
incidence of cerebral palsy in this patient cephalus, they are plagued with relatively high
population as well, likely secondary to infection rates and often occlude, requiring addi-
chronic cerebral ischemia from both the tional surgery. Additionally, shunts do not create
heart disease and its treatment. physiological pressures in the brain, since they are
apt to drain too much CSF due to siphoning with
the amount of drainage dependent on the patient’s
Treatment position. Because of these problems, surgeons
have searched for other treatment options.
Not all hydrocephalus needs to be treated. Starting in the 1980s, surgeons found that children
Enlargement of the ventricles has different conse- with obstructive hydrocephalus could be treated
quences in a young infant with a skull that can by creating an alternate passageway for CSF to
rapidly expand because of loose sutures than it leave the ventricular system. There is a thin mem-
does in an older child where the intracranial vol- brane at the floor of the third ventricle, and a small
ume is relatively fixed. Young infants rarely man- opening can be made using an endoscope,
ifest signs or symptoms of very high ICP since they connecting the third ventricle with the subarach-
can readily expand their intracranial volume. Some noid space in front of the pons. Endoscopic third
number of these infants will equilibrate between ventriculostomies are an increasingly popular
CSF production and absorption over time, devel- treatment option for hydrocephalus.
oping compensated or arrested hydrocephalus. It is
common to identify older children with large heads 1. Shunt – This is fundamentally plumbing, a
and enlarged ventricles but no apparent signs or means of moving CSF out of the cranium to
symptoms of increased ICP, highlighting the need somewhere else in the body where it can be
for caution in overtreating infants with some returned to the bloodstream. The primary
enlargement of the ventricles. Treatment is invention that made these possible was a
reserved for infants with clearly progressive hydro- valve that could limit flow to one direction
cephalus and/or symptoms of increased ICP. and maintain some positive pressure in the
There are no effective medical treatments for ventricles. This technology is far from perfect,
hydrocephalus. Carbonic anhydrous inhibitors, with a tendency to over drain due to siphoning
such as acetazolamide (Diamox), will diminish when the patient is upright. In addition, the
the amount of CSF production in the ventricles, valves have a high failure rate when exposed
but are not effective treatments of hydrocephalus to blood, and ventricular catheters have a high
since there remains a mismatch between CSF incidence of occlusion over time.
production and absorption. Effective surgical a. Subgaleal shunts/ventricular access devices
treatment of hydrocephalus started in the 1950s – Infants with intraventricular hemorrhage
490 J. Campbell
of prematurity are difficult to treat because normal intracranial CSF dynamics. Since
of the amount of blood in the CSF. Tradi- the distal sites are below the head, shunts
tional shunts have a very high likelihood for have a tendency to siphon and over drain
malfunction with clogging of the valves and when the child is upright. A number of
an infection rate that may top 20%. Various shunt valve designs have been developed
temporizing strategies have been used over to attempt to limit this effect, including
the years, including serial lumbar punctures incorporation of antisiphon devices and
or serial ventricular taps through the fonta- programmable valves where the pressure
nel. Most surgeons now place either a ven- can be changed with magnets through the
tricular access device or a ventriculo- skin. Unfortunately, the problem of over
subgaleal shunt. The former is a ventricular drainage persists.
catheter attached to a subgaleal reservoir Additionally, shunts are mechanical
that is tapped with a butterfly needle to devices and are prone to both infections
drain CSF as needed. The latter is much and malfunctions. The failure rate of a
the same but includes a catheter that extends shunt is roughly 30% in the first 6 months
into the subgaleal space, which is surgically and then 5% per year, with the average child
opened, allowing CSF to drain passively having two or three shunt revisions during
into this space. Some amount of CSF will childhood. The risk of infection is primarily
be absorbed from the subgaleal space, gen- in the first 6 months after an operation and
erally allowing sufficient drainage of CSF averages around 7% per procedure (Simon
without requiring serial taps. These tempo- et al. 2009). Many surgeons now use cath-
rizing measures continue until the CSF eters that have antibiotics impregnated
clears enough that either the hydrocephalus within the material that slowly leaches into
abates or a more permanent treatment is a the surrounding tissue to minimize the like-
reasonable option. All subgaleal shunt lihood of an infection.
eventually fail, since if the hydrocephalus 2. Endoscopic third ventriculostomy (ETV) –
persists, the volume of CSF produced Children with obstructive hydrocephalus can
outpaces the ability of the subgaleal tissue often be treated successfully by creating a new
to absorb it. passageway for CSF to leave the ventricular
b. Ventriculoperitoneal/pleural/atrial shunts – system, typically through a small opening in
A child with persistent hydrocephalus the floor of the third ventricle. An endoscope is
requires permanent diversion of CSF from navigated through the lateral ventricle and the
the intracranial spaces. Rather than the CSF foramen of Monroe into the third ventricle
accumulating under the scalp as with a sub- where the floor is usually quite thin. An open-
galeal shunt, the distal end terminates in a ing is made between the infundibular recess
site that allows for absorption of large vol- and the mammillary bodies, being careful to
umes of CSF. In a newborn, the typical avoid injury to the basilar artery below. This
distal sites include the peritoneal cavity opens into the prepontine cistern. The mem-
and the right atrium of the heart. In a brane of Liliequist is also opened to ensure free
school-age child, the pleural cavity is large flow of CSF into the subarachnoid spaces. In
enough to be an option as well. Occasion- younger children, the choroid plexus in the
ally none of these sites is available as an lateral ventricles can be cauterized to reduce
absorptive terminus for a shunt, and there the amount of CSF produced and raise the
are descriptions of using the gallbladder or likelihood of success.
one ureter as the distal site of the shunt. ETV is most successful in acquired
While shunts are an effective treatment aqueductal stenosis, where the subarachnoid
for hydrocephalus, they do not recreate spaces are normal and the CSF has been
Fig. 1 The ETV success

score, which predicts the
likelihood that a single ETV
will result in a long-term
successful treatment of
hydrocephalus. The scores
from the three columns are
totaled for a percentage of
success at 6 months after
surgery
adequately absorbed in the past. However, infections, malfunctions, and consequences of

given the high complication rate with shunts, nonphysiological patterns of CSF drainage.
ETV is increasingly used for other indications. There is also the lifetime burden of worry that
The ETV Success Score provides a reasonable every headache is a sign of impending shunt
estimate of the likelihood of the hydrocephalus failure.
being adequately managed with an ETV
according to the child’s age, etiology of hydro- 1. Infection – Most infections become symptom-
cephalus, and previous treatment with a shunt atic within 3 months, with the most common
(Kulkarni et al. 2010) (Fig. 1). pathogens being skin flora, particularly Staph-
ylococcus epidermidis. Nearly all shunt infec-
The score for each category is totaled to yield tions require removal of all of the infected
the approximate 6-month success rate. Few ETVs hardware, since antibiotics alone will rarely
fail after 6 months, so this percentage is largely clear the colonization of the shunt apparatus
durable over time. This is in contradistinction to because the bacteria produce a protective bio-
shunts, which have an initial failure rate that is film. A common strategy is to remove the
roughly 30% in the first 6 months but then a shunt, place an external ventricular drain
continued annual failure risk into future. Below (EVD), and treat with 1–2 weeks of antibiotics
are Kaplan-Meier curves of time to failure for depending on the bacteria. The EVD is then
ETV and shunts in a large series of 975 patients removed and a new shunt placed in a clean site.
with hydrocephalus (Beuriat et al. 2017) (Figs. 2 Some children will present with delayed shunt
and 3). infections from very indolent bacteria like Pro-
pionibacterium acnes. These children will
rarely exhibit constitutional signs of infection
Complications but present with shunt malfunctions or large
abdominal pseudocysts. There is a belief that
In many ways, hydrocephalus in these children shunt infections have a negative impact on
acts like a chronic disease that can have sudden intelligence, although the literature is not
acute exacerbations, especially in children treated definitive (Jackson 2010).
with a shunt. As previously noted, shunts are 2. Malfunction – As noted earlier, there is a
subject to a host of complications including lifetime risk of shunt malfunction, the
492 J. Campbell
1.0
0.8
Cumulated ETV Survival
0.6
0.4
0.2
0.0
0
80
40
00
60
20
80
40
00
60
20
80
40
00
60
20
80
40
00
36
72
10
14
18
21
25
28
32
36
39
43
46
50
54
57
61
64
68
72
Time (days)
Time (Years) 0 1 5 10 20
Number at risk 280 218 206 205 205
Fig. 2 Kaplan-Meier curve of time to failure for endo- initial period of around 6 months, failures become very
scopic third ventriculostomies in a large cohort of patients uncommon with no failures after 5 years
with long-term follow-up. This demonstrates that after an
1.0
0.8
Cumulated Shunt Survival
0.6
0.4
0.2
0.0
0
80
40
00
60
20
80
40
00
60
20
80
40
00
60
20
80
40
00
60
20
80
40
00
36
72
10
14
18
21
25
28
32
36
39
43
46
50
54
57
61
64
68
72
75
79
82
86
90
Time (days)
Time (Years) 0 1 5 10 20 25
Number at risk 695 490 444 420 389 389
Fig. 3 Kaplan-Meier curve of time to failure for VP shunts in a large cohort of patients with long-term follow-up. This
demonstrates a roughly 30% risk of failure in the first 6 months and then continued failures over decades
severity of which depends on the severity of are also associated with decline in cognition
the hydrocephalus and the rapidity in which according to one recent meta-analysis
the shunt is fixed. Other than the obvious (Arrington et al. 2016). In addition, there is
need for surgery and the resultant possible a risk of death, which in one long-term fol-
complications, multiple shunt malfunctions low-up series was over 8% and particularly
common in the spina bifida population ▶ Perinatal Stroke as an Etiology of Cerebral

(Paulsen et al. 2015). Palsy
3. Non-physiologic drainage – As previously ▶ Postnatal Causes of Cerebral Palsy
noted shunts tend to over drain when the ▶ Problems During Delivery as an Etiology of
child is upright because of siphoning. This is Cerebral Palsy in Full-Term Infants
a particular problem in children who receive
shunts very early in life. They can develop
very small ventricles, likely because the intra- References
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Sgouros S, Constantini S (2010) Predicting who will
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▶ Infectious Etiologies of Cerebral Palsy 6:310–315
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Part VIII
Psychologic and Psychiatric Problems
Psychiatric Disorders in Children
Rhonda S. Walter and Richard S. Kingsley
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 498
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 498
Identification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 499
Incidence/Prevalence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 499
Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 500
Treatment/Remediation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 501
Illustrative Case Study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 503
Recognition by IEP Regarding Motor Issues/Condition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 503
Conclusion/Areas for Future Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 503
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 504
Abstract learning. Parents, caretakers, and clinicians

Mental health issues including frank psychiat- can become familiar with signs of mental
ric disorders can be challenging to identify in health concerns in this population. This can
children given the complexity of attention, facilitate early referral for further testing, ther-
mood, and behavior regulation symptom pre- apeutic approaches (cognitive and pharmaco-
sentation over time. logical), and academic and social supports.
In children with cerebral palsy, identifica- Monitoring over time with more than one
tion can be further complicated by differences approach is discussed as warranted/necessary
in motor, communication, cognition, or based on a child’s individual progress and
developmental course.
R. S. Walter Keywords
Retired, Nemours, Alfred I. duPont Hospital for Children, Psychiatric disorders · Mental health issues ·
Wilmington, DE, USA
Attention deficit hyperactivity disorder · Mood
R. S. Kingsley (*) disorders · Anxiety disorders
Emeritus Staff, Division of Behavioral Health, Nemours,
Alfred I. duPont Hospital for Children, Wilmington, DE,
USA

https://doi.org/10.1007/978-3-319-74558-9_38
498 R. S. Walter and R. S. Kingsley
Introduction Association [APA] 2013), that may directly lead

to development of psychiatric illness, e.g., a def-
Cerebral palsy is a disorder of movement and icit in complex attention that results in a diagnosis
posture resulting from insult or injury to the devel- of ADHD. Alternatively, the brain disorder likely
oping brain that leads to static, nonprogressive conveys an indirect vulnerability factor that ulti-
impairment in motor function. While CP has a mately increases rates of psychiatric disorders.
wide spectrum of known causes, many cases are A full discussion of all symptoms associated
idiopathic (cause not known or yet to be discov- with pediatric mental health issues is beyond the
ered). Because the brain houses multiple areas of scope of this chapter. As a reference point, the
neural integration – motor, cognitive, language, DSM-5 defines ADHD as a persistent pattern of
emotional – if compromised, it is uniquely sus- inattention and/or hyperactivity that interferes
ceptible to conditions that affect multiple with functioning or development (APA 2013).
domains. This chapter will attempt to address Attention deficit is characterized by symptoms
some of the mental health conditions that can of impulsivity, inattention, and distractibility
be associated with cerebral palsy including with or without hyperkinesis. The symptoms
ADHD, depression, and anxiety, review known need to be observed developmentally, over time,
data on the topic, discuss relevant terminology and across multiple settings such as home, school,
and identification methods, survey known treat- and in play.
ment approaches, and delineate possible issues While no one label may best fit a particular
unique to evaluation and treatment of mental individual’s symptom presentation, generally
health issues in people with CP. As there is little accepted typology/diagnostic classifications for
published on this topic, the authors will provide a mood disorders include the depressive disorders
case study illustrating clinical approaches based (APA 2013) such as major depressive disorder,
on their experience and attempt to offer insights persistent depressive disorder, and disruptive
into directions for future study/inquiry. mood dysregulation disorder in addition to bipolar
and related disorders. Once again, as a reference
point, the DSM-5 characterizes major depressive
Natural History disorder as consisting of a period of at least
2 weeks during which time the symptoms of
As with the general population, children with CP either depressed/irritable mood or loss of interest
are susceptible to development of any psychiatric or pleasure are accompanied by several other
disorder; however, children with any brain disor- vegetative/neurovegetative symptoms such as
der including CP are at greater risk for psychiatric sleep, energy, and appetite disturbances. Persis-
disorders (Rutter 1977). Studies have also sug- tent depressive disorder is characterized by a
gested this risk to be non-specific (Brown et al. depressed mood for most of the day in more
1981). CP has its own unique set of presentations, days than not for at least 1 year in children and
and it is difficult to predict how a given set of 2 years in adults. Disruptive mood dysregulation
circumstances will affect the developing brain, disorder is characterized by severe recurrent tem-
but the model of insult from a mental health per- per outbursts that are grossly out of proportion in
spective is not unlike the sequelae of brain injury. intensity or duration to the situation or provoca-
The brain insult or injury attributed to CP may tion that is also inconsistent with developmental
affect any one or more of six neurocognitive level and occurs on average three or more times
domains, perceptual motor, language, learning per week.
and memory, social cognition, complex attention, Other mood disorders include bipolar disorders
and executive function, as outlined in the (APA 2013) which are generally categorized in
Diagnostic and Statistical Manual of Mental Dis- DSM-5 as bipolar I and bipolar II. For individuals
orders (5th ed.; DSM–5; American Psychiatric that experience bipolar I disorder, they must have
34 Psychiatric Disorders in Children with Cerebral Palsy 499
experienced a manic episode (characterized by a Identification

distinct period of at least 1 week of abnormally
and persistently elevated, expansive, or irritable Incidence/Prevalence
mood and increased goal-directed activity or
energy accompanied by other symptoms, e.g., According to the DSM-5, population surveys sug-
grandiosity and decreased need for sleep, that are gest that ADHD occurs in most cultures in about
sufficiently severe to cause marked impairment 5% of children and about 2.5% of adults (APA
in functioning). The individual with bipolar 2013). The percent of children estimated to have
I may also have experienced a hypomanic episode ADHD has changed over time and can vary by
(similar to mania but of shorter duration and with how it is measured. The American Psychiatric
less associated impairment in functioning) and/or Association (APA) states in the DSM-5 that 5%
a major depressive episode (see above, major of children have ADHD. However, other studies
depressive disorder). For a diagnosis of bipolar in the USA have estimated higher rates in com-
II disorder, the individual must meet the criteria munity samples including approximately 11%
for a current or past hypomanic episode (see of children in the age range of 4–17 years (http://
above) and a current or past major depressive www.cdc.gov/vitalsigns/adhd).
episode (see above). Depending upon how mood disorders are
DSM-5 anxiety disorders (APA 2013) such defined, there can be a broad range of frequency
as separation anxiety disorder, generalized anxi- recorded in childhood populations. For depressive
ety disorder, social anxiety disorder, and panic disorders, the DSM-5 suggests a prevalence in the
disorder may also be present in this population. 2–5% range over a 6-month to 1-year period for
Separation anxiety disorder is characterized by disruptive mood dysregulation disorder, 7% over
an excessive fear or anxiety concerning being a 12-month period for major depressive disorder
separated from those to whom the individual is (with marked differences by age group), and 0.5%
attached. Social anxiety disorder (social phobia) is over a 12-month period for persistent depressive
typically marked by fear or anxiety about one disorder/dysthymia (APA 2013). For bipolar
or more social situations where the individual is disorders, the DSM-5 suggests 0.6% prevalence
exposed to scrutiny. The social situation is often over a 12-month period in the USA for bipolar I
avoided or endured with intense fear or anxiety. and 0.8% prevalence over a 12-month period in
Panic disorder is typically characterized by recur- the USA for bipolar II. Bipolar I, bipolar II, and
rent unexpected attacks of intense fear or discom- bipolar disorder NOS (as defined in the DSM-IV)
fort associated with several physical symptoms, have the combined prevalence rate of 1.8% in the
e.g., accelerated heart rate and sensations of USA (APA 2013).
shortness of breath. Generalized anxiety disorder With respect to anxiety disorders, the DSM-5
involves excessive anxiety and worry occurring suggests a prevalence over a 12-month period of
more days than not for at least 6 months and with approximately 4% in children and 1.6% in ado-
associated symptoms such as sleep disturbance or lescents for separation anxiety disorders and a
irritability. prevalence of 7% over a 12-month period in the
In children as well as adults, any of the above USA for social anxiety disorder, with rates for
mental health concerns can be multifactorial in children and adolescents comparable to those of
origin – arising from within (endogenous), reac- adults. While panic attacks occur in children, the
tive (secondary to excitement/stimulation or being overall prevalence of panic disorder is low in
overwhelmed with the situation), or a combina- children before age 14 (less than 0.4%) with
tion of both. There is a significant component of rates gradually increasing in adolescence and
risk that is biologically based, but the role of peaking at around 2–3% for 12-month prevalence
environment is equally important and may convey rates during adulthood. Additionally, in the USA,
epigenetic risk. the 12-month prevalence rates of generalized
anxiety disorder are 0.9% for adolescents and prevalence of mental health disorders and symp-
2.9% for adults (APA 2013). toms in children and adolescents with cerebral
While these are standard definitions, none of palsy (Downs et al. 2018). In summary, it noted
these presentations are static, and they vary with that mental health symptoms are common and men-
various developmental stages and potentially with tal health evaluations should be incorporated into
the sex of the child. And, the clinician must be multidisciplinary assessments for these children.
cognizant of both how the child is presenting and
the various environmental and psychosocial fac-
tors that are involved in the child’s life that may Evaluation
have impact upon diagnosis.
While work has been done on looking In children with cerebral palsy, once symptoms
at the health-related abilities and medical concerning for mental health issues or psychiatric
comorbidities/measures in children with cerebral disorders are noted, further evaluation is war-
palsy (Gabis et al. 2015), there is less consensus ranted. The family should discuss such concerns
about the prevalence of mental health disorders in first with their child’s medical team, with subse-
children with cerebral palsy given definition dif- quent potential referral to the developmental pedi-
ferences and study variations. Reviewing interna- atrician, psychiatrist, and/or psychologist.
tional literature, ASD, ADHD, epilepsy, and CP Associated medical deficits such as vision,
were examined collectively in Norwegian chil- hearing, cognitive, nutrition, and orthopedic
dren (Suren et al. 2012). In a study of 462 Danish needs should be identified as part of the evaluation
children with CP in the age range of 8–15 years of mental health issues in a child with cerebral
screened with the Child Behavior Checklist palsy, as they as well as medication usage (pro-
(CBCL) parental questionnaire, the psychopathol- files) may add to the full picture of mental health
ogy screening was positive in 46.2% against concerns in children with cerebral palsy. Identifi-
15.1% in the general population (Rackauskaite cation and evaluation of mental health issues in
et al. 2016). In a study in Quebec using the the cerebral palsy population can be challenging
Strengths and Difficulties Questionnaire to evalu- for patients as well as families and caregivers.
ate 160 adolescents with CP, behavioral difficul- Understanding the communication of emotional
ties were present in 36.9% of the adolescents needs when a patient’s articulation or verbal
(Brossard-Racine et al. 2013). In a study evaluat- abilities are limited, recognition of fluctuations
ing the behavioral and emotional problems in in behavioral states in children who are motor
children and adults with CP using the CBCL, impaired, and measurements of symptoms fre-
Strengths and Difficulties Questionnaire (SDQ), quency and duration using standard rating
and the Vineland Adaptive Behavior Scale II scales/mental health inventories all need to be
(BABS), the findings suggest that the persistence tailored to the individual’s communication and
of psychological and social problems from child- cognitive and motor presentation. Individuals
hood into adulthood underlines the importance of and families should seek out clinicians who are
focusing on early intervention (Weber et al. 2016). familiar with these unique issues of presentation
Psychiatric disorders among children with cere- to assess the full picture of what is impacting the
bral palsy at school starting age in Norway were patient’s day-to-day function. Excess motor activ-
found in 57% of children when attention deficit ity for age may be challenging to delineate in
disorder is included (Bjorgaas et al. 2012). These children with CP; care must be taken to differen-
same researchers later noted that it may be diffi- tiate involuntary motor movements from restless-
cult for standard screening tools to capture the ness. Inattention must be differentiated from
significance of mental health issues in children staring or disconnects that can occur with neuro-
with cerebral palsy (Bjorgaas et al. 2013). The logic issues such as subtle seizure disorders.
most recent systematic review and meta-analysis Given the underlying neurologic issues con-
of studies from 1996 to 2016 reviewed the comitant with cerebral palsy, most children will
benefit from full psychoeducational testing to modifications, and possible judicious use of med-
assess intellectual ability (IQ), level of academic ication to maximize progress and prevent regres-
skills (educational levels), and confounding mood sion. The full scope of such approaches is beyond
or social factors. Testing tailored for motor and what this chapter can review.
communication/expressive output constraints is Cognitive behavioral therapy is both a stand-
imperative. This is often “easier said than done” alone and adjunct therapeutic approach. It is
as many clinicians do not have familiarity with important that the child and family have access
large numbers of children with cerebral palsy. to a therapist familiar with children whose visual
In children with attention deficit disorder, par- and verbal processing skills may be impaired,
ent, teacher, and child reports of concerns of inat- memory retrieval may be affected, and means
tention, focus, distractibility, and hyperactivity of output/expression may be impacted by cerebral
should be elicited, with particular attention to palsy or associated medical deficits up to
frequency and duration and in what environment and including those who may be nonverbal.
(during what task) they are noted. Standardized Adapting therapeutic techniques to increase visual
rating scales should be utilized both for home- and cues/reminders as well as the use of social stories
school-based environment, to assess the individ- can be helpful in this population.
ual and benchmark against age (and ideally cog- With attention deficiency, strategies for
nitively or developmentally)-matched peers to home, modeling appropriate behaviors,
assess degree of impulsivity, inattention, and dis- catching the child being “good” with positive
tractibility with or without hyperkinesis. reinforcement/praise, and including consistency
Delineation of psychosocial factors that may with rewards are proven approaches. Clear limit
be impacting a child’s presentation includes but setting and the ability to follow through on con-
is not limited to self-esteem/image concerns (per- sequences by parents and be understood by a child
ception that they “look or sound” different from at their cognitive and developmental level are
peers). Adolescence in particular is a time of self- necessary. Motor constraints are not a barrier to
examination; children with special needs may setting consistent limits, as long as the child’s
feel “less than” their peers. This needs to be ability to comply with the task is taken into
looked for and supports given that emphasize consideration.
the child’s unique presentation strengths. The At the school level remediation can include but
cerebral palsy population also may be at greater not be limited to an environment setup for free-
risk for subtle or overt bullying. This may make it dom from distraction – preferential seating toward
hard to concentrate on tasks at hand or create/ the front of the class, away from windows/doors
exacerbate anxiety – the possibility of such needs or overly visual displays, buddying with focused
to be considered in any child with cerebral palsy peers, and clear/concise directions with frequent
who is exhibiting changes in their school or play intervals to prompt back to task.
habits. Anticipatory sensory or motor breaks can be of
significant importance for children – the chance to
“go shake their sillies out” before they lose focus
Treatment/Remediation on the larger task. Checking that the child is
maximally comfortable with position of the body
Once an attention deficit, depression, anxiety, in space to approach the work and adaptive equip-
or mood issue has been identified, the goal is ment to achieve such (e.g., slant boards, gel cush-
remediation aimed at the individual’s symptoms ion seating, visually enhanced type) will have
and environmental changes. This is a multifacto- yield. For children with cerebral palsy and inat-
rial approach that includes work directly with tention issues, a copy of the material up on the
the individual, family/parents using cognitive board next to the student so that there is one
behavioral therapy and/or behavior modification focal point may be helpful. Organization of
techniques, home and school environment binder/materials in a way that aids easy retrieval
for the student (e.g., color-coded tabs by subject, Not all medications used to treat anxiety and
photos of class members with names, short-and depression in adults have FDA approvals in the
long-term calendars for assignments) can aid in pediatric population, but there are some medica-
school success. tions that are approved as effective and/or safe for
For children experiencing anxiety and/or use in certain age ranges. While at times there may
depression, it may be important to ally with appro- be a role for antianxiety-specific medications
priate school teachers and officials (e.g., guidance such as the benzodiazepines to specifically target
counselors, administrators) to consider therapeu- short-term panic symptoms and avoidant behav-
tic interventions that may already be available iors (e.g., school avoidance/school phobia), more
in the school setting (e.g., group therapy, student often the SSRI medications which typically target
mentors, buddies). Additionally, if the child’s self- both depressive and anxiety symptoms and disor-
esteem is suffering as a result of other students der are the treatments of choice. Of note, the
bullying and/or picking on the child with CP, it benzodiazepine anxiolytic medications may
may help to avoid the cycle of the CP child being have motor effects for children with CP that
accused of “tattling” by increasing awareness can and may be helpful, e.g., relief of spasticity.
of teachers and school officials so that children Other antidepressant medication, e.g., bupropion
targeting the child with CP may be “caught in the (Wellbutrin), may be potentially helpful for chil-
act” directly by authority figures. Appropriate dren that have depression and may even provide
interventions may then be implemented which some benefit for ADHD symptoms; however, its
may include consequences but preferably oppor- use would require careful consideration given the
tunities for other students to learn and better potential it has to lower seizure threshold with use
understand the challenges for a child with CP in individuals with seizure history and/or trau-
and how to become advocates and allies and in matic brain injuries (e.g., CP). Furthermore,
so doing to develop empathy for any students with bupropion may also cause a resting motor tremor
differences. that could adversely impact the child with CP. For
Individual therapies including CBT and children with mood dysregulation and/or aggres-
mindfulness-based cognitive therapies that incor- sive behaviors, e.g., a child with disruptive mood
porate practices of breathing and meditation may dysregulation or autism spectrum disorder comor-
be helpful. Additionally, family therapy and avail- bid with CP, the addition of mood-stabilizing
able group therapy may also be useful. medication may be appropriate. However,
In addition to individual- and family-based some mood-stabilizing medications, e.g., atypical
therapy, as well as school/classroom accommoda- antipsychotic mood stabilizers, confer dopamine-
tions, treatment of attention deficit and affective blocking effects that may cause/exacerbate move-
disorders may include medication. Pharmacologic ment disorders and motor effects that in turn could
approaches to attention deficit disorder are aimed adversely impact the child with CP with motor
at decreasing impulsivity, increasing focus, mod- issues.
ulating outbursts, and decreasing hyperkinesis Concerns for medication use in the cerebral
if present. Stimulant/psychostimulant class med- palsy population parallel those in typical children
ications have historically been the first line of but may be more exaggerated given the underly-
approach, including short- and long-acting ing neurologic concerns. These include but are not
forms of methylphenidate and/or mixed amphet- limited to appetite suppression, sleep cycle distur-
amine preparations. Non-stimulant alternatives bances, and potential dulling of reaction times in
such as alpha 2 adrenoreceptor/adrenergic ago- children who are motor bound. Stimulants can be
nists alone or in conjunction with stimulants nonselective in activity with paradoxical speed up
have added to the medications available for use of symptoms impacting focus (e.g., activate motor
in children. Alternatively, a selective norepi- system nonselectively).
nephrine reuptake inhibitor may be of consider- Less well supported but noted clinically in the
ation as well. literature is medication use that possibly lowers
the seizure threshold – while an area of debate, supports, work efficiency increased; several stim-
judicious monitoring for seizures in the CP popu- ulant preparations were trialed over 2 school years
lation is warranted anyway and may be more to find the least appetite suppression and sleep
imperative if medications for psychiatric-based cycle disturbance.
symptom are utilized. Non-stimulant alternative (Intuniv) trialed, but
focus issues persisted with difficulty titrating
medications versus somnolence/balance issues,
Illustrative Case Study so it was discontinued.
Over time low self-esteem from body image,
An 11-year-old male with a history of feeling different from peers, and targeting by other
32-week gestation early oral motor issues is now children as well as siblings, along with family
feeding well, in good general health other than history of depression and anxiety, lead to devel-
mild-moderate spastic diplegia. The latter has opment of major depression and social anxiety.
responded well to bracing/orthotics, physiother- Cognitive behavioral therapy along with fam-
apy, and one round of Botox injections. He faces ily therapy interventions was initiated and helpful,
possible future surgeries if tightening at heel cords but with family history and persistence of mood
becomes functionally limiting. He has crutches and anxiety symptoms, an SSRI medication was
but generally ambulates in the classroom without added, resulting in significant symptom relief.
such. He was cognitively thought by parents to be
“bright” regarding overall fund of knowledge, can
read at grade level, understands computations at Conclusion/Areas for Future Studies
age level, but often gets answers incorrect because
he rushes through or does not complete all steps Behavioral, emotional, attentional, and mood
(e.g., can mix up order of operations, columns are issues in children with cerebral palsy have long
sloppy so computations are thrown off). been noted by patients, families, and caretakers
He has some difficulties organizing himself familiar with this population. Identification of
to complete school-based tasks throughout the mental health symptoms may be complicated by
day, as well as long-standing challenges comply- associated medical issues and the variable suit-
ing with parents’ directions around non-preferred ability of assessment tools, but it is necessary to
activities. allow approaches to remediation. Children with
Cognitive testing shows no significant discrep- known or suspected psychiatric disorders may
ancies but does score high on both impulsivity and benefit from therapy and pharmacologic interven-
distractibility. tions as well as psychosocial and educational
supports.
Further work needs to be done to identify
Recognition by IEP Regarding Motor psychiatric disorders in the cerebral palsy popu-
Issues/Condition lation. Looking at how psychiatric issues present
based on type of cerebral palsy, correlation with
Psychoeducational evaluation recommended free- intellectual ability or level of adaptive function-
dom from distraction, cueing to task to maximize ing may help inform treatment approach. While
success. Positive reinforcement had some impact not yet available, advancements in genetic test-
in younger grades, but by mid-second grade, ing as well as neuroimaging may allow predict-
consideration was being given to medications to ability of psychiatric concerns, as well as
enhance attention and focus compliance with potentially guide pharmacologic interventions.
tasks at home. Long-term follow-up of cohorts (to adulthood)
Long-acting methylphenidate preparation at may yield clues into the natural history of pre-
low doses was initially efficacious for impulsivity; sentation as well as insight into the efficacy of
coupled with clear directions and on-task treatment approaches.
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▶ Family Stress Associated with Cerebral Palsy tematic review and meta-analysis. Dev Med Child
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and statistical manual of mental disorders, 5th edn. 8- to 15-year-old children with cerebral palsy. Res Dev
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health in children with cerebral palsy: does screening spectrum disorder, ADHD, epilepsy, and cerebral
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Brossard-Racine M, Waknin BA, Shikako-Thomas K et al and emotional problems in children and adults with
(2013) Behavioral difficulties in adolescents with cere- cerebral palsy. Eur J Paediatr Neurol 20(2):270–274
bral palsy. J Child Neurol 28:27–33
Autism Spectrum Disorder in the Child
Meghan Harrison and Persephone Jones
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 506
Definition of CP and ASD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 506
Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 506
Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 507
Challenges in ASD Diagnosis for Children with CP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 507
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 508
Comorbidities and Common Risk Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 508
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 510
Medical Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 510
Medical Treatments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 510
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 511
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 512
Abstract individuals that meet criteria for both of these

Cerebral palsy (CP) and autism spectrum dis- disorders. Although CP has a defining focus on
order (ASD) are separate complex and hetero- movement and posture and ASD is defined by
geneous disorders resulting from a range of difficulties in social communication, these dis-
etiologies impacting early brain development. tinct clinically defined disorders share many
Both CP and ASD are clinical descriptive associated features. Further, the diagnostic
terms that encompass many etiologies. At the evaluation of ASD may be uniquely challeng-
intersection of CP and ASD, there are ing in children with CP depending upon their
level of motor functioning. This chapter will
explore the relationship between CP and
M. Harrison (*) · P. Jones
Department of Pediatrics, Nemours/AI DuPont Hospital
ASD including incidence, causative factors,
for Children, Wilmington, DE, USA evaluation, and management of both clinical
Division of Developmental Medicine, Department of
disorders.
Pediatrics, Nemours/AI DuPont Hospital for Children,
Wilmington, DE, USA
e-mail: Meghan.Harrison@nemours.org; Persephone.
Jones@nemours.org

https://doi.org/10.1007/978-3-319-74558-9_212
506 M. Harrison and P. Jones
Keywords distinct clinically defined disorders share many

Autism spectrum disorder (ASD) · Social associated features.
communication · Neurodevelopmental · In addition to disordered movement, many
Applied Behavior Analysis (ABA) children with CP present with broader neurodeve-
lopmental difficulties, including impairment
in attention, communication, behavioral, and
Introduction social-emotional functioning (Christensen et al.
2014). ASD is one example of a neurodeve-
Cerebral palsy (CP) and autism spectrum disorder lopmental disorder that occurs with increased
(ASD) are separate complex and heterogeneous frequency in children with CP compared to the
disorders resulting from a range of etiologies general population (Kilincaslan and Mukaddes
impacting early brain development. Both CP and 2009; Kirby et al. 2011; Christensen et al. 2014;
ASD are clinical descriptive terms that encompass Delobel-Ayoub et al. 2017). In contrast to CP,
many etiologies. At the intersection of CP and motor delay and/or motor dysfunction are not
ASD, there are individuals that meet criteria for part of the diagnostic criteria for ASD. Instead,
both of these disorders. ASD is a neurodevelopmental disorder character-
ized by deficits in social skills and social commu-
nication. Children with ASD have decreased
Definition of CP and ASD social interest, difficulty using speech and nonver-
bal communication strategies to convey their
The definitions of CP and ASD have been debated basic wants and needs, and atypical or underde-
and changed over time due to the complexity and veloped play. The presence of restricted, repetitive
heterogeneity, as well as progress in understand- patterns of behavior, interests, or activities, as
ing, of these disorders (Rosenbaum et al. 2007). manifested by at least two of the following (ste-
Currently, CP “describes a group of permanent reotypies, behavioral rigidity, restricted interests,
disorders of the development of movement and and hyper or hypo-reactivity to sensory input) is
posture, causing activity limitation, that are also necessary for a diagnosis of ASD (American
attributed to non-progressive disturbances that Psychiatric Association 2013). Similar to the
occurred in the developing fetal or infant brain. motor deficits that are diagnostic of CP, the core
The motor disorders of cerebral palsy are often social communication deficits of ASD are typi-
accompanied by disturbances of sensation, per- cally notable in the early developmental period
ception, cognition, communication, and behavior, (Center for Disease Control and Prevention 2014).
by epilepsy, and by secondary musculoskeletal Knowing that ASD occurs more frequently in
problems” (Rosenbaum et al. 2007). In the current the CP population compared to the general popu-
Diagnostic and Statistical Manual of Mental lation, one must consider the possibility of
Disorders – fifth edition (DSM-V), ASD is common causative mechanisms. Is there a shared
defined by persistent deficits in social communi- genetic predisposition? Are there common
cation and social interaction across multiple non-genetic risk factors? Further, could the
contexts (deficits in social-emotional reciprocity, motor deficits that are diagnostic of CP alter the
non-verbal communication, and developing rela- typical developmental trajectory of social com-
tionships), as well as restricted, repetitive patterns munication skills? These considerations will be
of behavior, interests, or activities (American Psy- discussed in detail below.
chiatric Association 2013). Like CP, ASD is often
accompanied by disturbances of sensation, per-
ception, cognition, epilepsy, and motor skill Epidemiology
impairments (American Psychiatric Association
2013). Thus, although CP has a defining focus Several studies have attempted to estimate the rate
on movement and posture and ASD is defined of co-occurring ASD within populations of chil-
by difficulties in social communication, these dren with CP. Results have varied widely with
35 Autism Spectrum Disorder in the Child with Cerebral Palsy 507
rate of co-occurring ASD ranging from 6.9% while the social deficits of ASD are typically
(Christensen et al. 2014) to 15% (Kilincaslan and present prior to 2 years of age, the average age
Mukaddes 2009). The most recent study on this of ASD diagnosis is closer to 4.5 years (Center for
topic (Delobel-Ayoub et al. 2017) evaluated 1225 Disease Control and Prevention 2014).
children with CP and found that 8.7% had a - As mentioned, the diagnosis of ASD is clinical
co-occurring diagnosis of ASD. Although the and based on reported and observed deficits in
final number varies across all studies, it is clear the areas of social reciprocity, nonverbal commu-
that the prevalence of ASD within the CP popula- nication, and age-typical play. A certain number
tion is higher than the current estimate of ASD of restrictive and repetitive behaviors must also be
prevalence in the general population, which is present (American Psychiatric Association 2013).
1 in 68 or 1.5% (Center for Disease Control and The American Academy of Pediatrics (AAP)
Prevention 2014). Interestingly, the incidence of issued a policy statement in 2006 recommending
CP has remained stable over 30 years with 2.5 use of a standardized screening tool to assess for
cases of CP per 1,000 live births (Miller and ASD at the 18 and 24–30 month well child visits
Bachrach 2006), while the prevalence of ASD has (Council of Children with Disabilities 2006).
increased 123% from as recently as 2002 (Center If screening is positive or the clinician has further
for Disease Control and Prevention 2014). No concern, the child should be referred for a more
studies were identified that evaluated for change focused autism evaluation. This evaluation often
in the rate of ASD diagnoses within the CP popu- includes administration of level two ASD screen-
lation over time. Interestingly, Delobel-Ayoub et al. ing tools (SCQ, ADI-R CARS-2, ASRS), level
(2017) recently examined gender differences in CP two ASD interactive tests (STAT, RITA-T), or
and co-occurring ASD and found a male to female the Autism Diagnostic Observation Schedule
ratio of 2.1 to 1. This is far lower than the 3–4 to (ADOS). The ADOS, currently the gold-standard
1 male to female ratio of ASD in the general assessment tool used to evaluate children for ASD
population (Loomes et al. 2017; Center for Disease (Choueiri and Zimmerman 2017) is a semi-
Control and Prevention 2014). structured play-based evaluation that allows for
Studies have also evaluated the prevalence objective assessment of a child’s social commu-
of co-occurring ASD based on CP subtype nication skills including directing attention with
(hypotonic, spastic, dyskinetic, or ataxic) and eye contact and gestures, imitation, and functional
severity of impairment (walking ability or play (Molloy et al. 2011).
GMFCS). Regarding CP subtype, results are
variable, as some studies show increased inci-
dence of ASD with a non-spastic subtype Challenges in ASD Diagnosis
(Christensen et al. 2014) and some show no dif- for Children with CP
ference in incidence of ASD between spastic
vs. non-spastic subtypes (Delobel-Ayoub et al. Clinicians assessing the question of ASD evaluate
2017). However, several studies have consistently a child’s mastery of many social communi-
shown that CP patients who achieve independent cation skills (e.g., spontaneous eye contact, joint
walking have a higher incidence of co-occurring attention, protoimperative and protodeclarative
ASD compared to CP patients who do not walk pointing, social referencing, imitation, and func-
independently (Kirby et al. 2011; Christensen tional play). The type and quality of expected
et al. 2014; Delobel-Ayoub et al. 2017). skills depend on a child’s age and developmental
level. Many of these social skills rely on varying
degrees of motor ability. For example, the ADOS
Diagnosis is generally not administered prior to a child’s
mastery of independent ambulation. This allows
Though there is no upper age limit for a diagnosis the clinician to see a child’s preferences for mobil-
of CP, children are typically diagnosed prior to ity, for example, to see if children are indepen-
2 years of age (Lungu et al. 2016). However, dently seeking out social engagement (bringing
toys to show) or approaching others for social Maternal Infection and Inflammation
purposes (social smiles and requesting to be It is well known that there are critical periods
picked up). Children with spasticity or impaired in early development and that stress on the devel-
upper extremity function may show delay in skills oping brain can result in adverse neurodeve-
such as waving, pointing, gesturing, signing, or lopmental outcomes. Specifically, maternal
symbolic play. Thus, it can be challenging for infection during pregnancy is known to increase
diagnosticians to confidently separate the social the risk of neurodevelopmental disorders includ-
impairments of ASD from motor delays that may ing ASD and CP. An imbalance in the expression
be present in CP. of inflammatory markers including interleukin
6 (IL-6), IL-10, C-reactive protein (CRP), and
the complement system can be triggered by
Natural History many factors including infection, psychosocial
stress, increased body mass index, and maternal
Comorbidities and Common Risk psychopathology. These disruptions in the prena-
Factors tal immune environment can result in neurodeve-
lopmental disorders (Boulanger-Bertolus et al.
As mentioned above, there are many hypotheses 2018).
as to why children with CP appear to be at
increased risk for co-occurring ASD compared Perinatal Hypoxia/Ischemia
to the general population. The etiology of ASD Perinatal hypoxia is a strong risk factor for
and CP is multifactorial and both intrinsic and CP (Minocha et al. 2017). Several studies evalu-
extrinsic factors are known to influence whether ating ASD risk factors have also found a strong
a child develops these conditions. association between intrapartum/peripartum
hypoxic events and later development of ASD
Preterm Birth/Low Birth Weight (Modabbernia et al. 2017; Maramara et al. 2014;
The prevalence of CP is known to be higher in Kolevzon et al. 2007). In a twin study of ASD risk
preterm infants compared with term infants; this factors (Froehlich-Santino et al. 2014), respiratory
risk increases with decreasing gestational age and distress was the peripartum factor most strongly
birth weight. The prevalence of CP is the highest associated with ASD. The authors hypothesize
in children weighing 1000–1499 g (59.18 per that this may be due to associated cerebral hyp-
1000 live births) and lowest in children weighing oxia with subsequent neuronal damage.
over 2500 g (1.33 per 1000 live births) (Oskoui
et al. 2013). In addition, there is known to be a Genetic Factors
decrease in the prevalence of CP with increasing There have been significant gains in knowledge
gestational age. A meta-analysis of the prevalence of genetic factors contributing to both ASD and
of CP (Oskoui et al. 2013) found that the preva- CP. Unlike many other brain disorders, there is
lence of CP is higher in preterm infants born no unifying pathology; however, in many cases
before 28 weeks gestational age (111.80 per a genetic etiology is identified or suspected. There
1000 live births) and lowest among children is a great deal of heterogeneity contributing
born after 36 weeks gestational age (1.16 per to symptoms of ASD. There are many different
1000 live births). Prematurity is also a risk factor distinct genetic disorders or chromosome abnor-
for ASD; the overall prevalence rate of ASD in malities that are known to contribute to symptoms
children with a history of prematurity is 7% of ASD.
(Agrawal et al. 2018). Studies of the relationships ASD is known to have high heritability; how-
between ASD and preterm birth or low birth ever, in most cases the specific genetic cause of
weight in children with CP have been inconclu- a child’s ASD is unknown. There is no single
sive (Delobel-Ayoub et al. 2017). identifiable gene for ASD. Even when genetic
testing is performed, most commonly no defini- that 31.6% of children with ASD also had intel-
tive diagnosis is made. In children with ASD, de lectual disability (ID) (defined as an IQ score < 70
novo genetic copy number variations have been with impaired adaptive functioning), 24.5% had
found to be present in 3–10% (Sebat et al. 2007). borderline intellectual ability (IQ 71–85), and
Recently, use of exome and whole genome 43.9% had average or above average intelligence
sequencing methods has demonstrated a higher (IQ >85).
yield of clinically informative variants (Yu et al. CP also presents with variable intellectual
2013; Jiang et al. 2013). ability; Stadskleiv et al. (2017) evaluated the neu-
As is the case with ASD, there is no single ropsychological profiles of children with CP and
identifiable CP gene. While prematurity and reported cognitive quotients ranging from 19 to
hypoxic-ischemic injuries are often recognized 123 with a median of 81.9. In this cohort of
etiologies of CP, many children with CP do not 70 children with CP, 17 (24%) had a diagnosis
have easily identifiable risk factors. For some of of ID. In children with CP, risk of intellectual
these children, a genetic component is suspected. disability seems to be related to several variables,
Copy number variants (CNVs) may explain CP with increased rates of ID associated with increas-
in about 10–20% of cases (McMichael et al. 2014; ing GMFCS classification (more severe motor
Segel et al. 2015; Oskoui et al. 2015). In addition, impairments) and the presence of epilepsy
some studies have identified susceptibility genes (Stadskleiv et al. 2017). Conflicting results are
for thrombosis and hemorrhage, which increase reported regarding incidence of ID based on CP
vulnerability to CP (Fahey et al. 2017). subtype (Stadskleiv et al. 2017).
In children with CP, the incidence of both ASD
Epilepsy and ID are far higher than the incidence of those
Epilepsy is prevalent in children with both CP and disorders in the general population. In fact, studies
ASD. Children with CP often have seizures in the have shown that co-occurring ASD is seen
neonatal period; brain imaging demonstrates more frequently in children with both CP and ID
abnormal pathology in the majority of affected compared to children with CP and average intel-
children. The incidence of seizures is more com- lectual functioning (Delobel-Ayoub et al. 2017;
mon in certain types of CP, with children with Kilincaslan and Mukaddes 2009). Authors have
quadriplegic CP having the highest incidence questioned if the higher risk of ASD in children
of epilepsy ranging from 50–94% (Gururaj et al. with CP and ID is due to more severe brain
2003). In people with ASD, the prevalence of dysfunction (Kilincaslan and Mukaddes 2009).
epilepsy ranges from 11–39% (Ballaban-Gil and Certainly, there are several common causative
Tuchman 2000). Children with ASD and epilepsy factors for all three of these neurodevelopmental
but without CP were less likely to have abnormal disorders.
brain imaging than children with CP and epilepsy,
with a definite pathology identified in 22% of Motor Coordination Abnormalities
children with autism and epilepsy (Cooper et al. While motor delay is not a diagnostic criterion for
2016). It has been demonstrated that the presence ASD, several studies report that children with
of seizures is associated with ASD in children ASD demonstrate disordered motor development
with CP (Gururaj et al. 2003). compared to typically developing peers (Bhat
et al. 2012; Fournier et al. 2010). Early motor
Intellectual Disability difficulties have been associated with poorer
As previously discussed, autism spectrum disor- social communication outcomes in this popula-
ders are heterogeneous. As such, intellectual abil- tion (Bhat et al. 2012). This association seems
ity in children with ASD is widely variable. logical when one considers that timely achieve-
The most recent ASD prevalence data (Center ment of early gross motor skills provides children
for Disease Control and Prevention 2014) found increasing ability to interact with and explore
their social environment. Head control allows damage being most common (Korzeniewski et al.
children to engage in sustained eye contact and 2008). Structural brain differences in ASD are
reciprocal social exchanges such as smiling and also an area of interest. Several studies report
babbling. Postural stability with independent sit- increase in overall brain volume and overgrowth
ting encourages the emergence of joint attention, of the amygdala (linked to fear, anxiety, and
which is considered one of the earliest discrimi- a range of social behaviors). Conversely, there
nators of ASD (Bedford et al. 2016). Coordinated appears to be decreased volume of the corpus
upper extremity movements are important in the callosum (Dougherty et al. 2016). Despite these
development of gestural communication (waving, demonstrated structural differences and the role
pointing, and reaching). The onset of independent of neuroimaging in autism research, neuroimag-
walking is associated with increased frequency of ing is not routinely recommended in the clinical
vocalizations, intentional gestures, and initiation evaluation and diagnosis of ASD (Choueiri
of social interactions (Bedford et al. 2016). and Zimmerman 2017; Johnson et al. 2007).
The association between motor and social/ However, brain imaging with MRI should be
communication development is a possible reason considered for a child with focal neurological
that ASD is seen with increased frequency in findings on exam, epilepsy, or a focally abnormal
children with CP. EEG (Choueiri and Zimmerman 2017).
Whittingham et al. (2010) studied 122 children
with CP and found that lower motor skills at age
18, 24, and 30 months were associated with Medical Treatments
poorer social ability. However, this theory is
challenged when one considers that previously There are no medications or medical treatments
described studies note a higher incidence of that are curative for patients with ASD. In general,
co-occurring ASD and CP in children with better children with ASD have the same health care
motor skills, specifically independent ambulation needs as other children. They are at an increased
(Kirby et al. 2011; Christensen et al. 2014; risk for certain comorbid medical problems such
Delobel-Ayoub et al. 2017). as seizures, genetic disorders, gastrointestinal
problems, and sleep problems.
Treatment Pharmacotherapy
There are no medications that effectively treat the
Medical Testing core social deficits of ASD. There are only two
medications (Risperidone and Aripiprazole) that
Routine labwork is not recommended as part of are FDA approved for aggressive and self-
the diagnostic evaluation for ASD and should be injurious symptoms that can present in some
ordered based on specific symptoms, physical patients with ASD. However, these treatments
exam findings, or history (Johnson et al. 2007). have not been shown to improve social function-
However, first-tier genetic testing is ing (Choueiri and Zimmerman 2017). Other clas-
recommended for all children with ASD. This ses of medications can be used to treat associated
includes testing for Fragile X Syndrome and a symptoms such as anxiety, inattention, and hyper-
chromosome microarray (Schaefer and activity. Similarly, there are no medical treatments
Mendelsohn 2013). in CP that reverse the static motor deficits.
The American Academy of Neurology Instead, medications are used to treat associated
recommends brain imaging for all cases of CP symptoms. As in ASD, anxiolytics or stimulants
with unknown origin (Ashwal et al. 2004). are used to treat co-occurring anxiety, impulsive-
Approximately 83% of children with CP have ness, or inattention. Botulinum toxin is a well-
abnormal radiographic findings, with white matter established medical therapy to help manage
spasticity in patients with CP (Lungu et al. 2016). for alternative treatment options including
Other potential treatment options for spasticity treatment modalities that fall under the category
include diazepam and baclofen (oral or intrathe- of complementary and alternative medicine
cal) (Delgado et al. 2010). Melatonin is being (CAM). The National Center for Complementary
studied as a potential neuroprotective agent for and Alternative Medicine (NCCAM) of the US
neonates with hypoxic-ischemic injury (Hendaus National Institutes of Health (NIH) explains CAM
et al. 2016). as practices and products that are outside
the realm of conventional medicine (National
Rehabilitative Therapies Institutes of Health). Some complementary thera-
Treatment for children with CP and co-occurring pies that are used in children with CP include
ASD should focus on the motor and social com- hyperbaric oxygen, the Adeli Suit, patterning,
munication deficits present in both disorders. electrical stimulation, conductive education,
For children with CP, therapies in early childhood equine-assisted therapy, craniosacral therapy,
are focused on optimizing motor function (Lungu Feldenkrais therapy, massage, aquatherapy, and
et al. 2016). In both CP and ASD, physical ther- acupuncture (Liptak 2005, Hurvitz et al. 2003).
apy and occupational therapy support develop- Hurvitz et al. (2003) studied 213 families with
ment of tone, postural stability, self-help skills a child with CP and found that 56% use at least
such as self-feeding and dressing, and advance- one form of CAM, with massage (25%) and
ment of motor skills including independent aquatherapy (25%) being the most commonly
ambulation. Speech and language therapy should utilized. The strongest predictors of CAM use
be implemented to support feeding or speech included younger patients, more severe motor
difficulties. disability, and patients whose parents have also
used CAM.
Similarly, families of patients with ASD often
Early Intensive Behavioral Interventions explore CAM as part of a child’s treatment plan.
(ABA, Developmental Models) Some common CAM therapies that have been
An important component of ASD treatment is used in ASD include hyperbaric oxygen, chela-
behavioral therapy. This intervention targets tion, probiotics, N-acetylcysteine, vitamin B-12,
the core social deficits of ASD including joint omega-3 fatty acids, and certain restrictive diets
attention, reciprocal social interactions, and such as the gluten-free and casein-free diet (Bent
functional communication (Zwaigenbaum et al. and Hendren 2015). Results vary but studies
2015). Several types of behavior therapy are report that the majority of families of patients
available including Applied Behavior Analysis with ASD have utilized CAM as part of the child’s
(ABA) and Discrete Trial Training to name two. treatment (Hanson et al. 2007; Bent and Hendren
Behavioral interventions use the principles 2015). Harrington et al. (2006) found this number
of behavior analysis (antecedents and conse- to be as high as 92%.
quences) to help teach desired social behaviors
(Zwaigenbaum et al. 2015). Sensory disturbances
that are often present in ASD can be helped Conclusion
through a combination of behavior therapy and
occupational therapy. While CP and ASD are separate disorders, there
are many children who meet criteria for both
Complementary and Alternative diagnoses. The motor deficits of CP may impact
Medicine the diagnostic assessment of ASD. Nonetheless,
In addition to empirically supported medical treat- the incidence of ASD is higher in children
ments listed above, many families of children with CP compared to the general population.
with chronic diseases such as CP and ASD search CP and ASD share several common risk factors
including preterm birth, low birth weight, mater- Ballaban-Gil K, Tuchman R (2000) Epilepsy and epilep-
nal infection, and perinatal hypoxia. Epilepsy and tiform EEG: association with autism and language
disorders. Ment Retard Dev Disabil Res Rev
Intellectual Disability are common comorbidities 6:300–308
of both disorders. Children with both ASD and Bedford R, Pickles A, Lord C (2016) Early gross motor
CP benefit from early intensive rehabilitative ther- skills predict the subsequent development of lan-
apies including speech therapy, physical therapy, guage in children with autism spectrum disorder.
Autism Res 9(9):993–1001. https://doi.org/10.1002/
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fields grows, we may one day gain greater under- Bent S, Hendren RL (2015) Complementary and alterna-
standing of the complex relationship between CP tive treatments for autism part 1: evidence supported
and ASD. treatments. AMA J Ethics 17(4):369–374
Bhat AN, Galloway JC, Landa RJ (2012) Relationship
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Family Stress Associated with
Cerebral Palsy 36
Heidi Fritz and Carrie Sewell-Roberts
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 516
Parent Stress . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 531
Psychological Well-Being . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 531
Physical Health Outcomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 532
Disability Severity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 533
Family Adaptation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 535
Parent Personal Resources: Social Support and Self-Efficacy . . . . . . . . . . . . . . . . . . . . . 536
Assessment Tools and Interventions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 537
The Role of Respite Care Services . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 539
Financial Resources and Socioeconomic Status . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 539
Psychosocial Interventions and Parent Stress . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 540
Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 541
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 542
Abstract
The caregiving demands faced by parents of
children with cerebral palsy may elevate their
risk of stress-related health outcomes. We
reviewed 44 empirical studies of family stress
H. Fritz (*) in the context of cerebral palsy that were
Department of Psychology, Salisbury University, published from 1987 to 2017. We examined
Salisbury, MD, USA the relationship of caregiver status and child
e-mail: HLFRITZ@salisbury.edu
disability severity with caregiver stress and
C. Sewell-Roberts stress-related outcomes such as mental and
Wilmington, DE, USA physical health. Compared to parents of typi-
e-mail: Carrie.SewellRoberts@nemours.org cally developing children, parents of children

https://doi.org/10.1007/978-3-319-74558-9_213
516 H. Fritz and C. Sewell-Roberts
with cerebral palsy experienced greater stress, dependent upon them for their significant emo-
lower psychological well-being, and worse tional, social, physical, and financial needs.
physical health. Disability severity was not Indeed, many studies link caregiving in the con-
as clearly linked with stress outcomes as text of cerebral palsy with elevated parenting
expected, suggesting that important moderator stress and worse physical and psychological
variables may play a role in this relation. Sev- well-being as compared to parents of children
eral moderator and mediator variables emerged without disabilities and the general population
across studies, including characteristics of (see Rentinck et al. 2006, for a review of studies
the child (e.g., social, physical, and behavioral through 2004).
factors), parent (e.g., personal and social Why should practitioners be concerned about
resources), and family resources (e.g., coping caregiver chronic stress load? Prolonged exposure
norms, socioeconomic status, and access to to psychological stress results in adverse health
respite care services). Although little research outcomes, ranging from poor health behaviors to
currently exists examining the effectiveness of reduced psychological and physical well-being.
psychosocial interventions for parents of chil- Behavioral changes such as increased substance
dren with cerebral palsy, the existing evidence use, decreased physical activity, and impaired
suggests that the greatest benefits caregivers sleep often occur as coping mechanisms in
derive from support groups may stem primarily response to stress (Cohen et al. 2007). When
from the provision of practical and informa- individuals are unable to respond effectively to
tional support and by facilitating self-efficacy or gain reprieve from prolonged stressors, ineffec-
and social network size. Future research should tive behavioral and psychological responses may
further elucidate the essential qualities of effec- produce harmful physiological effects via endo-
tive psychosocial interventions and should uti- crine, immune, and cardiac pathways (McEwen
lize longitudinal rather than cross-sectional 1998). To the extent that caregiving for a child
designs when possible in order to better under- with cerebral palsy represents a chronically stress-
stand how caregiver health, coping, and family ful situation with little opportunity for reprieve,
adaptation processes unfold over time. we may expect alterations in immune, endocrine,
or cardiac function over time to produce elevated
Keywords risk of disease. Recent research regarding care-
Cerebral palsy · Caregiving stress · Parenting givers of children with other developmental dis-
stress · Psychological well-being · Physical abilities supports this compromised pathway
health · Resilience hypothesis: Compared to parents of typically
developing children, parents of children with
developmental disabilities such as autism, Down
Introduction syndrome, or ADHD have been found to have
lower antibody responses to medical vaccinations
A large body of evidence suggests that caring for (Gallagher et al. 2009a, b), higher levels of pro-
individuals with a chronic illness or disability is inflammatory cytokines (Lovell et al. 2012),
stressful (Bhimani 2014; Isa et al. 2016; Longacre greater disruptions in cortisol patterns (Seltzer
et al. 2012; Neely-Barnes and Dia 2008). It is et al. 2010), and elevated ambulatory blood
widely assumed that caring for a child with cere- pressure over a 24-h period (Gallagher and
bral palsy is similarly stressful, and a growing Whiteley 2012).
literature supports this premise. Raising a child Yet, not all parents of children with disabilities
with cerebral palsy often results in elevated levels fare poorly. Although many caregivers of children
of stress extending well beyond the time frame for with cerebral palsy show elevated stress and
raising a typically developing child. Many parents compromised well-being, some studies show no
foresee no end to the time when their child with detrimental effect of cerebral palsy caregiving per
cerebral palsy will live with them and remain se compared to parenting children with other
36 Family Stress Associated with Cerebral Palsy 517
developmental disabilities (Azad et al. 2013; some showed diagnosis group differences that
Blacher and McIntyre 2006; Eisenhower et al. made it difficult to extrapolate the results to the
2005; Roper et al. 2014). Many others show sig- unique experiences of cerebral palsy caregiving
nificant variability in parent stress and health out- (e.g., Eisenhower et al. 2005; Hauser-Cram et al.
comes, even at high levels of child disability 2001). While it is notable that the experiences of
severity. These equivocal results suggest that a parents raising children with cerebral palsy differ
variety of important family and environmental in some ways from the experiences of parents
moderator variables play a role in the complex raising children with other developmental disabil-
relation between cerebral palsy caregiving and ities, we felt that including mixed samples
stress outcomes. According to Lazarus and might muddy our interpretation of the literature
Folkman’s (1984) transactional stress model, the on cerebral palsy caregiving and exceed the scope
subjective experience of stress and physiological of this chapter.
sequelae arise not simply from objectively stress- In addition to the focus on parents of children
ful events; rather, stress response occurs when with cerebral palsy, our other main inclusion cri-
individuals perceive that the demands of the envi- terion was that the study assessed parental stress
ronment exceed their resources for coping. Child, levels or stress-related outcomes such as psycho-
parent, and environmental variables may affect logical well-being in terms of general mental
this appraisal process. Child characteristics such health, depression, or anxiety; physical health out-
as behavior difficulties, social skills, sleep and comes such as physical functioning, chronic ill-
feeding difficulties, and motor and cognitive ness, somatic symptoms, or health behaviors; or
abilities, parent characteristics, such as social sup- family system outcomes such as family adapta-
port, self-efficacy, coping, and personality, and tion. Our selection criteria yielded 44 empirical
environmental characteristics, such as parental studies with quantitative analyses, which appear
education, income, life stage of the child, access in Table 1. We summarized the sample, design,
to respite care, and availability of resources to measures, and main results for each study. Addi-
allow parents to engage in health-promoting tionally, we indicated whether each study found
behaviors, are all emerging as important path- elevated stress levels among parents of children
ways affecting outcomes for caregivers and ulti- with CP as compared to healthy controls or pop-
mately moderating the relation between caregiver ulation norms or showed effects of stress or child
status and family stress. Multiple factors may diagnosis status on parent psychological or phys-
buffer caregivers from stress or, in their absence, ical health outcomes; these results are summa-
exacerbate the negative effects of caregiving on rized as Yes (Y), No (N), or Did not specifically
family stress. test or report (–).
The present chapter reviews the literature on Thus, our goals for this chapter are to examine
family stress and caregiving in the context of studies linking cerebral palsy caregiving with
cerebral palsy. We searched the MEDLINE and stress and the stress-related domains of parent
PsychINFO databases for empirical articles from psychological well-being, physical health, and
1987 to 2017 for samples strictly defined as the family adaptation, highlight which studies show
parents of children with cerebral palsy; we also a positive relation as compared to those showing
included studies that examine parents of children no relation, and examine the role of disability
with cerebral palsy as compared to parents of severity across domains. Additionally, we exam-
typically developing children or population ine the evidence for specific categories of vari-
norms. We excluded studies that mixed parents ables that may moderate or mediate the
of children with multiple developmental disabil- caregiving-stress relationship: child social, physi-
ities within the same sample (e.g., cerebral palsy, cal, and behavioral characteristics, parental per-
autism, and Down syndrome together), because sonal and social resources, family adaptation
such studies often had relatively few participants characteristics, and family resources such as
in the cerebral palsy caregiver groups and because socioeconomic status and access to respite care
Table 1
518
Stress
higher Psych Physical
Author/year Sample Design Notable findings in CP? effect effect Measures
Barlow et al. 78 mothers of children with CP Cross-sectional Mothers of children with CP – Y Y Hospital anxiety and
(2006) age 0–16 in the UK reported higher levels of anxiety depression scale
and depression compared with Sleep difficulties
population norms. Depression and Self-efficacy
anxiety were associated positively
with children’s sleep difficulties
and inversely with self-efficacy
Basaran 143 parents of children with CP Cross-sectional Caregivers of children with CP Y Y Y Stress: MBI burnout
et al. (2013) and 60 health control parents of reported lower QOL on WHOQOL-BREF
TD environmental, general, physical, Beck depression and
psychological health, as well as anxiety scales
greater depression, anxiety, and
GMFCS severity
burnout. GMFCS severity was
correlated with worse physical and
general health and depression
Bella et al. 37 mothers of children with CP Cross-sectional CP and control groups reported Y – Y Stress: Cohen PSS
(2011) and 38 mothers of TD children in assessed cortisol 4 equivalent and high stress Caregiver burden
Brazil. Recruited from low SES in one 24-h period compared to norms. CP group had SF-36
areas lower SES than control. CP group:
Salivary cortisol
lower cortisol, physical well-
being, and social functioning.
Control group showed a negative
relation between cortisol and
SF-36 mental health, whereas CP
group showed no correlation.
Conclusion: Low SES/high-stress
mothers of healthy kids preserve
their HPA axis function, whereas
overwhelming stress among CP
mothers impairs HPA axis
function
Brehaut 468 mothers and fathers of Cross-sectional Compared with general – Y Y HUI: Distress, emotional
et al. (2004) children with CP in Ontario. population, caregivers of child and physical health
Compared to Canadian population with CP had lower income and problems, chronic
norms greater financial strain, although conditions
H. Fritz and C. Sewell-Roberts
36
not lower education. They were

less likely to be employed and
more likely to list caregiving as
main activity. CP caregivers
reported greater psychological
distress and emotional, cognitive
and physical problems
Britner et al. 87 mothers of children with CP Cross-sectional Mothers of children with CP Y – – Stress: PSI
(2003) 14–55 months of age. Severe CP, reported higher parenting stress Social support
mild CP, or no dx than mothers of children with no DAS marital quality
dx. Parenting stress negatively
correlated with marital quality and
viewing supporters as helpful. The
parenting stress/marital quality
relation did not differ across
groups
Family Stress Associated with Cerebral Palsy
Button et al. 64 families children with Cross-sectional plus Parents of children with severe CP Y – – Stress: PSI
(2001) moderate CP (25), severe CP (23), couple interview re: reported more evening care duties Vineland behavior
and a healthy controls (16) ages caregiving task compared to moderate or no CP, Child care involvement
15–54 months division with both parents indicating index
mothers do more. Disability
Social support
severity directly predicted
maternal stress: mothers in the Disability severity from
severe CP group reported medical records
significantly greater stress than
healthy controls. This effect was
mediated by social isolation.
Fathers’ caregiving involvement
unrelated to maternal stress. A
father support X CP severity
interaction suggested that the
highest maternal stress occurred
under high support X severe CP
Byrne et al. 100 mothers and 61 fathers of Cross-sectional Mothers scored worse than fathers – Y Y SF-36
(2010) children with CP in Ireland. on all SF-36 mental and physical GMFCS severity
Compared to population norms health composite indices. Ambulatory and ADL
Compared to the general independence
population, parents of children
with CP exhibited worse mental
519
(continued)
Table 1 (continued)
520
Stress
and physical functioning, but the
difference was more marked
among mothers than fathers.
Disability severity was unrelated
to SF-36, but greater time spent
caregiving was related to worse
functioning
Davis et al. Parents (24 mothers, 13 fathers) of Interviews Parents reported highly variable – Y Y Interviews coded for
(2010) children with CP ages 3–18 in QOL, dependent upon child’s parent QOL, distress,
Australia health challenges and ability to get social support, positive
out of the house. Frequently outcomes, and strain
reported negative effects: parent
physical health, sleep disruption,
social isolation, reduced
friendships, marital strain, limited
time and freedom, family
vacations, financial drain, long-
term dependence of child, impact
on mother’s identity and career,
accessing/fighting for funding for
equipment and services. Positive
outcomes: building new social
networks, self and others inspired
by child. No relation of disability
severity with parent distress
Davis et al. 201 parents of children with CP Cross-sectional Greater parent distress associated – Y Y CPQOL for children
(2011) age 4–12 in Australia with lower child social well-being, Distress: Kessler 10
family health, child physical GMFCS severity
health, emotional well-being,
acceptance of dx
Eker and 40 mothers of children with CP Cross-sectional Mothers of children with CP – Y Y SF-36
Tuzun compared to 44 mothers of reported lower functioning than GMFCS severity
(2004) children with minor health controls on all SF subscales except
problems. Mean age = 4.7. physical functioning. Disability
Turkey severity was associated with
36
worse function across role-

physical, vitality, role-emotional,
and mental health domains
Florian and Mothers of 80 children with CP Cross-sectional Main predictors of maternal well- Y Y – Stress: FILE
Findler and 80 with no dx ages 3–7 in Interviews being and marital adaptation: self- Mental health inventory
(2001) Israel mastery, self-esteem, and family Social support
network size. Mothers of children
Self-efficacy
with CP had smaller friend and
professional networks, lower Self-esteem
marital adaptation, mental health,
self-mastery, and greater stressful
life events than healthy controls.
Life event stress differences
driven by financial and medical
domains. Marital differences
driven by sharing tasks equally
and leisure time domains

Glenn et al. Mothers of 80 preschoolers with Cross-sectional Mothers of children with CP Y – – Stress: PSI
(2009) CP age 8–46 months in England HOME interview reported significantly greater GMFCS severity
and observation stress than population norms. HOME observation
High stress was mainly predicted
FACES-3
by high family needs, along with
low family adaptability and Family needs
cognitive impairment. High stress Family support
was also associated with role COPE
restriction, isolation, poor spouse Locus of control
support, external locus of control,
low HOME score and family
cohesion, and maladaptive
coping. Low stress was predicted
by children’s emotional
reinforcement and close bond to
parent. Relation of disability
severity with stress was
unreported
(continued)
521
522
Table 1 (continued)
Stress
Guillamon 62 parents (88% mothers) of Cross-sectional Parents of children with CP – Y Y WHOQOL-BREF
et al. (2013) children with CP age 0–18 (mean reported lower QOL and mental Beck depression
age = 8) in Spain health compared to general STAI anxiety
population. Social support was
Caregiving self-efficacy
associated with greater mental
health. Self-efficacy was CHIP coping
associated with better physical and
mental health QOL index, greater
satisfaction with relationships, and
less anxiety
Guyard 286 families of 13–18-year-old Cross-sectional 31.8% of parents experienced Y – – Stress: PSI
et al. (2017) patients with cerebral palsy from Interviews clinically significant high stress. Family impact of
four European disability registers Main adolescent stressors: level of childhood disability
motor impairment and behavioral GMFCS severity
disorders. Family functioning was
the strongest protective factor
against stress
Jayanath Parents of 104 children with CP in Cross-sectional Parents reported high and frequent – N – Depression, anxiety, and
et al. (2016) Malaysia. Majority of children levels of pain in children, stress scale
were severe/nonverbal especially among quad MSP social support
CP. However, parent mental CPCHILD
health, stress, social support, and
GMFCS severity
parent or child QOL were all
unrelated to frequency or intensity
of child pain. Relation of disability
severity with parent stress was
unreported
Kaya et al. Mothers of 81 children with CP Cross-sectional Mothers of children with CP – Y Y SF-36
(2010) and 60 healthy controls in Turkey reported greater MSP, LBP, and BDI depression
general pain than controls; they Musculoskeletal, lower
also reported greater depression back, and general pain
and lower physical-role and
mental health function
36
Krstic et al. Mothers of 100 children with CP Cross-sectional “Unresolved” status (i.e., mothers – Y – Stress: FILE
(2015) ages 2–7 in Serbia Survey and who had not cognitively and RDI
interview emotionally processed their Functional status
child’s diagnosis) associated with depression scale
more stressful life events, greater
depression, and poorer child
functional status. Maternal
education was associated with
greater resolution. Greatest source
of stress: financial stress due to
medical treatment
Lin (2000) 274 mothers and fathers of Cross-sectional Strongest predictors of family – – – Family adaptation
children with CP ages 0–21 adaptation: positive family Family coping
appraisal and spiritual support.
Life stage: Parents of school-aged
children used more positive
appraisal and social support than
families of young adults and

reported better adaptation. Parents
of infants/preschoolers sought
more information and support
than families of young adults
Majnemer 95 parents of children with CP Cross-sectional Parents of children with CP Y Y – Stress: PSI
et al. (2012) ages 6–12 in Quebec reported significantly higher stress Impact on family
than population norms. Higher Child health Q
parent stress was associated with
Vineland behavior
lower child physical well-being.
Family distress was associated SDQ
with child behavior, emotional, GMFCS severity
and motor difficulties. Child
prosocial behaviors had protective
effect on parent stress
Majnemer 95 parents of children with CP Cross-sectional High parent stress associated with – Y – Stress: PSI
et al. (2007) ages 6–12 in Quebec children’s lower physical and CHQ
psychosocial well-being Pediatric QOL
Vineland behavior
SDQ
GMFCS severity
523
(continued)
524
Table 1 (continued)
Stress
Manuel 270 mothers of children with CP, Cross-sectional Greater depression among – Y – Functional status
et al. (2003) who have been diagnosed for at mothers of children with CP GMFCS severity MOS
least 1 year, age 1–18 compared to population norms. social support, impact on
Disability severity and functional family
status did not predict maternal CES-D depression
depression. Social support
buffered against elevated
depression among mothers of
low-functioning children
McCubbin 130 2-parent families of children Longitudinal Among children with moderate – – – Stress: FILE
and Huang with CP ages 6–18 3-month follow-up (but not mild or severe) CP, family Child physical health Q
(1989) for physician-rated stress predicted decreased child Ambulatory severity
health improvement physical health over time. For
Family resources
mild and severe (but not
moderate) CP, maternal coping Family adaptation
predicted child’s health CHIP coping
improvement. For severe CP,
maternal psychological stability
predicted child health
improvement
Mobarak Mothers of 91 children with CP Cross-sectional Strongest predictor of maternal Y – Y Stress: SRQ
et al. (2000) ages 1.5–5 years in Bangladesh stress was child behavior Adaptation: Judson
problems, especially those related FSS social support
to “burden of caregiving” such as
sleep disturbance, incontinence,
temper tantrums, and attention-
seeking. Social support was
unrelated to stress, and baseline
spousal support was low
36
Mullen Parents of 120 children ages Cross-sectional Disability severity was correlated Y N – Stress: PSI
(1997) 1–4 years with severe CP (38), with parent stress but was Social support
mild CP (40), or no dx (42) unrelated to marital satisfaction or Vineland behavior
parent-child attachment
Motor impairment
DAS marital Satis
Attachment: Strange
situation Ainsworth
Olrick et al. Parents of 47 children with CP age Cross-sectional Parenting stress was unrelated to a – – – Stress: PSI
(2002) 17–54 months laboratory assessment of parent- Vineland child behavior
child feeding signals and DAS marital quality
behaviors. Mothers’ marital
satisfaction was related to
caregiving cooperation and father
involvement in responding to
child feeding signals
Ong et al. 174 mothers of children with CP Cross-sectional Mothers of children with CP Y – – Stress: PSI
(1998) (87) or no dx (87) in Malaysia. reported greater stress than SES
Mean age = 57 months healthy controls. Lower ADL ADL function
function, greater number of
hospitalizations in last year, and
lower parent education were
associated with greater parent
stress
Palisano 501 parents (77% mothers) of Cross-sectional Family needs predicted by greater – – – Family needs
et al. (2009) children with CP age 2–21 disability severity, but not by age. GMFSC severity
Families of children using
wheelchairs had highest needs,
especially with respect to access to
leisure and community activities,
financial support, and respite
services
Park et al. 101 parents (10 fathers and Cross-sectional Parents of children with CP Y – – Stress: PSI
(2012) 91 mothers) of children with CP reported significantly greater GMFCS severity
age 5–12 in Korea stress than population norms. PODCI function
Surprisingly, higher global
function was associated with
greater stress. Limit: only 6% of
children had severe CP
525
(continued)
Table 1 (continued)
526
Stress
Parkes et al. Parents (94% mothers) of Cross-sectional 26% of parents reported very high Y – – Stress: PSI
(2011) 818 children with cerebral palsy stress on the PSI. Caregiver stress GMFCS severity
recruited from 9 centers across most strongly associated with SPARCLE
Europe parent-child interaction
dysfunction and child negative
behavior. Child’s communication
impairment, intellectual
impairment, and severe pain were
also associated with high
caregiver stress. Disability
severity was unrelated to stress
Parkes et al. 102 parents of children with CP Cross-sectional Parents of children with CP Y – – Stress: PSI
(2009) age 8–12 in N. Ireland reported significantly higher stress CHQ
than population norms. Child SDQ
emotional and behavioral
GMFCS severity
difficulties predicted greater
parent stress, but disability
severity did not
Pimm 235 parents of children with CP Cross-sectional Compared to population norms, – Y Y GHQ-28
(1996) living at home age 1–16+ in Semi-structured parents of children with CP
Britain interview reported higher depression,
anxiety, and illness symptoms.
10% of mothers felt that fathers
provided insufficient help. 33% of
parents felt that their housing was
inadequate for the needs of their
child with CP, and 60% felt that
their TD children were neglected.
Parents identified most stressful
challenges as children’s physical
dependency, lack of mobility,
communication and behavioral
difficulties, need for supervision,
stigma, and limited parent-child
social activities
36
Prakash 62 mothers of children with CP Cross-sectional Mothers of children in GMFCS Y – – Caregiver strain index
et al. (2017) age 2–21 in India levels IV and V experienced high GMFCS severity
levels of caregiver stress
compared to mothers of children
with CP who were ambulatory
Raina et al. 632 families of children with CP Cross-sectional Parent physical and psychological – Y Y Stress: Caregiving
(2005) Survey and adjustment was predicted by child demands
interview behavior, caregiving demands, HUI
and family functioning. Parent SF-36
psychological adjustment was also
GMFCS severity
associated with greater self-
esteem, mastery, and stress
management. The relation of
disability severity with parent
adjustment was unreported
Rentinck 51 parents of toddlers with CP, Cross-sectional 77% parents classified as – Y – RDI
et al. (2009) mean age = 18.5 months. Interview “resolved” regarding child’s dx at GMFCS severity
Netherlands age 18mos. Severity of CP UCL coping
predicted unresolved status.
Avoidant coping and practical (but
not emotional) support were
associated with resolution status
Ribeiro 223 mothers of children with CP Cross-sectional 45.3% of mothers scored above Y – – Stress: PSI
et al. (2014) age 8 months to 20 years in Brazil. the PSI cutoff for very high stress. GMFCS severity
Excluded children of GMFCS Low SES and low social Sociodemographic Q
level 3 (moderate) participation were associated with
elevated maternal stress. Among
young children, parents of
children with severe CP reported
higher stress than mild CP;
however, among adolescents,
parents of children with mild CP
reported higher stress than severe
CP. Maternal paid work and
leisure predicted reduced stress
(continued)
527
Table 1 (continued)
528
Stress
Romeo et al. 100 families of children with CP Cross-sectional Parents of children with CP – Y Y WHOQOL-BREF
(2010) and 30 families of healthy reported lower psychological and CBCL behavior
controls. Mother and father in physical QOL compared to GMFCS severity
each family participated parents of healthy controls.
Mothers reported lower physical
QOL than fathers among children
with diplegia and quadriplegia but
lower psychological QOL among
children with hemiplegia.
Hemiplegic children reported
more externalizing behavior
problems than other groups
Sawyer 158 mothers of children with CP, Cross-sectional 24-h Mothers scored significantly – Y – General health Q
et al. (2011) age 6–17 time diary of higher on mental health CES-D depression
caregiving difficulties than population norms. ISEL support
Mental health difficulties were
Time crunch
correlated with time spent
caregiving, feelings of time Time diary
pressure, and maternal GMFCS severity
unemployment, with time
pressure more strongly predicting
mental health than caregiving
hours. Depressive symptoms were
correlated with time pressure;
severity was unrelated to mental
health
Sipal et al. 110 mothers of children with CP Longitudinal: 3-year Stress, severity, and low family – – – Life stressors and social
(2010) ages 9–13 in the Netherlands study social support predicted increases resources inventory
in child behavior problems over GMFCS severity
time. The strongest predictor of CLCB behavior
behavior problems was
“situational stress,” including
resources such as family income,
parent health, and job satisfaction.
Although behavior problems
36
decreased overall as children

aged, worsening behavior over
time predicted increases in stress.
Maternal stress was unrelated to
CP severity
Skok et al. Mothers of 43 school-aged Cross-sectional Disability severity was unrelated – Y – Stress: Cohen PSS
(2006) children with CP in Australia to parent well-being. Stress and Well-being: SWLS and
social support both predicted well- PAL-C
being, and social support mediated MSP support
the relation of stress with well-
GMFCS severity
being
Strom et al. 40 parents of children with CP Cross-sectional Compared to population norms, – Y Y ComQOL-45
(2012) ages 1–13 in Cambodia parents of children with CP
reported unsatisfactory QOL in
domains of material and emotional
well-being and physical health,
with health being lowest

Tseng et al. 167 parents of children with CP Cross-sectional Compared to population norms, – Y Y Stress: PSI
(2016) ages 4–12 (mean = 9) in Taiwan parents of children with CP WHOQOL-BREF
reported significantly lower QOL Strengths/difficulties
on physical and mental health and
GMFCS severity
social relationships. Parent mental
health was associated with lower Family coping
child emotional and behavioral CHQ health
difficulties, parenting stress,
family impact, and better coping.
Parent physical health was
associated with lower disability
severity and with better mental
health, marital satisfaction, and
coping
Wanamaker 84 parents (62 mothers, 22 fathers) Cross-sectional Among mothers, stress was – Y – Stress: PSI
and of children with CP ages 3–7. associated with greater depression BDI depression
Glenwick Excluded if child unable to speak and child behavior problems and PSOC self-efficacy
(1998) in sentences with lower social support,
SSQ6 social support
parenting satisfaction, and self-
efficacy. For fathers, stress was ECBI child behavior
associated with lower parenting
(continued)
529
530
Table 1 (continued)
Stress
satisfaction and greater child
behavior problems
Wang and 63 parents of children with CP Cross-sectional Parents of children with CP Y – – Stress: PSI
Jong (2004) (mean age = 4) and 40 healthy reported higher stress than healthy GMFCS severity
controls in Taiwan controls. Stress was correlated
with disability severity
Wayte et al. 40 mothers of children with CP Cross-sectional Children with CP experienced – Y Y Sleep: PSQI, CSHQ
(2012) compared to 102 controls age worse sleep quality and more MDI depression
4–12 (mean = 8) in the UK sleep difficulties than healthy
controls. Child sleep disturbance
was correlated with maternal sleep
disturbance, and maternal sleep
disturbance predicted maternal
depression, accounting for 50% of
the variance in depression. 40% of
mothers of children with CP
reported poor sleep quality
Note: US samples unless otherwise noted. The “Stress higher in CP?” column indicates whether results show that parents of children with CP report higher stress compared to
healthy controls or population norms. The “Psychological effect” column indicates whether results show effect of stress or child diagnosis status on parent mental health outcomes.
The “Physical effect” column indicates whether results show effect of stress or child diagnosis status on parent physical health outcomes. Y (yes), N (no), – (not tested or reported).
BDI Beck Depression Inventory, CBCL Child Behavior Checklist, CHIP Coping Health Inventory for Parents, CHQ Child Health Questionnaire, ComQOL-45 Comprehensive
Quality of Life Scale, COPE Coping Strategies, CPCHILD Caregiver Priorities and Child Health Index of Life with Disabilities, CPQOL Cerebral Palsy Quality of Life
Questionnaire for Children, CSHQ Child Sleep Habits Questionnaire, DAS Dyadic Adjustment Scale, ECBI Eyberg Child Behavior Inventory, FACES-3 Family Adaptability and
Cohesion Evaluation Scale, FSS Family Support Scale, GHQ-28 General Health Questionnaire, GMFCS Gross Motor Function Categorization System, HOME Home Observation
for Measuring the Environment, HUI Health Utility Index, IOF Impact on Family Scale, ISEL Interpersonal Support Evaluation List, MBI Maslach Burnout Inventory, MDI Major
Depression Inventory, MOS Medical Outcomes Study-Social Support Scale, MSP Multidimensional Scale of Perceived Social Support, PAL-C Profile of Adaptation to Life-
Clinical Scale, PODCI Pediatric Outcomes Data Collection Instrument, PSI Parenting Stress Index, PSOC Parenting Sense of Competence Scale, PSQI Pittsburgh Sleep Quality
Index, PSS Perceived Stress Scale, QOL Quality of Life, RDI Reaction to Diagnosis Interview, SES Socioeconomic Status, SF-36 Short-form 36 assessment of mental and physical
functioning from the Medical Outcomes Study, SPARCLE Study of Participation of Children with Cerebral Palsy Living in Europe, SRQ Self-Report Questionnaire, STAI State-
Trait Anxiety Index, SWLS Satisfaction With Life Scale, UCL Utrecht Coping List, WHOQOL World Health Organization Quality of Life index
services. Finally, we propose future directions for and spill over into an adverse stress response.
the field with respect to (1) targeted interventions For some families, having a child with a disability
to reduce family stress and (2) specific variables represents a large lien against their adjustment
and methodological strategies that future studies limit. One can imagine, then, that it would not
should employ in order to better understand the require many additional stressors to erode family
complex relationship between family stress and members’ coping reserves. Parents with a high
the unique experience of caring for a child with baseline stressor load may respond to objectively
cerebral palsy. Throughout the chapter, we com- minor events with large emotional reactions
bine our professional expertise as a health psy- because their coping resources are stretched thin,
chologist (HF) and clinical social worker (CSR) and as a result, they may “catastrophize” or view
with our personal expertise as parents raising chil- the small stressor in terms of negative future
dren with severe spastic quadriplegic cerebral implications. Imagine, for example, that a parent
palsy to interpret this literature, identify weak- lifts her child from wheelchair to bed in an awk-
nesses, and make recommendations for future ward manner and suffers a pulled muscle as a
directions in research, practitioner-parent interac- result. Whereas an outsider may view this as a
tion, and intervention. minor inconvenience, the parent may experience
distress seemingly disproportionate to the event
because to her, it represents a rapidly approaching
Parent Stress future in which her child grows bigger and heavier
while the mother grows older and weaker, even-
Twenty-six studies specifically examined cerebral tually making one-person transfers impossible
palsy caregiving and parent stress levels, broadly and perhaps necessitating expensive in-home
construed. Sixteen of these studies employed the caregiving help. Similarly, a mild cold or asthma
Parenting Stress Index (PSI), while most others attack may elicit seemingly disproportionate par-
employed well-validated measures such as Cohen ent distress because it brings to mind the possibil-
et al.’s (1983) Perceived Stress Scale, McCubbin ity that the child’s health may worsen, requiring
et al.’s (1983) Family Inventory of Life Events hospitalization and disruption to the family rou-
and Changes, or Moos et al.’s (1988) Life tine for weeks to come. Although stressor pileup
Stressors and Social Resources Inventory. Bella is a rather old concept, we feel it is a useful
et al. (2011), Prakash et al. (2017), and Raina et al. framework for explaining the links we see in the
(2005) measured caregiver burden, and Basaran literature between what might be construed as
et al. (2013) employed caregiver burnout as their minor or isolated stressful events and rather large
stress indices. Seventeen of these 26 studies spe- effects on parent mental and physical well-being.
cifically examined whether parents of children Accordingly, this concept also highlights for us
with cerebral palsy experienced elevated stress the impressive power that parent and child
levels as compared to healthy controls or popula- resources have in moderating stress effects.
tion norms. All 17 studies did, in fact, find signif-
icantly higher stress among the parents of children
with cerebral palsy, whereas none found an Psychological Well-Being
inverse or lack of relation between caregiving
status and parental stress. Twenty-six studies specifically examined psycho-
Much of the research in the study of disability logical well-being outcomes among parents of
and stress has been influenced by an early con- children with cerebral palsy. These studies
cept, first proposed by McCubbin et al. (1983), of employed mental health indices from the SF-36
stressor “pileup.” This is the idea that in any or the WHOQOL quality of life domains, the
family, stressful life events and changes “pile Beck and CES-D depression inventories, and
up” in a summative manner, and at a certain other measures assessing depression, anxiety, or
point, they reach the family’s adjustment limit general distress. Twenty-four of these 26 studies
found that greater parent stress levels or more Four studies also assessed child health out-
severe child diagnosis status was associated with comes: Davis et al. (2011), Majnemer et al.
worse parent mental health, whereas two studies (2007, 2012), and McCubbin and Huang (1989).
found no effect on parent mental health (Jayanath All four found that worse child health was
et al. 2016; Mullen 1997). Across the studies associated with parent stress and mental health
showing a detrimental effect, some common difficulties. Three of these studies employed cor-
themes emerged. The majority of studies exam- relational designs, so the direction of causality
ined maternal mental health only; among studies cannot be determined: It is plausible that poor
examining both mothers and fathers, stronger child health elicits high parent stress, but it is
effects tended to emerge on maternal than paternal also possible that high parent stress levels are
mental health outcomes. This was explained in detrimental to child physical health. However,
part by greater caregiving time by mothers than the longitudinal design employed by the fourth
fathers, which is consistent with the broader liter- study (McCubbin and Huang 1989) clearly
ature on parent caregiving of children with other showed among children with moderate cerebral
developmental disabilities such as autism, Down palsy that high levels of family stress at Time
syndrome, and muscular dystrophy (Bourke- 1 predicted worse child health at the 3-month
Taylor et al. 2012; Brehaut et al. 2004). Across follow-up physician’s exam. These results suggest
both mothers and fathers, a strong and consistent that interventions to reduce parent stress may be
predictor of both stress and poor psychological important for both parent and child physical
well-being was child behavior difficulties, which health. Notably, none of the 21 studies we
is discussed in more detail later. reviewed in this domain found a lack of relation
or inverse relation between stress and parent or
child physical health difficulties.
Physical Health Outcomes Four studies assessed sleep outcomes, and all
four found that families of children with cerebral
Seventeen studies specifically examined parental palsy reported high levels of sleep disturbance
physical health outcomes among parents of chil- among both parents and children. Parents in the
dren with cerebral palsy; all showed a negative Davis et al. (2010) and Mobarak et al. (2000)
effect of stress or diagnosis status on parent studies identified chronic sleep disruption among
physical health. Studies utilized well-validated their most significant caregiving burdens. Wayte
physical health indices from the SF-36 (n = 4), et al. (2012) found that children with cerebral
WHOQOL (n = 4), measures of sleep disturbance palsy experienced significantly more sleep diffi-
(n = 4), or other commonly used physical health culties across multiple dimensions as compared to
indices (n = 6); in addition, one assessed 24-h typically developing children and that sleep dis-
salivary cortisol (Bella et al. 2011), and one turbance accounted for 50% of the variance in
assessed musculoskeletal and lower back pain maternal depression. Similarly, Barlow et al.
(Kaya et al. 2010) (Note: some studies employed (2006) found that maternal anxiety was correlated
more than one physical health measure). A com- both with child’s sleep disturbance and with lower
mon theme across these studies is that parents of parenting self-efficacy and suggested that parent
children with cerebral palsy find less opportunity interventions targeting child sleep difficulties may
to engage in health-promoting behaviors such benefit maternal confidence in addressing sleep
as exercise, sleep, and leisure as compared to issues and, ultimately, maternal sleep and mental
healthy controls and population norms. These health. Bourke-Taylor et al. (2012, 2013) report
are the very health behaviors that are compro- similar sleep disturbance difficulties among
mised under conditions of chronic stress, and families of children with Down syndrome and
long-term neglect in these domains is hypothe- autism, and Lee (2013) reviewed the literature
sized to contribute to the development of chronic on maternal stress, well-being, and sleep impair-
illness (Cohen et al. 2007). ment among mothers of children with a variety of
developmental disabilities, concluding that sleep 12 reported a linear relation between severity
deprivation is a significant problem eliciting neg- and stress or mental health outcomes similar to
ative mental and physical health effects on care- that evidenced in other patient populations, such
givers. Anecdotally, both authors can attest to the that higher level of child disability (typically mea-
cumulative toll that multiple nighttime sleep inter- sured with the Gross Motor Function Classifica-
ruptions exert on parents’ daytime mood, energy, tion System or GMFCS) was associated with
concentration, critical thinking skill, and problem- worse parent outcomes. However, four studies
solving ability. These difficulties are often magni- showed a significant but nonlinear pattern of rela-
fied by child illness and/or hospitalization, when tions generally suggesting that mild or moderate
child and parent sleep may become even more disability was linked with worse parent out-
elusive and, simultaneously, the need for parent comes than severe disability (McCubbin and
patience, stamina, good humor, and ability to Huang 1989; Park et al. 2012; Ribeiro et al.
process complex information becomes even 2014; Romeo et al. 2010). The fact that 8 of the
more important. Indeed, the negative physiologi- 24 studies we reviewed on this question also
cal, psychological, and cognitive effects of sleep found no relation between disability severity and
deprivation are well-documented (e.g., Ibarra- parent outcomes suggests that this relation may be
Coronado et al. 2015; Motivala 2011). Practi- more complex in the context of cerebral palsy as
tioners should remain aware that ameliorating compared to other patient populations.
sleep difficulties in children with cerebral palsy While the nonlinear relation between disability
may translate into significant improvements for severity and parenting stress may seem counter-
both child and parent quality of life, particularly intuitive to us as researchers, our role as parents of
during acute illness episodes and/or conditions of severely disabled children provides us with some
high family stress. insight into how such a relation may come about.
Finally, Bella et al. (2011) assessed caregiver Our severely disabled children have many com-
burnout, mental and physical health, and 24-h plex medical and equipment needs, but at some
salivary cortisol as an index of HPA axis function. point in childhood, it became clear to each of us
They found that compared to parents of typically that broadly directed intensive therapies would
developing children, parents of children with not make significant gains in all areas of develop-
cerebral palsy exhibited lower physical well- ment for our children. Instead, we refocused our
being on the SF-36, lower cortisol production, expectations for improvement in our child’s func-
and a pattern of cortisol dysregulation suggesting tional status on specific areas where our children
compromised HPA axis function due to high showed strength and possibility for improvement.
levels of chronic stress. For instance, when it became apparent to CSR that
her daughter (age 10) would never be able to eat
orally or ambulate independently, her family
Disability Severity became more focused on making gains with aug-
mentative communication, where their daughter
Disability severity may be regarded as a main showed far more ability to progress, rather than
predictor of caregiver stress, as has been the case continuing fruitless feeding therapies and gait
among other disability populations such as intel- training. Similarly, when it became apparent to
lectual disability (Shahrier and Debroy 2016), HF that her son (age 15) was no longer making
progressive supranuclear palsy (Uttl et al. 1998), gains from intensive therapy even in areas of
and mental illness (Ohaeri 2003). We identified relative strength for him, such as speech and fine
24 studies that specifically examined the relation motor skills, they eliminated most therapy ses-
between child disability severity and caregiver sions to allow her son to participate in after-school
stress or mental health outcomes. Sixteen of activities that enabled him to use his speech and
those studies showed a relation between cerebral fine motor (power chair driving) skills in peer-to-
palsy severity and parent outcomes. Of those, peer situations. This change yielded no
discernible negative effect on his speech or fine Ribeiro et al. (2014) also found that mildly
motor skills, improved his social participation, disabled children exhibited greater emotional
and greatly increased his enjoyment of his after- and behavioral difficulties than did severely dis-
school hours. Thus, this ability to focus efforts abled children, which contributed to parent stress.
may give families of more severely affected chil- A similar pattern of results emerged in other stud-
dren the ability to free up time for meaningful ies we reviewed (e.g., Romeo et al. 2010). Such
family time, peer socialization, and other pursuits. results may occur in part because children with
By contrast, our interactions with parents of chil- mild to moderate cerebral palsy are more likely to
dren with mild to moderate cerebral palsy suggest be included in regular classrooms than children
to us that these parents continue to feel pressure to with severe cerebral palsy and therefore more
maintain a broad and rigorous therapy schedule often involved in interactions with typically
for their children, sometimes at the expense of developing peers (S. Bachrach, personal commu-
other after-school activities, family activities, or nication). These interactions may be difficult for
“downtime.” The reason for this may be that, children and parents alike, especially as children
particularly for children with mild or moderate age and social inclusion becomes more important.
cerebral palsy, therapy yields a noticeable func- To this point, Nadeau and Tessier (2006) surveyed
tional improvement, and the cessation of therapy 10-year-old children with cerebral palsy who were
may elicit greater backsliding for them as com- enrolled in mainstream classrooms. Compared to
pared to children with severe cerebral palsy. their same-age peers, the children with cerebral
Moreover, when additional stressors pile up in palsy had significantly fewer reciprocal friend-
such families, parents may feel a sense of guilt ships, exhibited fewer sociable and leadership
or failure when they are not able to maintain an behaviors, and were more isolated and victimized
intensive therapy schedule, thus compounding by their peers than their classmates without a
parenting stress. disability. Children with mild disability in
This pressure that parents feel to maintain mainstreamed classrooms may also have greater
intensive therapy in order to maximize child opportunity than children with more severe dis-
potential may be well-founded. Most telling, abilities to engage in unfavorable direct social
perhaps, is the longitudinal McCubbin and comparisons with peers. To the extent that they
Huang (1989) study, which found that when feel left out of peer activities, mildly disabled
families experienced additional, unexpected children may be more likely than severely dis-
stressful life events, children with moderate abled children to question “why me?” or to
(but not mild or severe) cerebral palsy experi- become attuned to the stigma of being different
enced health declines over time. These results from peers (S. Bachrach, personal communica-
dovetail nicely with those from Ribeiro et al. tion). We could find no research directly
(2014), who found that among parents of young addressing these questions among children or
children with cerebral palsy, those with children adolescents with cerebral palsy, but we identify
who had severe disability reported higher stress these as important questions for future research.
than those with children who had a mild disabil- Relatedly, Brossard-Racine et al. (2013)
ity; however, in adolescence, this trend reversed. administered the Strengths and Difficulties
Parents reported that as their child aged, the Questionnaire to younger (age 12–14) and older
prognosis and expectations were clearer for (age 15+) adolescents with cerebral palsy. Com-
their children with severe as opposed to mild pared to a norm-referenced groups of typically
disability. Whereas parents of severely disabled developing adolescents, adolescents with cerebral
children gained a sense of acceptance of the palsy exhibited significantly greater difficulties,
future, parents of mildly disabled children felt the most frequent of which was peer problems.
increasing pressure to prepare their child to live a Although parental stress was associated with
functionally independent existence outside the other difficulties including hyperactivity and con-
parental home. duct problems, it was not related to their child’s
peer problems in this study. In fact, very few disability severity and parental stress and are
studies to date have examined the relation of ado- important avenues for future research.
lescent peer conflicts or social isolation difficul-
ties with parental stress; this seems like an
important direction for future research. It is Family Adaptation
worth noting that Brossard-Racine et al. (2013)
found that older adolescents exhibited lower The family systems perspective considers the
levels of peer difficulties than did younger adoles- ways in which families may respond to stressors
cents, suggesting improvement in these skills across several domains of family functioning.
as teens move from middle to high school. Simi- Various family resilience qualities, such as spouse
larly, across two longitudinal studies of quality practical and emotional support, the development
of life issues among adolescents with cerebral of parent and sibling routines to facilitate caregiv-
palsy, social participation and social acceptance ing, chores, or travel, or the development of a
remained stable over time as children transitioned unique family norm (and a very high bar) for
from younger to older adolescence (Majnemer what constitutes an “emergency” worthy of a neg-
et al. 2015; Rapp et al. 2017), but no relation to ative emotional response, may all help to explain
parent stress was reported in these studies. why conditions that appear stressful to outsiders
To be clear, adolescence is stressful for parents do not necessarily result in decays of functioning
of children with severe cerebral palsy and is sig- within the family. Some special needs families do
nificantly more stressful for them than for the indeed develop strategies that allow them to take
parents of typically developing children. Adoles- disability-specific hurdles in stride. Little empiri-
cence for severely disabled children is often cal attention has been paid to this rather nebulous
accompanied by worries regarding the emergence resilience “X factor”; however, we have identified
of seizure disorders, orthopedic surgeries or wors- five studies taking a family systems approach to
ening health conditions, increasingly complicated the measure of adaptive coping strategies (Glenn
physical care, supervision of a young adult, and, et al. 2009; Guyard et al. 2017; Lin 2000; Sipal
for some families, concerns about the child’s more et al. 2010; Tseng et al. 2016). Family adaptation,
limited life expectancy. Yet, it is noteworthy that family cohesion, and family functioning are the
the relation between disability severity and paren- most common variables measured in this domain;
tal stress is not necessarily linear. Practitioners they are sometimes conceptualized as predictor
would be wise to design interventions and variables and sometimes as outcomes. Glenn
patient-provider interactions with an awareness et al. (2009) found that high family adaptability,
that parents of mildly disabled children are not family cohesion, and spouse support were associ-
necessarily less stressed than parents of severely ated with lower parenting stress; similarly,
disabled children and may, in some cases, become Guyard et al. (2017) found that family functioning
more stressed as their children age. No studies to was the strongest protective factor against parent-
our knowledge directly examine the questions of ing stress. Sipal et al. (2010) reported that “situa-
(1) the extent to which parent expectations change tional stress,” conceptualized as few family
from infancy to adolescence as a function of dis- material resources and low family support, pre-
ability severity, (2) the extent to which disability dicted increases in child behavior difficulties over
severity relates to parental pressure to maintain time. Tseng et al. (2016) found that parent mental
intensive therapy services in order to maximize health was associated with a constellation of
their children’s potential to become independent, family strengths, including lower impact of the
and (3) the extent to which disability severity disability on family functioning and adaptive
relates to social comparison, feelings of stigma, coping strategies.
peer problems, or social isolation among children Finally, to date, only Lin (2000) has attempted
and adolescents with cerebral palsy. These factors to assess the role of disability-specific norms
may mediate the nonlinear relation between and cognitive strategies as they relate to stress
and mental health outcomes among families of Interestingly, parent support is sometimes
children with cerebral palsy. Lin found that the based on the assumption that caregivers of chil-
strongest predictor of family adaptation is “family dren with disabilities experience mental health
reappraisal,” which is conceptualized as putting a difficulties due to a state of “chronic sorrow,” or
positive spin on disability-related challenges and continual grieving regarding the disability, as par-
confronting them directly. A similar concept was ents compare their child to other children or to the
examined by Cheshire et al. (2010), which they way they imagine their child would be if he or she
deemed “positive reinterpretation.” They did not did not have the disability. However, the data
relate it to stress or health (and thus was not herein paint a different picture of the roots of
included in Table 1); however, using a dovetailed parental distress and the effectiveness of social
interview and survey approach, they identified support. Whittingham et al. (2013) found that
two aspects of positive reinterpretation employed although some parents experienced deep sorrow
by parents of children with cerebral palsy: focus- immediately following their child’s diagnosis,
ing on the positive and finding meaning in the many others found the diagnosis to be a relief.
disability. As it turns out, this type of cognitive And although periods of intense health interven-
reframing of stressors has a long history in the tion or hospitalization can briefly reignite sorrow
health psychology literature and is associated with years later, Krstic et al. (2015) and Rentinck et al.
enhanced mental and physical adjustment to (2009) both report that within a few years of initial
diverse stressors among both healthy and chroni- diagnosis, the vast majority of parent caregivers
cally ill populations (see Park 2010, for a compre- move to a “resolved” emotional state of accep-
hensive review). Our role as parents of severely tance and no longer, or rarely, felt episodes of
disabled children compels us to believe that there deep sorrow when comparing their child with
may be some unique facets to the cognitive cerebral palsy to others. Yet, friends, family, med-
reframe strategies employed in the context of ical professionals, and support intervention pro-
cerebral palsy caregiving, and we identify this as grams sometimes presume that the root of parental
another fruitful area for future research. distress is sadness and that the remedy for this is to
provide ample emotional support. Both Rentinck
et al. (2009) and Florian and Findler (2001) sug-
Parent Personal Resources: Social gest that once families have accepted their child’s
Support and Self-Efficacy disability, the type of support that parents crave
most is practical support, rather than emotional
We identified 15 studies assessing the role of support. Practical support is direct help with the
social support in caregiving. Of these, 12 found physical tasks of lifting, transporting, feeding,
that greater support from network members was supervising, etc. that consume so much of care-
associated with reduced parent stress or mental givers’ time. Similarly, Bourke-Taylor et al.
health difficulties, one study found no relation (2012) suggest that some well-meaning parent
between spousal support and maternal stress support programs may miss the mark by provid-
(Mobarak et al. 2000, which also noted low base- ing emotional support at the expense of practical
line support in this sample of rural mothers in support interventions that may be more useful at
Bangladesh), and two assessed but did not report reducing parenting stress. As we will discuss more
on the relation between social support and care- below, parent support interventions that focus on
giver outcomes (Jayanath et al. 2016; Lin 2000). providing parents with practical support may be
Five studies specifically identified social isolation the most effective in mitigating caregiver stress.
or limited social network size as a notable chal- Five studies we reviewed specifically exam-
lenge for caregivers of children with cerebral ined the contributions of spousal support or
palsy (Button et al. 2001; Davis et al. 2010; marital quality to caregiver stress and health out-
Florian and Findler 2001; Pimm 1996; Tseng comes. Britner et al. (2003) and Mullen (1997)
et al. 2016). found that greater marital quality was associated
with reduced parenting stress, and participants in efficacy was inversely associated with maternal
the Davis et al. (2010) study identified marital anxiety and depression, and Wanamaker and
strain as one of the most challenging negative Glenwick (1998) reported that self-efficacy was
effects of having a child with cerebral palsy. inversely associated with maternal stress (but
Both Florian and Findler (2001) and Olrick et al. unrelated to paternal stress). Florian and Findler
(2002) found that greater paternal practical care- (2001) found that mothers of children with cere-
giving help was associated with enhanced mater- bral palsy reported lower self-mastery than
nal marital satisfaction. Although anecdotal healthy controls and that greater self-mastery
evidence might suggest that the elevated stress was associated with greater maternal well-being
associated with parenting a child with a disability and marital adaptation. Finally, Guillamon et al.
might lead to higher rates of marital dissolution in (2013) found among both mothers and fathers that
this population, we were unable to find any studies greater self-efficacy was associated with greater
addressing this specific question. The closest mental and physical health, greater relationship
insight we may gain on this issue comes from satisfaction, and lower anxiety. Barlow et al.
Kersh et al. (2006), who report on the Early Inter- (2006) suggest that providing practical caregiving
vention Collaborative Study, a longitudinal inves- skills training in difficult domains (e.g., sleep
tigation of 190 children with a variety of disruption) may positively influence caregiver
developmental disabilities and their families. self-efficacy and ultimately elicit health benefits
From the larger sample, they selected only fami- for both parents and children. Self-efficacy and
lies in which both biological parents had been skills training may be fruitful areas for psychoso-
married since the birth of their child 10 years cial interventions to reduce parent stress, as
prior. They found this comprised 44% of their discussed below.
sample, a rate of enduring marriage comparable
to the 45% rate of marriages lasting 10 years or
more in the USA, suggesting no overall negative Assessment Tools and Interventions
effect of caregiving on marital duration. However,
within this sample, parents reported significantly While there is growing knowledge of caregiver
lower marital quality compared to population stress in the context of cerebral palsy, less is
norms of parents married the same amount of known about how to assess the risk of stress in
time, with about one quarter of the sample scoring individual families and how to implement inter-
as “distressed” according to the Dyadic Adjust- ventions to support families experiencing stress.
ment Scale norms. Marital distress was unrelated One conceptual model developed to guide psy-
to child characteristics in this study. Clearly, many chosocial assessment and intervention for the
questions remain regarding the source and mag- pediatric population is the Pediatric Psychosocial
nitude of marital distress among caregiving par- Preventative Health Model (PPPHM), shown in
ents and its ultimate effect on marriage quality, Fig. 1 (Kazak 2006).
longevity, and family adaptation. PPPHM was originally developed to identify
Four studies examined the role of caregiver psychosocial risk in the pediatric oncology popu-
self-efficacy in parental stress and health out- lation and identifies three risk levels: clinical/
comes, and all four found a beneficial effect of treatment, targeted, and universal. At the univer-
high self-efficacy. In the caregiving literature, sal level, families are identified as stressed but
self-efficacy refers to caregivers’ perception of resilient. These families may require general
their own caregiving competence, including the information and support, and PPPHM recom-
ability to execute health-promoting skills, to mends the screening of individual family mem-
respond appropriately to care-related difficulties, bers for higher risk. The targeted level identifies
and to control negative thoughts and feelings acti- families who have some pre-existing difficulties
vated by caregiving activities (Guillamon et al. and are experiencing acute distress, and PPPHM
2013). Barlow et al. (2006) found that self- recommends providing interventions and services
Pediatric Psychosocial Preventive Health Model
CLINICAL/TREATMENT
Consult behavioral health specialist.
Intensify psychosocial services.
Severe, escalating, or Address impact on medical treatment.
persistent distress.
TARGETED
Monitor child / family distress and risk factors.
Provide interventions specific to symptoms
Acute or elevated distress. Other risk factors present. or adherence needs.
UNIVERSAL
Provide pychoeducation
and family-centered support.
Children and families are distressed but resilient. Screen for indicators of higher risk.
©2011 Center for Pediatric Traumatic Stress
Fig. 1 Reproduced with permission from the Center for any purpose without the express written permission of
Pediatric Traumatic Stress (CPTS) at Nemours Children’s CPTS. To obtain permission to use or reproduce the most
Health System © 2017–2018. All rights reserved. The recent version of the PPPHM, please contact CPTS at
PPPHM image may not be reproduced in any form for psychosocialassessmenttool@nemours.org
specific to their needs. At the highest level of risk, (internalizing, externalizing, social, cognitive),
the clinical/treatment level, families are identified sibling problems, family problems, family beliefs
as experiencing persistent and escalating distress and stress responses” (Kazak et al. 2015).
due to pre-existing, chronic, and complex prob- The PAT is an empirically validated tool, uti-
lems, and PPPHM recommends that these fami- lized widely in the pediatric oncology setting, and
lies consult a behavioral health specialist for has been found to be clinically reliable outside of
intensive intervention (Alderfer et al. 2009; the pediatric oncology population (Crosby et al.
Kazak et al. 2015). Alderfer et al. developed the 2015; Karlson et al. 2012; Kazak et al. 2015). The
Psychosocial Assessment Tool (PAT) to assist in PPPHM model and the PAT have been found
identifying where families may fall within this to have reliability when utilized in the assessment
psychosocial risk model. The PAT is a brief of risk in the sickle cell (a chronic illness) popu-
(5–10 min), parent-report screening tool that clas- lation, rather than acute disease population
sifies families into one of the three PPPHM risk (Crosby et al. 2015; Karlson et al. 2012). While
levels through the assessment of the following no evidence-based psychosocial assessment tool
domains: “demographic characteristics, diagno- is currently used widely to assess stress and risk in
sis, family structure, family resources, social sup- families of children with cerebral palsy, the PAT
port, child knowledge of disease, school may hold promise for being a useful tool for this
enrollment, school placement, child problems population as well. There are other psychosocial
assessment tools developed for assessing psycho- vacations (Davis et al. 2010), it is known that
social risk in pediatric populations that may also parents of children with disabilities who partici-
be explored (http://www.societyofpediatricpsychology. pate in healthy activities such as recreation, exer-
org/family_measures). Research regarding this cise, visiting with friends, and taking time out for
question is needed, as researchers and providers themselves have better overall mental health
seek to understand and address caregiver stress in (Bourke-Taylor et al. 2013). Therefore, in addi-
the cerebral palsy population. tion to accessing more formal evidence-based
A strength of the PPPHM model and the PAT is treatment interventions to address stress,
that it can assist providers in identifying not only assisting families in accessing services that will
whether psychosocial risk exists, but the acuity give them a break from caregiving responsibili-
level of the risk and what level of intervention ties, such as respite services, can be an important
may be necessary to meet the family’s needs. At part of an intervention. Respite care is associated
the highest level (clinical/treatment level), fami- with significant reductions in parental stress
lies can be expected to experience high levels of (Chan and Sigafoos 2001; Chetwynd 1985). Par-
stress, which are often caused by circumstances ents of children who are more severely disabled
that existed prior to the diagnosis of the child’s may be more willing to use formal respite ser-
medical condition (Kazak et al. 2015). These fam- vices (Damiani et al. 2003; Palisano et al. 2009),
ilies may require more intensive interventions although evidence suggests that these families
such as psychiatric consultations, evidence- also have more difficulty finding respite pro-
based individual or family therapy, or family- viders who are adequately trained to provide
based behavioral health services. Interventions care for severely disabled children (Damiani
may require the involvement of the entire treat- et al. 2003).
ment team and may require frequent patient care
meetings involving the families. At the targeted
level, families may benefit from evidence-based Financial Resources
interventions such as cognitive behavioral therapy and Socioeconomic Status
to address depression, anxiety and other symp-
toms that are caused by stress. And at the univer- Accessing financial assistance, for respite services
sal level, families may benefit from care and other needs for the child and family, is a
coordination, case management, education, and common source of stress in cerebral palsy families
psychosocial support as they navigate the chal- (Damiani et al. 2003; Davis et al. 2010). While
lenges of raising a child with special medical living in low socioeconomic conditions is a source
needs (Alderfer et al. 2009; Kazak et al. 2015). of high stress for any parent or caregiver, for
parents of children with cerebral palsy, it can be
an even greater hardship due to medical and care-
The Role of Respite Care Services giving expenses (Bella et al. 2011; Canning et al.
1996; Davis et al. 2010; Ribeiro et al. 2014).
For parents of children with cerebral palsy, stress Additionally, parents of children with cerebral
often appears to be exacerbated by the large palsy are less likely to work, and less likely to
amount of time that parents spend engaging in work full time, than parents of typical children due
caregiving activities, compared to parents of typ- to their caregiving responsibilities, leading to
ically developing children (Sawyer et al. 2011). greater financial hardship (Brehaut et al. 2004;
Parents of young adults with cerebral palsy in Ribeiro et al. 2014). Lower socioeconomic status
particular experience stress due to caregiver (SES) in families with children with developmen-
demands (Hallum and Krumboltz 1993; Ribeiro tal disabilities is known to be associated with poor
et al. 2014). And while parents of children with mental health for both mothers and fathers (Kersh
cerebral palsy may have less time to engage in et al. 2006; Motteno and Lochman 1996). Finan-
social and recreational activities as well as cial hardship is also associated with behavior
problems in children with cerebral palsy (Sipal Majnemer et al. 2012; Mobarak et al. 2000;
et al. 2010). Parkes et al. 2011; Pimm 1996; Raina et al.
Access to professional assistance in identifying 2005; Romeo et al. 2010; Sipal et al. 2010;
resources to help pay for respite services, medical Tseng et al. 2016; Wanamaker and Glenwick
expenses, nursing care, and other financial needs 1998). Therefore, interventions that help parents
is a concrete and effective way to help mitigate in learning appropriate child behavioral manage-
psychosocial risk and prevent stress (Neely- ment strategies may mitigate caregiver stress
Barnes and Dia 2008). Access to social work (Hastings and Beck 2004). The parent training
and case management support is often available therapeutic model Positive Parenting Program
in pediatric hospital settings for families, and (Triple P), modified to serve the needs of special
these services can also be accessed through populations called Stepping Stones Triple P
state-based service programs such as the Depart- (SSTP), has been shown to have promise in use
ment of Development and Disability Services in in the cerebral palsy population. In a focus group,
Delaware (http://dhss.delaware.gov/dhss/ddds/) parents found SSTP to be a positive parent train-
or through nonprofit organizations such as the ing program that helped them focus on their chil-
ARC or UCP (http://www.thearc.org/, http://ucp. dren’s strengths and helped them build confidence
org/). Information regarding how to access respite in their child (Whittingham et al. 2013). In addi-
funding and other financial assistance through tion, the modality assists parents with time man-
state-based programs can also be found online agement strategies, something that is essential for
(http://www.kidswaivers.org/). CSR, as a social caregivers who are constantly juggling the signif-
worker in a hospital setting, has found that receiv- icant demands of therapy and caregiving activities
ing help from a social worker in accessing finan- in addition to all of their other responsibilities
cial resources not only helps to lessen the financial (Whittingham et al. 2013).
burdens that families face but it also helps parents In addition to parent training, other mental
feel supported by their child’s medical team. health treatment options may help families in mit-
Additionally, it allows parents to focus on care- igating stress and managing its causes. Cognitive
giving and family responsibilities, maintaining behavioral therapy that assists parents with
employment, and self-care, rather than spend- problem solving and cognitive restructuring may
ing hours and days on trying to access needed be helpful (Hall et al. 2012; Hastings and
state-based assistance programs and disability- Beck 2004). Solution-focused therapies and
specific funding. problem-solving training programs (Hall et al.
2012) may also provide appropriate interventions
for parents whose stress may originate from spe-
Psychosocial Interventions and Parent cific challenges that can be addressed through
Stress methodological interventions. As described ear-
lier, parents of children with special needs
Psychosocial interventions should be multi- are generally at higher risk for mental health con-
disciplinary as well as multifaceted to meet the cerns such as depression and anxiety, and these
needs of parents at risk of caregiver stress mental health diagnoses often co-occur with care-
(Prakash et al. 2017). Therefore, while the giver stress. Therefore, caregivers who experience
abovementioned interventions are essential to depression and anxiety may benefit from
supporting many families of children with cere- evidence-based therapies that are designed to
bral palsy, mental health treatment may also play a treat these diagnoses such as cognitive behavioral
significant role in reducing psychosocial risk. Ten therapy, problem-solving therapy, or interpersonal
studies we reviewed assessed child behavior dif- therapy (http://www.div12.org/psychological-trea
ficulties; all ten found that child behavior prob- tments/disorders/depression/).
lems were the main predictors of parental stress In addition to these more formal therapeutic
and mental health difficulties (Guyard et al. 2017; modalities, many families find participation in
support groups with other special needs parents network (Krauss et al. 1993). At present, there
effective in coping with the stress and challenges has been little empirical investigation of the qual-
of raising a child with cerebral palsy. Parents ities that comprise an effective support group for
who build social relationships have a greater per- parents of children with cerebral palsy, and this
ception of being supported and happier (Florian should be a priority for future research.
and Findler 2001). Some parents find that while In addition to mental health providers and case
parenting a child with cerebral palsy can be iso- managers, medical providers and therapists who
lating, it can also allow parents to build new social directly treat the child with cerebral palsy can
support networks (Davis et al. 2010). Parents also play a very significant role in helping
who build relationships with other special needs reduce caregiver stress. Parents who are actively
families can connect with each other and cope involved in planning the child’s care, and are
with stress (Davis et al. 2010; Dyson 1997). Par- empowered to make medical decisions for their
ents can also benefit from connecting with parent child, are less likely to experience caregiver stress
mentors through peer-to-peer programs (such (Neely-Barnes and Dia 2008). Therefore, pro-
as Parent to Parent http://www.p2pusa.org/), viders who involve parents as a part of the child’s
allowing new parents to learn about their care team are contributing to the health of the
child’s disability and receive support from a par- parents, as well as the patients (Hall et al. 2012).
ent who has received training on mentorship However, it is also important for providers to
(Bray et al. 2017). allow room for parents and families to act as a
As discussed above, psychosocial interven- family, take a break from medical treatments and
tions that focus on practical support and infor- therapies, and spend time together engaging in
mation sharing are most likely to reduce more typical family activities (Neely-Barnes and
caregiver stress. Therefore, peer groups that Dia 2008). It may be the role of the entire multi-
focus on facilitating friendships and providing disciplinary team of medical providers, therapists,
information may be most appropriate for parents mental health providers, and case managers to
of cerebral palsy. CSR facilitates a support group support parents as they work to balance medical
for parents of chronically ill children, most of needs with the needs of the entire family to be a
whom are parents of children with severe cere- family.
bral palsy. This parent-directed group focuses
mainly on the sharing of practical knowledge
(e.g., how to work with insurance companies Conclusions
and how to obtain nursing care), as well as on
social support. Many of the participants experi- Our review of the literature suggests that provid-
ence social isolation due to their child’s illness ing care to their child with cerebral palsy is
and have come to see the group as a main source clearly linked with greater parenting stress,
of friendship. However, the benefits of support lower psychological well-being, and physical
groups are not universal, and participants can health difficulties. Important contributing factors
sometimes feel distressed as a result of compar- include lack of caregiving breaks, little opportu-
ing one’s own situation to that of others. Support nity for self-care, lack of adequate practical care-
group participants may feel distressed if they giving help, significant sleep disruption, social
perceive that others are coping or faring better isolation, child behavior difficulties, financial
than they are or if others’ situations give them an hardship, and concerns regarding their child’s
unfavorable glimpse into situations to come with lifelong care and supervision needs. However,
respect to future health or functioning difficulties not all parents fare poorly: There is variability
(e.g., Bogart and Helgeson 2000). Additionally, in parent stress and adjustment even at the
at least one study indicates that caregiver support highest level of disability severity. Parental resil-
groups do not always alleviate parent stress, ience is associated with greater practical (and to a
although they may increase a parent’s social lesser extent, emotional) support, marital quality,
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The Impact of Cerebral Palsy
on Siblings 37
Claire Shrader and Stephanie Chopko
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 548
Children: Playmates, Mentors, and Friends . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 549
Adults: Caregivers, Supports, and Friends . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 551
Advice to Healthcare Professionals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 554
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 555
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 555
Abstract a disability affects them just as much as it

Cerebral palsy causes significant challenges affects the parents and individual with the diag-
and unique opportunities not only for the indi- nosis. Despite this fact, the needs of the
viduals with the diagnosis but also for their neurotypical siblings are often overlooked by
siblings. Siblings of individuals with cerebral healthcare providers. Though research on sib-
palsy are often resilient and empathetic due to ling issues is becoming more common, the
their life experiences, but across their life-span, research is often limited by size, and results
they may also face unique challenges. Some of vary. This chapter will analyze the research
these challenges may include emotional stress literature that has been performed and discuss
and added responsibilities from a young age as the benefits and challenges of having a sibling
well as caregiving and the emotional and finan- with cerebral palsy across the life-span. The
cial burden that may present. The diagnosis of chapter includes testimonies from siblings
themselves, used with permission by the Sib-
ling Support Project.
C. Shrader
Mississippi College, Clinton, MS, USA Keywords
e-mail: ceshrader2@gmail.com; ceshrader@mc.edu Cerebral palsy · Siblings · Sibs · Children ·
S. Chopko (*) Adult
Nemours /Alfred I. duPont Hospital for Children,
Wilmington, DE, USA
Sidney Kimmel Medical College/Thomas Jefferson
e-mail: stephanie.chopko@nemours.org

https://doi.org/10.1007/978-3-319-74558-9_37
548 C. Shrader and S. Chopko
Introduction support may play a role in buffering stress

(Milevsky 2011). Given these findings as well as
While other chapters in this volume have focused others covered elsewhere, the role of siblings in a
on the impact of cerebral palsy on the child and on family system, including family systems where
parents, the purpose of this chapter will be to one child has a diagnosis of a developmental
focus on the siblings of children with cerebral disability, is important to examine and
palsy (CP). Sibling research has not been as com- account for.
mon as other family-based research and only According to the Americans with Disabilities:
recently has become the focus for some 2014 report (Taylor 2018), 27.2% of people living
researchers. Further, investigations of siblings in in the United States (or 85.3 million people) had a
families where one child has a disability or disability in the year 2014. “Disability” in this
chronic illness are even less common. This chap- report was defined as “impairments, activity lim-
ter will review some of the literature on siblings of itations, and participation restrictions a person
children with developmental disabilities in gen- may experience in their daily lives.” This chapter
eral and CP in particular. will specifically focus on siblings of individuals
Although research on relationships among fam- with cerebral palsy and other developmental dis-
ily members has been conducted for many years, it abilities (including Down syndrome, autism, and
often was focused on parents or parent-child inter- spina bifida), which are included because there is
actions. More recently, there has been growing not substantial research on siblings of individuals
interest in focusing on sibling relationships. Kluger with CP. Search terms used were cerebral palsy,
(2011) wrote that “the near universality of the sibling, and developmental disability.
sibling experience makes it something that power- Of those 85.3 million people with disability,
fully affects all families.” White and Hughes many will have siblings. Siblings have a unique
(2018) described sibling relationships as “ubiqui- role in special needs families. Often they will be in
tous yet invisible” for many years but noted that the life of a child with a disability longer than the
research on siblings has gradually been occurring parents are. In addition, the impact of their sib-
in multiple disciplines, ranging from sociology and ling’s disability can be substantial. In a pilot study
psychology to genetics. While a complete review of sibling support, Bonnie Lashewicz (2018)
of the current status of sibling research is beyond quotes Bank and Kahn’s volume “The Sibling
the scope of this chapter, we will provide a brief Bond” (1982) when she says, “Bank and Kahn
overview of relevant research. call brothers and sisters our ultimate fellow trav-
Siblings have been referred to as “collaborators elers. Siblings offer our first, longest lasting, and
and co-conspirators, role models, cautionary in many ways, most intense peer relationships and
tales” (Kluger 2011). They are often some of the hold the potential for support in adult life inherent
longest relationships an adult will have in their to longstanding relationships” (pg 1).
lifetime. White and Hughes (2018) report that in A neurotypical sibling’s role as “fellow trav-
contemporary Western culture, there are fewer set eler” to a sibling with CP or other disability will
expectations regarding sibling relationships. In look different in some ways than it does in a
other cultures, siblings are expected to assume a “typical” sibling relationship. Oftentimes, these
large role in the caregiving, socializing, and teach- siblings wear the hats of caregiver, physical/
ing of younger children. speech/occupational therapist, aide, recreational
Siblings may also play a role in the well-being and social companion, behavioral reward, and so
of family members. Studies have revealed that much more, in addition to their role of “sibling.”
children who reported having a positive relation- And because of those unique differences in a
ship with siblings are described as having greater special needs family, it is imperative that
emotional understanding, increased social under- healthcare professionals and care providers are
standing, greater cognitive abilities, and better equipped to meet the unique needs of these sib-
psychological adjustment. In addition, sibling lings. Just as it has become increasingly common
37 The Impact of Cerebral Palsy on Siblings 549
to consider the role of parents when treating a Siblings Australia is a sibling support organi-
child with special needs, we must also give con- zation for and with neurotypical sibs. It is based in
sideration to the important role siblings play. Australia and directed by Kate Strohm. A recent
Neurotypical siblings of children with disabil- study by Siblings Australia (2018) found that
ities, commonly referred to as “sibs,” can often be adult sibs reported that as children, 83.8% of
resilient, empathetic, and nurturing because of them felt family stress, 70.5% felt they missed
their life experiences. In this chapter, we will be out on time/attention due to the amount of time
referring to the neurotypical sibling as “sib” and their sibling needed care, 68.6% felt isolated/that
the sibling with disabilities as “sibling.” Histori- others didn’t understand them, 67.6% felt embar-
cally, the initial literature around sibling issues rassment about their sibling’s behavior, and
focused on the negative psychological effects of 66.7% felt emotions like anger, sadness, envy,
being a sib. There is more recent research, how- resentment, and guilt.
ever, that highlights the positive benefits of having According to Strohm and Loebel (2018),
a sibling with a disability. This chapter will focus young sibs may experience embarrassment about
on both the positives and the negatives in order to a sibling’s behavior or disability in public; they
represent a more complete view of the sibs’ expe- may struggle with feeling left out when their sib-
riences. Throughout their life-span, the sibs’ role ling requires so much of their parents’ time, which
in their sibling’s life, and how they are affected by sometimes leads to acting out for attention; and
that role, will be different. For that reason, this they may even fear contracting the disability. On
chapter will be divided by childhood/adolescent top of all of these emotions, there is sometimes
experiences and the experiences of adult sibs. guilt for feeling these things, and a pressure to be
perfect, to not add anything to their parents’
plates.
Children: Playmates, Mentors, It is common for sibs, especially as children, to
and Friends feel left out when their parents and other sibling
are constantly in therapy, doctor appointments,
This section will discuss some of the specific chal- etc. Beyond that, they often don’t understand
lenges as well as benefits that younger sibs and their sibling’s diagnosis, nor do they have the
adolescents face. Benefits as well as opportunities emotional maturity to process what they see and
will be examined from the perspective of both the hear of their sibling’s disability (Rana and Mishra
sibling with a disability and the neurotypical sib 2015). One study found that 64% of sibs
and will include empathy, compassion, and resil- interviewed had insufficient knowledge about
iency, as well as a unique opportunity for mentor- their sibling’s disability. Kate Strohm (Strohm
ship (Freeborn and Knafl 2014). and Loebel 2018), the director of Siblings
Australia and author of several books on the sib-
Challenges ling experience, shares the story of a sib whose
Regarding challenges, Barr and McLeod (2010) brother had his first seizure while he was playing
analyzed 676 posts in an Internet support website with her hat. That little girl never let her brother
for teenage sibs and found that some of the main play with any of her toys again, assuming that that
struggles for children sibs included the following, was what caused his seizure. In her book Siblings:
in their words: “Strangers stare and have negative Brothers and Sisters of Children with Special
attitudes toward my sibling with a disability; peers Needs (2014), she shares this quote from a sib
don’t understand what it’s like to be me, use named “Tara”:
certain words that upset me, say nasty things and
tease me about my brother/sister; although my There were times at night when I would listen to my
mother read to my brother in the next room. I would
family loves me, they don’t have a lot of time for hear the machinery helping him to breathe and tense
me, our plans are often disrupted, and they give at every break in the rhythm. I was not allowed to go
me a lot of responsibility.” into his room at those times. I suppose mum thought
she was protecting me. In reality I would curl into a more flexible (Burton and Parks 1994). The
small ball and cry endlessly, wishing myself far unique experience of having a sibling with a dis-
away, wishing for mum to read to me, wishing for
a time where I could be hugged and wanted around. ability can also teach resiliency and strength,
especially if sibs are well supported.
Ultimately, though there is much anecdotal and For the sibling with a disability, having a sup-
clinical evidence on sib experiences in the form of portive sib is hugely beneficial. Freeborn and Knafl
sib testimonies, the research on sibs’ adaptation (2014) interviewed eight women with CP and
and coping with their sibling’s disability is incon- found that the women with loving sibling relation-
sistent. For example, though Strohm’s research ships thrived in adulthood, because in their child-
through Siblings Australia, as well as the data hoods they were validated and understood by
from their sister organization in the United States, someone other than parents. Those sibs remained
the Sibling Support Project, points to sibs acting active members throughout their sibling’s adult life,
out because of the attention their sibling receives, which gave them not only community and com-
and many sibs relate to that, Breslau et al. (1981) panionship but also a support system for when they
found that to not be true. They note that when might need help. One of the women, however, did
studying the psychological effects on sibs of hav- not have a supportive family, neither with her par-
ing a sibling with a disability, the results were ents nor sibling. This negatively affected her whole
varied. For example, one study found that sibs adult life; she felt isolated, uncared for, and as if she
whose siblings with spina bifida are older than had a void in her life.
them are not at greater risk for abnormal psycho- Those seven women with supportive families
logic functioning than older sibs with younger often said the most important aspect of their sib-
siblings with spina bifida (Tew and Laurenc ling relationship was the way their sib treated
1973). And yet, a different study found increased them normally. For one participant, even fighting
behavior problems in males and no significant with her brothers was important: “So my brother
differences in behavior or adjustment due to and I fought. I wasn’t very big. He would pound
birth order (Lavigne and Ryan 1979). So, me. I couldn’t hit him hard enough to hurt so I
although many studies reference behavioral prob- would dig my nails into him.” Beyond simply
lems in sibs, they differ on what causes those including their siblings with cerebral palsy in
behaviors and maladjustment. their daily lives, participants in the study said
Additionally, the studies are often limited: that their sibs were also often mentors for them.
many of the research studies referenced here Several fondly referenced moments when their sib
have very small focus groups, from 4, 8, 50, or helped them through a difficult situation. One
64 children. Research has also shown that sib- quoted her sister’s advice: “Never be ashamed of
lings’ adjustment can also depend on the diagno- who you are and what you need help with. Don’t
sis. All that to say, there is a definite need for more ever take any crap from anyone.” These women
accurate research on young sibs and their specific were stronger self-advocates and more autono-
needs. mous because, in large part, of their close, positive
relationships with their sibs.
Benefits As great as the benefits of positive sibling rela-
Some central benefits for young sibs and their tionships are for the child with a disability, the
siblings are the things they teach each other, benefits of having a sibling with a disability can
with sibs often being their sibling’s number one also be great for the neurotypical sib. In Lashewicz
teacher of social skills, developmental milestones, (2018), five adult sibs were interviewed. Four of
etc. and siblings being the first to teach sibs empa- the five sib participants have a sibling with Down
thy and acceptance of differences. Sibs report that syndrome, and one has three siblings with devel-
their sibling has helped them be more responsible, opmental disabilities, one with an intellectual dis-
more tolerant, and better able to see the good in ability, one with cerebral palsy, and one with
others, develop a better sense of humor, and to be significant physical and intellectual disabilities.
Lashewicz defined sib roles as the following: in therapy, and even using them as motivation for
(1) childhood companions and protectors, (2) fol- therapy goals. According to James and Egel
lowers, (3) caregivers, and (4) within family pro- (1986), who conducted a study to see if siblings’
tectors. These roles differ from typical sibling roles, reciprocal interactions in play increased when sibs
and for children, the roles of protector and care- were used as motivation and mentors, it was found
giver may seem especially odd for sibs to take that after training by professionals on how to
on. Research has shown that when a child has CP, initiate play with their sibling with a disability,
it is common for them to assume the role of the the neurotypical sibs’ initiations of play increased
youngest child, regardless of his/her actual age. above 60%. That shows that just a little training on
Additionally, sibling interactions are found to be disability and a little extra help in interactions with
more static and unchanging, without constant com- their siblings can go a long way to creating a
plementary interactions between siblings. Aggres- relationship. The training benefitted the sibling
sion or fighting between siblings is sometimes with disabilities too; their initiations increased
much lower in sibling relationships where one of about 12%.
the siblings has CP, again, because of the differ- We know for sure from sibs themselves, and
ences in sibling roles. It isn’t uncommon for a the research of Siblings Australia and the Sibling
younger sib to copy the mother in the way they Support Project in the United States, that sibs are
relate to their sibling with CP, taking on more of a better companions, caregivers, and supports for
caregiver role. Though that has challenges, namely, their sibling with a disability when they them-
producing a dependency between siblings and dis- selves are educated, supported, and given oppor-
couraging independence in the sibling, it also pre- tunities to express their range of emotions about
sents an opportunity for sibs to teach social skills the diagnosis.
and other crucial skills their sibling will need
to know that their mother or father might not
know to teach them. There is anecdotal and clinical Adults: Caregivers, Supports,
evidence that these experiences can shape sibs’ and Friends
desires to go into helping professions such as spe-
cial education or therapy (though not empirical Research specific to adolescents and adults who
evidence). have siblings with any disability including CP
Comments such as the following were com- seems to have been sparser than the research
mon in Lashewicz (2018): “I would not be the with younger children. Most studies have noted
person I am today if I did not have [sibling with that the sibling relationship changes significantly
disability] in my life.” One sib said that the sibling as siblings move into adulthood. Very often, care-
with a disability has been instrumental to their giving concerns seem to become more prevalent.
family having “high standards for themselves A significant number of adult sibs report that they
and each other through a devotion to showing anticipate becoming the primary caregiver for
respect and kindness to others.” Sibs spoke of their sibling with a disability; in some cases, this
how important their siblings were in their dating number has been reported to be as high as 80%
lives, with one sister saying the day her brother (Williams 2013).
spoke her fiancé’s name aloud was the first time
his “place in the family became official.” Caregiving
Though parents may sometimes assume that In a study of adult sibs providing care for their
less information and less involvement in care/ adult siblings with CP and speech impairment,
therapy is better for their child without disabil- Kuo and Lach (2012) found that sibling caregiv-
ities, these quotes show that often the opposite is ing consisted of three parts: caring through inter-
true. Involvement is not just beneficial for the pretation, caring through protection, and caring
neurotypical sibs, either: the siblings with disabil- through sacrifice. These seem to be common
ities also hugely benefit from including their sibs themes in the adult relationship of siblings
affected by disability. First, sibs care for their are often at the forefront of young adult sibs’
sibling with CP by spending enough time with minds, whether they know how to express that
them to be able to act as interpreter between or not. And while they refer to their future of
them and the world. Second, as their siblings caregiving as stemming from love and dedica-
enter adulthood, parents’ role usually decreases tion for their siblings, they also refer to a sense
due to age, and the sibling becomes more vulner- of obligation and high levels of stress as they
able. As they enter the world of adult services, sibs navigate how to support their sib while raising
often step into the role of protector, securing high- families of their own. It is interesting to note
quality services and protecting their sibling from that in this small study, the sibs interviewed
abuse. Finally, in many cases they may sacrifice identified themselves as protectors and care-
by placing their sibling as first priority, for exam- givers for their sibling with disabilities, but
ple, in considering where to live and who to share many of those sibs had other neurotypical sibs,
their life with. This section will further explore as well, who chose not to take on the obligation
some of the difficulties associated with caring, as of caregiving. Those sibs were often brothers
well as the unique joys of being a sib and getting who the sisters described as “intolerant” of dis-
to walk alongside your sibling through adulthood. ability issues. Therefore, not all sibs respond to
It is important to distinguish between different the obligation of caregiving in such a positive
types of caregiving, as sibs will be affected differ- way. Typically, female sibs are the ones who
ently by this. Sibs typically anticipate (sometimes assume the greater caregiving roles. Addition-
positively, sometimes negatively) living with their ally, it has been found that the closer the sib-
sibling with a disability in the future. However, for lings are, the more likely a sib is to provide
many, caregiving actually looks more like manag- caregiving at some point in life. So, the more
ing residential placements, managing guardian- distant, male sibs might not be affected by the
ship work, financially supporting their sib, and sibling relationship in the same way the close
working with support staff and services to make female sibs are.
sure their sibling’s needs are being met (Burke The concerns of the sib who is anticipating
et al. 2015). caregiving in the future are different from the
Although caregiving often comes from a deep concerns of the sib who is actively providing
love for their sibling, its challenges are undeniable care. Burke et al. (2015) point out some of those
for adult sibs. Sibs commonly become caregivers differences. One difference is in the rewarding
for their sibling with a disability and in one study aspect of the work. For example, an adult
were found to be the second most commonly sib actively involved in caregiving for a sibling
reported support providers in both housing and is likely to be less protective than the parent,
recreation. In other words, sibs are often not just so their reward in caregiving may come from
caregivers and hosts but also friends (Lashewicz watching their sib gain new independence they
2018). didn’t have when the parent was the central
One of the participants in Lashewicz (2018) caregiver. This can be a really rewarding expe-
discussed how he pursued his interests in travel rience for an adult sib to usher their sibling into
at an early age, knowing that the time might soon their own adulthood and independence in a way
come when his parents were no longer able to care parents were not able to. This dynamic is nota-
for his sibling and he would need to be available. ble as the siblings’ relationship still changes
One participant left home to go to school and said as they move into adulthood, even if it looks
her father continues to remind her that though she different than a typical sibling pair. A younger
misses her brother now, ultimately she is helping sib who is still only anticipating caregiving,
him by leaving him to go get an education: it will however, is more likely to find the experience
allow her to “give [her] brother a future.” of spending time with their sibling rewarding
Thoughts, fears, and planning for a future in regard to the opportunity it provides for their
when they will be the caregiver for their sibling parents to have respite (Burke et al. 2015).
Benefits place.” (p 149). Sibs are active in their siblings’

As mentioned previously, initial reports on out- lives even before they officially are given the title
comes for sibs of individuals with disabilities of “caregiver.” Sibs consistently said they love
often painted a very bleak picture (Dyke et al. spending time with their siblings. Especially in
2009). One of the reasons may have been largely sibling pairs where one sibling had an intellectual
methodological, as researchers often relied on the disability, sibs reported how much fun they had
report of parents. However, more recent research with their sibling, that their personalities made it
has revealed fewer negatives. Dyke and col- enjoyable to spend time with them (Burke et al.
leagues have reported that recent research has 2015).
revealed some positive effects, including “an
increased tolerance and awareness of difference; Challenges
a caring and compassionate nature; increased In the Siblings Australia research project, when
maturity compared to their own peers; and an adult sibs were asked about their current chal-
enhanced appreciation of their own health and lenges, responses included a variety of themes.
abilities.” (p23). They also reported a tendency 65.7% of sibs endorsed anxiety, 53.7% described
for sibs of children with disabilities to go into symptoms of depression, 53.7% said low self-
health-related or “helping” professions like med- esteem, 46.1% said lack of confidence, and
icine or education. 35.3% said sleeping problems. In addition, guilt
Recently, Mophosho et al. (2010) conducted a can be a common feeling for sibs in many aspects.
pilot study on the relationships between adoles- Some sibs feel guilt regarding their own abilities,
cents and their siblings with CP by interviewing for the fact that they don’t see their sibling as often
four children in South Africa and conducting a as they feel they should, for their own apprehen-
thematic analysis. Questions asked ranged from sion and fear of caregiving, and for their own
“Do people act differently to your brother than inadequacies in caregiving (Burke et al. 2015).
they do to you?” to “How do you feel about your A very common struggle for sibs anticipating
brother being different?” to “What sorts of things caregiving is the fact that parents did not include
do you do with your brother?” Per the authors, them in future planning. Due to this, many sibs
results of the analysis revealed largely positive may feel uncertain about the future. Sibs who
themes, including acceptance, wishing (for their have already engaged in caregiving roles also
sibling to be able to do the same things they them- struggle when parents don’t communicate future
selves do), helpfulness, responsibility, friendship, planning, because they may encounter difficulty
and resilience. coordinating high-quality care for their sibling
Information provided via the Vanderbilt Ken- with little guidance from parents. According to
nedy Center revealed that a large study of adult Burke et al. (2015), nearly 60% of sibs may strug-
siblings revealed additional positive outcomes. gle with this. When asked, they comment that for
Per their report, as a group sibs felt they benefitted their parents, the system of support care and ser-
from their brother or sister with disabilities and vices for people with disabilities has been the focus
described themselves as being in good health. of much of their lives; however, for the sibs, it’s all
They also felt close to their sibling (Vanderbilt totally new and unknown. Heller and Kramer
Kennedy Center). (2009) surveyed 139 sibs about their involvement
In Burke’s 2015 study, over half (52.9%) of sibs in future planning for their sib with a disability.
who were not yet caregivers for their sibling still Their study revealed that while sibs were at times
participated in recreational activities with their sib- involved in some tasks (identifying caregivers for
ling, in a respite provider type role. One sibling the future and planning for residential options),
said, “It’s respite type stuff. If my parents go out of they were usually less involved in tasks such as
town, then he stays the weekend with me. Or I am power of attorney or special needs trusts. Their
the behavioral reward, so if he does good at school results revealed that sibs who were most involved
for the month, he gets to spend the night at my were those who were older. Overall, it was found
that few families had engaged in these future plan- Advice to Healthcare Professionals
ning activities (Heller and Kramer 2009).
Financial cost and difficulties can also become Because the sibling relationship is the longest
an issue for sibs taking care of their adult siblings. lasting relationship in the life of an individual
According to Williams (2013), only a third of sibs with disabilities, it is imperative to nurture that
in a recent study described themselves as financially bond. Including sibs in family support services is
prepared to assume caregiving for their sibling, not only important for that bond but also impor-
despite nearly 80% expecting to take on that role. tant so that they can better understand the system
Concepts such as Medicaid, guardianship, and spe- of support services when it becomes their respon-
cial needs trusts are often foreign for many sibs, and sibility. According to Floyd et al. (2016),
there is not a good system in place to provide neurotypical sibs are commonly ignored by fam-
education and support around those topics. ily support services, especially if they no longer
Thirty-six percent of caregiving sibs in the live at home. This neglects to notice the fact that
Burke et al. (2015) study were primary caregivers sibs can and do contribute to their sibling’s qual-
and found this to be a great responsibility. This ity of life even when they don’t co-reside. Floyd
responsibility was also difficult when there were et al. (2016) actually found that siblings’ close-
other sibs in the family who did not help out with ness was not related to co-residency at all, imply-
their sibling with disabilities. Sibs who were pri- ing that sibs are actually regularly living away
mary caregivers often felt alone and found it diffi- from their siblings and balancing caring for them
cult to even include spouses in the responsibilities and having a career and relationships outside of
of caregiving, especially since they struggled with their family. Because sibs are so important in
feelings of guilt for spending more time caregiving their siblings’ lives, healthcare professionals
than they spent with their spouses (Burke et al. would do well to take a family-centered approach
2015). It is common for caregiving siblings to be in their treatment of the individual with
sisters, who tend to provide more companionship disabilities.
and emotional support (Floyd et al. 2016). The list of resources for siblings of children
Adults with disabilities often are forced to with disabilities appears to be growing slowly.
depend on their siblings as they age. Only one in There are a number of books available; although
four adults with intellectual and developmental some are geared specifically to a certain diagnosis
disabilities in the United States receive formal/ (e.g., autism spectrum disorder, CP), others are
paid supports, according to Sanderson et al. less specific and apply to all. Other books target
(2017). These numbers are due to not enough certain ages (e.g., early childhood, school age,
funding and increasingly long waiting lists. adults). In addition, there are at least two sibling
Although the lack of adequate care and support projects that we know of: Siblings Australia and
services begins as soon as a diagnosis is made in the Sibling Support Project. The goal of each is to
childhood, at that time parents may be available to provide community and support to sibs as well as
act as primary, dedicated caregivers. However, for research and resources.
adult sibs who often have their own jobs and fam- The Sibling Support Project has conducted two
ilies and are not always in a position to dedicate different projects where they asked sibs to talk
themselves to the role of full-time caregiver, this about what they would like service providers to
lack of adequate services may prove to be a more know. The first set of excerpts are from a project
significant issue. Hence, increasing the amount and where sibs talked about their aging sibling with a
quality of support services available (i.e., housing, disability (“I’m Constantly Thinking About Bev
medical care with trained providers, support for and Her Future”: Siblings Speak About Aging)
transportation, recreation options, and job training) (Meyer 2010):
would increase quality of life not just for the recip-
ients of those services (people with disabilities) but Many of us live in fear: Fear of doing “right” for our
also for their sibs without disabilities. siblings and by our parents who expect that we will
follow their example and wishes despite our inability Conclusion

to do so. Fear about how further involvement with
one’s sibling will constrict one’s own life and that of
one’s family. Fear of wondering whether our siblings In conclusion, sibs have different needs all across
will recover from the loss of a caring parent—and the life-span, as do their siblings with disabilities.
who will take over if we no longer can. For some Service providers have an incredible opportunity
siblings, the whole service system is daunting and to invest in the lives of those sibs while also
they worry that they won’t be able to navigate it to
assure that their siblings get the services they need. meeting the needs of their patient. When this
happens, it makes the sib feel seen and acknowl-
edged, which is ultimately all they want. The more
They should know that we need as much support service providers acknowledge the needs of sibs
as parents. We need info and resources. We are
usually coming into this without the years of expe-
when they are younger, the better the bond
rience about the system. Many sibs are taking on the between sib and sibling. The more service pro-
responsibilities of supporting our sibs at the same viders acknowledge the needs of sibs when they
time we are helping our aging parents and raising are older, the better the sibs will be able to care for
our own kids.
their sibling. Sibs, the ones who wear the hats of
friend, caregiver, care coordinator, mentor, and
In general, service providers should understand fellow traveler, can be powerful forces for good
some sibling-guardians will be as involved as par- in the lives of their siblings and others, but we
ents in caring for their siblings—but some may not
because of commitments to their own families or
must give them the proper supports to be able to
professional lives. This isn’t necessarily a bad thing do so.
for the siblings who have the disability because
many times typical siblings will give them more
responsibility and autonomy than parents will.
Cross-References
The second set of excerpts come from a project
conducted by the Sibling Support Project which ▶ Family Stress Associated with Cerebral Palsy
provided guidance for how to work with young ▶ Life Care Planning for the Child with Cerebral
siblings (Meyer n.d.). Excerpts are provided Palsy
below (“How to Let Young Siblings Know You
Care”):
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Part IX
Neuromotor Function
Motor Control and Muscle Tone
Problems in Cerebral Palsy 38
Freeman Miller
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 560
Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 560
Anatomic Motor Control Structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 561
Development of the Anatomic Structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 562
Controller Mechanisms and Theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 563
Pathology Treatments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 568
Disorders of Muscle Tone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 568
Spasticity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 569
Hypotonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 572
The Effects of Hypotonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 572
Treatments of Tone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 573
Movement Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 573
Motor Control: Movement Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 574
Chorea and Ballismus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 578
Summary of Motor Control Treatments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 578
Disorders of Balance (Ataxia) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 579
Cases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 581
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 583
Abstract are well recognized as specific problems; how-

Children with cerebral palsy (CP) have a large ever, the pathophysiology connecting the
variety of motor impairments, all of which encephalopathy to the impairment and the dis-
are secondary to the encephalopathy. These ability is not well defined. Motor control
impairments, which directly emanate from the affects all of the systems which require mus-
encephalopathy and the disability that results, cles for control including oral motor function,
eye movement, and other various body seg-
ments which are controlled by muscles. The
F. Miller (*)
treatment goal for children with CP is to allow
Department of Orthopaedics, Nemours/Alfred I. duPont them to function in their environment, and
Hospital for Children, Wilmington, DE, USA ideally in the larger society, to the best of

https://doi.org/10.1007/978-3-319-74558-9_39
560 F. Miller
their abilities. The definition of motor control Bobath 1957). The treatment goal of children
means the central nervous system is conceiving with CP is to allow them to function in their
and then developing the program to be environment, and ideally in the larger society,
performed by the musculoskeletal system. to the best of their abilities. Their functional abil-
The execution of this movement should be ity is determined by many aspects of the environ-
smooth, efficient, and with the required accu- ment which may be larger impediments than
racy. This means that the muscles are required their personal motor control (Martins 2015).
to have the proper tension or tone in prepara- These children and adults continue to have CP,
tion of response. Pathologic abnormalities of and the changes made by the medical treatment
motor control develop into movement disor- are directed at decreasing these disabilities by
ders. Movement disorders include dystonia, altering the secondary impairments. To alter the
athetosis, chorea, hemiballismus, and tremors. impairments in ways that decrease the disability
Abnormalities of muscle tone range from requires that the interaction of different impair-
hypotonia to hypertonia also known as spastic- ments in a given individual must be well under-
ity. The goal of this chapter is to develop a stood. An understanding of the neurologic control
theoretical understanding of central nervous of motor activity is required to place a construct
system motor control and the importance of around these impairments.
muscle tone. The definition of the pathologic The definition of motor control means the
states and treatment options will be briefly central nervous system is conceiving and then
considered. developing the program to be performed by the
musculoskeletal system. The execution of this
Keywords movement should be smooth, efficient, and with
Cerebral palsy · Motor control · Spasticity · the required accuracy. For this function to work, it
Dystonia · Ataxia · Athetosis · Chorea · requires the correct order of muscle activation.
Ballismus · Hemiballismus The muscles also have to be prepared to respond
in an effective way to the commands received
from the central nervous system. This means
Introduction that the muscles are required to have the proper
tension or tone in preparation of response. Patho-
Children with cerebral palsy (CP) have a large logic abnormalities of motor control develop
variety of motor impairments, all of which are into movement disorders. Movement disorders
secondary to the encephalopathy. These impair- include dystonia, athetosis, chorea, and tremors.
ments, which directly emanate from the encepha- Abnormalities of muscle tone range from hypoto-
lopathy and the disability that results, are well nia to hypertonia also known as spasticity. The
recognized as specific problems; however, the goal of this chapter is to develop a theoretical
pathophysiology connecting the encephalopathy understanding of central nervous system motor
to the impairment and the disability is not well control and the importance of muscle tone. The
defined. Motor control affects all of the systems definition of the pathologic states and treatment
which require muscles for control including oral options will be briefly considered.
motor function (Benfer et al. 2014), eye move-
ment (Ego et al. 2014), and other various body
segments which are controlled by muscles. The Pathophysiology
importance of motor control in the pathology of
CP has been recognized for many years and was One of the most basic functions of living organ-
one of the earliest approaches to therapy for chil- isms is the ability to control and move the body
dren. The Bobath technique for physical therapy in space. After cognitive and reasoning abilities,
was primarily involved in encouraging the devel- motor function is what most defines an individual
opment of motor and postural control (Bobath and as a human being. There are wide variations of
38 Motor Control and Muscle Tone Problems in Cerebral Palsy 561
motor function in which some individuals, such as motion initiates in the cerebral cortex and is trans-
athletes, focus most of their activity on motor mitted to the peripheral motor nerves through the
skills and others focus more of their attention on cortical spinal tracts traversing the internal cap-
cognitive skills. However, even individuals sule and the spinal cord. These transmissions are
such as writers who are primarily engaged in not simple commands but are highly modulated
cognitive activity still depend on motor function based on inputs from many other areas. The com-
to relate and transmit their cognitive achieve- ponents that make up the basal ganglion are
ments. In children with CP, loss of motor function extremely important modulators of motion. The
is a major part of the disability. Motor function cerebellum also monitors sensory input and fur-
involves almost all tasks of living including ther modulates motion, especially smoothing the
speech, swallowing, upper extremity function, motion pattern. The relative function of each of
and all mobility. It is helpful to have some con- these structures has been somewhat defined by
ceptual construct of how control of the motor classic lesioning experiments in animals and
system works to develop treatment strategies. close observation of naturally occurring lesions
A common framework for understanding in humans. The very complex modulation occur-
motor control is learning the anatomic structure ring in the brain is not well understood in a way
and function of each part of the nervous system. that can help explain the problems in children with
Most physicians will remember this approach CP. Some problems of movement disorders have
from their medical school classes. This system is specific patterns that can be linked to specific
too complex to yield an understanding of how the problems in the basal ganglion (Fahn et al.
neurologic system really controls motion in a way 1998); however, even these are usually complex
that can be applied usefully to treat a child. This and not focal isolated lesions (Fig. 1). The spinal
anatomically based approach aids understanding cord is not only a series of connecting ascending
the difference between spinal cord injury and and descending tracts like a telephone cable, but it
brain injury in children. This approach also helps also has a very important modulating layer of
explain the difference between hemiplegic and interconnecting neurons in the motor control sys-
diplegic pattern CP involvement. With the ana- tem. Some of these interconnections are modu-
tomic approach, the nervous system can be lated by descending tracts, and others are
divided into central and peripheral. The central modulated by interconnections within the spinal
structures include the spinal cord and brain, and cord. For example, when the plantar flexors are
the peripheral system includes the peripheral stimulated to contract during the simple Achilles
motor, sensory nerves, muscles, bones, and joints. tendon reflex, another interconnection in the spi-
nal cord suppresses function of the dorsiflexors,
causing them to remain quiet. The specific role of
Anatomic Motor Control Structure these rather simple connections in complex activ-
ities such as walking is not well defined, and the
Central Motor System pathologic role of these reflexes in CP is even
Cerebral palsy, by definition, requires that the more difficult to understand.
pathologic lesion be in the brain. Therefore, the
spinal cord presumably does not have a primary Peripheral Motor Control
lesion, although there are children in whom this The peripheral motor system includes the nerves
may not be true. The control of motion is either and musculoskeletal system. The peripheral
volitional or automatic. Most activities are voli- motor nerves carry the impulses that cause mus-
tional; however, reflex responses, such as with- cles to contract, and the sensory nerves carry this
drawal after accidentally touching a hot stove, information to the central system. The sensory
are automatic responses. This type of automatic information includes tendon tension, muscle
response occurs as a relatively simple neuronal length, joint position, and cutaneous sensation.
reflex at the spinal cord level. All volitional In children with CP, there is no primary lesion in
562 F. Miller
Fig. 1 Although the

cerebral spinal tracts
transmit information from
the cerebral cortex to the
peripheral muscles to cause
motion, there are many
modulating influences
especially from the basal
ganglion, cerebellum, and
spinal cord. These
modulating influences are
not well defined as to the
specific changes that occur
in children after different
brain lesions
any of these peripheral systems; however, the of gestation, interconnections from the brain
effects of the central pathology cause these sys- to the muscles have developed, and the fetus
tems to develop in abnormal ways. These abnor- is beginning to make flexor movements. By
mal changes, such as lack of muscle growth, in the 18–30 weeks, extension movements are routinely
peripheral motor system can be positively seen (Connolly and Forssberg 1997). By the time
affected. These secondary responses to the pri- the baby is born, she has vigorous kicking and
mary central nervous system defect are the cause sucking movements and hand and toe grasp.
of many problems in children with CP. During this time, the anatomic synapses are
undergoing considerable remodeling, which is
best understood in the development of sight
Development of the Anatomic where external light stimulation is needed to
Structure develop a normal central neurologic system. The
role of external musculoskeletal movement on the
Central Nervous System maturation of the central nervous system is
The early development of the central nervous unknown. Maturation of the central nervous sys-
system begins with the neural tube structure, tem motor skills, especially in areas such as bal-
which folds and then is followed by development ance and the ability to learn complex motor skills,
of the anterior part of the brain. By 9–17 weeks is not complete until middle childhood.
Fig. 2 The H-reflex is

initiated by low-level
electrical stimulation of the
afferent muscle spinal fiber
in the same muscle. The
H-reflex has the same
pathway as the stretch reflex
and causes a contraction in
the same muscle that was
stimulated; however, it is
easier to control the timing
and quantity of the
stimulation
Peripheral Motor System Sensory System Feedback Versus Feed-

The peripheral motor system has some primitive Forward Control
function by the ninth week of gestation; however, at To conceptualize how the central nervous system
birth this system is a long way from being mature. controls motor function, a framework of what is
The nerve conduction velocity at birth is 28.5 m/s, possible needs to be considered. The system either
and by adulthood it reaches 82 m/s. However, can alter function in response to the sensory infor-
because of the large amount of length growth, the mation it receives or it can cause a motion and
H-reflex at the ankle still goes from 15 s at birth to then learn what has occurred from the sensory
28 s at adulthood, even though there is increased feedback system. Constantly changing the motor
velocity (Fig. 2). Also, skeletal muscle fiber types instructions based on sensory feedback is called
change to a more mature mix, and the whole system feedback control, and ordering a muscle activity
has to increase greatly in size. Abnormalities in this and then receiving the effect of that activity from a
growth and development will be considered when sensory perspective is called feed-forward con-
the specific pathologic patterns are evaluated. trol. These two models are important aspects of
control theory to understand how sensory infor-
mation is processed and incorporated (Fig. 3).
Controller Mechanisms and Theory Other terms that are very similar are closed-loop
control, which is almost the same as feedback
As was already noted, it is quite easy to under- control. Open-loop control means there is no con-
stand the concept of simple nerve reflexes, such as trol once the activity is initiated, which is slightly
the knee reflex; however, this concept has not led different from feed-forward control in which a
to an understanding of how the central nervous delayed reaction can cause impact on the activity.
system controls human gait. New understanding Firing a bullet from a gun is open-loop control
of ways to conceptualize the neuromotor control because the shooter has no ability to impact the
come from computer sciences and mathematics. path of the bullet after it is fired.
The role of these theories, and the benefit they Another example of this concept is demon-
provide, is in helping to place the function of strated best by the control system present in
a child with CP in a context that can be understood driving a car or firing a rocket. The control pri-
clinically as the child is growing and continuing marily used in driving a car is feedback control in
with neurologic maturation. which the driver, when going around a corner,
564 F. Miller
Fig. 3 Feedback control

depends on constant
sensory input, which
directly modulates the
action in progress. Feed-
forward control uses the
sensory information to learn
and calculate how much
muscle activity is needed to
make a specific movement
occur. The sensory
feedback cannot alter the
activity in progress but is
added to the learning
progress for the next
activity cycle
will steer into the corner and constantly correct Neurologic control uses both feed-forward and
the turn based on sensory feedback received of feedback control. An example of feed-forward is
how the car is progressing. With this type of jumping, where a determination is made similar to
control, if the car is going too far to the left, the a rocket launch in which the brain calculates the
driver turns more to the right, and if the car is amount of muscle force needed and then orders
going too far to the right, the driver turns back to the muscles to contract, generating the required
the left. In this way, the activity of driving force. Many aspects of walking are feed-forward
around the corner can be accomplished with in pattern, although this is less clear at times.
minimal prior experience and knowledge about Feedback systems are predominantly used for
the specific corner; appropriate adjustments are activities with which one has little experience
made as the task progresses. Launching a rocket and wants to make changes as the activity is
is an example of feed-forward control in which progressing, such as drawing a picture or painting.
the engineer knows where the rocket goes and Many functions probably contain some mix of
then calculates a trajectory. From the knowledge feed-forward and feedback control.
of the trajectory, and the rocket’s weight, a cal- Understanding feedback mechanisms is some-
culation of how much fuel is needed and the what difficult, especially because the concept of
angle of launch can be made. After all the calcu- muscles is that they are either activated or not
lations are completed, a program is given to the activated. Based on the understanding of neural
rocket’s engines. Then, when the rocket is anatomy, all feedback is similar to the knee reflex
started, it will execute this program to follow where the threshold of sensory stimulus is reached
the predetermined course based on the pro- and a fixed contraction occurs. However, staying
grammed engine thrust and angle of launch. with this concept makes it difficult to understand
There is minimal feedback or ability to change how complex feedback would work as feedback is
directions 2 s after launch if it is determined that experienced in a much more controlled response
the rocket is going in the wrong direction. There than the single synapse reflex. From the area of
is, however, usually the ability to explode the computer engineering, this feedback can be con-
rocket if it is perceived to be going off target. ceptualized in terms described as fuzzy feedback.
This rocket launch is an example of feed-forward This description uses a mathematical concept of
control. fuzzy logic based on graded response options (Nie
and Linkens 1995). When a stimulus is received, developed in a process of maturation by a combi-
the response does not need to be all or none but is nation of genetic encoding and direct learning.
chosen rather from a gradation of options, for This understanding of the function of the CPG is
example, five options of muscle activation. called the maturation theory of motor control
These options might be a maximum contraction, (Connolly and Forssberg 1997).
a moderate contraction, an average contraction, a
low contraction, or no response. Although it is Controller Options: Dynamic Systems
hard to relate this type of fuzzy control directly Theory
to the neuroanatomy, it is functionally a better The concept of dynamic systems self-organization
conceptual model to understand feedback control has arisen from many disciplines of natural sci-
in the motor system than the all-on or all-off ence and has more recently been applied to under-
concept that simple neuroanatomy would suggest. standing human motor control. An example of
This fuzzy control, or rheostatic-type control, is this application of dynamic systems theory is the
developed through the multiple levels of modula- understanding of the flow of fluids, such as the
tion and with many muscle fibers in each muscle. flow of a river or the flow of fluids through a
Variable whole-muscle activation can be obtained pipeline. As the speed and pressure of the liquid
by firing varying numbers of muscle fibers. flow changes, the flow pattern reorganizes itself
from a smooth laminar flow where the center of
Controller Options: Maturation Theory the water column has the highest velocity to the
In considering neurologic control theory, motor slowest velocity at the periphery, which is in con-
activities that most people experience in daily life tact with the immobile walls. At some point, this
can be understood in a simplistic way similar to flow reorganizes into turbulence. This turbulence
the function of a computer. In this context, it looks totally disorganized; however, in dynamic
seems natural to think about the computer as a theory, it has reorganized itself into another con-
model for the nervous system. For example, in this trol system, which is responding to demands
model the hardware is the anatomic structure in placed on the structure. This changing state from
which a software program is placed. Using this nonturbulent to turbulent is highly nonlinear and
analogy, the software program for the brain is is a transition from one state to another, both of
called a motor engram (Nass 1983) or a central which are stable.
program generator (CPG). The term central pro- Understanding this kind of system reorganiza-
gram generator is used here because it is more tion required the development of a new branch of
descriptive of the motor control concept. The mathematics called chaos theory (Gleick 2008;
CPG would be equivalent to a word processing Porter et al. 2001). In chaos, there are attractors,
program, which has complex but fixed responses which are defined as regions or states that are stable
to all inputs. Some of these responses are direct, or relatively stable (Fig. 4). For example, there is a
such as the keyboard response occurring when a rapid transition in fluid flow between turbulent and
specific key is pushed and commanding the nonturbulent flow. The fluid does not like to remain
word processing program to place a specific a mix of the two states; in other words, the fluid is
letter where indicated. Other instructions are attracted to one state or the other with varying
more complex responses, such as a predetermined strengths. This concept of attractors can be used
series of steps when a macro in the word pro- to understand motor control. An example in human
cessing program is executed. Using the analogy gait is walking speed, in which not all velocities
of the computer in understanding motor control, it have equal preference from standing to maximum
is also presumed that most of these movement running. The chaotic attractor of normal adult walk-
responses either are remembered by the genetic ing velocity tends to be strong, between 100 and
encoding of a motion, such as sucking or stepping 160 cm/s. If a person cannot walk close to 100 cm/
or are developed through a learning response, s, they will often walk at a comfortable speed, then
such as learning to ride a bicycle. The CPG is stop and wait for a while, then walk at a natural
566 F. Miller
applied most is in understanding variability of

heart rate. This principle is demonstrated espe-
cially well by the change from a variable heart
rhythm to ventricular fibrillation. These two states
of heart rhythms are both stable because they are
not easily changed without significant external
force.
The concept of dynamic systems theory for
motor control also aids understanding of how
Fig. 4 The concept of chaotic attractors is easy to visual-
ize as a landscape over which a ball is rolled. There may be individuals end up doing similar tasks with vari-
many areas where the ball could stop and be stable; how- able but similar patterns. For example, if a walk-
ever, a relatively small force would dislodge the ball and ing child is asked to pick a cookie up off the floor,
start it rolling again. There are a few deeper valleys in
the pattern used likely will be either predomi-
which the ball might roll and require a lot of force to start
it rolling again. Each of these landscape depressions sim- nantly bending at the hip and spine with the
ulates a chaotic attractor of varying strengths knees straight or flexing the hips and knees keep-
ing the spine straight. With all the muscle and
joints available, there are almost endless varia-
speed, then stop again. Standing and not moving is tions of how a task can be accomplished; how-
another velocity attractor. On the other hand, if an ever, there is a chaotic attractor toward two or
individual has to go faster than 160 cm/s, they three patterns of motion to accomplish a
typically break into a running gait pattern with a given task.
preferred comfortable speed between 250 and
300 cm/s. For speeds around 200 cm/s, most indi- The Cause of Chaotic Attractors
viduals alternate between running and walking Understanding the anatomic or mechanical origin
because these speeds are more comfortable than of these chaotic attractors is very difficult, and
trying to stay at an in-between level of not quite based on chaos theory, there are too many variable
walking and not quite running comfortably. Most inputs to the system to specifically define these
adults experience and respond to these velocity attractors; therefore, they are usually defined as
attractors by altering their speed to be in one of a region. For example, a chaotic attractor draws
the three stated gait patterns. normal human walking velocity to a relatively
Another feature of these attractors is that they stable attractor of around 100–160 cm/s. The
may be very stable or somewhat unstable. An strength and definition of this attractor are related
example of an unstable attractor is the body posi- to the length and mass of the legs, the speed of
tion taken in the middle of a jump. This position is muscle contraction, the speed of nerve conduc-
an unstable attractor because the body cannot stay tion, and the environment. It is impossible to
this way for long before it has to move to the next define the exact center of this chaotic attractor
attractor, which is the response for landing. because it is based on many things, from the
Understanding and defining these attractors in environment to the individual’s behavior and
motor control can be very helpful in understand- mood. Using this concept of dynamic systems
ing response to growth and development as well theory, a framework exists for understanding
as responses to treatment. To clarify the under- why different movement patterns develop in
standing, the term chaotic attractors is used in the children with CP. For example, children with
remaining text to define these attractors, although diplegic pattern involvement frequently develop
the more classic mathematical term used in chaos a crouched gait at adolescence. Depending on
theory is strange attractors (Gleick 2008). In med- what treatment is chosen, the child may continue
icine, the area where chaotic theory has been in the crouched pattern or may revert to a back-
kneeing pattern. This gait change is an example these subsystems might include sight, oral motor
of the chaotic attractor organizing the child’s function, and hearing. Although during muscu-
motion. The important thing for the surgeon to loskeletal management of children with CP we
understand is that the system does not want to focus mostly on trunk balance, muscle tone and
organize around normal knee extension, which is motor pattern generation is clearly a very impor-
the physician’s treatment goal. tant aspect of motor control by providing feed-
Another important concept arising from back to the motor control system.
dynamic systems theory is that the control system With each of these subsystems, there is a basic
is self-organizing and there is no need for a CPG level of organization programmed by genetic
or genetic encoding or learning. The example encoding and learning. Above some level of basic
from physics is that the fluid does not need function, dynamic systems theory best explains
genes, learning, or software to decide to reorga- actions. Some of the patterns coming out of
nize from turbulent to nonturbulent flow. Another dynamic systems theory may be further refined
area where dynamic systems theory is widely used through learning, especially activities that depend
is in understanding weather patterns. The weather heavily on feed-forward control. An example is an
patterns organize systems, such as high-pressure athlete’s activity, such as learning to broad jump.
areas with sunny days or severe storms, in patterns After middle childhood, with a fully mature neuro-
that can be explained with dynamic systems the- logic system, maturation to execute the concept of
ory, again all without learning, genetic code, jumping has developed. When a child is asked to
or software programs. This organization develops jump as far as she can, the natural general pattern,
around chaotic attractors, each of which can which is probably determined by dynamic control
be characterized somewhat; however, all the organizing the activity around the chaotic attractor
inputs and impacts to define this attractor cannot or series of attractors that are not very stable, will
be described. Because dynamic systems theory be used. However, if the individual wants to
requires no encoding program, such as a CPG, it become a champion broad jumper, they must
is directly opposed to the maturation theory of work on a specific pattern and be able to execute
motor control. Reports of the ability of mechani- this pattern consistently within a very narrow
cal robots to self-organize around movement pat- range. This part of the activity now becomes a
terns and studies with animals suggest that maturation activity around defining a specific
dynamic theory has some basis as an organiza- CPG, which helps to explain why the basic pattern
tional structure of motor control (Connolly and is seen but also allows for refinement. Also, much
Forssberg 1997). more energy is required to change the basic pattern
than to refine the current pattern.
A Unified Theory of Motor Control When considering individual pathologic prob-
The goal of having a concept of motor control is lems, the neurologic aspects of the motor impair-
to help in treatment of children with motor con- ments can be separated into abnormalities of the
trol problems and perhaps to develop a concep- three subsystems of motor control. These subsys-
tual context to test theories in an experimental tems are muscle tone, motor planning, and balance.
format. There is a need to combine both the The variety of abnormalities in these three subsys-
maturation and dynamic systems theories. One tems leads to almost all the motor problems in
way of combining them is to separate the func- children with CP. Some children have impairments
tions of the motor control system into subsys- in only one area, such as a spastic gastrocnemius in
tems. There is a subsystem for balance that child with a hemiplegic pattern involvement.
includes the sensory feedback areas, another sys- Others, such as children with severe quadriplegic
tem for controlling muscle tone, and a third sys- pattern involvement, have significant abnormalities
tem for motor pattern control. Other aspects of in all three subsystems.
568 F. Miller
Pathology Treatments synapse can be modulated to sending from the

brainstem and cerebral white matter by the
Disorders of Muscle Tone vestibulospinal and reticulospinal pathways
(Sussman et al. 1992). It is through these spinal
Muscle tone is defined as the stiffness of the pathways that monosynaptic reflexes are modu-
muscles or the limb as one tries to passively lated through a large variety of experiences, such
move the limb. This stiffness has a spring charac- as changes in the person’s mood, environment,
teristic, which is stiffer with small movements and the activity being performed.
than with large movements and is defined as a
nonlinear response to movement. The exact origin Motor Tone
of this tone comes from the passive stiffness ema- Normal motor tone has many important but poorly
nating from the shape of the soft-tissue envelope, defined functions in the control of the motor sys-
friction in the joint and soft tissue, and may also tem. Most of these functions are defined by prob-
have an undefined active neuronal element. In lems caused when the motor tone is too high or
studies using the leg drop test, a difference has too low. In general, high tone is called spasticity or
been seen between an awake and alert child com- hypertonicity, and low tone is called hypotonia.
pared with the same child under neuromotor The classic definition of spasticity typically
blockade anesthesia. In normal individuals, there includes an increased sensitivity of the normal
is less muscle tone under anesthesia than when stretch reflex in addition to a velocity-dependent
they are awake, which strongly suggests that there increase in resistance, which initiates a muscle
is an active stiffness in the muscle that is not due to contraction to resist the motion (Engsberg et al.
contraction induced by the motor neuron, as this 2000). This widely reported and often-repeated
stiffness is occurring with a silent electromyo- description of spasticity, which includes the
gram (EMG) (Fee and Miller 2004). velocity-dependent feature, sounds like a defini-
In addition to nonlinear passive and active tion of an increase of the viscous dampening of
spring stiffness, tone in the limb also has a com- normal muscle tone, but it is not. This description
ponent of viscoelastic dampening, which is veloc- is typically used as another definition of hyper-
ity-dependent resistance to movement. This reflexia, which is part of the syndrome. There are
dampening effect works very similar to a shock no reports documenting that spasticity is related to
absorber in a car. The dampener also has a non- velocity of angular joint motion in the mechanical
linear response to varying velocity and position of sense of the change of the joint angle over time. It
the limb. The function of the viscous dampener is is likely that in some patients, joint acceleration or
to provide passive tone in the normal motor sys- jerk is the main indicator of spasticity (Sloot et al.
tem, so the movement is smoothed. Muscle tone 2017). The term velocity is used in a general way
here is defined as some tension in the muscle, to mean movement. Also, there is a variability to
while it is not actively contracting. This tone spasticity that has been defined as a clasp-knife,
probably provides an important functional factor release, and catching characteristic. Spasticity is
to the muscle. If the muscle is completely loose, difficult to explain, and it is not clear if all the
without tension, it would have a slower response, characteristics used to describe it are different
and the fine control would be lacking. aspects of the same response or totally different
Also, there is some undefined important aspect responses occurring in the same muscle. The syn-
of this tone in allowing the muscle to maintain its drome of altered muscle tone is extremely easy to
strength and to regulate its growth in childhood. A recognize but much harder to define. In this way,
second major aspect of muscle tone is the motion- spasticity is like pornography, which has been
induced stretch reflex, which is commonly known described by a supreme court justice as “hard to
as the knee or ankle jerk reflex. This is a mono- define but easy to recognize when you see it.”
synaptic reflex induced through stretch reception Movement patterns, especially dystonia, may be
of the receptors in the muscles. The stretch reflex difficult to differentiate from spasticity when
the child is seen for only a short time; however, Other methods for assessing spasticity include
the presence of the secondary changes, especially the leg drop test in which the leg is allowed to
in the muscle, usually allows the differentiation to swing over the edge of a table and the oscillations
be easily made. and magnitude of the movement are measured.
This test only works in a child with mild to mod-
Measuring Muscle Tone erate spasticity and requires excellent cooperation
Muscle tone is such a basic aspect of motor from the individual being tested. Many mechani-
control that there have to be ways for it to be cal movement devices have been designed to
quantified (see ▶ Chap. 39, “Spasticity Assess- move and measure the torque generated by the
ment in Cerebral Palsy”). The most common movement as methods for measuring spasticity.
method has been the use of the Ashworth scale. None of these systems has gained wide accep-
This scale is a manual scale that evaluates resistance for clinical use. Many people have tried to
tance to motion of a specific joint; however, it record the EMG activity; however, it is impossible
only considers hypertonicity. The scale has been to determine any force data from electromyogra-
modified to include more levels and to allow phy. Another very old technique is to measure the
assessment of hypotonia in a scale called the H-response, which is a nerve potential recorded in
modified Ashworth scale (see Table 1). This the motor neuron that occurs when a sensory
scale is the most widely used scale for assessing nerve in close proximity is stimulated. The ampli-
spasticity; however, it is very subjective and at tude of this H-wave is thought to reflect the excit-
times difficult to separate limb stiffness resulting ability of the alpha motor neuron (Fig. 2). This
from muscle stiffness as opposed to the stiffness measurement has been correlated to hyperreflexia
induced by spasticity. but does not correlate well with the Ashworth
scale (Sussman et al. 1992); therefore, we still
Table 1 Ashworth scale and modified Ashworth scale are using the modified Ashworth scale for clinical
Ashworth scale evaluation of spasticity.
Score Description of the muscle tone
1 No increase in normal tone
2 Slight increased tone with a catch with rapid Spasticity
joint motion
3 Increased tone but the joint is still easy to move Spasticity is the most common presentation
4 Considerable increase in tone making passive of all neurologic alterations in children with
movement difficult
CP. Increased muscle tone expressed as spasticity
5 Limb is rigid, movement is difficult
must be a very strong chaotic attractor to the
Modified Ashworth scale
organization of residual activity in a child with a
Score Description of the muscle tone
central neurologic injury. It is very difficult to
00 Hypotonia
0 Normal tone, no increase in tone
understand what the components of the system
1 Slight increase in tone manifested by a slight are that make this spasticity such a strong attrac-
catch and release or minimal increased tor. Because it has persisted in humans but
resistance to joint range of motion is seldom seen in animals, this suggests that
1+ Slight increase in tone manifested by a slight there is a functional benefit to spasticity. Even
catch and minimal increased resistance to joint though spasticity is a strong chaotic attractor,
range of motion for more than half the joint
range any judgment about its benefit or harm to an
2 More marked increase of tone through most of individual cannot be made. From modern robotic
the whole joint range, but the affected joint is research, it is known that adding stiffness to joints
easily moved helps improve fine motor control; and also every-
3 Considerable increase in muscle tone; passive one has experienced a tendency to stiffen when
movement difficult but possible
wanting to do very fine delicate movements with
4 Affected joint is stiff and cannot be moved
their hands. It seems most conceivable that, on the
570 F. Miller
whole, when the neurologic system loses some temperature regulation and blood flow in the
function, but its organization still has the ability, extremities, some regulatory abnormality in the
muscle tone will increase to allow function with a sympathetic nervous system may be involved.
lower degree of neurologic control. Therefore, At this time, however, there is no direct evidence
when treating children with spasticity, the basic to support this theory.
supposition is that muscle tone is good and the
amount of muscle tone should be modulated for Effects of Spasticity on Muscles
their maximum benefit. and Tendons
Hypertonia and hypotonia have the most dra-
Effects of Spasticity on Nerves matic secondary effects on the muscle. The
Because the lesion in CP is central, all other more well-observed effects of spasticity on skeletal
distal changes are presumed to be secondary. The muscle include decreased longitudinal growth
best recognized change in spasticity is hyper- of the muscle fiber length, decreased volume of
reflexia, which occurs because of a decreased the muscle, change in motor unit size, and
inhibition from the cortical spinal tracts. As a change in the fiber type and neuromotor junction
normal child grows, the rate of muscle contraction type. In the mouse model, the spasticity causes
and the ability to increase power by cerebral cor- loss of approximately 50% of the longitudinal
tex modulation continues to increase until the growth of the muscle fiber, resulting in contrac-
child is approximately 10 years old. Although tures (Ziv et al. 1984). Muscles in children with
this change has been well documented by study- CP are always very thin in addition to being
ing the ability of increased rapid alternating move- short, which means that these muscles are also
ments in children and adults (Lin et al. 1996), it is weak, as a muscle’s strength is related to its
not clear where these changes occur. In CP, this cross-sectional area (Fig. 5). Understanding
more immature pattern of slow corticospinal and strength has been an extremely confusing topic
pyramidal tract potentials persists. There is an in spastic muscle evaluation. The mechanical
increased latency and a decreased ability to recruit definition of strength is defined by how much
large numbers of motor fibers at the same time load a structure can support. When discussing
(Dietz and Berger 1995). Some of this activity is strength of a limb, such as the strength of plantar
modulated through changes in the excitability of flexion at the ankle, the strongest ankle tends to
the spinal motor neurons, which are also sensitive have a severe fixed flexion contracture, but this is
to joint position or, probably more specifically, not the strength for which most clinicians are
muscle length. The strength of the ankle reflex is looking. Usually, the term strength is used to
very sensitive to ankle joint position as measured describe the ability to move a load or to do
by the H-reflex, which is initiated through stimu- work, which is called active strength, whereas
lation of a peripheral sensory nerve. This change the contracture is a passive strength. By creating
is much greater than can be explained by mechan- a significant contracture, the spastic muscle has
ical positioning. As noted earlier, there has to be great passive strength but low active strength
some tension in the muscle while the muscle is at compared with normal muscles. Active strength
rest for it to function properly. Some of this ten- is altered more in spastic children because of the
sion seems to disappear when the individual is difficulty of avoiding co-contraction, as there is
under neuromotor blockade anesthesia. It has less antagonist inhibition in spasticity. Motor
been postulated that active neuronal stimulation units tend to get larger and have slower
is required to maintain this muscle tone; however, responses with longer latency periods combined
no direct evidence of this has been found. It is this with a large shift to the slow-twitch type 1 fibers
element of increased neurologic stimulation not (Dietz and Berger 1995). All these changes mean
generating an active EMG that seems to increase the muscle responds slower during contraction
most when tone increases in CP. Because many of and, combined with the changes in the nerve, has
these children also demonstrate abnormalities in a longer latency period. Children with spasticity
Fig. 5 The effect of

spasticity on the growth and
development of skeletal
muscle results in a muscle
that has fewer muscle fibers,
shorter fiber length, and a
longer tendon. This
aberration results in a
muscle that is weaker
because of decreased cross-
sectional area and has less
excursion, resulting in
decreased joint range of
motion because of the
shorter fiber lengths
were recently found to be resistant to succinyl- the other side, it will become contracted in abduc-
choline, and on further investigation, it was tion. Therefore, both hyperadduction and hyper-
found that the neuromotor junction contains abduction are stable attractors. With a decreased
immature subunits (Robinson et al. 2013). The level of fine motor control and spasticity, the
effects of spasticity on skeletal muscle are per- neutral position of the hip is not a stable
vasive and often experienced by neuro- region. This concept also applies to other affected
orthopedists; however, a physiologic explana- joints.
tion of how increased tone causes all these
changes is still unknown. Functional Effects of Spasticity
on Sitting, Gait, and Activities of Daily
Effects of Spasticity on Bones Living
Changes in the bones caused by spasticity are There are many functional effects of spasticity,
modulated by muscular changes. The most some of which help children and some of
common effects are dislocated hips; scoliosis; which cause major problems. For children who
foot deformities, such as planovalgus feet or are ambulatory, the spasticity causes typical spas-
equinovarus feet; bunions; knee contractures; tic gait patterns (see ▶ Chap. 88, “Musculoskele-
and elbow, shoulder, and wrist joint contractures. tal Physiology Impacting Cerebral Palsy Gait”).
Torsional malalignments of the femur and tibia are Children who are able to do minimal weight bear-
common as well. A major part of this text dis- ing for transfers or household ambulation are
cusses the management of these deformities. often greatly aided in these activities by the spas-
These secondary deformities, such as dislocated ticity, which provides the strength and stability
hips, have been very well defined and have for weight bearing. These same children may
clear mechanical etiologies (Miller et al. 1999). have problems relaxing in seating positions and
These deformities all have clear and strong pulls therefore are difficult to seat. They may also have
to develop toward easily understood chaotic so much spasticity that activities of daily living,
attractors. In the hip, on one side the muscle will such as dressing and toileting, are difficult. Each
become contracted causing adduction, and on child requires a careful assessment of the specific
572 F. Miller
problems and benefits caused by the spasticity. The Effects of Hypotonia

There is a tendency for family members and
some clinicians to equate the spasticity to CP. It Just as secondary effects of spasticity are noted,
is often difficult for them to see the benefits pro- there are secondary effects of hypotonia. Muscles
vided by the spasticity. are the primary structures that are affected. The
muscles tend to be weak, meaning they do not
generate a high active force compared with a
Hypotonia normal child, and they tend to be excessively
long or do not have a good definite end feel during
Hypotonia is defined as lower than normal muscle an examination as a normal muscle would. These
tone. Hypotonia occurs less frequently than hypotonic muscles are very thin and gracile when
spasticity in children with CP, and although it is examined. Some children with severe hypotonia
still relatively common, it has not attracted the have a muscle that appears white during surgery.
attention that hypertonia has. Hypotonia is most There are no data to define what these changes
common in children with congenital CP, with reflect at the histologic level. Other common
lesions such as lissencephaly. Families usually changes in the limbs in hypotonic children are
perceive and describe the problem as the child long gracile bones with osteopenia and osteopo-
being weak, which most children with hypotonia rosis. Joint hypermobility is often associated.
are. Also, there is a common confusion between There is no recognized measurement of hypotonia
hypotonia and hyperlaxity or hypermobility of except the modified Ashworth scale, which
joints. Each of these is a separate problem, but assigns a single-scale group to separate hypotonia
they are often interrelated. For example, a child from normal tone (Table 1).
with Down syndrome has hypotonia, meaning a
decreased stiffness in the muscle, but also has Functional Problems
connective tissue laxity. Together, these condi- The main functional problem is poor trunk and
tions allow for joint hypermobility. In children head control. The joint laxity and poor strength
with hypotonia due to CP, it is usually associated also leads to a high rate of joint dislocations at
with severe quadriplegic pattern involvement and the hip and feet with the development of scoliosis.
mental retardation. These children have so little Because of the osteopenia, gracile bones, and
motor control that the system fails to even make osteoporosis, recurrent fractures become a prob-
an attempt to provide stability. Some children lem in a few children.
have hyperreflexia as a spastic feature but have Almost all the literature with respect to hypo-
low tone as a passive element. This group will be tonia and CP is concerned with diagnosing other
called the local mixed tone pattern. Also, there are common diseases (Lesny et al. 1990). As
children with definite increased tone and spastic- opposed to spasticity, the treatment options for
ity in the lower extremities but significant hypo- hypotonia are very limited because hypotonia is
tonia with their trunk and head control. This group a situation where there is not enough tone. In
will be called the anatomic mixed tone pattern. almost all situations of life, it is harder to treat
The anatomic mixed tone pattern is very common something that is not there than to remove some-
during middle childhood, especially in non- thing of which there is too much. This fact is well
ambulatory children. Many of these children demonstrated by all the options that are available
were initially hypotonic infants, which are much to decrease muscle tone in children with spastic-
more common than hypertonic infants. Most ity, whereas there is not one option available to
of these hypotonic infants develop spasticity increase muscle tone in hypotonic children. Sta-
slowly, usually starting distally and progressing bilizing hyperlaxed joints is limited to either
proximally. This proximal migration of increased surgery or external orthotics. The main problem
tone often helps the children to sit better as they of poor sitting is addressed with well-designed
get older. seating to provide a stable, upright posture. Foot
and ankle orthotics are used to stabilize the ankle The treatment of muscle tone may be applied at
and feet for standing in standers. These children different locations in the neuromuscular system.
often require supine standers because of poor Treatment options start in the central nervous
head control. When the joint instabilities system with the use of medications, electrical
become severe, stabilization by fusion, such as stimulation, or surgical ablation. In the peripheral
posterior spinal fusion for scoliosis and nervous system to the level of the muscle, medi-
foot fusion for planovalgus collapse, is com- cation and ablation are the main choices. At
monly performed. the muscle level, medication, electrical stimula-
tion, and surgical lengthening are the treatment
options. The listed chapter references go into
Treatments of Tone much more detail of the treatment options.
When planning for treatment of the spasticity,

the benefits and problems should be carefully Movement Disorders
considered (see ▶ Chaps. 40, “Medical Manage-
ment of Spasticity in Children with Cerebral Movement disorders are primary problems related
Palsy,” ▶ 41, “Focal Management of Spasticity to the ability of children to develop and
in Cerebral Palsy,” ▶ 42, “Intrathecal Baclofen control motor movement as a pattern. The specific
Therapy: Assessment and Medical Manage- description of these deformities is somewhat
ment,” and ▶ 44, “Dorsal Rhizotomy for Spas- confusing and varies among authors of different
ticity Management in Cerebral Palsy”). texts. Although there is a large body of scientific
Everyone must realize that no matter how suc- work evaluating the function and pathologies of
cessful the treatment of the spasticity is, the child the brain that lead to movement disorders, the
will still have CP. It should always be kept in complexities are so great that there is still no
mind that the goal in treating spasticity is to easy clear explanation of how motor control is
never remove all muscle tone. It is much better managed in the brain. The pathology of these
to conceptualize spasticity treatment similar to movement disorders has been localized to the
treating hypertension. Clearly, the treatment of basal ganglion and the communication process
hypertension would not be successful if all the between the cerebral cortex and the basal gan-
blood pressure were removed. There is consid- glion. The primary lesion in most movement dis-
erable similarity between no blood pressure and orders is in the basal ganglion, as demonstrated by
no muscle tone. The ideal treatment of spasticity the development of posttraumatic dystonia. Also,
would be a situation where the tone is decreased some movement disorders, such as ballismus,
only at the time and in the anatomic area when have been localized to occur primarily in the sub-
and where it causes problems. The spasticity thalamic nucleus. It is beyond the scope of this
would then be preserved in all situations in text to review all the biochemical and anatomic
which it is helping the child. It is also important bases of movement disorders that are currently
to remember that some of the secondary effects understood. Understanding the specific pathology
in the muscle noted above may also have direct in individual children may provide important
effects from the primary lesion. For example, the treatment options, such as medication or surgery.
strength of a muscle contraction is mediated by However, in many children, it is impossible to
the cerebral cortex impulse. Therefore, in a child specifically localize the pathology, or if it can
with CP, this ability to modulate strength may be be localized, it does not help in directly treating
a primary deficiency due to the brain lesion. these children.
After the child has been evaluated with an It is extremely important for the clinician
assessment of the specific benefits and problems treating these children to understand the differ-
of spasticity, available treatment options should ence between movement disorders and disorders
be considered. of tone, meaning primarily spasticity. The
574 F. Miller
treatments for these disorders are often diametri- attractor again. These attractor positions in indi-
cally opposed, especially the options that the vidual patients become very well recognized and
orthopedist would consider. A helpful approach can be described easily by the patients themselves
for the orthopedic clinician who deals with these as the positions to which their limbs seem to want
children is to approach them through the concep- to go.
tualization of dynamic control theory. In this As noted earlier, both dystonia and spasticity
approach, their function will tend to be drawn can be present in the same limb, although in our
toward a chaotic attractor, which is called the experience, this is not a common occurrence in
movement disorder. Many of these patterns are localized limb dystonia. The presence of both
not clearly separate from each other, and they is much more common in generalized dystonia.
may be best visualized as different strength It is especially difficult to separate generalized
attractors. The three movement patterns that can dystonia from generalized spasticity, especially
be used to categorize most children with CP are when it presents as extensor posturing with
dystonia, athetosis, and chorea or ballismus. opisthotonic patterning. The difference exists
because opisthotonic patterning originates pri-
marily from brainstem defects as opposed to
Motor Control: Movement Disorders dystonia, which originates primarily from basal
ganglion lesions. Also, the children with
Dystonia opisthotonic patterning are often in this hyper-
There are many different types of movement dis- extended position all the time, including during
orders, which may also be mixed up with disor- sleep. Children with dystonia tend to be in a
ders of tone. Separately quantifying specific more relaxed and normal position during sleep.
movement disorders and abnormal tone is often The secondary effects of dystonia and spasticity
not possible, and many may be considered mixed are also very different.
tone movement disorder. Dystonia is a movement
disorder that has a torsional component with Secondary Effects of Dystonia
strong muscle contractions with major recurrent It cannot be overemphasized how important it is
movement patterns. An example of such a pattern for the orthopedist to identify isolated limb dys-
is strong shoulder external rotation extension and tonia from spasticity because on the initial eval-
abduction combined with elbow extension, then uation, for example, the limb may present in
alternating with the opposite extreme of elbow fixed wrist and elbow flexed position, which
flexion, shoulder internal rotation, adduction, has an appearance exactly like a hemiplegic,
and flexion. Dystonia may occur in a single spastic limb. This same position occasionally
limb, in a single joint, or as a whole-body disorder. occurs with the foot in equinovarus or
These movements cannot be volitionally con- planovalgus, having the same initial appearance
trolled, although there is a sensory feedback ele- whether the child is spastic or dystonic. The
ment that sometimes allows them to be stopped or major difference between spasticity and dystonia
reversed. For example, a specific pressure point or is determined by a good physical examination
body position may stop the forceful elbow and and patient history. On physical examination, it
shoulder external rotation contraction. Some- often becomes clear in the limb with dystonia
times, moving a finger passively will break up that there is no fixed contracture and the muscle
the forceful dystonic wrist flexion. There is no appears to be hypertrophic, like a child who has
good anatomic understanding of how these sen- been a weight lifter. During the examination, the
sory inputs function. The attraction to individual child’s muscles will often release and have a
patterns is weak, which means various perturba- temporary appearance of normal tone. When
tions can push the system out of the pattern; how- the muscle releases, the joint will have a full
ever, the system is very unstable, being drawn to range of motion with no contracture present.
either another attractor or back to the same This appearance is very different compared
with a child with a spastic limb in whom the dopamine receptor-blocking drugs. None of
contracted deformity is stiff in all conditions these drugs has a highly selective effect on dysto-
and the muscle often has a short, thin appearance nia, and the positive and negative effects of each
on physical examination. A child with a severe drug have to be balanced, preferably by a clinician
equinovarus positioning of the foot from spas- with experience in their use (see ▶ Chap. 45,
ticity will always have some level of muscle “Dystonia and Movement Disorders in Children
contracture present. The important question to with Cerebral Palsy”). Also intrathecal baclofen
ask in the history taking is if the foot or hand and deep brain stimulation (DBS) may be used for
ever goes in any other position except the one selective cases (see ▶ Chaps. 42, “Intrathecal
that it is in now. If the problem is dystonia, Baclofen Therapy: Assessment and Medical Man-
the parents and the child often will say very agement” and ▶ 46, “Deep Brain Stimulation for
readily that sometimes instead of the wrist Pediatric Dystonia”).
being in a flexed position, it is stuck back with For children with localized dystonia who
the fingers flexed but the wrist extended. The have failed oral medication treatment, a careful
history of how the child positions when relaxed, assessment of the area and level of maximal
the appearance of the muscles, and the sense of functional impairment is required. The first-line
the child’s underlying tone when relaxed are the approach is an evaluation with the use of orthot-
important parameters to use in separating spas- ics to stabilize the deformity. Orthotics are espe-
ticity from dystonia. This distinction is especially likely to work if the dystonia is affecting
cially true for a quadriplegic child, where the the foot. If this simple mechanical approach
child with pure dystonia will often have very fails, the next line is to use Botox in the
large well-formed muscles and no underlying offending muscle; however, the family and
contractures. A child with significant hyperex- child need to be warned that this is a temporary
tension posturing spasticity often has significant measure. After the Botox fails, an intrathecal
contractures, sometimes of the extensor muscles baclofen trial is considered, or if the problem is
of the neck and often of hip extensors and quad- localized to the foot, a fusion stabilization pro-
riceps of the knee. cedure is considered. If the baclofen trial is suc-
Objective measurement of degrees of dystonia cessful, a pump is implanted. If the pump is not
is an extremely difficult problem. There has been successful, DBS is the next option.
an attempt made to measure dystonia by the devel-
opment of the Barry-Albright Dystonia (BAD) Athetosis
Scale, which focuses on generalized dystonia Athetosis is a movement disorder presenting as
and mainly measures the stiffness of the child large movements of proximal joints. Athetosis
(Barry et al. 1999). This scale is not much differ- tends to be worse in the upper extremity with
ent from the Ashworth scale applied to the trunk, external rotation and abduction movements of
and as such really has no ability to separate dys- the shoulder, often with extension and fanning of
tonia from spasticity. This scale cannot be applied the fingers. The movement is induced by volun-
to isolated limb dystonias. Another scale relies tary effort, although sometimes this effort is as
more on visual assessment of movement using remote as trying to speak. A variable amount of
video (Burke et al. 1985). voluntary control is often improved in the context
The primary treatment of both generalized dys- of more complex movements, such as a move-
tonia is oral medication management. The avail- ment associated with walking. Athetosis is also a
able drug options are many, and the rationale for major component of the hyperkinetic pattern,
use of a specific drug is not well defined. The which is the term used by some neurologists.
available options include levodopa, anticholiner- Traditionally, athetosis has been associated with
gics such as trihexyphenidyl hydrochloride and neonatal kernicterus and hyperbilirubinemia. This
diphenhydramine, and benzodiazepines, baclo- direct relationship has become less clear as the
fen, carbamazepine, and a large variety of treatment of kernicterus and hyperbilirubinemia
576 F. Miller
has improved. There has been a significant Treatment

decrease in the number of children with predom- The use of diazepam as an oral medication will
inantly athetosis in the past 30 years (O’Reilly and decrease athetoid movement but only at very high
Walentynowicz 1981). The pathologic etiology doses. Except for acute situations, such as follow-
classically involves kernicterus in the palladium; ing surgery, diazepam has little use because of the
however, investigations into cases with unclear severe sedative effects at the dosage that controls
etiology have found lesions also involving vari- the movement. There are no other medications
ous parts of the basal ganglion. Children with that have gained widespread use. Botox has little
isolated athetosis tend to have no intellectual def- or no usefulness because of the whole-body nature
icits but often have motor speech problems that of the athetoid involvement. There is rarely a
make communication difficult. The natural his- single problem caused by one or two muscles
tory of athetosis is an infant who initially is hypo- (Vidailhet 2013).
tonic and then between 12 and 24 months of age There is a long history of central nervous
starts to have increased movement with an under- system surgery, mainly ablative procedures or
lying hypotonia. As these children get to be implanted electrical stimulation; however, none
2–4 years old, the hypotonia resolves and many of these has demonstrated any consistent benefit
develop some level of increased tone that helps to in individuals with athetosis (Trejos and Araya
modulate their movement. Typically, by age of 1990). Currently, there is no role for central ner-
5, the full expression of the movement disorder vous system surgery for athetosis.
is present. Musculoskeletal surgery is limited to stabiliz-
ing joints where they might provide functional
Sensory Motor Effects of Athetosis benefit. Fusion of the subtalar joint and spinal
In individuals with athetosis only, there are almost fusion for scoliosis are the most commonly
no secondary effects in childhood. There may indicated operative procedures. However, most
be some increased mobility of finger extension, children with athetosis only will need no muscu-
especially at the metacarpal phalangeal joint. The loskeletal surgery. Many children have a mix of
muscles tend to be hypertrophic, although less spasticity and athetosis, so they develop the sec-
so than with dystonia where the maximum con- ondary problems of muscle contractures from the
traction is held for a longer period of time. In spastic component. As the patient is evaluated to
athetosis, there is a large amount of motion, but determine if the contracted muscle should be
the muscle is not held in maximum contraction for lengthened, caution should be exercised when
an increased amount of time. The difference trying to determine how much spasticity is damp-
between athetosis and dystonia for the muscles is ening unwanted athetosis.
similar to the difference between a weight lifting A common combination is a hamstring con-
athlete and a long-distance runner. Dystonia is tracture with or without a knee flexion contrac-
similar to weight lifting, and athetosis is similar ture, which makes it difficult for a young adult or
to running. Children with athetosis have a very adolescent to stand. Often, the standing is an
high energy need, as opposed to children with important function for the adult-sized individual
quadriplegic spasticity where the energy need is because it will allow one attendant to provide for
considerably less than normal. Athetosis usually their needs as opposed to needing two attendants
involves significant problems of trunk control, to do a dependent patient lift transfer. In this
with trunk hypotonia often significantly limiting situation, lengthening the hamstrings and knee
a child’s ability to gain sitting stability or to walk. capsule may provide a substantial functional ben-
Facial movements are usually part of the athetoid efit; however, the postoperative management may
pattern and are often associated with increased be very difficult, as the athetosis tends to get
drooling. This movement disorder also appears worse with pain. Although this can be a very
to affect the vocal cords, causing a major motor difficult time for the patient, family, and medical
speech impairment. team, it often provides excellent functional gain in
the end. A major advantage is that the patient motor function or change in motor function in an
usually has excellent understanding of the goals individual with athetosis, a full workup of the
and will be very willing to work hard to achieve cervical spine including radiographs and MRI
the goals. scans is required. The degenerative joint disease
Undertaking a major surgical reconstruction and the cervical spine instability usually require
in a child with severe athetosis and underlying cervical spine fusion and decompression.
spasticity requires a very experienced postopera- We have seen several children with athetosis
tive management team. Often, there is an element who developed lumbar spondylolisthesis in child-
of great hesitation with families and young adults hood, and the only fusion for spondylolisthesis
or adolescents to undertake any major surgical that we have done was in an adolescent with
changes. This hesitation in families and patients athetosis (Case 2). There is no specific informa-
often develops because of their own experience tion on the incidence of spondylolysis or the inci-
with the unpredictableness of athetosis. They are dence with which it progresses to an unstable
hesitant to undertake a treatment that they fear will spondylolisthesis.
leave them even worse than they are currently.
Many of these families and patients have also Treatment: Therapy
had experience with physicians who did not The main treatment for a child with athetosis is
appreciate the unpredictable nature of athetosis excellent therapy by an experienced therapist.
and were not willing to listen to their experience This treatment focuses on educating the family
with this condition (Case 1). and working with the child to help them find
Because of the excellent cognitive function in what works and what does not work. Good seating
most individuals with athetosis, their input into is required to maximize upper extremity function;
rehabilitation often significantly enhances the however, the family and therapist also have to
rehabilitation period because they will know allow the child to explore with bare feet and use
what works and what does not work. This great her head as a motor control device. Because
insight by these patients in understanding of their athetosis is usually worse in the upper extremity,
own body can lead to a dynamic in which thera- there is a small group of children who have good
pists feel the patients are not willing to listen or control of their lower extremities and can do fine
want to try something new. On the other hand, motor skills with their feet. Skills such as drawing,
these patients may feel that the therapists are not writing, and playing musical instruments are
listening and only want to follow a fixed thera- occasionally mastered. Unless the child is given
peutic plan. This is the situation in which both the options to explore these skills, they will not be
therapists and the patients have to listen to each recognized. The most common skill a child with
other and both have to be open to try different athetosis can learn is to use a joystick to drive a
techniques to arrive at a maximum rehabilitation wheelchair. Because the function of these children
potential of each individual. is often apparent by the time they are 4–5 years
Another major musculoskeletal problem of old and they are very intelligent, they are the only
athetosis is degenerative joint disease changes in candidates with CP for whom an early power
the cervical spine from the increased cervical wheelchair fitting is a reasonable option. The
spinal mobility. We have never seen these power wheelchair does require the family to
changes as a problem in a child or an adolescent; have transportation to carry it and an adapted
however, they have been well reported to occur in home. Also, many children benefit from the use
middle age, although the exact incidence is of weights on the wrists when they are trying to do
unclear. There are many small series reporting specific tasks with the upper extremity or the use
myelopathy with this degenerative joint disease of ankle weights when they are working on walk-
process as the cervical spine develops instability ing. Weighted vests can also help some children
and subluxation (Nishihara et al. 1984; Jameson during seated activities. These weights may pro-
et al. 2010; Onari 2000). If there is any decreased vide dampening of the movement similar to the
578 F. Miller
presence of spasticity, or there may be a more ballismus movements start to develop in children
complicated control interaction. The weights do with CP, additional workup frequently defines a
seem to move these children to a different and more specific diagnosis, often one with a degen-
more stable chaotic attractor in the motor control erative process. These movement disorders may
abilities area. Each child is quite variable, requir- get slowly worse if there are no mechanisms for
ing an experienced and patient therapist to try controlling them.
many options and ascertain which combination The primary pathology for chorea and
is working best for the individual child. Some ballismus occurs in the basal ganglion; therefore,
parents become excellent at defining the specific many drug options similar to the treatment of
circumstances in which their child can best dystonia are considered as the first line of treat-
function. ment. There have also been positive reports of
In summary, the treatment of athetosis primar- ablative surgery on the internal capsule. There
ily revolves around experienced therapists who are no specific treatments for the musculoskeletal
can help these children access the most useful affects of ballismus and chorea in children
functional motor abilities and allow them to with CP.
express their generally high cognitive function.
These children often benefit greatly from the use
of augmentative speech devices, and as such need Summary of Motor Control Treatments
to have access to excellent assistive communica-
tion services. Musculoskeletal procedures are It is often very difficult to separate out exact
useful only to stabilize joints and, in rare circum- treatment recommendations between the move-
stances, to treat the underlying spasticity when it ment disorders, especially because there is not
causes more functional problems than benefits. a clear pathoanatomic basis of one movement
There is rarely any role for medication in the disorder compared with another. These disorders
treatment of athetosis. are somewhat overlapping in their presentation
and probably reflect movement patterns best
understood as chaotic attractors in dynamic
Chorea and Ballismus motor control without a clear anatomic separation.
An analogy of these patterns might be the differ-
Chorea is a movement disorder defined by jerky, ence between a wind and rainstorm compared
rhythmic, small-range movements. These move- with a thunderstorm or a tornado. Each of these
ments are more predominant distally in the limb storms is a definite recognized pattern, all occur
and on the face; however, they are present in the same geographic region, and the cause of
as proximal movements of the head and trunk as each is similar and not completely understood.
rhythmic, jerky motion as well. Ballismus is large This same analogy applies between the move-
movement based at the proximal joints, primarily ment disorders of dystonia, athetosis, chorea,
the shoulder and elbow or hip and knee. These and ballismus. These movement patterns are
large movements are unpredictable and jerky and fairly different and recognizable although a
often have a violent character to them. Some pathoanatomic understanding of the exact differ-
neurologists believe that chorea and ballismus ences is not clear. However, because the patterns
are two ends of the same movement spectrum, can be recognized, specific treatment algorithms
and from the musculoskeletal treatment perspec- for each can be defined. From the musculoskeletal
tive, this concept works well. These movement perspective, dystonia is a nonvolitional movement
patterns are the most rare of the movement disor- pattern that is difficult to treat because of the
ders in children with CP. When these movement persistent nature of the symptoms and the strength
disorders are seen to be developing, especially if of the muscle forces. Athetosis is more predictable
significant chorea develops, the diagnosis of CP and is often under some volitional control that
should be questioned. If significant chorea or can be accessed through physical therapy
intervention. There is very little musculoskeletal to have a mixed pattern of spasticity and ataxia
treatment that is beneficial for chorea and or hypotonia and ataxia. Many children with
ballismus. athetosis probably also have ataxia, but it is very
difficult to separate out ataxia in the presence
of significant athetosis. Having good balance
Disorders of Balance (Ataxia) requires that the individual have a stable physical
base of support and a good sensory feedback
Ataxia is a term used to describe poor balance in system that can interpret where the body is in
children with CP due to central nervous system space and how its position should be corrected.
processing (see ▶ Chaps. 47, “Ataxia and Disor- The lack of a stable base of support is demon-
ders of Balance in Children with Cerebral Palsy” strated by an individual’s experience of walking
and ▶ 48, “Assessing Dynamic Balance in Chil- on slippery ice where the physical base of support
dren with Cerebral Palsy”). Poor balance can also is poor. An example of decreased balance occurs
be due to vestibular dysfunction, and often a com- when an individual is under the influence of alco-
plete workup is required to ascertain the etiology. hol, in which sensory feedback and interpretation
Some children with CP seem to have an isolated are dulled. In the musculoskeletal treatment plan
ataxia, usually related to congenital cerebellar of children with ataxia, it is important to evaluate
malformations. Often, these are normally devel- the components of balance, such as their base of
oping infants until 12 months of age, when it is support or their sensory feedback, that are con-
noticed that they are not progressing with their tributing to most of their functional problems
normal motor skills development. These children (Case 3).
have delayed independent sitting and delayed Measurement of balance in children is difficult.
walking, often not until 2 or 3 years of age. The Most of the balance studies in adults and children
problem with their balance is most clear in the involve an assessment of postural stability by
development of independent walking, but as measuring the impact of different sensory sys-
the children start doing fine motor skills, they tems, such as eyesight, the inner ear vestibular
demonstrate clumsiness in writing and other fine system, and joint sensory position feedback. The
motor skills. Ataxia often affects speech as well. gross motor function measure (GMFM) has
Typically, the normal development of balance become a common clinical evaluation tool for
reaches its maximum in middle childhood and children with CP. Although this test does not
remains stable during the adolescent growth specifically evaluate and measure ataxia, it has
spurt; however, these children appear to be losing a significant component, especially in domain
balance ability. This apparent loss of balance abil- 4, where tasks such as single-leg stands are
ity is due to the rapid height gain that occurs evaluated. These tasks require separating out bal-
during the adolescent growth spurt. The poor ance from motor control problems based on sub-
balance is a demonstration of the balancing sys- jective evaluation of these children. Also, on gait
tem having trouble controlling a taller structure analysis, temporal spatial characteristics such
that is mechanically harder to control than a as step length and cadence tend to have high
shorter structure. This phenomenon is also seen variability in children with significant ataxia.
in completely normal children and is usually Children with only spasticity but good balance
called the adolescent clumsy stage of develop- have less variability than normal children, and
ment. After a year at the end of maximum growth, those with predominantly ataxia will have much
the balancing system will again gain control, and higher variability.
these children will typically have the same func- This variability is also true of trunk motion and
tion they had at 8–10 years of age before the the ability to walk in a straight line. Understand-
adolescent growth spurt started. ing balance deficits during walking is difficult
Although there are children with CP whose because momentum can make unstable children
only problem is ataxia, it is much more common look much more stable than they really are. An
580 F. Miller
example is a child who seems to walk very well who cannot learn to stop and stand in one place
while walking; however, every time she tries to will have to switch to the use of an assistive
stop, she has to grab the wall or fall to the floor. device, usually forearm crutches, in middle child-
This is the analogy of riding a bicycle where the hood or adolescence. This step may seem like a
rider is very stable due to the momentum of regression to parents; however, it is moving the
motion. However, if the rider stops the motion child forward to a more stable gait pattern that is
and tries to sit on the bicycle, she becomes very socially acceptable and functional into adulthood.
unstable. A child who can walk well only at a It is appropriate for 3-year-old children to run and
certain speed may be an excellent walker; how- then fall when they get to where they are going
ever, developing good functional walking skills and want to stop; however, this method in a
requires that an individual be able to stop without 13-year-old would be both unsafe for the child
falling over. and socially unacceptable. Finding the appropri-
ate device requires some trial and error. There are
Treatment of Ataxia rare children who can use single-point canes.
Therapy to help children with ataxia improve Three- or four-point canes are a poor choice
their walking should focus on two areas. First, because they slow the child too much and are
they must learn how to fall safely and develop generally very inefficient. Either forearm crutches
protective responses when falling. They should or a walker is typically the best assistive device for
be taught to recognize when they are falling, direct an individual child. Some children’s ataxia is so
the fall away from hazards, and fall forward severe that it requires the use of a wheelchair for
with their arms out in front to protect themselves. safe and functional mobility.
Until these children develop a good protective The sensory perception and processing of bal-
response to falling, they should be wearing pro- ance cannot be altered in any predictable known
tective helmets and have supervision when walkway with surgery; however, the mechanical sta-
ing. There are some children who cannot learn this bility can be altered. Mechanical stability means
protective response, and they will have a tendency that children have a stable base of support upon
to fall like a cut tree; this is especially dangerous if which to stand. Children with severe equinus at
the individual has a tendency to fall backward, the ankle, such that they can only stand on their
which places them at high risk of head injury. toes, will be unstable even if their balance is
These children will have to be kept in wheelchairs otherwise normal. Other examples of mechanical
except when they are under the direct supervision instability are severe planovalgus or equinovarus
of another individual. The second area of treat- feet, severe fixed scoliosis, or severe contractures
ment focus for children with ataxia should be of the hip and knee. In general, the spine, hip, and
directed at exercises that stimulate balancing. knee contractures need to be very severe before
These exercises include single-leg stance activi- they substantially affect balance. Fixed ankle
ties, walking a narrow board, roller skating, and equinus is the most common situation that is
other activities that stimulate the balancing sys- seen in early and middle childhood. Many of
tem. These exercises have to be carefully struc- these children walk very well on their toes when
tured to the individual child’s abilities, with the they are moving with sufficient speed; however,
goal of maximizing each child’s ability safely and they have no stable ability to stand in one place;
effectively. this means that the children have to hold onto a
Walking effectively as an adult requires an wall, keep moving around in a circle, or fall to the
individual to be able to alter gait and speed and floor when they want to stop. When these same
especially to slow down speed to reserve energy children are made more stable by lengthening
as she tires. This may mean using an assistive the gastrocnemius muscle to allow their feet to
device, such as forearm crutches. For safety and become plantigrade, their walking velocity slows,
social propriety, it is important that an individual but they can now stop and stand in one place. This
can stop walking and stand in one place. Children trade-off of stability and stance versus the speed of
walking needs to be explained to parents to avoid through the use of orthotics and assistive devices
their disappointment in the slower walking. This in young children, and as they get to middle
kind of fast toe walking is not a reasonable long- childhood, selective muscle lengthening can be
term option for older children for the safety rea- utilized to improve their mechanical stability and
sons already explained. The safety and social stance. The treatment plan should always con-
inappropriateness of this gait pattern have to be sider how safe these children are to avoid falls,
carefully explained to parents for them to under- which might cause them significant injury. Chil-
stand the trade-off in stability for speed provided dren with significant ataxia are at significant risk
by gastrocnemius lengthening. for falls that may cause permanent additional
head injuries, and because of this risk, some
Orthotics children with ataxia need to be kept in wheel-
For young children with dynamic plantar flexion chairs or use protective helmets based on their
causing them to toe walk, correcting the plantar ability to learn protective maneuvers and the
flexion with the use of orthotics provides the severity of their ataxia.
same improvements in stability as was described
for surgical lengthening of tendons. By remov-
ing flexibility of the ankle, and especially by
decreasing plantar flexion and toe walking, Cases
these children will be in a more stable position
to focus on controlling large joints, such as the
hip, knee, and trunk. Therefore, these children Case 1 Nicholas
will gain better experience in upright stance Nicholas, a 16-year-old male with severe
required for stable walking. The use of orthotics knee flexion contractures and torsional
is the primary stabilizing structure that is pro- malalignment of the left hip with
vided to young children, usually beginning at planovalgus feet, was having increased dif-
approximately 18–24 months of age and then ficulty in walking. He had normal cognitive
gradually decreasing instability as they get function and was academically at the top of
older. The orthotics also have the advantage his high school class. It was recommended
that they can provide children a period of stabil- that he have a left femoral osteotomy,
ity when standing with their feet flat, as well bilateral knee capsulotomies with ham-
as allowing them to have time when they string lengthenings, and arthrodesis for
are walking up on their toes. This toe walking planovalgus feet. After extensive discus-
allows them to experience the stability of sion, he and his family agreed to proceed,
momentum, which stimulates the young devel- although with a lot of hesitation. Postoper-
oping nervous system. These orthotics work atively, he had severe spasms requiring very
especially well until these children are high doses of diazepam and morphine. On
5–7 years of age. the left side, he also developed a sciatic
nerve palsy. After 1 week, the pain and
Summary of Treatment: Ataxia spasms subsided, and he started a long reha-
Children with ataxia need a planned approach of bilitation period requiring slow extension
treatment combining a therapy environment in stretching of the left knee, as tolerated by
which the balance, sensory, and integration sys- the sciatic palsy. After 1 year of rehabilita-
tems are stressed, so they can learn to maximize tion, he was standing and walking much
balancing function. These children also need to more upright, and he was very glad he had
have their mechanical base of support stabilized gone through the procedure. There were
to provide a stable base upon which they can many times following the surgery where
gain confidence and learn to use their motor
control skills. Mechanical stability is gained (continued)
582 F. Miller
Dorsiflexion 29.5
both Nicholas and his family felt like he
would never recover from the surgery and 0.0
Ankle
the related complications. However, the
Motion -25.0
sensory and motor defects of the sciatic
palsy completely resolved, and the final -50.0
Plantarflexion -64.5
expected outcome was similar to the expec-
tations going into the procedure. Flexion 101.3
Left
Knee 50.0
Motion
Case 2 Zackery 0.0
Zackery, a 12-year-old boy, presented with Extension
-24.1
a complaint of back pain, especially after
Up 1.70
walking long distance. A gait analysis
showed very high variability in step length
GRF 1.00
and most kinematic parameters (Fig. C2.1).
Vertical
He had no fixed contractures on physical
examination. A radiograph of his spine
demonstrated L5 spondylolysis with grade Down -0.22
one spondylolisthesis (Fig. C2.2). An
attempt at conservative treatment with a Fig. C2.1
lumbar flexion jacket for 6 months demon-
strated no significant decrease in the pain;
therefore, it was recommended to have a
posterolateral arthrodesis from L4 to the
sacrum. After this healed, all his back pain
resolved.
Case 3 Kerstin
Kerstin, a girl who had a normal birth his-
tory and mild mental retardation, started
walking independently at 4 years of age.
She had made very little progress in the
control of her gait, often having periods
when she seemed to have more problems
with her balance around periods of rapid
growth. However, by the time she reached
full maturity, her gait stabilized by being a
little slower and less variable. On physical
examination, she had normal reflexes, mus- Fig. C2.2
cle strength, and motor control. This is the
typical pattern of primary ataxia. The main
treatment is to try to teach her to know her such as crutches or canes, which she resists
own limitations and to use assistive devices, because she does not feel she needs them.
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Spasticity Assessment in
Cerebral Palsy 39
Lynn Bar-On, Jaap Harlaar, and Kaat Desloovere
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 586
Joint-Level Assessments to Infer About Muscle Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 586
Definitions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 587
Measurement Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 588
Measurement Errors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 589
Qualitative Assessment Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 589
Quantitative Assessment Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 590
Clinical Interpretation of Instrumented Assessments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 595
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 598
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 598
Abstract
L. Bar-On (*)
Department of Rehabilitation Sciences, KU Leuven, Spasticity is an important, but not the only,
Leuven, Belgium component contributing to the increased joint
Department of Rehabilitation Medicine, Laboratory for resistance experienced by children with spastic
Clinical Movement Analysis, MOVE Research Institute cerebral palsy. Conventional clinical spasticity
Amsterdam, VU University Medical Center, scales, based on physical examination of the
Amsterdam, The Netherlands passive muscle, are easy to apply in pediatric
e-mail: Lynn.baron@kuleuven.be
populations. Unfortunately, these have low
J. Harlaar reliability and are unable to differentiate
Department of Rehabilitation Medicine, Laboratory for
Clinical Movement Analysis, MOVE Research Institute between the different components of joint
Amsterdam, VU University Medical Center, hyper-resistance. To correctly differentiate
Amsterdam, The Netherlands spasticity from other neural and non-neural
Department of Biomechanical Engineering, Delft contributions, instrumented assessments that
University of Technology, Delft, The Netherlands integrate electrophysiological and biomechan-
e-mail: j.harlaar@tudelft.nl ical measures are required. In the last 15 years,
K. Desloovere great advancements in clinically applicable,
Department of Rehabilitation Sciences, KU Leuven, instrumented assessments were made.
Leuven, Belgium
e-mail: kaat.desloovere@kuleuven.be However, the translation from research to

https://doi.org/10.1007/978-3-319-74558-9_40
586 L. Bar-On et al.
clinical setting is lagging behind. Simple, assessments of the resistance during passive joint
yet accurate, instrumented assessments are rotation. Examples of such assessments include the
expected to greatly advance clinical practice maximum passive range of motion (ROM) assess-
in terms of treatment planning based on ment, the (Modified) Ashworth Scale (Bohannon
etiological classification and subsequent out- and Smith 1987), and the (Modified) Tardieu Scale
come evaluation. In addition, the transfer of (Tardieu et al. 1954). These examinations are clini-
the research findings to functional outcome cally used to assess the degree and nature of muscle
would require to extend our research agenda hyper-resistance. Moreover, in combination with
to include assessments of hyperreflexia in the other clinical assessments on impairment and func-
active muscle. Altogether these instrumented tional levels, it is regarded an important factor to
methods are not only needed to classify differ- inform decisions on treatment options (Boyd and
ent aspects of joint hyper-resistance but will Graham 1999). However, much doubt has been
also provide further insight into its pathophys- raised regarding the reliability and validity of such
iology enabling the development of future joint-level assessments (Malhotra et al. 2009;
treatment options for children with spastic Fleuren et al. 2010).
cerebral palsy. The difficulty of developing an assessment of
muscle impairment in CP is related to the degree
Keywords to which its findings represent the underlying
Cerebral palsy · Spasticity · pathology, i.e., what is actually being assessed?
Electromyography · Hyper-resistance · Firstly, a limited maximum passive joint ROM,
Instrumented assessment assessed with goniometry, is often interpreted in
terms of muscle contracture. However, any deduc-
tion of pathology in a single muscle based on this
Introduction assessment is confounded by other muscular and
nonmuscular soft tissue structures spanning the
Muscles in children with spastic cerebral palsy joint. Moreover, even when the other parallel
(CP) tend to have higher tone, hyperactive stretch structures are assumed not to contribute, passive
reflexes, and an altered structure. These alter- joint ROM only allows to infer about the length of
ations manifest themselves as muscle hyper-resis- a muscular tendon complex, whereas the proper-
tance or “increased resistance perceived during ties of the tendon, and not just the muscle belly,
passive muscle stretch” (van den Noort et al. will affect joint rotation. Although tendon pathol-
2017). Lower limb muscles that exhibit ogy has not extensively been studied in CP, its
hyper-resistance due to spastic CP are the properties and interaction with the muscle, both
mm. gastrocnemius, m. soleus, m. tibialis poste- during passive and active elongations, will affect
rior, mm. hamstrings, m. rectus femoris, muscle behavior (Kalsi et al. 2016).
mm. adductors, and the m. psoas. In the upper Secondly, in CP, both neural and non-neural
limb, spasticity is most frequently observed in components may contribute to any resistance to
the shoulder external rotators, the elbow, wrist muscle elongation during passive joint rotation.
and finger flexors, and the elbow pronators While these terms are very broad, neural compo-
(Klingels et al. 2012). nents generally refer to features originating from
the central nervous system resulting in increased
muscular activation. Such increased muscle acti-
Joint-Level Assessments to Infer About vation includes spasticity, defined by Lance as “a
Muscle Function motor disorder characterized by a velocity depen-
dent increase in tonic stretch reflexes (muscle tone)
Direct assessment of hyper-resistance of the distinct with exaggerated tendon jerks, resulting from
muscle during clinical examination is impossible. hyper-excitability of the stretch reflex, as one com-
Therefore, routine physical examination includes ponent of the upper motor neuron syndrome”
39 Spasticity Assessment in Cerebral Palsy 587
(Lance 1980). It is generally assumed that in spas- However, as will be further discussed in the next
tic CP, spasticity is the primary neurological com- section on existing clinical spasticity assessment
ponent contributing to muscle hyper-resistance. scales, any resistance that relies on an examiners’
This neurological feature is related to the lack of subjective interpretation cannot truly isolate spas-
inhibition of the stretch reflex and occurs as a ticity, and therefore, this is not a very useful def-
direct result of the upper motor neuron lesion. inition. To avoid equating all resistance to muscle
The hyperactive stretch reflex, which is elicited elongation during passive joint rotation with
during fast passive muscle elongation, such as in spasticity, it is important to clearly define all the
the (Modified) Tardieu Scale assessment, will expected neuromuscular responses to passive
result in involuntary muscle contraction. This muscle stretch separately.
pathological muscle contraction will resist the In 2005, a European Thematic Network to
movement of the manipulated joint, being felt by Develop Standardized Measures of Spasticity (the
the examiner. Next to spasticity also non-velocity- SPASM consortium) suggested the opposite and
dependent neural components may increase mus- broadened the representation of spasticity by defin-
cle tone by involuntary muscle contraction during ing it as: “disordered sensory-motor control,
joint manipulation (see below and “Introduction”). resulting from an upper motor neuron lesion, pre-
The non-neural component of increased resistance senting as intermittent or sustained involuntary
during passive examination is a result of changes activation of muscles” (Pandyan et al. 2005).
in the muscular tissue thought to be a result of Both the previously mentioned narrow definitions
tissue adaptations to the pathological neural regu- and this broader approach have shortcomings.
lation. Distinguishing between the neural and When translating research findings to the clinic,
non-neural contributors to muscle hyper- the narrow definition results in a compromise on
resistance is imperative for understanding disease internal validity due the inability to isolate spastic-
progression and for determining treatment options. ity. On the other hand, a broad definition hinders
the development of etiologically targeted treat-
ments. Rather than compromising and broadening
Definitions the definition, efforts should be directed at effec-
tively isolating and measuring the underlying path-
The definition of spasticity by Lance acknowl- ophysiological components in a clinical setting.
edges that spasticity is only one of the many The lack of consensus on the definition has
features of the upper motor neuron syndrome. especially led to the use of the terms hypertonia
Many reflex circuits such as proprioceptive, cuta- and spasticity interchangeably, which has resulted
neous (Burke et al. 2013), and nociceptive in further confusion. A review by Malhotra et al.
(Kamper et al. 2001) can be affected by an upper in 2009 highlighted the inconsistent use of the
motor neuron syndrome. These lead to a variety term spasticity in research articles. They found
of pathophysiological mechanisms that give rise that 31% of articles referred to the definition of
to involuntary muscle contractions. Therefore, in Lance, 35% equated spasticity with the term
clinical settings, different features are commonly hypertonia, 31% provided no definition, and 2%
assessed in combination and spasticity is, included their own definition (Malhotra et al.
wrongly, referred to in a broader sense (van den 2009). Due to the variations in definitions,
Noort et al. 2017). whether in clinical or scientific reporting, it is
In 2003, the North American Task Force for important either to clearly specify what is meant
Childhood Motor Disorders redefined spasticity by the different terms or to avoid them all together.
as: “a velocity dependent increase in hypertonia In the latest attempt to clear up the controversy
with a catch when a threshold is exceeded” regarding spasticity and its definition, from 2014
(Sanger et al. 2003). This description is a good to 2016, a European consensus study was
reflection of how spasticity can impede muscle performed. Rather than redefining spasticity, the
elongation during the physical examination. consensus aimed to summarize the neuromuscular
responses to passive muscle stretch in subjects background tone). The non-neural components
with an upper motor neuron syndrome. Thirty involve muscle tissue changes including increased
European clinicians and researchers participated. elasticity, viscosity, and shortening. Such adapta-
Using the Delphi approach for reaching consensus tions predominantly occur due to reduced muscle
(Hasson et al. 2000), a conceptual framework was growth (in terms of length and volume) and stiff-
defined as a guideline for understanding the neu- ening of the muscle tissue due to increased
romuscular responses to passive muscle stretch in amounts of extracellular matrix (Mathewson et al.
subjects with an upper motor neuron syndrome 2014). The consensus recommended being aware
and for designing the requirements of an assess- that muscle stiffness cannot directly be equated to
ment method to quantify the different contributing joint-level stiffness (the relation between joint
components (van den Noort et al. 2017). angle and joint moment) as it is not necessarily a
The term muscle hyper-resistance was con- reflection of the muscles intrinsic stiffness.
ceived in the meeting and defined as “increased As we will show, having a well-defined frame-
resistance perceived during passive muscle stretch.” work of unambiguous terminology of the neuro-
It was agreed that the neural and non-neural contri- muscular response to passive muscle stretch has
butions to hyper-resistance have to be distin- many advantages for the management of spasticity
guished. Furthermore, it was unanimously agreed in CP. Firstly, it facilitates communication between
that spasticity cannot be equated with hyper- patients and caregivers, clinicians, and researchers.
resistance but, given the definition offered by Secondly, it creates the requirements for developing
Lance, was a contributor. Therefore, it was valid, standardized, and objective clinical assess-
recommended that the term spasticity should only ments of muscle hyper-resistance and its compo-
be used next to the term “stretch hyperreflexia,” nents. Thirdly, it promotes the development of
thus helping to avoid its laden historical context. feature-targeted individualized treatment.
In conclusion, three subgroups of components
of hyper-resistance were defined in the consensus
(Fig. 1). The neural contributions were subdivided Measurement Methods
into stretch hyperreflexia (velocity dependent, e.g.,
spasticity) and involuntary background activation How to assess a phenomenon whose definition is
(non-velocity dependent, e.g., postural reflexes, not agreed upon has been a matter of debate for
non-selective activation, tonic reflexes, and fixed several decades. A thorough set of reviews on the
Fig. 1 Conceptual framework of pathophysiological neuromuscular responses to passive muscle stretch. (With permis-
sion from van den Noort et al. 2017)
topic were published in 2005 by the SPASM con- Tardieu Scale (MTS) (Boyd and Graham 1999),
sortium (Burridge et al. 2005; Voerman et al. are an established part of a standardized clinical
2005; Wood et al. 2005). Approaches to assess assessment for children with CP (Boyd and
the neuromuscular responses to passive muscle Graham 1999; Graham et al. 2000). Other clinical
stretch when the subject is at rest can be divided tools have also been suggested, but their sensitiv-
into clinical qualitative approaches and instru- ity to treatment effect is less investigated in CP
mented quantitative approaches. Quantitative (Jamshidi and Smith 1996; van den Noort et al.
approaches can further be divided into those 2010; Jethwa et al. 2010; Morris and Williams
methods that assess a neurophysiological 2018). The MAS is a qualitative 6-point ordinal
response to passive muscle elongation and scale to subjectively classify the resistance felt
those that assess the biomechanical response. during passive stretch (Bohannon and Smith
Furthermore, a distinction can be made between 1987). It has been developed for lower and
robotic designs where the passive limb is manip- upper limb muscles and is performed by moving
ulated by a motor-driven system and manual a joint passively through its ROM at one velocity.
designs, where an examiner applies the muscle The MTS is often performed on muscles that
stretches. The following section will briefly dis- score 1 or above on the MAS. During the MTS,
cuss the different methods. The literature regard- the angle (R1) at which a spastic catch is felt
ing instrumented, manually controlled spasticity during a quick passive stretch is defined relative
assessments is summarized in a systematic review to the maximum available ROM (R2) defined
(Bar-On et al. 2014b). when the joint is moved at slow velocity (Boyd
and Graham 1999). We prefer the MTS over the
MAS as it assesses the muscle reaction at two very
Measurement Errors distinct velocities, thus incorporating the velocity-
dependent characteristic of spasticity. However,
With any assessment method, it is important to both tests have been criticized for their low inter-
quantify and consider associated measurement rater reliability (Morris and Williams 2018). For
errors. Common sources of measurement error example, it has been shown that reliability of the
include inaccuracies in the measurement instru- MTS catch angle is compromised by the difficulty
ment, variability in the phenomenon being mea- of repositioning the distal segment after a catch in
sured, and, in case of manually performed order to read the angle using a goniometer (van
assessments, the individual taking the measure- den Noort et al. 2010). SEM values for passive
ments. Most measurement errors can be quantified ROM and for catch angles in lower limb muscles
using well-designed reliability studies. Such as assessed with the MTS are provided by Fosang
studies help establish standard error of measure- et al. (2003). Among six raters, the SEM values in
ment (SEM) and minimally detectable difference spastic hamstrings ranged from 6 to 10 for
(MDD) values that are imperative when inter- assessing the knee catch angle during fast passive
preting measurements results (de Vet et al. stretch with the MTS (Fosang et al. 2003). This
2006). For example, for a treatment effect to be translates to an MDD value of 20 (de Vet et al.
considered successful or unsuccessful, any post- 2006). To correctly infer the effect of treatments,
-treatment changes assessed with the instrument any post-treatment changes in the catch angle will
should at least be larger than the MDD. need to exceed this value. However, in a group
of 40 medial hamstring muscles treated with
botulinum toxin A and casting in children with
Qualitative Assessment Methods spastic CP, the average change in the MTS catch
angle post-treatment was only 5 (15 ) (Bar-On
The most common clinical spasticity assessment et al. 2014f).
scales, the Modified Ashworth’s Scale (MAS) Importantly, since no specific physiological
(Bohannon and Smith 1987) and the Modified phenomena are being assessed using these clinical
scales, the scales cannot convincingly differenti- responses. A commonly assessed example is
ate the neural from the non-neural components of the Hoffman reflex (H-reflex), elicited by
muscle hyper-resistance (Fosang et al. 2003; low-threshold electrical stimulation of a mixed
Biering-Sørensen et al. 2006; Haugh et al. 2006; peripheral nerve. Alternatively, a tendon tap will
Fleuren et al. 2010) thus limiting their construct elicit the tendon reflex (T-reflex), which follows
validity (Platz et al. 2005). The definition of spas- a similar pathway to that of the H-reflex, but
ticity as provided by Lance refers to the activation may also include the stretch reflex. Higher stimu-
of stretch reflexes. However, multiple studies lation intensity of the mixed peripheral nerve
have reported poor correlations between exagger- results in the production of an M-wave and the
ated stretch reflexes measured by electromyogra- eventual disappearance of the H-reflex. Lower H-
phy and the clinical assessment scales (Pandyan and T-reflex latencies and higher reflex ampli-
et al. 2001; Fleuren et al. 2010). In the highly cited tudes are indicative of increased α-motor neuron
article entitled “Stop using the Ashworth Scale,” excitability. The ratio of M-wave and reflex
Fleuren et al. were the first to unmask the con- amplitudes (Hmax/Mmax and Tmax/Mmax) has
struct validity of the Ashworth Scale using surface been used as a measure of spasticity. However,
electromyography (sEMG) and dynamometry. there is much overlap in the values of these ratios
They showed low associations of the Ashworth between healthy and spastic muscles, reducing
Scale with these simultaneously assessed electro- their diagnostic ability (Voerman et al. 2005).
physiological and biomechanical measurements Eliciting Mmax also requires a supramaximal
(Fleuren et al. 2010). Similarly, the MTS catch stimulation, which is uncomfortable and therefore
angle was found to have little association with rarely used in children.
increased work assessed at the joint (Gholami Neurophysiological responses can be com-
et al. 2017). Also disconcerting is the finding bined with measures of the biomechanical behav-
that some subjects diagnosed as having spasticity ior of muscles, joints, and limb segments. The
by the clinical scales showed no signs of increased most common way of doing this is recording
reflex activation as measured with EMG (Sinkjaer sEMG synchronized with recordings of angular
and Magnussen 1994; Galiana et al. 2005). velocity and joint moments during various,
Clinical scales can already be markedly improved well-defined conditions (such as electrical stimu-
by simultaneously measuring sEMG from the lation, passive oscillations and pendulum tests,
assessed muscle, which at least confirms the pres- ramp-and-hold stretches, or various types of
ence of hyperactive stretch reflexes. active movements) (Voerman et al. 2005; Wood
Given the important limitations of clinical et al. 2005).
scales, it is commonly agreed upon that more Highly sophisticated, motor-driven devices are
robust spasticity assessments that are valid, objec- the most accurate in standardizing and controlling
tive, and provide quantitative data are needed. joint trajectory and movement velocity. Modeling
Only through proper assessment can the mecha- the behavior of muscles to such systems provides
nisms underlying the pathology be efficiently insight into the different components contributing
addressed through treatment. to the measured hyper-resistance (de Vlugt et al.
2010; Gäverth et al. 2014; Sloot et al. 2015b).
However, these methods are deemed impractical
Quantitative Assessment Methods for clinical use, especially in pediatric popu-
lations. They may also be less representative
Passive Muscle Assessments of functional joint motion (Sloot et al. 2016).
Quantitative passive assessments can be divided Alternatively, several manually controlled
into those methods that assess the neuro- methods that integrate signals have also been
physiological response and those that assess developed (Pandyan et al. 2006; Fleuren et al.
the biomechanical response. Neurophysiological 2010; van den Noort et al. 2010; Wu et al. 2010;
assessments help quantify elevated reflex Bar-On et al. 2014b). These methods resemble the
clinical assessment scales but additionally collect angle; and work (the integral of joint moment
quantitative data using synchronized instruments. versus position) (Bar-On et al. 2014a). A similar
Collecting instrumented data during clinical application for the elbow flexors has been vali-
assessments provides the means to regulate per- dated for children with CP (Wu et al. 2010).
formance, creating a measure of standardization, The combination of EMG with biomechanical
as well as a method to decompose the sources signals (e.g., joint angle, angular velocity, angular
of measured hyper-resistance. Lately, the use of acceleration, net joint moment, or power) allows
manually applied instrumented spasticity assess- quantification and exploration of the biomechan-
ments in clinical trials involving children with ical triggers and effects of reflex activity. For
spastic CP is increasing (Flamand et al. 2013; example, by expressing the timing of EMG onset
Bar-On et al. 2014b; Pennati et al. 2016). in terms of joint angle, angular velocity, or angular
However, there is a paucity in reports on acceleration, a particular parameter of the neuro-
the associated measurement errors of outcome muscular system like the “spastic threshold” can
parameters hindering the transfer of instrumented be quantified (Calota and Levin 2009). In the
manual methods to the clinic. gastrocnemius and medial hamstring muscles, it
We developed a manual instrumented clinical was found that a reduced stretch-reflex threshold
assessment that combines neurophysiological and constrains peak muscle lengthening velocity dur-
biomechanical measurements for the lower limb ing gait in children with CP (Bar-On et al. 2014e).
muscles of children with CP (Bar-On et al. 2012a, Also, in preliminary work, lower spastic thresh-
b, 2014a, c, d, f). The method involves simulta- olds were associated with a poorer response
neous collection of sEMG, angular velocity, and to treatment with botulinum toxin A (Bar-On
net joint moment during ramp-and-hold passive et al. 2015).
joint manipulations through the full ROM. Study of the biomechanical signals following
Several parameters, extracted from signals EMG onset allows quantification of the effect
collected during the joint manipulations and of the reflex on the joint. An example is the catch
compared between movement velocities, have angle, which can be quantified in several ways (van
proven sensitive to distinguish between muscles den Noort et al. 2010; Wu et al. 2010; Bar-On et al.
with differing levels of hyper-resistance and to 2012a). The quantified catch was found to be the
the effects of treatment. Figure 2 shows examples most related to reflex activation when defined as the
of such signals collected during fast passive angular position corresponding to the first local
ankle rotations in three different children with minimum of power after a local maximum of
spastic CP. Despite being manipulated at similar power (with power defined as the product of
angular velocities, the EMG reactions and conse- angular velocity and joint moment) (Bar-On et al.
quent joint moment are markedly different 2012a) (Fig. 2). However, it should be realized
between subjects. In the first example, the EMG that the relationship between evoked EMG and
signal continues for a longer duration than in force production is not straightforward. Moment-
example 2 where only a short burst was recorded. related biomechanical parameters collected
In example 3, a clear clonus is triggered by the during passive stretch have proved to be less sensi-
manipulation. Examples of parameters that can be tive to the construct of spasticity than the simulta-
extracted from such data include the amount neously collected EMG-related parameters
of reflex hyper-activation (average root mean (Voerman et al. 2005; Pandyan et al. 2006;
square-EMG) (Bar-On et al. 2012b, 2014a); the Bar-On et al. 2012a). In the medial hamstring and -
degree of hypersensitivity to reflex activation gastroc-soleus, studies show less response
(the spastic threshold) (Bar-On et al. 2014c); to botulinum toxin A in the moment compared to
the presence, location, and severity of a spastic the EMG-related parameters (Bar-On et al. 2014a,
catch (Bar-On et al. 2012a); the type of muscle d, f). These findings suggest that these moment-
reflex activation pattern (phasic or tonic) (Bar-On related parameters may not adequately capture the
et al. 2014c); joint moment at a particular joint contribution of hyperactive reflexes to hyper-
592
Fig. 2 Electrophysiological and biomechanical signals collected during fast passive (AOC) is defined as the first local minimum of power after a local maximum of power.
stretches to the medial gastrocnemius from three different children with spastic cerebral Despite being stretched at a similar angular velocity, it can be appreciated that there is a
palsy. Time at EMG onset is indicated by the dotted vertical line. The angle of catch large variability between the signals collected from each muscle
L. Bar-On et al.
resistance. To do this, a more sophisticated decom- during controlled slow and fast full range ankle
position of the moment signal is required. rotations in typically developing subjects and sub-
Several models to decompose the net joint jects with spastic CP. The authors reported good
moment have been developed to better understand reliability of the extracted parameters that were
hyper-resistance (Sinkjaer and Magnussen 1994; sensitive to the effects of botulinum toxin A and
Galiana et al. 2005; Chung et al. 2008; de Vlugt selective dorsal rhizotomy (Sloot et al. 2015b).
et al. 2010; Lindberg et al. 2011), although only All three mentioned studies reported a large vari-
few have been applied in CP (de Gooijer-van de ability between patients and muscles in the con-
Groep et al. 2013; Willerslev-Olsen et al. 2013). tribution of stiffness and neural components to
The straightest forward of these models describe ankle joint resistance. Variability could not be
only the behavior of the non-neural components explained by measurement error or age differ-
of hyper-resistance, such as passive stiffness ences and may therefore reflect different clinical
(Harlaar et al. 2000) and viscosity (Meyer and phenotypes. This emphasizes the need to individ-
Lieber 2011). These non-neural components ually define the components of joint hyper-
have been extensively studied in both healthy resistance in order to better tailor treatment.
and hemiplegic subjects and have been previously Using a simplified version of the same model
described by polynomial or exponential mathe- as Sloot et al., Bar-On et al. (2014d) extracted the
matical models (Harlaar et al. 2000; de Vlugt neural component based on measurements from a
et al. 2010). More sophisticated mathematical manually controlled instrumented assessment
algorithms have additionally modeled the (Bar-On et al. 2014d). The model, which included
neural contribution to the resistance measured only stiffness and viscosity, was fitted to the joint
during passive stretch (Chung et al. 2008; de moment-position data collected at the ankle dur-
Vlugt et al. 2010; de Gooijer-van de Groep et al. ing low velocity full range manipulations. This
2013). De Gooijer-van de Groep et al. reported model was then fitted to stretches in which a
that reflex-related joint moment in the stretch reflex was evoked (high velocity manipu-
plantarflexors of children with CP was almost lations). The amount of deviation between
six times higher and tissue stiffness twice as high the modeled and measured moment during these
than that of controls (de Gooijer-van de Groep latter stretches represented the pathological
et al. 2013). Contradictory findings were reported neural component. This “deviation parameter”
by Willerslev-Olsen et al. where the majority was found to be repeatable between assessments
of assessed soleus muscles exhibited abnormal and to distinguish between healthy and spastic
non-neural-related stiffness, and only a minority muscle. Additionally, unlike the previously
showed a reflex-related joint moment that was described net joint moment-related parameters
higher than that of controls (Willerslev-Olsen containing both neural and non-neural compo-
et al. 2013). These contradictions may be a nents, the deviation parameter was found to
reflection of different perturbation methods decrease post-treatment with botulinum toxin A
(small (6 ) movements in de Gooijer-van de (Bar-On et al. 2014d). These methods help break
Groep et al. (2013) vs. ramp-and-hold rotations down the measured net moment into a clinically
over the entire range of motion in Willerslev- relevant representation of the contribution
Olsen et al. (2013)) and different joint moment of stretch reflexes to joint hyper-resistance.
decomposition models. Additionally, while de Unfortunately, model assumptions on the relation
Gooijer-van de Groep et al. (2013) included all between muscle lengthening and joint rotation
three plantarflexors, Willerslev-Olsen et al. prevent accurate and realistic estimates of the
(2013) analyzed only the soleus. Another example amount of muscle tissue stiffness that contributes
by (Sloot et al. 2015b) applied a modified model to joint hyper-resistance. To achieve this, a com-
(de Vlugt et al. 2010) with ten neuromuscular bination of muscle imaging to measure the actual
parameters to fit the relation between the ankle muscle belly lengthening from the different mus-
angle and the ankle net joint moment measured cles acting on the joint is required and is scope for
further study (Zhao et al. 2011; Haberfehlner et al. gait pathology among children with CP (Van
2016). Campenhout et al. 2014).
When quantifying muscular responses to The difference between passive and active
passive joint perturbations, it is important to muscle assessment lies in the role of the healthy
consider that the stretch-reflex response may stretch reflex. When a healthy relaxed muscle is
differ between muscles possessing different mor- suddenly stretched, stretch reflexes are inhibited
phology (e.g., mono- vs. biarticular, short vs. long by the central nervous system (CNS). In muscles
tendon, pennate vs. parallel). In a study carried out affected by CP, due to lack of CNS inhibition,
with a manual instrumented assessment on several the same stretch results in a hyperactive reflex
lower limb muscles in children with CP, we identi- response. In active muscle, these mechanisms
fied lower stretch-reflex thresholds and less are different. When a healthy active muscle is
velocity-dependent activation in the hamstrings and suddenly stretched, CNS inhibition is depressed
adductor muscles when compared to the gastrocne- such that stretch reflexes are activated. In active
mius and rectus femoris muscles (Bar-On et al. muscles affected by CP, the already depressed
2014c). Similarly, Kamper et al. found earlier reflex CNS inhibition cannot be depressed any further,
thresholds and greater reflex responses in the finger and thus stretch reflexes are also active. This
flexors than in the elbow flexors (Kamper et al. makes the distinction in stretch-reflex contribu-
2001). Activation differences between muscles tion to overall muscle resistance between healthy
may be caused by differences in central and periph- and affected muscles when activated less obvious
eral stretch-reflex modulation and/or by the differ- (Nielsen et al. 2005). The phenomenon is further
ent morphology. For example, muscle force complicated by task dependency of stretch-reflex
generation is influenced by muscle-specific proper- inhibition. For example, stretch reflexes play an
ties such as moment arm, cross-sectional area, and active contribution to joint stability during healthy
pennation angle. Differences may also reflect the stance phase of gait, but during swing, they are
dependence of a reflex response on joint position inhibited (Jansen et al. 2014). Furthermore, unlike
prior to stretch (Musampa et al. 2007). The rectus in the passive muscle, reflex regulation during gait
femoris and gastrocnemius have been found to be in pediatric populations is age-dependent, proba-
less sensitive when stretched from initially longer bly due to maturation of the central control of gait
lengths (Meinders et al. 1996), while in the ham- (Willerslev-Olsen et al. 2014).
strings, the opposite has been reported (Sheean Several research groups have sought to relate
2008). In biarticular muscles, the position of both neurophysiological measures (muscle activation)
joints is important when considering length depen- to biomechanical measures (muscle lengthening)
dency (Musampa et al. 2007). Therefore, subject using instrumented 3D gait analysis. 3D gait anal-
positioning and measurement setup are important ysis involves the simultaneous capture of joint
confounders when assessing spasticity and must be kinematics using a motion analysis system. Joint
standardized for each specific muscle being kinematics entered into musculoskeletal models
assessed. can be used to derive muscle lengths and muscle
lengthening velocities during gait (Delp et al.
Active Muscle Assessments 2007). Capturing ground reaction forces with
The ultimate goal of spasticity management in CP force plates embedded into the walkway enables
is to improve function, such as gait. Since joint the computation of net moment around each joint,
hyper-resistance in CP has mainly been assessed computed using inverse dynamics. Lastly, muscle
in response to imposed stretches on relaxed activity during gait can be simultaneously
muscle, little is known about the role of hyper- recorded using sEMG.
resistance during purposeful movements involv- As spasticity is velocity dependent, it is pre-
ing voluntary muscle contraction. Consequently, sumed that a faster muscle lengthening velocity
the level of hyper-resistance assessed in relaxed during gait triggers stretch reflexes in a spastic
muscles cannot fully explain the variability in muscle. Therefore, one approach to evaluate the
effect to spasticity on gait has been to record the to heel strike in children with CP and controls.
changes in muscle length and sEMG data with The authors therefore argue that spasticity is
increasing walking velocity (van der Krogt et al. unlikely to contribute to foot drop and toe walking
2009; Van Campenhout et al. 2014). However, it in children with CP. Rather, they proposed that
has been found that children with CP apply similar altered central drive to the ankle muscles and
mechanisms to increase walking speed as typi- increased passive muscle stiffness are the main
cally developing children (Schwartz et al. 2008; causes of foot drop and toe walking (Willerslev-
Van Campenhout et al. 2014). Therefore, isolating Olsen et al. 2014).
the effects of spasticity from those changes The debate about the contribution of each com-
required to increase walking velocity has proven ponent to joint hyper-resistance during movement
challenging. continues because it remains hard to experimen-
A more direct approach to assess spasticity tally assess in vivo muscle function. Therefore,
during gait is to examine the motor output more comprehensive datasets are required (e.g.,
(EMG) over the lengthening phases of the dynamic ultrasound imaging combined with
involved muscle groups (Crenna 1998; EMG in a variety of different passive and active
Lamontagne et al. 2001; van der Krogt et al. muscle conditions) complemented by neuro-
2009, 2010). Studies that have followed such an musculoskeletal modeling. The assessment of
approach have shown that during particular hyperreflexia in the active muscle is needed such
phases of the gait cycle, the relationship between that future research findings can be used to opti-
EMG and muscle lengthening velocity differs mize the functional outcome of children with
between typically developing children and chil- spastic CP. This requirement necessitates broad-
dren with CP (Crenna 1998; van der Krogt et al. ening our research agenda.
2010). Sloot et al. (2015) investigated whether
belt accelerations and decelerations of five differ-
ent intensities applied during the stance phase of Clinical Interpretation of Instrumented
treadmill walking evoked reflexes in the gastroc- Assessments
nemius, soleus, and tibialis anterior in healthy
subjects (Sloot et al. 2015a). They found clear In contrast to the clinical scales whose outcome
changes in muscle length and stretch velocity is limited to ordinal subjective scoring,
relative to unperturbed walking and that stretched instrumented assessment, capturing both the bio-
muscles showed a surplus in muscle activity, i.e., mechanical and electrophysiological reactions to
EMG bursts on top of the reference activity fol- passive muscle stretch, potentially yields relevant
lowing perturbation, exposing a clear stimulus information to identify etiology of joint hyper-
response relation (Sloot et al. 2015a). This method resistance. As an example, in this section, we will
of evoking stretch reflexes during gait now needs present data collected from two clinical cases
to be investigated in children with spastic CP. In a concerning spastic cerebral palsy where clinical
more complex setup in children with CP and and instrumented data were collected during pas-
controls, Willerslev-Olsen et al. (2014) used an sive ankle joint manipulation. Case 1 is a 5-year-
orthotic device during treadmill walking to old girl with spastic right hemiplegia, and case 2 is
directly apply an ankle perturbation to the soleus an 8-year-old girl with spastic left hemiplegia. Both
muscle, either lengthening or shortening it during children received intramuscular injections of botu-
crucial phases of the gait cycle (Willerslev-Olsen linum toxin A to the medial gastrocnemius as part
et al. 2014). They reported that short-latency of a multilevel treatment. Injections were followed
reflexes were enhanced in children with CP, by 2 weeks of lower leg casting and intensive
while long-latency reflexes were depressed. physical therapy. The children were assessed with
Given the aforementioned role of healthy stretch the MAS, with the MTS, and with an instrumented
reflexes during the gait cycle, this resulted in the assessment (Bar-On et al. 2012b), before and about
same amount of m. soleus muscle activation prior 8 weeks after treatment.
Fig. 3 Medial gastrocnemius rms-EMG and net ankle joint moment collected during slow (gray) and fast (black)
velocity ankle angle rotations pre- and post-treatment with Botulinum toxin A (BoNT-A)
Results from the clinical and instrumented the same angular velocity. Furthermore, changes
assessments can be found in Fig. 3 and Table 1. post-treatment were detected with the
Pre-treatment assessment with the clinical scales instrumented tests, but not with the clinical scales.
resulted in the same values being assigned to the Given the variable response to treatment
muscles. The parameters calculated from the between the clinical cases, it is worthwhile to
instrumented assessments for the two clinical investigate whether instrumented assessments
examples clearly reflect the effect of increasing can help us understand this. The 3D graphs in
stretch velocity on acquired root means square of Fig. 4 illustrate the degree of length dependency
the EMG (rms-EMG) signal and on the resulting versus velocity dependency of muscle activation
ankle joint moment. Unlike the clinical sores, the in the medial gastrocnemius during passive ankle
values established for the two clinical examples dorsal flexion of the two clinical cases pre-
are markedly different, despite being stretched at -treatment. On the y-axis, three different angular
Table 1 Details of clinical and instrumented assessments in two clinical examples

Clinical case 1 Clinical case 2
Age 5 years old 8 years old
Diagnosis Spastic CP, right Spastic CP, left
hemiplegia hemiplegia
Amount of injected botulinum toxin A in medial gastrocnemius as part 3 U/kg 3 U/kg
of multilevel treatment
Gastrocnemius Modified Ashworth’s Scale score
Pre-treatment 1+ 1+
Post-treatment 1+ 1+
Gastrocnemius catch angle (Modified Tardieu Scale)
Pre-treatment 15 15

Post-treatment 15 10
Average rms-EMG from the medial gastrocnemius during fast passive stretch minus average rms-EMG during slow
passive stretch
Pre-treatment 6.65 μV 4.42 μV
Post-treatment 1.96 μV 4.10 μV
Net ankle joint moment assessed at 0 during fast passive stretch minus value at 0 during slow passive stretch
Pre-treatment 3.40 Nm 1.98 Nm
Post-treatment 1.03 Nm 3.25 Nm
Fig. 4 Average normalized rms-EMG measured during equally spaced position zones spanning 10–90% of the
joint motions applied passively to the ankle at three joint joint range of motion (ROM)
angular velocities (low, medium, and high) across three
velocities are represented. On the x-axis, the ankle calculated. These values were normalized by
ROM has been divided into three equal zones expressing them as a percentage of the peak
between 10% and 90% of the joint’s ROM from rms-EMG value of three maximum voluntary
plantar to dorsal flexion. The zones are defined contractions (Bar-On et al. 2014c). Inspecting
as the time windows corresponding to 10–36.6% the 3D graphs, it can be seen that in case 1, the
ROM, 36.6–63.3% ROM, and 63.3–90% ROM. muscle reacts only when lengthened at very high
Average rms-EMG per position zone was velocity. On the other hand, in case 2, activation
occurs already during a slow stretch, with the ▶ Focal Management of Spasticity in Cerebral
amount of activation increasing with increased Palsy
joint ROM. Interestingly, pilot studies have ▶ Gait Analysis Interpretation in Cerebral Palsy
shown that muscles with larger amounts of Gait: Developing a Treatment Plan
length-dependent activation also tended to be ▶ Muscle Changes at the Cellular-Fiber Level in
poorer responders to treatment with botulinum Cerebral Palsy
toxin A, both in terms of the reduction in ▶ Measuring Outcomes in Children with Cerebral
rms-EMG post-treatment as assessed during pas- Palsy
sive stretch and on gait kinematics (Bar-On et al. ▶ Muscle Changes at the Cellular-Fiber Level in
2015). In the presented clinical examples, case Cerebral Palsy
1, with a more velocity-dependent activation pat-
tern, reacted better to treatment than case 2, whose
pre-treatment activation pattern showed more References
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Medical Management of Spasticity
in Children with Cerebral Palsy 40
Maura McManus
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 602
Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 604
Treating Spasticity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 605
Therapy Services . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 605
Bracing and Positioning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 605
Chemodenervation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 605
Oral Medications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 606
Intrathecal Baclofen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 607
Neurosurgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 607
Orthopedic Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 608
Summary Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 608
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 608
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 609
Abstract probably due to an imbalance between inhibi-

Spasticity is the most common motor disorder tory and excitatory impulses in the spinal cord.
in cerebral palsy (CP). It is a component of the In CP, there is believed to be a deficiency of
upper motor neuron syndrome. Spasticity is descending impulses that typically stimulate
the release of the inhibitory neurotransmitter
gamma-aminobutyric acid (GABA). Although
some spasticity may be necessary for function
M. McManus (*)
Nemours Alfred I Dupont Hospital for Children, in children with neurologic impairment, it is
Wilmington, DE, USA often a problem that can be difficult to treat.
e-mail: mmcmanus@nemours.org; Multiple approaches are available for treatment
Maura.McManus@nemours.org

https://doi.org/10.1007/978-3-319-74558-9_41
602 M. McManus
of spasticity in patients with CP including ther- Pathophysiology

apies, oral medications, chemodenervation,
and intrathecal baclofen therapy. Orthopedic The physiology of spasticity includes the stretch
and neurosurgical procedures are also avail- reflex which is the basic neural mechanism
able. A multidisciplinary team should be responsible for maintaining muscle tone. It is
involved in defining reasonable treatment mediated in large part by monosynaptic connec-
goals including the patient, and family, tions in the spinal cord. Excitability of the stretch
physical and occupational therapists, nurses, reflex depends critically on descending control
physiatrist, neurologist, orthopedist, and from higher brain centers. This reflex can be tested
neurosurgeon. by tapping the patella tendon (Rymer and Katz
1994). The basic circuitry of the stretch reflex
Keywords includes a skeletal muscle being stretched which
Spasticity · Cerebral palsy · Function · leads to stretch of the muscle spindle that stimu-
Chemodenervation lates sensory ending Ia which monosynaptically
excites alpha motor neurons to the same muscle
from which they arise and to motor neuron of
Introduction synergistic muscles. This also inhibits the motor
neurons to antagonist muscle inhibitory interneu-
In patients with cerebral palsy, spasticity is ron. Gamma motor neuron functions to adjust the
the most common motor disorder and is seen length of the intrafusal fibers to allow it to be
in approximately two thirds of the population ready for the next stretch (Gilman and Newman
(Gans and Glenn 1990). It is part of the upper 1987) (Fig. 1).
motor neuron syndrome and is often defined as a Several supraspinal pathways are felt to be
velocity-dependent increase in resistance to pas- involved in the control of muscle tone. Cortex,
sive stretch associated with increased deep ten- basal ganglia, and cerebellum all provide
don reflexes (Lance 1980). Spasticity is noted in important modulation of brainstem structures in
children with other neurologic impairment as normal motor control. Selective destruction of
well including brain injury and spinal cord injury. corticospinal tracts does not result in spastic
It is probably due to an imbalance between inhib- hypertonia but rather hypotonia. Interruption of
itory and excitatory impulses in the spinal cord. extrapyramidal fibers is likely needed before
In CP, there is believed to be a deficiency of spastic hypertonia develops (Katz and
descending impulses that typically stimulate the Campagnolo 1994). Possible mechanisms for
release of the inhibitory neurotransmitter spasticity include increased neuronal excitation
gamma-aminobutyric acid (GABA). GABA acts because of loss of inhibitory effects of descending
presynaptically to inhibit the release of excitatory tracts. Also alterations in segmental interneural
neurotransmitters such as glutamate and aspar- responsiveness and changes in segmental reflex
tate, resulting in relative excess of excitatory function are likely play a role in these changes in
impulses and resultant hypertonia (Gormley tone (Sheean and McGuire 2009). The pontine
1999). Some spasticity is necessary for function reticulospinal tract and vestibulospinal tract are
in children with neurologic impairment, but it excitatory tracts, while medullary reticulospinal
can also be a difficult problem to treat. Multiple tract is an inhibitory tract. pyramidal tracts are
approaches are available for treatment of spastic- involved in muscle strength. The synaptic effects
ity in patients with CP including therapies, of descending pathways may be categorized as
oral medications, chemodenervation, and intra- mediating changes in the excitability of spinal
thecal baclofen therapy. Orthopedic and neuro- motoneurons and/or as mediating changes in the
surgical procedures are also available (Ried et al. responses of segmental reflex pathways (Katz and
1998). Campagnolo 1994).
40 Medical Management of Spasticity in Children with Cerebral Palsy 603
Fig. 1 Stretch reflex
Fig. 2 Percentage of
children with CP with
spasticity in gastroc-soleus
muscle group as grade 2 or
more on Modified
Ashworth Scale related to
age (Hagglund and Wagner
2008)
There are felt to be differences in spinal and primitive reflexes, and clonus. Negative signs
cerebral spasticity. Spinal spasticity is thought to include weakness, fatigue, and poor dexterity
be due to removal of inhibition on segmental (Gormley 1999). It is important to be able to
polysynaptic pathways which lead to a slow, pro- recognize all of these signs, not just spasticity, as
gressive rise of excitatory state. Afferent activity they all impact function. Spasticity may cause
from one segment may lead to muscle response pain, limit sleep, lead to joint deformity, and inter-
many segments away. Flexor and extensor mus- fere with function. It may also interfere with care
cles may be excited. Cerebral spasticity is thought including transfers, toileting, bathing, and dress-
to be due to enhanced excitability of monosynap- ing (Krach 2001). In children with cerebral palsy,
tic pathways which lead to a rapid buildup of spasticity is typically not a problem during the
reflex activity. There is a bias toward over activity first 6 months of life. It can be noted between
in antigravity muscles (Katz 1988). 6 and 24 months. A baby with cerebral palsy
Spasticity is felt to be part of the upper motor may actually be quite floppy during first 6 months
neuron syndrome. This is an abnormal motor (Miller and Bachrach 2017). Spasticity may
function secondary to lesions in cerebral cortex, become more obvious as their nervous system
subcortex, or spinal cord. There are positive signs matures, such as with increased myelination. In
including increased muscle tone, hyperreflexia, 2008, data from Hagglund and Wagner’s CP
604 M. McManus
Table 1 Modified Ashworth Scale and modified Tardieu Scale

Modified Ashworth Scale:
0 No increase in tone
1 Slight increase in tone with catch or minimal resistance at end of ROM
1+ Slight increase in tone with minimal resistance through less than half of ROM
2 Marked increase through most of ROM
3 Considerable increase, PROM difficult
4 Rigid in flexion and extension
Modified Tardieu scale:
R2 – The angle of full ROM when velocity of stretch is as slow as possible
R1 – The angle of muscle reaction when velocity of stretch is as fast as possible
Spasticity angle = R2–R1
Large spasticity angle indicates a greater degree of spasticity (dynamic component)
Smaller spasticity angle indicates a greater degree of contracture
group in Sweden described the natural history of there are often other functional issues that a
spasticity. They reported that in children with CP, patient is dealing with at the same time including
muscle tone increases up to 4 years of age and weakness, fatigue, and poor dexterity. Impaired
then decreases up to 12 years of age (Fig. 2). balance and motor planning are also common
issues in this population. It is important to be
able to recognize all of these, not just spasticity,
Assessment as they all impact function. Treating one of these
issues does not necessarily improve another.
Multiple approaches are available for the evaluation A family needs to know that treating spasticity
and treatment of spasticity in patients with CP. The will not improve motor planning, for example.
goals for treatment should be realistic You, as a provider, need to be able to describe
and individualized, and they need to be agreed and define these different elements of function to a
upon by patient, family/caregiver, and medical patient and family. One of the most important
team. Ideally, a multidisciplinary team should be issues to understand when a patient comes to
involved in the decision-making. Such a team you for treatment of spasticity is how much weak-
should include patient, family, physical and occu- ness is present in these spastic muscles. Many
pational therapists, nurse, physiatrist, neurologist, children with CP who have spasticity and func-
orthopedist, and neurosurgeon (Massagli 1991). tionally stand and/or take steps are using some of
Clinical assessment requires an understanding of their spasticity to maintain their upright functional
motor patterns such as co-contractions, synergy position. Taking too much tone away from such a
patterns, and static vs. dynamic tone. One needs to patient may significantly decrease their overall
appreciate the chronicity and severity of the spas- function.
ticity. The distribution and location are important. There are scales that have been developed
You must understand what muscles are involved. to measure tone. The Ashworth Scale or the
The approach to treatment is different for general- Modified Ashworth Scale are often used to
ized versus localized spasticity. It is very important quantify spasticity but are not always able to
to understand what noxious stimuli can increase distinguish between spasticity and soft tissue
spasticity such as joint pain or a urinary tract infec- tightness (Damiano et al. 2002). The Tardieu
tion. You need to treat what is causing the noxious Scale or Modified Tardieu Scale is better at
stimuli before trying to reduce the tone directly. this distinction but is not as good at quantify-
Since spasticity is part of the upper motor ing in a clinical setting (Sheean and McGuire
neuron syndrome, we need to remember that 2009) (Table 1).
Treating Spasticity Scale and Modified Tardieu Scale to measure

tone (Sheean and McGuire 2009). They also use
Consider treating spasticity if it is interfering with many functional assessment scales such as Gross
some level of function, care, or comfort. This Motor Function Measure (GMFM) (Miller 1998)
may include a need to alleviate pain, improve and Pediatric Functional Independence Measure
hygiene, or decrease caregiver burden. It is appro- (WeeFIM) (Krach et al. 2015) as well as Shriner’s
priate to treat spasticity to prevent complications Hospital Upper Extremity Evaluation (SHUEE)
such as pressure ulcers and joint contractures. and Quality of Upper Extremity Skills Test
Working through spasticity to enhance function (QUEST) (King 2005). These tools are also help-
for a patient with CP can be challenging. ful in measuring the effectiveness of certain inter-
Treatments that are available include physical and ventions. It can be helpful for families to learn a
occupational therapy, orthoses, oral medications, home exercise program to allow for carryover. As
chemodenervation, intrathecal baclofen, orthope- children with spastic cerebral palsy get older and
dic surgery, and neurosurgery. Many children various surgical interventions are performed, the
with spastic cerebral palsy receive multiple inter- therapeutic intervention increases in the commu-
ventions especially throughout their growing years. nity and sometimes in the school setting.
Since stretching, splinting, and positioning are con-
sidered the first-line approach to treatment, physi-
cal and occupational therapists typically meet Bracing and Positioning
patients very early. These other medical and surgi-
cal interventions can be used in conjunction with In a patient with spasticity, orthoses/splints can
these therapies when further tone reduction is felt help to improve function, optimize joint alignment,
to be necessary (McMahon et al. 2015). Noting a control abnormal tone, prevent soft tissue defor-
patient’s medical comorbidities is necessary so as mity, and protect tissues postoperatively. Ankle-
not to complicate other medical issues while foot orthoses (AFO) can be solid, articulating,
treating spasticity. For example, when used in com- static, or dynamic. Improvement in joint
bination with anticonvulsants, muscle relaxants position and function are often seen with these.
can significantly increase risk of sedation. Knee-ankle-foot orthoses (KAFO), although less
commonly used in CP, can be very helpful for
standing and transfers. Upper extremity splints
Therapy Services include wrist/hand resting splint, cock-up splint,
and opponens splint. Upper extremity static splints
Physical and occupational therapies are essential are more common than dynamic splints as the latter
to patients dealing with spasticity. Many children often decrease sensory feedback during functional
with cerebral palsy have had the support of ther- activities and children can be reluctant to use them
apists since they were in the NICU. These services (Miller 1998). Appropriate seating systems that
can fortunately extend into a patient’s home at help to reduce tone are essential including wheel-
discharge from the nursery in the form of Early chairs and feeding chairs (Gans and Glenn 1990).
Intervention Services. The first-line treatment
includes therapeutic exercises that focus on
stretching, strengthening, splinting, and position- Chemodenervation
ing. By 12–24 months the spasticity in CP is
usually much more obvious, and therapy interven- Botulinum toxin (BoNT) injections, motor point
tion may need to become more intensive. Various blocks, and nerve blocks are used to treat local-
physical modalities such as heat/cold and func- ized spasticity. Botulinum toxin type A or B is a
tional electrical stimulation (FES) have been neurotoxin released by clostridium botulinum. In
noted to be helpful. Therapists use tools, as the USA, three toxins are available on the market,
described above, such as Modified Ashworth Botox, Myobloc, and Dysport. Botox and Dysport
606 M. McManus
are BoNT type A and Myobloc is BoNT type B has been in patients with spinal cord injury and
(Sheean and McGuire 2009). BoNT acts presynap- multiple sclerosis. Sedation is the most disabling
tically at the neuromuscular junction to block the side effect especially for someone with spasticity
release of acetylcholine. These nerve terminals do of cerebral origin. These can have a very long
not regain function. In 3–6 months, new nerve half-life due to active metabolites. The use of
terminals grow secondary to collateral axonal benzodiazepines may lead to physical dependence
sprouting. Limit treatment to no more frequently (Katz and Campagnolo 1994).
then every 3 months, secondary to risk of antibody Baclofen is a GABA analog that acts at the
formation. All muscle identification techniques presynaptic level in the spinal cord and interferes
begin with anatomical localization, but some with the release of excitatory neurotransmitters. It
providers also use supplemental techniques to is lipophilic and crosses the blood-brain barrier
maximize the accuracy of needle placement. poorly; as a result large doses may be necessary to
These techniques include electromyography see an effect. It has been noted to be most effective
(EMG) guidance, EMG auditory signal amplifiers in patients who have spasticity of spinal origin
(EMG-SA) (Walker et al. 2015), electrical stimula- including spinal cord injury. There is limited evi-
tion, and ultrasound guidance (Henzel et al. 2010). dence that oral baclofen improves function and
Alcohol motor point blocks and nerve blocks even some evidence that some GABAergic med-
involve a chemical neurolysis that denatures pro- ications may impair function. Overdose may lead
tein in the myelin sheath of a nerve. 3% or 5% to respiratory suppression, hypotension, and bra-
phenol are most commonly used. It is generally dycardia. Abrupt withdrawal could lead to mental
performed with conscious sedation. There is a risk status changes or seizures (Krach 2001).
of painful dysesthesias. You need to use electrical Dantrolene sodium acts directly on muscle,
stimulation for guidance to get as close as possible decreasing release of calcium from sarcoplasmic
to motor point (Gormley 1999; Elovic et al. 2009). reticulum. It is rarely used to decrease spasticity in
patients with cerebral palsy as there is limited evi-
dence in literature that it is effective in this popula-
Oral Medications tion. The potential for the serious side effect of
hepatotoxicity can also limit its use. Liver function
Several oral medications have been used to tests should be done before starting treatment and
reduce spasticity including diazepam, baclofen, periodically while taking the medication (Katz and
dantrolene sodium, tizanidine, and clonidine. Campagnolo 1994).
Although they can decrease spasticity, their sedating Clonidine is a centrally acting alpha
side effects are not well tolerated in children 2-adrenergic agonist that is felt to decrease sym-
(Massagli 1991). None of these medications have pathetic outflow from the brain. At the spinal cord
been universally effective in treating spasticity. Bac- level, its effects are thought to be related to both
lofen has been noted to be moderately helpful when presynaptic inhibition of sensory afferents and
taken orally for spasticity of spinal origin in adults. inhibition of the release of glutamate, which is
It has been relatively unhelpful in treating spasticity an excitatory amino acid. It is lipophilic and
of cerebral origin, especially in children with crosses the blood-brain barrier poorly. While an
CP. Intrathecal baclofen has been shown to reduce enteral form is available, it is also very effective in
spasticity with fewer side effects (Watanabe 2009). the form of a transdermal patch that is changed
Diazepam is the most frequently used benzo- every 5–7 days. Side effects are hypotension,
diazepine and is one of the oldest antispasticity bradycardia, and sedation (Watanabe 2009).
medications in use today. It has an inhibitory Tizanidine is a newer alpha 2-agonist that is
effect at spinal cord level and at the supraspinal chemically related to clonidine. It binds to receptors
level. It acts postsynaptically, and while it doesn’t at spinal and supraspinal levels. At the spinal level, it
bind directly to GABA receptors, it increases increases presynaptic inhibition of motor by decreas-
GABA’s affinity to bind to GABAa receptors. ing the release of excitatory amino acids. It is more
The greatest clinical efficacy of benzodiazepines commonly used in spasticity of spinal origin rather
Table 2 Medications used to treat spasticity in children

Drug Mechanism of action Side effects/precautions
Diazepam Has an inhibitory effect at spinal cord and at CNS depression with sedation, impaired
supraspinal level. It acts postsynaptically to cognition, long half-life
increase GABA’s affinity to bind to GABAa
receptors
Baclofen GABA analog that acts at the presynaptic level in Sedation, overdose may lead to respiratory
the spinal cord and interferes with the release of suppression, hypotension, and bradycardia
excitatory neurotransmitters Abrupt withdrawal can cause seizures
Dantrolene Acts directly on muscle decreasing release of Risk of hepatotoxicity
sodium calcium from sarcoplasmic reticulum Must monitor LFTs
Clonidine Centrally acting alpha 2-adrenergic agonist that Sedation, hypotension, bradycardia
acts both in brain and spinal cord by enhancing
presynaptic inhibition and decreasing excitatory
output. Transdermal patch form available
Tizanidine Alpha 2 agonist that acts both in the brain and Sedation, hypotension
spinal cord by enhancing presynaptic inhibition
and decreasing excitatory output
than spasticity of cerebral origin. Improvements in determine whether someone is a good candidate
tone have been noted, but there is limited evidence for intrathecal baclofen therapy. Baclofen is an
on improvements in function (Watanabe 2009). analog of GABA, and when delivered intrathe-
One controversial treatment is cannabis or tet- cally, it can diffuse to where GABAB receptors are
rahydrocannabinol (THC) which is the main believed to be located in the brain and spinal cord
active ingredient in cannabis. Cannabinoids have (Keenan et al. 2000). Intrathecal baclofen pump is
been shown to have efficacy in treating spasticity implanted for delivering a continuous infusion of
of spinal origin and are currently being studied. baclofen directly into the spinal fluid. This treat-
Some literature supports the hypothesis that the ment works very well in quadriplegic CP patients
relaxing effect of marijuana on muscles in patients and also diplegic CP patients (Armstrong 1992). It
with spasticity of spinal origin is due to an anti- involves mcg dosing. The pump reservoir is
spastic effect, perhaps inhibition of polysynaptic refilled by percutaneous puncture through a sep-
reflexes, rather than simply due to a general relax- tum in the pump at intervals of 1–6 months
ation response. It is not routinely used in children depending on the rate of delivery. Topical anesthetic
with CP at this time (Adams and Hicks 2005). cream can be used to numb the skin over the pump
As mentioned earlier, understanding a patient’s refill site to make the procedure more comfortable for
medical comorbidities is necessary so as not to com- the pediatric patient. Dosage adjustments are made
plicate other medical issues while treating spasticity. via an external programmer and transmitted to the
For example, many muscle relaxants can cause con- pump by a handheld radiofrequency wand. The
stipation and urinary retention. When used in com- pump can be programmed to deliver the baclofen
bination with anticonvulsants, muscle relaxants can in several modes including simple continuous infu-
significantly increase risk of sedation (Table 2). sion, complex continuous infusion (i.e., rate changes
at set times during the day), and bolus infusion mode
(Medtronic, Inc., Minneapolis, MN 2017).
Intrathecal Baclofen
Intrathecal baclofen has been found to be very Neurosurgery

helpful in patients with cerebral palsy who
have significant generalized spasticity (Albright Neurosurgical options for spasticity include
et al.1993). It has also been noted to help to selective dorsal rhizotomy (SDR). This involves
decrease dystonia in this population (Albright sectioning a portion of sensory rootlets. It is
et al.1996). Careful assessment is needed to typically restricted to lumbosacral plexus
608 M. McManus
L1–L2 to S1–S2. Approximately 40% sensory these are in a series over a few years. In ambula-
nerves are sectioned. The idea is to decrease the tory patients, orthopedic surgery may be consid-
sensory input which then decreases the motor ered during middle childhood. If a child is noted to
output. Extensive therapies after this procedure have significant generalized spasticity, intrathecal
have been felt to be helpful in maximizing out- baclofen therapy may be considered. Depending
come. One meta-analysis described the ideal on the needs over time, the interventions may
candidates as children between 3 and 8 years change.
of age and GMFM level III or IV. For severe
spastic quadriplegia, this procedure has been
attempted for comfort and to decrease caregiver
burden, with less success (Abbott 1996). Meta- Conclusion
analysis of SDR patients demonstrated that if
there is any benefit, it is only in a few points of Treat spasticity only if it is a problem. While some
improvement and not dramatic functional spasticity may be necessary for function in chil-
improvements. Use of intrathecal baclofen in dren with neurologic impairment, it is often a
the pediatric patient having CP has yielded as problem for which patients and families seek
good a reduction in tone as dorsal rhizotomy and treatment. Since spasticity is part of the upper
does not represent an ablative procedure. This is motor neuron syndrome, we need to remember
important because, unlike rhizotomies, intrathe- that there are often other issues that a patient is
cal baclofen therapy is entirely reversible dealing with at the same time including weakness,
(Albright et al. 1995). fatigue, and poor dexterity. Impaired balance and
motor planning are also common in CP. It is
important to be able to recognize all of these
Orthopedic Surgery issues not just spasticity, as they often all impact
function. Treating one of these issues does not
Spasticity in children with cerebral palsy often necessarily improve another. Multidisciplinary
leads to muscle imbalance with joint deformities team approach is always the most helpful. This
and bony changes. Surgical goals range from team includes the patient, family/caregiver,
improved comfort to maximizing function. Ortho- nurses, therapists, and physicians who work
pedic surgery for the management of spasticity can closely together to set appropriate goals for
include tendon releases, muscle lengthenings, treatment.
osteotomies, tendon and muscle transfers, arthrod-
esis, and spinal fusion (McMahon et al. 2015).
Depending on goals of surgery, postoperative ther-
apies might be recommended. Cross-References
▶ Dorsal Rhizotomy for Spasticity Management

Summary Discussion in Cerebral Palsy
▶ Focal Management of Spasticity in Cerebral
Managing spasticity can be challenging through- Palsy
out the life of a child with CP. In a very young ▶ Intrathecal Baclofen Therapy: Assessment and
child, under the age of 3 years, we focus on Medical Management
physical and occupational therapy techniques. ▶ Intrathecal Medication Administration in Cere-
As mobility advances we often add AFO’s to bral Palsy
help improve functional gait. As tone increases ▶ Motor Control and Muscle Tone Problems in
over time, if it interferes with function, comfort, or Cerebral Palsy
care, we consider Botox injections. Sometimes ▶ Spasticity Assessment in Cerebral Palsy
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Focal Management of Spasticity
Freeman Miller
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 612
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 613
Effects of Spasticity on Nerves . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 613
Effects of Spasticity on Muscles and Tendons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 614
Effects of Spasticity on Bones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 615
Functional Effects of Spasticity on Sitting, Gait, and Activities of Daily Living . . . . . . 616
Treatments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 616
Peripheral Nervous System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 616
Neuromotor Junction and the Muscle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 617
Alcohol and Phenol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 621
Direct Surgical Treatment of the Musculotendinous Unit . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 621
Orthotics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 622
Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 623
A Global Approach to Managing Spasticity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 623
Cases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 625
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 626
Abstract this response over reacts and it develops path-

Spasticity is the most common presentation ologic spasticity which causes impairment.
of all neurologic alterations in children with Therefore, when treating children with spastic-
CP. When the neurologic system loses motor ity, the basic supposition is that muscle tone is
control function and postural stability or good and the amount of muscle tone should be
weakens but has organizational ability to func- modulated for the individual’s maximum ben-
tionally respond, it will increase muscle tone to efit. Spasticity may be generalized affecting
compensate. However, there are cases where almost all the muscular system, and general-
ized increase in tone may be associated with
mixed tone conditions where it is combined
F. Miller (*) with movement disorders. The spasticity for
Department of Orthopaedics, Nemours/Alfred I. duPont these individuals may be very beneficial to
modulate the movement disorder. Treatments

https://doi.org/10.1007/978-3-319-74558-9_43
612 F. Miller
for generalized spasticity require an approach but has organizational ability to functionally
that reduces whole body tone. Children with respond, it will increase muscle tone to compen-
diplegia often have more localized spasticity sate. However, there are also clear cases where
problems such as the plantar flexors but may this response over reacts and it develops patho-
also involve the whole lower extremities. Man- logic spasticity which causes impairment. There-
agement options include whole body methods. fore, when treating children with spasticity, the
In children with hemiplegia or unilateral CP, the basic supposition is that muscle tone is good and
spasticity tends to be localized to a single side, the amount of muscle tone should be modulated
and the treatment should be more focused on the for the individual’s maximum benefit.
local problem. There are many treatment Spasticity may be generalized affecting almost
options for spasticity including those that affect all the muscular system, which is the common
the whole body to those that have a very local- situation in children with GMFCS IV and V
ized affect. Some of the treatments also are level function. This generalized increase in tone
permanent and cannot be reversed, while others may be associated with mixed tone conditions
are temporary whose effect disappears when the where it is combined with dystonia and athetoid
treatment ends. The remaining discussion in this movement disorders. The spasticity for these indi-
chapter will focus on the localized effects of viduals may be very beneficial to modulate the
spasticity and localized treatments of spasticity. movement disorder. Treatments for generalized
spasticity require an approach that reduces whole
Keywords body tone. The whole-body tone management
Cerebral palsy · Spasticity · Botulinum toxin · approaches available are oral medications and
Phenol · Alcohol · Baclofen · Rhizotomy · intrathecal baclofen discussed in separate
Neurectomy ▶ Chaps. 45, “Dystonia and Movement Disorders
in Children with Cerebral Palsy,” and ▶ 42,
“Intrathecal Baclofen Therapy: Assessment and
Introduction Medical Management”. Children with diplegia
(lower extremity bilateral) in the GMFCS I, II,
Spasticity is the most common presentation and III levels often have more localized spasticity
of all neurologic alterations in children with problems such as the plantar flexors but may also
CP. Increased muscle tone expressed as spasticity involve the whole lower extremities. Management
must be a very strong chaotic attractor to the options include whole body methods as noted
organization of residual activity in a child with a above as well as dorsal rhizotomy, which is a
central neurologic injury. It is very difficult to technique of cutting sensory nerves from the
understand what the components of the system lower extremities to reduce spasticity. The indica-
are that make this spasticity such a strong attrac- tions for this technique which provides permanent
tor. Because it has persisted in humans but is decrease in spasticity remain under significant
seldom seen in animals, this suggests that there debate. The risks of removing beneficial tone
is a functional benefit to spasticity. Even though and creating a weak patient who is unable to
spasticity is a strong chaotic attractor, any judg- increase tone when needed in addition to the sur-
ment about its benefit or harm to an individual gical compilations have to all be considered
cannot easily be made. From modern robotic ▶ Chap. 44, “Dorsal Rhizotomy for Spasticity
research, it is known that adding stiffness to joints Management in Cerebral Palsy”. In children with
helps improve fine motor control; and also every- hemiplegia or unilateral CP, the spasticity tends to
one has experienced a tendency to stiffen when be localized to a single side, and the treatment
wanting to do very fine delicate movements with should be more focused on the local problem.
their hands. It seems most conceivable that, on the There are many treatment options for spasticity
whole, when the neurologic system loses motor including those that affect the whole body to those
control function and postural stability or weakens that have a very localized affect. Some of the
41 Focal Management of Spasticity in Cerebral Palsy 613
The spasticity tends to develop from about the first

to the third or fourth year of life. Its gradual
increase in tone is often one of the major abnor-
malities parents notice. After peaking at approxi-
mately age 3–5 years of age, the spasticity tends to
slowly decrease into the adolescent years. This
change in spasticity has been the best documented
from the Swedish database as reported by
Hagglund (Hagglund and Wagner 2008) (Fig. 2).
Fig. 1 This chart shows treatment options from permanent Effects of Spasticity on Nerves
to reversible on the horizontal axis and from generalized
body effects to anatomically localized effects on the vertical
axis. In this concept the oral medications and intrathecal
Because the lesion in CP is central, all other more
baclofen (ITB) fall into the reversible generalized effects. distal changes are presumed to be secondary. The
Rhizotomy (SDR) falls into the permanent with some gen- best recognized change in spasticity is hyper-
eralized effects quadrant, although the rhizotomy effects reflexia, which occurs because of a decreased
involve primarily the lower extremities only. Orthoses and
botulinum toxin are in the focal reversible quadrant, while
inhibition from the cortical spinal tracts. As a
phenol and tendon surgery fall into the permanent focal normal child grows, the rate of muscle contraction
quadrant. It is not completely this simple as tendon length- and the ability to increase power by cerebral cor-
ening of contractures which may also reduce spasticity tends tex modulation continues to increase until the
to slowly reoccur, and botulinum toxin has permanent scar-
ring effect on the muscle (This concept was originally
child is approximately 10 years old (Connolly
presented to me by Kerr Graham.) and Forssberg 1997). Although this change has
been well documented by studying the ability
treatments also are permanent and cannot be of increased rapid alternating movements in chil-
reversed, while others are temporary whose effect dren and adults (Lin et al. 1996), it is not clear
disappears when the treatment ends. These treat- where these changes occur. In CP, this more
ment options can be demonstrated graphically immature pattern of slow corticospinal and pyra-
with a four quadrant chart (Fig. 1). The remaining midal tract potentials persists (Connolly and
discussion in this chapter will focus on the local- Forssberg 1997). There is an increased latency
ized effects of spasticity and localized treatments and a decreased ability to recruit large numbers
of spasticity. of motor fibers at the same time (Dietz and Berger
1995). Some of this activity is modulated through
changes in the excitability of the spinal motor
Natural History neurons, which are also sensitive to joint position
or, probably more specifically, muscle length.
The long-term and chronic effects of spasticity The strength of the ankle reflex is very sensitive
upon the localized structures are significant. Spe- to ankle joint position as measured by the
cifically, the spasticity has an impact on the H-reflex, which is initiated through stimulation
neuromotor junction by causing some disorgani- of a peripheral sensory nerve. This change is
zation, it has a direct effect on muscle growth much greater than can be explained by mechanical
causing reduced muscle fiber growth and positioning (Connolly and Forssberg 1997). As
increased tendon length. The chronic effects also noted earlier, there has to be some tension in the
include impact bone configuration and bone muscle while the muscle is at rest for it to function
growth. An overview of these impacts will be properly. Some of this tension seems to disappear
discussed. Another important element of spasticity when the individual is under neuromotor blockade
is that it has the natural evolution during growth of anesthesia. It has been postulated that active neu-
the child. Babies at birth are almost never spastic. ronal stimulation is required to maintain this
614 F. Miller
Fig. 2 This chart showing the percent of gastrocsoleus muscles with Ashworth 2 level spasticity from age 1 to 15. This
data is abstracted from 266 children who had 3521 recorded examinations (Hagglund and Wagner 2008)
muscle tone (Connolly and Forssberg 1997); how- very thin in addition to being short, which
ever, no direct evidence of this has been found. means that these muscles are also weak, as a
It is this element of increased neurologic stimula- muscle’s strength is related to its cross-sectional
tion not generating an active EMG that seems to area (Fig. 3). Understanding strength has been an
increase most when tone increases in CP. Because extremely confusing topic in spastic muscle eval-
many of these children also demonstrate abnor- uation. The mechanical definition of strength is
malities in temperature regulation and blood flow defined by how much load a structure can support.
in the extremities, some regulatory abnormality in When discussing strength of a limb, such as
the sympathetic nervous system may be involved. the strength of plantar flexion at the ankle, the
At this time, however, there is no direct evidence strongest ankle tends to have a severe fixed flex-
to support this theory. There is evidence that the ion contracture, but this is not the strength for
neuromotor junction becomes more disorganized which most clinicians are looking. Usually, the
with chronic spasticity (Robinson et al. 2013), but term strength is used to describe the ability to
how this impacts spasticity over time is not clear. move a load or to do work, which is called active
strength, whereas the contracture is a passive
strength. By creating a significant contracture,
Effects of Spasticity on Muscles the spastic muscle has great passive strength but
and Tendons low active strength compared with normal mus-
cles. Active strength is altered more in spastic
Hypertonia and hypotonia have the most children because of the difficulty of avoiding
dramatic secondary effects on the muscle. The co-contraction, as there is less antagonist inhibi-
well-observed effects of spasticity on skeletal tion in spasticity. Motor units tend to get larger
muscle include decreased longitudinal growth of and have slower responses with longer latency
the muscle fiber length, decreased volume of the periods combined with a large shift to the slow-
muscle, change in motor unit size, and change in twitch type 1 fibers (Dietz and Berger 1995;
the fiber type and neuromotor junction type. In the Castle et al. 1979). All these changes mean the
mouse model, the spasticity causes loss of approx- muscle responds slower during contraction and,
imately 50% of the longitudinal growth of the combined with the changes in the nerve, has a longer
muscle fiber, resulting in contractures (Ziv et al. latency period. Children with spasticity were recently
1984). Muscles in children with CP are always found to be resistant to succinylcholine, and on
Fig. 3 The effect of

spasticity on the growth and
development of skeletal
muscle results in a muscle
that has fewer muscle fibers,
shorter fiber length, and a
longer tendon. This
aberration results in a
muscle that is weaker
because of decreased cross-
sectional area and has less
excursion, resulting in
decreased joint range of
motion because of the
shorter fiber lengths
further investigation, it was found that the is able to move in space, although at a slower rate
neuromotor junction contains immature subunits. than normal. Although there are no good detailed
The effects of spasticity on skeletal muscle are explanations at this time from the maturation
pervasive and often experienced by neuro- perspective of exactly what determines these
orthopedists; however, a physiologic explanation of changes, they all make sense in the dynamic con-
how increased tone causes all these changes is still trol model. The major problem of this chaotic
unknown (Robinson et al. 2013) ▶ Chap.15, “Neu- attractor is that it seems too stable and there is an
romuscular Junction Changes in Spastic Cerebral overreaction in many children, with the changes in
Palsy”. themselves becoming functionally limiting and
There is a grave need for basic research causing problems ▶ Chap. 168, “Muscle Perfor-
and understanding of muscle response to spastic- mance in Children and Youth with Cerebral
ity. There has been much more interest in under- Palsy: Implications for Resistance Training”.
standing the muscle changes due to spasticity in
the last 10–15 years. Most recent detailed findings
are reported in associated, ▶ Chap. 16, “Muscle Effects of Spasticity on Bones
Changes at the Cellular-Fiber Level in Cerebral
Palsy”. In the context of dynamic control theory, Changes in the bones caused by spasticity
these changes seem to be revolving around a are modulated by muscular changes. The most
strong, stable attractor whose basic factor seems common effects are dislocated hips; scoliosis;
to be a simplifying control for a damaged motor foot deformities, such as planovalgus feet or
control system, which is slowing the response time, equinovarus feet; bunions; knee contractures;
stiffening the system, and providing passive and elbow, shoulder, and wrist joint contractures.
strength in the face of absent active strength. This Torsional malalignments of the femur and tibia
stable chaotic attractor seems to be organizing are common as well. A major part of this text
around the functional benefit of the organism, discusses the management of these deformities.
which can now support weight in stance and These secondary deformities, such as dislocated
616 F. Miller
hips, have been very well defined and have remove all muscle tone. It is much better to con-
clear mechanical etiologies (Miller et al. 1999). ceptualize spasticity treatment similar to treating
These deformities all have clear and strong pulls hypertension. Clearly, the treatment of hyperten-
to develop toward easily understood chaotic sion would not be successful if all the blood
attractors. In the hip, on one side the muscle will pressure were removed. There is considerable
become contracted causing adduction, and on similarity between no blood pressure and no mus-
the other side, it will become contracted in abduc- cle tone. The ideal treatment of spasticity would
tion. Therefore, both hyperadduction and hyper- be a situation where the tone is decreased only at
abduction are stable attractors. With a decreased the time and in the anatomic area when and where
level of fine motor control and spasticity, the it causes problems. The spasticity would then be
neutral position of the hip is not a stable region. preserved in all situations in which it is helping the
This concept also applies to other affected joints. child. It is also important to remember that some
of the secondary effects in the muscle noted above
may also have direct effects from the primary
Functional Effects of Spasticity lesion. For example, the strength of a muscle
on Sitting, Gait, and Activities of Daily contraction is mediated by the cerebral cortex
Living impulse. Therefore, in a child with CP, this ability
to modulate strength may be a primary deficiency
There are many functional effects of spasticity, due to the brain lesion. After the child has been
some of which help children and some of which evaluated with an assessment of the specific ben-
cause major problems. For children who are efits and problems of spasticity, available treat-
ambulatory, the spasticity causes typical spastic ment options should be considered.
gait patterns. These gait patterns are discussed in The treatment of muscle tone may be applied at
▶ Chap. 90, “Cerebral Palsy Gait Pathology”. different locations in the neuromuscular system.
Children who are able to do minimal weight Treatment options start in the central nervous
bearing for transfers or household ambulation are system with the use of medications, electrical
often greatly aided in these activities by the spas- stimulation, or surgical ablation. In the peripheral
ticity, which provides the strength and stability for nervous system to the level of the muscle, medi-
weight bearing. These same children may have cation and ablation are the main choices. At the
problems relaxing in seating positions and there- muscle level, medication, electrical stimulation,
fore are difficult to seat. They may also have so or surgical lengthening are the treatment options.
much spasticity that activities of daily living, such Treatment options to be further discussed in this
as dressing and toileting, are difficult. Each child chapter will be limited to focal or localized
requires a careful assessment of the specific prob- treatments.
lems and benefits caused by the spasticity. There is
a tendency for family members and some clinicians
to equate the spasticity to CP. It is often difficult for Peripheral Nervous System
them to see the benefits provided by the spasticity.
Another way to decrease spasticity is by interven-
tion at the level of the peripheral nerves. The
Treatments only options involve lesioning of the nerve, either
chemically or by physical transection. This
When planning for treatment of the spasticity, the lesioning mainly involves addressing the motor
benefits and problems should be carefully consid- nerves instead of the sensory nerves, which are
ered. Everyone must realize that no matter how addressed by a rhizotomy. Chemical lesioning is
successful the treatment of the spasticity is, the often at least partially reversible. The chemical
child will still have CP. It should always be kept in agents range from short-acting to long-acting
mind that the goal in treating spasticity is to never local anesthetics, alcohol, and phenol. The use
of local anesthetics to block nerve transmission extremity (Msaddi et al. 1997), where the flexor
was usually advocated as a way of doing diagnos- muscles can be denervated by dissecting out the
tic tests to see if a child would benefit from a motor branches of the ulnar nerve. Also, there are
surgical lengthening procedure (Carpenter 1983). reports of doing gastrocnemius neurectomy or
This concept makes little sense today because neurotomies to control ankle equinus (Doute
the blockade of nerves does not affect the contrac- et al. 1997; Deltombe et al. 2001); however, this
ture, which usually is the major problem to be is not a good idea from a mechanical perspective,
surgically addressed. With today’s modern diag- as the muscle would lose strength. Overall, for the
nostic gait laboratories, this type of diagnostic control of spasticity, peripheral neurectomy has a
evaluation has little use. In the 1970s, the use of minimal role in the management of spasticity in
alcohol was also advocated as a diagnostic and the child with CP.
therapeutic way to reduce spasticity. Alcohol Localized management of severe spasticity and
injections generally provide a decrease in tone movement disorder in the upper extremity can be
for 1–3 months (Carpenter and Seitz 1980). Phe- especially difficult. This is the situation where the
nol is an even more caustic agent and will destroy combination of denervation utilizing neurotomy
the nerve, so the spasticity will stay reduced for and chemodenervation is often most applicable.
18–24 months; however, it is a very painful injec- There is a significant problem with pain from the
tion usually done under general anesthesia. Both impact on sensory nerves with these techniques to
alcohol and phenol were very popular in the 1970s the point where the goal of making the limb flail
and into the early 1980s. Because of the toxic may be achieved but the chronic pan becomes a
nature of these drugs and because the injections major problem. Exploring all options such as
were painful, general anesthesia was required. intrathecal baclofen and, when movement disor-
With the availability of botulinum, there is only der is a component, deep brain stimulation before
a rare role for their use to manage spasticity today. moving to aggressive denervation is preferred.
The use of the alcohol or phenol for chemo dener- Experience with one patient shows this problem
vation has very low data support in the published as he ended, finally as a young adult having his
literature combined with the risks of scarring arm amputated at the shoulder to be relieved of the
fibrosis have little indication excepted for very pain (Case 1).
limited indications such as anterior branch obtu-
rator nerve denervation (Quality Standards Sub-
committee of the American Academy of et al. Neuromotor Junction and the Muscle
2010; Park et al. 2014; Tilton 2003).
Direct surgical ablation of the motor nerve also Botulinum Toxin (Botox)
has a long history as a means of reducing spastic- Botulinum toxin (Botox) is a neurotoxin that is
ity. Sectioning of the obturator nerve to decrease extracted from Clostridium botulinum, an anaero-
adductor spasticity at the hip is the most common bic bacteria that typically causes food poisoning.
indication (Matsuo et al. 1986; Sharma et al. Botulinum toxin was initially used to treat strabis-
1989). In general, this procedure should be mus in 1973 (Jankovic and Brin 1997). It
done only in nonambulatory children, and then was approved for use to treat blepharospasm in
only the anterior branch of the obturator nerve 1987 and, since that time, has been approved to
should be sectioned. Anterior branch obturator treat cervical and oral dystonia in adults. Almost
neurectomy is typically done in adolescents with every medical problem seems to have developed
severe adductor spasticity or in younger children a reason to use botulinum toxin. The uses of
with severe hip dysplasia in whom an attempt is this drug include spasticity, dystonia, cystitis,
being made to reduce the hip and allow the dys- essential hyperhidrosis, facial wrinkles, facial
plasia to recover without doing hip reconstruction. asymmetry, bruxism, stuttering, headaches, back
Occasionally there may be a child in whom spasms, bladder spasms, achalasia, anal spasms,
neurectomy is a reasonable option in the upper constipation, vaginismus, tongue protrusion, and
618 F. Miller
nystagmus. There are very few drugs on the mar- the turbulence created could potentially denature
ket today with such widespread use. Botox is some of the protein. When Botulinum toxin is
serotype A and is currently the most available injected into the muscle, it causes a decreasing
therapeutic toxin of the seven available serotypes, gradient of denervation approximately 3 cm in
although botulinum serotype B is sold as radius from the injection site (Borodic et al.
MYOBLOC. The differing therapeutic effects of 1994). Therefore, botulinum toxin injected into
the different serotypes are not clearly defined. In the muscle will cause temporary denervation
my experience, patients who develop resistance to followed by reinnervation, which takes approxi-
serotype A will often respond to several injections mately 3–4 months. Significant weakness occurs
of type B toxin. The botulinum toxin binds irre- with a decrease in spasticity. The effect of this
versibly to the neuromotor junction, preventing decrease in active spasticity is clear; however,
the junction from functioning. This creates a per- this drug has no effect on the fixed contracture
manent blockade, and the current theory holds that may also be present.
that the peripheral nerve sprouts new distal fibers The role of botulinum toxin for children with
and forms a new neuromotor junction. CP is continuing to evolve; however, its main use
This process requires approximately 3–4 months. is to control spasticity. Others have promoted
After new neuromotor junctions are formed, botulinum toxin as a pain control drug to use
normal motor function returns (Fig. 4). This postoperatively to decrease postoperative muscle
widely held view is not well documented scientif- spasms (Barwood et al. 2000), a concept that does
ically (Bonner et al. 1994; Ma et al. 2005). The make some sense. We have found this especially
toxin is a large protein molecule approximately helpful after rectus femoris and hamstring surgery.
150 kilodaltons (kDa) in size (Brin 1997). Botu- The major use of botulinum toxin to treat children
linum toxin is frozen to preserve the drug and its with CP is to decrease localized spasticity in a
function and requires reconstitution with saline at situation where some functional gain is expected.
the time it is thawed. Because it is a large mole- The typical situation is a 3- to 4-year-old child
cule, the solution should not be vigorously shaken with a very spastic gastrocnemius who has prob-
or injected rapidly through a small-bore needle or lems wearing an orthosis. The botulinum toxin
Fig. 4 Botulinum toxin

affects the neuromotor
junction by irreversibly
binding to the synaptic
receptors to which the
synaptosomal vesicles bind.
This prevents the
synaptosomal vesicles from
releasing the acetylcholine
into the neuromotor
junction; therefore,
activation of this
neuromotor junction is no
longer possible
injection allows much more comfortable brace

wear. Botulinum toxin can be used in the cervical
paraspinal muscles for severe hyperextension,
opisthotonic posturing, upper extremity contrac-
tures with severe spasticity, or in hamstrings
or adductors with significant spasticity. Botuli-
num toxin injection to the adductors is not
recommended as a treatment of spastic hips,
except in a closely controlled clinical research
trial, because there is a well-documented treat-
ment that yields excellent results and deviation
from these guidelines may increase the risk that
more children will need hip reconstructions. A
well-controlled study showed no benefit to the
prevention of hip displacement (Willoughby
et al. 2012); however several other less well-
controlled studies suggest a potential to delay
subluxation (Yang et al. 2008; Fehlings 2005). A
dose of 5–10 units per kilogram of weight is
typically used and can be divided between two
or three sites. Some studies report using up to
20 units/kg (Kawamura et al. 2007) or 30 units/
kg (Delgado et al. 2017). The dose should be
diluted with 1–2 ml saline per 100 units of Botu-
linum toxin and injected with a small (25- to
27-gauge) needle into the neuromotor junction-
rich zone of the target muscle. This zone is gen-
Fig. 5 Botulinum toxin is diluted with 1–2 ml saline and
erally at the junction of the proximal and middle injected into the neuromotor junction-rich zone of the
one-third of the muscle. The injections are usually muscle to be blocked. This neuromotor-rich zone is usually
done in a fan-shaped fashion to help diffusion, and in the proximal one-third and two-thirds junction area. The
botulinum is injected in a fan-shaped pattern with an
only local topical anesthetic is used, such as Emla
understanding that it diffuses over approximately 3 cm
cream (Fig. 5). Care should be taken not to inject from the injection site. For the gastrocnemius, separate
the drug intravascularly; however, this has never medial and lateral injections may be made
been reported as a significant problem. Parents
should expect the maximum effect to become
present in 48–72 h. It is possible to reinject other have about 50% less benefit with each subsequent
muscles in 4 weeks, by which time all the drug injection, and all children whom we have treated
will be tissue fixed or degraded. with more than four or five injections have devel-
Botulinum toxin is a short-acting drug by the oped complete non-responsiveness. This lack of
nature of the way the neuromotor junction response is very frustrating for the child and fam-
recovers. This character of the drug is good if ily because the drug initially provided a very
the result of an injection is not considered benefi- positive beneficial effect (see Case 1).
cial; however, it is usually a drawback because the The well-documented effect of botulinum
injection does provide a positive effect, which is toxin is to decrease spasticity and strength in the
subsequently lost. Repeat injections after injected muscle, with the tone and strength recov-
3–6 months are possible, but an immunity or ering in the subsequent 3–6 months. This has been
decreased response to the toxin develops in the outcome of many well-controlled studies and
many children. In our experience, most children multiple systematic reviews (Fonseca et al. 2017;
620 F. Miller
Quality Standards Subcommittee of the American As more companies develop other serotypes, per-
Academy of et al. 2010; Hoare et al. 2010). The haps competition will cause the price to drop.
documentation of the functional long-term bene-
fits is very limited (Ryll et al. 2011; Baird and Complications of Botulinum Toxin
Vargus-Adams 2010). The limited functional ben- After the initial wide spread use of botulinum
efit beyond short-term spasticity reduction in toxin in children with CP, there was a general
upper extremity use is also widely reported sense that there was almost no risk involved;
(Wasiak et al. 2004; Rawicki et al. 2010). Some however, there were sporadic personal comments
families report a longer beneficial side effect; of deaths occurring. This first received wide
however, most studies looking at objective find- spread concern in 2009 with the publication by
ings see little change after the initial positive the US FDA with a block box warning including
effect. There may be longer-lasting functional death as a risk (Kuehn 2009). At this time, they
gains in some children, which may suggest that noted reports of four deaths to be temporally
there is a reorganization that occurs such that the related to botulinum injection. At this time, it is
patient may settle around a slightly different not clear which children are at greatest risk for
chaotic attractor. It should also be noted that death; however, it is a general consensus among
almost all the studies are evaluating children and CP specialists that whole-body, spastic quadriple-
few studies have good case control or follow gic children receiving high doses of botulinum
children for more than 6 months. Therefore, it is toxin are at greatest risk although this is not con-
very hard to sort out botulinum effect from normal firmed. From personal report, I am aware of at
growth and neurologic development. The tempo- least six to ten other deaths related to botulinum
rary change related to botulinum injection may injection that are unreported, although I have not
also allow physical therapy to have a positive had a personal patient die. There is only one
effect on the individual’s motor control system reported study in the literature which reports a
to shift the dynamic function. Also, many clini- death due to botulinum in a study treating scolio-
cians believe that botulinum toxin should be used sis in spastic quadriplegia (Wong et al. 2015). It is
in conjunction with other modalities, such as ther- our recommendation to limit the dosage to a max-
apy, bracing, or casting (Molenaers et al. 2010; imum of 10–12 unit/kg total body dose and to be
Love et al. 2010). Because of its temporary nature, especially careful with children with severe spas-
this concept has good merit as a way of trying to tic quadriplegia.
gain more long-term functional improvement. There are multiple other complications that
Combining modalities makes it even harder to have been reported, the list note in the black
determine the impact of a specific treatment box warning related to cerebral palsy include
and how it impacts normal neurologic develop- asthenia, generalized muscle weakness, diplopia,
ment. Also if considerable effort with multiple blurred vision, ptosis, dysphagia, dysphonia, dys-
modalities only pushes a child slightly away arthria, urinary incontinence, and breathing diffi-
from a very stable chaotic attractor, the long- culties; life-threatening swallowing and breathing
term prognosis is poor because the child will settle difficulties can occur. When asked, weakness is a
back to where she was when the efforts started. relatively common complaint. I have had two
It is unclear at this time how often botulinum toxin patients with single gastroc injections of botuli-
can benefit a child by truly moving the dynamic num develop incontinence for 3 months. It is
motor control to a substantially new attractor area. unclear why there are so many complications
There are many mentions in the literature that the listed by the FDA and almost no study reporting
use of botulinum toxin with other therapies may the outcome of botulinum treatment reports com-
delay or reduce the need for orthopedic surgery; plications. I suspect treating clinicians are often
however, to date there is no scientific evidence to willing to find another excuse to assign to the
support this claim. Another major problem with complaints and are not willing to acknowledge
botulinum toxin is that it is extremely expensive. the problems.
In addition to global complications, there has the same problems when they are injected into the
been increased concern with local complications, neuromotor junction as when they are used for
specifically that the muscle does not recover nor- neurolysis. In addition, if large volumes of the
mally and there are long-lasting negative effects. drugs are injected into muscles, intramuscular
Studies in rabbits show that the muscle does fibrosis can develop (Calderon-Gonzalez and
not recover in 6 months (Fortuna et al. 2015) and Calderon-Sepulveda 2002). The use of alcohol
the non-injected distant muscle also have long- and phenol for neuromotor junction injections is
lasting effect of reduced strength (Fortuna et al. rarely indicated for the treatment of spasticity in
2013). With repeated injections the muscle damage children today. The combination use of phenol and
and recovery deficit seem to get worse (Hart et al. botulinum toxin has been reported and is used in a
2017; Rogozhin et al. 2008). A study of two normal few centers, which would seem to cause the most
humans found reduced gastroc muscle volume by complications. The results are not very convincing
MRI assessment and neurogenic atrophy of muscle considering the risks (Gooch and Patton 2004;
fibers 1 year after injection (Schroeder et al. 2009). Kolaski et al. 2008; Ploypetch et al. 2015). The
This limited scientific data supports my personal use of phenol on the anterior branch of the obtura-
experience that there is lasting effect with weak- tor nerve which has no sensory elements is safe,
ness and increased muscle stiffness which gets well tolerated, and equal likely to nerve crush or
worse with repeated frequent injections. One to neurectomy (Khot et al. 2008; Kwon and Kim
three injection cycles in a young child likely do 2009). The use of phenol nerve blocks with or
not have a significant long-term impact; however, without botulinum toxin do not have enough sci-
there are physicians who inject patients every entific data to suggest that they are effective (Qual-
4–6 months without regard for any functional ben- ity Standards Subcommittee of the American
efit, presumably under the assumption that they are Academy of et al. 2010) and the complication
preventing the rise of spasticity. There is no profile of phenol is significantly higher especially
published evidence that repeat injections are of with dysesthesia to make botulinum a much better
benefit especially in the face of there being no choice (Wong et al. 2004). Although mentioned by
functional impact. Based on the limited available a number of authors as possibility, intramuscular
data, this only further damages the muscle. injection of phenol has no reported benefit and only
In summary, botulinum toxin to manage spas- severe fibrosis as a side effect. There is currently no
ticity in children with CP is clearly documented to role for intramuscular phenol injection.
decrease local spasticity for 4–6 months after the The use of intramuscular alcohol has been
initial injection. Current documentation of benefit reported to be short-acting paralytic with no
of repeated injections is not available. There is no long-lasting effect (Carpenter and Seitz 1980).
evidence available to support long-term func- The use of alcohol for nerve block has a more
tional benefit from botulinum injections. These variable period of effectiveness compared to alco-
benefits have to always be balanced against the hol (Ghai et al. 2012). Since there is very little
known and possible complications. Considering published data on the use of alcohol either for
this marginal risk/benefit ratio, it is an extremely intramuscular injection or as a neurolytic agent
popular treatment with a large literature base. and I have no personal experience, there seems
A current search of “botulinum” and “cerebral to be no role for its use currently.
palsy” yielded 907 abstracts in Pubmed.
Direct Surgical Treatment

Alcohol and Phenol of the Musculotendinous Unit
Injections into the neuromotor junction region with A very common and old treatment of spastic mus-
alcohol and phenol were also popular for a time, cles is lengthening of the tendon, thereby releas-
especially in the 1970s. Alcohol and phenol have ing the contracture. In reality, the contracture
622 F. Miller
is due to a muscle that has not grown sufficiently ankle articulations. All reported studies that
to its anatomically required length. The classic objectively evaluated these claims have not
wisdom often repeated is that muscle tendon found any benefit beyond the mechanical con-
lengthening does not directly treat spasticity but straint these orthoses provide (Ricks and Eilert
only addresses the secondary effects of decreased 1993; Crenshaw et al. 2000). Based on these
muscle growth. This understanding of the effects published data, there is no direct evidence of an
of muscle tendon lengthening is only partly true impact on tone by the use of orthotics. There may
because the hyperreflexic component of spasticity be some benefit to decreasing sensory input and
depends on the specific length and tension where thereby decreasing muscle tone in some children.
the muscle is being stimulated (Connolly and Also, based on subjective experience reported by
Forssberg 1997). Thus, the muscle is much more many clinicians, there are a significant number of
sensitive to initiate a hyperreflexic contraction children, especially those with quadriplegic pat-
when the most sensitive region of the length- tern involvement, whose motor control system
tension curve is under tension. For an example, shifts to a different chaotic attractor. For example,
with the gastrocnemius having its most sensitive by keeping the ankle at neutral in an ankle-foot
length-tension curve set at 20 plantar flexion, orthosis (AFO), a child has less extensor postur-
hyperreflexia demonstrated clinically as clonus ing and sits better and has better arm control. This
will be easily initiated in 20 of plantar flexion. change in motor control is hard to directly relate to
By lengthening the tendon and allowing this most a reduction in spasticity; however, this change
sensitive aspect of the muscle length to rest at 10 does occur. The orthotics have the opposite effect
of dorsiflexion, there will be significant decrease in some children. Often, these children are driven
in the spasticity or the ability to initiate clonus to push into more plantar flexion and hyperexten-
when the ankle is at 20 of plantar flexion. By this sion. These children get a sensory stimulus from
method, lengthening the tendon has direct func- the orthotic that drives them toward more of the
tional effects on the spasticity by moving the extensor posturing attractor.
sensitive region to an area where it is less likely Special tone-reducing casts with molded-in
to be initiated during an activity such as gait. Also, pressure point areas in the soles and extended
lengthening the muscle will give it the ability to toe plates have been advocated as a technique
generate active plantar flexion moment at the for reducing spasticity (Ricks and Eilert 1993;
place in the joint range where it is needed, instead Bertoti 1986). Only small case studies have been
of in significant plantar flexion in which children reported that suggest a benefit with this technique.
get little additional mechanical advantage from However, it seems that the positive effects of
the contraction. This complex effect of muscle wearing casts are directly related to the length of
length is discussed further in the section on gait time they are worn (Otis et al. 1985). It is well
▶ Chap. 90, “Cerebral Palsy Gait Pathology”. known that cast wear causes muscle atrophy and
Adjusting muscle length through the use of ten- weakness, which is the likely effect seen and
don lengthening is one of the primary options for labeled as decreased spasticity in these children.
treating the major secondary muscular effects of In our experience, the benefit of casting usually
spasticity and also has some direct impact on the is approximately two times the length of the cast
spastic response of the local muscles. wear time; therefore, if a child is in casts for
4 weeks, the benefits will last 4–8 weeks. Parents
tire quickly of placing the child in casts and then
Orthotics having the effects quickly lost. Casting is very
disruptive to the child’s lifestyle because they
There has been much discussion in different cannot bathe, dressing is difficult, and the appli-
venues of tone-reducing orthotics, specifically cation of the cast is very time consuming. For
the use of various orthotic designs, such as ele- these reasons, we do not find the use of tone-
vated toe plates, peroneal arch, calcaneal bar, and reducing casts of much benefit in children with
spastic CP. The ankle orthotics, when they perception and motor control program generator
are fitting well, provide similar gains as the use interactions. From dynamic motor theory, this
of tone-reducing casts. There are many benefits may also result from pushing the individual
of these orthotics over casts, including that the toward a different chaotic attractor that is not
orthotic can be removed for bathing, the ankle very stable, and as soon as the perturbation has
range of motion can be maintained, and there is subsided, the stronger attractor comes back into
less muscle atrophy. force and the individual’s motor control system
The use of serial casting continues to make settles back to where it was before the activity.
good therapeutic sense in very spastic children in This explanation best describes what patients
the acute recovery phase from closed head injury report; however, it is not very helpful in concep-
or any other circumstance where the spasticity is tually understanding what is happening from an
resolving. The use of casts in these children can anatomic perspective.
provide a bridging effect until the spasticity Passive stretching is a widely accepted modal-
resolves, and they are easier to maintain in orthot- ity for maintaining range of motion; however,
ics. The primary mechanism for decreasing spas- objective documentation of the exact benefit is
ticity by immobilization is probably due to lacking. We have seen many children in pat-
immobilization atrophy of the muscles and per- terning therapy programs where they were receiv-
haps some stretching of connective tissue. There ing passive range-of-motion exercises 18–20 h a
are no convincing data available that suggest that day. These children do have less spasticity and
it is possible, through immobilization techniques, better range of motion compared with similar
to make spastic muscles grow longer. Another children who get very little passive range-of-
reasonable use of serial casting is in cases of motion stretching. However, it is unclear how
severe fixed knee flexion contracture where the much passive range of motion is required to get
goal is to do a knee extension osteotomy. If there a significant benefit, because it is neither practical
is a 60-degree fixed knee flexion contracture and nor healthy for children’s overall development to
this can be reduced to 30–40 , the extension be doing 18–20 h per day of passive stretching.
osteotomy will be much easier and require less The use of vibrators, usually at 100–120 hz,
rotation of the distal femur. This may provide also has been shown to decrease muscle tone, and
some stretch to the muscles and the neurovascular they are often used by individuals who feel stiff.
structures as well. Some patients with CP report that the use of a
vibrator makes their muscles feel less tight. This
feeling is a temporary phenomenon and may be
Therapy related to similar benefits that others report from
deep muscle massage.
The use of physical therapy techniques, such as
active and passive range of motion, is a well-
accepted treatment modality in children with spas- A Global Approach to Managing
ticity. There is no objective evidence that a spe- Spasticity
cific therapy can impact the degree of spasticity
permanently, although there are activities, such as There are many options available to treat spastic-
horseback riding, which patients, parents, and ity. In developing an algorithm, clinicians first
therapists almost uniformly report to decrease have to remember and educate families that spas-
spasticity temporarily. This same effect has been ticity is not CP, and by removing spasticity, the CP
reported to us by individuals while riding in boats will not be cured. Also, the spasticity is an exag-
or doing other rhythmic activities. The effects on geration of a normal phenomenon, muscle tone,
spasticity by these activities are hard to explain, which is an extremely important aspect in normal
but we believe they occur and probably are medi- motor function. Therefore, the goal is never to
ated through complex cerebral cortex sensory remove all muscle tone but to adjust the tone so
624 F. Miller
it provides maximum functional benefit to the nighttime sleeping problems is small, and it is
individual. never very clear whether these sleep problems are
The first function of an evaluation for spasticity related to spasticity or whether they are a primary
treatment is to tally the negative and positive sleep disorder. This group, whose primary problem
aspects of the spasticity. Based on the specific prob- is nighttime sleeping, should be treated with a trial
lems the spasticity is causing, the clinician can of oral antispasticity drugs, which occasionally
choose from the available treatment options. First, work. Usually, diazepam is our first treatment pref-
the clinician needs to determine whether these prob- erence, and we have several patients in our practice
lems are due to a global increase in spasticity or to for whom this works well. Intrathecal baclofen also
increased spasticity in a local region, such as one improves sleep and can be used if the oral trial fails.
joint or one limb. For example, the increased tone in For children with daytime functional problems
the gastrocnemius of a hemiplegic child has very caused by global spasticity, the specific functional
different implications compared with a child who problems need to be identified. These functional
has severe total body involvement and has prob- problems may include difficulty with dressing,
lems being seated in a wheelchair. seating, and toileting or gait problems. This group
For local problems that involve two to four should be further divided into those children with
specific muscles, the focus should initially be on multiple functional problems and those with a sin-
local treatment. Examples of such localized spas- gle problem.
ticity are spastic wrist flexors and elbow flexors, For children with multiple functional problems
equinus foot position, and spastic hamstring mus- due to global spasticity, there usually are signifi-
cles causing knee flexion contractures. After iden- cantly more problems than functional benefits of
tifying the problem as local, the clinician has to the global spasticity. However, it is always impor-
decide if it is supple spasticity only with full tant to consider what the functional benefits of the
underlying joint range of motion, mainly a fixed spasticity are for the individual child. If these
muscle contracture due to a short muscle, or a benefits can be preserved or are much less benefi-
combination of both supple spasticity and fixed cial than the problems being caused by the spas-
contracture. If the problem is dynamic spasticity ticity, the main treatment option is the intrathecal
with no underlying contracture, then the primary baclofen pump.
treatment options are botulinum toxin injection For children with single functional problems,
and an orthotic. If the problem is a fixed contrac- such as gait or problems with seating, attention
ture, the only option is surgical lengthening of the should be focused on specific local treatments.
tendon. If the problem is mixed spasticity and For example, for children who have seating prob-
fixed contracture, the options can be combined lems, a careful assessment of the seating system
by starting with a trial of botulinum toxin and can often correct the problem by adjusting and
orthotics. To gain an adequate result when the providing a well-fitting seating system. For chil-
botulinum toxin fails, a muscle lengthening dren whose primary problem is gait, a very careful
should subsequently be done. By far the most assessment, usually requiring a full instrumented
common situation is children who fall into the gait analysis, should be completed to fully under-
mixed group with dynamic spasticity and contrac- stand the interactions of the spasticity, contrac-
ture; however, there are also children who clearly tions, and skeletal malalignments, which all
fall into one or the other groups. may be components of their gait impairment. For
Children whose functional problems related most children who are independent ambulators
to spasticity involve more than four muscle groups and have global increase in spasticity, the primary
should be considered as the globally involved treatment is correcting the specific individual
group. These children should be divided based on components of the disability, such as correcting
whether the problems are mainly caused by bony malalignments, lengthening contracted mus-
sleeping difficulties at night or daytime functional cles, and transferring muscles that are functioning
problems. The group of children with primarily in the wrong phase of gait. The use of intrathecal
baclofen may be an option, although the specific

indications for its use in this population are still dystonia was so severe that finger flexion
not well developed. For children who are ambu- was causing skin breakdown in the palm,
latory with diplegia, dorsal rhizotomy or intrathe- which was very painful. Motor point injec-
cal baclofen can be considered between the ages tion alcohol of the biceps and finger flexors
of 3 and 8 years in those individuals with no bony provided only 3 months of relief. The same
deformities or muscle contractures and only motor nerves, as well as the motor branches
dynamic spasticity. of the radial nerve, were then injected with
Children with global spasticity who are having phenol. This injection caused a severe neu-
significant upper extremity problems should usu- ritic pain syndrome for 6 weeks because the
ally be considered for surgical reconstruction. For phenol also affected the sensory nerves.
children with global spasticity who have specific This injection provided almost 12 months
problems related to functional tasks of daily liv- of improvement in the dystonic movement.
ing, such as self-dressing or toileting, the first However, elements of the dystonia returned.
treatment should be an intensive evaluation by The shoulder tended to go into extension
an experienced physical or occupational therapist. and abduction, which was very annoying,
In summary, by combining all the options and because as he walked in school the arm
careful assessment, children with CP can usually would suddenly fly into extension and
be treated in a way that makes the spasticity abduction, hitting walls or other people
become a benefit and not a major component of (Fig. C1.1). This was extremely annoying
their impairment. and frustrating to him. Because of the
severe pain from the previous phenol injec-
tion, he refused it and other phenol injec-
Cases tions, actually requesting amputation of the
limb. It was recommended that Joe go for an
evaluation for possible central lesioning to
decease the dystonia; however, he refused
Case 1 Joe
this because he blamed his first brain sur-
At age 4 years, Joe developed a mild bleed
gery for all his current problems. With few
from a brain arteriovenous malformation.
other options left, he had a surgical dener-
This condition was surgically treated, and
vation of the upper extremity, cutting the
following the procedure. he was left with
suprascapular nerve, motor branches to the
mild left hemiplegia. This appeared to be a
triceps, and deltoid muscles. At the forearm,
typical spastic hemiplegia until he entered
the motor branches to the finger and wrist
puberty at age 14 years. A significant dys-
flexors and extensors were cut. Because it
tonic movement disorder developed in his
was difficult to cut all motor nerves without
left upper extremity, in which the elbow
cutting sensory nerves, some isolated motor
would flex along with strong wrist and
function remained and got stronger over
finger flexion. An attempted treatment
the next year following the denervation. At
with trihexyphenidyl was unsuccessful.
this time, the tendons on several finger
The biceps, forearm flexors, and finger
flexors, the wrist extensor, and the biceps
flexors were then injected with botulinum
were released. He continued to have pain
toxin, which provided excellent relief, allo-
from the denervation and still some muscle
wing the limb to remain in good position.
movement and in his mid-20s had a shoul-
Repeat injections were performed every
der disarticulation which has brought him
4–6 months over the next 2 years with grad-
relief.
ually diminishing effect. At this time, the
626 F. Miller
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(2007) A randomized controlled trial comparing botu- single-event multi-level chemoneurolysis with botuli-
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Intrathecal Baclofen Therapy:
Assessment and Medical Management 42
Maura McManus
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 630
History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 631
Pharmacology of Baclofen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 631
Criteria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 631
Screening Trial . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 632
Pump Implantation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 632
Pump Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 633
Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 634
Outcomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 635
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 635
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 636
Abstract candidate for intrathecal baclofen therapy. Ide-

Intrathecal baclofen therapy has been used in ally a multidisciplinary team including the
the treatment of generalized spasticity in chil- patient and family should work together to
dren since 1996. It has also been noted to help create realistic goals for treatment including
decrease dystonia in this population. It is very improving function, comfort, and ease of
important to understand the pathophysiology care. All medical issues need to be understood
of these conditions and the range of treatments and followed closely before and after intrathe-
available. Careful assessment is needed to cal pump implantation. A screening trial can be
determine whether someone is a good performed but is not necessary prior to pump
implantation. Optimizing dose titration and
catheter tip positioning can help to maximize
treatment effects. Medical and surgical compli-
M. McManus (*)
Nemours Alfred I Dupont Hospital for Children,
cations have been recognized and need to be
Wilmington, DE, USA worked up and managed efficiently. The bene-
e-mail: mmcmanus@nemours.org; fits of intrathecal baclofen therapy have been
Maura.McManus@nemours.org

https://doi.org/10.1007/978-3-319-74558-9_44
630 M. McManus
widely published and include improvement in release of the inhibitory neurotransmitter gamma-
comfort and function but most importantly in aminobutyric acid (GABA). GABA acts presynap-
quality of life. tically to inhibit the release of excitatory neurotrans-
mitters such as glutamate and aspartate, resulting in
Keywords relative excess of excitatory impulses and resultant
Baclofen · Spasticity · Dystonia · Intrathecal · hypertonia (Gormley 1999).
Cerebral palsy Although some spasticity may be necessary
for function in children with neurologic impair-
ment, it is often a problem that can be difficult to
Introduction treat. Spasticity may cause pain, limit sleep, lead
to joint deformity, and interfere with function.
Spasticity is the most common motor disorder in It may also interfere with care including transfers,
cerebral palsy (CP) and is seen in approximately toileting, bathing, and dressing (Krach 2001).
two thirds of the population. Although some spas- Multiple approaches are available for treatment
ticity may be necessary for function in children of spasticity in patients with CP. These include
with neurologic impairment, it is often a problem therapies, bracing, and positioning. Oral medica-
that can be difficult to treat. Multiple approaches tions have been used as well as local treatments
are available for treatment of spasticity in patients such as botulinum toxin (BoNT) injections and
with CP including therapies, oral medications, phenol motor point block injections. Orthopedic
chemodenervation, and intrathecal baclofen ther- surgery may be necessary, and this may include
apy. Orthopedic and neurosurgical procedures are soft tissue releases and/or osteotomies (Reid et al.
also available (Reid et al. 1998). Spasticity is 1998). Neurosurgical procedures such as selective
probably due to an imbalance between inhibitory dorsal rhizotomy are also available (Abbott 1996).
and excitatory impulses in the spinal cord. In CP, The goals for treatment should be realistic and
there is believed to be a deficiency of descending individualized, and they need to be agreed upon
impulses that typically stimulate the release of the by the patient, family/caregiver, and medical
inhibitory neurotransmitter gamma-aminobutyric team. Ideally, a multidisciplinary team should be
acid (GABA). Baclofen is an analogue of GABA, involved in the decision-making. Such a team
and when delivered intrathecally, it can diffuse to may include patient and family, physical and
where GABAB receptors are believed to be located occupational therapist, nurse, physiatrist, neurol-
in the brain and spinal cord (Keenan et al. 2000). ogist, orthopedist, and neurosurgeon.
Intrathecal baclofen therapy has been approved Several oral medications have been used
for the treatment of generalized spasticity in to reduce tone, including diazepam, baclofen,
children since 1996. Over these years dystonia has dantrolene sodium, tizanidine, and clonidine.
also been successfully treated (Butler and Campbell Although they can decrease spasticity, their sedat-
2000). Spasticity is the most common motor disor- ing side effects are not well tolerated in children
der in CP and is seen in approximately two thirds of (Gormley 1999).
the population. It is a component of the upper motor Baclofen has been noted to be moderately
neuron syndrome and is described as a velocity- helpful when taken orally for spasticity of spinal
dependent increase in resistance to passive stretch origin in adults. It has been relatively unhelpful in
associated with increased deep tendon reflexes treating spasticity of cerebral origin, especially in
(Lance 1980). Spasticity is thought to be due to an children with CP. It is lipophilic and crosses the
imbalance between inhibitory and excitatory blood–brain barrier poorly. Intrathecal baclofen
impulses that terminate on or near the alpha motor has been shown to reduce spasticity with fewer
neurons in the spinal cord (Gans and Glenn 1990). side effects (Krach 2001).
In CP, there is believed to be a deficiency of Neurosurgical interventions have been avail-
descending impulses that typically stimulate the able for over 20 years. The first was that of dorsal
42 Intrathecal Baclofen Therapy: Assessment and Medical Management 631
root rhizotomy, which has met with mixed Criteria

reviews. Meta-analysis of affected patients dem-
onstrates that if there is any benefit, it is only in a For the success of intrathecal baclofen, careful
few points of improvement and not dramatic func- patient selection is critical. Patients with moder-
tional improvements. Use of intrathecal baclofen ately severe spasticity of spinal and cerebral origin
in the pediatric patient having CP has yielded (i.e., CP, traumatic or anoxic brain injury) have
as good a reduction in tone as dorsal rhizotomy been successfully treated with intrathecal baclo-
and does not represent an ablative procedure. This fen (Meythaler et al. 2001). Intrathecal baclofen
is important because, unlike rhizotomies, it is alone or with other treatments should not be
entirely reversible (Albright et al. 1995). exclusively reserved for individuals who have
failed other approaches. Patients with dystonia
have also responded to this treatment, often at
History higher doses. Patients with athetosis, ataxia, and
myoclonus have not noted significant improve-
In 1984 Penn and Kroin pioneered the use of ment. Spasticity is considered severe with
intrathecal baclofen for spasticity in patients Ashworth scale greater than 3. Spasticity and dys-
with multiple sclerosis and spinal cord injury. tonia are believed to be problematic when they are
Albright et al. did their first study in 1991 and generalized and significantly interfere with move-
a follow-up study in 1993 noting successful ment, positioning, or care. Patients may also expe-
decrease in spasticity in patients with spasticity rience spasticity-related pain during the day and at
of cerebral origin. In 1992 the Federal Drug night, and this sometimes limits sleep. Many
Administration (FDA) approved the use of intra- patients with spasticity are at risk of severe joint
thecal baclofen in the form of the Medtronic deformity. Other important issues to consider
SynchroMed implantable infusion system for before recommending implantation of a baclofen
treatment of spasticity of spinal origin. This pump include whether the patient has significant
same treatment was approved by the FDA for body mass to maintain the pump; the patient and
treatment of spasticity of cerebral origin in adults family need to understand and accept the cosmesis
in 1992, but it was not approved for use in chil- of the pump; the entire team must agree upon
dren until 1996 (Albright et al. 2007). appropriate goals. The patient and family must
be motivated to achieve these goals and be com-
mitted to the follow-up required to maintain
Pharmacology of Baclofen the pump’s function (Saulino et al. 2016a). Ide-
ally, the assessments should be made with a multi-
Baclofen (Lioresal) is an analogue of GABA, disciplinary team in a spasticity management
which is the main inhibitory neurotransmitter in clinic where families can have access to adequate
the central nervous system (CNS). Intrathecal information. Gait analysis should be part of the
baclofen diffuses into the superficial layers of the evaluation in ambulatory patients (Miller 1998).
dorsal gray matter of the spinal cord (layers II–III) There are additional clinical considerations
where GABAB receptors are believed to be located that are not true contraindications for intrathecal
(Price et al. 1984). These receptors have been baclofen pump implantation. For example, a trial
noted in the brain stem as well. Muller et al. of oral baclofen is not a prerequisite for patients
noted that the concentration of baclofen in the with spasticity of cerebral origin. Patients who
cerebrospinal fluid (CSF) is ten times higher have had a spinal fusion cannot undergo a trial,
than levels achieved by oral administration but this is not a contraindication for pump implan-
(Muller et al. 1988). Also, there is a concentration tation. A history of seizures is not a contraindica-
gradient from the lumbar to cervical region of tion to intrathecal baclofen therapy. The presence
4 to 1 (Kroin 1992). of a ventriculoperitoneal (VP) shunt is not a
632 M. McManus
contraindication. Patients with VP shunts may clinically significant response to intrathecal bac-
require less baclofen. Prior soft tissue lengthen- lofen (i.e., Ashworth or modified Ashworth scores
ings, tendon releases, and selective dorsal rhizot- decreasing by 1 or more), the pump implantation
omy are not contraindications. For patients with can be scheduled. Before pump implantation
cervical or trunk weakness, the benefits of baclo- the patients and caregivers should understand the
fen in reducing extremity spasticity must be commitment necessary for intrathecal baclofen
weighed against the potential for loss of the therapy (Boster et al. 2016b).
patient’s function if the trunk and cervical tone is
reduced (Saulino et al. 2016a).
Pump Implantation
Screening Trial This will be reviewed in greater detail in the

chapter by Dr. Sees (▶ Chap. 43, “Intrathecal
Once a patient is felt to be a potential candidate, a Medication Administration in Cerebral Palsy”).
screening trial can be scheduled. Because of the The intrathecal baclofen delivery system consists
risk of respiratory depression during the trial, it is of a programmable subcutaneously implanted pump
probably most appropriately performed in a hos- with a reservoir attached to an intraspinal catheter.
pital setting. Prior to the trial, a baseline physical The current 20-ml reservoir Medtronics baclofen
exam is completed. If conscious sedation is used, pump is approximately 3 in. by 0.75 in. (similar to
a short-acting sedative such as midazolam may be the size of a hockey puck). The thickness of the
used in conjunction. The lumbar puncture is 40-ml reservoir pump is slightly more at approxi-
performed, and a test dose of either 50, 75, or mately 1 in. (Medtronic ITB 2017a, b).
100 μg is injected into the intrathecal space. The pump is inserted under general anesthesia
After the lumbar puncture is performed and intra- into a lateral abdominal subcutaneous location or
thecal baclofen is injected, patients should remain under the external oblique and rectus fascia
flat for at least 1 h to avoid spinal headache. (Fig. 1). A catheter is tunneled subcutaneously
Cardiopulmonary parameters should be checked and connected to an intrathecal catheter. The cath-
frequently for the first 2 h postinjection. It takes eter enters the subarachnoid space of the spinal
1–2 h for the baclofen to penetrate the spinal cord
to produce clinical effect. Peak effect is believed
to be at 4 h. Spasticity measures should be
assessed at least twice within 4 h. It is important
to assess patients out of bed in their seating/wheel-
chair system. It is often difficult to obtain a func-
tional assessment during the screening trial.
Evaluation of mobility in an ambulator may be
challenging as underlying weakness may limit
function during the trial. Such a patient may still
be a candidate for the pump because a lower dose
of intrathecal baclofen can be programmed
through the pump than can be achieved during
the trial. Observation postinjection continues
until the patient is stable (Boster et al. 2016a).
Although bolus injections are preferred for
screening trial, continuous infusion trials using Fig. 1 Baclofen pumps may be very prominent in thin
children. Implanting the pump under the fascia makes it
an externally placed catheter can be performed.
less prominent, and it is very important to implant the
This may be important in patients in whom dys- pump so the scar is not overlying the implant, as this has
tonia is being evaluated. If the patient had a a higher risk of breaking down than normal skin
canal at the lumbar spinal level (Albright et al. simple continuous infusion and flexible dosing.
1993). The catheter can be placed at various Flexible dosing includes complex continuous
heights depending on whether upper extremity infusion where the rate can change at set times
relaxation is also a goal. To increase the effect of during the day and intermittent bolus infusion
intrathecal baclofen on the upper extremities, the mode (Medtronic ITB 2017a, b).
catheter can be placed at midthoracic level All patients start out with simple continuous
(T6–T7) rather than T11–T12. The mean dosing dosing at implant. It often takes a few months of
may also be lower (Grabb et al. 1999). The pump titrating the dose with simple continuous dosing
is programmed to deliver a continuous infusion. before you understand what specialized dosing
Simple continuous dosing is typically set up at would be helpful. For example, some patients
implant. For patients who are ambulators, we have very high tone in the morning making
often start at a dose of 50 mcg/day at implant. morning care very difficult for a caregiver. If that
For patients who need to weight bear daily, an child wakes up at 6 a.m., you can set the dose to
initial dose of 75 mcg/day is reasonable. For run at a higher rate (perhaps 10–20% higher)
quadriplegic patients who do not stand as part of from 4 a.m. to 7 a.m., and this should allow for
their daily care, 100 mcg/day is a common start ease of care. By the time he gets off his school bus
dose. at 8:30 a.m., his tone will be slightly higher at a
Postoperatively the patient is well hydrated and lower daytime rate.
remains supine for 48 h to limit spinal leak and Patients with dystonia typically need higher
headache. For nonambulators, postoperative dose doses of ITB and many have responded well to
adjustments can be made daily even during bed intermittent bolus dosing. In these cases I have
rest. For ambulators, it may be necessary to wait noticed a difference at doses of approximately
until they are cleared to be out of bed to ambulate 800 mcg/day. At this dose I have switched to
before adjusting the dose (Keenan et al. 2000). intermittent bolus dosing by running 500mcg/
Adjustments should be made once daily while in day as basal rate and splitting the other 300 mcg
the hospital postoperatively. Patients are typically as 50 mcg boluses set every 4 h (each over 15 min)
discharged to home at 3–4 days post-op. starting at 1 a.m. The basal rate technically runs in
for 22.5 h as the intermittent boluses take up
1.5 h (15 min 6 boluses).
Pump Management During every follow-up visit, I am asking
patients and caregivers about the level of tone
The first follow-up visit after implantation should noted, comfort during the day and night, and any
be at 7–10 days after discharge and then at least changes in caregiver burden. I also ask about
monthly for the first 6 months. It may take bowel and bladder function. In our experience
6–9 months to gradually titrate the dose to we have seen constipation as the most common
the desired clinical response. In some cases, the side effect in more then half of our patients. We
dose may need to be adjusted for the first 2 years have noted bladder relaxation in a much smaller
after implantation (Meythaler et al. 2001). Typi- percentage, approximately 10%. Prior to pump
cally, the dose of intrathecal baclofen is not related implant, if a patient voids three or less times per
to age or weight. As noted above, patients with VP day, our urology team does an abbreviated
shunt may require a lower dose. The pump reser- urodynamic study so we know how someone’s
voir is refilled by percutaneous puncture through a bladder functions even before the pump is
septum in the pump at intervals of 1–6 months implanted. For someone with a relatively relaxed
depending on the rate of delivery. Dosage adjust- bladder, we start out at a lower dose at implant,
ments are made via an external programmer and and we titrate the ITB dose more slowly to allow
transmitted to the pump by a handheld radio- the bladder to adjust. For issues of constipation we
frequency wand. The pump can be programmed typically recommend a stool softener and a peri-
to deliver the baclofen in several modes including staltic agent often several times per week.
634 M. McManus
During these follow-up visits, a physical exam without rash. Muscle rigidity, rhabdomyolysis,
is completed that includes a strength exam and multiorgan system failure, and death have been
range of motion as well as examination of static reported but are quite rare (Sampathkumar et al.
and dynamic tone. We use Modified Ashworth 1998). If acute withdrawal is suspected, immedi-
Scale (MAS) most commonly in our clinic. We ate medical care is recommended. High-dose oral
evaluate gait in all ambulators and often repeat baclofen is often first recommended but may
gait videos several times per year. Based on the not alleviate all of the symptoms. Oral baclofen
exam and interim history, we speak with patients and IV diazepam may be used. Some surgeons
and caregivers about dose titration. If tone is still have infused intrathecal baclofen through a lum-
significantly impacting care or if MAS is 3 or bar drain. Cyproheptadine, a serotonin antagonist,
higher, we often increase the ITB dose by 20%. has also been used as an adjunct to baclofen and
If care is easier but intermittent tightness is still diazepam. If rhabdomyolysis is suspected as a
noted or MAS is 2–3, we often increased the dose result of withdrawal, dantrolene sodium can be
by 10%. considered (McMahon et al. 2015).
Other complications are more easily divided
into immediate postoperative and late complica-
Complications tions (▶ Chap. 42, “Intrathecal Baclofen Therapy:
Assessment and Medical Management” Sees J
Complications seen with the intrathecal baclo- this publication). Immediate postoperative com-
fen infusion system may be related to the med- plications include infection at pump or catheter
ication, the pump, the catheter, or the surgical site, meningitis, wound dehiscence, seroma, or
procedure. Complications related to the medi- cerebrospinal fluid (CSF) leak. Infections have
cation may be seen during the trial, immediately lead to pump removal, but the overall number of
postoperatively, or during maintenance therapy postoperative infections has decreased with use of
especially at the time of dose adjustments. Com- prophylactic antibiotics (Bayhan et al. 2016). CSF
mon adverse affects of the medication include leak may be suspected if postoperative spinal
somnolence, headache, nausea, vomiting, hypo- headache persists. Fluid collection and/or leakage
tonia, dizziness, and increased constipation at the catheter site in the lumbar region may also
(Yoon et al. 2017). Transient urinary retention/ present as a CSF leak. Such a leak usually seals off
hesitation has been noted after dose adjustment, within 1–2 days but may take as long as
and this appears to respond to decreasing the 2–3 weeks. If the spinal leak persists, a blood
dose (Keisswetter and Schober 1975). The patch may be considered.
most serious side effects of medication over- Late complications can involve pump and
dose include respiratory depression and loss of catheter problems and skin breakdown, as well
consciousness progressing to coma. There is no as human error. Skin breakdown over the pump
specific antidote for treating overdose, but site has been seen under braces or seatbelts. Close
reports suggest that intravenous monitoring of pump site and adjustments to
(IV) physostigmine may reverse the central wheelchairs and braces can limit this problem
effects, most notably drowsiness and respiratory (Bayhan et al. 2016). Human error can lead to
depression (Muller-Schwefe and Penn 1989). programming errors, improper filling of the reser-
Pediatric dosage of physostigmine is 0.02 mg/ voir, and errors in dosing concentration. The
kg IV, with no more than 0.5 mg/min. This dose highest probability of seeing these problems is
may be repeated at 5- to 10-min intervals if within 48 h after refill (Saulino et al. 2016a).
necessary, with a maximum dose of 2 mg. Pump problems may include positional and
Complications of intrathecal baclofen with- mechanical problems. Pumps have been reported
drawal have been well documented in the litera- to flip over, especially in obese patients, and more
ture. They include rapid increase in spasticity, secure suturing may limit this. Mechanical prob-
irritability, hallucinations, seizures, and pruritus lems include battery failure and rotor lock/stall
problems. Low battery level can be detected by Decreased pain and improved sleep have also
interrogating the pump. Current batteries have a been noted. Many families have reported
life-span of 4–7 years. With a low reservoir increased smiling, engaging, and socializing at
volume, less than 2 ml, the pump will slow the home and at school (Meythaler et al. 2001). Func-
rate automatically, and this can lead to an tional improvement has been noted in upper
underinfusion of programmed dose. If a rotor extremities as well as lower extremities (Albright
lock/stall problem develops, this may also present et al. 1995).
with the patient receiving less medication Although the benefits of intrathecal baclofen in
than was programmed. Medtronic SynchroMed the spastic quadriplegic population are well
pumps are designed to automatically resume oper- documented, the role of intrathecal baclofen in
ation after an MRI procedure. The pump is ambulatory patients has been more challenging
designed to restart within 2 h, but may potentially to prove (Gerszten et al. 1997; Pin et al. 2011).
be up to 24 h, after MRI exposure. To be sure that Intrathecal baclofen treatment in CP may reduce
the pump has restarted, it is important to have the the need for subsequent orthopedic surgery
patient return to the primary pump clinician to related to spasticity and may decrease the need
confirm pump status after an MRI (Medtronic for multiple orthopedic procedures (Gerszten
ITB 2017a, b). et al. 1998).
Catheter problems can include a kink, fracture, Some challenges to outcome include the fact
blockage, migration, and disconnection. Patients that there is more effect from intrathecal baclofen
can present with signs of limited clinical response on lower extremities than upper extremities. If
or even clinical withdrawal. After interrogating patients and families feel strongly about optimiz-
the pump, a radiologic examination with ing upper extremity function, they need to be
anteroposterior and lateral views of the pump aware that standing, transfers, and ambulation
and catheter system should be obtained. If an may be lost.
X-ray provides minimal information, a check of One great advantage of intrathecal baclofen
the catheter patency to the site of delivery with compared to selective dorsal rhizotomy is that
either contrast media or radiolabeled indium is the dose of intrathecal baclofen can be titrated to
indicated. After the cause of intrathecal baclofen carefully reduce tone while not completely elim-
interruption is determined, either surgical repair, inating it. This has been demonstrated to be very
revision, or replacement of system components is helpful in children who have significant spasticity
carried out. Catheter problems overall have been with lower extremity weakness who inherently
reduced since catheters have been made more use some of the spasticity in their lower extremi-
flexible and since the one-catheter system has ties to ambulate. Another advantage is if patients
replaced the two-catheter system (Saulino et al. and families are not completely satisfied with the
2016a). intrathecal baclofen therapy, the system may be
removed (Albright et al. 1995).
Outcomes
Summary
The benefits of intrathecal baclofen have been
published in the spinal cord injury literature and Intrathecal baclofen treatment has been shown
in the CP literature (Butler and Campbell 2000; to successfully decrease generalized spasticity in
Albright et al. 2007). Functional improvements patients with CP. The benefits in spastic quadri-
and improved quality of life have been reported plegic patients have been easier to demonstrate in
in the treatment of both spasticity and dystonia. areas of comfort and care than in ambulatory CP
These benefits include increased comfort patients where function is measured.
and ease of positioning, with increased seating Success of the intrathecal baclofen therapy
tolerance and decreased caregiver burden. does seem to be related to appropriate patient
636 M. McManus
selection, setting of achievable goals, patient and Gans B, Glenn M (1990) In: Glenn M, Whyte J (eds)
family motivation and compliance, and dedicated The practical management of spasticity in children
and adults. Lea & Febiger, Philadelphia, pp 1–7
multidisciplinary team. Gerszten PC, Albright AL, Barry MJ (1997) Effect on
ambulation of continuous intrathecal baclofen infusion.
Pediatr Neurosurg 27:40–44
Gerszten PC, Albright AL, Johnstone GF (1998)
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320:1517–1521 e7472
Intrathecal Medication Administration
Julieanne P. Sees and Freeman Miller
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 640
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 640
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 640
Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 642
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 648
Abstract direct injection through the overlying skin. The

Administering medication directly into the intra- administration may be continuous or the pump
thecal space, especially in the spinal canal, has can be programmed to have higher doses over a
continued to be of interest. A drug concentrated in short time and utilize a flexible dosing regimen as
this region of the nervous system should provide desired. Rare potential side effects have been
the most direct effect. The current administration reported including infection, catheter malfunc-
of intrathecal baclofen has been used for this tion, and weakness uncovered with reduction in
reason by means of a battery powered pump spasticity. The treatment of intrathecal infusion of
implant that is placed in the abdomen and an baclofen is widely beneficial in the management
intrathecal catheter that is introduced into the of movement disorders, severe spasticity,
intrathecal space within the spine. The pump is enhancement of range of motion, increase in
controlled with an external radiowave-mediated motor function and mobility, alleviating discom-
controller, and the pump reservoir is filled by fort, and aids in overall care whether used stand
alone and/or in conjunction with common modal-
ities of pharmacology agents, physical therapy,
J. P. Sees (*) and orthopedic surgery for nonambulatory and
Nemours Alfred I. DuPont Hospital for Children, ambulatory patients with cerebral palsy.
Wilmington, DE, USA
e-mail: JSees@nemours.org; julieanne.sees@nemours.org
Keywords
F. Miller Intrathecal baclofen pump · ITB · Intrathecal
Department of Orthopaedics, Nemours/Alfred I. duPont
medication administration · Antispasticity
e-mail: freeman.miller@gmail.com medication · Movement disorder management

https://doi.org/10.1007/978-3-319-74558-9_45
640 J. P. Sees and F. Miller
Introduction space. At our institution, typically trials are not

necessary on all patients, but for the ambulatory
Over the past 30 years, the significance in admin- patients, this is strongly recommended and
istering medication directly into the intrathecal performed often with concurrent gait laboratory
space, especially in the spinal canal, has continued analysis to assist in the decision-making process.
to be of remarkable interest and development. Caretakers and the medical team then monitor
Since there is a general perception that spasticity the child and a joint decision is made as to the
originates in the spinal segments, a high dose benefits. For especially difficult cases, an indwell-
of drug concentrated in this region of the nervous ing catheter, which can be left in place for several
system should be given to provide effect. This days, may be used so the dose can be adjusted.
route was initially developed to administer This implanted catheter is used for children with
morphine (Erickson et al. 1985) but has quickly greatly variable tone, or individuals in whom
been applied to administration of baclofen adjustable doses of baclofen are to be monitored.
(Zierski et al. 1988). The intrathecal pump is a
battery powered implant which is placed in the
abdomen, and an intrathecal catheter is introduced Treatment
into the intrathecal space within the spine. This
catheter is tunneled subcutaneously around the The initial recommendation was to do a series
lateral side of the trunk to the anteriorly implanted of three injections on consecutive days starting
pump site and connected to the pump. The pump with 25 mg, then 50 mg, and then 100 mg on the
is controlled with an external radiowave-mediated third day (Albright et al. 1991). We have not
controller, and the pump reservoir is filled by found this algorithm very useful and prefer to
direct injection through the overlying skin give a single dose of 75–100 mg via the inserted
(Case 1). The primary medication used to manage catheter (Albright et al. 1996). Children either do
spasticity by intrathecal pump administration is or do not respond, and the small dose differences
baclofen. The administration may be continuous, in the prior recommendation add little to under-
or the pump can be programmed to have higher standing the effect. Also, the recommendation that
doses over a short time, then greatly reduced for children be tried on oral baclofen (Albright et al.
a period of time, and thus utilize a flexible dosing 1991) has little merit, as there are no data
regimen as desired. suggesting that it is helpful in children with
CP. Our experience has been that oral baclofen is
almost never of any beneficial predictive value.
Natural History As suggested in the “Best Practices for Intrathecal
Baclofen Therapy: Screening Test (Boster et al.
The use of intrathecal administration of baclofen 2016),” the algorithm our colleagues and we use
was first approved by the FDA for use in children for intrathecal baclofen is to do a clinical evalua-
in 1997. At the time of approval, there were fewer tion, if warranted followed by one injection trial,
than 200 children with implanted pumps. In the then the pump delivery system is implanted sur-
past 20 years, these pumps have become much gically and adjustment of the dose is done on
more common. These pumps have the tremendous bi-monthly basis until maximized therapeutically
advantage of being adjustable and can be to the child’s needs. We infrequently use the small
discontinued at any time should the results not 20-ml pump because it is only minimally smaller
be thought of worth the trouble. Usually in than the 40-ml pump but has a capacity that is
an initial consultation, the clinician makes a care- almost 50% less. This capacity becomes very
ful assessment with a listing of the caretakers’ significant when the child requires a high dose of
concerns. If the child has not had a spinal baclofen, such as 1000 mg per day. If the 20-ml
fusion, a trial dose may be performed with pump is used, it must be filled much more fre-
75–100 mg injected as a bolus dose in the epidural quently even if the 2000 mg/ml concentration for
43 Intrathecal Medication Administration in Cerebral Palsy 641
baclofen is used. This type of dose is not uncom- The outcome of administering baclofen via
mon, and the size of the child is not related to their intrathecal pump is a clear reduction in spasticity
baclofen needs. in most children. After the initial implantation, it
may take 3–6 months before a constant level of
Case 1: 8 Year Old Girl drug that will keep the spasticity decreased is
Here is an 8-year-old girl who is mentally found. The drug accommodation effect is well
challenged with severe spastic quadriplegia. She known in the oral use of baclofen and occurs
is completely dependent for all care needs. Her with intrathecal dosing as well. However, when
mother’s complaint is that she has difficulty with a certain optimal dose is reached, this accommo-
diapering, dressing, and bathing. Sometimes dation effect no longer occurs. The required
the child would have severe extensor posturing dosing for individual children varies greatly and
which made seating rather difficult. She would is not related to body size. The dose requirements
sleep well, fed by gastrostomy tube, and has vary from 100 mg to 2000 mg per day. The correct
seizures several times a day, which were felt to dosing can be determined only by slowly
be well controlled, and weighed 16.7 kg. increasing the dose and evaluating the effect on
A pump was inserted with good spasticity the child. After spasticity reduction has been
relief (Figs. 1 and 2). Over 6 months, she contin- accomplished, the functional gains are extremely
ued to have rapid accommodation to the drug; variable, with the clearest gains occurring in chil-
however, a plateau dose of 650 μg was reached dren with quadriplegic pattern involvement
that continued to control her spasticity. She had
little body fat with the pump visible with slight
prominence on her abdomen (Figs. 3 and 4).
Fig. 1 Pump inserted with good spasticity relief Fig. 2 Pump inserted with good spasticity relief
Fig. 3 The baclofen pump placed externally in the loca- Fig. 4 Pump visible with slight prominence on abdomen
tion where bit will be implanted in the right lower quadrant
of the abdomen
weakness. Namely, in our study, three adolescents,
one GMFCS II and two GMFCS III, preferred more
based on subjective reports from caretakers. These spasticity because it provided a sense of stability
caretakers report improved ease of dressing and and strength to them, assisting in their ambulatory
other activities of daily living (Albright 1996a; ability (Pruszczynski et al. 2017). Our experience,
Almeida et al. 1997). Improved sleeping has been as well as the experience reported to us from other
noted in many of our patients, as well as behavior gait laboratories, suggests that children’s speed does
improvements. Improved sitting and upper extrem- not change, but there may be some increased range
ity use are also reported quite often by the families of motion at the knee to enhance potential for
(Armstrong et al. 1997; Albright 1996b). All these strengthening in gait while in some children the
functional gains are subjective reports that usually tone reduction instead may lead to further crouch.
make the families very happy with the device. The Uncovering an underlying component of weakness
use of intrathecal administration of baclofen in especially during the adolescent growth period can
ambulatory children has very minimal experience confound the pump benefit.
and is used mostly in older children with severe gait
disturbances (Albright 1996b; Gerszten et al. 1997).
Attention must be given particularly to those Complications
patients where a decrease in tone may lead to a
decrease in ambulatory function. We found in our Complications with the use of the intrathecal
study of ambulatory children that some gait kine- pump vary; however, the rates are worth men-
matic improvements such as knee flexion at initial tioning. Incidence of infection in the literature
contact was helpful to gait; however, it can be has been reported anywhere from 0% to 25%
difficult to determine whether reduced tone is (Albright 1996a; Armstrong et al. 1997; Wiens
improving function or uncovering underlying 1998). In our experience, infection of the pump
system is 2.4% per procedure, while the risk of

late infection over 5-years was 0.95% per year
(Bayham et al. 2016). Mechanical catheter
problems have been reported as well, including
catheter breakage, disconnections, and kinking
(Zierski et al. 1988; Albright 1996a; Armstrong
et al. 1997). Pump pocket effusion and persistent
cerebrospinal fluid (CSF) leakage have also
been reported (Almeida et al. 1997). The acute
withdrawal of baclofen, if it is given either intra-
thecally or orally, may cause children to have
hallucinations and acute psychosis (Kita and
Goodkin 2000). The complications of the
baclofen pump are generally easy to treat and
do not have permanent consequences. Most
infections that involve the pump require that
the pump be removed and the infection cleared;
then the pump can be reinserted. We have been
able to treat initial pump pocket infections dur-
ing the same surgical setting insertion by placing
a new pump at a different anatomical site from
the infected pump pocket. (Fig. 5) The new fresh
pump is then connected to the old catheter at a Fig. 5 A child with a pump pocket infection who was
site removed from the infection site. This treated with removal and reimplantation of new baclofen
pump at different anatomical site
approach with removing of the infected pump
has been successful when the infection is local-
ized to the pump pocket and the patient is not strongly encouraged with a high level of suspi-
septic. Most infections of the spinal catheter are cion for any sign of infection or malfunction.
treated with removal of the catheter and upon An important technical detail that will avoid
subsequent infection clearing, then reinsertion wound problems over the pump in thin children is
of the catheter. We also have treated one patient to make sure the incision used to insert the pump
who presented with a ventriculoperitoneal is very proximal so none of the scar resides over
(VP) shunt infection with a course of intravenous the pump or catheter after implantation. This
antibiotics and acute intrathecal catheter means that the incision to insert the pump may
exchange with no complications, and there is be at the level of the lower ribs. All wound prob-
one report in the literature where intrathecal van- lems we have encountered have been in cases
comycin hydrochloride was used in the pump where the incision ended crossing the underlying
and the pump was saved (Bennett et al. 1994). pump, usually at the junction where the catheter
In our series of 313 children managed with inserts into the pump (Fig. 6). Inserting the pump
intrathecal baclofen therapy, 31 children under the external oblique fascia is another option
had VP shunts, with two patients having that will help with soft-tissue coverage. The major
infection of both systems and three patients had problem with catheter complications is diagnos-
infection in one system (Abousamra et al. 2017). ing the problem. Sometimes children are not
Our recommendation suggests if aspiration from responding as expected, or suddenly stop
both systems shows positive cultures, treatment responding, to the baclofen. If this occurs, there
should be removal of both systems, while if the may be a possible catheter problem. The first
primary system does not show positive cultures, study should be a radiograph to evaluate the
it may not need removal but close follow-up is catheter. Sometimes the radiograph will be able
to visualize catheter discontinuity (Fig. 7). An developed a protocol using the computed tomog-
attempt in the clinic can be made to aspirate raphy study for a safe and an effective modality
from the catheter aspiration portal which may in locating defects along the intrathecal baclofen
itself demonstrate discontinuity with a dry tap. delivery system with ultimately having
Injection with a radiopaque material may also be advantage to guide surgical specific solutions
used followed by a radiograph or as we have (Abousamra et al. 2016). Normal CT findings
with the injected material flowing freely through
the catheter are depicted on axial cuts as a per-
fectly layering fluid which forms a crescent shape
around the catheter tip in Figs. 8 and 9 and the
fluid gradually dilutes as the cuts proceed in the
caudal direction. Inadequate contrast pooling can
be noticed on the CT scan as in Figs. 10 and 11
where the fluid distribution layers lose the
crescent shape. Areas of leakage such as fluid
collection around the pump (Fig. 12), along the
catheter (Fig. 13), or sequestration at the catheter
tip (Fig. 14) are easily evident with CT scan eval-
uation. If this study is inconclusive, there is
a serious concern; the child should be taken back
to the operating room and methodically investi-
gated where the anterior catheter pump connec-
Fig. 6 The incision for the baclofen pump should be tion is exposed, the catheter is removed, and there
higher than the expected placement site of the pump. This should now be the ability to obtain CSF from the
is to prevent the incision from being directly across the catheter. If not, the posterior catheter has to be
connectors of the pump, as shown in this picture, since
there is a higher risk of wound breakdown and possible exposed, disconnected, and whichever section is
complication. Ideally the incision should be well away not patent should be replaced.
from the pump pocket, as shown by the yellow line
Fig. 7 A plain radiograph

showing a catheter fracture
with the two ends of the
fracture (arrows)
Fig. 8 Normal CT scan

with the contrast medium
forming a perfect crescent
free from the catheter
Fig. 10 Inadequate pooling of the contrast. The fluid fails

to form the crescent shape and it does not flow free from the
catheter
child in a supine position for up to 2 weeks to see

if this leak resolves. The primary symptom from
this CSF leak is a severe headache and nausea. In
most cases, with time the leak stops, and to assist
Fig. 9 Three dimensional CT reconstruction of the same
if swelling is visible at the spinal incision, a pres-
patient in Fig. 6 with the cut level shown (arrow). The
whole catheter length can be tracked on this type of sure dressing with abdominal binder may also be
imaging used. We have had children who continued to
leak despite conservative measures. One child
Another complication that may occur is in had a posterior spinal fusion in which the fusion
a child who maintains a CSF leak after insertion mass had been opened. This wound again was
of the catheter. The initial treatment is to leave the opened, and the fascia was placed over the dura
Fig. 13 Fluid seen in the lumbar spinal canal at and below

the catheter level (arrow) indicative of a leak just before the
catheter enters the canal
Fig. 11 Three dimensional CT reconstructions with the

cut level of Fig. 8 shown (arrow)
Fig. 12 Fluid collection around the pump indicates a leak

at the pump catheter connector
Fig. 14 Fluid sequestration seen around the catheter tip

with closure of the bone defect with methyl
methacrylate. If an opening in the fusion mass is
done to insert the catheter, the bone defect is now following a trial injection, and, in some cases, in
routinely closed with a Tisseel Fibrin or hemo- stopping leaks around inserted catheters. In this
static matrix sealant. If the child has not had situation, the insertion site may also need to be
a spinal fusion, an epidural blood patch may be exposed and the catheter insertion site covered
tried. This patch works well if a leak occurs with a fascial patch.
If there is a sudden malfunction of the 2 years after the implantation. An organized

implanted pump, it will stop functioning instead approach must be in place to help optimize
of pumping too much. This safety feature of intrathecal baclofen therapy and provide
the pump has not been reported to fail. In this troubleshooting in cases of under dose and over-
circumstance, if there is a question of pump dose. Evaluation includes a targeted history of
function, the pump needs to be replaced. The onset, duration, course, physical examination,
battery that powers the pump has an implanted radiographic/imaging testing, and pump interro-
life of approximately 7 years. When the battery gation (Saulino et al. 2016). In cases of somno-
loses power, the whole pump has to be replaced. lence or autonomic instability, children may
The catheter does not need to be replaced. We need more emergent care with hospitalization.
recently have observed when vagal nerve stimu- If a child has had an increasing need for baclo-
lator magnets are placed close to the pump pocket fen, or is requiring a sudden increase in baclofen
the pump has been observed to stall and restart after having been stable, catheter malfunction
inconsistently. If there is any question as to should be considered. After the full workup for
whether a child’s pump is functioning or there is catheter malfunction, or after demonstration that
a catheter malfunction, the child should be placed the catheter is functioning, another option for
on oral baclofen to prevent the withdrawal dosing is to use a drug holiday. In this treatment,
psychosis that occurs in some children with the intrathecal baclofen is reduced and then
appropriate assessment performed. Baclofen also slowly decreased to zero to avoid a withdrawal
has an antihypertensive effect (Sweet et al. 1979); psychosis. The pump may be left in the turned-
however, this is seldom a significant problem. off position for 1 month and then the drug slowly
There may be a sympathetic blockade-type effect reintroduced. This drug holiday should allow
decreasing the overreacting peripheral basal the nervous system to redevelop sensitivity to
motor response that creates blue feet when the the drug. Another way to use this concept of
feet get cold (Rode et al. 1999). This is a normal a drug holiday is to give large intrathecal
response also seen in adolescent and older boluses several times a day instead of continuous
individuals who are nonambulatory. dosing. Therefore, instead of giving a continuous
Another well-documented effect of baclofen dosing rate of 2000 mg, the child may be
in rats is a decrease in the number and frequency given 1000 mg just before bedtime, and then
of penile erections (Agmo and Paredes 1985; another 1000 mg over a 30-min period the
Leipheimer and Sachs 1988). There is one report first thing in the morning. These different
involving adult males with spinal cord injury- dosing regimens may provide a better benefit
induced spasticity treated with intrathecal in some children compared with continuous
baclofen. In this report, a significant number of administration.
men reported a decreased time and rigidity The current role of intrathecal baclofen in
of erections, and two men reported losing the the treatment of children with severe spasticity
ability to ejaculate (Denys et al. 1998). One is primarily in nonambulatory children. From
of our patients was a young man whose main a theoretical standpoint, this treatment should
complaint with intrathecal baclofen was also be ideal for the 3–8-year-old spastic
a decreased quality of his erection and a prolonged ambulatory child for whom a rhizotomy could
latency period between erections. This complica- be considered. The size of the pump and
tion should be mentioned to patients for whom it the need for long-term maintenance, with filling
might be a concern. at least every 3–6 months, has made it
A small group of children require a very high sometimes challenging to convince parents and
dose of intrathecal baclofen, sometimes physicians that this is a good treatment option.
2000–3000 mg per day. Also, some children Also, there are no objective published data to
who are on a lower dose suddenly need increased guide recommendations for the best modality
doses if their spasticity is increasing 6 months to of tone management. This question would be
an excellent project for a well-controlled study a pump implant (Saulino et al. 2015). With both
similar to the randomized rhizotomy studies of these studies, as previously noted in the literature,
(Steinbok et al. 1997; McLaughlin et al. 1998). the successful cost effectiveness of the intrathecal
We do have insight with one investigation of baclofen delivery system does provide our only
the long-term results of intrathecal baclofen adjustable tone management tool improving the
therapy for children with spastic cerebral quality of life for children with cerebral palsy.
palsy where there was an improvement in
quality of life in children and participants
would recommend this mode of treatment and Cross-References
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Dorsal Rhizotomy for Spasticity
Management in Cerebral Palsy 44
P. Nilsson, N. Wesslén, H. Axelsson, G. Ahlsten, and L. Westbom
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 652
Some History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 652
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 653
Patient Selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 653
Postoperative Rehabilitation Program . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 657
Expected Outcome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 658
Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 658
Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 659
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 659
Abstract
Selective dorsal rhizotomy (SDR) is a neuro-
surgical procedure for the relief of spasticity
interfering with motor function in children
with spastic cerebral palsy (CP). The goal of
P. Nilsson (*) · N. Wesslén the treatment is to improve function as well as
Department of Neuroscience, Neurosurgery, University reduce pain and discomfort related to severely
Hospital, Uppsala, Sweden
e-mail: pelle.nilsson@neuro.uu.se; increased spasticity. SDR is an ablative proce-
Nils.Wesslen@neuro.uu.se dure that results in lifelong effects on function
H. Axelsson in the central nervous system. One must also be
Department of Neuroscience, Neurophysiology, aware that performing SDR does not guarantee
University Hospital, Uppsala, Sweden that other treatments for spasticity or orthope-
e-mail: Hans.Axelson@akademiska.se dic corrective procedures can be avoided. For
G. Ahlsten SDR to be an effective treatment, it must be
Department of Pediatrics, University Hospital, Uppsala, combined with specific physiotherapy over a
Sweden
e-mail: Gunnar.Ahlsten@kbh.uu.se long period of time. Today there exists a good
L. Westbom
Department of Pediatrics, University Hospital, Lund,
Sweden
e-mail: lena.westbom@med.lu.se

https://doi.org/10.1007/978-3-319-74558-9_46
652 P. Nilsson et al.
body of evidence that SDR is an effective Some History

means of treating patients with the CP subtype
spastic diplegia, as long as selection criteria are Dorsal root rhizotomy as a treatment for spasticity
rigorously adhered to. The procedure is also is an old procedure. The method was introduced
safe with little risk of short or long-term com- by Foerster (1911) and was based on experimental
plications. Further studies on long-term effects findings from Sherrington’s work with a spasticity
late in adulthood will show if the treatment model in cats (Sherrington 1898). In Foerster’s
effects are stable over time. procedure, electric stimulation was used to iden-
tify dorsal roots from L2 to S2 that were then
Keywords subsequently completely cut. He also described
Selective dorsal rhizotomy · Spasticity · in this study that postoperative physiotherapy was
Spastic diplegic cerebral palsy mandatory for a good outcome. Gros et al. (1973)
introduced some measure of selectivity in the
procedure by only cutting 80% of the dorsal
Introduction roots between L1 and S1. The method was further
developed and refined by Fasano et al. (1979).
Selective dorsal rhizotomy (SDR) is a neurosur- Outcome was improved by introducing
gical procedure performed for the relief of spas- intraoperative EMG to determine which rootlets
ticity interfering with motor function in children should be cut. However, Fasano’s method still
with spastic cerebral palsy (CP). The goal is to entailed bladder dysfunction since S2 was
improve function and reduce pain and discomfort included in the sectioning. Peacock and Arens
related to severely increased muscle tone. It is one (1982) made further improvements on Fasano’s
of the tools for the treatment of muscle hypertonia. method by changing the surgical approach from
The most frequently used neurosurgical treatment Th12–L2 to L2–L5, thereby making it easier to
is insertion of a pump to infuse intrathecal baclo- identify sacral nerve roots and subsequently
fen (ITB). Deep brain stimulation (DBS) has also reducing the risk of bladder dysfunction. The
been an option during the last 10 years; ITB and selective dorsal rhizotomy procedure as described
DBS are mostly used in cases where a dystonic by Peacock and Arens, including indications and
component is involved. contraindications for the intervention, has now
SDR is the only treatment that reduces spasticity been used in many countries around the world
permanently, giving new prerequisites for func- for the last 30 years. During this period, some
tional training and contracture prevention. Together centers have adopted Park’s modification of the
with goal-directed physiotherapy, SDR improves procedure, which entails a more limited
motor function development in carefully selected laminectomy at the conus level coupled with
cases (HQO 2017). SDR is included among the rare EMG (Park and Johnston 2006).
interventions in CP that have enough scientific evi- In the beginning of the modern SDR era,
dence to be fully recommended (Novak et al. 2013). expectations on outcome were high among many
Selective dorsal rhizotomy (SDR) is now professionals. However, after a decade or two,
performed at the lumbosacral level on children disappointment with the results increased in
diagnosed with bilateral spastic cerebral palsy many centers. Severe lumbar lordosis and fre-
(BSCP), but the intervention has also been used in quent occurrence of spinal problems in the
adults with BSCP and in unilateral spastic CP. In SDR-operated patients were reported even if
this chapter, we will only discuss lumbosacral SDR there hadn’t been control groups (HQO 2017).
for spasticity management in BSCP, specifically the Spinal problems in other patients with spastic
type of BSCP with more severe involvement of the diplegia are also common (Harada et al. 1993).
lower than of the upper limbs (CP spastic diplegia) At the same time, as the reports of disappointing
including all levels of gross motor function defined results were being published for SDR, new treat-
by GMFCS levels I–V. ments for spasticity were introduced. Intrathecal
44 Dorsal Rhizotomy for Spasticity Management in Cerebral Palsy 653
baclofen administered via implanted pumps (ITB) The OMG motor growth curves show that the
and intramuscular injections with botulinum toxin average gross motor development, as measured
became widely used and were seen as attractive with GMFM-66, levels off much earlier than pre-
alternatives since they were methods that were not viously recognized and occurs earliest in the most
based on permanent lesions in the patient’s ner- severe CP (GMFCS level V) at 2–3 years of age
vous system. Since the indications for these two and latest in milder CP (GMFCS I) just before
therapies and SDR partially overlap, many centers 5 years of age. After plateauing of the gross motor
abandoned the SDR procedure. development, deterioration was seen in the
Other centers that had experienced good GMFCS III–V groups between about 7 years
results, probably because of strict adherence to and 13–15 years of age (Hanna et al. 2009).
indications and contraindications for the opera- Increasing body size with age and muscle weak-
tion as described by Peacock and Staudt (1991), ness (a part of the CP syndrome), malnutrition,
continued to perform SDR. A comparative contracture development, and pain were shown to
meta-analysis from three randomized controlled be major causes of this deterioration (Bartlett et al.
trials (RCTs), comparing SDR with intense 2010). Continuing decrease of motor function,
physiotherapy (PT) against controls receiving pain, and fatigue are described in several cross-
only the same PT intervention as the operated sectional studies which include adults with com-
patients, showed clinically and statistically sig- paratively good motor function during childhood,
nificant motor function improvement up to GMFCS levels I–II (Opheim et al. 2009).
2 years after inclusion in the study
(MacLaughlin et al. 2002).
Scientific reporting on long-term outcome has Treatment
increased steadily, but skepticism toward SDR
still remains among many professionals working Patient Selection
with CP patients. Despite this skepticism, the
amount of operations has increased during recent As stressed in this chapter, correct patient selec-
years, probably because of increased awareness tion is essential for achieving good results with
among parents and patients that the procedure SDR. The potentially beneficial effect of spastic-
exists (the Internet) and that the operation has ity must be evaluated when assessing the patient.
become regarded as an evidence-based interven- Spasticity may be needed for antigravity control
tion (Novak et al. 2013; HQO 2017). as it can compensate for muscle weakness and
Parallel to increased knowledge on outcome even high levels of spasticity may not interfere
from long-term follow-up of surgery over the with function or well-being. Since SDR is an
past three decades, a greater understanding of irreversible intervention that has lifelong conse-
natural gross motor development in children quences and can lead to deterioration of motor
with CP has developed. This has been possible function if selection criteria are not adhered to,
through the Ontario motor growth study (OMG all aspects of the patient’s function must be eval-
study) and the creation of the OMG curves uated prior to surgery.
(Rosenbaum et al. 2002). The OMG curves are A review of the literature shows that selection
based on long-term follow-up using valid and of patients for SDR varies in different studies
reliable classifications and measurements of (Grunt et al. 2013). Some centers focus on ambu-
motor function, the Gross Motor Function Classi- lant young children (GMFCS I–III, 2–7 years),
fication System (GMFCS) (Palisano et al. 1997), while other centers have wider ranges regarding
and the Gross Motor Function Measure (Russel age and included all GMFCS levels. The contra-
et al. 2002). Both of these were developed at indications for SDR also vary between centers.
CanChild. The OMG study sample included all The selection criteria and procedures are not con-
CP subtypes and excluded children with ITB or sistently described, classified, or quantified (Grunt
SDR treatment. et al. 2013). The decision procedures and criteria
used in the SDR programs in Lund and Uppsala, regarded as a contraindication as well as severe
Sweden, are described here. contractures and previous orthopedic operations
(except for adductor tenotomy). Hip dislocation
Decision Procedure and spinal abnormalities are in most cases contra-
A child where spasticity is judged to be a major indications for SDR in ambulant children. Cogni-
underlying problem for motor function should be tive disability is not seen as a contraindication as
referred to a clinic with a broad experience of the long as the child shows a drive to improve and
different treatments for motor problems. A thor- willingness to train motor activities. Three
ough medical history and physical examination through seven years of age are considered as
should be performed by both a physiotherapist optimal timing for surgery, at least in ambulant
and a pediatric neurologist. Repeated examina- children (GMFCS I–III). Children with any
tions are often necessary. The child’s motor func- GMFCS level could be considered as candidates
tion is assessed in many situations and activities if the spasticity is judged to be the main problem
and with different instruments including the and if there is no major contraindication (such as
GMFM. The GMFCS level should be determined. dystonia or a severe spinal abnormality). In Upp-
The level of spasticity is quantified according to sala, ITB treatment is usually chosen for children
the methods of Ashworth and Bohannon or Tar- with GMFCS III–IV and severe spasticity, while
dieu (Bohannon and Smith 1987; Gracies et al. in Lund, SDR is also recommended for these
2000). Tendon reflexes and presence of clonus are children provided that there are no dystonic traits.
noted. Goniometry of joints in the legs should be To set realistic individual functional goals for
performed. the procedure are very important. The goals are of
The underlying diagnosis of CP should be ver- course related to the GMFCS level of the child. It
ified. In most of the cases, the diagnosis is is important to discuss the goals in detail with the
supported by neuroimaging. parents and also with the local physiotherapist.
The presence of the parents at the examination SDR should also always be combined with long-
is very important. It is of great advantage if the lasting physiotherapy in order to reach the best
child’s personal physiotherapist can participate in possible result.
the evaluation. When SDR or ITB are considered It is very important to have a detailed docu-
as treatment options, the child should meet the mentation of the child’s motor function using the
entire multidisciplinary team (pediatric neurolo- methods described above. The findings of the
gist, physiotherapist, neurosurgeon, and orthope- preoperative evaluation are also important for
dic surgeon) for further evaluation. the neurosurgeon and neurophysiologist as a
For children regarded suitable for SDR, some basis for decisions during the operation.
special aspects of the evaluation are very impor- Preoperative X-ray of the spine is often valu-
tant. Muscle strength in the trunk and legs should able. If there is any doubt regarding the CP diag-
be evaluated in various activities. Selective motor nose, neuroimaging is sometimes relevant and has
control is also estimated as well as trunk stability in many cases been performed earlier. If earlier
and balance in the sitting position. If the muscle imaging exists, a reevaluation of previous imag-
strength is suspected to be low, the child can be ing is recommended to look for changes in the
put on a training program for a few months and thalamus, basal ganglia, or cerebellum which are
then reevaluated. The ability of the child and contraindications for the operation. Findings of
family to cooperate in intensive physiotherapy, white matter injury of immaturity on imaging
for mobilization and future training, is of utmost strengthen the clinical diagnosis of spastic diple-
importance to be evaluated as well as the possi- gia. Since the procedure is on the lumbosacral
bility to organize such training in the long term. level, continence functions should be evaluated,
In Lund and Uppsala, the criteria proposed by and a bladder scan of the urinary bladder should
Peacock and Staudt (1991) are used in the selec- be performed. Standard preoperative blood tests
tion process. Presence of ataxia and dystonia is should be taken.
General Selection Criteria for SDR rounded spine (thoracolumbar kyphotic

• A confirmed diagnosis of cerebral palsy. There position)
must not be any signs of progressive brain 3. Periodic functional improvement and less
disorder and no neurometabolic disorder. CP muscle pain with repeated injections of bot-
due to postneonatally acquired brain injury is ulinum toxin, but with too little or too short
excluded. effect, or with problems to carry out regular
• Confirmed subtype spastic diplegia, as classi- repeated treatments
fied in the Swedish classification of CP sub- • Enough muscle control and strength under the
types (Westbom et al. 2007), with more spasticity to reach the individually formulated
involvement of the legs than of the arms. goals. Previous lengthening operations of
• Pure spasticity. CP subtypes are classified Achilles tendons or hamstring muscles are con-
according to “dominant neurological symp- traindications for SDR if the goals include
tom” meaning that also other neurological standing transfers, standing without support,
signs may coexist with the dominating spastic- or walking.
ity in spastic CP. Ataxic or other than subtle • Available physiotherapy and orthotic services
dyskinetic signs are regarded as contraindica- and willingness to perform pre- and postoper-
tions for SDR. ative functional training activities and to use
• Absence of dystonic traits or dystonia is an orthoses when needed
important selection criterium. Dystonia may • Any gross motor function level – GMFCS I–V
be mistaken for spasticity. Spasticity is also
often present in the dystonic CP subtype, Individual Selection Criteria for SDR
although dystonia is the dominating neurolog- Every child’s individual goals, as expressed by
ical sign. Foot clonus and positive Babinski are themselves or for young children by the parents,
often present in dystonic CP, often times with are important parts of the selection criteria. The
more intense clonus, toe-spread, and spontane- goals should be established by the family and the
ous Babinski sign than you see in pure spastic child’s personal PT together with the SDR team.
CP. Young children with dystonia (tonus- The goals should be based on the child’s actual
changing CP) are often relaxed during sleep. function and the child’s and family’s priorities.
Another clinical sign of dystonia is that the General goals in GMFCS I–II are improved
child may stiffen especially when held stand- balance, endurance, and flexibility in standing,
ing in an upright position. Children with CP walking, running, and jumping; in GMFCS III
after severe asphyxia at term usually have stability and variability in sitting, to attain and
hyperkinesia and/or dystonia, and some even maintain standing, walking, and enabling self-
have severe spasticity. SDR is contraindicated propelled wheeled transfers; and for GMFCS
in these patients. Children with CP following IV–V independent sitting, supported standing,
term asphyxia have neonatal hypoxic ischemic enabling wheelchair transfers, and to ease daily
encephalopathy often evident in the thalamus burden for caregivers. Reduction of pain and dis-
and basal ganglia on brain MRI. comfort from spasticity or inactivity may be a goal
• Spasticity interfering with functional develop- for some children in all GMFCS levels. To “pre-
ment – operationalized as: serve joint ROM” is usually not a goal formulated
1. Spasticity involving both proximal and dis- by the child but is important in order to reach
tal muscle groups in the lower parts of the many of the mentioned functional goals.
body with difficulties to preserve joint range
of motion (PROM), despite full conserva- Timing of SDR Surgery
tive treatment (physiotherapy, orthoses, In practice, it is good to operate young children as
plasters) soon as the diagnosis is clear and the individual
2. Poor sitting ability with pelvis tilt due to child’s development has been followed for some
spasticity, with too small sitting base and time. Effective contracture prevention becomes
easier after SDR and is important at a young age in Once the dura is open, nerve stimulation is
severe spasticity to avoid nonreversible contrac- used to identify the motor and sensory nerve
tures and tendon-lengthening operations which roots for L2–S2 and L1 if sectioning is being
will reduce muscle power permanently. SDR in considered at this level (i.e., in patients with hip
early preschool years coincides with ongoing flexor spasticity). This is done with Peacock pro-
gross motor development and is a time when the bes. Silicone nerve retractors, cut silicone strips,
child may have more time and interest for the or cut surgical cottonoids can be used to keep the
intense physiotherapy needed during the first sensory and motor nerves separated once they
postoperative year than they have once they have been identified. The sensory roots are then
have started school. In older children, 6–8 years subdivided into rootlets using sharp dissection.
of age, the initial postoperative period seems to be At this point, a systematic stimulation of the
more demanding before they have regained their afferent rootlets with intraoperative EMG is
usual function and independence. performed for each level. Pathological rootlet
Depending on individual goals, SDR in pure response is graded according to the degree of
spastic CP may be beneficial also in older age, spread beyond the nerve’s normal myotome.
even in adults, but this and other new indications This stimulation response is evaluated using
have to be scientifically evaluated. both neurophysiological measures and manual
evaluation of relevant muscle response by a
Surgical Procedure physiotherapist. The sensory rootlets with abnor-
Under general anesthesia, the patient is placed in mal spread are sectioned but should not exceed
the prone position. Muscle relaxants should not be 70% of the total amount of rootlets. Different
used after induction of anesthesia. Appropriate centers describe sectioning percentages that
bolstering is placed under the chest and pelvis. vary between 40 and 80% (Grunt et al. 2013).
EMG needle electrodes are inserted into muscles At the L4 and S2 levels, special considerations
bilaterally including all spinal root levels that are should be made concerning muscle strength in
potential candidates for sectioning (see descrip- the quadriceps muscles and in sphincter
tion neurophysiology strategy). responses, respectively.
Access to the spinal canal follows standard Following the sectioning of the sensory root-
neurosurgical procedures for midline approach to lets, hemostasis is controlled, and the dura is
the intradural space. Today, SDR is commonly closed in a watertight manner with running
performed through single-level laminectomy sutures. Different means of administering analge-
(Park and Johnston 2006)/laminoplasty (Funk sia are used in different centers and include
and Haberl 2016) at the L1 level or multilevel intradural, epidural, or intravenous strategies. If
laminoplasty at L1–L5. Peacock and Arens’ intra- or epidural catheters are used, it is at this
(1982) original approach was a multilevel stage of the operation that they are put in place.
laminectomy L2–S1 but has been replaced by The laminoplasty is performed with sutures or
single-level laminectomy/laminoplasty or multi- wires. The paravertebral muscles, fascia, and
level laminoplasty instead of laminectomy to skin are sutured in a conventional manner for
reduce the risk of developing spinal deformity spine surgery.
(Turi and Kalen 2000; Johnson et al. 2004; Spie- Patient mobilization and physiotherapy can
gel et al. 2004). The single-level approach is con- start 2–3 days postsurgery according to local
sidered to be more difficult because of the limited protocols.
exposure to the nerve roots that it gives at the
conus level. With the multilevel opening, there Neurophysiologic Intraoperative
are clear anatomical landmarks since the nerves Monitoring
can be followed to the level where they exit the The key procedure in SDR is repetitive (50 Hz)
spinal canal. electrical stimulation of the afferent rootlets for
Next the dura mater is opened in the midline. 1 s, which reliably (Mittal et al. 2001) identifies
those rootlets that upon stimulation generate path- avoid common pitfalls, it is important that EMG
ological reflex activity from those that produce interpretation is performed by an experienced
normal muscle reflex activity and consequently examiner. For instance, “crosstalk” between differ-
should be spared. ent recording sites, i.e., a phenomenon where activ-
Irrespective of the surgical approach to expose ity in one muscle is detected in a nearby
the cauda equina, it is imperative to identify the non-contraction muscle, may easily be mis-
different sensory roots (commonly L2–S2 bilater- interpreted as widespread pathological reflex activ-
ally) before longitudinally subdividing the dorsal ity. In similar situations, where reports from the
roots into several natural rootlets. Even if anatom- physiotherapist and the neurophysiologist contra-
ical landmarks are helpful in identifying lumbo- dict each other, stimulation should be repeated and
sacral nerve roots (particularly after L2–S1 results reassessed. To determine the extent of spas-
laminotomy exposing the entire cauda), it is ticity, the EMG response from stimulation is
important to realize that muscle innervation is graded according to criteria that commonly focus
variable (Phillips and Park 1989) and that section- on the spread of reflex activity beyond the spinal
ing dorsal rootlets based on anatomical textbook segment stimulated (Fasano et al. 1979). This is
knowledge solely is unacceptable in this context. based on a grading scale from 0 to 4 where the most
With the aid of intraoperative electrical stimula- severe grade 4 represents reflex activity that not
tion and electromyography (EMG), it is possible only engages multiple ipsilateral spinal levels
to identify the different lumbosacral roots and (grade 3) but also produces contralateral muscle
their target myotomes. In case of uncertainty, it activity. Typically, rootlets producing such abnor-
is also possible to distinguish posterior from the mal responses from electrical stimulation are sec-
anterior (motor) roots. Typically, a tenfold higher tioned. The physiotherapist, familiar with the
stimulus intensity is required for a single electrical patient’s clinical pattern of spasticity, should also
pulse to elicit a reflex response from a sensory root be influential in deciding the extent of rootlet sec-
compared to obtaining a direct motor response tioning at a given level (Mittal et al. 2001).
from anterior root stimulation. However, the The use of intraoperative neurophysiology
main purpose of this single pulse stimulation tech- may also prevent permanent bladder and bowel
nique is usually made with the intent to determine dysfunction from SDR. For instance, at sacral root
the stimulus threshold for the actual subsequent levels, reflex activity from the anal sphincter indi-
“spasticity” test (i.e., the 1 s train stimulation of cates that the stimulated posterior root carry sen-
the surgically separated rootlets). Long-lasting sory information from the pudendal area. In this
muscle relaxants are avoided, and anesthetic reg- situation, it is possible to use another probe for
imens that abolish spinal reflex activity should not recording sensory nerve action potentials from a
be used. An indication of suppressed spinal reflex single sacral rootlet and examine whether stimu-
activity related to inappropriate anesthesia level or lation of pudendal afferents in the genital and/or
agent is when test stimulation of anterior roots anal region elicits a response in the recordings
elicits a motor response, while concurrent stimu- (Mittal et al. 2001; Huang et al. 1997) that
lation of sensory roots does not. would in turn preclude sectioning of that rootlet.
Ideally, the intraoperative classification into nor- In summary, intraoperative neurophysiology is
mal or pathological (spastic) reflex motor responses an integral part of SDR and requires expert knowl-
from electrical stimulation should be performed in edge in EMG stimulation and recording
collaboration with a neurophysiologist and a phys- techniques.
iotherapist. Whereas the physiotherapist, positioned
close to the patient, is able to observe the strength
and pattern of stimulus-induced muscle contrac- Postoperative Rehabilitation Program
tions, the neurophysiologist is provided with
records of the corresponding EMG reflex pattern After the operation, there is marked hypotonus
from multiple lumbosacral root myotomes. To and weakness in the lower extremities. The child
stays in the hospital for about 10 days and the SDR results are better (as measured with
mobilization follows a tight schedule. In our cen- GMFM) in GMFCS I–II than in the more severe
ters, the child is transferred to the pediatric habil- GMFCS levels.
itation unit for a further 2 weeks of intensified In a meta-analysis of three RCTs, it was shown
physiotherapy. that children with spastic diplegia at follow-up
Initially the physiotherapy is focused on mobi- about 1 year after SDR had gained more in
lization such as sitting, rolling, and different func- motor function after SDR in combination with
tional activities. Later on standing is introduced. intense physiotherapy than after intense physio-
The training should be incorporated in common therapy alone (MacLaughlin et al. 2002). Out-
daily activities and play. Hydrotherapy can be come in the short term (1–2 years) after SDR has
introduced after the scar has healed. also been reported in systematic reviews with
After the first intensive postoperative weeks, positive results regarding reduced spasticity,
the responsibility for the rehabilitation is trans- increased passive range of motion in joints in the
ferred to the local habilitation unit. In Lund, this legs, improved gait, and improvement in gross
includes repeated assessments and discussions motor function (Grunt et al. 2011; Novak et al.
with the SDR team PTs regarding goals, treatment 2013; Ont Health Technol Assess Ser 2017).
content, and orthoses (Nordmark et al. 2008; Long-term follow-up reports (>5 years
Josenby et al. 2014). Recommended frequency postop) give somewhat conflicting results.
of physiotherapy is 1 h twice a week for the first There are also few studies with a high scientific
6 months and thereafter 1 h once a week, but this level. Most studies however show positive
may vary. Parents and preschool teachers are results after SDR. Gross motor function, func-
advised how to include training and contracture tional independence, and caregiver assistance
prophylaxis (standing shells and other orthoses) have been shown to improve, although most of
into daily and leisure time activities. Improvement the improvement takes place during the first
in motor function and daily functional perfor- years postoperatively. Spasticity is reported to
mance can be seen many years after SDR be permanently reduced, but in the systematic
(Josenby et al. 2012, 2014). reviews, no evidence was found regarding
effects in the ICF activity and participation
domains. In scientific studies regarding long-
Expected Outcome term treatment satisfaction from the patients
and their relatives, the information is scarce.
Differences in patient selection between studies However, in many studies, parents and children
as well as the extent and intensity of the postop- report improvements and satisfaction at follow-
erative rehabilitation program and other surgical up. Future studies with long follow-up periods
interventions affect the outcome after SDR. are needed to further clarify the long-term
Most studies show a positive effect of SDR in effects of SDR (Grunt et al. 2011; Novak et al.
carefully selected children, but there are no 2013; HQO 2017).
RCTs with follow-up beyond 1–2 years postop-
eratively. The results in different studies must
also be looked upon in the context of the knowl- Complications
edge of the normal motor development for chil-
dren with CP, since it has been shown that the SDR has shown to be a safe procedure. Postoper-
capacity to acquire new motor skills levels off at ative problems during the first weeks are not
low age (Rosenbaum et al. 2002). The notion in uncommon and include dysesthesia/hypoesthesia
the literature of better results of SDR in the legs, urinary incontinence or retention, uri-
(as measured by GMFM) in younger than in nary tract infections, and constipation. Transient
older children is probably due to this difference postoperative hypotonia in the lower extremities
in “natural development,” as also the notion that is also common.
There are few reports regarding manifest last- Bohannon RW, Smith MB (1987) Interrater reliability of
ing continence problems related to SDR. A sig- modified Ashworth scale of muscle spasticity. Phys
Ther 67:206–207
nificant proportion of CP children have urinary Fasano VA, Barolat-Romana G, Zeme S, Sguazzi A (1979)
incontinence as a part of the clinical picture. Last- Electrophysiological assessment of spinal circuits in
ing sensory abnormalities after SDR are uncom- spasticity by direct dorsal root stimulation. Neurosur-
mon (HQO 2017). gery 4:146–151
Foerster O (1911) Resection of the posterior spinal nerve.-
An area of concern has been the reports of roots in the treatment of gastric crisis and spastic paral-
spinal bony abnormalities and back pain years ysis. Proc R Soc Med 4(surg sect):226–246
after SDR. Scoliosis and lumbar lordosis are Funk JF, Haberl H (2016) Monosegmental laminoplasty for
reported with rather high frequencies. Kyphosis, selective dorsal rhizotomy- operative technique and
influence on the development of scoliosis in ambulatory
spondylolysis, and spondylolisthesis are not children with cerebral palsy. Childs Nerv Syst
uncommon but reported to be less common (Turi 32:819–825. https://doi.org/10.1007/s00381-016-3016-3
and Kalen 2000; Johnson et al. 2004; Golan et al. Golan JD, Hall JA, O’Gorman G, Poulin C, Benaroch TE,
2007; Langerak et al. 2008). The frequency of Cantin MA, Farmer JP (2007) Spinal deformity
following selective dorsal rhizotomy. J Neurosurg
spinal abnormalities increases with age in all chil- 106(6 suppl):441–449
dren with CP and marked spasticity. It is therefore Gracies JM, Marosszeky JE, Renton R, Sandanam J,
unclear if SDR increases this risk significantly. Gandevia SC, Burke D (2000) Short-term effects of
The proportion of patients that have undergone dynamic lycra splints on upper limbs in hemiplegic
patients. Arch Phys Med Rehabil 81:1547–1777
SDR and later need spinal surgery seems to be low Gros C, Frerebeau PH, Kuhner A, Perez-Dominguez E
(HQO 2017). (1973) Technical modification in the Foerster opera-
Regarding hip problems, the situation was tion. Selective posterior lumbar root section. The
radiologically stable for most children after SDR results of 18 years of practice. 5th International Con-
gress of Neurosurgery, Tokyo 1973
on follow-up (HQO 2017). Grunt S, Becher JG, Vermeulen RJ (2011) Long-term
outcome and adverse effects of selective dorsal rhizot-
omy in children with cerebral palsy: a systematic
review. Dev Med Child Neurol 53:490–498
Conclusions Grunt S, Fieggen AG, Vermeulen RJ, Becher JG,
Langerak NG (2013) Selection criteria for selective
Lumbosacral SDR is an effective method for per- dorsal rhizotomy in children with spastic cerebral
manently reducing spasticity and is not associated palsy: a systematic review of the literature. Dev Med
Child Neurol 56:302–312. https://doi.org/10.1111/
with major negative side effects. SDR as a treat- dmcn.12277
ment for spastic diplegia in young patients pro- Hanna SE, Rosenbaum PL, Bartlett DJ, Palisano RJ, Wal-
vides lasting functional benefits over a period of at ter SD, Avery L, Russel DJ (2009) Stability and decline
least 10 years postoperatively if the procedure is in gross motor function among children and youth with
cerebral palsy aged 2 to 21 years. Dev Med Child
combined with physiotherapy. A prerequisite for Neurol 51:295–302
good results is adherence to strict selection criteria Harada T, Ebara S, Anwar MM, Kajiura I, Oshita S, Hiro-
and that there is a systematic follow-up of chil- shima K, et al (1993) The lumbar spine in spastic
dren. A multiprofessional approach is necessary. diplegia. A radiographic study. J Bone Joint Surg Br
75(4):534–537
SDR is a safe procedure since severe peri- and Health Quality Ontario (HQO) (2017) Lumbosacral dorsal
postoperative problems are rare and long-term rhizotomy for spastic cerebral palsy: a health technol-
complications are uncommon. ogy assessment. Ont Health Technol Assess Ser Jul
17(10):1–186. Available from: http://www.hqontario.
ca/evidence-to-improve-care/journal-ontario-health-
technology-assessment-series
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Dystonia and Movement Disorders in
Children with Cerebral Palsy 45
Freeman Miller and Stephen Falchek
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 662
Dystonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 663
Athetosis, Chorea, and Choreoathetosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 665
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 666
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 667
Dystonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 667
Medications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 667
Global Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 667
Focal Dystonia Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 668
Secondary Effects of Dystonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 669
Athetosis and Choreoathetosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 670
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 670
Treating Secondary Effects of Athetosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 671
Chorea and Ballismus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 672
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 673
Cases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 673
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 675
Abstract
Movement disorders are primary problems
related to the ability of children to develop
F. Miller (*) and control smooth targeted motor movement.
Department of Orthopaedics, Nemours/Alfred I. duPont The specific description of these abnormalities
Hospital for Children, Wilmington, DE, USA is somewhat confusing and varies among
authors of different texts. The main movement
S. Falchek disorders in children with cerebral palsy
Division of Pediatric Neurology, Department of Pediatrics,
(CP) that impair function are dystonia and
Wilmington, DE, USA choreoathetosis. These disorders are often
e-mail: Stephen.Falchek@nemours.org

https://doi.org/10.1007/978-3-319-74558-9_42
662 F. Miller and S. Falchek
combined with spasticity and are termed mixed are brief and jerk-like. Athetosis comprises slow,
movement disorder. There are many varieties continuous, smooth, involuntary, writhing move-
of dystonic movements, sometimes involving ments, often involving proximal more than distal
only one limb, but in most children with CP, musculature and usually involving facial and oral
there is involvement of the whole body. muscles. In children with CP, chorea and athetoid
Choreoathetosis also involves the whole movements are most commonly comingled,
body, often being more disabling in the upper wherein the term choreoathetosis is often used.
extremities then the lower extremities, and usu- Myoclonus is a movement pattern sequence of
ally has significant facial and oral motor repeated, nonrhythmic, brief shock like jerks due
involvement. Treatment for dystonia requires to sudden involuntary contraction or relaxation of
a complete medical evaluation, to exclude pro- muscles. When myoclonus is the predominant
gressive neurodegenerative disorders. For chil- movement pattern in children, it usually indicates
dren with CP, treatments include good stable other underlying pathologies such as active sei-
seating, comfortable orthotics, and exercise. A zures or some other underlying central nervous
range of medications have been proven to be system disease (Kruer 2015). Tremors are rhythmic
helpful in some circumstances. When they are back-and-forth or oscillating involuntary move-
not, intrathecal baclofen therapy and deep ments across a single joint axis, and multiple joint
brain stimulation are currently the main alter- locations may be affected simultaneously. Tremor
native options. Treatment of choreoathetosis is subclassified as resting or, more commonly in
also should focus on therapy options such as children, action or intention (activated by move-
good seating support, weighted vests, wrist or ments). Children with significant spasticity may
ankle weights, and exploring the best posture develop similar single joint movements due to
for an individual patient. clonus, which is a disinhibition of the deep tendon
stretch reflex arc, resulting in perseveration of the
Keywords reflex jerk. Clonus can be distinguished from
Cerebral palsy · Dystonia · Chorea · tremor in that clonus usually can be stopped with
Athetosis · Choreoathetosis mild pressure, while tremor tends not to respond to
holding the limb, and will resume when the pres-
sure is released (Sanger et al. 2010). Clonus is also
Introduction easily provoked in the spastic patient with a deep
tendon stretch reflex response. Tremor is seldom a
Movement disorders are primary problems related problem deriving from CP in children and is typi-
to the inability of individuals to smoothly execute cally associated with other causes, the most com-
controlled, targeted motor movement. The specific mon of which are benign familial essential tremor
description of these abnormalities is somewhat and medication-induced tremor. When tremor is
confusing and varies among authors of different identified, a prevailing concern is Parkinson’s dis-
texts. To address this confusion of terminology, ease; however, juvenile-onset Parkinson’s is char-
the National Institutes of Health (NIH) funded a acterized by episodic rigidity, and the hallmark
consensus conference in April 2001 (Sanger et al. resting tremor is most commonly seen only in
2003). The description of movement patterns adult-onset cases. Tics are repeated, individually
developed from this meeting are still widely used recognizable, stereotyped intermittent movements
today (see Table 1). The most common movement or movement fragments, are briefly voluntarily
disorder in children with cerebral palsy (CP) is suppressible, and are usually associated with an
dystonia, described as involuntary sustained or awareness of the urge to perform the movement.
intermittent muscle contractions, which cause Tics may occur in children with CP, and, as with
twisting and/or repetitive movements and abnor- tremor, normally derive from other causes. How-
mal postures. Chorea involves ongoing, random- ever, recognizing the tic movement separate from
appearing sequences of one or more discrete invol- the other hyperkinetic movements is difficult. Con-
untary movements or movement fragments, which sequently, few children with CP have a separate
45 Dystonia and Movement Disorders in Children with Cerebral Palsy 663
Table 1 Definition of movement disorders

Movement Definition Features that are not present
Dystonia Involuntary sustained or intermittent muscle Not present during sleep, individual patient
contractions which cause twisting and/or repeats similar patterns, but pattern varies greatly
repetitive movements and abnormal postures between patients
Chorea Ongoing random-appearing sequence of one or Not rhythmic, or predictable, cannot be
more discrete involuntary movements or voluntarily suppressed, if it involves large
movement fragments which are brief and appear proximal joints (hip or shoulder) and causes
jerky flailing movements it is called ballism
Athetosis Slow, continuous, smooth, involuntary writhing Does not maintain a stable position or posture, no
movement often involving distal segments more repeatable movement pattern
than proximal and involves facial and oral
muscles
Myoclonus A sequence of repeated, nonrhythmic, brief shock If it is repetitive, it is called myoclonic tremor,
like jerks due to sudden involuntary contraction or may occur during sleep, no identifiable preferred
relaxation of muscle posture
Tremor Rhythmic back-and-forth or oscillating Movement similar to clonus but cannot be
involuntary movement in one joint axis triggered like clonus, not highly common in
children
Tics Repeated individually recognizable intermittent Movement and duration of the movement do not
movements or movement fragments that are vary, usually worse when patient under stress
briefly suppressible and usually associated with
an awareness of the urge to perform the
movement
Stereotypies Repetitive simple back-and-forth movements that Commonly associated with but not diagnostic for
can be voluntarily suppressed. Typically waving autism, usually not unilateral or involving lower
or flapping of hands or arms extremities
These definitions are abstracted from the publication on definitions of hyperkinetic movements in childhood developed by
the Task Force on Childhood Movement Disorders convened at the National Institutes of Health in 2008 (Sanger et al.
2010)
diagnosis of tics. Stereotypies are repetitive, pur- difference between spastic, ataxic, and dystonic
poseless movements, under a greater degree of movements, but this also has limited reliability as
voluntary control than tics. Typically they com- an objective measure but can be used to provide
prise simple back-and-forth movements such as good subjective monitoring (Eggink et al. 2017).
waving or flapping of hands or arms. Stereotypies Since the main movement disorders in children
are very common in childhood but can be a hall- with CP that cause functional impairment are dys-
mark of autism spectrum disorder when they are tonia and choreoathetosis, we will focus the
extreme. They are not uniquely a feature of patients remainder of this chapter on these movement dis-
with CP. orders. These disorders are often in a mixed com-
Although there have been extensive efforts to bination with spasticity, but the management of
define each of the specific movement disorders, spasticity is addressed separately in a subsequent
including spasticity, many children with CP expe- (▶ Chap. 40, “Medical Management of Spasticity
rience a seamlessly mixed combination of move- in Children with Cerebral Palsy”).
ment disorders. There have been a number of
mechanical attempts to measure spasticity and
dystonia separately, by measuring forces and Pathophysiology
assessing movement overflow (Gordon et al.
2006) as well as surface EMG (Sanger 2004). Dystonia
None of the methods have entered into general
medical practice, mainly due to poor reliability Dystonia is a movement disorder in children with
and reproducibility. There has been a significant CP that has a torsional component, with strong
focus on use of video recording to assess the sequential muscle contractions involving
multiple, often opposing, muscle groups, and runner’s dystonia (Ahmad et al. 2018;
resulting in major, recurrent movement patterns. Cutsforth-Gregory et al. 2016). In addition to
An example of such a pattern is strong shoulder these overuse- and trauma-initiated dystonias,
external rotation, extension, and abduction com- there are also well-described functional or psy-
bined with elbow extension and then alternating chogenic dystonias (Czarnecki and Hallett
with the opposite extreme of elbow flexion, shoul- 2012). The separation between psychogenic and
der internal rotation, adduction, and flexion. Some physical origins of these movement disorders has
children, especially those with hemiplegia been extensively investigated. Most researchers
manifesting hyperreflexia and spasticity, may have found that patients with movement disor-
also have a torsional element to the movement. ders, whether organic or functional, have a high
Using the above example, this might appear as prevalence of comorbid psychiatric disorders,
internal shoulder rotation, forearm supination, and including personality disorders, depression, and
wrist ulnar deviation. Due to the spasticity, how- anxiety (Defazio et al. 2017; Ioannou and
ever, there is never a complete reversal into the Altenmuller 2014; Newby et al. 2016). Most of
opposite posture. This can be a source of confu- these studies have been done in adults or adoles-
sion, because some clinicians call this dystonia. cents. There are no current studies exploring the
However, we prefer to call it typical spastic hemi- association between movement disorders and psy-
plegic posturing. Because dystonic movements chological features in children or adolescents with
present in children with CP tend to have recurring CP. The presence of a single limb dystonia may
patterns, it makes the separation between dystonic arise in adolescents with CP. Although rare, it may
movement and spastic movement often a matter of relate to an overuse form of dystonia and in our
subjective clinician assignment. Dystonia also has experience is often combined with psychological
repeating patterns across large groups of patients. comorbidity.
In one video assessment of 172 children with CP Although there have been great scientific
dystonia, they identified seven recurring move- efforts to explore the functions and pathology in
ment patterns in 152 children (Sanger and Ferman the brain that lead to movement disorders, the
2017). complexities are so great that there is still no
Dystonia may occur in a single limb, across a clear explanation of all motor control phenomena
single joint, or as a whole-body disorder. These in the brain. However, the basal ganglia, and
movements cannot be volitionally controlled, connectivity between the cerebral cortex and
although sometimes there is a sensory feedback the basal ganglia, have been identified as the
element that allows them to be passively stopped primary locations of pathology for most move-
or reversed. For example, a specific pressure point ment disorders. In one analysis, individuals with
or body position may stop the forceful elbow and positive MRI findings and dystonia presented
shoulder external rotation contraction. Some- with two separate and distinct patterns: one
times, moving a finger passively will break up involving damage to the putamen and the other
the forceful dystonic wrist flexion. There is no pan-lenticular damage involving both the puta-
good anatomic understanding of how these sen- men and the globus pallidus (Aravamuthan and
sory inputs function. The category of reversible Waugh 2016).
dystonia is also applied to a wide variety of abnor- Dystonia can be classified as either primary or
mal repetitive movements that can have a range of secondary. Primary dystonias derive from a bio-
initiating factors, such as trauma or overuse. Into chemical or genetic abnormality. Some primary
this category fall diagnoses like golfer yips dystonias may begin as focal limb dystonia and
(Dhungana and Jankovic 2013), table tennis dys- slowly progress to involve much of the body (Low
tonia (Le Floch et al. 2010), billiards dystonia and Honey 2008). Many of these children present
(Smilowska et al. 2018), musicians’ dystonia with no history of either prematurity or other
(Ioannou and Altenmuller 2014), tennis dystonia identifiable etiology of their CP. Nevertheless,
(Mayer et al. 1999), trauma (Schwarz et al. 2000), they often are categorized and presumed to have
CP. These children include those affected by the remembered in ordering genetic testing that
primary dystonias and hereditary degenerative next-generation techniques cannot see trinucle-
diseases such as Wilson’s disease. A small but otide gene expansions or mono-allelic deletions
important subgroup of primary dystonia is dopa- and duplications; hence many disorders, includ-
responsive dystonias. These are due to a net defi- ing the spinocerebellar ataxias, may be missed if
ciency of dopamine due to mutations in the this technique alone is used.
GCH1, TH, or SPR genes, which encode GTP
cyclohydrolase 1, tyrosine hydroxylase, and
sepiapterin reductase enzymes, respectively. Athetosis, Chorea,
Together they are called Segawa syndrome or and Choreoathetosis
Segawa variant, although this term is preferred
for GCH1 mutation-positive patients. Clinical Athetosis is a movement disorder presenting as
diagnosis is often made based upon response continuous, smooth, involuntary writhing move-
to empiric trials of carbidopa/levodopa, but ments often involving the proximal more than
genetic testing is the preferred method, as there distal musculature. Athetosis tends to be worse
are several other neurodegenerative conditions, in the upper extremity, with external rotation and
including hereditary spastic paraplegia type 11, abduction movements of the shoulder, often with
spinocerebellar ataxia type 3, and ataxia telangi- extension and fanning of the fingers. The move-
ectasia, which can also manifest some early ment is induced by voluntary effort, although
improvements with carbidopa/levodopa but sometimes this effort is as anatomically and orga-
which require other treatment and prognostic con- nizationally remote as speech production. A vari-
siderations (Wijemanne and Jankovic 2015; able amount of voluntary override is often
Roubertie et al. 2002). One example from our demonstrated in the context of more complex
clinic is a girl with normal intelligence who grad- movements, such as a movement associated with
ually lost the ability to walk and speak during walking or specific activities like brushing the
adolescence, until at age 16 she underwent a teeth. A child may not be able to bring the hand
genetic evaluation that identified Segawa syn- to the face when asked to do an activity like
drome. She was subsequently treated with levo- “touch your nose,” but when given a candy can
dopa, with return to spontaneous ambulation and place it in the mouth. Children with isolated
speaking. There are many other similar case athetosis tend to have no intellectual deficits but
reports (Slawek et al. 2003). often have motor speech problems that make com-
In addition to these primary causes of dysto- munication difficult.
nia, there are also secondary dystonias caused By contrast, chorea comprises nonrhythmic,
by potentially treatable medical conditions such jerky, or rapid movements, more prominently
as glutaric aciduria. Based on the complexity of displayed in the distal than proximal musculature,
childhood dystonia, it is very important to have that can appear to flow from one muscle or muscle
a full workup of those children who do not have group to the next. It does not resemble myoclonus
a clear etiology of their neurologic injury. This in rapidity. These movements may be of low
workup should include MRI of brain with MR amplitude and subtle and can sometimes look
spectroscopy, biochemical analysis including like “piano-playing” movements of the digits in
potentially CSF amino acid fractionation, neu- which the fingers move independently and invol-
rotransmitter and neurotransmitter metabolite untarily in the plane of the hand, in such a manner
assays, and comprehensive genetic testing. that would be difficult or impossible to reproduce
Genetic testing may include specific dystonia volitionally (and unlike true piano technique).
gene analyses, based upon clinical suspicion, Because chorea and athetosis often manifest
or next-generation massive parallel sequencing together, they are often difficult to distinguish,
techniques such as dystonia gene panels and and so the term choreoathetosis is often used to
whole-exome sequencing. It should be describe a continuous state of hyperkinetic,
nonstereotyped movement involving proximal 2013). A wide range of other genetic and meta-
and distal musculature, with both a writhing and bolic disorders, including phenylketonuria,
jerky quality. glutaric aciduria, glucose transporter (GUT-1)
Choreoathetosis can be a major component of a mutations, and neurodegeneration with brain
general hyperkinetic pattern of movement disorder iron accumulation, can create a clinical phenotype
including dystonia, often referred to as “mixed consistent with CP with predominant chorea or
movement disorder,” which may be the predomi- choreoathetosis, but which would need to be man-
nant pattern in many children with CP (Monbaliu aged in very distinct ways (Hermann and
et al. 2016). There have been efforts to develop Walker 2015).
measurement tools to objectively measure athetoid
movements separately from dystonia. The Dyski-
nesia Impairment Scale has separate sub-scores for Natural History
dystonia and athetosis (Monbaliu et al. 2012). This
tool has been used to measure overflow movements The natural history of movement disorders in chil-
in children with CP, and reported results suggest dren with CP is variable or unclear and highly
that more of the overflow movements are due to dependent upon causation. There are no reported
dystonia than athetosis (Vanmechelen et al. 2019). studies of longitudinal follow-up of children with
The reproducibility and the utility of this assess- CP and movement disorders in general, in part
ment remain unclear. There are currently no tools to because of the difficulty in objectively measuring
separately assess choreiform movements from both dystonia and choreoathetosis. This was one
athetosis in children with CP, and this distinction reason for the development of the Dyskinesia
is likely of no clinical value. Impairment Scale with the goal of long-term mon-
Traditionally, athetosis has been associated itoring (Monbaliu et al. 2012). Based on personal
with neonatal kernicterus and hyperbilirubinemia experience, most infants and young children under
(Przekop and Sanger 2011). This direct relation- age 5 who subsequently developed significant
ship has become less obvious to practitioners, as movement disorders initially presented with signif-
the treatment of kernicterus and hyper- icant motor delay and hypotonia. The abnormal
bilirubinemia has improved and greatly reduced movements become more apparent as a child’s
the incidence of the relatively pure athetoid or motor skills emerge. As the child’s central nervous
choreoathetoid pattern of CP. There has been a system matures and intentional motor movements
significant decrease in the number of children develop, abnormal motor overflow is often the first
with predominant athetosis in the past 30 years evidence of movement disorder. During early-to-
(O'Reilly and Walentynowicz 1981). The patho- middle childhood, the movement disorder tends to
logic etiology classically involves kernicterus become more apparent but usually not significantly
with neuropathology of bilirubin-induced brain more disabling. This seems to be a period of time
injury, where the deep nuclei of the brain stain when the child’s motor development and the ability
yellow (Przekop and Sanger 2011); however, to do functional activities are improving at the same
investigations into cases with unclear etiology speed or slightly better than the movement disorder.
have found lesions also involving various parts A significant increase in movement disorder sever-
of the basal ganglion (Monbaliu et al. 2016). As ity, to the point of causing more functional impair-
with dystonia, when there is progression of the ment, is commonly seen during puberty. During this
severity of the movement disorder beyond expec- period of rapid developmental change, neuropsy-
tations, full and further workup with imaging, chological and behavioral issues also become more
biochemical and genetic testing are indicated. evident. In cases with unclear etiology and
Huntington’s disease is the classic primary neuro- increases in movement disorder associated with
degenerative disease characterized by chorea. significant functional loss, repeat diagnostic
While it can start in childhood, early-onset cases workup is usually indicated to rule out a primary
are more marked by dystonia (Velez-Lago et al. dystonia or an undiagnosed degenerative process.
After the completion of growth typically by the indicated, after workup for confounding causes.
middle teenage years, movement disorders often There is some interest in treating young children
plateau. with carbidopa/levodopa even in the absence of
significant dystonia, primarily for spasticity and
stiffness (Brunstrom et al. 2000; Brin and
Treatment Bakhteev 1995). In our experience there does
not seem to be much benefit to this approach.
Dystonia There are many pharmacologic agents available
to treat dystonia, but often the rationale for use of
The inability to accurately and reliably quantify a specific drug is not well defined. The available
the magnitude of dystonia has been a major prob- options include levodopa as previously discussed,
lem in assessing treatment outcomes. There have anticholinergics such as trihexyphenidyl hydro-
been multiple attempts to develop quantifying chloride and diphenhydramine (an antihistamine
tools to assess dystonia, but clinical utilization of but with good anticholinergic qualities), the ben-
these tools has not been widespread. The Hyper- zodiazepines, baclofen, carbamazepine, and a
tonia Assessment Tool (HAT) is a seven-item tool large variety of dopamine receptor-blocking
utilized to determine the predominant motor pat- drugs. There are reports of significant benefit
tern between spasticity, rigidity, and dystonia from using the anticholinergic drug tri-
(Jethwa et al. 2010). The Barry-Albright Dystonia hexyphenidyl in increasing doses for children
(BAD) scale is a video and physical examination with a significant component of dystonia in CP
tool assigning five ordinal levels of severity to (Ben-Pazi 2011; Carranza-del Rio et al. 2011).
eight body locations, modeled on the pattern of Individual case experiences with excellent
the Ashworth scale for spasticity. The purpose of responses (Case 1) also show that there is little
this tool is to assign a severity ranking of an risk in an empiric trial. One study reported greater
individual patient’s dystonia (Rice et al. 2017; benefit in younger children compared to older
Barry et al. 1999). children (Hoon Jr. et al. 2001). By contrast,
The Burke-Fahn-Marsden Movement Scale though, a literature review concluded that evi-
(BFMMS) (Burke et al. 1985) and the Unified dence for a beneficial effect from trihexyphenidyl,
Dystonia Rating Scale (UDRS) (Comella et al. when used in children with CP dystonia, was
2003) tools are based on analyzing video record- lacking (Harvey et al. 2018). Another study eval-
ings of children and quantifying dystonic move- uated the effect of levodopa in teenagers with CP
ments. Although the severity scales BAD, dystonia and found no benefit (Pozin et al. 2014.
BFMMS, and UDRS do have some internal con- There has been increasing interest in the popular
sistency, there are limitations on reliability and press for the medical use of cannabis, and this has
content validity (Monbaliu et al. 2010). These extended to children with CP, but investigation
measures of dystonia are used to assess specific has been limited. One report of a positive effect
treatment responses, mainly in a research environ- has been published (Libzon et al. 2018). Our
ment; they have not realized widespread clinical limited experience with only a few patients sug-
application. In addition to the problems of reli- gests that it may have a role in reducing functional
ability and content validity, these scales are also impairment.
time-consuming to administer, with a significant
subjective element.
Global Treatment
Medications Although some children with CP may have focal

dystonia, most have diffuse involvement includ-
For children with CP and predominant dystonia, ing upper and lower extremities, as well as the
attempted treatment with levodopa may be trunk. If there is no response to medication, or the
side effects of the medication are judged more Neurosurgical interventions for dystonia have
severe than the beneficial effects, then consider- had a long history, primarily with ablative pro-
ation of a holistic management strategy is indi- cedures, usually of the pallidum. Although there
cated. Rehabilitation approaches include are some positive responses, due to the permanent
providing stable comfortable orthotic support, nature and complication risks, this procedure has
good customized seating support, and distal foot largely been supplanted by deep brain stimulation
and ankle support with AFOs and upper extremity (DBS). Our understanding of the indications and
support with forearm splints. Sometimes these the outcome of DBS for secondary dystonia is still
orthotics cause discomfort and may even increase evolving, but there is a subsequent chapter in this
the movement abnormality, in which case they text with the current options (▶ Chap. 46, “Deep
should be removed. Some children can be taught Brain Stimulation for Pediatric Dystonia”). Cur-
to develop volitional strategies that are more func- rently the differential indications for ITB versus
tional, such as by finding positions of the trunk or DBS in CP patients are not clearly defined. We
head that allow better limb control. If there are have a longer clinical experience of using ITB,
major psychiatric disorders, management with and the risk profile seems to be lower. There is one
cognitive and behavioral therapy, or appropriate report investigating approximately matched
medication if needed, is an important aspect of groups, which found the positive benefits were
treatment (Dressler 2011). better for ITB compared to DBS (Kim et al.
The next level of management to consider is 2019). At this time we would first try ITB and
intrathecal baclofen (ITB) for global dystonia. Ini- follow up with DBS if the response to ITB is not
tially this treatment was developed to manage adequate, for dystonia complicating CP. Dorsal
severe spasticity. However, it was found to also rhizotomy has a very unpredictable outcome in
decrease dystonic movements, which are often these patients (Steinbok 2007; Buizer et al. 2017)
part of the mixed movement disorder in children and is not recommended except for relatively pure
with GMFCS IV and V level CP. Based on this spasticity (Dressler 2011).
initial experience, the indications were extended to
include those children with predominant dystonia,
with equally good results. Efficacy of ITB is now Focal Dystonia Treatment
supported by a number of reports (Dekopov et al.
2019; Motta et al. 2008; Albright et al. 1996, 1998). A number of patients with CP tend to have dysto-
We have found that, to decrease dystonia or spas- nia involving a specific somatic area, in which
ticity in the upper extremities, placement of the there is one predominant movement or set of
intrathecal catheter in a relatively high position, movements around a particular joint set, often in
usually in the cervical spine between C2-5, is pref- the context of a less severe global movement
erable. The baclofen dosing with dystonia is highly disorder. In this situation, attempts should be
variable, with some patients being sensitive to low made to address the focal problem. These focal
doses and others requiring gradual titration to very areas may include a single shoulder abduction and
high doses. There are reports of using intraventric- external rotation, severe wrist and finger flexion,
ular baclofen administration as a more effective or varus or valgus foot posturing. The
way to control dystonia (Rocque and Leland recommended foundation level of treatment com-
Albright 2012; Ruggiero et al. 2019; Turner et al. prises rehabilitation modalities, such as
2012; Waqar et al. 2014). We have no experience stretching, orthotics, and practiced seating pos-
with intraventricular administration of baclofen. tures. The next level of intervention should be
Although the use of ITB can decrease dystonic intramuscular botulinum toxin injection into the
movements and improve motor function, common affected muscles, which are the main source of
complaints of weakness, hypotension, urinary deforming forces. The typical response is reduc-
retention, seizures, and impotence in adult males tion in the strength of the abnormal movements
may be limiting in individual cases (Case 2). for approximately 6 months. In cases of positive
response with little or no unintended weakness, with a spastic limb, in which the contracted defor-
the injections can be repeated every 4–6 months. mity is stiff at all times, and the involved muscles
In our experience the response is greatly reduced usually have a shortened, thin appearance on
after 3–5 injections, making further injections rel- physical examination. Limb length discrepancy,
atively useless, although individual patients may due to delayed growth of the affected limb, is also
experience benefit for a much longer period of a hallmark of a spastic limb. A child with a severe
time. There are no series reports of focal dystonia equinovarus positioning of the foot from spastic-
management in children with CP; however, there ity will always have some level of muscle con-
are positive reports in adults, especially for cervi- tracture present. An important historical question
cal dystonia (Yi et al. 2018; Lin et al. 2018; Keam for the examiner is to ask, “does the foot or hand
et al. 2011). Historically, peripheral neurectomies, ever go in any other position except the one that it
phenol injections, and alcohol injections were is in now?” In dystonia, the parents and the child
used to denervate a severe focal dystonia. These will normally observe that postures may reverse,
have fallen out of favor due to unpredictable out- e.g., sometimes instead of the wrist being in a
comes and high complication rates. flexed position, it is hyperextended with the fin-
gers flexed. Historical details, such as how the
child positions when relaxed, the appearance of
Secondary Effects of Dystonia the muscles, and the sense of the child’s underly-
ing tone when relaxed, are important parameters
Perhaps because dystonia is frequently a compo- to use in differentiating spasticity from dystonia.
nent of a mixed movement disorder with spastic- The distinction between spasticity and dystonia is
ity, secondary deformities do occur, especially best visualized in the case of the quadriplegic
with joint and muscle contractures, impairing child, with contractures and limb atrophy, versus
function. When evaluating these secondary defor- the child with pure dystonia, with robust, well-
mities, it is important for the orthopedist to iden- formed muscle groups and no underlying
tify the limb with predominant dystonia, contractures.
compared to the limb with mainly spasticity. On Understanding the degree of dystonia present
the initial evaluation, it should be remembered compared to spasticity is an essential feature of
that the dystonic limb may present with a flexed medical care and especially important in surgical
posture at the wrist and elbow, mimicking a hemi- planning. Responses to muscle tendon surgeries
plegic, spastic limb. This same position occasion- in a child with mainly dystonia will be very
ally occurs with the foot in equinovarus or unpredictable and may result in a disabled limb
planovalgus position, having the same initial stuck in the opposite postural direction. In patients
appearance whether the child is experiencing pri- with predominantly dystonia, the most appropri-
marily spasticity or dystonia. The differentiation ate surgical treatment options focus on joint
of spasticity from dystonia is determined by a fusions or realignments, and not soft tissue
thorough physical examination and patient his- balancing. In mixed movement disorders with
tory. On physical examination, clues to dystonia significant spasticity, joint fusion seems to modu-
include relatively minimal fixed contractures and late the dystonic posture.
hypertrophy of the involved muscle groups, as if In severe cases of upper extremity focal dysto-
the child had been lifting weights. This is due to nia, the limb may need to be denervated and
involuntary, repeated isometric exercise of these allowed to be flaccid. Also, doing fusions of the
muscles. During the examination, the child’s mus- wrist and shoulder joints may be reasonable
cles will often eventually release, with the tempo- options. One adolescent patient of our practice,
rary emergence of normal tone. When the muscle whose limb was made flaccid with neurectomy,
releases, the joint may have a full range of motion eventually requested a shoulder level amputation
with minimal or even no contracture present. This as a young adult. While some scapular dystonia
appearance is distinctly different from the child remained, he reported much greater comfort post
amputation. Focal dystonia at the knee and hip is develop better controlled movements with
especially difficult, because denervation of these weighted restraints. Weighted vests are commer-
muscles or fusion of these joints will significantly cially available for use, but the responses vary
impair function. We have seen a rectus transfer greatly between individuals. Wearing wrist
on an adolescent whose knee stiffness was weights or ankle weights also allows some indi-
thought to represent spasticity but afterward was viduals to maintain better control of extremity
found to be dystonic. For 9 months after the rectus movements.
transfer, she held the knee in flexion when she
tried to stand. Persistent physical therapy and
orthotic use converted this patterning back to Treatment
extension at about the time we were contemplat-
ing reversing the rectus transfer. Medication management for choreoathetosis in
the CP population is limited by the number of
available agents, their efficacy, and the scarcity
Athetosis and Choreoathetosis of clinical studies. Targeted treatment strategies
include blockade of either dopamine or acetylcho-
Treatment of athetosis, which tends to be worse in line transmission, GABA and adrenergic modula-
the upper extremity, also normally begins with tion, immunotherapy, and lessening of neural
rehabilitation therapy approaches, by providing irritability (anticonvulsants). The primary treat-
stable trunk support. This stability is especially ment philosophy usually involves blocking dopa-
important, while the child focuses on fine motor or mine transmission. Neuroleptics, which block
upper extremity skills. In cases of asymmetric postsynaptic dopamine receptors, are normally
involvement, passively restraining the more the first line of choice (Russ et al. 2018). These
affected extremity may allow for improved func- include most prominently the atypical antipsy-
tion of the less-affected side for tasks like key- chotics olanzapine, risperidone, and quetiapine
board use, feeding, or writing. However, many (Hermann and Walker 2015; Schultz et al. 2018).
children cannot accomplish these tasks. Since The hallmark treatment for chorea, developed and
choreoathetosis tends to be worse in the upper FDA approved specifically for Huntington’s cho-
extremity, options for young children include rea, is tetrabenazine, which, like reserpine,
exploring use of the feet for dexterity and fine depletes dopamine (and other monoamine neuro-
motor skills. There are rare cases where an indi- transmitters) at presynaptic junctions by blocking
vidual has no functional control of the upper vesicular monoamine transporter 2 (VMAT2).
extremity, but may develop the ability to write This drug has been explored in a number of appli-
and use keyboards with the feet. (One such case cations in the literature, including in CP with
was made famous in the movie “My Left Foot.”) choreoathetosis and CP with mixed movement
Unless the child is given options to explore these disorder. Its use both in the United States and in
skills, they will not be recognized. The most com- other nations is limited by the restricted FDA
mon use of the foot in children with athetosis is approval, extreme high cost, and data suggesting
the use of a joystick to drive a wheelchair. that it may not be superior (in Huntington’s cho-
Because the function of these children is often rea) to the less expensive atypical antipsychotics
apparent by the time they are 4–5 years old, and like olanzapine and tetrabenazine. These facts
many are of normal intelligence, they are the ideal render it almost inaccessible for the majority of
candidates among the population with CP for an patients with choreoathetosis as well as dystonia.
early power wheelchair. The power wheelchair Nonetheless, there are significant literature cita-
does pose some challenges, such as expense, its tions supporting its utility in these CP-related
weight in transportation, and arrangement of an applications (Lumsden et al. 2019; Hermann and
adapted home. While many individuals with Walker 2015; Schultz et al. 2018; Kruer 2015).
athetosis do not tolerate rigid orthotics, they may Other treatment strategies are less specifically
trophic for the CNS motor pathways. The use of worsening of gait in chorea secondary to
diazepam as an oral medication will decrease Huntington’s chorea (Velez-Lago et al. 2013).
athetoid movements but often requires high
doses. Because of this, except for acute situations,
such as following surgery, diazepam has limited Treating Secondary Effects of Athetosis
efficacy due to the excessive sedative effects at the
required dosage (Vidailhet 2013). Oral baclofen In individuals with athetosis only, there are almost
will reduce the tone, which may actually remove a no secondary musculoskeletal effects in child-
restraint from athetoid movements. Gabapentin hood. There may be some increased mobility of
and clonidine also enjoy practical use in the man- finger extension, especially at the metacarpal pha-
agement of choreoathetosis. In a prospective eval- langeal joint. The muscles tend to be hypertro-
uation of a cohort of 275 patients treated at nine phic, although less so than with dystonia, where
centers in the United Kingdom, baclofen, the maximum contraction is held for a longer
gabapentin, diazepam, clonidine, and tri- period of time. In athetosis, there is a large amount
hexyphenidyl were used in declining order of of motion, but the muscle is not held in maximum
prevalence in children and youth with CP and contraction for an increased amount of time. The
choreoathetosis. In mixed movement disorders difference between athetosis and dystonia for the
with a combination of choreoathetosis, dystonia, muscles is similar to the difference between a
and spasticity, the spasticity may act like a “shock weight lifting athlete and a long-distance runner.
absorber” to dampen the movements. In these In this paradigm, dystonia is similar to weight
cases, measures that reduce spasticity may inad- lifting and athetosis is similar to running. Children
vertently accentuate the other movement compo- with athetosis have a very high energy need (John-
nents. In predominantly athetoid CP, botulinum son et al. 1996) as opposed to children with quad-
toxin has little or no usefulness because of the riplegic spasticity where the energy need is
diffuse geographic nature of athetoid involve- considerably less than normal. Based on our expe-
ment. Immunomodulatory therapies like IVIG rience with several adolescents, during the growth
and corticosteroids, while highly useful in move- period, attention has been directed to adequate
ment disorders deriving from immune-mediated caloric intake, which may be two or three times
encephalitides, generally have no place in the the need of a similar-sized adolescent. Facial
management of long-term movement disorders, movements are usually part of the athetoid pattern
such as in the CP patient. and are often associated with increased sialorrhea,
There is a long history of central nervous which may require treatment. This movement dis-
system surgery, mainly ablative procedures order also may affect the vocal cords, causing a
(Heimburger et al. 1973; Fraioli et al. 1977) or motor speech impairment and requiring the atten-
implanted electrical stimulation (Davis et al. tion of a speech therapist and in some individuals,
1980); however, none of these have demon- augmentative communication systems.
strated any consistent benefit in individuals Musculoskeletal surgery is limited to stabiliz-
with athetosis. More recently, deep brain stimu- ing joints, when this might provide functional
lation, especially of the globus pallidus pars benefit. Fusion of the subtalar joint and spinal
interna, has attracted interest, but mainly in pri- fusion for scoliosis are the most commonly indi-
mary choreiform disorders like Huntington’s cated operative procedures. However, most chil-
disease and chorea-acanthocytosis (Liu et al. dren with athetosis will need no musculoskeletal
2018). Currently, there are no reports on the surgery. Many children have a mixed movement
use of DBS for pure choreoathetosis; however disorder with spasticity and athetosis, so they
there are reports of its utility in mixed develop the secondary problems of muscle con-
choreoathetosis and dystonia (Wolf et al. 2019; tractures from the spastic component. During pre-
Vidailhet 2013). There is one report of using surgical evaluation for muscle lengthening
DBS with reduction of movements but procedures in these patients, caution should be
exercised in determining the degree to which including radiographs and MRI scans, is essential.
spasticity is dampening potentially problematic The degenerative joint disease and the cervical
athetosis. spine instability usually require cervical spine
Surgical reconstruction in a child with severe fusion and decompression.
athetosis and underlying spasticity requires a very We have seen several children with athetosis
experienced postoperative management team. who developed lumbar spondylolisthesis in child-
Often, there is great reluctance in young adults hood. This often presents with a vicious cycle of
or adolescents and their families to undertake any back pain, leading to increased reactive move-
major surgical procedures. This hesitation in fam- ment disorder, worsening the pain. If pain is not
ilies and patients often derives from their own relieved after a (short) trial period of lumbosacral
experience with the unpredictable aspect of orthosis, spinal fusion is required (Case 3). There
athetosis, rendering them fearful to undertake a is no specific information on the incidence of
treatment that might leave them worse than they spondylolysis or the incidence with which it pro-
are currently. Many of these families and patients gresses to an unstable spondylolisthesis.
may have had experience with physicians who did
not appreciate the unpredictable nature of
athetosis and were not willing to listen to their Chorea and Ballismus
experience with this condition. Because of the
excellent cognitive function in many individuals Chorea involves ongoing, random-appearing
with athetosis, patient input into treatments and sequences of one or more discrete involuntary
rehabilitation often significantly enhances the movements or movement fragments, which are
rehabilitation experience. This great insight by brief and jerk-like. These movements are more
these patients in body awareness can lead to a predominant distally in the limb. Ballismus, also
dynamic in which therapists feel that a patient is called ballism, is similar in pattern but involves
not willing to listen or want to try something new. fundamentally larger movements based at the
On the other hand, these patients may feel that the proximal joints, primarily the shoulder and
physicians and therapists are not listening and elbow or hip and knee. These large movements
only want to follow a therapeutic protocol. In are unpredictable and jerky and may appear to
these situations, listening skills and communica- have a violent character to them. Current defini-
tion are essential, and all involved should be open tions categorize chorea and ballismus as different
to try different techniques, in order to arrive at the severities on a spectrum of similar movement
maximum rehabilitation potential of each pattern (Sanger et al. 2010). Ballismus is the rarest
individual. of the movement disorders in children with
Another major musculoskeletal problem in CP. When these movement disorders develop,
patients with athetosis is degenerative joint dis- especially if accompanied by significant chorea,
ease. Arthritic changes in the cervical spine from the diagnosis of CP should be questioned. If sig-
the increased cervical spinal mobility are common nificant chorea or ballismus movements start to
in middle and older age persons. We have never develop in children with CP, additional workup
seen these changes as a problem in a child or an frequently defines a more specific diagnosis, often
adolescent; they have been well reported in mid- a neurodegenerative process. These movement
dle age, although the exact incidence is unclear. disorders may get slowly worse in the absence of
There are many small series reporting myelopathy mechanisms for controlling them.
together with this degenerative joint disease pro- As previously discussed, the predominant
cess, as the cervical spine develops instability and pathology for pure chorea and ballismus lies in
subluxation (Epstein 1999; Harada et al. 1996; the basal ganglia; therefore, many drug options
Ogawa et al. 2006). If there is any decline or that are used for the treatment of dystonia are
change in motor function in an individual with considered as the first line of treatment for chorea.
athetosis, a full workup of the cervical spine, There have also been positive reports of ablative
surgery on the internal capsule (Vitek et al. 1999; and improved medical treatment of these disor-
Lin et al. 1999). There are very few secondary ders. This has been especially true in the reduction
musculoskeletal deformities from chorea except of athetosis with better management of neonatal
in severe late-stage cases, all of which were hyperbilirubinemia.
caused by progressive encephalopathies in our
experience.
Cases
Conclusion
Case 1 Sarah
Separate treatment recommendations for specific Sarah, a 7-year-old girl, was referred after
movement disorders are complicated because having seen many other physicians. Her
there is often not clear neuropathologic/anatomic mother complained that she could not run
distinction between them. These disorders often or walk well. Sarah tended to get her feet
overlap and combine in their presentation, proba- tangled up and tripped over herself,
bly reflecting movement patterns best understood according to her mother. Sarah herself was
as using mathematical models used in weather getting very frustrated and did not want to
prediction, without clear neuroanatomic distinc- play with friends or go to school. She had
tions. This is why children who have varying been evaluated by a psychiatrist who felt
complex combinations of brain pathology may there was an underlying physical motor
have similar MRI imaging but present with very movement disorder magnifying her anxiety.
different movement patterns. An analogy might The physical examination was completely
be the difference between a windstorm and normal, but observation of her gait demon-
rainstorm compared with a thunderstorm or a tor- strated great variability with torsional ele-
nado. Each of these storms is a definite recognized ments and hyper hip and knee flexion.
pattern, all occur in the same geographic region, Kinematics showed erratic variability with
and the cause of each is similar and perhaps not extremes that indicated different patterns
completely understood. This same analogy (Fig. C1.1). With the diagnosis of torsional
applies to the movement disorders of dystonia, dystonia, she was started on tri-
athetosis, chorea, and ballismus. However, hexyphenidyl, and after 1 month, almost
because distinct patterns can be recognized, and all the symptoms resolved.
there are distinctions in treatment, specific algo-
rithms for each can be defined. Dystonia is an
involuntary movement pattern that is difficult to
treat because of the persistent nature of the symp-
toms and the strength of the muscle forces. Case 2 Paul
Athetosis is more predictable and may be suscep- Paul, a 15-year-old boy, was referred to the
tible to volitional modification accessed through orthopedic clinic by a psychiatrist who had
physical therapy interventions. Medical manage- been treating him because of depression and
ment of these movement disorders includes new a conversion reaction with a very peculiar
medications, improved understanding and appli- gait. Because of Paul’s persistent complaint
cation of DBS, and the use of ITB. Due to of feeling that his knee was giving way,
improved diagnostic techniques with DNA there was a concern that he had some
sequencing and better understanding of biochem- mechanical knee instability. This walking
ical syndromes, the number of patients with com- pattern had been slowly and intermittently
plex movement disorders who continue to receive getting worse since middle childhood, when
only an undifferentiated diagnosis of CP is declin-
(continued)
ing. This has led to both a better understanding
Fig. C1.1 Kinematics Dystonia Normal

showing erratic variability 85.3 60.8
with extremes indicating Flexion
different patterns 50.0
25.0
HIP 25.0
0.0
0.0
Extension –24.7 –30.1
Int Rot 17.8 14.2
0.0
HIP 0.0
–20.0 –20.0
Ext Rot –28.8 –32.3
Dorsiflex 24.5 24.3
ANKLE 0.0 0.0
–20.0 –20.0
Plantarflex –34.8 –33.3

FC TO FC TO
he started living with an aunt. She had no he continued to get slightly worse. After a
history of his early childhood. Paul stated positive trial of intrathecal baclofen, he had
that the problem was somewhat variable an intrathecal baclofen pump implanted
but seemed worse when he wanted to that improved his gait pattern, but he
walk fast or run and got worse when he complained of being weak when the drug
was anxious. He expressed great frustra- dose was high enough to really suppress
tion with the problem, especially with the the movement. He finally also reported that
left leg, which did not support him. On his most bothersome problem was partial
observation of his gait, he had a consistent impotence; however with careful dose
instability of the left leg with hyperflexion adjustment, he continued with the ITB
and some torsional control problem. His treatment because of the significant func-
physical examination was completely nor- tional improvement in his gait.
mal with no joint contractures, no instabil-
ities, and no increase in muscle tone. His
biochemical studies and brain MRI were
normal. His muscle strength was excellent Case 3 Zackery
with manual muscle testing. On kinematic Zackery, a 12-year-old boy, presented with
evaluation, he showed several patterns of a complaint of back pain, especially after
motion with great variability that was walking a long distance. A gait analysis
clearly not around a bell-shaped distribu- showed very high variability in step length
tion. A diagnosis of dystonia was made, and most kinematic parameters (Fig. C3.1).
and he had trials of trihexyphenidyl, ankle He had no fixed contractures on physical
orthotics, and botulinum toxin, all without examination. A radiograph of his spine
significant benefit. Over this 2-year period,
(continued)
Dorsiflexion 29.5
demonstrated L5 spondylolysis with grade
0.0 one spondylolisthesis (Fig. C3.2). An
Ankle
Motion –25.0
attempt at conservative treatment with a lum-
bar flexion jacket for 6 months demonstrated
–50.0 no significant decrease in the pain; therefore,
Plantarflexion –64.5
it was recommended to have a posterolateral
Flexion 101.3
Left
arthrodesis from L4 to the sacrum. After this
healed, all his back pain resolved.
Knee 50.0
Motion
0.0
Extension
–24.1
Up 1.70 Cross-References
GRF 1.00 ▶ Deep Brain Stimulation for Pediatric Dystonia

Vertical ▶ Diagnostic Gait Analysis Technique for Cere-
bral Palsy
▶ Focal Management of Spasticity in Cerebral
Down –0.22
Palsy
▶ Intrathecal Baclofen Therapy: Assessment and
Fig. C3.1 Gait analysis showing very high variability in
step length and most kinematic parameters Medical Management
▶ Medical Management of Sialorrhea in the Child
with Cerebral Palsy
▶ Medical Management of Spasticity in Children
with Cerebral Palsy
▶ Surgical Options for Sialorrhea Management in
Children with Cerebral Palsy
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Deep Brain Stimulation for
Pediatric Dystonia 46
Michelle A. Wedemeyer and Mark A. Liker
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 680
Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 680
Preliminary Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 681
History of Surgical Interventions for Dystonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 681
Theoretical Mechanism of DBS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 682
Preoperative Planning and Lead Implantation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 682
Implantable Pulse Generators . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 684
Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 684
Functional Outcome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 684
Future Directions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 685
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 686
Abstract
Dystonia is defined as a movement disorder in
which “involuntary sustained or intermittent
muscle contractions cause twisting and repeti-
M. A. Wedemeyer (*) tive movements, abnormal postures, or both.”
Department of Neurosurgery, University of Southern Dystonia may be classified as primary or sec-
California, Keck School of Medicine, Los Angeles, CA,
ondary. Primary dystonia is characterized by
USA
e-mail: Michelle.Wedemeyer@med.usc.edu isolated dystonia and is the result of a number of
hereditary mutations. Secondary or symptom-
M. A. Liker
Division of Neurosurgery, Children’s Hospital of Los atic dystonia is acquired from any number of
Angeles, Los Angeles, CA, USA insults to the brain, most commonly cerebral
Department of Neurosurgery, University of Southern palsy, kernicterus, or other toxic/metabolic
California, Keck School of Medicine, Los Angeles, CA, insults to the brain. Secondary dystonias pre-
USA sent earlier in life and are associated with other
e-mail: liker@usc.edu

https://doi.org/10.1007/978-3-319-74558-9_47
680 M. A. Wedemeyer and M. A. Liker
neurologic symptoms including epilepsy, improvements in quality of life and ease of care-
developmental delay, spasticity, and hypertonia. giving burdens (see ▶ Chap. 36, “Family Stress
Any child presenting with a clinical exam Associated with Cerebral Palsy”). Although his-
concerning for dystonia should be referred to a torically surgery consisted of lesionectomies and
neurologist specializing in movement disor- carried a high risk of neurologic deficits, modern
ders as dystonia is associated with the devel- approaches rely on the use of stereotactic implan-
opment of skeletal abnormalities in the tation of electrodes and have a favorable safety
growing child. Initial management is medical; profile.
however, some patients are refractory to med-
ical management and may be candidates for
surgical evaluation. Epidemiology
Deep brain stimulation (DBS) is the treat-
ment of choice for dystonia and involves ste- Epidemiologic studies in Europe have found cere-
reotactic placement of neurostimulators bral palsy to affect as many as 2 per 1000 live
powered by an implantable pulse generator births (Odding et al. 2006). One common mani-
into the basal ganglia. Although patients with festation of cerebral palsy is dystonia. Formally
primary dystonia may have marked improve- defined as “a movement disorder in which invol-
ments with stimulation, patients with second- untary sustained or intermittent muscle contrac-
ary or progressive dystonias characteristically tions cause twisting and repetitive movements,
have more variable responses and on average abnormal postures, or both,” dystonia may be
show more modest improvements on clinical found both in isolation and, more commonly,
measures of dystonia. Despite its invasive combined with other movement disorders such
nature, this procedure is relatively safe with as spasticity and hypertonia (Sanger et al. 2003).
low mortality although reduction in the rate Dystonia may be isolated as in the primary or
of surgical site infections, the most common monogenic dystonias or coexistent with other
complication, remains an active area of movement disorders as in secondary or heredode-
research. generative disorders. Dystonias may be classified
by etiology or by symptomology. Primary
dystonias include the monogenic dystonias such
Keywords as DYT1 dystonias that present with symptoms in
Dystonia · Deep brain stimulation · a single muscle group in teenagers and subse-
Pallidotomy · Thalamotomy · Basal ganglia quently generalize. Patients with primary
dystonias have isolated dystonia with previously
normal development, intelligence, and magnetic
Introduction resonance imaging studies. Secondary dystonias
comprise the majority of patients with dystonia
Movement disorders are a common manifestation and include diverse acquired etiologies, most
in cerebral palsy and can be a combination of commonly cerebral palsy, kernicterus, trauma,
spasticity and dystonia. In the growing patient, and anoxic brain injury. Heredodegenerative dis-
these disorders can lead to progressive joint con- orders such as glutamic acid decarboxylase defi-
tractures and deformities if not addressed in a ciency (GAD), neurodegeneration with brain iron
timely fashion. Dystonia consists of involuntary accumulation (NBIA), and pantothenate kinase-
contractions or repetitive motions and may be associated neurodegeneration (PKAN) are pro-
caused by genetic mutations, as in primary gressive neurodegenerative disorders whose
dystonias or secondary insults to the brain. symptomology may include dystonia (Albanese
Although first-line therapy remains medical, et al. 2013; Koy et al. 2016; Sanger et al. 2003).
many patients fail medical management and are Distinguishing dystonia from related disorders
referred for surgery that can result in such as spasticity and hypertonia presents a
46 Deep Brain Stimulation for Pediatric Dystonia 681
diagnostic challenge, as these disorders may be carbidopa; however, a substantial fraction of

present simultaneously. Additionally, dystonia patients do not respond. Although patients with
may be focal, as in torticollis, multifocal, segmen- focal dystonia may respond to repeat focal treat-
tal, hemi-, or generalized. Given the heteroge- ments with Botox, there are practical limitations
neous etiologies, presentations, temporal to long-term therapy with Botox including the
patterns, and physical distribution, a concerted need for repeated administration and the develop-
effort has been made to develop standardized ment of tolerance. For more generalized disease,
classifications for research purposes. The most patients have been shown to respond to tri-
current consensus classifies patients by both clin- hexyphenidyl, gabapentin, clonidine, baclofen,
ical presentation and etiology (Albanese et al. and benzodiazepines (Dijk and Tijssen 2010;
2013). Koy et al. 2016; Sanger et al. 2003). Patients
Dystonia may be static or progressive and may who continue to have severe symptoms such as
exhibit temporal fluctuations including diurnal var- pain or limited activities of daily living and
iations. Improvement with sleep is a distinguishing patients with refractory status dystonicus are
feature of the disorder, and treatment of severe referred for surgical management.
exacerbations of dystonia, known as status Retrospective studies of DBS have indicated
dystonicus, typically involves benzodiazepines or that surgical interventions offer limited benefit in
other sleep-inducing medication (Albanese et al. patients with longer duration of disease and that
2013; Sanger et al. 2003). Severe, refractory status increased proportion of life lived with dystonia is
dystonicus may lead to rhabdomyolysis with renal a predictor of worse response to pallidal stimula-
failure or aspiration requiring intubation and tion (Lumsden et al. 2013; Markun et al. 2012). It
mechanical ventilation. Severe status dystonicus is unclear at this time whether the poorer out-
that does not respond to medical interventions has comes are results of skeletal deformities from
been shown to improve with emergent deep brain long-standing dystonia in growing children or
stimulation (DBS) (Koy et al. 2016). merely represent the known poorer outcomes of
patients with secondary dystonia whose disease is
the result of insults sustained in infancy. Addition-
Preliminary Management ally while patients with primary dystonia have
normal basal ganglia on magnetic resonance
Suspicion of the development of dystonia should imaging, many patients with dystonia have abnor-
warrant prompt referral to a pediatric neurologist, mal basal ganglia or ventriculomegaly that may
as untreated the abnormal postures in the growing interfere with the accuracy of stereotactic lead
child may progress to permanent skeletal defor- placement. As the category of patients with sec-
mities. Care must be taken to distinguish dystonia ondary dystonia is largely comprised of cerebral
from spasticity that may be better managed by palsy patients who suffered insults before 1 year
implantation of a baclofen pump or dorsal rhizot- of age, the worsened outcomes with prolonged
omy. A study of children with dystonia in a move- dystonia may merely represent the manifestation
ment disorders clinic revealed that more than half of diffuse or global insults sustained by infants
of patients had fixed musculoskeletal deformities prior to maturation of their movement circuitry.
at the time of initial referral with 74% of patients
with deformities exhibiting hip deformities and
42% exhibiting spinal deformities (Lumsden History of Surgical Interventions
et al. 2016). Patients with more severe scores on for Dystonia
the Gross Motor Function Classification System
(GMFCS) progressed to skeletal deformities at an While initial attempts at surgery on the basal
earlier age than higher functioning children. ganglia were plagued by complications, the devel-
Initial management for childhood-onset dysto- opment of the stereotactic frame by Lars Leksell
nia is dopaminergic therapy with levodopa- in the late 1940s was the technological
advancement needed to target the basal ganglia in attributed to purported focal depolarization and
a precise and minimally invasive fashion. Neuro- subsequent inhibition of the target site – a
surgical interventions for dystonia date back to the “reversible functional lesion” (Benabid et al.
1950s when Cooper performed the first of more 1991; Karas et al. 2013). Other proposed mecha-
than 200 thalamotomies for treatment of general- nisms include suppression of pathologic, inhibi-
ized dystonia (Hudson et al. 2017). Although 25% tory β-oscillations of the corticobasal loop, target
reported “good” and another 45% reported “mod- activation, and combined activation and inhibi-
erate” improvement, this procedure was only tion (Karas et al. 2013). The β-oscillation hypoth-
performed unilaterally due to the 15% risk of esis is at least in part supported by evidence,
speech decline with bilateral lesions (Loher et al. including single-photon emission computed
2004). Many patients required multiple surgeries, tomography (SPECT) of the cortex showing an
and other groups reported morbidity as high as increase in cortical activation after initiation of
20% as well as a mortality rate of 2% for repeat DBS and studies showing that cortical oscillation
surgeries. The subsequent development of the frequencies vary depending on the etiology of
pallidotomy for Parkinson’s disease led to the dystonia (Katsakiori et al. 2009; McClelland
adaption of this approach for dystonia; however, et al. 2016). Unlike DBS for essential tremor
the incidence of intracranial hemorrhage was and Parkinson’s disease, the full extent of the
reported to be as high as 15% even if the mortality stimulation effect on dystonia takes up to a year
rates remained less than 1%. Additional compli- suggesting that effects may at least in part be
cations such as cognitive decline, verbal decline, attributed to neuroplasticity or reorganization of
and hemiplegia combined with a permanent com- existing neural circuits (Romito et al. 2015;
plication rate of 9% limited wider adoption of the Vidailhet et al. 2005; Volkmann et al. 2012).
pallidotomy for the treatment of dystonia. The
development of antidopaminergic therapy slowed
the use of functional neurosurgical interventions Preoperative Planning and Lead
for movement disorders until the development of Implantation
deep brain stimulation in the 1990s. Unlike lesion
surgeries, deep brain stimulation is largely revers- The decision to proceed with surgery is reached in
ible, and bilateral stimulation is well tolerated. a multidisciplinary fashion with the input of
Although cardiac pacers had been tested for movement disorder specialists, functional neuro-
neurostimulation since the 1960s, it was the stud- surgeons, and patients/families. A high-quality
ies by Benabid in 1987 that led to the broader use magnetic resonance image of the brain is obtained
of deep brain stimulators for Parkinson’s disease prior to surgery for surgical planning. Patients are
and essential tremor. By the late 1990s, success in typically admitted to the hospital the day of sur-
the treatment of primary dystonias expanded the gery. Prior to surgery, patients are administered a
indications for deep brain stimulation to include prophylactic antibiotic, typically vancomycin.
dystonia (Benabid et al. 1996; Benabid et al. Depending on the age and/or cognitive status of
1991). Today, deep brain stimulation has the child, lead placement may be performed
supplanted pallidotomy and thalamotomy as the awake to facilitate microelectrode recording dur-
surgical treatment of choice for medication- ing placement or under general anesthesia for
refractory dystonia. stereotactic placement of leads alone. Most cen-
ters use a stereotactic frame that fixes the head to
the bed, classically the Leksell frame first intro-
Theoretical Mechanism of DBS duced by Lars Leksell in the 1940s (Elekta AB,
Stockholm, Sweden). Briefly, at the Keck School
Our understanding of the mechanism behind of Medicine of USC, our standard protocol is to
DBS has continued to evolve since approval by place a local scalp anesthetic block followed by
the FDA in 1997. Initially, the effect was frame fixation to the head with pins (Fig. 1a). The
Fig. 1 A stereotactic Leksell frame is placed with a scalp frame is in place, the patient is taken for a stereotactic CT
block for anesthesia. Procedures may be placed under (b). Temporary leads are placed stereotactically via small
general anesthesia or moderate sedation (a). Once the burr holes and tunneled under the scalp (c)
patients are sent for a stereotactic CT with In some patients with secondary dystonia, the
1-millimeter cuts (Fig. 1b). This image is then severity of the dystonia or associated contractures
fused with the preoperative high-quality (3.0 may limit positioning for these procedures. Alter-
tesla) MRI for planning of the trajectory for lead natively, “frameless” systems have been developed
placement. A simple burr hole is placed at the site in which small radiopaque “fiducials” are placed in
of the lead placement. The lead is placed with the scalp in clinic the day before surgery and used
stereotactic guidance, fixed in place by a cap, for registration in lieu of a frame; however, these are
and tunneled under the scalp. When performed not in widespread use. The most commonly used
awake to facilitate microelectrode recording, lead is the four-contact Medtronic DBS 3387 and
sedation may be provided with dexmedetomidine 3389 leads (Medtronic Inc., Minneapolis, MN).
hydrochloride and intermittent boluses of pro- After implantation of the leads, a high-resolution
pofol (Marks et al. 2009). Care is taken to limit CT or MRI is obtained to confirm placement and
propofol and avoid inhalant anesthetics that may look for hemorrhage at the tract site. Although
suppress microelectrode signals. A team of neu- hemorrhage is noted in <1% of patients, it is rarely
rologists is frequently present to assist with micro- symptomatic. Patients are observed overnight and
electrode monitoring as well as monitoring for may be discharged the following day.
off-target side effects. With the exception of Due to the high potential rate of infection, par-
hemidystonic patients, leads are typically placed ticularly in the pediatric population, our center has
in the bilateral globus pallidus intermedius adopted a 3-day antibiotic protocol in which
(GPi) although other targets are an active area of patients are administered vancomycin and
investigation at multiple institutions, including ceftazidime intravenously for 3 days beginning
our own (Air et al. 2011; Katsakiori et al. 2009; 1 hour prior to surgery and discharged with a
Olaya et al. 2013). 10-day course of dicloxacillin (Olaya et al. 2013).
Implantable Pulse Generators deformities. Additionally, growth of the cranial

vault may lead to migration of the cranial lead,
Most institutions perform implantation of leads vertical growth may put traction on connections,
and generators or batteries as separate surgeries. and repeated dystonic postures may lead to fracture
Typically generator implantation is performed as of hardware or dehiscence of wounds. There is
an outpatient procedure under general anesthesia evidence that the rate of wound complications is
approximately 2 weeks after lead implantation. lower with newer, smaller hardware, possibly
The battery is placed subcutaneously below the reflecting the difficulty placing large implants into
clavicle, and cables are tunneled for connection smaller, poorly nourished patients with limited sub-
with the leads at an incision behind the ear. cutaneous tissue reserves (Kaminska et al. 2017).
Programming of DBS generators is typically
performed by a neurologist on an outpatient basis.
Modifiable variables include frequency, ampli- Functional Outcome
tude, and duration of each pulse, although higher
stimulation settings will drain the battery leading While up to 80% improvements on the Burke-
to more frequent need for surgical replacement of Fahn-Marsden Dystonia Rating Scale (BFMDRS)
the generator. Newer rechargeable batteries have have been reported after DBS for patients with
been developed to obviate the need for repeat primary DYT1 dystonia, results in patients with
surgeries; however, some clinicians, patients, secondary dystonia have been decidedly more
and families prefer primary cell batteries as bat- modest (Air et al. 2011; Eltahawy et al. 2004;
tery charging may be inhibited by fixed postures Keen et al. 2014; Kupsch et al. 2006; Marks
of patients with skeletal deformities. et al. 2013; Olaya et al. 2013; Vidailhet et al.
2005; Volkmann et al. 2012). Unlike DBS for
Parkinson’s disease and essential tremor, the full
Complications benefit of DBS for dystonia may not be seen for
6 months to a year which suggests that the thera-
While placement of DBS stimulators is relatively peutic effect is at least in part dependent on
safe with a <1% risk of intracranial hemorrhage and neuroplasticity. Studies with longer-duration fol-
no deaths in published series, rates of surgical site low-up are lacking; however, the studies available
infections and hardware complications are relatively show efficacy for >5 years after implantation –
common. Reported infection rates are as high as information that is particularly relevant to the
40% in some small series with a rate of 10.3% for pediatric patient (Romito et al. 2015). Addition-
new implants in the largest series to date (Kaminska ally, while the outcomes may be variable, the
et al. 2017; Keen et al. 2014). One group has more extreme cases may experience dramatic
reported a higher rate of infection for patients less improvements. Both in our practice and reports
than 10 years old (Air et al. 2011). Hardware com- in the literature, there are examples of wheelchair-
plications, including lead fracture, lead migration, bound patients recovering ambulation (Olaya
early generator failure, and others, have been et al. 2013; Parr et al. 2007).
reported to occur in nearly 20% of pediatric patients Patients with secondary dystonias may have
(Kaminska et al. 2017). Postulated reasons for the overlapping movement disorders, skeletal defor-
higher rate of complications in these groups include mities, cognitive deficits, or even progressive eti-
poorer general health of pediatric and in particularly ologies that may contribute to functional deficits
secondary dystonia patients, who may be medically and limit the degree of recovery. Despite these
ill, undernourished, and reliant on tube feeding to drawbacks, a meta-analysis of the available data
begin with. While adult patients presenting for is consistent with average of ~20% improvement
placement of deep brain stimulators are typically in the BFMDRS although there is a wide distribu-
well nourished and skeletally mature, in children, tion of response rates, including a number of non-
the hardware must accommodate the growth of the responders (Koy et al. 2013). A smaller
patient as well as any preexisting skeletal prospective study of patients with normal or near
normal cognition and dystonia-choreoathetosis small, randomized double blind trial of adult
CP also found an improvement of about 20% on patients with dystonia suggested that the STN
the BFRMDRS suggesting that an appropriately was better tolerated than the GPi.
screened patient with secondary dystonia may At our institution, we have adopted the practice
experience benefits (Vidailhet et al. 2009). of targeting multiple locations in patients with
secondary dystonia. Patients are placed in a
Leksell frame under general anesthesia (Fig. 1a),
Future Directions and a stereotactic CT scan is obtained to guide the
placement of up to five temporary Adtec leads in
Future areas of study include determining the nuclei of the subthalamus, the thalamus, and the
optimal target for DBS in dystonic patients and palladium (Fig. 1b and c). Patients are subsequently
further refining which subset of patients with sec- monitored for several days in an epilepsy-
ondary dystonia stand to benefit from DBS. monitoring unit (EMU) to select the most effica-
Although the most common target is the GPi, a cious sites for implantation (Fig. 2). This 24-h
Fig. 2 Epilepsy Monitoring Unit. (a). Following phase I and wake cycles as well as during motor tasks to aid with
implantation of temporary leads, patients are placed in a selection of the most efficacious leads for permanent
24-hour epilepsy monitoring unit. (b). Recordings from all implantation
temporary leads are monitored continuously during sleep
Fig. 3 A 15-year-old female patient with striatal degener- globus pallidus internus and bilateral ventral intermedius
ation presented with severe dystonia (a). b. Skull radio- nuclei of the thalamus (b). At follow-up, the patient
graph showing implantation of stimulators in bilateral showed significant improvement in dystonic posturing (c)
monitoring permits recording throughout sleep- classification of dystonia: a consensus update. Mov
wake cycles to assist with selection of the optimal Disord 28:863–873
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deep brain stimulation in both primary and secondary Sanger TD, Delgado MR, Gaebler-Spira D, Hallett M,
childhood dystonia. Dev Med Child Neurol Mink JW (2003) Task force on childhood motor D:
55:567–574 classification and definition of disorders causing hyper-
Lumsden DE, Gimeno H, Tustin K, Kaminska M, Lin JP tonia in childhood. Pediatrics 111:e89–e97
(2015) Interventional studies in childhood dystonia do Vidailhet M, Vercueil L, Houeto JL, Krystkowiak P,
not address the concerns of children and their carers. Benabid AL, Cornu P et al (2005) Bilateral deep-
Eur J Paediatr Neurol 19:327–336 brain stimulation of the globus pallidus in primary
Lumsden DE, Gimeno H, Elze M, Tustin K, Kaminska M, generalized dystonia. N Engl J Med 352:459–467
Lin JP (2016) Progression to musculoskeletal defor- Vidailhet M, Yelnik J, Lagrange C, Fraix V, Grabli D,
mity in childhood dystonia. Eur J Paediatr Neurol Thobois S et al (2009) Bilateral pallidal deep brain
20:339–345 stimulation for the treatment of patients with
Marks WA, Honeycutt J, Acosta F, Reed M (2009) Deep dystonia-choreoathetosis cerebral palsy: a prospective
brain stimulation for pediatric movement disorders. pilot study. Lancet Neurol 8:709–717
Semin Pediatr Neurol 16:90–98 Volkmann J, Wolters A, Kupsch A, Muller J, Kuhn AA,
Marks W, Bailey L, Reed M, Pomykal A, Mercer M, Schneider GH et al (2012) Pallidal deep brain stimula-
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Ataxia and Disorders of Balance
Robert O’Reilly and Erin Field
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 690
Balance Components . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 690
Ataxia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 690
Vestibular System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 691
Common Vestibular Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 691
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 692
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 693
Abstract frequently are multifactorial. Visual impair-

In healthy individuals, static and dynamic bal- ments, lack of muscle coordination, sensory
ance is maintained by a seamless interaction of integration deficits, and vestibular deficits
three senses – vision, proprioception, and the should all be considered when evaluating bal-
vestibular system. The vestibular system is the ance deficits in children with cerebral palsy.
first sensory system to develop in humans and This chapter will review ataxia, the vestibular
is fully developed at birth. The remaining system, the assessment of gross motor function
matures over a 15-year period. Ataxia or the in cerebral palsy, common vestibulopathies,
lack of balance can be associated with a variety and important considerations for the evaluation
of neurologic disorders – including cerebral and treatment of balance disorders in children
palsy. Difficulties with general balance in chil- with cerebral palsy.
dren with cerebral palsy may include ataxia but
Keywords
Balance · Ataxia · Cerebral palsy · Vestibular ·
R. O’Reilly (*) Vertigo
Children’s Hospital of Philadelphia, Philadelphia,
PA, USA
e-mail: oreillyr@email.chop.edu
E. Field
Otolaryngology, Children’s Hospital of Philadelphia,
Philadelphia, PA, USA
e-mail: erinwfield@gmail.com

https://doi.org/10.1007/978-3-319-74558-9_48
690 R. O’Reilly and E. Field
Introduction over an approximately 15-year period (O’Reilly

et al. 2013).
Ataxia or the lack of balance can be associated
with a variety of neurologic disorders – including
cerebral palsy. Difficulties with general balance Ataxia
in children with cerebral palsy may include
ataxia but frequently are multifactorial. Visual Ataxia is defined as lack of balance or incoordi-
impairments, lack of muscle coordination, sen- nation (Miller and Bachrach 2017; Winchester
sory integration deficits, and vestibular deficits et al. 2013). This uncoordinated movement occurs
should all be considered when evaluating bal- without loss of muscle power. Ataxia is a clinical
ance deficits in children with cerebral palsy. symptom and is associated with a variety of neu-
This chapter will review ataxia, the vestibular rologic disorders (Palau and Espinos 2013). To
system, the assessment of gross motor function compensate for ataxia, children may attempt to
in cerebral palsy, common vestibulopathies, and walk very rapidly in an effort to maintain their
important considerations for evaluation and center of gravity. They may also compensate by
treatment of balance disorders in children with employing a wide-based stance. For many chil-
cerebral palsy. dren, their main limitation in ambulation is due to
severe ataxia (Miller and Bachrach 2017).
In cerebral palsy, the motor ability, balance,
Balance Components and coordination vary greatly among children.
The Gross Motor Function Classification System
Balance is maintained by the complex interaction or GMFCS can be used to classify the child’s
of three senses – vision, proprioception, and the motor ability. See Table 1.
vestibular system. The eyes provide three- The problems with general balance in children
dimensional visual input on how a person is ori- with cerebral palsy may include ataxia but fre-
ented relative to objects in their environment. quently are multifactorial. Visual impairments,
Proprioception is information from the skin, mus- such as restricted visual fields, strabismus,
cles, and joints that send impulses to the brain that reduced visual acuity, and abnormal refractive
help determine how the body is oriented in space. errors, are commonly seen in cerebral palsy
The vestibular system operates as the brain’s (Almutairi et al. 2018). Lack of muscle coordina-
“gyroscope,” providing information about motion tion can also contribute to imbalance, as well as,
of the head in the angular and linear directions, as spasticity and leg alignment issues. Balance is
well as, orientation of the head relative to the also affected by the need for rapid central
vector of gravity. In the healthy individual, this
information is rapidly and seamlessly fused in the Table 1 Gross Motor Function Classification System
central nervous system allowing for appropriate
GMFCS Walks without major limitations but not
output to motor pathways to allow for static and I completely normally
dynamic balance (O’Reilly et al. 2013). II Walks without any device or assistance but
The vestibular system is the first sensory sys- has problems keeping up with peers or
tem to develop in humans and is fully developed uneven ground or stairs
at birth. Balance function continues to mature III Requires a walker, cane, or crutches for most
walking
after birth with sequential development of general
IV Mostly in a wheelchair, may do standing
motor milestones – such as head control, sitting, transfers, may use a walker for exercise,
standing, and walking. This is paralleled by the requires assistance with transferring from
ability to stabilize vision during head movements the wheelchair
(the vestibulo-ocular reflex) and all of this pro- V Requires a wheelchair for all transport and is
gresses through experiential learning and adapta- dependent or requires full support to transfer
from the wheelchair
tion until adolescence. The entire balance matures
47 Ataxia and Disorders of Balance in Children with Cerebral Palsy 691
processing of the sensory inputs. In cerebral palsy, testing in cerebral palsy patients. They found that
sensory integration (the ability to process these objective research is limited and more is
sensory inputs) can be impaired leading to an warranted (Almutairi et al. 2018). One of the few
overshoot or undershoot motor response resulting studies that examined vestibular function in cere-
in deficits in balance. There is no single treatment bral palsy patients was done by Akbarfahimi and
available to improve global balance, but each colleagues. Cervical vestibular-evoked myogenic
deficit, whether it be visual or motor, must be potentials were tested in children with CP and
evaluated and addressed individually to maximize compared with typically developing children.
function. Treatment is typically focused on They found that there was an asymmetry and
correctable visual and orthopedic issues and on decrease in overall saccular function, compared
physical therapy to improve balance and teach the to normally developing children. More studies are
child how to safely fall (Miller and Bachrach needed to examine the function of the semicircu-
2017). lar canals and utricle in children with CP
(Almutairi et al. 2018; Akbarfahimi et al. 2016).
Anecdotally the authors have observed several
Vestibular System cases of a pronounced acoustic startle response in
some children with CP. In the few patients tested,
It is important to consider the contribution of the the VEMP response was found to have an abnor-
child’s vestibular system in balance, particularly mally low threshold suggesting that perhaps there
in children with cerebral palsy that may have is a disorder of either peripheral saccular function
visual and proprioception impairments. A func- or central sensitivity to this reflex in these patients.
tional vestibulo-ocular reflex (VOR) is important
in maintaining gaze stability with head move-
ments. This reflex is necessary for activities such Common Vestibular Disorders
as walking and running. This reflex is driven by
stimulation of the paired semicircular canals in the As seen in normal developing children, peripheral
labyrinth that drive the eye muscle response to vestibular disorders may also be found in children
maintain visual fixation on a target when the with cerebral palsy. In a study by O’Reilly et al., a
head is in motion. This reflex can be simply dem- retrospective chart review was completed on
onstrated by spinning a subject on a stool and 132 patients that were seen in a tertiary care pedi-
watching their eye movements (termed nystag- atric vestibular program. In this review, the most
mus) that allow them to track the visual surround. common diagnoses were peripheral vestibulopathy
There are also receptors termed “otolith organs” in (29.5%), migraine/benign recurrent vertigo of
the vestibule that sense the direction of “down” childhood (24.2%), motor/developmental delay
(gravity vector) and sense fore-aft and up-down (10.6%), traumatic brain injury (9.8%), and cen-
movements and provide the appropriate eye tral nervous system structural lesion (9.1%)
response and head orientation. (O’Reilly et al. 2011).
The function of the semicircular canals and Peripheral vestibulopathies included: otitis
otolith organs of the vestibular system can be media or otitis media with effusion, benign par-
tested using video head impulse tests (VHIT), oxysmal positional vertigo (BPPV), and vestibu-
caloric stimulation, rotary chair testing, and ves- lar neuritis and labyrinthitis.
tibular-evoked myogenic potentials (VEMP). It Otitis media and otitis media with effusion is
has been hypothesized that children with cerebral very common in the pediatric population and
palsy have impaired function of the peripheral may amplify balance dysfunction. It has been
vestibular system, but there is a paucity of studies documented that vestibular end organ, balance,
employing vestibular testing in this population. In and motor function are acutely worse in the pres-
a review of literature, Almutairi and colleagues ence of a middle ear effusion and that this dete-
noted this in their review of the vestibular function rioration reverses upon spontaneous resolution
692 R. O’Reilly and E. Field
or treatment of the OME. Several theories have benign recurrent vertigo of childhood. In these
been proposed as to the pathophysiology of bal- children, there are multiple episodes of head –
ance dysfunction in the presence of AOM or tilt, nystagmus, nausea and vomiting, and pallor
OME. One theory is that the inflammatory medi- with associated fear. The episodes are very short
ators present in the middle ear fluid can enter the lived and intercurrent balance is not affected. The
inner ear through the round window membrane episodes typically resolve over time. In more clas-
and cause a serous labyrinthitis, while another sic migraine with aura symptoms include dizzi-
theory has been proposed that pressure changes ness, motion intolerance, nausea and vomiting,
in the middle ear may cause a displacement of the sensitivity to light and sounds, and loss of bal-
round and oval windows. Treatment involves ance. These symptoms can be present with or
observation (depending on the number of epi- without a headache. The sensation of vertigo is a
sodes of ear infections or the duration of the manifestation of the “aura” of migraine and rep-
middle ear fluid) and may necessitate resents abnormal activity in the central vestibular
myringotomy with tube placement (O’Reilly pathways, much as the visual aura represents
et al. 2013). abnormal activity in the central visual pathways.
Benign paroxysmal positional vertigo (BPPV) This is a diagnosis of exclusion and vestibular
is classically described as sudden onset of vertigo testing must be performed to rule out other causes
that lasts for seconds and is triggered by head of vertigo. Treatment involves prevention/reduc-
movements. BPPV occurs when otoconia from ing migraine triggers, diet modification, and phar-
the otolith organs become dislodged and migrate macologic management (O’Reilly et al. 2013).
into the endolymph-filled semicircular canals.
When these otoconia accumulate, they cause
aphysiologic displacement of the receptor organ Conclusion
of the semicircular canal, resulting in vertiginous
episodes. In children, BPPV is commonly seen In the assessment of children with cerebral palsy,
following significant head trauma and can be it is important to consider the role of the vestibular
effectively treated through a series of head posi- system as it relates to balance concerns and ataxia.
tionings to displace the otoconia from the Common vestibulopathies should be considered
involved canal (O’Reilly et al. 2013). in the assessment. Although research is limited in
Vestibular neuritis and labyrinthitis are caused children with cerebral palsy, vestibular testing
by inflammation or damage to the nerve(s) that should be considered in children with concerns
connects the vestibular apparatus to the brain or for a vestibulopathy. Treatment in children with
by direct infection of the inner ear (as in menin- ataxia and balance concerns should be focused on
gitis). This may be caused by viral infections, correcting any underlying visual and orthopedic
particularly the herpes family viruses that have a deficits and optimizing physical therapy to
tropism for cranial nerves. The typical presenta- improve balance and teach the child safe falling
tion is the relatively rapid and severe onset of techniques.
vertigo, nausea/vomiting, imbalance, and nystag-
mus. Hearing is affected in labyrinthitis but not in
vestibular neuritis. Symptoms can last for days to Cross-References
weeks and treatment initially involves antinausea
medications, possibly steroids, and, after the sub- ▶ Assessing Dynamic Balance in Children with
acute stage, vestibular rehabilitation (O’Reilly Cerebral Palsy
et al. 2013). ▶ Musculoskeletal Physiology Impacting Cere-
Vestibular migraine is one of the most common bral Palsy Gait
causes of vertigo in the pediatric population. In ▶ Postural Control in Children and Youth with
very young children, this can occur as so-called Cerebral Palsy
47 Ataxia and Disorders of Balance in Children with Cerebral Palsy 693
References pediatric population. Otolaryngol Head Neck Surg

144(2):142–148
Akbarfahimi N, Hosseini SA, Rassafiani M et al (2016) O’Reilly RC, Morlet T, Cushing SL (2013) Manual of
Assessment of the saccular function in children with pediatric balance disorders. Plural Publishing, San
spastic cerebral palsy. Neurophysiology 48(02):141–149 Diego
Almutairi A, Christy JB, Vogtle L (2018) Vestibular and Palau F, Espinos C (2013) Approach to the differential
oculomotor function in children with cerebral palsy: a diagnosis of cerebellar ataxias. In: Handbook of the
scoping review. Semin Hear 39(3):288–304 cerebellum and cerebellar disorders. Springer, Dor-
Miller F, Bachrach S (2017) Cerebral palsy: a complete drecht, pp 1799–1817
guide for caregiving, 3rd edn. Johns Hopkins Univer- Winchester S, Singh PK, Mikati MA (2013) Ataxia. In:
sity Press, Baltimore Handbook of clinical neurology, vol 112. Elsevier,
O’Reilly RC, Greywoode J, Morlet T et al (2011) Compre- Philadelphia, pp 1213–1217
hensive vestibular and balance testing in the dizzy
Assessing Dynamic Balance
Timothy A. Niiler
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 696
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 696
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 698
Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 698
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 711
Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 718
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 720
Abstract is the method of balance assessment used, and

Individuals with cerebral palsy routinely suffer these range from semi-qualitative task-oriented
from dynamic balance deficits during gait that and functional tests that require few resources
affect their safety and mobility. Although bal- to quantitative and instrumented that require a
ance can be expected to improve throughout full gait laboratory and staff. This chapter dis-
childhood and adolescence for most patients, cusses the natural history of balance deficits in
this improvement levels off or even reverses in individuals with cerebral palsy, the methods by
adulthood due to orthopedic reasons or the which balance is assessed, and, finally, the
decrease in physical activity seen in many interventions used to improve balance includ-
adults. Fortunately, there exist many effective ing the evidence backing them up.
therapies which can improve balance regard-
less of age. These include a number of strength Keywords
and vestibular training methods as well as Dynamic balance · Posture · Stability ·
some innovative therapies involving virtual Proprioception · Vestibular system
reality, vibration, and electrical stimulation.
Key to judging the success of an intervention
T. A. Niiler (*)
Gait Laboratory, Nemours/AI duPont Hospital for

https://doi.org/10.1007/978-3-319-74558-9_49
696 T. A. Niiler
Introduction As children master sitting up and reaching,

they then begin to progress to crawling, pulling
Balance is related to the ability to maintain pos- up, cruising, and eventually walking. In TD chil-
ture or vertical orientation throughout tasks rang- dren the progression to early walking occurs
ing from sitting to standing to walking and is between 8 and 12 months (Leonard et al. 1991),
dependent on the complex interactions of neural while in children with CP, the progression is
control of muscles, strength, proprioception, posi- delayed dependent on the severity of involve-
tioning, vision, and the vestibular system. In ment. McCoy et al. (2014) studied balance in
cerebral palsy, observed balance deficits are the children with CP aged 18 – 60 months using the
result of early brain injury during pregnancy or Early Clinical Assessment of Balance tool
birth. The exact nature of these balance deficits (ECAB) detailed in Part 3. The ECAB allows
depends on the brain region affected. In spastic clinicians to evaluate balance of young children
CP, the most common form, there is damage to the based on performance during sitting, standing,
motor cortex and associated white matter of the and dynamic balance tasks on a hundred point
brain. In this case, the symptoms involve hyper- scale where a higher score reflects better balance.
tonicity of the affected muscle groups. Spasticity Results were broken down by age group and
affects balance directly by limiting one’s ability to Gross Motor Function Classification Scale
respond to postural perturbations or by changing (GMFCS) level and indicated that older and less
the kinematics of gait so as to predispose one to severely involved children had better balance. In
tripping. In dyskinetic CP, the damage is to the particular, the oldest GMFCS level I children
basal ganglia, and this results in involuntary scored 44% higher (about 27 points) than the
movements and fluctuations in muscle tone. youngest children, while the oldest GMFCS
These, in turn, make it difficult to maintain upright level V children scored only 5% (0.4 points)
posture. Only in ataxic CP is the damage specifi- higher than the youngest. Figure 1 from McCoy
cally to the cerebellar structures. Since the anterior et al. (2014) shows the mean ECAB results by age
cerebellum controls sensorimotor integration and GMFCS level. It’s noteworthy that age and
(Craig and Doumas 2017), this last form of CP is GMFCS level together differentiate ECAB scores
especially problematic for balanced gait for pri- implying that children between these ages will not
mary rather than secondary reasons. improve their balance enough to graduate to a
lower GMFCS level. Additionally, although bal-
ance improves in all GMFCS levels, these find-
Natural History ings point to a decreased acquisition of balance in
more severely involved cases.
Studies of early postural control in both typically Whereas young children use balance strategies
developing (TD) children and those with cerebral that are highly dependent on vision (Shumway-
palsy (CP) indicate that TD children have an earlier Cook and Woollacott 1985), by the time they are
ability to recruit postural muscles in response to 7 – 8 years of age, they begin to transition to
reaching (de Graaf-Peters 2007). While TD chil- including proprioception and vestibular systems
dren are able exert consistent directional postural in their balance strategies. There is also some
control by the age of 7 – 8 months, in children with evidence that increases in strength and decreases
CP, this control may not manifest until as late as in response time, especially of the lower leg,
15 months dependent on the degree of involve- improve balance throughout childhood and early
ment. As CP becomes more involved, muscle adolescence (Sundermier et al. 2001). During this
activity during reaching is less controlled, and period, improvements in motor speed are also
EMGs indicate that muscles are either overactive seen (Gasser et al. 2010), and these, in turn,
or poorly controlled. In short, there is difficulty improve the ability of children to respond to per-
recruiting the appropriate muscles to regulate mus- turbations in balance. At this point, vision still
cle length or velocity (de Graaf-Peters et al. 2007). plays a major role, and refinements in peripheral
48 Assessing Dynamic Balance in Children with Cerebral Palsy 697
Fig. 1 Mean ECAB scores

by GMFCS level and age.
ECAB scores clearly
increase with age except for
GMFCS levels IV and
V. (From McCoy et al.
2014. Used with
Permission)
vision further improve balance during gait each GMFCS level have been published by Hanna
(Assaiante and Amblard 1992). In competition et al. (2008) (Fig. 2). These data indicate that to a
with these improvements in children with spastic point, all GMFCS levels improve their GMFM-66
CP are deformities which can manifest over time. scores with increasing age. However, in GMFCS
Due to the constant forces present from spastic levels III–V, GMFM-66 scores decline slightly
muscles, the underlying bony structures can after ages 7–8 years, while GMFCS levels I and
deform, and these changes will, in turn, lead to II level out at GMFM-66 of 89.5% and 66.5%,
increased difficulty in walking. For example, in respectively, around 10 years of age (Hanna et al.
children with contractures involving groin mus- 2009). If GMFM score is considered to be a proxy
cles, it is common to progress to painful deformi- for dynamic balance, then the inference is that
ties in the hip joint. Children with ataxic or balance in CP generally improves with age.
dyskinetic CP are less likely to experience such Other balance scales mirror these age-based
deformities though it is not unheard of. Balance results. Both the Pediatric Balance Scale (PBS)
tests such as the ECAB show less discriminatory and the Berg Balance Scale (BBS) have been used
ability in dynamic balance by mid-childhood to evaluate the balance of adolescents with CP and
since walking ability is now well established and show discriminant validity between different
few items on the ECAB are gait related. Addition- GMFCS levels with the levels being inversely
ally, since there is evidence that static and proportional to the balance scores (Jantakat et al.
dynamic balance are not necessarily correlated 2015).
(Owings et al. 2000; Kang and Dingwell 2006; There are clear differences in balance observed
Karimi and Solomonidis 2011), tests that involve between different types of CP as well as between
gait rather than standing are more important in this children with CP and TD children. Observations
age group. of center of mass (COM) motion in children hav-
The Gross Motor Function Measure (GMFM) ing hemiplegic or diplegic CP show that there is
has also been used to quantify balance in children greater variability in standing balance in the
with CP (see section “Treatment”). Reference diplegic population (Rojas et al. 2013). This is
curves showing normative GMFM-66 scores for reinforced by Hsue et al. (2009a, b) who showed
698 T. A. Niiler
Fig. 2 GMFM-66 curves

showing increase in
function till mid-childhood
and then decrease for
GMFCS levels III, IV, and
V. (From Hanna et al. 2009.
Used with Permission)
that during gait COM lateral displacement, veloc- loss, but it should be assumed that the same pro-
ity, and acceleration was more similar between TD cesses that affect TD adults are also at play in
and hemiplegic CP patients than between hemiple- individuals with CP.
gic and diplegic patients. Work by this author has
likewise shown that the excursion of the COM is
larger in children with CP than in their typically Treatment
developing peers (Niiler et al. 2009, 2017).
As individuals with CP age into adulthood, Despite the known balance deficits of individuals
variable outcomes with ambulatory ability and with CP, deriving growth curves for dynamic bal-
balance have been reported (Andersson and ance is somewhat problematic due to the multi-
Mattsson 2001). In this study of 363 adults aged faceted presentation of CP (type, severity) and the
20 – 58 years, 35% of ambulatory adults reported lack of a standard index for the measurement of
decreased walking ability, and 19% reported dynamic balance. Therefore comparison of bal-
improved walking ability. Where walking ability ance studies between authors in order to conclu-
was impaired, it was generally due to a variety of sively describe progression of balance with age is
reasons including knee pain, increase of spastic- difficult at best. This section presents a large num-
ity, or decreased physical activity. In a survey of ber of methods for testing dynamic balance as
25 older adults with CP aged 30–65 years, well as treatment methods that have some evi-
decreases in walking ability were reported by dence of efficacy.
60% of respondents, and of them 80% attributed
this to impaired balance (Morgan and McGinley
2013). It should be noted that TD adults also Testing
report a decline in balance for a number of reasons
including decreasing physical activity, declines in That there are myriad methods now in use for
muscle strength, osteoarthritis, neuropathies, neu- balance testing is a testament to the difficulty
ronal loss, hair cell loss in the vestibular system, that exists in quantifying dynamic balance. For
and decreased vision (Iwasaki and Yamasoba the purpose of this chapter, dynamic balance is
2014). It is not clear how much of the decline the ability to keep the center of mass (COM) over
seen in individuals with CP is due to the condition the base of support during gait, turning, or other
itself, or how much is due to aging-related balance transitions involving movement of the feet.
However, during transitions where one or both as accelerometers, walkways, or gait analysis,
feet (running) are not on the ground, the base of since these are in common use. A few assessment
support (BOS) is poorly defined, and dynamic methods that are promising, but currently
balance must fall back to an assessment of posture underutilized, are also noted.
during the activity. In this case it must be defined
as an ability to maintain posture throughout the Task-Oriented Assessment of Dynamic
activity, or else the definition of the BOS must be Balance
extended. For example, during gait, the COM Task-oriented tools are among the most popular
moves beyond the base of support, and in such a tools for assessment of balance due their ease of
case, some type of margin of support (MOS) use clinically and the need for little or no equip-
based on COM velocity has been proposed as a ment beyond the form used to record the results.
useful construct for balance assessment Most of these tools are functional in nature: they
(Hof 2005). require the participant to accomplish a variety of
Balance assessment can be organized in a num- progressively more difficult tasks, and the asses-
ber of different ways. Balance can be thought of as sor rates the participant’s ability to complete them.
the measurement of the ability to maintain, One of the most commonly utilized is the
achieve, or restore balance (Saether et al. 2013). Gross Motor Function Measure (GMFM) which
It can also be thought of in terms of its postural, quantifies competence in motor function. It scores
vestibular, or proprioceptive components. There individuals on either 66 or 88 tasks which fall
is static balance in which the BOS is not mobile under dimensions: (A) lying and rolling,
and dynamic balance in which case it is. Testing (B) sitting, (C) crawling and kneeling,
can be objective, making use of motion capture (D) standing, and (E) walking, running, and
technology, or subjective, involving trained jumping (Russell et al. 1989). The dimensions
observers and rating scales. A full review of a progress in developmental order, and higher total
number of these tests can be found in the chapter scores are indicative of further motor develop-
“Measures to Determine Dynamic Balance” in the ment. Each item is scored based on relative com-
Handbook of Human Motion (Niiler 2018). This pletion of the task: 0, did not initiate; 1, initiated;
section will summarize those methods and discuss 2, partially completed; or 3, completed. The
additional methods that have been applied in the GMFM-88 takes approximately 45 – 60 min to
assessment of children with cerebral palsy. administer dependent on the cooperation and
A fairly comprehensive review of tools to comprehension of the child, while the GMFM-
assess balance in CP published from 1946 to 66 can be administered in less time. The full
2012 was made by Saether et al. (2013) which score sheet for both tests can be found in the
aimed to establish internal consistency, test-retest references to this chapter (CanChild.ca n.d.).
reliability, and level of evidence for each tool. Although GMFM-66 has only been validated for
After excluding papers that were case studies CP, GMFM-88 can be used with all individuals.
and reviews, studies where fewer than 30% of Another difference in the tests is that the GMFM-
participants had CP, and tools which were not 66 must be administered to patients without shoes,
primarily designed to assess balance, 22 tools while in the GMFM-88, this does not matter
were selected for evaluation. Additionally, the (Beckers and Bastieanen 2015). Dimensions D
selected tools could not require laboratory equip- and E are used by many researchers to assess
ment for their usage. We focus here on the subset balance since the tasks involved are functionally
of those tools with the highest validity which also related to balance. A number of other balance
addressed some form of dynamic balance (trans- measures are based, at least in part, on the
fers, turns, or walking) or which have been devel- GMFM, and due to its comprehensiveness and
oped since Saether et al.’s review and were based ability to quantify deficits in specific balance-
on one of the reviewed tools. We also include related tasks, the GMFM is often thought of as a
tools which involve laboratory equipment such gold standard for balance assessment. However, a
700 T. A. Niiler
recent study of 30 children with hemiplegic or non-fallers varies dependent on the population
diplegic CP showed no correlation between (Santos et al. 2011; Shumway-Cook et al. 1997;
GMFM scores and fall risk (Callahan 2017). The Muir et al. 2008). There have also been floor and
resolution of this quandary, the frequency with ceiling effects reported with this scale when used
which CP researchers use the GMFM as a balance with CP (Jantakat et al. 2015), stroke (Blum and
metric, yet its failure to correlate with falling, may Korner-Bitensky 2008), or with Parkinson’s dis-
have to do with the fact that fall risk is often ease (Downs et al. 2013). For individuals with CP,
quantified based on the number of actual falls the floor effects arise when the test is used with
rather than the number of near misses. Still, GMFCS levels III and higher, while the ceiling
since many task-oriented balance assessments effects occur for individuals at the higher end of
have been correlated directly with fall risk, deter- GMFCS level I. Its use in quantifying balance in
mination of dimensions D and E cutoff scores for individuals with CP has been relatively common,
which fall risk increased would be a useful addi- and it has been used with children and adolescents
tion to the literature. (Kembhavi et al. 2001; Jantakat et al. 2015;
The Berg Balance Scale (BBS) is one of the Moraes et al. 2016) through adults (Morgan and
more popular balance scales in use and can be McGinley 2013). However, the use of the BBS as
considered to be a practical subset of the a balance assessment with hemiplegics should be
GMFM, even if its genesis was independent. It done with caution since the final score will depend
was originally created by a team of 32 clinicians on whether the involved or noninvolved side was
for the assessment of balance in the elderly at used for one-legged stance items (Kembhavi
about the same time as the GMFM (Berg et al. et al. 2001).
1989) and has been extensively evaluated for con- Despite the popularity of the BBS, some addi-
tent validity and reliability (Berg et al. 1989, tional problems with its usage in children have
1992, Yi et al. 2012; Blum and Korner-Bitensky been noted. Specifically, children have a lower
2008; Gan et al. 2008; Wrisley and Kumar 2010; attention span and ability to follow directions
Saether et al. 2013; Downs et al. 2013). The BBS while also having decreased endurance. There-
is now commonly used to assess balance in addi- fore, Franjoine et al. (2003) developed a related
tional populations including patients with stroke, test called the Pediatric Balance Scale (PBS)
concussion, Parkinson’s disease, multiple sclero- which modified the BBS to be more easily admin-
sis, vestibular dysfunction, and also CP (Downs istered to children. Specifically, the test included
et al. 2013; Niiler 2017; Feld et al. 2001; Jantakat the same 14 items, but these were reordered and
et al. 2015) and has become commonly used both clarified and time was reduced from 2 min to 30 s
for its correlation with balance deficits and also for the activities of standing unsupported, sitting
because it can be completed in 15–20 min. The unsupported, and standing unsupported with feet
scale evaluates 14 different activities ranging together (Franjoine et al. 2003). The same total
from sitting, standing, reaching, turning, and score (56) is possible on this scale as with the
transfers and is therefore considered by many to BBS. Since its introduction, the PBS has gained
be a good indicator of both static and dynamic relatively wide acceptance and has been validated
balance. However, there is no gait component, so in both typically developing children (Franjoine
its validity to assess functional walking is limited. et al. 2010) and those with CP (Her et al. 2012; Yi
Each activity is rated on a five-point scale (0–4) so et al. 2012; Saether et al. 2013; Kim 2016). In
that the maximum score is 56. Patients who score addition to being correlated with other motor con-
41 or higher are considered to be a low fall risk, trol metrics such as GMFCS level, the PBS has
those who score between 21 and 40 are considered also been shown to have actual predictive power
to be moderate fall risks, and those who score with regard to fall frequency. In children with CP,
below 20 are considered to be high fall risks. PBS scores of less than 45.5 were found to iden-
However, several studies have shown that the tify individuals who fell two or more times in the
cutoff score for discriminating fallers from preceding 6 months (Kim 2016). However, it has
been noted that just as the BBS has ceiling effects, be positively correlated with age and negatively
so too does the PBS in that it can fail to distinguish correlated with GMFCS level. A second study by
balance deficits in high-functioning children with Randall et al. (2014) compared the ECAB to the
CP (Kembhavi et al. 2002). The PBS is also able GMFM-66 (B&C) and the Pediatric Reach Test
to avoid a floor effect in younger or lower- (PRT) in 28 children with CP aged 2–7 years and
functioning individuals due to its decreased time found that it correlated highly with the GMFM-66
limits in the static balance items (Jantakat et al. and showed lower measurement error than the
2015). Finally, the use of PBS over BBS in youn- PRT. (The PRT, which is not covered here, is
ger children is supported by studies that show essentially a subset of the BBS.) It should be
better test-retest reliability in the PBS (Franjoine noted that, unlike the BBS or PBS which have
et al. 2003). Despite this, some authors offer cau- been used to evaluate balance in CP, the ECAB
tion in the use of the PBS. When used with the was specifically created for use with the CP pop-
intention of detecting changes in balance in youn- ulation, but it is still new enough that it has not
ger children due to therapeutic intervention, care been independently reviewed as thoroughly as
must be taken in interpretation of the score since it either the BBS or PBS. Also, it has limitations
is not possible to deconvolve the effects of matu- when applied to dynamic balance in that there is
ration of balance and gait from those of the inter- no gait component to the test.
vention in question (Rine and Moore 2010). This One of the earliest tests developed for measur-
point is emphasized by Sival (2012), since there is ing balance in motion that is still in common use is
not, as of yet, an established natural history of the Tinetti Performance-Oriented Movement
PBS improvement with maturation in children Assessment test (POMA) (Tinetti 1986). This
with CP either as a whole or by subtype. test was developed to assess balance and gait
Because of the noted problems in assessing functionality in older adults and is similar in
balance during early childhood and the need to many ways to the BBS. The test is broken into
assess balance differently in preambulatory chil- two parts. In the first part, balance is assessed in
dren, another tool was created to quantify balance both sitting and standing positions but also in
in very young children (McCoy et al. 2014). The transitions between and turning 360 . In the sec-
Early Clinical Assessment of Balance (ECAB) ond part, gait is assessed including gait initiation,
was based on the composite of two other metrics: symmetry, continuity, stance, and the presence of
the Movement Assessment of Infants (MAI) and typical gait features like foot crossing or atypical
the PBS. Seven ECAB items (Part I) were taken features like foot dragging. The test has been
from the MAI involving assessment of head and validated on a number of populations including
trunk postural control. However, five of these the elderly (Tinetti 1986), stroke patients (Canbek
items are bilateral, so there are effectively 12 ques- et al. 2013), patients with Parkinson’s disease
tions in Part I. Six ECAB items (Part II) were (Kegelmeyer et al. 2007), and patients with knee
taken from the PBS and involve sitting and stand- osteoarthritis (Parveen and Noohu 2017). In the
ing postural control, including turning 360 and CP population, the POMA has been validated
transitions from sitting to standing. Each question against other balance metrics, such as the
in Part I is worth 0–3 points for a total of 36 points, Dynamic Gait Index (Robinson et al. 2015) and
while questions in Part II are variably weighted: Timed Up and Go Test, and shown to be inversely
the two questions involving sitting are worth 0–6 correlated with GMFCS levels (Talu 2015). The
points, the three involving standing are worth POMA has also been shown to have a high spec-
0–10 points, and the two involving dynamic ificity and sensitivity in individuals with paretic
motion are worth 0–16 points for a total of conditions such as CP (Chiba et al. 2009). It is not
64 points. To validate the ECAB, McCoy et al. yet widely used to assess dynamic balance in CP,
(2014) scored 410 children with CP aged although its usage with this population seems to
1.5–5 years. Internal consistency of the ECAB be on the rise based on the author’s review of
was found to be high, and the score was found to literature involving the use of the POMA to
702 T. A. Niiler
quantify improvement in gait and balance due to been conducted that specifically evaluates the
various interventional strategies (Robinson et al. validity of the DGI in the CP population.
2015; Jaume-i-Capó et al. 2014; Sunwoo et al. El-Basatiny and Abdel-aziem (2015) found com-
2012; Mikołajczyk et al. 2017). Only mensurate improvements in both DGI and BBS in
Mikołajczyk et al. has used the POMA in a pedi- children with CP who had been trained to improve
atric population, and these were children aged posture with trunk control exercises. Robinson
8–13 years. et al. (2015) found that both DGI and POMA
The Dynamic Gait Index (DGI) is a set of eight improved as a result of functional electrical stim-
tasks which are completed while walking in order ulation. Sharan et al. (2016) noted improvement in
to test functional mobility and dynamic balance. the DGI postsurgically with concurrent improve-
Due to its composition, this assessment can be ment in the physician’s rating scale and functional
considered to be more challenging than the mobility scale. The DGI is a promising metric for
POMA which in its gait section has the assessor estimation of dynamic balance in cerebral palsy,
rate the typical gait of the participant on several but it is underutilized at the moment due to the
points during their typical gait rather than having lack of larger scale validation of the score in this
the participant complete different tasks. While all population.
tasks demand some level of dynamic balance, one,
in particular, was designed to stress vestibular and Timed or Distance-Based Walking Tests
visually based balance by requiring the participant of Dynamic Balance
to walk with vertical then horizontal head turns. Another class of test seeks to tease out dynamic
This dual-task paradigm is generally more diffi- balance more quantitatively without necessarily
cult for all ability levels and is intended to serve to identifying the root cause as do the aforemen-
limit the ceiling effect for higher-performing indi- tioned tests. Among these tests are the Timed Up
viduals. Each task is evaluated on a four-point and Go Test (TUGT), the Timed Up and Down
scale (0–3) such that higher scores indicate better Stairs Test (TUDST), the one-minute walk test
performance. In adults it has been shown that a (1MWT), the six-minute walk test (6MWT), and
cutoff score of 19 (out of 24) discriminates fallers the 10-meter walk test (10mWT). Most of these
from non-fallers (Boulgarides et al. 2003), but tests involve requiring the subject to walk a fixed
despite the increased number of tasks compared distance or time and very simple directions. The
to the gait portion of the POMA, a ceiling effect premise of these tests is that slower completion of
has, in fact, been found in community-dwelling timed tests or walking shorter distances is evi-
individuals under 60 years of age (Vereeck et al. dence of instability since by moving more slowly,
2008). However, the DGI may be more applicable subjects are allowing themselves more time to
over a range of ages in individuals with balance compensate for perturbations while also allowing
impairments. Validation of the DGI as a measure themselves more time to perceive and adapt to
of dynamic balance is fairly extensive in patients possible obstacles. The advantage of most of
with stroke (Jonsdottir and Cattaneo 2007), mul- these tests over the previous ones is that they
tiple sclerosis (McConvey and Bennett 2005), and have been shown to actually test for dynamic
vestibular disorders (Wrisley et al. 2003). In addi- balance directly while also taking less time to
tion, the DGI has a high inter-rater and test-retest complete. However, as previously noted, these
reliability as well as a high sensitivity and speci- tests do not help the clinician to determine specif-
ficity (Shumway-Cook et al. 1997). The use of the ically where the balance deficit occurs (Table 1).
DGI has also been validated in children with fetal In the TUGT, the assessor records the time it
alcohol syndrome as well as typically developing takes for a subject to rise from a chair, walk 3 m,
children (Lubetzky-Vilnai et al. 2011). Recently, turn 180 , walk back, and sit down (Fig. 3)
various authors have started to use the DGI to (Podsiadlo and Richardson 1991). This test
evaluate the gait and balance of higher- involves a single trial, is short, and extremely
performing children with CP, but no study has easy to conduct while also testing sit-to-stand,
Table 1 Comparison of task-oriented tests of balance. An subject, is not indicated in this table. The GMFM tests are
“x” indicates that the item, in some form or another, is not included here due to length but may be found at
present in the test. The order of items, as presented to the CanChild.ca (2017)
Item BBS PBS ECAB POMA DGI
Head righting – lateral (right and left) x
Head righting – extension x
Head righting – flexion x
Rotation in trunk (right and left) x
Equilibrium reactions in sitting (right and left) x
Protective extension – side x
Protective extension – backward x
Sitting to standing x x x x
Attempts to rise x
Standing to sitting x x x
Transfers x x
Standing unsupported x x x
Immediate standing (first 5) x
Sitting unsupported x x x x
Standing with eyes closed x x x x
Standing with feet together x x x
Nudged while feet together x
Standing with one foot in front x x
Standing on one foot x x
Turning 360 x x x x
Turning to look behind x x
Retrieving object from floor x x
Placing alternate foot on stool x x x
Reaching forward with outstretched arm x x
Initiation of gait (no hesitancy) x
Step length and height x
Step symmetry x
Step continuity x
Path (deviation) while walking x
Trunk sway while walking x
Walking stance (wide vs. narrow) x
Walking x
Walking with speed changes x
Walking with horizontal head turns x
Walking with vertical head turns x
Walking with a quick pivot stop x
Walking over objects x
Walking around objects x
Walking up and down stairs x
gait, turning, and stand to sit. A cutoff time is used cutoff time is variable as it is dependent on the
to assess whether or not subjects are at increased population being assessed (Bischoff et al. 2003;
risk of falling. For example, if a subject is faster Trueblood et al. 2001; Whitney et al. 2005) with
than the cutoff time, he or she is not considered to values ranging from 12 to 15 s. In addition to
have an elevated fall risk. Unfortunately, this being validated in typically developing adults
704 T. A. Niiler
Fig. 3 Directions for the

Timed Up and Go Test
and children, there are a number of studies that standard gait and, as such, poses more of a chal-
have validated it for use with the CP population, lenge to participants. Using a timed stair test is
and according to a review of recent literature thought to be able to separate out higher-
involving the TUGT, it was most frequently used functioning individuals and avoid potential ceil-
in evaluating balance of children with CP or trau- ing effects found with level walking tests. Addi-
matic brain injury (Nicolini-Panisson and tionally, stairs are relatively standard due to
Donadio 2013). Williams et al. (2005) examined building codes and easy to find. Although there
the TUGT’s reliability on 176 typically develop- are a number of very similar stair tests which
ing children aged 5.75 1.66 years along with generally vary based on the number of steps
41 children with CP aged 8.91 4.25 years find- climbed (Nightingale et al. 2014), it seems that
ing a high reliability in TD children similar results occur for most variations of the test.
(ICC = [0.83–0.89]) and an even higher reliability In the classic TUDST, the subject starts 30 cm
in children with CP (ICC = 0.99). In the children from the bottom of a 14 step flight of stairs and is
with CP, TUGT times were positively correlated timed on his or her “quick but safe” ascent, turn,
with GMFCS level in the CP group. In a study by and descent until both feet return to the original
de Campos et al. (2011) involving six children level. Subjects can traverse the stairs in any man-
with CP, it showed a negative correlation between ner, one or two steps at a time, and using a hand-
TUGT times and GMFM dimensions D and E rail or not (Zaino et al. 2004). Zaino’s study of
scores. Work by Gan et al. (2008) has also showed 27 TD children and 20 children with CP indicated
negative correlations between the TUGT and the increasing times with increasing involvement
GMFM in children with CP. However, in this case including a positive and significant correlation
they were not able to distinguish between between these times and TUGT times in the sub-
GMFCS levels I and II using this metric. This jects with CP. High test-retest and inter-rater reli-
last result may be due to the broadness of ability was established with this test. Chrysagis
GMFCS categories rather than an inherent weak- et al. (2014) tested the validity of a four step
ness in the test. The test is the only one of the TUDST in 35 adolescents with CP
balance tests thus far which is recommended for (14.97 2.03 years) compared to other measures
dynamic balance assessment by the Centers for such as the TUGT and GMFM-88 and found
Disease Control and Prevention (CDC 2016). TUDST times to be significantly negatively cor-
Another class of walking tests involves having related with the GMFM-88 and positively corre-
subjects climb stairs rather than walking a straight lated with the TUGT. In addition, longer TUDST
path along a walkway. Stair walking involves times were found for higher GMFCS levels. A
more motor skills, strength, and flexibility than negative correlation between the TUDST and
GMFM dimension E was found by de Campos reliability (ICC = 0.94) (McDowell et al. 2009).
et al. (2011). Due to increased difficulty in stair A yet longer test, the six-minute walk test
climbing compared to typical gait, it is possible (6MWT) in which the distance a subject walks
that the TUDST is a better test for quantifying over 6 min is recorded, is typically used as a
balance in higher-functioning individuals than measure of cardiovascular fitness in the CP popu-
the TUGT, but this remains to be shown explicitly. lation (Nsenga Leunkeu et al. 2012) but is also
Some other walking tests have shown correla- thought to reflect balance and motor function. In
tions with other balance scores and are therefore particular, Maanum et al. (2010) reported that log-
thought to implicitly measure dynamic balance transformed times in the TUGT in 126 adults with
during gait. Walking speed is predictive of health CP explained 67% of the variability observed in
outcomes in general including motor function and the 6MWT. Likewise, Chong et al. (2011) found
falls (Middleton et al. 2015). The 10-meter walk high convergent validity of the 1MWT and the
test (10mWT) is most similar to previously 6MWT and that these tests correlated with
described tests like the TUGT but requires fewer GMFCS level. As the 6MWT has also been
instructions. The test is often administered at self- found to have high test-retest reliability (Nsenga
selected speed but is sometimes done as the Leunkeu et al. 2012), it is possible that the test
10-meter fast walk test in which subjects are could serve as a proxy for more direct balance
instructed to cover the distance as quickly as pos- measures in individuals for whom the test is
sible. Subjects who walk the distance faster are already being administered to assess fitness.
thought to have better balance. However, cutoff
velocities to discriminate fallers from non-fallers Marker-Based Assessment of Dynamic
in the CP population have not been established. Balance
Mean velocities for the 10mWT by GMFCS Although a number of task-oriented and timed/
levels were established to be 1.63 0.28 m/s distance-based walking tests have shown both
(GMFCS I), 1.13 0.30 (GMFCS II), and validity and reliability with regard to measuring
0.58 0.35 (GMFCS III) (Bahrami et al. 2017). dynamic balance, the former are qualitative, and
According to Thompson et al. (2008), test-retest the latter cannot distinguish the precise cause of
reliability of the 10mWT is questionable with ICC the balance deficit. Essentially, one type of test is
confidence intervals ranging from 0.65 to 0.90. not quantitative enough, while the other type is
For GMFCS subgroups, there was a similar intra- not qualitative enough. Instrumented gait analysis
rater reliability (ICC > 0.67) but a higher inter- is capable of providing the best of both worlds by
rater reliability (ICC > 0.993) (Bahrami et al. quantitatively tracking body parts or the COM as a
2017). It is possible that the variability of out- whole. A number of different methods exist for
comes for this test has to do with gait initiation such data capture including accelerometer, pres-
rather than the walking speed itself, but this has sure sensitive mats, and depth cameras (like the
not been investigated. Another timed test, the Microsoft Kinect), but the gold standard for gait
one-minute walk test (1MWT), the distance a analysis involves utilization of a motion capture
subject walks over a minute, is recorded by the system. These are generally multi-camera systems
assessor. Subjects who can walk longer distances which are used to track markers placed on bony
in this time are thought to be more functional and landmarks throughout the body as an individual
have better dynamic balance. This was reinforced walks, runs, jumps, or does some other activity
by a study of 34 adolescents with CP in which the within a capture volume accessible to the cameras.
distance walked was shown to have a significant From the marker positions and using anthropo-
positive correlation to the GMFM-88 (Distance metric data appropriate to the population, the
(m) = 1.84 GMFM – 83.3, r2 = 0.84) and GMFM- COM position can be calculated throughout the
66 (Distance (m) = 122.9 ln(GMFM) – 447.4, activity being tracked. These data are time series
r2 = 0.80) (McDowell et al. 2005). The 1MWT which can be analyzed for patterns that are char-
was also shown to have a high test-retest acteristic of various populations. This stands in
706 T. A. Niiler
contrast to the aforementioned balance tests which hemiplegics from diplegics as well as TD children,
often spit out a single number which is intended to with more severely affected individuals showing
imply that a subject is balanced or not. Further- larger deviations and velocities (Hsue et al.
more, because these data also include marker 2009a, b). Where ML balance deficits occur, it is
positions from around the body, an unbalanced thought that this is due to limitations in hip adduc-
pattern of COM motion can be further broken tor strength or function (Hilliard et al. 2008).
down to determine precisely what body motions We have proposed that assessing COM
contribute the most to the balance loss. motion relative to the foot positioning during
A number of methods of analyzing COM gait is more efficacious in detecting balance devi-
motion have emerged, all with the purpose of ations than considering only the ML component
detecting patterns in the motion that are more of the motion since typically the ML direction is
indicative of balance deficits. Several studies defined by the laboratory reference frame rather
have concluded that excessive lateral deviation than the subject’s reference frame and, among
of the COM trajectory is present in individuals other things, does not account for intentional
with dynamic balance problems in gait (Hof et al. changes in direction (Niiler et al. 2017). The
2007; Hsue et al. 2009a, b; Schrager et al. 2008; subject’s reference frame is considered to be the
Chou et al. 2003). In Hof et al.’s study of above- line joining the centers of the feet which can be
knee amputees, lateral deviation of the COM was computed from heel and toe markers of most
much larger in the amputees than in the control marker sets in current use. The distance between
group of typical adult controls (Hof et al. 2007). A the projection of the COM (pCOM) and the floor
study of six elderly adults having balance prob- from this “inter-foot line” (IFL) represents an
lems and nine healthy age-matched peers indi- effective gravitational moment arm for the body
cated no difference in gait speed but larger and is the metric (DIFL) used to judge balance.
mediolateral (ML) deviations and velocities of the DIFL is sometimes normalized to half the foot
COM in the balance-impaired group (Chou et al. length to provide an indicator of when the
2003). Increases in step width, ML deviations, and moment arm exceeds the base of support
ML velocities of the COM have also been (Fig. 4). This metric, DN, has been found to be
documented with increasing age in older adults less than unity during gait for TD children during
(Schrager et al. 2008). In children with CP, ML slow, normal, and fast self-selected walking
COM motion can be used to distinguish speeds (Niiler et al. 2017). Analysis of both TD
Fig. 4 Geometry
illustrating relationship of
DIFL to the inter-foot line
subjects and passive dynamic mechanical

walkers has indicated that, throughout the gait
cycle, the moment of inertia about the IFL is
smaller than the moment of inertia about the
anteroposterior axis of the feet, indicating that
destabilizing rotation is more likely to occur
about the IFL than in other directions (Niiler
and Janick 2017). Likewise, the IFL has signifi-
cance as a rotational axis since in slipping (Niiler
2017) and tripping the feet are usually touching
the ground at initiation and the falls proceed as
rotational events. For those with spastic CP
involving the legs, tripping is a common mode
of falling since with little toe clearance, it is more
likely that such individuals will catch a toe dur-
ing swing phase and fall forward (Klemetti et al.
2014). Comparison of DIFL with ML COM devi-
ation in TD children and those with hemiplegic
and diplegic CP has shown that DIFL is signifi-
cantly larger in all groups than the ML COM Fig. 5 Geometry illustrating the relationship of the margin
deviation and that DIFL increases with increasing of support (MOS) to the extrapolated center of mass.
severity of affliction (Niiler et al. 2017). Notice that when xCOM is behind umax, the MOS is pos-
itive. Otherwise, it is negative
A more sophisticated method of assessing bal-
ance via the COM involves estimation of the
position of a velocity-adjusted COM, termed the
extrapolated center of mass (xCOM): When the MOS is larger, it suggests that there
is enhanced stability. This concept can also be
vo applied with lateral motion. The xCOM was first
xCOM ¼ xo þ (1)
ωo introduced by Hof (2005) and has since been
adapted by many for the assessment of balance
where xo is the position of the COM, ωo is the in many populations.
angular frequency of rotation of an inverted pen- Recent work by Dixon et al. (2016) has exam-
dulum with length, l, and vo is the velocity of the ined the use of the xCOM and related MOS in TD
COM (Fig. 5). According to this theory of bal- children and children with CP. Participants were
ance, COM velocity is just as important in asked to complete straight walking trials at a self-
dynamic balance as is COM position. For exam- selected speed and then complete trials where they
ple, if the feet are positioned directly under the turned 90 either left or right. During the straight
body when a person is motionless, this will suffice walks, there was no difference between groups in
for the maintenance of balance. However, if the MOS. However, during the turns, significant dif-
COM is moving quickly, although it is in the same ferences emerged: stride length was shorter and
position as before, in order that balance be stride width wider in the CP group. During turn
maintained, the individual must take a step. In approach, the average MOS was smaller for the
forward motion, if umax is the forward boundary CP group than for the TD group indicating
of the BOS, the margin of stability, MOS is the increased instability. Conversely, comparison of
difference between this forward boundary and the the difference between the more typically calcu-
xCOM: lated average COM and BOS distance between
groups showed significant differences between
MOS ¼ jumax xCOM j (2) groups at all stages of the motion except turn
708 T. A. Niiler
approach. These findings suggest that, while support leg does not bend. Additionally, the
xCOM and MOS have been successful in evalua- motion that is modeled is passive rather than
tion of balance in other populations, the measure- active. The math involved in using the FPE is a
ment may not be sensitive enough to detect bit more complex, however. Coordinates are
balance differences in the CP population except transformed into the sagittal plane, and then an
under certain very specific conditions. estimation is made of how far the COM must
A promising but underutilized measure that is swing to move over the foot. If m is the subject
related to the MOS is the foot placement estimator mass, vx and vy are the horizontal components of
(FPE). Rather than estimate the velocity-adjusted the COM velocity, ICOM is the moment of inertia
position of the pCOM and the distance from the about the COM perpendicular to the projection
current boundary of the support foot, this measure plane, h is the height of the COM, and the follow-
estimates where the swing foot must be placed in ing equation for motion of an Euler pendulum is
order for an inverted three-dimensional solved for φ:
(3D) pendulum whose COM is moving with a
2
certain velocity to come to a stand in an upright mh vx cos ðφÞ þ vy sin ðφÞ cos ðφÞ þ I com :θ cos2 ðφÞ
0¼
position. The difference between this metric and mh2 þ I com cos2 ðφÞ
the MOS is subtle. In the first case, one is estimat- þ2mgh cosðφÞð cos ðφÞ 1Þ
ing where the BOS must move to in order to be (3)
underneath the COM given the current velocity,
whereas in the second case, one estimates where where φ is the angle of the pendulum with respect
the BOS must move in order that when motion to vertical (Fig. 6). The results are then trans-
stops the COM is directly over the BOS. The formed back into 3D coordinates to estimate the
MOS can be thought of as a more conservative distance from the support foot that the swing foot
estimate of foot placement and therefore may fall should be placed (Bruijn et al. 2013). By compar-
short (quite literally) of determining where the ing this estimate to the actual foot placement in the
support foot should be placed in order to maintain mediolateral direction (DML) or anteroposterior
balance. Both measures have a number of (DAP) directions, dynamic stability can be
assumptions tied to them; the most prominent of assessed. So a larger difference would imply a
which is that the modeled pendulum is greater instability. The FPE was tested in 11 chil-
non-telescoping, or in anatomical terms, the dren with CP aged 7.83 2.98 years and 24 TD
Fig. 6 Geometry of the 3D

Euler pendulum used in the
foot placement estimator. In
this diagram from (Bruijn
et al. 2013), JCOM is the
moment of inertia about the
center of mass (I COM in the
text). (Used with
Permission)
children aged 9.40 2.16 years to determine if it It should be noted that many of these more
could discriminate between the two groups complex methods of assessing stability remain
(Bruijn et al. 2013). In the ML direction, at faster purely academic at this point since their imple-
speeds there was a significant difference between mentation remains impractical for many labs and
groups with the CP group having a smaller DML their populations, and it’s not clear that they bring
than the TD group. This can be interpreted that the better discriminant ability to the table than do
CP group had a wider stance to better improve other more accessible measures. This is not to
lateral balance. On the other hand, DAP was larger say that they are without insight. Implicit in DIFL
for the CP group, perhaps due to the need to retain is the idea that the magnitude of instability mea-
some angular momentum in the forward direction sured may be dependent on the chosen reference
to make up for lack of push-off ability. frame. In the MOS and FPE metrics, it is recog-
For populations that are able to walk continu- nized that continuous gait requires a specific foot
ously for hundreds of stride cycles, Lyapunov Sta- positioning for the maintenance of dynamic sta-
bility Analysis (LSA) has been used to assess bility. Finally, the Floquet multiplier method takes
stability of gait. However, in the CP population, advantage of the fact that perturbations to gait are
such an assessment may be problematic except at not isolated events but create echoes in time that
the very highest levels of function. A related anal- can be seen in subsequent gait cycles. Whereas the
ysis which makes use of Floquet multipliers (FM) DIFL and FPE metrics attempt to characterize sta-
does not require so many cycles for valid results bility as a function of time, the FM metric charac-
and has shown some promise in the assessment of terizes stability in a more global sense assigning
balance in children with CP (Kurz 2012). In stability to a person or trial as a fixed value.
Floquet analysis, periodic data such as COM
motion is assessed for convergence or divergence Other Instrumented Assessment
from a set trajectory. In short, if gait is perturbed of Dynamic Balance
from its norm, the perturbance propagates into suc- As technology has improved, it has become pos-
cessive gait cycles creating irregularity that sible to estimate dynamic balance via methods
emerges in the analysis. The larger the FM, the that are not dependent on expensive multi-camera
more irregular the trajectory, and thus the less stable technology. Such methods are generally based on
the motion. Studies of FM have linked higher FM the understanding that a more variable COM tra-
with balance deficits in specific populations indi- jectory reflects balance impairment in many
cating that irregularity of motion may be an indica- populations. However, some methods are more
tor of balance problems just as difficulties in direct in nature, while others measure behaviors
maintaining posture are (Kao et al. 2014; Kurz that would result from a more deviated COM
et al. 2012) Kurz et al. (2012) assessed in nine position during gait. For example, a more variable
children with spastic CP (aged 7.8 2.8 years) COM position might necessitate a wider stance to
and six TD children (aged 8.0 2.4 years) to compensate for the variability.
determine if the FM method was sensitive to dif- One direct measurement method uses acceler-
ferences in gait. Children walked on treadmills for ometers which have become relatively ubiquitous
2 min. In this case rather than tracking the COM, over the past several years and are in many com-
the experimenters tracked lower body sagittal plane mon devices. Many adults have smartphones with
joint angles to create a state vector (S) whose tra- onboard accelerometers, and there are now fitness
jectory was subjected to FM analysis. Results indi- bands worn on the wrists that also have them
cated that the CP group had significantly higher FM built-in. Accelerometer apps for Android abound:
values than did the TD control group implying that a quick search on the Google Play Store at the
motion was less stable in the CP group. Likewise, time of writing found 48 free apps for cell phone
FM multiplier results correlated negatively or tablet. More than 20 were found for iOS by this
(ρ = 0.60) with GMFM dimensions D and E non-iPhone user, but few were free. Most of these
indicating some balance deficit. apps allow the user to email themselves the data or
710 T. A. Niiler
otherwise copy it from the device to be further attenuated accelerations from the COM. Not sur-
analyzed. The accuracy of such devices is now prisingly, the children with CP had larger COM
being tested in direct comparison to clinical tools. accelerations but also showed less of an ability to
Alberts et al. (2015) demonstrated that results attenuate this signal as it propagated through their
from the iPad 2 were similar enough to the more torso to their head. This result provided quantifi-
expensive NeuroCOM sensor so as to implicitly able evidence of the expected deficits in postural
recommend the lower cost hardware. As the hard- control in children with CP and lends support for
ware gets better and cheaper, and the software for the use of this method or similar ones in assessing
such devices more sophisticated, it is likely that balance in this population.
clinics will be able to do accelerometer-based Besides COM motion, other there are other
balance assessment with consumer-grade telltale signs that have been noted in individuals
electronics. with balance deficits. These include the temporal-
In practice, accelerometers can be used to help spatial parameters of gait, and children with CP
quantify the motion of the COM by attaching are known to have a greater postural sway than
them to the sacrum or lower back (Yang et al. TD children which is compensated for by differ-
2011; Alberts et al. 2015; Schütte et al. 2015). ences in step length and step width (Donker et al.
While this is not precisely the COM location, it 2008). A sensor that is well suited to measure such
is close enough that the measured accelerations parameters is the instrumented walkway. Such
have been found to be similar to what is seen in walkways are capable of recording foot pressures
analysis of 3D motion capture data (Schütte et al. and positions throughout several gait cycles and,
2015). Since perturbations to balance that are as such, can return information about stride width,
either proactive or reactive change the trajectory stride length, velocity, foot orientation, timing of
of the COM in gait, they create deviations in the stance and swing, foot placement timing, and
accelerometer signal, and those with balance asymmetries in gait. One version, in particular,
impairments have been shown to have both higher has been extensively validated, the GAITRite
frequencies and amplitudes of acceleration (Cho mat (Thorpe et al. 2005; Sorsdahl et al. 2008).
and Kamen 1998). Senden et al. (2012) showed Thorpe et al. demonstrated that the walkway had
that accelerometer may be able to capture subtle a high reliability in typically developing children
changes in gait that subjective tests like the except for the toe-in/toe-out measurements, while
POMA are unable to spot. Signals from acceler- Sorsdahl et al. validated the walkway’s temporal-
ometers may be analyzed for frequency and spatial measures with children with CP. Fritz et al.
amplitude which is easiest or can be further pro- (2011) used the GAITRite mat in combination
cessed to obtain additional information. In partic- with other tests including the DGI and BBS to
ular, accelerations may be integrated to obtain examine changes to gait parameters in children
COM velocities and positions, although these are with CP who had an intensive therapy after a
heavily dependent on the sampling rate for accu- post-cerebral hemispherectomy. Post-therapy
racy. Repeated integration with a low sampling values in both balance indices were increased as
rate without some additional means of on-the-fly was step length. Barr et al. (2017) also used such a
calibration will usually result in poor accuracy. In walkway to assess balance in 10 individuals with
addition, methods like Floquet analysis can be cervical dystonia (CD), a condition which can
used for prolonged trials to determine the stability cause balance deficits similar to those seen in
of motion. Accelerometers may also be used in CP. Results indicated moderate to good correla-
combination to determine individual body seg- tions between measured parameters and the
ments’ contributions to stability in gait. As an TUGT with stepping decision time (ρ = 0.767),
example, Summa et al. (2016) used three acceler- stepping response time (ρ = 0.831), and step
ometers attached at the pelvis, sternum, and head length (ρ = 0.622) being the most important
of 20 children with CP age and gender matched correlations. These studies further highlight how
with 20 TD children to study how the body instrumented gait analysis can zero in on the
components of motion that are most problematic sessions. As a result of the training, average
to maintenance of balance. GMFM increased significantly from 84.8 to
90 due to increased ability to stand and hop on
one leg, and there was a nearly significant
Treatment increase in stride length. Another at-home pro-
gram involving sit-to-stand and stepping exer-
Treatment of balance impairment due to cerebral cises to develop lower body strength was used
palsy is multifaceted and often successful in by Katz-Leurer et al. (2009) to improve balance
improving both static and dynamic balance. Phys- in children with CP (10) or children with trau-
ical therapy of varying types can be an effective matic brain injury (10). Children were trained
modality so long as patient motivation is using progressive sit-to-stand and step-up tasks
maintained. So while the traditional therapy ses- five times a week for 6 weeks. A significant
sion involving therapy bands, balance boards, improvement of 1.6 2.1 s from the
stretching, and weights may be productive for a 10.1 3.0 s baseline score was noted in the
motivated individual, it is not something that TUGT after 6 weeks. Furthermore, the improve-
many people are able to maintain by themselves ment was maintained in this group over the
either due to motivational factors or due to lack of 6-week follow-up. Since strength training often
equipment. Therefore, there has been an effort to produces rapid outcomes, long-term therapy ses-
find therapies that are equally or more effective sions may not be needed to notice improvement
and which have either long-term results or which in patients. When task-oriented strength training
will be continued outside of the clinic because of the lower extremities was used in a group of
they are fun. Juxtaposed against these are inter- 10 children with CP for 5 weeks, improvement in
ventions which cannot be completed at home balance was still noted by improved GMFM
because of the equipment that is needed or scores (dimensions D and E) and by significantly
because they are surgical in nature. The therapy decreased TUGT times (Salem and Godwin
of choice depends on a combination of factors 2009). Despite the fact that these studies were
including the severity of involvement, the age of rather small, all pointed to the efficacy of strength
the patient, the efficacy of prior therapies, avail- training to improve balance in the CP population.
ability of insurance, and individual preference. In
general more conservative and less costly thera- Vestibular Stimulation
pies should be tried first prior to surgical Vestibular stimulation (VS) training attempts to
interventions. improve balance and gait via exercises that
improve gaze stability and somatosensory integra-
Exercise/Therapy tion (Tramontano et al. 2017). VS techniques
Ideally, a patient’s deficits in both sensory and range from passive swinging in upright and
motor networks should be addressed by balance prone positions (An 2015) to horizontal, vertical,
therapies (Dewar et al. 2015). However, it has and lateral head movements and full body rota-
been shown that even basic strength training can tions (Tramontano et al. 2017). Gait components
improve balance in children with CP (Eek et al. involving dual tasks such as walking and head
2008; Katz-Leurer et al. 2009; Salem and Godwin turning may also be added. Studies using VS as
2009). Eek et al. (2008) studied the balance of a balance training therapy generally show
16 children with CP who trained 4 muscle groups improvement of balance compared to control
in the legs including the hip abductors/adductors, groups without such training. Hosseini et al.
hip flexors/extensors, knee flexors/extensors, and (2015) recruited 16 children with CP aged 3 to
ankle flexors/extensors three times a week for 10 years to validate the impact of VS on balance.
8 weeks, using standard weight training proto- Half were placed in a control group with “stan-
cols. Twice a week training was done at home dard” occupational therapy, while the other half
and once a week at the therapists in group were in the experimental group which got VS
712 T. A. Niiler
during the latter half of their therapy sessions. et al. 2016). It is therefore surprising that there is
Therapy was conducted 45 min twice a week little in the literature regarding Taijiquan as a
over a period of 6 weeks. At the conclusion of balance intervention in the CP population.
the study, those children who had VS showed Recently, Morgan et al. (2015) conducted a pilot
slower COM velocities implying a better ability study with 17 adults with CP to test balance train-
to control COM motion. ing using Taijiquan compared to more traditional
In a crossover study of 14 children with CP balance therapy. After 24 weeks, both groups had
comparing neurodevelopmental therapy (NDT) improved their balance, and there were no signif-
with VS over a period of 10 weeks where therapy icant differences between the groups in objective
sessions occurred once per week for 50 min at a balance measures. However, the Taijiquan train-
time, GMFM-88 scores improved on average by ing group had improved confidence in walking
4 5% due to VS compared to 1 1% for NDT and balance change. Since Taijiquan is often
(Tramontano et al. 2017). Parashar et al. (2017) conducted in a class-type setting with the benefit
compared VS to whole body vibration (discussed of social interactions, it is possible that adherence
later) in 30 children with spastic CP and found to such a program may be easier for individuals
larger gains in PBS due to VS (21.1 points) than than solo therapy or training.
for whole body vibration (9.9 points). Unlike
many other therapies for balance training, VS Body Weight-Supported Treadmill
does not require lots of equipment and may be Training
implemented rather inexpensively. As such, VS Body weight-supported treadmill training
may be one of the more commonly used therapies (BWSTT) is a therapy in which patients are placed
for the improvement of balance. on a treadmill with partial weight support so that
they are more capable of walking on the treadmill
Taijiquan without falling. Often support harnesses are
Another therapy that is gaining favor for func- rigged so that, if a fall does occur, the patient
tional balance training is Taijiquan (T’ai Chi). will be held up prior to hitting the ground. Under
Taijiquan is a martial art originating from China such conditions, when a patient is placed on a
which is now often used for health and wellness moving treadmill, the legs will engage in a motion
rather than self-defense. Study of Taijiquan starts called reciprocal stepping. It is thought that this
with learning techniques to assess one’s weight motion is at least partially driven by the existence
distribution and then moves toward mobile stance of a spinal cord level central pattern generator
training. Movements are completed in slow which enables the leg muscles to engage in cyclic
motion so as to reinforce muscle memory and movements such as gait (Mattern-Baxter 2009). A
improve proprioception. While many studies review of ten studies of this therapy indicated that
have identified the positive effects Taijiquan has results could be variable dependent on study
on measures of health in the elderly, there are also design but that improvements in gait velocity,
a number of studies which indicate the efficacy in GMFM-88 dimensions D and E, were relatively
improving health outcomes in much younger common (Mattern-Baxter 2009). However, most
adults (Webster et al. 2016). Positive health of these studies were very small: four out of ten
effects have been shown to include increased flex- were case studies, and in the other studies, the
ibility (Yu and Yang 2012), upper and lower body largest group size was seven. In a more recent
muscle strength, endurance, balance (Taylor- study involving eight children with CP and using
Piliae, et al. 2006), and improved cardiovascular a crossover design to test conventional gait train-
health (Lai et al. 1995; Lan et al. 1998). Research ing against BWSTT, significant increases in
has also found that elderly Taijiquan practitioners GMFM-66 dimensions D and E were also found
use fewer cognitive and motor resources while after the study period (Su et al. 2013). Although a
completing balancing exercises when compared crossover design can give more power to the study
to non-practitioners of the same age (Varghese for the number of individuals enrolled, it can also
be subjected to washout effects if the period in gyroscopes for which postural feedback applica-
between different treatments is not long enough tions can be written.
for initial treatment effects to subside. This In addition to the large number of balance
seemed to be the case here despite the 10-week measuring applications available for such
long washout period. This may imply that devices, there are also some virtual reality games
BWSTT has some persistence. Sadly, the expense that have been developed which may be used to
of body weight support systems likely explains improve balance by training sensorimotor integra-
why they are not found in more clinics and tion. Those with Android phones can experience
laboratories. virtual reality (VR) type applications using Goo-
gle Cardboard (Fig. 7a). Cardboard viewers allow
Virtual Reality and Interactive Gaming the user to use the phone as a VR headset so as to
One of the challenges with any therapy, especially obtain all visual input from the device. One game
those that are long term, is to keep the patient the author has experienced is called “Rope Cross-
motivated to continue. So although traditional ing Adventure VR.” This is a challenging VR
physical therapy approaches seem to work in game which requires the user to walk a tight
improving balance, there is a need for additional rope to cross over deep gorges. Although this
therapies which inspire participation because they game is not completely realistic, it did induce a
are more fun. feeling of vertigo, and an increased wobble in the
Advances in video gaming technologies COM was experienced. While it seems that the
which have enabled players to participate using commercial offerings on the app stores have not
their bodies as controllers have inspired yet been tested for their efficacy in improving
researchers and clinicians to adapt such technol- balance, to overcome this, some labs have written
ogies for therapeutic purposes. For the most part, their own VR apps. Ross and Root (2017) pre-
the technologies involved are off-the-shelf sented a case study involving a 35-year-old
implementations of many of the motion capture woman with visual vertigo. After training once
technologies and algorithms previously used per day with a Google Cardboard application for
only in high-end motion analysis laboratories 5 days a week over 6 weeks, improvements in
now made available and affordable to the several tests of vertigo and sensorimotor integra-
public. As previously noted, many Android and tion were noted. Lubetzky et al. (2017) presented
iOS devices now have accelerometers and three game-like applications they developed for
Fig. 7 Virtual reality

hardware: (a) the Google
Cardboard viewer into
which a cell phone with
preloaded software is
placed (Evan-Amos 2015),
(b) the Oculus Rift headset
(Evan-Amos 2017), and (c)
the Xbox 360 Kinect (Evan-
Amos 2011). Images by
Evan-Amos (own work)
placed into the Public
Domain
714 T. A. Niiler
challenging balance in visual vertigo patients game-based therapy to a 7-year-old boy with
using another commercially available VR head- CP. After 6 weeks with two 45-min sessions per
set, the Oculus Rift (Fig. 7b). None of these week, balance as measured by the PBS was
devices have been reported to be tested on indi- improved. Another study of 11 children with CP
viduals with CP at the present time, but the using a game-based VR therapy was shown to
ENLAZA, a similar device specifically developed improve balance, locomotion, and dexterity over
as an inertial mouse for individuals with CP, has a period of 8 weeks (Luna-Oliva et al. 2013).
been (Raya et al. 2010). The ENLAZA has a More recently, Moldovan et al. (2017) presented
number of sensors on board, and rather than a case study of a child with CP who willingly
being worn like goggles, it is attached to a hat. It trained with the Kinect for a period of 14 months,
does not provide a VR interface unless matched three times a week for a period of 30 min each
with a video screen. Velasco et al. (2017) adapted time. In addition to improving balance score from
six commercially available games for play with 49 to 54 on the PBS, she also reported decreased
this controller and enrolled ten children aged spasticity on the affected side. Although there
4.8 3.0 years in their study, assigning half to a have been few studies specific to CP, these results
traditional therapy group and the other half to the in combination with results from studies of other
VR therapy with ENLAZA. After ten sessions, populations suggest that balance training with the
improvements to balance were measured in both Kinect using gaming is a viable way to improve
groups with larger improvements in trunk control dynamic balance in this population.
being noted in the experimental group. It should
be noted that all the aforementioned devices Hippotherapy
require address balance deficits by requiring In hippotherapy, a patient is seated on a horse
users to learn to modulate head or body tilt in which is led by a therapist in a slow walk
order to control the game. Furthermore, the (Fig. 8). The rhythm of the horse’s gait in combi-
game-like experiences provided by these environ- nation with the 3D perturbations induced by its
ments are generally found to be enjoyable by users motion is thought to move the rider’s pelvis in a
and may, therefore, promote more frequent ther- manner similar to that encountered in human
apy or practice. walking. Although it has been in use for several
One of the most popular sensor systems used in decades, recently there has been some debate
dynamic balance training is the Microsoft ® about its efficacy. A meta-analysis by Tseng
Kinect ® which has a 3D depth camera that is et al. (2013) which reviewed 14 articles on
capable of tracking the human body in near real- hippotherapy for evidence of efficacy in improv-
time using posture recognition (Fig. 7c). Unlike ing posture, balance, muscle tone, and gait found
VR headsets which may respond to a user even inconsistent results in many of these parameters.
when they are seated, VR experiences with the However, there were some results that were note-
Kinect require whole body participation. Addi- worthy: asymmetries in bilateral muscle tone were
tionally, unlike static balance devices like the decreased; there was a significant decrease in
Wii balance board, dynamic motion such as energy expenditure and an improvement in bal-
jumping, hopping, walking, and other forms of ance as measured by the PBS (Kwon et al. 2011).
locomotion may be involved in the games with Since Tseng et al.’s review, other research has
the Kinect. A review by Hondori and Khademi supported the balance benefits of hippotherapy.
(2014) indicated a wealth of studies using the In a study by Moraes et al. (2016), 15 children
Kinect to improve the balance of participants with CP aged 5–10 years completed 30-min
from a number of balance-impaired populations. hippotherapy sessions twice a week for
Very few studies have been completed involving 12 weeks. BBS scores improved from a mean of
using the Kinect to train balance in individuals 27.93–32.53. Mikołajczyk et al. (2017) likewise
with CP. Pavão et al. (2014) used this system in validated the beneficial effects of hippotherapy in
combination with an Xbox ® 360 to present a 30 children aged 8–13 years with spastic diplegia
Fig. 8 A teenage boy

experiencing hippotherapy.
(From karakal (2007)
Licensed as Creative
Commons BY-SA 3.0)
showing significant improvements in both POMA analysis of 13 studies of the usage of this method
and TUGT after just 2 weeks. A study by Lee et al. in older adults indicated that it was capable of
(2014) compared the results of hippotherapy significantly reducing TUGT times and improv-
using live horses to that using a horse-riding sim- ing POMA scores (Lam et al. 2012). A compari-
ulator in 26 children with CP. Both groups showed son of WBV and vestibular stimulation done by
a significant gain in PBS, and there was no differ- Parashar et al. (2017) found that both techniques
ence between outcomes, suggesting that the sim- improved PBS scores in children with CP after a
ulator may be a valid alternative therapy. Since the single 10-min treatment but that vestibular stimu-
key issues with hippotherapy are cost and avail- lation resulted in more than twice the improve-
ability, having a mechanical analog as an alterna- ment (21.1 vs. 9.9 points, respectively). In PV, the
tive where traditional hippotherapy is not vibrations act as a stochastic noise which can act
available provides patients with additional thera- to effectively amplify proprioceptive signals com-
peutic options. ing from the feet and thereby improve balance
perception and response (Aboutorabi et al.
Vibrational Therapies 2017). Due to improvements in technology, cur-
Two types of vibrational therapies have been uti- rent vibrational systems are usually insole based
lized to train balance, whole body vibration using electromagnetics, piezoelectrics, or vibra-
(WBV) which involves low frequency tory motors, and a number of them are battery
(35–40 Hz), low amplitude vibration of the entire operated and tether free (Fig. 9) so that patients
body and plantar vibration (PV) which involves can benefit from their usage outside of clinical
applying higher frequency (25–500 Hz), lower settings. A review study of PV in elderly patients
amplitude vibrations to the plantar surface of the has concluded that it is an effective technique for
feet. In the former technique, the patient is typi- improving balance as evidenced by increased
cally seated, while the vibrations are applied, speed and step length, decreased postural sway,
whereas in the later, the patient may be standing and improved TUGT times (Aboutorabi et al.
on a vibrational plate or walking using vibrational 2017). Li et al. (2016) have shown that children
insoles. In WBV, the vibrations act to activate the with CP respond to PV signals such that the body
muscle spindles which then reflexively cause the COM moved away from the part of the foot that
muscles to contract (Ko et al. 2017). This, in turn, was stimulated. For example, if the rear foot was
has been shown to increase isometric strength in stimulated, the subject leaned forward, and if the
the lower extremities (Torvinen et al. 2002). Meta- left foot was stimulated, the subject leaned to the
716 T. A. Niiler
Fig. 9 Vibrational balance therapy system used by Lipsitz et al. 2015. (Used with Permission)
right. While it is suspected that current PV insoles the within-system noise and thereby provide a
may benefit the CP population without modifica- level of enhancement of sensory function. This,
tion, these findings have implications for the cre- in turn, is thought to improve balance (Fujimoto
ation of feedback capable insoles which sense et al. 2016). Evidence of efficacy was found by
when the wearer is out of balance and offer cor- application of this method to 30 older adults who,
rective signals to steer the COM back into as a result of the treatment, exhibited less devia-
equilibrium. tion of their COM traces as recorded by dynamic
posturography (Fujimoto et al. 2016). In a study
Electrical Stimulation Therapies of 13 healthy adults, Mulavara et al. (2015) dem-
There are several types of electrical stimulation onstrated that, when the signal was applied during
for balance improvement: galvanic vestibular treadmill walking, RMS accelerations of the trunk
stimulation (GVS), transcranial direct current decreased. Although this treatment seems to be
electrical stimulation (tDCS), and electro- promising, its persistence is transient: the effect
acupuncture (EA). In GVS, electrodes placed on seems to wear off after a brief time. Also, GVS has
the right and left mastoids are activated with a not yet been applied to patients with CP in any
low-level stochastic signal, while a subject stands research study.
on a foam pad (Fig. 10). Due to the proximity of An electrical stimulation method that has been
the electrodes with the vestibular system, this tested in patients with CP is tDCS. In tDCS, a low
added noise is able to effectively cancel some of amplitude direct current is applied across two
Fig. 10 Noisy galvanic

vestibular stimulation setup
from Fujimoto et al. 2016.
(Image licensed under
Creative Commons BY
License (4.0) by authors)
electrodes placed on the scalp. Since patients with may be dependent on implementation of the tech-
CP have lesions on the brain which interfere with nique as well as the specific population it is
the proper electrical activity, it is thought that the applied to. Additionally, it is not clear that the
application of tDCS changes the membrane hypothesized mechanism of action explains all
potential of the cortex and enhances local synaptic the observed effects (Angius et al. 2017). In any
efficiency. This modulation of cortex activity is event, more exploration of tDCS is needed before
hypothesized to enhance motor learning (Duarte it becomes a standard balance therapy, despite the
et al. 2014b), and this has led to increasing popu- promise it shows.
larity of the tDCS technique in recent years. In Another closely related technique is electro-
fact, a company called Halo Neural now does acupuncture (EA) in which two fine wire elec-
good business selling a headset intended to trodes are inserted subcutaneously in a region
“neuroprime” the athlete to improve performance around/in the area of/in the vicinity of, the motor
(Hutchinson 2016). Application of tDCS for bal- cortex, and a low frequency (2–80 Hz), low cur-
ance training was done by Duarte et al. (2014a), rent (1–4 mA) signal is applied (Svedberg et al.
who recruited 24 children with CP to test a train- 2003; Kim et al. 2017). As early as 2003, Sved-
ing protocol using tDCS. Half of them walked on berg et al. utilized EA over a period of 3 months to
a treadmill while receiving tDCS for a period of improve muscle tone in a child with low grade
20 min, while the other half received a placebo CP. As a result, range of motion and strength in the
involving the electrodes and an initial pulse of affected limb increased, and furthermore, these
current to make it convincing. Training sessions changes were maintained over at least 12 months.
were conducted five times a week for 2 weeks. To investigate this further, Kim et al. (2017)
The training group had a significant increase (4.2 subjected young rats to hypoxia-ischemia to
points) in their PBS compared to the control group simulate CP and then tested the efficacy of
which experienced no change in PBS. Ante- electroacupuncture (EA) as a treatment. The rats
roposterior and mediolateral oscillations for the participated in treadmill training, half with EA
training group also decreased significantly. How- and half without. Those with EA showed
ever, it should be noted that not all tDCS studies improved sensorimotor recovery as well as
have shown such significant effects and that they better motor coordination and memory. At the
718 T. A. Niiler
conclusion of the study, the rats were sacrificed scores for dimensions D and E improved 20.5 and
and their brain tissue was examined. Rats sub- 16.7 points, respectively, indicating that a large
jected to EA had increased thickness of the corpus component of the improvement was due to better
callosum leading the experimenters to conclude dynamic balance. In a review of articles
that EA had the potential to regularize behavior addressing changes due to SEMLS, Lamberts
via the “upregulation of myelin and et al. (2016) found that proxies for balance such
neurogenesis.” While there have been no studies as stride length and walking velocity both
that have tested balance improvements using this increased significantly due to surgery. Similarly,
technique in the CP population, it has been shown after selective dorsal rhizotomy, patients tended to
to improve balance in individuals with have less COM sway velocity and displacement
Parkinson’s disease (PD) (Lei et al. 2014, 2016). and a smaller COM vibrational frequency, all
In particular, a pilot study using this technique signs of improving balance (Rumberg et al.
with ten patients showed that, after treatment 2016). In short, if the surgery normalizes other
consisting of 3 weeks of 30-min sessions once parameters for a patient, it is also likely to improve
per week, there was significant improvement in balance.
walking speed (10%), stride length (5%), and a
reduction in TUGT time indicating the potential
benefits of this technique in the treatment of Complications
balance.
Compared to many therapies, the risk of compli-
Surgical Interventions cations from any balance therapy is relatively low,
To be clear, surgery is never the first-line inter- but this does depend on the therapy. Primarily,
vention for the improvement of balance. Rather, therapies involving any exercise program may
surgery is used to address a number of orthopedic result in muscle soreness, and this includes the
difficulties simultaneously. Surgical interventions majority of the treatments listed above. Delayed
may be used to reduce crouch, improve knee onset muscle soreness (DOMS) is generally
flexion, or reposition a limb after a contracture invoked by changes in pattern of exercise, large
induced deformity among other things. It is com- increases in intensity, or eccentric contractions
mon practice to use a single-event multilevel sur- (Kim and Lee 2014). While it may be possible to
gery (SEMLS) to address several orthopedic mitigate its effects by a gradual start to any ther-
issues in one fell swoop instead of subjecting apy program, fear of experiencing DOMS in new
patients to serial surgeries throughout their child- exercisers remains a barrier to participation even
hood. Investigations of changes in balance due to for healthy individuals. Although some soreness
SEMLS or other surgeries are now taking place, due to training was reported by Damiano and Abel
and there is the realization that improvements in (1998) in their study of how strength training
balance are more or less a desirable side effect of improves function in children with CP, such
the surgical intervention. Our own research has reporting seems to be the exception rather than
demonstrated postsurgical improvements after the rule in the literature. Considering that in addi-
rectus transfer surgery as part of a SEMLS proce- tion to microtrauma to muscle cells being a caus-
dure in 18 children with CP (Niiler et al. 2009). ative factor (Mautner and Sussman 2016), DOMS
Postsurgically, the balance index DN decreased may also be neutrally regulated (Racinais et al.
significantly by a factor of two on average even 2008), and as such, it may be that DOMS may
though pre to post walking velocities remained present differently in patients with CP. Clinicians
constant. A significant improvement was also should be attentive to children undergoing any of
found by Delalić et al. (2010) who evaluated these therapies since the ability to communicate
44 CP patients using GMFM-88 both prior to pain or discomfort may be impaired as well.
and post SEMLS surgery. Not only did average Many of the treatment protocols noted above
GMFM total scores improve from 35.7 to 58.6 but involve at least some cardiovascular component.
Due to decreased physical activity of many indi- with EA or GVS, the current must be kept at levels
viduals with CP, there is an increased risk of that are comfortable to the patient. While the
coronary vascular disease in young adults with physiological threshold of perception ranges
CP, and this should be considered in any balance from 2 to 10 mA, this varies based on frequency,
training or exercise prescription (van der Slot et al. mass of the individual, and moisture level of the
2013). For therapies such as BWSTT or skin. As moisture level of the skin increases, skin
hippotherapy that require continuous activity resistance decreases, and otherwise safe voltages
over an extended period, an assessment of a can result in higher than expected currents. Let-go
patient’s physical condition should be done a current, which is the current that causes a
priori, and for deconditioned individuals training sustained muscle contraction which can result in
frequency, duration, and intensity should be mod- injury, can be as low as 6 mA at frequencies
ified appropriately. Based on literature review, between 10 and 100 Hz. In particular, the path of
Verschuren et al. (2016) recommend that for the current through the body should be considered
such a group, the frequency start at no more than (Olson 2010). Electrodes placed proximal to sinus
one to two sessions per week. Duration and inten- nodes or which will result in a current path across
sity of training could then progress as per the them can result in changes to cardiac rhythms or
American College of Sports Medicine guidelines cardiac arrest (Cummings 2011). Likewise, hav-
(Verschuren et al. 2016, Garber et al. 2011). ing large wire loops connecting a patient to an
In addition to the general effects experienced electrical device can subject the patient to induc-
by any population in training, there are risks spe- tively induced currents from the magnetic fields of
cific to some of the therapies noted above. Both other nearby devices, and so leads should either be
virtual reality-based and vestibular simulation twisted to minimize loop area or non-tethered
therapies can result in motion sickness, but such instrumentation should be used as available.
effects are generally transient when they occur Direct current (DC) conveys less of a risk than
(Bergeron et al. 2015). Body weight-supported AC since it does not resemble the action potentials
treadmill training requires a harness that can that are part of human physiology, but it does
chafe if not fit properly. Likewise, any training carry the risk of burns at higher amplitudes.
involving a treadmill has safety concerns as tread- Patients can feel DC current at amplitudes as low
mills have moving parts which can catch clothing as 10 mA at which point the skin feels warm
or body parts if the user is unwary, and the con- (Olson 2010). Electroacupuncture has some addi-
sequences of a fall can lead to the patient being tional risks compared to other electrical stimula-
thrown backward from the treadmill. Nearly tion techniques (Cummings 2011). These include
24 thousand people in the United States were direct injury related to improper needle insertion
hospitalized in 2014 due to treadmill-induced as well as possible infection should the needles
injuries (BBC News 2015). Hippotherapy has not be sterilized.
the risk of any equine activity which includes Balance impairment is an ongoing issue for
falling or being trod on but more generally can many individuals with CP. It presents early in
result in muscle soreness. For those that require life as infants have difficulty in maintaining head
surgery, the risks and complications are myriad or trunk posture when learning to sit up, and later
dependent on the specific treatment, and of it progresses to an exaggerated COM trajectory
course, any surgical intervention has the risk of during gait compared to TD children the same
being life threatening from infection, or not age. For most children with CP regardless of
proceeding as planned due to unforeseen GMFCS level, after an initial improvement in
circumstances. balance throughout childhood and adolescence,
The use of electrical stimulation therapies balance ability often declines as CP patients
carries the standard risks that occur when bringing enter adulthood. However, several balance train-
electricity in close proximity with the human ing interventions have been shown to be effective
body. When using alternating (AC) current as in improving dynamic balance, speed, and
720 T. A. Niiler
confidence. In general, the side effects of balance An S-JL (2015) The effects of vestibular stimulation on a
training are mild, and since the gains from many child with hypotonic cerebral palsy. J Phys Ther Sci
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Part X
Gastrointestinal
Overview of Feeding and Growth
in the Child with Cerebral Palsy 49
Devendra I. Mehta, Nneka Ricketts-Cameron, and
Heidi H. Kecskemethy
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 730
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 731
Prevalence and Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 731
Etiology of Feeding and Growth Problems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 731
Evaluations/Assessments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 733
Ability to Take in Adequate Nutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 733
Growth and Anthropometric Measurements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 733
Physical Examination . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 734
Swallow Study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 735
Adequacy of Intake and Energy Needs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 735
Laboratory Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 735
GI Concerns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 736
Social History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 736
Treatment/Management of Problems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 736
Intake of Nutrition/Feeding Interventions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 736
Nutritional Adequacy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 737
Other Medical Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 738
D. I. Mehta (*)
Center for Digestive Health and Nutrition, Arnold Palmer
Hospital for Children, Orlando, FL, USA
The Florida State University, Tallahassee, FL, USA
e-mail: devendra.mehta@orlandohealth.com
N. Ricketts-Cameron
Center for Digestive Health and Nutrition, Arnold Palmer
Hospital for Children, Orlando, FL, USA
e-mail: nneka.ricketts-cameron@orlandohealth.com
H. H. Kecskemethy
Departments of Biomedical Research and Medical
Imaging, Nemours/Alfred I. duPont Hospital for Children,
Wilmington, DE, USA
e-mail: Heidi.kecskemethy@nemours.org

https://doi.org/10.1007/978-3-319-74558-9_50
730 D. I. Mehta et al.
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 739
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 739
Abstract achieving and maintaining good nutrition and

The goal of feeding children with cerebral subsequent adequate growth because of
palsy is to ensure optimal growth and develop- comorbidities, sometimes resulting from the cere-
ment to maximize their potential, quality of bral palsy, including musculoskeletal, gastrointes-
life, comfort, happiness, and health. Just as tinal, and cognitive problems. For children with
the degree and type of cognitive, neurologic, cerebral palsy who have minimal muscular issues,
muscular, and skeletal involvement varies intake of food is less a problem than for those
widely in persons with cerebral palsy (CP), so children who have complex medical involvement;
does the range of issues potentially impacting a the more severe the medical status, the greater the
child’s ability to take in adequate nutrition to likelihood of feeding problems and nutritional
support growth. Generally, the more medically deficits (Stallings et al. 1993b; Dahl et al. 1996;
involved the child, the greater the risk for sub- Stevenson et al. 1995). Feeding and nutritional
optimal nutritional status. Early identification problems can compound throughout childhood,
of feeding and nutritional concerns as the child resulting in growth failure. A variety of medical
ages and as medical comorbidities develop, care providers are pivotal in identifying and man-
along with appropriate interventions by a aging the broad concerns that impact feeding and
multidisciplinary team of care providers, growth in children with cerebral palsy (CP),
helps to mediate problems. The family and including those with expertise in developmental
care providers, who manage daily provision pediatrics, gastroenterology, nutrition, physiatry,
of food and nutrition, are an equally important and orthopedics, as well as nurse case managers,
part of the feeding and nutrition team. In this occupational, physical and speech therapists, die-
chapter, we will review the natural history of titians, feeding specialists, seating specialists, and
CP related to feeding and growth, present the social workers. The family and direct care pro-
etiology and assessment of nutritional prob- viders are equally important in the feeding and
lems including challenges with food intake growth equation, because they directly observe
and gastrointestinal (GI) concerns, discuss and identify concerns and participate in the daily
growth assessment and evaluation, and sum- provision of food/nutrition. Likewise, the school or
marize management and treatments to opti- day program (for those residing at home) or resi-
mize feeding and growth in the child with CP. dential program is also key. In this chapter, we will
review the natural history of CP related to feeding
Keywords and growth, present the etiology and assessment of
Cerebral palsy · Growth failure · Nutrition nutritional problems including challenges with
evaluation · Feeding · Growth assessment food intake and GI concerns, discuss growth
assessment and evaluation, and summarize man-
agement and treatments. Early identification of
Introduction nutrition and growth concerns followed by evalua-
tion and management of them serves to fulfill the
Adequate nutritional intake is required for optimal goal of optimizing growth and development in
growth for all children. Children with cerebral children with cerebral palsy, to maximize potential,
palsy may experience a variety of challenges quality of life, comfort, happiness, and health.
49 Overview of Feeding and Growth in the Child with Cerebral Palsy 731
Natural History 8 years (Stallings et al. 1993a). A comprehensive

study of 58 children with moderate to severe
Neurological deficit in cerebral palsy (CP) and spastic CP showed that 92% had clinically signif-
related upper motor neuron disorders may under- icant gastrointestinal symptoms, including
mine the ability to ingest enough nutrients and swallowing disorders in 60%, regurgitation or
lead to undernutrition and growth failure. Histor- vomiting in 32%, abdominal pain in 32%, chronic
ically, children severely affected by spastic CP pulmonary aspiration in 41%, and chronic consti-
and other neurological disorders were prone to pation in 74% (Del Giudice et al. 1999).
significant morbidity from pressure sores, sepsis,
aspiration pneumonias, fractures, and recurrent
hospitalizations when inadequately nourished Etiology of Feeding and Growth
without use of supportive enteral feeds. Appropri- Problems
ate and early enteral nutrition intervention can
prevent such morbidity and early mortality. Oral-Motor Dysfunction
Early intervention and routine monitoring by a Atypical sensation and muscular tone, control,
multidisciplinary team of physicians of multiple and strength in the oropharyngeal cavity can
specialties, nurses, dietitians, occupational and cause a variety of challenges for children with
speech therapists, psychologists, and social CP, ranging from difficulties managing food in
workers are now considered essential to meet the mouth to uncoordinated swallowing and
nutritional requirements (Andrew et al. 2012). breathing, resulting in aspiration. Low muscle
tone can result in poor posture, head, and neck
control, placing the child at further risk for aspi-
Prevalence and Pathophysiology ration. Poor lip closure, protuberant tongue,
hypertrophy of the gums and malocclusion, as
Undernutrition has been documented in 29–46% well as the inability to bite and chew in a coordi-
of children with cerebral palsy with linear stunting nated manner add to the dysfunction. Addition-
in 23%; micronutrient deficiency is the most com- ally, lack of progression past an immature
mon type of undernutrition (Stallings et al. 1993a; suckling feeding pattern can result in the child
Dahl et al. 1996; Stevenson et al. 1995). Markers being unable to lateralize tongue movements to
of disease severity, GMFCS level/ambulatory sta- manipulate food in the mouth.
tus, type and severity of neurological disability, Feeding problems occur frequently in children
cognitive status, and advanced age, contribute to with cerebral palsy and vary from mild to severe.
undernutrition and growth failure in neurologi- One study estimated that 90% of preschool chil-
cally impaired children (Andrew et al. 2012). dren with cerebral palsy had oral-motor dysfunc-
Children with seizures or spastic quadriplegia tion during their first year of life; 57% had sucking
and those who are non-ambulatory have lower problems, 38% had swallowing problems, and
height Z-scores (Stevenson et al. 1994). Children 80% were fed non-orally at least once as infants
with spastic hemiplegia have smaller measures of (Reilly et al. 1996). Poor suck, difficulty breast-
breadth and length on the affected side, a direct feeding, problems with the introduction of solid
effect of neurological defect-induced atrophy foods, difficulty drinking liquids, difficulty biting
(Stevenson et al. 1995). Generally, in spite of or chewing solids, and coughing and choking with
interventions, neurologically impaired children meals were common parental complaints (Reilly
are usually shorter and weigh less than healthy, et al. 1996). The severity of feeding dysfunction is
typically developing children. strongly associated with indicators of poor health
Nutritional status has a stronger effect on linear and nutritional status (Fung et al. 2002). Children
growth in younger than in older children above with more severe impairment who are unable to
lift their head or feed themselves have a higher viewed as very important and gratifying to par-
risk of aspiration (Yilmaz et al. 2004). Even chil- ents. However, parents of children with CP may
dren with mild CP exhibit oral-motor dysfunction perceive mealtime as a stressful, unpleasant expe-
that impacts feeding skills (Gisel et al. 2000) rience, and 60% of children with cerebral palsy
are completely dependent on care providers for
Inappropriate Dietary Intake food intake (Marchand et al. 2006).
Inappropriate dietary energy intake relative to
needs is the primary cause of undernutrition, Abnormal Energy Expenditure
growth failure, and in up to 14%, of overweight Energy needs and expenditure are governed by
in neurologically impaired children (Sanders et al. metabolic processes and can be high for a child
1990; Fried and Pencharz 1991). Children with with athetosis or hypertonia and can be low for a
cerebral palsy consume less dietary energy than child with flaccidity and low muscle tone. Chil-
children without CP (Stallings et al. 1996). The dren with spastic quadriplegic cerebral palsy may
reasons for this lower caloric intake are multifac- grow normally with energy intakes as low as
torial and can include combinations of the abilities 61 15% of the Dietary Reference Intake (DRI)
to communicate, physically consume food, con- for age and sex or at a value of 1.1 resting
sume enough volume of food, tolerance to food energy expenditure (REE) because of their low
components (allergies and intolerances), and use lean body mass (Fried and Pencharz 1991;
of certain medications. The inability to communi- Azcue et al. 1996). Some adolescents with
cate (hunger, food preferences, and satiety) leaves athetoid cerebral palsy may require up to
care providers responsible for regulating a child’s 6,000 cal daily (Culley and Middleton 1969).
dietary intake. Caretakers often overestimate the Resting energy expenditure in well-nourished,
child’s energy intake and underestimate the time non-ambulatory children with cerebral palsy is
spent feeding the child (Stallings et al. 1996; significantly lower than that predicted from equa-
Reilly et al. 1996). Because the task of feeding tions based on age, sex, and weight in healthy
may be difficult and time consuming, the amount children (Bandini et al. 1995). It is important to
of food consumed may be insufficient to meet the remember that energy equations for this popula-
child’s growth needs. For those receiving enteral tion are only an estimate and should be
tube feedings, careful monitoring may be neces- individualized.
sary to avoid overfeeding, and consequently over- During periods of rapid growth, such as
weight, in these children. puberty, if the increased energy requirements
are not accompanied by increased skills or tol-
Caregiver Dependency erance to feedings, the result will be energy
Dependency on a caregiver beyond early child- deficit and compromised growth. In some
hood and the inefficiency of the feeding process, cases, the rapid growth can seem to worsen
including the amount of food ingested, the amount swallowing skills, and the extra time needed to
spilled or lost on the bib, and the time required for deliver the calories may finally overwhelm the
feeding, influence the child’s nutritional status. child’s support systems. Postpubescent energy
Children with cerebral palsy take 2–12 times lon- needs decrease as the child moves into
ger to swallow pureed food and up to 15 times adulthood.
longer to chew and swallow solids compared with Exogenous factors, such as surgeries, illness,
unaffected children (Trier and Thomas 1998; and use of medications, can alter energy require-
Gisel and Patrick 1988). In one report, 28% of ments. Energy and nutrient requirements may
parents required more than 3 h daily to feed their change to improve wound healing, and medica-
child and 3% required more than 6 h daily (Sulli- tions to decrease muscle tone will decrease caloric
van et al. 2000). Meals and eating together are needs. Seasonal allergies and illnesses can nega-
social times for most children and families, and tively impact energy intake and tolerance to
the provision of sustenance to a child is often feedings.
Evaluations/Assessments and variety of food offered and consumed, and the

nutrient composition of the diet. Food intake
Evaluations related to feeding and growth center records should be completed by everyone
around the etiology of problems described above. involved in providing food and beverage to the
The assessments are performed by the team of child and usually include school personnel, care
care providers and together provide insight into providers, and family members. Food records
the multifactorial aspect of growth in children should include at least 1 weekend day, as the
with CP. weekend schedule is typically different than dur-
ing the week.
Ability to Take in Adequate Nutrition

Growth and Anthropometric
Feeding Assessment: A team of therapists experi- Measurements
enced in feeding evaluation should perform the
feeding assessment and includes a speech- Growth and anthropometric measurements are
language therapist to perform the oral-motor func- indicators of a child’s nutritional status. Accurate
tional evaluation and an occupational therapist measurements of weight and height/length (or a
and/or a physical therapist to evaluate seating proxy measure in children for whom these mea-
and positioning. A variety of presentations and surements are not obtainable) should be obtained
textures are offered during the assessment, as using consistent and standardized techniques and
well as use of therapeutic feeding devices such equipment at every medical encounter.
as specific spoons, straws, and cups. Cervical Weight: Weight is measured on the same scale
auscultation, which involves listening to with the child wearing little or no clothing, a dry
swallowing sounds via a stethoscope placed on diaper, and free of extra weight like shoes, AFOs
the cricoid cartilage, may be used to detect possi- and splint, braces, body jackets, etc. Children who
ble aspiration and determine the need for a video- are unable to stand may be weighed several dif-
fluoroscopic study. ferent ways: (1) children who are GMFCS 1–2 can
Meal Observation: Meal observation is useful stand on a scale unassisted; (2) children who are
for the entire team involved in the feeding and GMFCS 3 may be able to stand on the scale
provision of nutrition process: speech-language unassisted; and children who are GMFCS 4 and
and occupational and/or physical therapists and 5 can stand while being held by a parent or care
the dietitian. Observation of meals can provide provider who is standing on the scale or while
useful information to identify family and care seated in a wheelchair or chair.
provider training needs, assist with therapeutic Length/Height: Length is obtained supine in
decision-making for the child, and reveal oppor- children younger than 2 years or in older children
tunities to fine-tune and improve nutritional qual- unable to stand. Many alternative or proxy mea-
ity. Classification systems based on measures of sures can be used to estimate height. Arm span,
growth and patterns of food consumption, such as while valid for use in healthy adults, cannot usu-
eating efficiency and oral-motor feeding skills, ally be accurately measured in children with
may be helpful to assess the effectiveness of oral elbow and wrist contractures or with limited
feeding interventions (Gisel and Alphonce 1995; range of motion. Height proxy techniques used
Gisel 1996). for children with CP include measurements of
Food Intake Records: Food intake records upper arm length (ulnar length) or lower leg
(3–5-day food record) are evaluated by a regis- length (knee height, tibial length) (Gauld et al.
tered dietitian and are an extremely valuable com- 2004; Stevenson 1995; Chumlea et al. 1994;
ponent of the nutrition evaluation. Food records Hogan 1999). These may be obtained to estimate
can provide insight into the amount of time body length in children who have contractures
required for feeding, the timing of meals, volumes and severe scoliosis or who are unable to stand.
Table 1 Height estimate Segmental Prediction equation for Standard error of the
equations from segmental measurement height (cm) estimate (cm)
measures
Upper arm length (4.25 UAL) + 21.8 1.7
(UAL)
Tibial length (TL) (3.26 TL) + 30.8 1.4
Knee height (KH) (2.69 KH) + 24.2 1.1
Source: Samson-Fang and Bell 2013
Conversion equations are available for upper arm skinfold thickness better identifies children with
length and lower leg measures (Table 1). The age undernutrition than weight-for-height or BMI.
ranges for which the techniques were validated Decreased triceps skinfold thickness identifies
must be considered, and some are race-specific. 96% of children with depleted fat stores, whereas
The standard deviation of measures for the tech- weight-for-height less than the 10th percentile
nique used should be considered when evaluating identifies only 55% (Frisancho 1981; Samson-
results. Another technique, known as “recumbent Fang and Stevenson 2000).
segmental measurements” for measuring children Growth Charts: A variety of growth charts can
who are unable to stand, involves using a tape be used to assess and monitor growth. CP-specific
measure to quantify body segments in an additive growth charts are available but have limited utility
manner (e.g., crown of head to shoulder + shoul- because these charts reflect how children with CP
der to hip + hip to knee + and knee to heel). While have grown, rather than how they can be expected
some view this technique as unreliable, others find to optimally grow (Brooks et al. 2011; Kuperminc
it to be useful to monitor growth over time if done and Stevenson 2008; Krick et al. 1996). The
in a consistent manner and by the same person. CDC/NCHS or WHO growth charts for typically
Standing height, measured with a stadiometer, developing healthy children are most commonly
should be obtained without shoes and braces and used and are useful to monitor serial growth
is recorded in children with CP who are able to trends. Children with CP are typically lighter
stand. Whatever the technique used, consistent and shorter than their typical peers, and it is com-
methodology coupled with careful attention to mon for height and weight Z-scores to be low.
repeatability of the measures will provide the Each child, however, is expected to follow their
most accurate results for interpretation of growth own growth curve; this can be assessed with serial
over time. monitoring of height/length and weight.
BMI: BMI can be calculated from height and
weight measurements of children 2 years and
older. However the usefulness of this measure Physical Examination
for children with CP, if used at all, is limited to
evaluation of growth trend over time (Stallings Physical examination focuses on signs of undernu-
et al. 1995; Samson-Fang and Stevenson 2000). trition, linear stunting, overweight, and specific
As a single assessment of nutritional status, BMI nutrient deficiencies. Muscle tone, activity level,
is not valid in children with CP because these and the presence of athetoid movement influence
children have lower lean muscle mass than typi- dietary energy needs. Contractures and scoliosis are
cally developing healthy children (Kuperminc noteworthy for positioning during meals. Abnormal
and Stevenson 2008). breath sounds may be suggestive of chronic respi-
Fat Fold Measures: Triceps skinfold thickness ratory problems associated with aspiration. Abdom-
is affected more than the subscapular skinfold inal distension in conjunction with palpable masses
thickness in neurologically impaired children suggests constipation. Examination of the skin may
(Marchand et al. 2006; Romano et al. 2017) and reveal the presence of decubitus ulcers. Pallor, skin
therefore is thought to be a better measure. Triceps rashes, smooth tongue, gingival bleeding,
petechiae, bone deformities, or pedal edema may water) and micronutrients (vitamins and minerals)
suggest micronutrient deficiencies. will be calculated as part of the assessment. There
are several formulae and methods for estimating
energy needs in children with CP, including cal-
Swallow Study culating resting energy expenditure (REE) and
basal energy expenditure (BEE), and calories/
An oropharyngeal motility study (OPMS) is height. For additional information, see ▶ Chap.
performed by a radiologist and speech therapist 24, “General Nutrition for Children with Cerebral
and is used to further assess swallowing skills and Palsy.” Estimated needs should be compared to
identify optimal textures and positioning and risk actual intake to help determine the child’s needs to
of oral aspiration. Findings then guide support growth. The RDA/DRI levels for age and
recommended textures of foods and drinks and sex for vitamins and minerals and fluid and pro-
ideal positioning and guide therapy goals. If aspi- tein are recommended.
ration is suspected clinically, on chest x-ray, or
from the OPMS, additional tests may be
warranted and are summarized in Table 2. Laboratory Evaluation
Through these tests, any swallow deficits and
foregut dysmotility can be characterized to guide Basic laboratory assessment of nutritional status
treatment. includes a comprehensive metabolic panel and
serum magnesium and phosphorus. Serum elec-
trolytes and blood urea nitrogen reflect hydration
Adequacy of Intake and Energy Needs status; however, blood urea nitrogen may be low
because of poor protein intake and low muscle
The dietitian evaluates adequacy of the diet mass. Abnormal serum phosphorus, alkaline
through a nutrition assessment, which includes phosphatase, calcium, and 25-OH vitamin D
examination of food records, diet history, current levels may reflect poor bone mineral status.
feeding regimen, laboratory values, medication Urine calcium should be evaluated if calcium
use for drug-nutrient interactions, anthropometric supplements are being used, and there is concern
measures, and growth records. Estimated needs for calcium oxalate kidney stone formation with
for macronutrients (kilocalories, protein, fat, and low fluid intake. A complete blood count and
Table 2 Swallowing evaluation tests

Name What evaluate Possible findings Who involved
Fiber-optic endoscopic Aerodigestive Vocal cord paresis, Ear, nose, and throat surgeon in
evaluation of swallow using evaluation of pseudobulbar palsy, presence of a pulmonologist,
indirect laryngoscopy swallow poor clearance of offered gastroenterologist, and speech
(FEES) foods therapist
Nuclear salivagram Oral aspiration Aspiration of food/drink Nuclear medicine
Bronchoscopy Airway amylase Aspiration of gastric Pulmonology
and pepsin A fluid
Upper endoscopy Visual assessment Esophagitis, Barrett’s Gastroenterology
of mucosa esophagus, and hiatal
hernia
Impedance testing Gastroesophageal Reflux Gastroenterology
reflux
Nuclear gastric emptying Neurogenic Microaspiration Nuclear medicine, gastroenterology
scan gastroparesis from
vagal nerve injury
serum ferritin may identify iron deficiency ane- assistance to the family. The multidisciplinary
mia. C-reactive protein indicates inflammation medical team is key to treatment and management
and may guide energy requirements. Other tests of feeding and growth problems. Frequency of
are indicated by symptoms. monitoring is governed by the nature and severity
of the concerns.
GI Concerns
Intake of Nutrition/Feeding
If vomiting or intolerance to feeding leads to Interventions
inadequate intake, studies are warranted to docu-
ment gastroesophageal reflux and gastroparesis. Oral-Motor Feeding Therapy: Outpatient,
Feeding intolerance may be associated with recur- in-school, or home therapy with a speech therapist
rent acid or often nonacid reflux, delayed gastric and OT or PT for 1 h up to three times a week can
emptying, gas/flatulence from aerophagia, and be helpful to develop eating skills, increase effi-
constipation. Intercurrent illness, orthopedic com- ciency, ensure safety, and increase amount of
plications, urinary retention or urinary tract infec- ingestion. In select cases with adequate cognitive
tions, and cholelithiasis or pancreatitis need to be function that allows response to positive feed-
considered. back, intense feeding therapy with sessions com-
pressed over 4–8 weeks can significantly improve
ability to feed and diversify the types of food
accepted. Behavioral therapy can also improve
Social History
the quality of feeding interactions between the
caretaker and the child (Linscheid 2006). Oral-
The neurologically impaired child requires a con-
motor therapy addresses movements, strength,
siderable amount of care, a factor that impacts the
coordination, endurance, and awareness in the
parent’s ability to work and the family’s social
child.
activities. The child’s scheduled activities, such
Positioning: Head and trunk stability with
as school or physical therapy, and the siblings’
properly aligned hips, knees, and feet provides
school and parents’ work schedules require con-
the optimal conditions for safe feeding; this is
sideration when planning nutritional interven-
best accomplished in a chair adapted for the
tions. Financial issues, medical insurance, and
child. Care providers and feeders should be
the availability of home care require exploration.
trained on proper positioning.
All individuals involved in the care and feeding of
Textures: Many children will require modified
the child (extended family members, aides,
textures to ensure safety and allow for improve-
teachers, babysitters) and all settings in which
ments in skill with therapeutic feeds. Textures
feeding occurs (school, day care, home) require
range from a variety of mixed textures that require
inquiry to ensure that nutritional interventions can
the full ability to chew and manipulate food in the
be integrated into the family or institutional
mouth and throat to pureed, requiring no chewing.
routines.
However, even pureed foods vary in texture:
thicker ones are easier to control in the mouth,
while thinner ones can create risk for aspiration.
Treatment/Management of Problems However, thicker purees can pose other risks for
aspiration depending on the child’s swallowing
Because the relationship between feeding and ability. Mixed-texture foods can be problematic
growth is so complex, the management and treat- and confusing to those children who are learning
ment of problems is diverse, spanning from thera- eating skills. Similarly, thin beverages are harder
peutic feeding, to nutrition support and to control and pose an increased risk for aspiration
gastrointestinal management of problems, to social in some children. The speech-language therapist
(often with the help of the swallow study) will dense food, extra fat can exacerbate gastroesoph-
determine best textures for the child’s abilities and ageal reflux or delayed gastric emptying. See
with the occupational therapist will determine any ▶ Chap. 36, “Family Stress Associated with Cere-
assistive feeding equipment needed (e.g., cut out bral Palsy” for further discussion on calorie
cups, specific spoons, etc.). boosters. A wide range of commercially available
Environment: Sensory impairments can result supplements or drinks are a popular source of
in overstimulation and increased startle response. additional calories and nutrients. Whether increas-
Excessive noise and confusion during the meal- ing or decreasing calories to address over or
time add to the burden of eating, creating addi- undernutrition, a prudent approach is a 10%
tional mealtime stress. Some children require a change (up or down) in calories with close mon-
calm quiet environment to be able to focus on itoring of weight to assess impact and suitability
the skills of eating. of the new calorie level.
Feeding therapy, along with the proper food Fluids: Ensuring adequate hydration can be
and beverage textures, positioning, and environ- challenging in the child with volume intolerance,
ment, in conjunction with OMPS study, can max- who has excessive drooling or who has difficulty
imize the amount of food eaten before exhaustion, safely swallowing liquids. Adequate fluid intake
while teaching skills and ensuring safety. Oral- is important for constipation management. If
motor therapy is especially beneficial for children drinks require thickening, use of a commercially
with severe CP (Gisel 1994). available thickening agent is recommended
because the fluid remains as free water for the
body when digested. Evaluation of fluid intake is
Nutritional Adequacy part of the nutrition assessment.
Micronutrients: Supplementation of individual
Energy: Chronic over- and undernutrition result in nutrients is frequently provided if dietary intake is
growth deviations. Regular monitoring of anthro- below the RDA/DRI or when deficiency is iden-
pometric measures is important to track growth and tified through laboratory assessment. Many prac-
nutritional status, so energy intake can be adjusted titioners recommend a daily pediatric
as needed. Overnutrition can result when monitor- multivitamin/mineral supplement to ensure ade-
ing occurs too infrequently, particularly if a child is quate intake, particularly in children who are
receiving supplemental or full feeds through a tube. 100% orally fed. Certain nutrients of concern,
Accommodation to overnutrition includes modest for example, calcium and vitamin D, may be
reduction in calories while ensuring adequacy of all routinely supplemented because of the risk of
other nutrients. Hypocaloric, nutrient-rich formulas low bone density.
are available for children with very low-energy Feeding Tubes: Tube placement, whether short
needs. or long-term, guarantees a way to provide medi-
Undernutrition occurs when energy intake is cations, fluids, and feedings. In some instances,
less than needs and when these energy needs are tubes are placed in early childhood to support
not met. Accommodations for undernutrition growth, and as the child grows and develops and
range from increasing caloric density of foods to with therapy learns to eat, the tube can be
tube placement for supplemental feeds. The tech- removed. In other instances, tube placement is
nique used to boost energy intake depends on delayed until growth has been severely impacted,
opportunities for improvement as revealed compromising the child’s ability to learn and
through evaluations and assessments discussed develop skills. The decision to place a tube is
above. Common approaches to “boosting calo- sometimes difficult and can be emotionally
ries” include the use of higher-calorie versions of charged for families. After thorough assessment
foods, such as full-fat dairy products, or the addi- and evaluation, over time, and after different feed-
tion of supplements to foods, such as carbohy- ing interventions, the child’s multidisciplinary
drate or fat. While fat is the most calorically team can provide input to a family who is deciding
Fig. 1 Growth after placement of gastrostomy tube improvement in bone density, as shown by serial DXA
(GT) for supplemental nutrition including calcium and scan (DXA) with lumbar spine (L1–L4) Z-scores and
vitamin D. This shows catch-up weight gain and bone mass density (gm/cm2)
about tube placement for their child. See Other Medical Management
▶ Chap. 50, “Gastrostomy and Jejunostomy
Feedings in Children with Cerebral Palsy” for Medications: A review of medications is impor-
more information on tube feedings. tant because drugs prescribed for gastroesopha-
If all nutrition is provided via a tube, the feed- geal reflux, constipation, or seizures may
ings must be nutritionally balanced to meet all influence the child’s eating pattern and nutrient
macro- and micronutrient needs of the child. Ben- absorption. Gastric acid inhibitors and laxatives
efits in terms of growth, medication delivery and often minimize gastrointestinal discomfort and
bone density, as well as effectiveness of therapies reverse feeding refusal. Valproic acid, gabapentin,
such as physical therapy, may be realized (Fig. 1) topiramate, zonisamide, and felbamate may affect
Commercially available feedings with a host of appetite and result in weight gain or loss. Baclo-
different properties are available. Blenderized fen, used to reduce muscle spasticity, reduces
feedings of whole foods are gaining in popularity, energy needs. Many anticonvulsants influence
whether homemade or commercially purchased. the level of consciousness and have a secondary
Blenderizing feeds can be a meaningful way for effect on oral-motor skills and airway protection.
families to participate in feeding a child who is Medications that promote acid suppression (hista-
unable to eat all foods by mouth. Blenderized mine antagonists, proton-pump inhibitors) and
feeds can be a very healthy and well-tolerated motility (bethanechol, metoclopramide, erythro-
way to meet the nutritional needs of the child mycin, and domperidone (not available in the
with CP, but these feeds should be carefully eval- USA)) may improve tolerance to feeds but may
uated by the dietitian to ensure nutritional ade- affect bone density and nutrient absorption.
quacy. All types of tube feedings have advantages Constipation: Managing constipation is impor-
and disadvantages, and a specialist in nutrition tant, because neurogenic bowel can negatively
(dietitian or gastroenterologist) can best advise impact the amount of intake and create a vicious
which product is most appropriate for the circum- cycle of inadequate intake, especially fluids, lead-
stances and medical condition of the child. ing to worsening constipation, small bowel
microbial overgrowth, and subsequently further ▶ Gastroesophageal Reflux in the Child with
reduced intake from early satiety or abdominal Cerebral Palsy
cramps. Furthermore, constipation can exacerbate ▶ Gastrostomy and Jejunostomy Feedings in
gastroesophageal reflux. Options to address con- Children with Cerebral Palsy
stipation include adding fiber, fluids, single or ▶ General Nutrition for Children with Cerebral
multiple laxative agents with stool softening, and Palsy
stimulatory effects (polyethylene glycol- ▶ Growth Attenuation for the Child with Cerebral
electrolyte solution, magnesium hydroxide, Palsy
senna extract, lactulose, bisacodyl tabs), and rec- ▶ Measuring Outcomes in Children with Cerebral
tal bisacodyl suppositories or enemas. Palsy
▶ Medical and Surgical Therapy for Constipation
in Patients with Cerebral Palsy
Conclusion ▶ Medical Management of Spasticity in Children
with Cerebral Palsy
Feeding and nutrition for the child with cerebral ▶ Motor Control and Muscle Tone Problems in
palsy pose specific challenges that require signif- Cerebral Palsy
icant attention early on and throughout childhood. ▶ Occupational Therapy Elements in the Man-
In addition to neurogenic dysphagia, presence of agement of the Child with Cerebral Palsy
gastrointestinal comorbidities, especially gastro- ▶ Outpatient-Based Therapy Services for Chil-
esophageal reflux, gastroparesis, and constipa- dren and Youth with Cerebral Palsy
tion, adds to the challenge. A multidisciplinary ▶ Physical Therapy Elements in the Management
team approach creates the opportunity for safe, of the Child with Cerebral Palsy
efficient feeding and targeted medical and nutri- ▶ Short Stature in Children with Cerebral Palsy
tional intervention to ensure normal growth, opti- ▶ Speech, Language, and Hearing Practice Ele-
mal functional status, health, and quality of life for ments in the Management of the Child with
both the child and their family. Cerebral Palsy
▶ The Child, the Parent, and the Goal in Treating
Cerebral Palsy
Cross-References ▶ When and How to Evaluate the Child with
Possible Cerebral Palsy
▶ Activities of Daily Living Supports for Persons
with Cerebral Palsy
▶ Aspiration in the Child with Cerebral Palsy
References
▶ Augmentative and Alternative Communication
for Cerebral Palsy Andrew MJ, Parr JR, Sullivan PB (2012) Feeding difficul-
▶ Communication in Children and Youth with ties in children with cerebral palsy. Arch Dis Child
Cerebral Palsy Educ Pract Ed 97:222–229
Azcue MP, Zello GA, Levy LD et al (1996) Energy expen-
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Gastrostomy and Jejunostomy
Feedings in Children with Cerebral 50
Palsy
J. Fernando del Rosario
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 742
Oropharyngeal Dysphagia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 742
Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 742
Gastroesophageal Reflux . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 743
Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 743
Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 743
Gastrostomy Tube . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 744
Gastrojejunostomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 744
Complications of Gastrostomy and Gastrojejunostomy Tubes . . . . . . . . . . . . . . . . . . . . 745
During Placement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 746
Post-placement Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 747
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 748
Cases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 748
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 749
Abstract reflux, which may put children with severe

Feeding problems are common in children cerebral palsy at risk for aspiration and chronic
with cerebral palsy. The causes vary and respiratory disease. Persistent uncorrected
include poor oral motor function, poor gener- feeding problems will lead to severe malnutri-
alized tone and motor function, and cognitive tion. It is important to evaluate these children
impairment. These in turn can result in poor for causes of feeding problems so that appro-
airway protection and severe gastroesophageal priate intervention, including tube feedings,
may be initiated in a timely manner.
J. F. del Rosario (*) Keywords

Pediatric Gastroenterology, Hepatology and Nutrition, Feeding problems · Oropharyngeal
Nemours/A.I. DuPont Hospital for Children, Wilmington, dysphagia · Gastrostomy · Jejunostomy ·
DE, USA Cerebral palsy
e-mail: Fernando.delrosario@nemours.org

https://doi.org/10.1007/978-3-319-74558-9_51
742 J. F. del Rosario
Introduction poor tongue function, exaggerated bite reflex,

tactile hypersensitivity, delayed swallow initia-
Children with cerebral palsy (CP) commonly have tion, reduced pharyngeal motility, and drooling
feeding problems. The causes may be due to poor (Arvedson 2013). Delay in swallow initiation
oral motor function, poor general motor function coupled by reduced pharyngeal motility may
and tone, and cognitive impairment (Dahlseng result in pooling of oral secretions that could
et al. 2012). These problems may result in dys- subsequently penetrate into the airway resulting
phagia, gastroesophageal reflux, intestinal in aspiration. A malfunctioning epiglottis may be
dysmotility, poor nutrition, failure to thrive, and another risk factor for aspiration due to loss of the
growth failure. epiglottis’ protective function of the airway dur-
Spastic CP is the most common subtype of CP ing the pharyngeal phase of swallowing.
(Ferluga et al. 2013). Up to 30% of children with
severe spastic CP require assisted feeding
(Venkateswaran and Shevell 2008). The Oxford Evaluation
Feeding Study reported significant correlations
between severity of motor impairment, feeding There are several historical pieces of information
problems, and the need for tube feedings (Sullivan that are important to obtain that would help guide
et al. 2000). the evaluation and management of children with
This chapter will discuss (1) common prob- CP and feeding problems (Arvedson et al. 1994).
lems in children with CP that result in feeding These include the following:
difficulties, (2) diagnostic tests that may be nec-
essary to assess the causes of feeding difficulties, 1. Duration of feeds
and (3) different strategies of tube feedings that 2. Presence of stress on the child or parents
may benefit these children. during meals
3. Weight gain
4. Presence of respiratory problems
Oropharyngeal Dysphagia
If the child takes longer than 30 min to feed,
Oropharyngeal dysphagia along with gastro- meal times are stressful to the child or parent, the
esophageal reflux can be risk factors for chronic child is not gaining weight, or there are obvious and
aspiration resulting in recurrent respiratory infec- unexplained respiratory symptoms, like congestion,
tions. Chronic pulmonary disease due to aspira- wheezing, or a “gurgly” voice, then the child will
tion is the leading cause of death among patients need evaluation to rule out aspiration.
with severe CP (Evans et al. 1990; Maudsley et al. A videofluoroscopic swallowing study (VFSS)
1999; Reid et al. 2012). According to Reilly et al. provides visualization of the swallow process to
(1996), over 50% of children with CP during the help pinpoint the phase of swallowing that may be
first year of life have problems with sucking, and abnormal. In a study conducted by Kim et al.
more than 90% have clinically significant oral (2013), VFSS showed that reduced lip closure,
motor dysfunction. Chronic aspiration may be inadequate bolus formation, residue in the oral
difficult to determine when there is no cough cavity, delayed triggering of pharyngeal swallow,
response to aspiration events (Arvedson et al. reduced larynx elevation, coating on the pharyn-
1994). It is important to assess the swallowing geal wall, delayed pharyngeal transit time, multi-
function of a child with CP so that appropriate ple swallows, and aspiration were significantly
interventions can be initiated to keep the child safe more common in the severe group of children
during feedings. with CP. Fifty percent of children with severe CP
The types of oropharyngeal problems that chil- had aspiration compared to only 14.3% with mod-
dren with CP have include reduced lip closure, erate CP, and none of them with mild CP had
50 Gastrostomy and Jejunostomy Feedings in Children with Cerebral Palsy 743
abnormalities. Five of the seven aspiration cases Evaluation

occurred silently. A modified barium swallow,
which is performed by offering different consis- An Impedance pH probe study is the best way of
tencies of a barium bolus to swallow while fluo- assessing the frequency and type of gastroesopha-
roscopy is done, can identify what consistencies geal reflux. An impedance probe has sensors along
may be safe to swallow. its length that detects differences in gradients. It can
A flexible endoscopic evaluation of therefore identify retrograde flow from the stomach
swallowing (FEES) provides direct visualization to the proximal esophagus. Combined with a pH
of the upper airway to determine if there is sensor, this test is then able to differentiate between
obstruction and/or vocal cord paralysis or paresis. acid and nonacid reflux and can quantify how much
A combination of VFSS and FEES has been found reflux occurs during a 24-h period of study. When
to increase the detection of penetration, aspiration, combined with a diary of non-gastrointestinal
and pharyngeal residue (Park et al. 2015). symptoms that occurred during the study, one
A salivagram is another test that may deter- could also ascertain temporal correlation between
mine occurrence of aspiration of oral secretions in gastroesophageal reflux and these symptoms.
children with CP. This test involves instillation of An upper endoscopy is not ideal for quantify-
99mTc-sulfur colloid in saline in the pharynx ing how much gastroesophageal reflux occurs.
followed by a nuclear medicine study to detect However, it can identify whether mucosal disease
the presence of the tracer in the lungs (Baikie is present due to gastroesophageal reflux or other
et al. 2009). A salivagram may help determine conditions.
whether aspiration is due to inability to handle Fluoroscopy is valuable in identifying struc-
oral secretions as opposed to aspiration due to tural abnormalities, such as a hiatal hernia, gastric
gastroesophageal reflux. Presence of aspiration outlet obstruction, small bowel strictures,
due to an abnormal swallow would necessitate malrotation, and position of the stomach. The
tube feedings. latter is important, especially if gastrostomy
placement is being considered for management
of a child with cerebral palsy.
Gastroesophageal Reflux A gastric emptying scan may be helpful in
determining whether there is delay in gastric emp-
Gastroesophageal reflux disease (GERD) is com- tying that could result in poor tolerance of
mon in children with CP. Up to 67% of children intragastric feeds, whether taken by mouth or via
with CP had GERD in a study by Campanozzi a tube. A gastric emptying scan may also detect
et al. (2007). Another study by Caltepe et al. aspiration of stomach contents into the airway. The
(2016) found that GERD was common in children test can either be a liquid or solid gastric emptying
with CP and up to 70% of reflux was nonacidic. scan. The radioactive material used is 99mTc-sulfur.
Gastroesophageal reflux can present as obvious Liquid gastric emptying scan utilizes milk, as nor-
regurgitation, but can occur silently. A small study mative values were determined using milk (Hauser
comparing children with GERD and normal chil- et al. 2016). For solid gastric emptying scans, the
99m
dren identified silent reflux in up to 9% of those Tc-sulfur is added to egg whites and given as a
with GERD (Wang et al. 1998). The prevalence sandwich (Donohoe et al. 2009).
rate of silent reflux associated with recurrent
lower respiratory tract infections in children was
20–40% (Thomas et al. 2003). Given that chronic Management
respiratory disease is the leading cause of death
among patients with CP, it is important to assess It is critical that management of the nutritional
for the presence and severity of gastroesophageal needs of a CP patient be a multidisciplinary
reflux so that it can be optimally managed. approach, including dietitians and speech and
feeding therapists. The dietitian will be instru- or plastic flange. This technique may be
mental in developing the nutritional prescription performed under moderate sedation or general
that would ensure that a child will get sufficient anesthesia, and initiation of formula tube feed-
calories for growth. It is also important to ings is usually within 24 h from placement.
have ongoing oral/feeding therapy to preserve Conversion to a low-profile gastrostomy is
and improve swallowing function and feeding often performed 12 weeks after initial place-
skills to receive oral nutrition once deemed ment to allow for sufficient healing of the
safe. Even non-nutritive oral activities, such gastrostomy site. It is recommended that the
as sucking on a pacifier, may facilitate oral gastrostomy button is replaced every 3 months.
feeding skills (Arvedson et al. 1994, 2010; 2. Surgical gastrostomy tube placement: This
Bingham et al. 2010). involves making a small incision down to the
For those who have chronic respiratory disease stomach in the left upper quadrant or midline,
and are suspected to be at risk for aspiration with and through direct visualization, a gastrostomy
oral feedings, have GERD refractory to medica- tube is placed through this incision and secured
tions, or are unable to consume sufficient calories by sutures. A surgically placed gastrostomy
for maintenance of good growth, then initiation of tube is often needed if a suitable gastrostomy
tube feedings and consideration for a Nissen site cannot be safely identified by endoscopy or
fundoplication may be necessary (Sleigh and a fundoplication is necessary due to severe
Brocklehurst 2004; Snider and Darsaklis 2011; GERD refractory to medical therapy. Place-
Vandenplas et al. 2009). ment of a low-profile gastrostomy tube can
sometimes be done primarily, or the initial
gastrostomy tube can be converted to a
Gastrostomy Tube low-profile gastrostomy tube 8 weeks later.
As above, gastrostomy button replacement is
A Norwegian population study by Dahlseng et al. recommended every 3 months.
(2012) showed that 14% of children with CP have 3. Percutaneous radiological gastrostomy (PRG)
gastrostomy tubes. The mean age of gastrostomy tube placement: This technique involves infla-
tube placement was 21.3 months. Longer duration tion of the stomach using an NG tube and
of gastrostomy tube feeding was associated with a visualization of the inflated stomach via fluo-
higher body mass index and was independent of roscopy or CT. The stomach can then be
gross motor impairment of the child. secured by T-fasteners (gastropexy) or not. A
A gastrostomy tube can be placed by gastroen- needle is then used to puncture the selected site
terologists, surgeons, or interventional radiolo- and a gastrostomy tube placed either via the
gists. How it is placed is largely dependent on an push method or in a retrograde fashion (Lyon
individual child’s medical condition. A child with and Pascoe 2004).
CP who may have oropharyngeal dysphagia, but
no excessive gastroesophageal reflux, may
undergo gastrostomy tube placement in one of Gastrojejunostomy
the following three ways:
For those children with CP, severe GERD, and
1. Percutaneous endoscopic gastrostomy (PEG) poor airway protection due to oropharyngeal dys-
tube placement: This involves a small incision phagia, it is important that they are not fed orally.
typically made in the left upper quadrant or They must also be protected from gastroesopha-
midline under direct endoscopic visualization geal reflux that may reach the oropharynx with
through which a gastrostomy tube is placed via subsequent aspiration.
a guidewire in a retrograde manner and secured A Nissen fundoplication can be performed
in place by an internal bumper and outer silicon along with gastrostomy tube placement to prevent
further gastroesophageal reflux. It is a major sur- Figure 1 is a potential pathway for evaluation
gical procedure that is not reversible. Sometimes and management of children with CP who have
it cannot be performed because a child is chronic respiratory disease and/or malnutrition.
too unstable. It is also possible that the Children with severe cerebral palsy often suffer
fundoplication can loosen within 1 year of place- from both conditions, so the workup and treatment
ment allowing for recurrence of reflux symptoms for each are concurrently done. A child with cere-
(Cheung et al. 2006). bral palsy who aspirates and requires tube feedings
Total esophagogastric dissociation (TOGD) is still needs oral and speech therapy to help develop
another surgical intervention for managing GERD the skills required for competent swallowing
in severely neurodisabled children that have been should the child’s overall neurological function
studied. TOGD had similar efficacy to a laparo- improve to allow for safe oral feedings. Children
scopic fundoplication with suggestion of lower with chronic respiratory disease and GERD refrac-
failure and comparable morbidity. However, tory to anti-reflux pharmacotherapy, as noted on
TOGD was more invasive requiring longer impedance probe testing, have the option of either
periods of rehabilitation (Lansdale et al. 2015). undergoing a Nissen fundoplication with
Gastrojejunostomy (GJ) placement is a mini- gastrostomy tube placement or undergo primary
mally invasive procedure that can prevent gastro- GJ placement if fundoplication is too risky or GJ
esophageal reflux with aspiration and is a placement is preferred. This also holds true for
reasonable alternative to fundoplication (Wales those children with gastroparesis refractory to pro-
et al. 2002). Placement is similar to that of a kinetic therapy but without severe gastroesopha-
PRG, but a longer feeding tube is used so that the geal reflux who simply need transpyloric feedings.
tip will pass the pylorus and reside in the jejunum. Those with GERD refractory to medications but
GJ placement can be done utilizing a pre- with normal gastric emptying and no risk for
existing gastrostomy or placed as the initial inter- reflux-related aspiration, who are not able to main-
vention. The former situation often occurs when a tain adequate nutrition through oral feeds, may just
child with a gastrostomy develops gradual deteri- need gastrostomy tube placement. This may also be
oration in gastric emptying function necessitating the case for those children with no interest to eat
transpyloric feedings or in a child who is too small and who do not have significant respiratory disease
to have a standard-size single-unit GJ placed. or GERD.
Therefore, a gastrostomy first needs to be created
and once mature, it can be converted to a GJ. A GJ
can be primarily placed when it is clear that Complications of Gastrostomy
intragastric feedings are ineffective or pose and Gastrojejunostomy Tubes
an aspiration risk, but performing a Nissen
fundoplication is not feasible or preferred. Placement of gastrostomy or gastrojejunostomy
The advantages of GJ tube placement is that it tubes for nutritional support is safe and effective.
is minimally invasive, reversible, and effective in However, a number of complications can occur.
the management of GERD refractory to medica- Reported rates of complications can be 33–51.5%
tions. A disadvantage of the GJ tube is that it (Hansen et al. 2017; McSweeney et al. 2015).
needs fluoroscopic assistance when replaced The majority are minor complications (McSweeney
every 6 months, so the family cannot do this on et al. 2015). Major complications include peritoni-
their own, unlike the gastrostomy button. Another tis, colocutaneous fistula, subcutaneous abscess,
disadvantage is that bolus feedings cannot be septicemia, and excessive gastrointestinal bleeding
given via the jejunum, as the jejunum cannot (Soscia and Friedman 2011). Minor complications
handle large volumes of fluid within a short period include tube dislodgement/migration, tube leakage,
of time. Therefore, only continuous feeds can be site infection, and tube obstruction (Soscia and
given via the GJ tube. Friedman 2011).
Chronic respiratory disease Failure to thrive/Malnutrition
Suspect oropharyngeal Suspect GERD Inability to consume

dysphagia adequate calories orally
Trial of anti-reflux medications

VFSS/FES
Volume Disinterest
S Poor oral skills
intolerance
Improvement in Improvement in
Aspiration
respiratory symptoms oral intake
+ GERD GES
Normal
no yes emptying
no yes no
Delayed
Continue emptying
Impedance pH probe anti-reflux in spite of
Oral medications
/speech prokinetic
therapy Excessive GER
No Look for
on medications other
significant
GER causes of
respiratory
Nissen disease
fundoplication
GJ TUBE
FEEDINGS
GASTROSTOMY
FEEDINGS
Legend: VFSS (videofluoroscopic swallow study); GERD (gastroesophageal reflux disease); GES (gastric
emptying scan); GJ (Gastrojejunostomy)
Red lines connote different options for management are possible.
Fig. 1 Pathway for evaluation and management of children with CP who have chronic respiratory disease and/or
malnutrition
During Placement Another rare complication is the creation of a

colocutaneous fistula, which can occur during
A complication that can occur during gastrostomy PEG placement when excessive insufflation of
tube placement is excessive bleeding. This is a the gastrointestinal tract results in the interposi-
rare complication, especially in someone without tion of a segment of colon between the gastric and
a prior history of coagulopathy. The risk for exces- anterior abdominal walls (Saltzberg et al. 1987).
sive bleeding can be reduced by discontinuing any The colon is then perforated and entrapped when
nonsteroidal anti-inflammatory medications or the gastrostomy tube is placed. This complication
selective serotonin reuptake inhibitors 1 week can be minimized by avoiding overinflation of the
prior to the planned procedure. upper gastrointestinal tract prior to placement of
the gastrostomy tube and paying meticulous atten- Gastrostomy tube blockages can be managed
tion to the site of greatest transillumination and by the use of any carbonated fluid to help dissolve
the most defined impression on digital palpation the formula residue buildup. Prevention of
when selecting the gastrostomy site. Since buildup can be accomplished through water
patients for whom this complication occurred are flushes of the gastrostomy tube after medication
often asymptomatic, this complication is often administration and feeds.
discovered at the time the original gastrostomy Inadvertent dislodgement of the gastrostomy
tube is removed, and a new gastrostomy tube tube can be a very serious problem, as the
cannot find its way back into the stomach. Treat- gastrostomy site can close very quickly if the
ment involves removal of the gastrostomy tube to gastrostomy tube is not replaced in a timely man-
allow the fistula to close, but sometimes surgery is ner. If the gastrostomy site is mature, a replace-
required to correct the gastric colon fistula (Berger ment gastrostomy tube or an appropriate size
and Zarling 1991). Foley catheter can be reinserted and secured to
keep the gastrostomy site open. If the gastrostomy
tube becomes dislodged within the first 4 weeks of
Post-placement Complications initial placement, the position of the replacement
gastrostomy tube should be confirmed via a water-
Early post PEG complications include soluble contrast study, which will also help make
pneumoperitoneum and ileus. Pneumoperitoneum sure that the gastrostomy site was not disrupted.
results from escape of air used to insufflate the The patient should be monitored for development
stomach into the peritoneum upon needle punc- of peritonitis.
ture of the gastric wall. In the absence of perito- Deterioration of the gastrostomy site may also
nitis, this does not require treatment and occur. Deterioration of the gastrostomy site could
spontaneously resolves. If the pneumoperitoneum be due to malnutrition or skin maceration from
does not resolve, then imaging may be necessary excessive leakage of gastric fluid. This could
to confirm proper position of the PEG tube. result in enlargement of the gastrostomy tract or
Patients who develop an ileus post PEG place- development of tissue overgrowth (granulation
ment will need bowel rest to allow the ileus to tissue) at the site. The presence of granulation
resolve prior to attempts at feedings. tissue could result in local irritation and bleeding.
Infections at the gastrostomy site can occur at Enlargement of the tract could be managed by
any time, and most are minor. Infections can be removing the gastrostomy tube and allowing the
avoided by giving a patient one dose of IV first- site to shrink so that it will be snug around the
generation cephalosporin prior to PEG placement. gastrostomy tube. Upsizing the gastrostomy tube
Topical antibiotic or antifungal ointments can be is not an option because this will only result in a
placed at the PEG site as needed, if the site larger tract. Local gastrostomy irritation can be
appears infected. managed by using mild steroid ointments to
Necrotizing fasciitis is a rare complication of reduce inflammation, barrier protection sprays,
PEG placement (Cave et al. 1986). Patients with creams, and protective pads.
malnutrition, diabetes mellitus, and impaired Buried bumper syndrome is a long-term con-
immune system are at increased risk (Hucl and sequence of the external bolster being too tight
Spicak 2016). Treatment with antibiotics and sur- against the abdominal wall. This will result in the
gical debridement is necessary. internal bolster of the gastrostomy tube eroding
Tube-related problems are relatively common into the gastric wall and into the tract. Prevention
complications. These problems include blockage of this complication requires proper care of the
of the gastrostomy tube from formula residue, gastrostomy site. Attention should be paid to signs
premature bursting of the gastrostomy tube of the external bolster being too tight against the
balloons, and inadvertent dislodgement of the gastrostomy site, as noted by development of a
gastrostomy tubes. skin indentation at the gastrostomy site. If this
were to occur, the external bolster should be loos-

ened. If a low-profile gastrostomy tube or a endoscopy which revealed no esophagitis.
gastrojejunostomy tube is in place, it may need He then underwent an impedance probe
to be replaced with one that has a longer shaft study which showed that he had 5.3% reflux
between external and internal bolsters. off anti-reflux therapy. Another problem
that he had was that it took him 45 min to
feed. A modified barium swallow (MBS)
Conclusion was performed which revealed a dysfunc-
tional swallow, nasopharyngeal reflux, pen-
Children with severe cerebral palsy are at high etration, and aspiration without a protective
risk for chronic aspiration, feeding problems, cough with thin liquids. He was able to
and malnutrition due to poor oral and generalized tolerate thickened liquids without aspira-
motor function and cognitive impairment. It is tion. Speech and feeding therapy was
important to identify these problems early and consulted. Because of his difficulty gaining
intervene with tube feedings to reduce morbidity. weight, the length of time it took for him to
Both gastrostomy and gastrojejunostomy feeding finish a meal, and his risk for aspiration with
strategies are effective in supporting nutrition and thin liquids, he underwent PEG placement
reducing the risk for chronic aspiration due to without fundoplication at 27 months of age.
oropharyngeal dysphagia and GERD in a mini- The rationale for not performing a
mally invasive manner. fundoplication at the time was absence of
significant reflux that was refractory to anti-
reflux therapy, and no evidence of aspira-
tion with thickened fluids. After the
Cases gastrostomy tube was placed, he experi-
enced intermittent difficulty tolerating the
volume of his gastrostomy feeds resulting
Case 1 in inadequate weight gain. Four years later,
A male patient was born full term and he underwent repeat MBS for surveillance
healthy until 2 months of age when his of his dysphagia, and at that time he was
father rolled onto him during their sleep. found to have laryngeal penetration for all
He suffered significant anoxic brain injury consistencies and silent aspiration with
leaving him with chronic encephalopathy, thick puree. He was also still having diffi-
severe cognitive impairment, and quadri- culty tolerating his gastrostomy tube feeds
plegic cerebral palsy. He was referred to and exhibited ongoing reflux. A GES
GI at 22 months of age due to severe con- showed that he had mild delay in gastric
stipation, GERD, and feeding and respira- emptying and some reflux. Because of the
tory problems. He was on anti-reflux deterioration of his swallowing function
therapy consisting of ranitidine (Zantac) and his ongoing difficulty with intragastric
and metoclopramide (Reglan) (a prokinetic) feeds, his gastrostomy tube was converted
at the time of the referral. He was eating to a gastrojejunostomy tube at the age of
stage 3 baby food thickened with rice 8 years. Thereafter, he was able to tolerate
cereal, pureed foods, and a commercial for- jejunal tube feedings, and he was able to
mula. Because of persistent fussiness, he maintain his nutrition and gain weight. He
was changed from ranitidine (Zantac) to continued to receive oral/speech therapy in
lansoprazole (Prevacid) (a proton pump an effort to maintain whatever oral skills
inhibitor), and he underwent an upper he had.
Arvedson J, Clark H, Lazarus C et al (2010) Evidence-

Case 2 based systematic review: effects of oral motor interven-
tions on feeding and swallowing in preterm infants.
A female patient who was born full term but
Am J Speech Lang Pathol 19(4):321–340
experienced prenatal asphyxia. She suffered Baikie G, Reddihough DS, South M, Cook DJ (2009) The
from epilepsy, respiratory distress, cerebral salivagram in severe cerebral palsy and able-bodied
palsy, microcephaly, neurogenic bladder, adults. J Paediatr Child Health 45(6):342–345
Berger SA, Zarling EJ (1991) Colocutaneous fistula
and feeding problems. Due to her neurolog- following migration of PEG tube. Gastrointest Endosc
ical condition, her oral intake was limited. 37(1):86–88
She subsequently underwent a PEG. How- Bingham PM, Ashikaga T, Abbasi S (2010) Prospective
ever, she had ongoing significant GERD study of non-nutritive sucking and feeding skills in
premature infants. Arch Dis Child Fetal Neonatal Ed
refractory to anti-reflux therapy as noted 95(3):F194–F200
on a GES at age 10 years. She subsequently Caltepe G, Yuce O, Comba A (2016) Detection of gastro-
had her gastrostomy converted to a gastroje- esophageal reflux in children with cerebral palsy using
junostomy tube to optimize GERD therapy, combined multichannel intraluminal impedance-ph
procedure. Turk J Pediatr 58(5):524–531
as well as management of her intolerance to Campanozzi A, Capano G, Miele E et al (2007) Impact of
intragastric feeds. malnutrition on gastrointestinal disorders and gross
These two cases are good examples of how motor abilities in children with cerebral palsy. Brain
various tests were able to provide helpful Dev 29(1):25–29
Cave DR, Robinson WR, Brotschi EA (1986) Necrotizing
assessments of a child’s capability for safe fasciitis following percutaneous endoscopic
swallowing as well as tolerance for oral or gastrostomy. Gastrointest Endosc 32(4):294–296
intragastric feedings. The results ultimately Cheung KM, Tse HW, Tse PW et al (2006) Nissen
dictated whether each of these children fundoplication and gastrostomy in severely neurologi-
cally impaired children with gastroesophageal reflux.
underwent gastrostomy tube vs. gastroje- Hong Kong Med J 12(4):282–288
junostomy tube placement and whether a Dahlseng M, Finbraten A, Juliusson P et al (2012) Feeding
fundoplication was necessary at the time of problems, growth and nutritional status in children with
the gastrostomy tube placement and the timing cerebral palsy. Acta Paediatr 101(1):92–98
Donohoe KJ, Maurer AH, Ziessman HA (2009) Procedure
by which these interventions took place. guideline for adult solid-meal gastric-emptying study
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Gastroesophageal Reflux in the Child
Arieda Gjikopulli, Erika Kutsch, Loren Berman, and
Sky Prestowitz
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 752
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 752
Pathophysiology and Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 752
Clinical Presentation and Symptoms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 753
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 754
Diagnosis and Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 754
Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 755
Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 761
Reflux Esophagitis and Peptic Strictures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 761
Barrett Esophagus and Adenocarcinoma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 761
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 762
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 762
Abstract
Gastroesophageal reflux disease (GERD) is
defined as the objective pathologic sequelae of
A. Gjikopulli · E. Kutsch (*) retrograde movement of gastric contents into the
Division of Pediatric Gastroenterology and Nutrition, esophagus as it leads to troublesome symptoms
Nemours/Alfred I. duPont Hospital for Children, or complications. Patients with cerebral palsy
Wilmington, DE, USA
(CP) are at increased risk for GERD due to a
e-mail: Arieda.Gjikopulli@nemours.org; Erika.
Kutsch@nemours.org number of contributing factors such as anatomy,
altered gastrointestinal motility, posture, and
L. Berman
Division of Pediatric Surgery, Department of Pediatrics, other comorbidities. There is no gold standard
Nemours/Alfred I. duPont Hospital for Children, diagnostic tool for the diagnosis of GERD. The
Wilmington, DE, USA diagnosis is often made clinically, based on
e-mail: Loren.Berman@nemours.org
signs and symptoms. There are different testing
S. Prestowitz methods that can be used to document the pres-
Philadelphia College of Osteopathic Medicine,
ence of pathologic reflux and complications.
e-mail: skypr@pcom.ed One should have a high index of suspicion for

https://doi.org/10.1007/978-3-319-74558-9_52
752 A. Gjikopulli et al.
GERD in children with CP in order for timely main underlying mechanism of GER is transient
diagnosis and management. Treatment includes lower esophageal sphincter (LES) relaxation
lifestyle modifications, pharmacotherapy, and (TLESR). TLESR is mediated primarily through
surgical options. Suboptimal treatment of vagal pathways via the brainstem. Somatostatin
GERD can lead to complications such as erosive and γ-aminobutyric acid B (GABAB) play an
esophagitis and Barrett esophagus. inhibiting role in TLESR generation. Agents
affecting these sites, such as the GABAB agonist
Keywords baclofen, have begun to be explored as therapies
Cerebral palsy · Gastroesophageal reflux · for GERD but with ambiguous results (Kleinman
Gastroesophageal reflux disease · Pediatrics et al. 2017).
In addition to TLESR, there are other aspects
of gastric function that may provoke reflux by
Introduction affecting the gastric pressure-volume relation-
ship. Gastric accommodation is the stomach’s
Gastroesophageal reflux (GER) refers to the retro- ability to accommodate increased volumes. Gas-
grade movement of gastric contents into the esoph- tric emptying is the function of emptying gastric
agus. Gastroesophageal reflux disease (GERD) is contents into the duodenum. Impaired gastric
defined as the objective pathologic sequelae of accommodation or delayed gastric emptying
such retrograde movement as it leads to troublesome can lead to increased GER episodes. Gastric
symptoms or complications (Kleinman et al. 2017; emptying is delayed by increased meal osmolal-
Vandenplas et al. 2009). GERD is one of the most ity. In addition, there are extra gastrointestinal
common gastrointestinal disorders in both children phenomena that affect intragastric pressures
and adults. The general pediatric population preva- such as obesity, certain postures (supine posi-
lence of symptoms suggestive of GERD ranges tion), tight clothing, and episodes of straining,
from 1% to 8% (Nelson et al. 1997, 2000). Patients coughing, or wheezing.
with cerebral palsy (CP) are at increased risk for Patients with CP are at a higher risk for
GERD. Although the pediatric literature is scarce, GERD due to a number of different contributing
the incidence of GERD in children with CP has been factors. In regard to posture, chronic supine
reported to be anywhere from 31% to 75% by position is common for patients with more
different studies (Gangil et al. 2001; Bozkurt et al. severe forms of CP (GMFCS IV–V), and it
2004; Reyes et al. 1993; Staiano et al. 1991). In leads to impaired clearance of the refluxate.
neurologically impaired children, risk factors asso- Additionally, CNS disease in children with CP
ciated with severe GERD include early onset of may have a direct effect on upper gastrointestinal
central nervous system (CNS) disease, abnormal tract motility and LES function. Gastric antral
EEG, and mitochondrial disease (Kim et al. 2017). dysrhythmias are related to dysfunction of the
The diagnosis of GERD can be challenging gastric pacemaker and delayed gastric emptying.
and often delayed. Therefore, clinicians caring Vomiting secondary to gastric antral dysrhyth-
for children with CP should have a high index of mias has been well documented in children with
suspicion for the disease to ensure a timely diag- CNS disorders (Ravelli and Milla 1998). In CNS
nosis and appropriate management. disease the LES tone also may be decreased
(Tovar et al. 1986).
Common comorbidities in children with CP
Natural History include scoliosis, chronic respiratory disease,
and seizure disorder. Scoliosis may displace the
Pathophysiology and Etiology stomach and stretch the lower esophageal sphinc-
ter and therefore promote GERD (Hoeffel et al.
The pathophysiology of GERD is complex. 1992). In addition to this, scoliosis, as well as
GERD is driven by a number of promoting and spasticity, induces GER by increasing the intra-
protective mechanisms as outlined in Fig. 1. The abdominal pressure. Respiratory diseases and
51 Gastroesophageal Reflux in the Child with Cerebral Palsy 753
Fig. 1 Protective and

promoting mechanisms
involved in the
pathophysiology of
gastroesophageal reflux
disease
chronic cough can affect the abdominal-thoracic microscopically. The presence of dysphagia
pressure gradients and therefore predispose to and/or odynophagia is suggestive of esophagitis.
GERD (Kleinman et al. 2017). Lastly, as poly- The differential of esophagitis should include
pharmacy is common in children with CP, it is erosive esophagitis as a result of chronic, poorly
important to review medication side effects as a treated GERD, eosinophilic esophagitis, and
potential exacerbating factor. Anticonvulsants are infectious or caustic esophagitis. Additional
commonly used in this population of patients, and signs that may result from GERD include feed-
many of them can lead to side effects such as ing difficulties, such as feeding refusal or intol-
nausea, vomiting, heartburn, and dysphagia that erance, and malnutrition (failure to thrive).
can exacerbate GERD. Other than the esophageal symptoms
mentioned above, GERD might present with
extra esophageal symptoms and disorders as
Clinical Presentation and Symptoms well. GERD and respiratory diseases share a
reciprocal relationship. It was mentioned above
GERD is one of the common gastrointestinal how respiratory diseases may worsen GERD. On
disorders that children with CP may experience. the other hand, GERD may exacerbate and
Clinically, the symptomatology of GERD varies. worsen respiratory diseases, either by aspiration
In children with CP, the inability to communi- of refluxate leading to inflammatory changes
cate, in those who are nonverbal, can make in the respiratory tract or by reflexive responses
the distinction among the different presenting of the airway to refluxed material in the esopha-
symptoms challenging. In contrast to the gus such as cough, laryngospasm, and apnea
healthy population, in children with neurodeve- (Thach 2001; Orenstein 2001). Respiratory
lopmental delays, onset of symptoms of GERD diseases affected by GERD include both
occurs at an older age (Sondheimer and Morris otolaryngologic and lower respiratory tract
1979). disorders such as otitis media, sinusitis, laryngi-
Common symptoms secondary to GERD tis, poorly controlled asthma, and pneumonia.
include regurgitation or vomiting, nausea, heart- Chronic cough or chronic hoarseness may be a
burn, and pain in the chest or epigastric presenting symptom of GERD as well (Borrelli
region. Heartburn or pain may be associated et al. 2011). Lastly, dental erosions may be a sign
with erosive esophagitis but may be present of extraesophageal GERD and usually affect the
even in the absence of any inflammatory changes lingual aspects of the posterior teeth (Dahshan
of the esophagus both macroscopically and et al. 2002) (Table 1).
Table 1 Signs and symptoms associated with gastro- eosinophilia, elongation of papillae, basal hyper-
esophageal reflux disease in children with cerebral palsy plasia, and dilated intercellular spaces. None of
• Signs these findings are sensitive or specific for reflux
• Apnea esophagitis as they are nonspecific reactive
• Recurrent pneumonia changes that may be found in esophagitis of
• Feeding difficulties (feeding refusal or intolerance) other causes. Barrett esophagus requires endo-
• Erosive esophagitis scopic visualization to be diagnosed (see section
• Barrett esophagus “Barrett Esophagus and Adenocarcinoma”) and
• Dental erosions
surveilled.
• Dystonic neck posturing (Sandifer syndrome)
• Symptoms
Esophageal pH Monitoring (EpHM)
• Regurgitation
EpHM measures the frequency and duration of
• Vomiting
• Chest pain (heartburn) or abdominal pain
acid esophageal reflux episodes over a 24-h
• Dysphagia, odynophagia period. Data is collected via an esophageal cath-
• Cough eter placed intranasally, with 1 or more pH elec-
• Hoarseness trodes arrayed along its length that detect the pH
• Wheezing at each site. A drop in intraesophageal pH <4.0
has been conventionally defined as an acid
reflux episode. Esophageal pH monitoring is
inadequate in identifying weakly acid and
Treatment non-acid reflux events. Pertinent measurements
obtained from EpHM include the total number of
Diagnosis and Testing acid reflux episodes, the number of those
episodes lasting >5 min, the duration of the
As GERD is a clinical diagnosis, there is no gold longest reflux episode, and the reflux index
standard diagnostic testing method. The (RI) (percentage of the entire record that
clinical history and physical examination are esophageal pH is <4.0). The RI is the most
therefore critical. Nevertheless, there are a num- commonly used summary score. A RI >7% is
ber of testing modalities that may be helpful in considered abnormal, an RI <3% is considered
the diagnosis of GERD but also in the identifica- normal, and an RI between 3% and 7% is inde-
tion and surveillance of complications from terminate (Vandenplas et al. 2009). Neverthe-
GERD and in the assessment of adequacy of less, these values cannot be extrapolated and
treatment. may not apply in children with cerebral palsy.
Esophageal pH monitoring is useful for evaluat-
Esophagogastroduodenoscopy (EGD) ing the efficacy of acid-blocking therapy and
and Biopsy temporal correlation of symptoms (cough, chest
An EGD allows direct visual examination of the pain) with acid reflux episodes. Overall, the sen-
esophageal mucosa. During this exam mucosal sitivity and specificity of pH monitoring are not
biopsies can be obtained. The combination of an well established.
EGD with biopsy for histology comprises the
most accurate testing method to identify any Combined Multiple Intraluminal
esophageal damage caused by GERD. Reflux ero- Impedance and pH Monitoring (CMII)
sive esophagitis visually appears as breaks (ero- CMII is a newer technique that allows the mea-
sions) in the esophageal mucosa above the surement of movement of fluids, solids, and air
gastroesophageal junction (GEJ). Additional in the esophagus by measuring changes in the
macroscopic findings may include exudate, electrical impedance, or resistance, between
ulcers, and polyps of the esophagus. Histologic multiple electrodes located along an esophageal
findings suggestive of reflux esophagitis include catheter. In many cases it has replaced EpHM as
it provides a more detailed description of reflux

episodes and can detect non-acid reflux episodes
as well. It is proven useful for the evaluation of
correlation between reflux episodes and symp-
toms such as apnea, episodic cough, or other
respiratory symptoms. Normal values in the
pediatric population have not been established
yet (Lopez-Alonso et al. 2006; Mousa et al.
2011). A recent prospective study of 29 children
with CP diagnosed with GERD that underwent
CMII off acid suppressive therapy for at least
5 days concluded that 70% of reflux episodes
were non-acid and therefore would not have
been identified by EpHM alone (Galtepe et al.
2016) (Image 1).
Barium Contrast Radiography/Upper GI

(UGI) Series
Image 1 Impedance probe placement confirmed by x-ray
The use of fluoroscopy to visualize the upper GI
tract is useful in assessing for any gastrointestinal
anatomic or motor abnormalities that may present
with symptoms similar to GERD. Such conditions
include intestinal malrotation, pyloric stenosis,
hiatal hernia, achalasia, and esophageal stricture.
However, due its low sensitivity and specificity in
diagnosing GERD, an UGI is not useful for
GERD diagnosis alone (Thompson et al. 1994)
(Image 2).
Nuclear Scintigraphy/Gastric Emptying

Scan (GES)
This technique uses a solid or liquid meal
labeled with technetium 99 m to assess for
delayed gastric emptying. It can also demon-
strate reflux of gastric contents in the esophagus.
A final additional use of a GES is to evaluate
for aspiration that may occur shortly after a
meal. Scintigraphy is not recommended in the
routine diagnosis and management of
Image 2 Upper GI series in a pediatric patient with cere-
GERD. Nonetheless, in infants and children, it bral palsy showing normal anatomy
may be useful in identifying patients with
delayed gastric emptying that may benefit from
therapy with prokinetic agents. Interestingly, in a
Management
single center study of 76 children with CP and
GERD, the presence or severity of GERD did
Conservative Management
Nonmedical management of GERD in children
not correlate with gastric emptying time when
with CP holds an important role. Certain lifestyle
compared to controls (Spiroglou et al. 2004)
and feeding adjustments can be made to help with
(Image 3).
Image 3 Gastric emptying scan in a pediatric patient with cerebral palsy showing severe reflux and delayed gastric
emptying
symptoms related to GERD. These adjustments Another approach is thickening food for those
can be used as supplement to the medical children that receive enteral formula via a feeding
treatment. tube. Adding various thickening agents to food
As feeding and swallowing dysfunction is very has been shown to decrease the frequency and
common in children with CP, some may require extent of regurgitation episodes in infants and is
feeds via a feeding tube. Gastrostomy tube feed- recommended in the management strategies of
ing has been shown to not only improve growth addressing GERD (Vandenplas et al. 2009). In
and nutritional status but also have a positive children with CP, the addition of liquid pectin to
impact on the quality of life of those caring for enteral formula lessens GER, decreases the fre-
children with CP (Sullivan et al. 2005, 2004). quency of vomiting, and improves respiratory
When it comes to GERD, consideration should symptoms such as cough and wheezing
be given to each feeding regimen and how that can (Miyazawa et al. 2008). Lastly, ensuring an
be adjusted to minimize symptoms related to upright position – especially during meals – can
GERD. Adjustments to the feeding volume, fre- help by decreasing the frequency of reflux
quency, and length of administration can be made episodes.
to decrease the gastric volume and allow adequate
time for gastric clearance. For those primarily Pharmacologic Management
receiving enteral formula, the choice of formula There are three main categories of medications
may have an impact on GERD. Lower osmolality used to manage GERD: antacids, prokinetic
formula enhances gastric emptying and therefore agents, and barrier agents.
can be beneficial. Also, as cow’s milk protein Antacids. Antacids work by neutralizing
allergy is common in the general population and stomach pH, thereby decreasing the exposure of
children with CP (Audiffred-González et al. gastric acidity to the esophageal lining. Antacids
2013), a trial of a hydrolyzed formula in cases of are recommended for short-term relief of heart-
persistent GERD should be considered. burn in older children, adolescents, or adults with
infrequent, less than once weekly, symptoms of preparations are “delayed release” and may take
reflux. Antacids work quickly, providing relief of up to 4 days to achieve maximal acid suppression
heartburn symptoms within a few minutes but (Hunt 2005). Also, long-term use has been linked
have a short duration of effect of 30–60 min. to an increased risk of infectious, metabolic, and
Commercially available preparations typically nutritional disorders. Possible safety concerns
contain a combination of magnesium and alumi- include increased risk of both Clostridium difficile
num hydroxide or calcium carbonate. The long- (Jimenez et al. 2015) and community-acquired
term safety has not been well studied, and chronic pneumonia (Camani et al. 2006), vitamin B12
use is not generally recommended, especially in deficiency (Valuck and Ruscin 2004), nephritis
infants due to the possibility of causing hypo- (Geevasinga et al. 2006), and bacterial over-
phosphatemic rickets (Pivnick et al. 1995). growth (Williams and McColl 2006). Dosing rec-
H2 receptor antagonists (H2RAs) decrease ommendations for PPIs vary considerably.
stomach acid secretion by blocking histamine-2 Younger children appear to metabolize some
receptors on gastric parietal cells. Pharmacoki- PPIs more rapidly, thus requiring a higher dose
netic studies in younger children showed that per kilogram than adolescents and adults (Ander-
peak plasma ranitidine concentration occurs son et al. 2000). PPIs currently FDA approved for
2.5 h after dosing with a half-life of 2 h. After children in North America include omeprazole,
administration, gastric pH will begin to rise within lansoprazole, and esomeprazole.
30 min, and the affects can last for up to 6 h Prokinetic agents. A prokinetic agent can
(Orenstein et al. 2002). Studies in adults have improve contractility of the body of the esopha-
demonstrated H2RAs are superior to placebo for gus, increase lower esophageal sphincter tone,
the relief of symptoms and healing esophageal and increase the rate of gastric emptying. Some
inflammation related to reflux; however the effi- commonly used prokinetic medications include
cacy of these drugs to achieve mucosal healing metoclopramide, bethanechol, erythromycin, and
was greater in those with only mild esophagitis baclofen. Other medications, such as cisapride
(Sabesin et al. 1991). A drawback to H2RAs use is and domperidone, are currently only available in
the development of tachyphylaxis, a diminution restricted limited-access programs because of
of response, within days to weeks of beginning potential risk of cardiac arrhythmia and sudden
treatment, limiting efficacy for long-term manage- death. Currently, there is insufficient evidence to
ment (McRorie et al. 2014). The four commer- support routine use of prokinetic agents for reflux
cially available H2RAs in North America are treatment in children.
cimetidine, ranitidine, famotidine, and nizatidine. Metoclopramide is an antidopaminergic agent
Proton pump inhibitors (PPIs) block gastric that facilitates gastric emptying. It also has
acid production by irreversibly binding to and cholinomimetic and mixed serotonergic effects,
inhibiting the hydrogen-potassium ATPase pump while domperidone, which is no longer commer-
on parietal cells. PPIs are able to maintain cially available in the United States, is a peripher-
intragastric pH at or above 4 for longer periods ally selective dopamine D2 receptor antagonist.
of time and are able to block meal-induced When metoclopramide was compared to placebo,
acid production when compared to H2RAs both reduced reflux-related symptoms in infants.
(Vandenplas et al. 2009). The effect of PPIs does Metoclopramide also reduced, but did not normal-
not diminish with chronic use, an advantage over ize, the reflux index on pH probe studies in these
H2RAs. Studies have shown that PPIs lead to patients (Tolia et al. 1989). Common adverse
higher and faster rates of healing in patients with effects may include lethargy, irritability, gyneco-
erosive esophagitis compared to H2RAs and pla- mastia, galactorrhea, extrapyramidal reactions,
cebo (Kahrilas et al. 2008). Despite their superior and tardive dyskinesia.
efficacy, there are limitations to PPIs. The bio- Bethanechol is a direct cholinergic agonist
availability of PPIs is decreased if they are not thought to increase lower esophageal sphincter
taken before mealtime. Also, most available tone and decrease esophageal acid clearance
times. Its efficacy on reflux is uncertain (Miller effective as cimetidine for treatment of esophagi-
et al. 1977) and may produce adverse reactions, tis (Arguelles-Martin et al. 1989). However,
such as dystonia, in pediatric patients (Shafrir because of the short duration of action, possible
et al. 1986). Erythromycin, a dopamine-receptor aluminum toxicity with long-term use, and limited
antagonist, has been used in patients with efficacy as compared to PPIs, sucralfate is not
gastroparesis to facilitate stomach emptying. Its routinely used in the treatment of GERD
use is limited because of side effects and (Vandenplas et al. 2009).
tachyphylaxis, and it has not been widely studied
in the treatment of reflux. Surgical Management
Baclofen is a γ-amino-butyric-acid B-receptor Neurologically impaired (NI) children are partic-
agonist that inhibits the transient relaxation of the ularly prone to reflux (GERD may be seen in up to
lower esophageal sphincter. There is limited 75% of patients with NI), and half of all pediatric
evidence that baclofen can reduce reflux in adults anti-reflux procedures are performed in neurolog-
and children (Ciccaglione and Marzio 2003) ically impaired children (Vernon-Roberts and Sul-
(Vadlamudi et al. 2013). The use of baclofen livan 2013; Lasser et al. 2006).
may cause dyspeptic symptoms, drowsiness, diz- Surgical procedure. The most commonly
ziness, and fatigue and may lower seizure thresh- performed anti-reflux procedure is a Nissen
old. Because of its side effects, baclofen is rarely fundoplication (NF) and is considered the gold
used to treat reflux in children without neurolog- standard for treatment for refractory GERD
ical impairment. However, it is frequently used for (Coran and Adzick 2012; Fukahori et al. 2016).
patients with cerebral palsy to decrease spasticity. In the NF procedure, the fundus of the stomach is
In a small trial to investigate the effects of baclo- wrapped around the esophagus. This action pro-
fen on GERD in neurologically impaired children, vides several anatomic changes that improve
repetitive administration of baclofen reduced the GERD including increased length of the
frequency of emesis and the total number of acid intraabdominal esophagus and revision of the
refluxates without major side effects (Kawai et al. angle of His. These changes repair and improve
2004). the function of the gastroesophageal junction as a
Barrier agents. Barrier agents help create a valve that blocks retrograde passage of food bolus
coating on the luminal surface of the digestive (Tovar et al. 2007).
tract to decrease acid injury. Two agents that Anti-reflux surgery can be performed openly or
have been studied in the treatment of GERD laparoscopically, with comparable short-term
include sodium alginate and sucralfate. clinical outcomes (Jancelewicz et al. 2017).
Alginates are insoluble salts of alginic acid Some studies have suggested that laparoscopic
derived from seaweed. This agent forms a surface surgery may have a higher risk of long-term com-
gel that creates a physical barrier on the esopha- plications such as wrap migration into the chest
geal and gastric mucosa. Studies comparing the cavity (Knatten et al. 2012). The laparoscopic
efficacy on symptoms and decreasing esophagus approach to surgery can provide enhanced visual-
acid exposure showed conflicting results (Buts ization to the surgeon due to magnification. Ben-
et al. 1987). There is a commercially available efit to the patient is also achieved by reducing
alginate tablet combined with an antacid that is postoperative pain and providing a better abdom-
used for the temporary relief of heartburn symp- inal cosmetic appearance than open procedures
toms in adults. (Coran and Adzick 2012). During a laparoscopic
Sucralfate is a compound containing sucrose, Nissen fundoplication (LNF), three to five inci-
sulfate, and aluminum that forms a gel in acidic sions measured in millimeters are made to accom-
environments that binds to mucosal erosion, pro- modate laparoscopic instruments. Usually, the
moting healing and protecting from further peptic abdomen is entered through the umbilicus, and
injury. Only one randomized comparison study insufflation with carbon dioxide gas is achieved.
in children demonstrated sucralfate was as Inside the abdomen, the short gastric vessels and
the gastrohepatic ligament are divided to mobilize

the stomach. The crura of the diaphragm are iden-
tified, but minimal crural dissection is performed
in order to minimize risk of transhiatal migration
of the wrap into the chest (St Peter et al. 2007). A
retroesophageal window is created, and the fun-
dus of the stomach is wrapped around the esoph-
agus 360 degrees. Three interrupted,
nonabsorbable sutures are placed to secure the
wrap. The superior suture usually incorporates
esophagus and either side of the fundus, and the
two inferior sutures secure fundus to fundus.
Length of the fundoplication can range from
1.5 cm in infants to 3.0 cm in older children. It is
important to use a large rubber tube (bougie) in the
esophagus while performing the fundoplication,
so that the lumen of the esophagus is not narrowed
by the wrap. The incisions are closed, and a local
anesthetic such as bupivacaine is used for pain Image 4 Nissen fundoplication wrap seen on retroflexion
during an upper endoscopy
control. Emphasis is placed on the importance of
a floppy or loose Nissen as it may provide more
mobility in the event of vomiting or retching. medications, and readmissions for mechanical
While the LNF procedure is a 360-degree, or ventilation have been demonstrated in the litera-
full, wrap of the stomach around the esophagus, ture (Knatten et al. 2016) (Srivastava et al. 2009a)
other procedures such as the laparoscopic Thal as benefits of surgical treatment of GERD. It is
and Toupet procedures provide the option of a important to note, however, that some studies
270-degree or partial wrap. Studies have been have shown rates of aspiration pneumonia after
done to compare these two partial procedures NF to be as high as 37% (Wales et al. 2002).
with the LNF and have not shown any significant Esophageal manometry and pH monitoring have
difference, but Nissen fundoplication is the one led to the discovery that mucosal integrity is
most commonly performed for the management improved in patients post-surgery possibly pro-
of reflux (Miyano et al. 2017; Hu et al. 2016) tecting against undesirable downstream sequelae
(Image 4). of GERD such as Barrett Esophagus (Fukahori
Benefits of surgery. For patients in whom et al. 2016).
medical management of GERD has failed, surgi- Complications of surgery. As a proven surgi-
cal treatment is a viable option. Surgical treatment cal management for refractory GERD, complica-
may improve the quality of life for neurologically tions of NF have been widely studied and remain
impaired children by reducing vomiting, regurgi- low. The most common complication of NF is
tation, and meal discomfort. Such improvements wrap failure, a “slipped Nissen,” in which crural
can lead to easier feeding and improved growth. breakdown and resultant migration of the wrap
In addition, fundoplication can prevent complica- into the chest causes hiatal hernia. In the general
tions that are related to reflux that result in aspira- pediatric population, herniation occurs at a rate of
tion, including aspiration pneumonia and reactive 2–5% but increases up to 8–24% in patients with
airway disease. Neurologically impaired patients comorbidities (Langer and Albanese 2005; Diaz
are especially prone to these complications as they et al. 2005). Herniation is more likely to occur in
may be less able to protect their airway in the patients with hypertonic cerebral palsy (Langer
setting of reflux. Reductions in the incidence of and Albanese 2005). In addition, the majority of
aspiration pneumonia, need for daily airway reoperations occur in neurologically impaired
patients (Coran and Adzick 2012). Recurrent no evidence that reflux-related hospitalization
GERD is another complication after surgery. rates differ in neurologically impaired patients
Recurrence of reflux or wrap failure after NF has who received both GT and fundoplication com-
been reported to be as high as 40% in NI patients pared with those who received GT alone (Barnhart
(Jancelewicz et al. 2017). Risk factors for recur- et al. 2013). Secondly, fundoplication with GT
rence include age younger than 6 years, postoper- increases the morbidity of the procedure (Berman
ative hiatal hernia, postoperative retching, and Sharif 2015). As these considerations are
neurologic impairment, and postoperative dys- raised especially in the neurologically impaired
phagia requiring esophageal dilation (Heinrich population, it is important to emphasize the need
et al. 2017). Other complications include dumping for an entirely informed decision concerning con-
syndrome, gas bloat, and tight wrap (Coran and current fundoplication and GT placement. Often
Adzick 2012). The best diagnostic study to eval- children with neurological impairment have
uate a patient who develops recurrent symptoms increased gastrointestinal symptoms resembling
of reflux or feeding intolerance after GERD such as vomiting and pain localized to
fundoplication is an upper GI series. This study the gastrointestinal tract that are caused by central
provides important information regarding the nervous system impairment (Hauer 2014). This
anatomy of the fundoplication and will show emphasizes the importance of discerning the dis-
whether the wrap is still intact and whether trans- tinction upon preoperative examination of neuro-
hiatal migration has occurred. logically impaired children’s nervous system,
In the general population, mortality is a rare respiratory function, dysphagia, and intolerance
complication, occurring in 0.08% of operations. It to gastric feedings (Knatten et al. 2016).
is more often related to the underlying condition Nissen Fundoplication with gastrostomy
of the patient than to the operation (Coran and (FG) may carry significantly higher risks of mor-
Adzick 2012; Tovar et al. 2007). The mortality bidity in neurologically impaired patients com-
rate after fundoplication in NI patients has been pared to neurologically normal patients. NI
reported to be as high as 27% (Jancelewicz et al. patients appear to be more prone to retching and
2017). gas bloat syndrome, which may predispose them
Special considerations. In discussion of NF to wrap failure and continued reflux requiring
procedures for the neurologically impaired popu- additional surgery (Veenker 2008). Some obser-
lation, it is important to draw attention to times vational studies have compared the use of FG with
when fundoplication is considered as a concomi- the less invasive alternative of a gastroje-
tant procedure with placement of a gastrostomy junostomy (GJ) tube placement. The GJ tube can
tube (GT). Gastrostomy is the practice of placing a be removed or converted to G tube if symptoms of
tube that passes from outside of the abdomen GER improve; however, GJ tubes necessitate a
directly into the stomach, anchoring the stomach continuous feeding regimen, require additional
to the abdominal wall. These tubes are often procedures if the tube becomes dislodged or has
placed in the neurologically impaired child to aid repositioned, and, in rare circumstances, can
with feeding, nutrition, and growth. Many GT cause life-threatening intussusception (Livingston
placement operations in this population raise a et al. 2015). In addition, most institutions recom-
difficult decision of whether or not to proceed mend routine changes every 3 months to prevent
with concurrent fundoplication (Berman and complications, and studies have found that often
Sharif 2015). There has been a tendency to per- many children need their tubes replaced even
form the fundoplication prophylactically in more frequently (Veenker 2008).
infants who may or may not have experienced Differences in outcomes between the two pro-
complications of GER and especially in those cedures have been compared in several retrospective
with neurological impairment. Recent studies studies. One argument in favor of FG is reduction in
have brought to light the question of whether risk of aspiration pneumonia, but studies have
this is necessary for two reasons. First, there is shown that this complication occurs at a similar
rate after either procedure (Srivastava et al. 2009b;

Livingston et al. 2015). Readmission rate also does
not appear to differ following FG or GJ. Anti-reflux
medications are more likely to be continued after a
GJ. Major complications such as small bowel
obstruction, peritonitis, deep wound infection, and
wrap failure requiring redo fundoplication are more
frequent following FG (Livingston et al. 2015).
Most authors who undertake the task of comparing
these two procedures agree that the lack of evidence
to support one approach over the other results in
clinical equipoise. The absence of prospective stud-
ies and randomized control trials contributes to the
reality that the decision to proceed with one of these
two options is strongly associated with institutional
Image 5 Erosive esophagitis in a pediatric patient with
culture guiding the clinicians’ choice. Ideally, both cerebral palsy
options should be presented to patients and families
along with accompanying risks and benefits so a
choice can be made that is consistent with their Barrett Esophagus
preferences. and Adenocarcinoma
Barrett esophagus is rather uncommon in chil-

Complications dren but has been reported (Jeurnink et al. 2011).
Children with neurological disability are at
GERD may result in a number of complications if higher risk (Hassall 1997). The prevalence of
left chronically untreated. Such complications Barrett esophagus in intellectually disabled
include reflux erosive esophagitis, peptic adult individuals is estimated to be 12–26%
strictures, Barrett esophagus, and esophageal (Bohmer et al. 1999; Roberts et al. 1986). This
adenocarcinoma. may be the case because GERD in this patient
population often goes undiagnosed and
untreated for a prolonged period of time. In addi-
Reflux Esophagitis and Peptic tion, as the columnar lining is less sensitive to
Strictures acid, symptoms may be minimal or absent
(Loffeld 2001). Histopathologically, Barrett
Reflux esophagitis refers to the presence of esoph- esophagus is defined as the change of the normal
ageal mucosal inflammation seen endoscopically squamous epithelium of the distal esophagus to a
as a result of chronic acidic exposure from GERD. columnar-lined intestinal metaplasia. The diag-
In a large population-based study of more than nosis requires the presence of salmon-colored
7000 neurologically normal children with GERD mucosa extending into the tubular esophagus
and without esophageal congenital abnormalities, 1 cm proximal to the gastroesophageal junc-
erosive esophagitis was found in 12.4% of the tion (GEJ) with biopsy confirmation of intestinal
cases (Gilger et al. 2008). Peptic strictures are metaplasia (Shaheen et al. 2016). The abnormal
generally located in the distal esophagus. They epithelium of Barrett esophagus may progress to
arise as a result of chronic exposure to the acidic dysplasia and lead to esophageal adenocarci-
gastric contents and may be the end result of noma. Adenocarcinoma is extremely rare in
reflux esophagitis. Their management requires childhood, but it does occur and should be con-
surgical interventions with different degrees of sidered in those with Barrett esophagus (Hassall
success (Pearson et al. 2010) (Image 5). et al. 1993) (Image 6).
▶ Overview of Feeding and Growth in the Child

with Cerebral Palsy
▶ Postoperative Care of the Cerebral Palsy
Patient
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Medical and Surgical Therapy for
Constipation in Patients with 52
Cerebral Palsy
Erin A. Teeple, Roberto A. Gomez Suarez, and

Charles D. Vinocur
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 768
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 768
Physiopathology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 768
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 768
History and Physical Exam . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 768
Abdominal Radiography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 770
Sitz Marker Study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 770
Motility Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 771
Rectal Biopsies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 772
Medical Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 773
Retrograde Enemas and Fecal Disimpaction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 773
Antegrade Enteral Cleanout at Home . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 773
Admission for Bowel Cleanout . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 774
Maintenance Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 774
Diet . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 774
Medications that Induce Constipation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 775
Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 775
Surgical Therapy and Interventions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 775
Medically Refractory Constipation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 775
Volvulus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 777
Perforation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 778
E. A. Teeple (*) · C. D. Vinocur

Department of Surgery, Nemours/A.I. Dupont Hospital for
e-mail: Erin.teeple@nemours.org; Charles.
vinocur@nemours.org
R. A. Gomez Suarez
Department of Gastroenterology, Nemours Children’s
e-mail: Roberto.gomezsuarez@nemours.org

https://doi.org/10.1007/978-3-319-74558-9_54
768 E. A. Teeple et al.
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 778
Case Example . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 778
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 779
Abstract bladder dysfunction, and poor tolerance of feed-

Constipation is one of the most common gas- ings (Silva et al. 2010; Cooney and Cooney 2011;
trointestinal symptoms in patients with cere- Lee et al. 2013; Martinez-Lage et al. 2008). When
bral palsy (CP). Its prevalence ranges initial therapy options prove inadequate, these
between 25% and 75%. Constipation and patients are referred to pediatric gastroenterology
fecal incontinence is a source of embarrass- and surgery for further management.
ment and affects quality of life in close to
60% of adolescents and adults with
CP. The pathophysiology of constipation Natural History
in this patient population is multifactorial
including inherent abnormalities in neuro- Physiopathology
modulation, compounded by immobility,
chronic dehydration, and medication. If left There is not a single etiology that explains consti-
untreated, constipation can lead to significant pation in these patients. Several mechanisms have
complications such as intolerance of feeds, been implicated, including poor neuromodulation
bladder dysfunction, fecal impaction, volvu- of the colon, abnormal colonic motility, delayed
lus, and even perforation. When initial therapy transit times, spasticity of the pelvic floor, and
options prove inadequate, these patients are inability to push. Additionally, other factors may
referred to pediatric gastroenterology and sur- be contributory including diet, inadequate water
gery for further management. and/or fiber intake, particular medications, and
associated partial or total immobility (van den
Keywords Berg et al. 2006).
Cerebral palsy · Constipation · Fecal
impaction · Dysmotility · Appendicostomy
Treatment
Introduction History and Physical Exam
Constipation is one of the most common gastro- The diagnosis of constipation is mainly clinical.
intestinal symptoms in patients with static enceph- Key features of a careful history include number
alopathy, cerebral palsy (CP), and developmental of bowel movements per week, the shape and
delay. Its prevalence ranges between 25% and consistency of the stool using the Bristol stool
75% with the severity varying according to the chart (Fig. 2) (Chumpitazi et al. 2016), and history
CP Gross Motor Function Classification System of blood in the stool or painful bowel movements.
(Fig. 1) (Del Giudice et al. 1999; Erkin et al. Fecal impaction is suspected if there is presence of
2010). Constipation and fecal incontinence is a a full abdomen or a suprapubic mass or if stool is
source of embarrassment and affects quality of life palpable in the distribution of the colon. The
in close to 60% of adolescents and adults with examination should include assessment of the
cerebral palsy (Marciniak et al. 2015). If left anal area for fissures or perianal dermatitis,
untreated, constipation can lead to severe compli- which is frequently associated with fecal inconti-
cations such as volvulus, intestinal obstruction, nence, constipation, and CP (Nava et al. 2014).
52 Medical and Surgical Therapy for Constipation in Patients with Cerebral Palsy 769
The Gross Motor Function Classification System (GMFCS) categorizes a patient's motor
function based on their age and usual performance in various settings; school, home, and
community. The example below is for ages 6 to 12 years (modified descriptions of these
categories are used for younger age groups):
●Level I – Walks without limitations
●Level II – Walks with limitations
●Level III – Walks using a hand-held mobility device (canes, crutches, and anterior and
posterior walkers that do not support the trunk)
●Level IV – Self-mobility with limitations; may use powered mobility
●Level V – Transported in a manual wheelchair
Fig. 1 CP Gross Motor Function Classification System. (Del Giudice et al. 1999)
Fig. 2 Bristol stool scale. (Chumpitazi et al. 2016)
Digital rectal exam is essential to assess pelvic “Fecal impaction” is a term used to describe the
floor and anal tone as well as to quantify rectal presence of a fecal mass in the colon or rectum,
stool burden. with symptoms or signs of obstruction attributed
Fig. 4 Megasigmoid in a child with long-standing consti-

pation (E. Teeple)
Fig. 3 Patient with severe rectal and sigmoid impaction
(R. Gomez Suarez)
useful in discriminating between children with
to this fecal mass. Although fecal impaction is constipation and normal controls; however, there
frequently diagnosed clinically, baseline abdomi- is not yet enough evidence to support its routine
nal radiographs are valuable, both in confirming clinical use (Joensson et al. 2008).
the diagnosis and in assisting parents and patients
in understanding the issue (Fig. 3) (Tabbers
et al. 2014). Sitz Marker Study
Colonic transit time can grossly be measured

Abdominal Radiography using a Sitz marker study. There are variations
in how this test is administered. One approach is
Although the diagnosis of fecal impaction can be to give the patient a Sitz marker capsule filled
made clinically, it is useful to obtain an abdominal with 24 radiopaque markers and check a single
film as a baseline as mentioned above. It may also abdominal X-ray 5 days after the capsule is
reveal signs of secondary ileus or obstruction that ingested. Motility is then estimated by how
may alter the management. many markers are seen on the left side of the
Contrast enemas are used when standard treat- colon on the abdominal X-ray. Colonic transit
ment has been unsuccessful, when the plain film time is frequently delayed in children with CP. In
suggests a chronically dilated segment, or if sur- a study performed in 3- to 8-year-old children
gery may be necessary. In general, the portion of with CP, prolongation of colonic transit time was
colon most commonly dilated is the sigmoid more evident at the level of the left colon and
colon (Fig. 4) (Reid et al. 2000). rectum in 56% of the patients, suggesting more
Transabdominal rectal ultrasonography has left-sided colonic dysfunction. In another study,
been studied in the diagnosis of children with the investigators found a delay of the proximal
constipation, although it is not routinely used in colon transit time, suggestive of right colonic
clinical practice. The transverse diameter of the dysfunction. Right-sided dysfunction was more
rectal ampulla is measured and compared with the associated with the lack of ambulatory abilities
diameter of the pelvis. This technique may be and increased severity of cognitive dysfunction.
Even patients with no obvious clinical constipa- (Del Giudice et al. 1999; Staiano and Del
tion had higher retention of the markers at Giudice 1994; Park et al. 2004).
the level of the rectum suggestive of baseline
outlet dysfunction in this population (Fig. 5)
Motility Studies
Anorectal manometry consists of placing a long,

thin, multichannel catheter in the rectum to mea-
sure the pressures in the anorectal area including
rectal sensitivity, resting anal pressure, and
presence of rectoanal inhibitory reflex (Fig. 6).
Dependent on patient cooperation, this outpatient
study is either performed on an awake patient or
under general anesthesia.
It is presumed that children with CP have an
increase in pelvic floor as well as anal tone due to
the spasticity inherent to the condition. However, in a
study done by Staiano et al., there was no difference
between the control group and patients with CP in
any of these parameters (Staiano and Del Giudice
1994).
Similar to sitz marker studies, colonic manom-
etry has been useful in distinguishing between
colonic inertia, distal colonic dysmotility, and
Fig. 5 Presence of outlet dysfunction in a patient with
outlet dysfunction constipation in patients with
severe constipation. 15/24 sitz markers were accumulated CP. The results can help discern segmental from
in the rectum after 5 days of ingestion (R. Gomez Suarez) total colonic dysmotility as well as degree of
Fig. 6 Anorectal manometry. Arrow shows presence of dyssynergia with severe paradoxical contraction during
rectoanal inhibitory reflex (RAIR). Triangle and star Valsalva (R. Gomez Suarez)
(3D reconstruction) show the presence of pelvic floor
Fig. 7 Colonic manometry. (a) Normal colonic manome- Abnormal colonic manometry showed distal colonic dys-
try showed progression of HAPCs through the entire colon function in a patient with slow transit constipation and
in a patient with outlet dysfunction constipation. (b) outlet dysfunction (R. Gomez Suarez)
dysfunction (van den Berg et al. 2006). Colonic Rectal Biopsies

manometry is a more cumbersome study com-
pared to anorectal manometry, as it involves an Rectal biopsies are mainly indicated in patients
admission for bowel cleanout and a full colonos- when the diagnosis of Hirschsprung’s disease is
copy with placement of a colonic manometry considered. These children may have a history of
catheter (Fig. 7). delayed passage of meconium at birth, intractable
constipation, failure to thrive, or an abnormal 3 consecutive days, before significant results are
anorectal manometric study showing the absence seen. It is important to educate the caregivers to
of rectoanal inhibitory reflex. Without a need to expect only brown liquid stool after the enema and
rule out Hirschsprung’s disease, a rectal biopsy not to expect that the mass will be removed in total
does not contribute to the management of consti- with the enema. Patients with fecal impaction may
pation. In fact, in children with chronic constipa- present with a large hard rectal mass or multiple
tion, there are often histological abnormalities of masses throughout the colon. As a rule, patients
unknown significance on biopsy which may cre- with intestinal obstruction, ileus, and severe rectal
ate a confusing picture (Tabbers et al. 2014; van impaction need manual rectal disimpaction
den Berg et al. 2009). under anesthesia before beginning an antegrade
cleanout with polyethylene glycol or another
osmotic laxative. To perform manual fecal
Medical Therapy disimpaction, the patient would ideally be placed
in lithotomy position, although this is not always
Several therapeutic modalities are used for the possible in patients with cerebral palsy due to
treatment of constipation in patients with spasticity and contractures. The anal canal should
CP. Initially, if indicated, rectal disimpaction is be lubricated and slowly distended manually to
an essential step to relieve anorectal obstruction avoid anal fissures. During this procedure, a large,
and allow antegrade flow of stool during subse- soft rectal catheter, usually a red rubber catheter
quent therapy. Otherwise, if maintenance therapy measuring 18–20 French, is connected to a
is started, it will lead to abdominal pain and, 1000 ml warm saline bag. The volume and
ultimately, will be unsuccessful. Only after warmth are important to distend the rectum and
cleanout should maintenance therapy be initiated soften the anal mass. We start by filling the rectum
for the prevention of relapsing constipation. with 200–400 ml of saline, and then proceed to
morcellate the mass into pieces using the second
and third finger of the right hand while we push
Retrograde Enemas and Fecal the lower abdomen with the left hand. We repeat
Disimpaction this process several times until the mass(es) are
removed. A nasogastric or nasoduodenal tube is
If the patient is not fecally impacted but has firm then inserted for an antegrade cleanout once the
stool in the rectum, treatment may be aided by the patient returns to the floor.
use of rectal enemas. There are a variety of
enemas available, including sodium and potas-
sium phosphate, mineral oil, saline, and sodium Antegrade Enteral Cleanout at Home
docusate. If the stools are hard, using a mineral oil
enema first may soften the stool and make it easier Several authors have proposed enteral laxative
to pass with subsequent enemas. Enemas are regimens as an efficient method for achieving
administered using the enema bottle, or preferably large volume reduction of stool when fecal impac-
using an enema bag with a soft, non-latex catheter, tion is not present. This can be accomplished
which is more comfortable for the patient. Many using polyethylene glycol at a dose of 1.5 g/kg
of the children with CP have lax anal tone, making body weight for 3 days. In addition, other authors
it difficult to retain the enema long enough for the propose an escalating dose, up to 78 g, during a
medication to be effective. In this instance, using a period of 6 days (Candy and Belsey 2009;
balloon catheter can be very helpful. The patient Youssef et al. 2002). This is done using polyeth-
should lie in the left lateral decubitus position with ylene glycol diluted in water or Gatorade.
the knees bent, avoiding too much tension on the Dilution of the medication varies with 17 g
legs to prevent fractures or dislocation of the hips. being mixed with anywhere between 4 and
Enemas are usually necessary daily, during 2 or 8 ounces of fluid. The solution is then given
slowly at 4–8 ounces per hour through a nasogas- (1–2 ml/kg/day) or polyethylene glycol
tric gastrostomy or jejunostomy tube in patients (0.8 g/kg/day) are used until stool appears light
with low risk of aspiration and absence of signs of brown (Nurko et al. 2008).
obstruction or ileus. Some authors have supported the use of
sennosides. The maximum dose varies with age.
In a typical child less than 6 years old, a maximum
Admission for Bowel Cleanout dose of 6.6 mg twice a day is recommended.
Children 6–12 years old have a maximum dose
Patients that do not respond to enemas or home of 13.2 mg twice daily, and children over 12 years
cleanouts are admitted for bowel cleanout. They old have a maximum dose of 24 mg twice a day.
require enteral access with either placement of a However, not all patients are typical, and esca-
nasogastric tube or use of a preexistent lated doses may be necessary. Typical concentra-
gastrostomy or jejunostomy tube. If placement tion of the liquid solution is 8.8 mg per 5 ml.
of a nasogastric tube is required, it is In patients with CP and a high risk of aspira-
recommended to obtain an abdominal X-ray to tion, the use of mannitol, mineral oil, liquid par-
confirm the position in the stomach. There have affin, glycerin, polyethylene glycol, and any other
been several cases of reported aspiration of poly- hyperosmotic solution should be used with cau-
ethylene glycol into the lungs leading to signifi- tion (Mosquera et al. 2014). As a maintenance
cant pulmonary edema (Marschall and Bartels drug, enemas can be given once or twice a week
1998). Polyethylene glycol with an electrolyte as needed if the patient has no bowel movements
solution is preferable for antegrade cleanout. The in 24–48 h (Elawad and Sullivan 2001).
infusion should begin at a slow rate, initially
5–10 ml/kg/h, and can slowly be increased to
20 ml/kg/h. If the patient has a high risk of aspi- Diet
ration, it would be desirable to start the solution
directly into the jejunum. An antegrade approach Lack of enough water and fiber and modular
is contraindicated in patients with intestinal diets have been proposed as factors in the
obstruction, ileus, or high risk of aspiration. The perpetuation of intestinal dysmotility and constipa-
infusion should continue until the stool output tion in patients that are mainly fed through
changes color from dark brown liquid to light gastrostomy or jejunostomy tubes (see ▶ Chap. 50,
brown liquid. Frequently patients have vomiting “Gastrostomy and Jejunostomy Feedings in Chil-
and abdominal distention during these periods. At dren with Cerebral Palsy”). Frequently there is not
that time, the solution is placed on hold, and the enough water or fiber added to these formulas
patient can receive antiemetic medications. resulting in chronic dehydration. Recently, the
Sometimes placement of a soft rectal rubber cath- European Society for Paediatric Gastroenterology,
eter, again measuring 18–20 French, is used to Hepatology and Nutrition published guidelines for
decompress the fluid from the abdomen. This the evaluation and treatment of gastrointestinal and
subset of patients usually demonstrate poor intes- nutritional complications in children with neurolog-
tinal motility and inability to move the liquid ical impairment. The guidelines recommend that
efficiently. careful attention is necessary to maintain proper
hydration status (Romano et al. 2017).
Children with spasticity have increased meta-
Maintenance Therapy bolic demands and need more energy intake (see
▶ Chap. 49, “Overview of Feeding and Growth in
Once the large volume of colonic stool has the Child with Cerebral Palsy”). They also may
been passed, multiple laxatives are used for have gastroesophageal reflux with a resultant
maintenance therapy to prevent recurrent increased risk of aspiration, making them intoler-
constipation. Osmotic laxatives such as lactulose ant to large volumes of gastric feeds (see
▶ Chap. 51, “Gastroesophageal Reflux in the (Zeller et al. 2012). Medications used for urinary
Child with Cerebral Palsy”). One solution is the incontinence (see ▶ Chap. 59, “Neurogenic Blad-
use of hypercaloric formulas to decrease the vol- der in Cerebral Palsy: Upper Motor Neuron”) are
ume needed to achieve the same caloric goal. frequently in the category of anticholinergics and
There are several ways to calculate maintenance are associated with increased constipation.
fluids in children, including many online fluid The use of certain antiepileptic medications
calculators. In general, children with CP need such as valproate, phenytoin, and levetiracetam
the same volume of fluid as children without are also associated with constipation. Frequent
CP. For infants 3.5–10 kg, the requirement is application of Botox also has been implicated in
often 100 ml/kg/day. In children 11–20 kg, the the exacerbation of dysmotility (Papavasiliou
daily fluid requirement is 1000 ml + 50 ml/kg et al. 2013).
over 10 kg. In children more than 20 kg, daily
fluid requirements are 1500 ml + 20 ml/kg for
every kilogram over 20 with a maximum of Complications
2400 ml/day. In our institution, we subtract the
amount of formula given during the day from the Surgical Therapy and Interventions
total daily fluid requirement. The remainder is
divided by the number of feeds and given as Surgery can play an important role in the manage-
postprandial free water flushes. ment of the chronically dysmotile child. This is
The amount of fiber in the diet is also important best done in a multidisciplinary fashion including
to prevent constipation, and giving 17–25 mg/day discussion among surgery, gastroenterology, urol-
may result in a slight reduction in constipation ogy, and other services as appropriate. The goal of
(Fischer et al. 1985). As a rule, the amount of this multidisciplinary team is for the child to
recommended fiber per day can be calculated achieve fecal continence at school or at play and
using the age plus 5 in grams. Wheat dextrin is a to allow for socialization with prevention of ostra-
commercial over-the-counter fiber that can be cism by peers.
added to the patient’s formula. The dose varies There are many indications for surgery in this
according to the age of the child: 1–3 years require patient population. These include medically
19 g/day; 4–8 years require 25 g/day; 9–13 years refractory constipation and subsequent complica-
require 26–31 g/day; and 14–18 years require tions including the development of a dilated seg-
26–38 g/day. Slow increases are necessary, due ment of the colon (typically the sigmoid),
to side effects of bloating and feeding intolerance. volvulus, and perforation.
Extra fiber should be avoided in patients with
fecal impaction (Slavin et al. 2009).
Medically Refractory Constipation
Medications that Induce Constipation Medically refractory constipation can be aided by

surgical intervention in many patients. The choice
In patients with CP, there are multiple medications of operation depends on many factors including
and procedures that are associated with induction previous operation, findings on investigative stud-
or worsening of constipation because of their ies, and goals of care. Ultimately, the goals of
effect on gastrointestinal motility. Anticholinergic treating constipation, both medically and surgi-
medications such as glycopyrrolate, used fre- cally, are to maintain fecal continence in a socially
quently for the therapy of excess drooling in acceptable manner as mentioned above, as well as
patients with CP (see ▶ Chap. 53, “Medical Man- prevent untoward complications of chronic
agement of Sialorrhea in the Child with Cerebral constipation.
Palsy”), have been directly associated with wors- If the child has relatively normal anatomy but
ening constipation in around 20% of the patients is plagued with severe constipation with or
without encopresis, consideration should be given

to an enema program. Enemas can be adminis-
tered in a retrograde fashion using a standard
program consisting of enemas per rectum typi-
cally along with other enteral medications (Chait
et al. 1997; Mousa et al. 2006; Wong et al. 2008).
The Peristeen system is an example of a commer-
cially available retrograde enema system. One of
the reasons standard enema programs per rectum
may fail is because of the lack of anal sphincter
tone. As the fluid enters, the balloon will slip out,
or the caregivers are unable to gain a seal with the Fig. 8 Gastrostomy button on the left and Chait button on
enema, and the liquid medication is evacuated the right (C. Vinocur)
before it can achieve the desired effect. The first
solution created to solve this problem was to
instill the solution in an antegrade fashion. Ante-
grade continence enema (ACE) was first
described by Malone (MACE) in 1990 (Malone
et al. 1990). He used the appendix to create access
to the cecum to provide antegrade enemas. This
resulted in controlled stooling and reduction in
fecal burden and incontinence. Since his original
description, the procedure has had several modi-
fications, including wrapping the appendix in the
wall of the cecum to provide an antireflux mech-
anism so stool does not leak from the opening of
the appendix, as well as the addition of laparos-
copy to create the MACE. Other mechanisms of
providing access to the cecum to establish an
antegrade enema program are via a surgically or
radiographically placed percutaneous cecostomy
(Rivera et al. 2001; Cascio et al. 2004). A surgi-
cally fashioned cecostomy involves placement of Fig. 9 ACE site (C. Vinocur)
a tube typically used for a gastrostomy, including
both low-profile as well as long gastrostomy not noticeable once the tube is removed (Fig. 9).
tubes. Radiographically placed cecostomies can Potential complications include stenosis of the
use a low-profile gastrostomy tube but also have aperture and tract as well as injury to the appendix
the option of using a Chait button (Fig. 8). The resulting in superficial or deep space infection.
Chait button was developed by Dr. Chait, a radi- Knotting of the catheter can also occur making
ologist in Toronto who first described radiograph- removal difficult. Because a percutaneous
ically placed cecostomies (Shandling et al. 1996). cecostomy tube remains in place, the tract does
Each approach to cecostomy carries its own risks not have to be manipulated daily. The drawbacks
and benefits. After surgical creation of an ACE, a of this approach include permanent foreign body
flexible Silastic tube is placed in the orifice in the abdominal wall, formation of granulation
nightly, the flush is administered, and then the tissue, potential dislodgement, and need for seda-
tube is removed. Benefits include the ability to tion to facilitate tube replacement or exchange.
remove the tube and cosmesis. Because it is typ- Complications common to all approaches include
ically located within the umbilicus, the orifice is leakage at the skin and skin infection.
Prior to placement of antegrade enema access, well as the risks and benefits must be fully
retrograde enemas are undertaken in children with discussed and evaluated prior to proceeding.
dysmotile bowel to gauge the potential for suc-
cess. If a temporary retrograde enema program
is successful, antegrade access is established. Volvulus
Flushes through the antegrade enterostomy are
escalated over the postoperative days to achieve Acute and chronic intermittent colonic volvulus
20 ml/kg of normal saline in a nightly flush. The are unusual events in children (Samuel et al.
child will sit on the toilet, begin the flush, and sit 2000). Constipation and abnormal colonic fixa-
for an average of 45 min, allowing the flush to tion are thought to be predisposing factors. Types
pass through the colon and anus along with a large of volvulus include cecal, transverse colon, and
quantity of stool. If saline alone is ineffective at sigmoid colon. Presentation varies but usually
achieving fecal continence during the day, addi- includes abdominal distention, intolerance to
tives can be dissolved into the antegrade enemas, feeds, increased gastrostomy tube output, facial
including irritant laxatives, lubricants, and pro- grimace, or expression of pain and even peritoni-
motility laxatives. The percentile success of ante- tis. Volvulus is diagnosed on abdominal radio-
grade enemas is variably dependent on underlying graph and confirmed on computerized axial
disease process. Some children with CP seem to tomography (CT) or magnetic resonance imaging
be at higher risk for refractory constipation and (MRI), contrast enema, or colonoscopy (Fig. 10).
soiling due to their potential for significant Once discovered, in the case of transverse or
dysmotility (Mugie et al. 2012). sigmoid colon volvulus, the bowel can be
During the workup of the constipated child, a detorsed with colonoscopy. This reduces ischemic
contrast enema may demonstrate an abnormally
dilated colon or segment of colon. This typically
is the sigmoid colon but can also present in other
segments of the colon or the entire colon.
The mechanically dysmotile segment can also be
confirmed or elucidated on manometry. In this
instance, this segment can be excised and
reanastomosed in an attempt to improve transit
time while restoring continuity. This can be done
in conjunction with the creation of an ACE or if
the child fails to achieve goals of care after the
optimization of ACE flushes (Bonilla et al. 2013).
If the contrast enema and colonic manometry
demonstrate total colonic dysmotility with diffuse
distention, there exists a variety of surgical
options. These include creation of an end
ileostomy with or without removal of the colon,
removal of the colon with ileorectal anastomosis,
removal of the colon and rectum with creation of
end ileostomy or creation of ileal pouch anal anas-
tomosis, or creation of permanent end colostomy
with or without resection (Scarpa et al. 2005;
Woodward et al. 2004; Nicholls and Kamm
1988; Asipu and Jaffray 2010). Discussions of
these surgical approaches are beyond the scope Fig. 10 Abdominal X-ray of sigmoid volvulus in a child
of this chapter, but the goals of the operation as with long-standing constipation (E. Teeple)
risk to the colon by straightening the mesentery changing for the child and the family. The child
and may even allow bowel preparation prior to feels better without a constant stool burden. The
definitive treatment. Definitive treatment consists caregivers find that they no longer are the only
of segmental resection and anastomosis. If volvu- people who can care for their child as the fear of
lus is the presenting symptom of constipation, unanticipated accidents is gone. Children and
attempt at reduction with aggressive medical man- their caregivers find that their lives have improved
agement may be attempted for transverse colon when the worry of accidents is essentially
and sigmoid volvulus, but the rate of failure is resolved.
high (Asipu and Jaffray 2010; Ballantyne et al.
1985; Brothers et al. 1987).
Case Example
Perforation Patient is a 16-year-old male with past medical his-

tory significant for developmental delay, seizure dis-
If volvulus is present long enough to compromise order, spastic hemiplegia, and Angelman syndrome.
blood supply to the colon, the presenting symp- He was delivered at 35 weeks as a result of preterm
tom may be perforation. Other processes leading labor. He stooled within the first 24 h of life. He
to spontaneous perforation include long-standing began with evidence of constipation at 8 months of
and increasing dilation of the colon or acute intes- age. He was initially treated with lactulose and
tinal pseudo-obstruction (Ogilvie’s syndrome). enemas. His constipation progressed, and he required
Ogilvie’s syndrome can present in a postoperative multiple admissions for cleanouts. He was escalated
period or occur as a result of any other systemic to osmotic agents as well as stimulants. He continued
derangement including but not limited to to have encopresis requiring diapers. His mother
infection, pancreatitis, electrolyte abnormality, or used frequent “rescue medications,” including
respiratory process. In the instance of ongoing enemas and bisacodyl. Throughout this time, he
dilation, the most common site of perforation is underwent medical workup including complete
the cecum given its proximal position as well as blood count, complete metabolic panel, erythrocyte
thin wall. This is further supported by the law of sedimentation rate, C-reactive protein, thyroid-
Laplace (wall stress = [(transmural pressure) x stimulating hormone, free T4, tissue trans-
(radius)]/wall thickness). Should colonic perfora- glutaminase Ig A, and total IgAwhich were all within
tion occur, treatment is with segmental resection normal limits. The lumbar spine was imaged with
and primary anastomosis or end colostomy depen- magnetic resonance imaging and was without ana-
dent on peritoneal contamination and physiologic tomic abnormality. He underwent sitz marker test by
status of the patient (Szmulowicz and Hull 2011). ingesting 3 pills of 8 markers for a total of 24 markers.
Follow-up abdominal X-ray per protocol showed the
presence of the markers throughout the colon, con-
Summary sistent with slow transit constipation. A contrast
enema was obtained demonstrating marked dilated
The etiology of constipation is multifactorial in colon relative to a smaller rectosigmoid colon that
patients with CP including abnormalities in normalized with instillation of retrograde contrast.
neuromodulation, immobility, and diet. The diag- This rectosigmoid ratio less than one raised the ques-
nosis is made with history, physical exam, and tion of Hirschsprung’s disease. Therefore, the patient
confirmatory tests. Medical management should underwent anorectal manometry that showed normal
begin with medications which can be escalated. resting pressures of the anal sphincter and the pres-
If this is unsuccessful, retrograde or antegrade ence of rectoanal inhibitory reflex (RAIR), refuting
enemas can be initiated. the diagnosis of Hirschsprung’s disease. Colonic
Surgery is not the first line of treatment for manometry demonstrated the presence of multiple
constipation in this population but can be life- high amplitude propagated contractions (HAPCs)
from the hepatic flexure to the rectum with the placement–a prospective study. Radiology 203(3):
presence of a bowel movement after colonic stimu- 621–624
Chumpitazi CP et al (2016) Bristol stool form scale reli-
lation. Because of ongoing symptomatic constipa- ability and agreement decreases when determining
tion and encopresis, the patient began with a Rome III stool form designations. Neurogastroenterol
retrograde enema program after an antegrade Motil 28(3):443–448
cleanout. This was successful at keeping the patient Cooney DR, Cooney NL (2011) Massive acute colonic
pseudo-obstruction successfully managed with conser-
clean. Therefore, he underwent placement of a vative therapy in a patient with cerebral palsy. Int J
cecostomy tube. He concurrently had placement of Emerg Med 4:15
a gastrostomy due to ongoing malnutrition and dehy- Del Giudice E et al (1999) Gastrointestinal manifestations
dration. He began antegrade flushes with 20 ml/kg of in children with cerebral palsy. Brain and Development
21(5):307–311
saline mixed with glycerin. This was sufficient to Elawad MA, Sullivan PB (2001) Management of consti-
produce daily or every-other-day bowel movements. pation in children with disabilities. Dev Med Child
His quality of life greatly increased for 4 years. At Neurol 43(12):829–832
this time, the flush was no longer sufficient to pro- Erkin G et al (2010) Feeding and gastrointestinal problems
in children with cerebral palsy. Int J Rehabil Res
duce evacuative bowel movements, and he again 33(3):218–224
began with constipation and encopresis. An ante- Fischer M et al (1985) The effects of dietary fibre in a liquid
grade cleanout was performed through the diet on bowel function of mentally retarded individuals.
gastrostomy using MiraLAX and Dulcolax. Castile J Ment Defic Res 29(Pt 4):373–381
Joensson IM et al (2008) Transabdominal ultrasound of
soap was added to his flush as a stimulant laxative. rectum as a diagnostic tool in childhood constipation.
This was unsuccessful. Nightly Senokot was added J Urol 179(5):1997–2002
via gastrostomy with reduction but not elimination in Lee EK et al (2013) A case of cecal volvulus presenting
soiling. A second colonic manometry was performed with chronic constipation in lissencephaly. Pediatr
Gastroenterol Hepatol Nutr 16(2):131–134
which demonstrated the absence of HAPCs at any of Malone PS, Ransley PG, Kiely EM (1990) Preliminary
the channels and presence of low amplitude propa- report: the antegrade continence enema. Lancet
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contrast enema was performed which demonstrated Marciniak CM et al (2015) Cross-sectional study of bowel
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Marschall HU, Bartels F (1998) Life-threatening compli-
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Dis Child 95(11):867–870 Mosquera RA, McDonald M, Samuels C (2014) Aspira-
Ballantyne GH et al (1985) Volvulus of the colon. tion pneumonitis caused by polyethylene glycol-
Incidence and mortality. Ann Surg 202(1):83–92 electrolyte solution treated with conservative manage-
Bonilla SF et al (2013) Management of pediatric patients ment. Case Rep Pediatr 2014:872634
with refractory constipation who fail cecostomy. Mousa HM et al (2006) Cecostomy in children with defe-
J Pediatr Surg 48(9):1931–1935 cation disorders. Dig Dis Sci 51(1):154–160
Brothers TE, Strodel WE, Eckhauser FE (1987) Mugie SM et al (2012) Ten-year experience using ante-
Endoscopy in colonic volvulus. Ann Surg 206(1):1–4 grade enemas in children. J Pediatr 161(4):700–704
Candy D, Belsey J (2009) Macrogol (polyethylene glycol) Nava E, Heininger U, Weber P (2014) Perianal streptococ-
laxatives in children with functional constipation and cal dermatitis is not a major cause of constipation in
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94(2):156–160 226(5):299–300
Cascio S et al (2004) MACE or caecostomy button for Nicholls RJ, Kamm MA (1988) Proctocolectomy with
idiopathic constipation in children: a comparison of restorative ileoanal reservoir for severe idiopathic con-
complications and outcomes. Pediatr Surg Int 20 stipation. Report of two cases. Dis Colon Rectum
(7):484–487 31(12):968–969
Chait PG et al (1997) Fecal incontinence in children: Nurko S et al (2008) PEG3350 in the treatment of
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Reid JR et al (2000) The barium enema in constipation: tional constipation in infants and children: evidence-based
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Part XI
Ear, Nose, and Throat
Medical Management of Sialorrhea
in the Child with Cerebral Palsy 53
Jeremiah Sabado and Laura Owens
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 784
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 784
Physiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 784
Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 785
Clinical Assessment of Drooling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 786
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 787
Non-pharmacologic Management of Drooling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 787
Pharmacologic Interventions for Drooling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 789
Botulinum Toxin Injections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 791
Outcomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 791
Technique . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 792
Adverse Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 795
Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 795
Future Directions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 795
Cross-Reference . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 796
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 796
Abstract unintentional loss of saliva from the mouth.

Drooling is defined as the inability to control This distressing condition chronically afflicts
and swallow oral secretions resulting in many patients with cerebral palsy and has
numerous deleterious effects such as skin
irritation, perioral infection, aspiration pneu-
J. Sabado (*) monia, soiled clothing, assistive equipment
Division of Pediatric Radiology, Department of Medical
Imaging, Nemours/Alfred I. duPont Hospital for Children, damage, increased caregiver burden, lowered
Wilmington, DE, USA self-esteem, social isolation, and an overall
e-mail: Jeremiah.Sabado@nemours.org lower quality of life. Clinical assessment and
L. Owens quantification of drooling are important for
Nemours/AI duPont Hospital for Children, Wilmington, planning and monitoring the effectiveness of
DE, USA interventions. Common assessment scales
Thomas Jefferson University, Philadelphia, PA, USA include the Drooling Quotient, the Drooling
e-mail: laowens@nemours.org

https://doi.org/10.1007/978-3-319-74558-9_61
784 J. Sabado and L. Owens
Severity and Frequency Scale, and the be problematic for multiple reasons. Excessive
Drooling Impact Scale. Treatment may initially anterior salivary leakage can lead to irritated facial
involve non-pharmacologic, noninvasive or neck skin, unpleasant odors, perioral infection,
methods such as behavioral modifications hygiene issues, or even dehydration (Lew 1991).
and oral-motor exercises. Medical therapy Drooling may also damage clothes or equipment
typically includes anticholinergic medica- (including communication devices and other
tions, such as glycopyrrolate and scopolamine electronics) and can cause embarrassment and
patches. When conservative therapies are reduced self-esteem in children and adolescents
insufficient, direct injection of botulinum with CP, resulting in social isolation (Blasco
toxin into the salivary glands is frequently and Allaire 1992). Posterior drooling due to
performed. In patients with more severe dysphagia and poor oral-motor control places
drooling that is inadequately managed with individuals at risk for coughing, gagging, and
other therapies or in patients who desire more vomiting which may lead to aspiration pneumonia
permanent solutions, a variety of surgical and other respiratory complications (Jongerius
options are available. et al. 2003). Patients, families, and clinicians
must work together to assess the severity of
Keywords drooling, along with its risks and burdens, and
Cerebral palsy · Drooling · Sialorrhea · decide on appropriate treatment actions (Walshe
Salivary glands · Botulinum toxin et al. 2010).
Introduction Natural History
Cerebral palsy (CP) refers to a group of non- Drooling is normal in infants and young toddlers,
progressive neurologic disorders of movement up to 2–3 years of age, and salivary “continence” is
and posture due to disturbances in the developing reached with development of neurological control
fetal or infant brain (Rosenbaum et al. 2007). CP is of the oral and bulbar musculature. Continued
one of the most common neurodevelopmental dis- drooling after the age of 4 years is considered to
abilities, with a prevalence of approximately 1.5 be abnormal. Sialorrhea may be acute, related to
per 1000 live births (Paneth et al. 2006). Motor inflammation or infection in the oral cavity, or may
function and control are impaired to varying be more chronic, seen in patients with neurologic
degrees in these children, from those with the abil- dysfunction, oromotor issues, or as a medication
ity to walk and live independently to those who side effect. Chronic drooling occurs in approxi-
remain dependent for physical care throughout mately 0.6% of normally developing children.
their lives. In children with more involved motor However, the incidence is reported to be anywhere
disability, there is an increased incidence of addi- from 10% to 53% of the cerebral palsy population,
tional medical comorbidities, with up to 50% of with a higher prevalence in spastic quadriplegic
children with CP noted to have cognitive impair- cerebral palsy (Fairhurst and Cockerill 2011).
ment, seizures, sensory disturbances (vision, hear- A 2010 study in Northern Ireland reported
ing, etc.), or oromotor dysfunction including an estimated 22% of the 1357 CP patients in
drooling (Reid et al. 2005). the surveyed cohort with drooling (Parkes
Drooling, or sialorrhea, is defined as the et al. 2010).
inability to control and swallow oral secretions,
resulting in uncontrolled spillage from the
oral cavity (Brodsky 1993). Anterior drooling Physiology
refers to spillage of excess saliva beyond the lip.
Posterior drooling occurs when saliva spills pos- Saliva is a complex biofluid containing important
teriorly through the faucial isthmus. Drooling may proteins, digestive enzymes, immunoglobulins,
53 Medical Management of Sialorrhea in the Child with Cerebral Palsy 785
lysosomes, electrolytes, and microorganisms, the smallest, lying in the anterior floor of the
which have many important functions including mouth, and producing a small amount of thick
maintenance of oral health and early digestion mucinous saliva that coats the teeth (Fairhurst
of nutrients (Bavikatte et al. 2012). Saliva keeps and Cockerill 2011; Lakraj et al. 2013).
the oral mucosa lubricated and facilitates food A complex interplay of signals, including
bolus formation and clearance from the oral cav- gustatory, olfactory, temperature, mechanical,
ity. It supports wound healing and helps guard and tactile stimuli, can evoke the secretion of
against ulceration, infections (such as Candida), saliva from the major and minor salivary glands.
and tooth decay. The presence of calcium and Sensory stimuli cause the initiation of afferent
phosphate are additionally important for mainte- signals, which travel to the salivary nuclei in
nance of tooth mineralization (Proctor 2016; the medulla oblongata (Proctor 2016). As part
Bavikatte et al. 2012). Bicarbonate content buffers of the salivary reflex, efferent signals then stimu-
the saliva, which creates the environment neces- late the salivary glands via the autonomic nervous
sary for breakdown of dental plaques (Bavikatte system (both sympathetic and parasympathetic).
et al. 2012). Parasympathetic stimuli have been found to
Normal salivary production in teenagers and increase the volume and rate of salivary secretion,
adults is approximately 1–1.5 l of saliva per day. whereas sympathetic input increases protein-rich
Younger children average 750–900 mL of saliva secretion, stimulates muscular ductal contraction,
per day. Saliva is produced in three pairs of sali- and acts on the blood vessels to augment
vary glands: the submandibular, sublingual, blood supply to the gland (Bavikatte et al. 2012).
and parotid. Additionally, there are numerous The parotid gland receives innervation from the
minor salivary glands scattered throughout the glossopharyngeal nerve (CN IX), and the sub-
oral submucosa. The major salivary glands are mandibular and sublingual glands are innervated
composed of a tree-like ductal system, and at by the facial nerve (CN VII) (Lakraj et al. 2013).
the terminal branches, there are clusters of Higher level central neural activity also modulates
saliva-secreting epithelial cells referred to as salivation. Decreased salivary output has been
acini (Proctor 2016). Acinar cells produce one of observed during sleep, induced anesthesia, and
the two types of saliva; mucin-containing and under conditions of anxiety or fear. It has also
nonmucin-containing. Saliva with high mucinous been shown that simply thinking about food
content tends to have viscoelastic properties promotes salivation (Proctor 2016).
important for adhering to mucosal surfaces and
maintaining surface lubrication and hydration
(Proctor 2016). Saliva with low mucin content Pathophysiology
has a more watery consistency. The parotid
gland is the largest of the three and is located in Drooling is generally thought to be caused by
the preauricular area, along the posterior surface either overproduction of saliva (hypersalivation)
of the mandible. They are responsible for produc- or by neuromuscular inability to adequately man-
ing ~20% of salivary volume and secrete the age the oral secretions. There is a controversy
watery, low mucin saliva important for chewing regarding which of these is the primary etiology
and swallowing. The parotids are primarily of drooling in children with CP. Limited data
responsible for the dramatic increase in salivary exists regarding the exact volumes of saliva pro-
output that occurs during the stimulated state. duced by both typically developing children
The submandibular glands are the second largest, and those with cerebral palsy due to difficulties
located in the submandibular triangle. These with precise collection and measurement.
glands produce approximately 65–70% of the Nevertheless, available studies have not found a
total production, with a mixture of mucinous and significantly increased volume of production in
watery saliva that bathes the oral cavity in a children with CP (Senner et al. 2004). Senner
non-stimulated state. The sublingual glands are et al. conducted a study comparing children with
cerebral palsy who were classified as having the the devices (Sochaniwskyj 1982). Additional
presence or absence of drooling. The study looked approaches have included measuring via absor-
at 14 age- and gender-matched pairs, ages 7–18, bent cotton dental rolls inserted into the oral
comparing swallowing and saliva production cavity or by weight of bibs used (Reid et al.
in the drooling and non-drooling populations. 2010). Due to difficulties with collection, pro-
Results found no correlation between measured viders and researchers more commonly use obser-
saliva volume and amount of drooling. vational scales.
Interestingly, GMFCS level was not strongly cor- The Drooling Quotient (DQ) is a common
related with drooling; however, dysarthria and tool cited in intervention studies to help quantify
disordered swallowing were positively correlated drooling using observation. It was initially pro-
with increased drooling. Research has also noted posed by Rapp in the 1980s and subsequently
that children with CP tend to have decreased revised (van Hulst et al. 2012). The DQ requires
oromotor strength and coordination, leading to observation of a subject over two 10-min sessions
decreased bolus formation and management in separated by 1 h. During the observation time,
swallowing and reduced lip closure (Lespargot the presence or absence of saliva on the lips or
et al. 1993). In addition, many patients with CP chin is recorded every 15 s. These observations
have poor head and neck control resulting in a must be completed, while the subject is awake
forward leaning posture and may also have and alert. In addition, one session should be com-
decreased oromotor and facial sensation (Nunn pleted, while the subject is at rest, and the second
2000). These findings suggest that drooling in observation is completed during a focused task.
CP is related to postural, oromotor, and The mean of the observations is plotted on a
swallowing dysfunction and not excessive sali- numeric scale. Additional studies have looked at
vary production (Senner et al. 2004). modifications to the DQ, including shortening to
5-min observation periods, which was shown to
be equivalent in reliability (van Hulst et al. 2012).
Clinical Assessment of Drooling Due to the length of time needed for observation,
this study is difficult to use in a fast-paced practice
In order to assess the burden on patients and setting but still maintains use as a valid and reli-
families, as well as, to study possible management able option for studies as a semiquantitative obser-
options, it is helpful to be able to quantify vational method (Rashnoo and Daniel 2015).
drooling to monitor and assess an intervention’s The Drooling Severity and Frequency Scale
effectiveness. Quantification of drooling has been (DSFS) by Thomas-Stonell was described in
difficult to assess in an easy manner. Measurement 1988 and has been used to measure the frequency
tools have been grouped into three main catego- and severity of drooling, forming the basis of
ries: (1) basic clinical observation (i.e., wet some variations on this type of scale. It is com-
bibs per day), (2) more in-depth clinical quantifi- prised of two sections, a 4-point scale describing
cation using severity and frequency scales, frequency of drooling (1 = never, 4 = constantly
and (3) volumetric measurement using physical drools) and a secondary 5-point scale describing
quantification of saliva (Blasco 2002). Studies the severity (1 = dry, 5 = profuse [hands, objects,
have used radioisotopes to quantify volume; clothes wet]). When compared to the DQ,
however, this is a cumbersome and inefficient the DSFS showed a strong association between
technique for the average patient and clinic the subjective and objective measurements
(Ekedahl and Hallén 1973). Saliva collection (Rashnoo and Daniel 2015).
methods and devices have also been studied In addition to severity and frequency, measur-
using cups or suction bags. These methods were ing the impact on patient and family is also impor-
problematic due to leakages and tolerance of tant for quantifying drooling severity and its
response to treatment. The Drooling Impact Scale “bad” days may be sufficient to track clinical
was formulated by the Saliva Control Clinic at the outcomes in the office.
Royal Children’s Hospital in Melbourne,
Australia. This scale is composed of ten questions,
each scaled from 1 to 10, inquiring about fre- Treatment
quency, severity, and medical/social issues related
to drooling over the course of the prior week. Conservative treatment options can be catego-
The measure assesses both the amount of drooling rized into non-pharmacologic therapy such as
but also adds components assessing patient and behavioral modification and physical/oromotor
caregiver burden. In addition, it allows for valid therapy and pharmacologic treatments such
and reliable measurement of change in these areas as systemic anticholinergic medications. When
following intervention (Reid et al. 2010). conservative treatment is ineffective or poorly
Other scales have been used, including a visual tolerated, more invasive options may be
analogue scale, the Drooling Scale (Mier et al. considered, including botulinum toxin (BoNT)
2000), and the Teacher Drool Scale and Behavior injections or surgery. Other minimally invasive
and Medical Rating Scale (Camp-Bruno et al. therapies such as image-guided chemical ablation
1989; Walshe et al. 2010). with ethanol have shown promise in animal
In addition to quantification of drooling to studies, but data in humans is still very limited.
assess severity and measure treatment outcomes,
additional history should be elicited. While these
scales provide measurement options for anterior Non-pharmacologic Management
drooling, careful attention should be paid to of Drooling
signs of posterior salivary loss, as well. Clini-
cians should ask about signs of chronic aspira- The presence of drooling in children with CP may
tion, including coughing or choking on saliva influence their daily care and needs. Patients
and any history of recurrent chest infections (Lit- with CP often have other medical comorbidities
tle et al. 2009). Patients should also be assessed and require medications for management, all of
for the presence and adequate control of gastro- which may have varied side effects. As such, the
esophageal reflux (GERD). If not well con- use of non-pharmacologic options is of interest to
trolled, reflux may cause hypersalivation, which patients, families, and clinicians to prevent the
can compound drooling related to oromotor dys- need for additional prescription agents. A review
function. Attention should also be paid to the of treatments for drooling by the Cochrane
patient’s current medication list to help identify Collaboration in 2012 did not find any random-
medications which may exacerbate saliva pro- ized controlled or controlled clinical trials regard-
duction. Common medications include those ing therapies, behavioral interventions, devices,
with cholinergic effects, such as anticonvulsants or other non-pharmacologic treatments (Walshe
(clonazepam, clobazam, etc.) (Fairhurst and et al. 2010). Many studies involving these options
Cockerill 2011). Additional assessment should are drawn from case reports or small sample sizes.
include discussion with the family regarding Despite the lack of robust evidence, these options
their goals with drooling management. The use are generally low risk, and many families choose
of any particular measurement tool should align to optimize the use or trials of these interventions
with the clinician and family goals. Unless the prior to or in conjunction with additional medica-
patient is in a clinical trial for an intervention, use tion or surgical options.
of simple bib counts per day, improvement in Patients with sialorrhea may benefit from
skin or respiratory status, or patient/family sub- absorbent bibs or bandanas to catch excess saliva
jective report of improvement over “good” and and prevent the need for clothing changes or
staining. In addition, those that are able to engage therapies focused on the internalization and self-
in their own care can consider the use of terrycloth monitoring and response initiation for individuals
sports wristbands or carrying a cloth to wipe with higher cognitive function. Seventeen articles
themselves. Additionally, deterrence of mouthing from 1970 through 2005 were reviewed, with all
hands or objects through reminders, distractions, noting small study populations of 2–20 patients,
or positioning can prevent stimulation of excess and all except one showed positive improvements
saliva production. Various oral appliances have in drooling, with those most successful tending
also been developed with the aim of improving to have higher cognitive function and more
oral-motor function. Palatal training devices, sim- mild drooling. The studies were limited by small
ilar to orthodontic appliances, can be helpful in population numbers and design and had the
improving lip, tongue, and palate movement to additional limitation of limited follow-up of
improve posterior movement of saliva. These outcomes after study interventions were com-
devices can be helpful for patients with adult pleted or discontinued (van der Burg et al. 2007).
dentition and adequate oral-motor control, with Oral-motor exercises (OME) have also been
contraindications for patients with epilepsy or at utilized to help reduce drooling. As many patients
risk for aspiration or airway blockage with with CP have decreased swallowing frequency
the device (Fairhurst and Cockerill 2011). and diminished oromotor strength and coordina-
Published studies on these devices have remained tion, OME interventions posit that an improve-
limited, generally case studies, retrospective ment in these areas will help with drooling as
group studies, or small controlled groups well as other oral functions. Patients must be
(Johnson et al. 2004). able to participate in the exercises and have inter-
Proper seating and positioning are also of est in the activities for any success. There are three
significant importance. Assessment of seating to main categories of OME: active exercise, passive
provide optimal positioning should be completed exercise, and sensory applications. Active exer-
and monitored. Children with sialorrhea often cises require the patient to work through activities
benefit from upright or slightly reclined seating, of range of motion (ROM), strengthening, and
and those with low truncal tone may require addi- stretching to improve strength, flexibility, and
tional head and neck support, such as a Hensinger endurance to reduce tone and improve oral-
collar, to prevent excess forward posturing. motor control. Passive exercise can include
Behavioral interventions take various forms massage, vibration, or other forms of stimulation.
for drooling reduction, with most focused on These may be helpful in improving sensory input
signals and reminders for swallowing or and reducing negative oral reflexes or over-
secretion management (Koheil et al. 1987). sensitization. Sensory applications can include
Intervention types have been broken down the use of heat, cold, or electrical stimulation.
into four major areas by van der Berg et al.: These techniques are used to encourage initiation
(1) instruction, prompting, and positive reinforce- of swallowing or to strengthen the swallowing
ment; (2) negative social reinforcement and musculature. Arvedson et al. completed an
decelerative procedures; (3) cueing techniques; evidence-based systematic review of oral-motor
and (4) self-management procedures (van der exercises in 2010. This review identified studies
Burg et al. 2008). Instruction and prompting inter- looking at the effects of OME as a treatment for
ventions include reminders for swallowing and oromotor dysfunction as well as treatment out-
wiping; negative or decelerative interventions comes on nutrition, pulmonary health, and
relate to negative comments or reinforcement for drooling. Of the literature reviewed, four studies
drooling with positive rewards for lack thereof. included data on the effect of OME on drooling
Cuing interventions involve the use of devices management in children with CP. All studies were
with sensory reminders for self-monitoring, such small, with 3 studies comprised of 2 patients
as auditory, tactile, or electrical timers or inputs to and the fourth with a study population of 20.
cue swallowing or wiping. Self-management The interventions were varied, with three of four
using passive or sensory techniques. The literature benztropine, benzhexol hydrochloride (tri-
currently yields limited study data; there has not hexyphenidyl), and atropine. Their original uses
been consensus on the effectiveness of OME as a vary, from treatments for motion sickness, move-
treatment. As it remains a noninvasive and safe ment disorders, or gut “spasms,” but have the
option, it may be appropriate as part of a therapy commonality of a reduction of oral and respiratory
and drooling management program, with more secretions. These medications vary in route, some
definitive research needed. given orally/enterally, sublingually, intrave-
Acupuncture of the tongue has been trialed nously, intramuscularly, or via inhalation or der-
as an intervention for drooling. A study of mal patches. The anticholinergic effects are not
ten patients completed by Wong et al. in 2001 specifically limited to the salivary glands, and,
described daily acupuncture to five points on unfortunately, this often results in other undesir-
the tongue for a 30-day course. Both the drooling able systemic effects. Common side effects noted
severity and frequency improved on all outcome with anticholinergic medications include thick-
measures during treatments and at the ened secretions, dry mouth, dehydration, urinary
6-month follow-up mark (Wong et al. 2001; retention, urinary tract infections, constipation,
Gold et al. 2009). facial flushing, rash, fever, dizziness, headache,
dilated pupils, blurred vision, and behavioral
changes (Mier et al. 2000).
Pharmacologic Interventions Transdermal hyoscine, or scopolamine
for Drooling patches, has been useful in the treatment of
sialorrhea. The medication is contained in a
While many patients maintain a good quality of small time-release transdermal patch, which is
life with non-pharmacologic interventions for worn on the skin behind the ear and changed
drooling, there are those that benefit from the every 2–3 days. Pupillary dilation and urinary
addition of medications. The non-medication retention are noted to be the most common side
interventions described focus on improving oral- effects of this medication, as well as some reports
motor control, swallowing, and prevention of of skin irritation at the patch site and excessive
related complications. Medications as a group oral or eye dryness (Lewis et al. 1994). There have
reduce the volume of saliva but do not have sig- been limited studies completed in children using
nificant bearing on the mechanical aspects of scopolamine, but the literature does note subjec-
saliva management. While there have been small tive and anecdotal improvements. A small pro-
trials of multiple medications, all pharmacologic spective, randomized double-blinded placebo
interventions are currently used as “off-label” for crossover study of adolescents and adults with
management of sialorrhea. As cited in a 2012 various developmental and medical issues and
Cochrane Review, there are not sufficient studies persistent drooling was completed in 2010.
of any interventions; however, there have been The study showed a majority of the 30 patients
small trials of several medications showing posi- in the trial had a subjective reduction in drooling
tive results (Walshe et al. 2010). while using the scopolamine patch, with 4 patients
Salivary gland secretion is stimulated by dropping out due to side effects (Mato et al. 2010).
the parasympathetic autonomic nervous system, Glycopyrrolate, an anticholinergic medication,
and acetylcholine is the key neurotransmitter has also shown effectiveness in reducing
involved. The majority of medications currently sialorrhea. Glycopyrrolate is structurally related
used for sialorrhea are anticholinergic agents, to atropine but has a longer duration of action,
which work to decrease salivary flow by their most often dosed three times per day for sialorrhea
inhibitory action on postsynaptic acetylcholine management. It is available in tablet, solution, and
receptors in salivary gland tissue (Oliveira et al. suspension formulations. Glycopyrrolate has a
2017). Commonly used options in this rapid-onset effect, within minutes of IV dosing
family include scopolamine, glycopyrrolate, and 15–30 min for oral. Glycopyrrolate reaches
peak effect within 1–4 h with an average duration but may also allow for better oral-motor control
of 6–8 h. Mier et al. completed a small placebo- due to decreased dystonic movements and may
controlled, double-blind crossover dose-ranging be a good option for patients with both dystonia
study published in 2000. The study group and sialorrhea.
included 39 children with CP and other Benztropine is another option in the anticho-
neurodevelopmental impairments who were linergic family for treatment of sialorrhea.
reported to have excessive drooling. The 4-month Limited study data is available, though in a small
study aimed to look at effectiveness and dosing, double-blind placebo-controlled study of
along with side effects, using a parent-reported 27 patients, most patients showed significant
9-point drooling scale. Nearly all children who reduction in drooling. Three patients discontinued
completed the study were able to tolerate the the study medication due to adverse effects, and
highest dosing of 3 mg per dose, for those over common anticholinergic side effects were
30 kg, and reported drooling improved incremen- reported, including constipation, urinary reten-
tally with each dose increase. Adverse effects tion, dry mouth, and behavioral changes (Camp-
were increased with higher doses, with behavioral Bruno et al. 1989). Inhaled ipratropium bromine,
changes, constipation, and mouth dryness the a quaternary ammonium derivative of atropine
most commonly cited side effects. A total of with bronchodilator properties, has also been
eight children withdrew from the study due to used to reduce sialorrhea in patients with
issues with side effects. The study recommended Parkinson’s. To date, there have been no trials
starting doses of 0.04 mg per kilogram per specific to its anti-sialorrheic effects completed
dose, with weekly increases up to 0.1 mg/kg in children (Fairhurst and Cockerill 2011).
(maximum of 3 mg per dose). The study authors Sublingual use of ophthalmic atropine drops
reported that glycopyrrolate can be very effective has recently been looked at as an option to help
for sialorrhea; however, the use may be limited control drooling in children with neurodeve-
by side effects in some patients (Mier et al. 2000). lopmental disabilities. In addition to the ophthal-
Overall, nearly half of patients reported side mologic uses, this formulation has also been used
effects (behavior changes, dry mouth, constipa- as an adjunct for controlling secretions at the
tion, urinary retention, flushing), though not all time of endotracheal intubation and has also
required stoppage of the medication. been used to manage sialorrhea associated with
Trihexyphenidyl is a medication that is more clozapine use and as part of palliative care
commonly used for management of dystonia; (Rapoport 2010). Two small studies have been
however, as an anticholinergic it also has a role completed, looking at a total of 51 children with
in reduction of drooling. The majority of studies drooling and various disabilities, with the Dias
of trihexyphenidyl have looked at its use in dys- study focused on children with CP. Dosing was
tonia, but the study by Carranza-del Rio et al. generally standard across ages and weights, due
reviewed the use of this medication for both con- to the available formulation of the ophthalmic
ditions. Trihexyphenidyl was tolerated similarly solution, with 1–2 drops given one to three
to other anticholinergic medications, with approx- times per day. Side effects included dry mouth,
imately two-thirds noting side effects and 8% behavioral changes, and flushing but was overall
discontinuing treatment due to adverse effects well tolerated (Norderyd et al. 2017; Dias et al.
during the study noting anticholinergic side 2017). This appears to be a promising option, as
effects. In assessment of drooling, 60% of patients it should have less systemic absorption than
reported improvement along with a similar num- enteral options and therefore fewer side effects
ber noting improvement in dystonia (Carranza-del would be expected. Additional research regard-
Rio et al. 2011). Improvement in drooling with ing dosing as well as the possibility of a specific
trihexyphenidyl likely stems from the anticholin- sublingual dosing format may be helpful in the
ergic properties resulting in saliva production future.
Limited investigation into other medications is Ach neurotransmission (Oliveira et al. 2017).
available at this time. Small case studies exist, For normal neurotransmission, synaptic vesicles
including a case series of two patients started on containing Ach fuse with the presynaptic mem-
modafinil, an atypical dopamine reuptake inhibi- brane of the nerve cell and then subsequently
tor used for wakefulness and spasticity manage- release Ach into the synapse. Botulinum toxin
ment. Providers noted significantly decreased type A (BoNT-A) disrupts the release of Ach by
drooling following initiation of the medication binding to a cytoplasmic protein, SNAP 25, which
(Hurst and Cedrone 2006). In addition, manage- is involved in the fusion of synaptic vesicles to the
ment of gastroesophageal reflux (GERD) with presynaptic membrane. Botulinum toxin type B
medications has been theorized to help prevent (BoNT-B) cleaves VAMP/synaptobrevin, another
increased salivation due to increased esophageal protein required for synaptic vesicle fusion
acidity; however, small studies did not show (Oliveira et al. 2017). When administered locally
decreased salivation with improved esophageal through needle injection, the toxin diffuses
pH (Heine et al. 1996). Given the current data throughout the glandular tissue. Acetylcholine
limitations, there is no consensus on efficacy release is subsequently disrupted, resulting in
and usage recommendations in children with chemical denervation of the salivary gland and
CP. Several medications have had positive out- diminished salivary secretion.
comes in small studies and case reports; however, In 1989, the FDA classified botulinum toxin as
additional research is needed to allow for compar- safe and effective for use in movement disorders
ison and meta-analysis (Jongerius et al. 2003). (Oliveira et al. 2017). Botulinum toxin types A
There have been no significant head-to-head and B have both been approved for medical use,
studies of most medications versus other pharma- and both are now used to treat drooling and
cologic options or versus non-pharmacologic hypersalivation disorders in adults and children.
interventions. Most literature on individual medi- Local administration of BoNT directly into
cations does show significant improvements in the salivary glands has the potential benefit of
drooling in 50–80% in study patients, and while decreasing salivary output without the side effects
side effects are common, most children tolerated of systemic medications. Use of botulinum toxin
the medications (Camp-Bruno et al. 1989). There for the treatment of sialorrhea was first reported in
have been general dosage ranges reported for 1997, in which toxin was directly injected into
most medication options; however, all require the parotid glands of patients with amyotrophic
titration based on individual optimization. lateral sclerosis (Bushara 1997). A few years later
in 2001, Jongerius et al. reported the first case
series of the successful use of botulinum toxin
Botulinum Toxin Injections type A for the treatment of drooling in children
with cerebral palsy (2001). Since the publication
Anticholinergic medications such as atropine, of these case series, there have been numerous
benztropine, and glycopyrrolate are useful to other reports on the efficacy and safety of botuli-
help decrease salivary flow due to their inhibitory num toxin injection for the treatment of drooling
action on postsynaptic acetylcholine receptors in both children and adults with a variety of
in salivary gland tissues (Oliveira et al. 2017). neurological conditions including CP.
Certain neurotoxins are also known to interfere
with acetylcholine (Ach) neurotransmission and
thereby inhibit parasympathetic stimulation of Outcomes
the salivary glands. Clostridium botulinum pro-
duces a variety of serotype toxins (A, B, C, D, Numerous publications have reported on the use
E, F, and G), which each differ in mechanism of botulinum toxin (BoNT) in adults and children,
of action, but all play a role in blockade of which include prospective controlled clinical
trials and randomized clinical trials. Several com- differences in outcome based on the use of
prehensive reviews have compiled studies that BoNT-A versus BoNT-B, preparation techniques,
specifically looked at the population of children dosage calculations, or choice of glands to inject
with CP. (Walshe et al. 2010).
Rodwell’s systematic review in 2012 was one Reviews that combine studies from both
such study, which investigated the use of BoNT adults and children were able to make conclusions
for drooling in children with CP and neurodeve- based on higher level of evidence. Lakraj’s review
lopmental disability. They identified 16 studies found that BoNT-A (level B evidence) and BoNT-
meeting inclusion criteria, which included 5 ran- B (level A evidence) were the most effective
domized controlled trials and 11 prospective stud- methods for treating sialorrhea (2013). Both
ies. There were 315 unique patients combined toxins were found to have similar efficacy and
across all studies. Lack of standardized protocol adverse events (Lakraj et al. 2013). Reddihough’s
made it difficult to formulate generalizable con- consensus statement and review found beneficial
clusions about technique. Of note 15 of 16 studies outcomes with the use of BoNT injections in all
used BoNT-A, 13 of 16 employed ultrasound for 15 studies included in their review (2010).
guidance, 7 of 16 injected both parotid and sub-
mandibular glands, and 15 of 16 injected bilateral
glands. Similar to other review papers, there was Technique
also significant heterogeneity in choice of out-
come measures. Objective outcome measures Most studies and reports share a similar basic
included salivary weight (two studies), number strategy for the application of botulinum toxin
of bibs used (two studies), and drooling quotient in the treatment of drooling, usually involving
(three studies). Subjective measures included the injection of low doses of botulinum toxin into
DFSS (five studies), drooling impact scale (one two or more salivary glands. There is substantial
study), and patient- or teacher-rated quality of life variability in the specific institutional protocols
(two studies). Overall, Rodwell concludes that and techniques, and the available data is insuffi-
BoNT results in moderate to strong reduction in cient to determine superiority of any one method
drooling. Effects lasted for at least 12 weeks in all or technique. Dosing volume, dilution method,
studies, except one where very low doses were number of glands injected, number of injection
used (5 units/gland). Adverse events ranged from sites per gland, dose distribution between the
2% to 41% and included coughing, chest infec- glands, choice of toxin (type A or B), timing of
tion, xerostomia, salivary thickening, severe dys- repeat injections, use of ultrasound for needle
phagia requiring hospitalization, and deterioration guidance versus anatomic landmarks, and level
in feeding and swallowing (Rodwell et al. 2012). of sedation are all factors that vary in published
Another article by Porte in 2014 also specifi- reports.
cally reviewed studies on the use of BoNT for As an example, we will review the protocol
sialorrhea in children with cerebral palsy. for BoNT injections at our institution, which was
Porte concluded that there was an overall positive developed using many of the most commonly
effect with the use of BoNT injections, but there reported strategies. Most of our patients are chil-
is a shortage of studies and insufficient evidence dren with cerebral palsy, and ages generally
to validate its efficacy (2014). A Cochrane Data- range from 4 years to adulthood. Older and
base review came to a similar conclusion: more cooperative patients may tolerate the injec-
although the available studies seem to consis- tions without any sedation. However, a majority
tently report improvement in drooling post- will receive some form of anesthetic, most fre-
intervention, there is insufficient evidence to sup- quently moderate sedation using nitrous oxide.
port the use of BoNT injections over other inter- Depending on patient risk factors, sedation may
ventions (Walshe et al. 2010). Additionally, they be performed by our dedicated sedation team
were unable to identify any significant providers (which includes physicians and
advanced practice nurses) or by anesthesiolo- repeat injections as needed, though generally no

gists. Patients are prepped using aseptic tech- sooner than 3 months.
nique. A weight-based dose is predetermined: Reviews by Reddihough, Rodwell, and
typically 1–2 BoNT type A units per kilogram. Walshe found that most investigators demon-
We usually do not exceed a dose above 2 units/kg strated beneficial outcomes from intraglandular
except occasionally in patients who have had injection of either both submandibular glands,
limited or no response to previous injections. both parotid glands, or all four glands (2010,
BoNT type A is reconstituted from 100 unit 2012, 2012). The dose was often divided equally
vials using either 1 or 2 mL of saline. The dose between all injected glands, though some investi-
is then equally divided into four 1 mL syringes gators will administer a higher relative dose to
while taking care to evacuate air bubbles from either the parotids or the submandibular glands
the syringe and needle. The target glands are (Reddihough et al. 2010; Rodwell et al. 2012;
localized with ultrasound. We typically use a Walshe et al. 2010). Sublingual glands are gener-
high-frequency 15 mHz linear array transducer, ally not injected, likely due to the difficulty of
though larger patients may require the use of a localizing these glands even with the use of ultra-
9 mHz linear probe. While directly visualizing sound. In children, Botox ® (botulinum toxin A)
the needle with ultrasound in a longitudinal was administered at a median dose of 2 units/kg
plane, a 27-gauge needle is advanced into an (Rodwell et al. 2012). On the high end, a report by
avascular area of the target salivary gland. Dopp- Khan et al. describes using a total dose of 5 units/
ler is used to confirm that there are no nearby kg of BoNT-A with no apparent increase in toxin-
blood vessels. BoNT is then injected into the related complications (2011).
gland, and ultrasound is used to confirm infiltra- There is some debate about whether or not
tion of the medication into the glandular paren- ultrasound is necessary for safe and effective
chyma. Figures 1 and 2 provide examples of the injections. Ultrasound guidance allows definitive
ultrasound appearance of the salivary glands localization of the target gland, resulting in greater
prior to and after injection. Typically, we inject certainty that toxin is being delivered into
both parotid and both submandibular glands in a the gland, rather than the adjacent muscle
single treatment episode. Patients may return for or neurovascular structures. This theoretically
Fig. 1 (a) Ultrasound depicts the relatively homogeneous subcutaneous tissues. (b) A 27-gauge needle (white
parotid gland tissue (black arrows), scanned using a arrows) has been advanced into an avascular area of the
15 mhz linear array probe. Depending on scan technique gland. BoNT solution has been injected and is seen infil-
and patient adiposity, salivary gland tissue may appear trating the substance of the gland (black arrows)
either hyper- or hypoechoic relative to the overlying
Fig. 2 (a) Ultrasound was used to guide a needle (white Doppler confirms the absence of major vascular structures
arrows) into an avascular area of the submandibular gland. near the needle tip. (c) BoNT solution has been injected and
(b) Larger blood vessels are commonly seen within or can be seen infiltrating gland tissue immediately around the
adjacent to the submandibular gland. In this case, color needle tip (black arrows)
increases the likelihood of successful treatment it is advisable to use ultrasound when the equip-
and lowers the risk of complications from blind ment and expertise are available.
or imprecise injections. For example, direct nee- Studies comparing botulinum toxin A (Botox)
dle visualization within the parotid gland could versus toxin B (Myobloc) for the treatment of
prevent inadvertent injection into the nearby drooling or hypersalivation in adults or children
masseter muscle, thereby preventing undesirable have generally shown similar efficacy and safety.
side effects such as dysphagia or chewing Therefore, there is no specific recommendation
difficulties. For similar reasons, the use of color for which agent to select. However, the prepon-
Doppler may decrease the risk of intravascular derance of data in children appears to involve type
injection. Ultrasound guidance was used in the A toxin, and both Porte and Rodwell reported that
majority of studies included in Porte’s and toxin A was used in the vast majority of studies
Rodwell’s reviews (2014, 2012). Reddihough’s included in their reviews of children with CP
consensus statement recommends using ultra- (2014, 2012). It is important to note that the
sound, particularly for injection of the subman- acquired resistance to botulinum toxin may
dibular glands, which are more difficult to localize occur due to the formation of specific antibodies,
anatomically (2010). Based on these publications, and this is usually recognized by lack of a
therapeutic response to treatment. In these cases, occur due to diffusion of toxin or inadvertent
switching to the other toxin type will often be injection of toxin into adjacent muscles
effective. (Reddihough et al. 2010). This is especially a
The effect of treatment with botulinum toxin is concern with parotid injections, where the mas-
temporary, lasting anywhere from 6 weeks to seter muscle’s proximity just beneath the gland
many months. Lakraj et al. found in their review makes it vulnerable to needle misplacement
that most studies reported 3-month duration of (Reddihough et al. 2010). Systemic botulism
effect, and one study reported up to a 6-month due to intravascular injection is extremely rare
benefit (2013). Patients who have a good clinical due to the low doses of toxin used. Close obser-
response to treatments will usually benefit from vation in the hours and days following injection
repeat and ongoing treatments. There is no will enable early recognition and management of
consensus or conclusive evidence regarding the these events and their potential consequences.
optimal timing of repeat injections. It has been Ultrasound may have a role in improving the
suggested that repeat injection intervals less than precision of botulinum toxin delivery into the
3 months apart may predispose to antibody target glands, thereby lowering the risk of
formation, which in turn can result in a diminished adverse events associated with accidental intra-
clinical response (Reddihough et al. 2010). vascular or intramuscular injections.
The manufacturer of Botox recommends a mini-
mum interval of 3 months between injections
(Reddihough et al. 2010). Thus, repeat injections Surgery
should be undertaken when symptoms return, but
it is prudent to wait at least 3 months between There are multiple surgical techniques designed
treatments. Time of year may also be important to to control or reduce salivary production. Although
consider, since good saliva control before winter more invasive, surgery has the potential
reduces the morbidity of the accompanying benefit of permanent improvement in drooling.
seasonal respiratory illnesses. Surgical interventions center on salivary gland
denervation, salivary duct relocation, salivary
duct ligation, or salivary gland resection (Walshe
Adverse Effects et al. 2010). Due to their large contribution to
salivary volume, most interventions are targeted
Botulinum toxin injections have been shown to toward either or both pairs of submandibular and
be safe by numerous studies, but there have been parotid glands. Combining techniques have
frequent reports of minor side effects and rare become common practice to improve efficacy
instances of serious adverse events. Common, while still preserving some of the benefits of sal-
though typically less serious, effects are often ivary production. The following chapter is
related to injection site trauma and include pain devoted to a detailed discussion of surgical treat-
or hematoma at the injection site, mild oral ment and outcomes.
bleeding, gland swelling, temporary swallowing
difficulties, and infection (Reddihough et al.
2010). Injury to the facial nerve is a hypothetical Future Directions
possibility; however, it has not been widely
reported to occur in practice. Transient effects For chronic and severe drooling, the available
related to the toxin may include dry mouth (too treatment options are sometimes less than ideal.
little saliva) and thickening of saliva, due to Medications may be insufficient to control severe
disproportionate blockade of the serous compo- symptoms or may cause unacceptable side effects.
nent of saliva and relative increase in the mucin- Surgery is often definitive, but it suffers from
ous component (Reddihough et al. 2010). occasionally serious complications. To better
Difficulties with chewing and swallowing may manage this potentially lifelong and burdensome
condition, effective, less invasive, and longer- offer the potential for long-term durable benefit,
acting therapies are needed. without the risks associated with surgical interven-
Botulinum toxin injections are effective and tion. A study by Burch et al. found that ethanol
low risk; however, based on current understand- injection into submandibular glands of rats induced
ing, the effects are generally temporary, and fibrosis and dramatic reduction in gland size within
patients should expect the need for repeat treat- just a few weeks of treatment (2017). Similarly,
ments. Recent studies have been seeking to better another study reported that ethanolamine injection
understand the long-term effects of botulinum into canine submandibular glands induced scarring
injections on the salivary glands, which could and fibrosis and was associated with a reduction in
help determine if there are more permanent bene- acinar cells (Abbas et al. 2013). Glandular fibrosis
fits for BoNT injections than originally thought. would be expected to have a more durable reduc-
A study by Cardona evaluated 22 patients who tion in salivary function compared with botulinum
had multiple BoNT injections (at least 3 treat- toxin injections, but long-term data to support that
ments) and compared them to 38 healthy control hypothesis is not yet available. There is one human
subjects. Ultrasound was used to measure salivary study on salivary gland ablation involving ethanol
gland dimensions and calculate surface area, as injection into the submandibular glands. In this
well as qualitatively describe the morphologic study, an improvement in drooling was noted in
changes in the glands. They found a significant 24 of 25 patients with one reported complication of
size reduction in all injected glands, especially temporary marginal mandibular nerve palsy
the submandibular glands. The authors also (Shiels 2012). To our knowledge, there are
noted changes in sonographic appearance of no other similar published studies in humans. Fur-
the treated glands, including increased ther research is needed to determine whether
echogenicity, more heterogeneous echotexture, these treatment options have a valuable role in the
and a more lobulated and irregular contour management of drooling.
(Cardona et al. 2015). Although the underlying
cause of these changes could be multifactorial,
it raises the possibility of treatment-induced
apoptosis or atrophy (Cardona et al. 2015). Cross-Reference
By extension, salivary gland atrophy might predict
long-term durable response to repeat BoNT injec- ▶ Surgical Options for Sialorrhea Management in
tions. Pathologic studies to help define the under- Children with Cerebral Palsy
lying reasons for decreased gland size are
necessary but lacking in humans. A study in rats
found that intraglandular BoNT injection resulted References
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Surgical Options for Sialorrhea
Management in Children 54
with Cerebral Palsy
Christopher Tsang, Steven Cook, and Udayan Shah
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 800
Noninvasive Therapies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 801
Pharmaceutical Therapies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 802
Botulinum Toxin Injections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 803
Surgical Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 804
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 808
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 808
Abstract
C. Tsang Sialorrhea is a condition that affects many chil-
Division of Pediatric Otolaryngology, Department of
Surgery, Nemours Alfred I. DuPont Hospital for Children,
dren with cerebral palsy. It can lead to a myriad
Wilmington, DE, USA of problems, ranging from irritation of the
e-mail: Christopher.Tsang@nemours.org peri-oral skin to recurrent aspiration causing
S. Cook respiratory compromise. There exist several
Division of Pediatric Otolaryngology, Department of medical and surgical options for the treatment
Surgery, Nemours Alfred I. DuPont Hospital for Children, of this condition. Behavioral and physical
Wilmington, DE, USA
therapy can help in milder cases, especially
Sidney Kimmel Medical College, Thomas Jefferson in children with better neurocognitive ability.
e-mail: scook@nemours.org
Botulinum toxin injections have been shown
to be helpful in decreasing salivary gland
U. Shah (*)
output. Surgical interventions include sali-
Surgery, Nemours Alfred I. DuPont Hospital for Children, vary duct diversion, salivary duct ligation,
Wilmington, DE, USA salivary gland removal, or a combination of
Department of Otolaryngology - Head and Neck Surgery the aforementioned procedures. The most re-
and Pediatrics, Wilmington, DE, USA fractory cases involving recurrent aspiration
Sidney Kimmel Medical College, Thomas Jefferson may necessitate a tracheostomy for pulmonary
University, Philadelphia, PA, USA hygiene, or a laryngotracheal separation, which
e-mail: Udayan.Shah@nemours.org

https://doi.org/10.1007/978-3-319-74558-9_63
800 C. Tsang et al.
physically separates the airway from the diges- content, whereas the parotid glands produce a
tive tract. No one treatment is guaranteed to more serous saliva that is rich in enzymes (e.g.,
work, and proper management requires tailor- amylase). The submandibular glands produce
ing the therapy to the individual child. approximately 70% of the daily amount of
saliva, with the parotid glands producing 25%,
Keywords and the sublingual and minor salivary glands
Sialorrhea · Salivary · Drooling · Aspiration making up the difference. However, during stim-
ulated salivary production (e.g., eating), the
parotid glands are responsible for the majority
Introduction of saliva production, with rates reaching as high
as 7 mL/min.
Drooling is part of most children’s physical devel- Sialorrhea is classified as either anterior or
opment. This behavior usually disappears posterior. Anterior sialorrhea is characterized by
between the ages of 12 and 18 months, when salivary spillage out of the oral cavity and onto
oral-motor and oral sensory skills improve. Per- the lips and chin. This can cause chronic skin
sistent sialorrhea after age 4 is usually considered irritation and perioral infections and can poten-
abnormal. In neurologically impaired children, tially damage medical equipment and communi-
such as those with cerebral palsy (CP), the prev- cation devices (e.g., external cardiopulmonary
alence of sialorrhea ranges from 22% to 78%. One monitors, portable mechanical ventilators, tablet
recent study utilizing an electronic questionnaire computers). This also has the potential effect of
sent to parents of children aged 7–14 years of age increasing social isolation, decreasing self-
with CP in Australia demonstrated that approxi- esteem, and increasing burden of care to the fam-
mately 40% of children with CP will demonstrate ily (Montgomery et al. 2016). Posterior sialorrhea
some degree of sialorrhea after age 4, with 15% is characterized by salivary spillage into the
classified as “severe” (Reid et al. 2012). hypopharynx and possibly into the larynx, caus-
Usually, sialorrhea is the result of a lack of ing symptoms such as coughing, gagging, and
coordination of the oral and oropharyngeal choking. This may also result in aspiration into
muscles that control the oral phase of swallow- the airway, which has the potential to cause life-
ing. This may be exacerbated by poor oral threatening lower respiratory tract infections, such
and/or oropharyngeal sensation, dysfunctional as pneumonia. While the management of aspira-
swallowing, poor head/neck posture, dental tion is outside the scope of this chapter, it is vitally
disease, maxillofacial dysmorphisms such as mal- important to assess whether a child has both
occlusion and macroglossia, gastroesophageal sialorrhea and aspiration, as management of one
reflux, and medication side effects (Daniel and of those conditions may not necessarily guarantee
Kanaan 2015). Children with CP typically exhibit control of the other.
some degree of motor impairment, although this There is currently no objective standard for
may range from mild (walking independently) to grading the severity of sialorrhea. There have
severe (wheelchair-bound). Children with poor been several attempts in recent years to objec-
motor function have been shown to have both tively measure the degree of sialorrhea, such as
increased prevalence and severity of sialorrhea collecting suctioned saliva, weighing bibs/cloth-
(Reid et al. 2012). ing, and even using radioactive isotopes, but these
The average adult produces 1–1.5 L of saliva methods have not proven to be accurate. There do
over a 24-h period (approximately 1 mL/min), exist several subjective rating scales to estimate
although there are, to date, no similar data for the frequency and severity of sialorrhea including
children (Montgomery et al. 2016). The subman- the Teacher’s drooling scale (TDS) and the
dibular and sublingual glands produce a thicker, drooling impact scale (Reid et al. 2010). These
more mucinous saliva with a higher glycoprotein are most often used in recent sialorrhea literature
54 Surgical Options for Sialorrhea Management in Children with Cerebral Palsy 801
History & physical
Is the child aspirating?
No Yes
Oro-motor training Tracheostomy*

Biofeedback Laryngotracheal separation
Tracheo-esophageal diversion
Systemic medications
Is the child drooling?
Botulinum toxin injections

Is the child aspirating?
Ductal relocation/ligation
Gland excision
Fig. 1 Proposed treatment algorithm for sialorrhea man- appropriate to choose any option based on the child’s
agement. Note that multiple treatment modalities may be individual needs and response to prior treatment. *Trache-
utilized for optimal control of sialorrhea, and if present, ostomy does not prevent aspiration, but can reduce the
aspiration. Furthermore, while the algorithm suggests a incidence of aspiration-related sequela through improve-
step-wise progression of management options, it is quite ment in pulmonary toilet
as clinical endpoints, given the aforementioned Noninvasive Therapies

difficulties in objectively measuring salivary pro-
duction, as well as taking into the account the The simplest way to manage sialorrhea is to
reality that sialorrhea is usually not a disorder of provide a means to remove the excess saliva.
hypersecretion. This includes bibs and, in the cases of chil-
Management of sialorrhea is best approach- dren who are more independent, absorbent wrist-
ed in a multifaceted manner and varies by the bands or handkerchiefs. For more severe cases
severity of the condition. Some children only of sialorrhea, there are specialized bibs that
require oral-motor/behavioral training, at times utilize sport-grade absorbent materials in
supplemented by a number of pharmaceutical age-appropriate sizes (i.e., not just infant). Simi-
agents. Several surgical options do exist and are larly, avoidance of foods or activities that may
usually reserved for refractory cases of sialorrhea increase salivary production (placing fingers in
that fail to be managed through medical means the mouth, sugary or sour snacks/drinks, etc.)
alone (Fig. 1). can provide small but measurable benefits.
802 C. Tsang et al.
Rehabilitation exercises and behavior therapy The flexibility in terms of dosage and frequency
can be useful in managing both anterior and is quite useful for titrating to effect in children
posterior sialorrhea, especially in children with and can be very helpful for controlling nighttime
milder forms of CP. Patients and caretakers can secretions (Garnock-Jones 2012). Side effects
be taught exercises that improve head and neck include xerostomia, blurred vision, behavioral
posture, which in turn will optimize positioning. changes, constipation and urinary retention, all
There are also oral-motor and oral-sensory exer- of which appear to increase in incidence and
cises that can improve the strength and proprio- severity with higher doses (Eiland 2012).
ception of the oral and facial musculature. These Several recent studies have validated the short-
may also improve other motor skills such as term efficacy of oral glycopyrrolate for man-
tongue mobility, lip closure, and swallowing agement of sialorrhea in children with CP. A
(Fairhurst and Cockerill 2011). These techniques double-blinded crossover trial of 27 patients (age
take advantage of behavioral therapy mecha- range, 4–19 years) demonstrated a reduced mean
nisms, such as positive reinforcement and cueing drooling score (modified Teacher’s Drooling
(especially in the case of biofeedback, in which Scale (TDS) [1 = never drools to 9 = clothing,
an auditory cue via headphones is utilized to hands, and objects frequently become wet]) for
condition a patient to swallow more frequently). glycopyrrolate compared with placebo of 1.85
They have been proven to be safe and non- vs. 6.33, respectively ( p < 0.001) (Mier et al.
invasive, although efficacy is contingent on the 2000). A Phase III randomized controlled trial
child’s ability to follow simple verbal and/or (RCT) examining the use of an oral glycopyrro-
visual commands. late solution for sialorrhea management also
Several intraoral devices are currently avail- demonstrated a significant short-term (8-week)
able that aim to promote active lip and tongue benefit, utilizing a similar modified 9-point
movement. Most are essentially modified plastic TDS. When comparing 19 patients given an oral
braces with textured surfaces (e.g., ridges, glycopyrrolate solution to 17 patients given a pla-
bumps) that encourage oral-motor movements cebo medication, the mean reduction in the mod-
that can help to bring saliva to the posterior oral ified TDS was statistically significant ( 3.94
cavity and oropharynx for swallowing. However, vs. 0.71, p < 0.0001) (Zeller et al. 2012). How-
given the risk for possible aspiration of the ever, it should be noted that there are no reliable
device, this is usually reserved for children with studies in the literature describing the long-term
better baseline oral-motor skills and is contra- efficacy and safety profile of glycopyrrolate for
indicated in children with epilepsy (Inga et al. sialorrhea management only.
2001). Another popular medication is scopolamine,
which is a widely utilized pre- and postanesthetic
antiemetic agent. It is most commonly available
Pharmaceutical Therapies as a transdermal patch that is applied behind the
ear, and requires changing every 48–72 h. It has
There are several medications currently in use a similar side-effect profile to glycopyrrolate,
for the treatment of sialorrhea. Most pharma- although there have been reports of localized
ceutical agents for sialorrhea leverage their anti- skin reactions at the patch site and decreased
cholinergic effects, which block parasympathetic seizure threshold. Additionally, there is some
signals to the salivary glands. One of the most evidence that long-term use of the patches pro-
commonly used is glycopyrrolate, which is avail- duces diminishing returns over time (Mont-
able as an oral liquid or tablet, as well as an gomery et al. 2016). Other agents that have been
injection. It has a rapid onset (15–30 min) and trialed on smaller bases include trihexylpheni-
lasts for approximately 6–8 h. It is usually given dyl (an anticholinergic drug commonly used in
2–4 times per day, preferably with mealtimes. the treatment of movement disorders, such as
Table 1 List of common Medications for sialorrhea

medications for sialorrhea,
Name Forms Side effects
currently available
formulations, and potential Glycopyrrolate Oral tablet Blurred vision
side effects Oral liquid Xerostomia
Injection Irritability/altered mental status
Constipation
Urinary retention
Scopolamine Transdermal patch Xerostomia
Blurred vision
Dizziness
Irritability/altered mental status
Constipation
Urinary retention
Benztropine Oral tablet Xerostomia
Injection Blurred vision
Tachycardia
Constipation
Urinary retention
Atropine Oral tablet Tachycardia
Sublingual liquid Dizziness
Xerostomia
Blurry vision
Flushing
Constipation
Urinary retention
Parkinson’s disease, and which may be useful for is especially important considering the tendency
children with concomitant muscle dystonias), for the more serious side effects to manifest at
benztropine (a first-generation antihistamine), higher dosages (Table 1).
and inhaled ipratropium bromide.
There are also several case reports of sub-
lingual ophthalmic atropine solution being used Botulinum Toxin Injections
to great effect with minimal systemic side effects
(Rapoport 2010). A larger prospective cohort Botulinum toxin is a naturally occurring neu-
study of 26 children with CP examined the effect rotoxin produced by the bacterium Clostridium
of daily and twice-daily administration of sub- botulinum. There are seven identified types
lingual atropine drops over an 11-week period (A through G) with different antigenic distinc-
(3 weeks without treatment, and 4 weeks each tions, but the most commonly used in medical
with once-daily and twice-daily dosing). Using practice is botulinum toxin A. The toxin exerts
a 100-point visual analog scale, they demon- its effect at the presynaptic neuromuscular junc-
strated that caregivers noted a statistically sig- tion, preventing the release of presynaptic acetyl-
nificant reduction in the degree of sialorrhea choline vesicles. While it is well known for its
from baseline ( p = 0.004) (Norderyd et al. musculoskeletal and cosmetic applications, it
2017). was utilized as early as 1997 in an off-label indi-
It should be noted that, irrespective of choice, cation for management of sialorrhea in adults with
all of these systemic medications may produce amyotrophic lateral sclerosis, with the aim of
individual responses with significant variance. decreasing salivary production by blocking ace-
Therefore, it is usually prudent to start a child on tylcholine transmission across the neuroglandular
the lowest possible dose and titrate to effect. This junction (Bushara 1997). A few years later, in
804 C. Tsang et al.
2001, the first case study of three patients was only 5% of patients experienced temporary local
published detailing the use of intraglandular side effects (Jongerius et al. 2004).
Botox injections for the management of pediatric
sialorrhea (Porte et al. 2014). Since then, several
follow-up studies have been published, which Surgical Management
have examined the safety and efficacy of the
drug specifically in the pediatric population. Surgical management is usually reserved for chil-
When utilized for intraglandular injections, dren who have failed conservative or medical
the average onset of action is roughly management for 6 months. Surgery is usually
2–3 days, and the chemical denervation of the deferred until after 5 years of age to allow for
gland lasts for 6–9 months, although this may adequate oral-motor development, or to at least
vary widely. There is currently no standardized give it as much of a chance as possible to develop
dosing regimen or template for intraglandular normally. In cases of children suffering from
Botox injections, and different studies have var- chronic aspiration-related illnesses such as pneu-
ied significantly, with some authors using as monia or comorbid airway issues (e.g., obstruc-
little as 10 units per gland (bilateral submandib- tive sleep apnea, ventilator/positive airway
ular and/or bilateral parotid glands), and other pressure dependence), surgery may be considered
authors using as much as 50 units per gland at earlier ages. There are several surgical tech-
(Porte et al. 2014). One large multicenter study niques available that may help with sialorrhea,
involving 111 neurologically impaired children most of which fall under two schools of thought:
produced a 68% success rate, with “success” one aims to decrease the amount of saliva pro-
being defined as at least a 1-point improvement duced and the other aims to redirect salivary flow
from baseline on a subjective 5-point Likert to make it more easily swallowed. Advocates of
scale at a 2-month follow-up (Lungren et al. relocation argue that the primary difficulty in
2016). A 2012 Cochrane review of sialorrhea sialorrhea is in the transfer of saliva to the poste-
management identified four other studies (all rior oropharynx, and relocation would not reduce
cohort studies or RCTs), all of which demon- salivary production, which could adversely influ-
strated good short-term efficacy of Botox on ence oral hygiene, leading to xerostomia and dental
salivary flow and quality of life at approximately caries. Conversely, surgeons who favor decreasing
1 month after administration. However, the production raise the concern that redirecting sali-
authors did note that there was a significant vary flow posteriorly could increase the risk of
amount of variability in methodology between lower airway complications such as aspiration.
the studies, and therefore, no definitive conclu- These advocates of reducing salivary production
sion could be reached on the efficacy of Botox contend that sufficient salivary flow to maintain
for sialorrhea (Young et al. 2012). oral hygiene is primarily supplied by the minor
There are several known side effects to Botox salivary glands, and so oral hygiene would not be
injections, including temporary dysphagia, neck affected by procedures on the major glands
pain, diarrhea, and altered gait. These are usually (Greensmith et al. 2005; Stern et al. 2002).
temporary and limited to the head and neck. How- One of the oldest procedures aimed at decreas-
ever, the rate of these complications falls off dra- ing salivary production is bilateral tympanic
matically when the medication is administered neurectomy. Postganglionic parasympathetic
under image guidance. One controlled trial com- fibers innervating the submandibular, sublingual,
paring ultrasound-guided Botox injections with and parotid glands all pass through the middle ear
an oral anticholinergic agent noted a similar space. Fibers to the parotid gland run along
reduction in sialorrhea (49% to 53%), but there Jacobsen’s nerve (a branch of cranial nerve IX),
was a significantly higher rate of systemic side whereas innervation to the submandibular and
effects in the oral anticholinergic treatment arm sublingual glands course along the chorda tym-
(73%) compared to the Botox cohort, in which pani nerve (a branch of cranial nerve VII),
respectively. There are also parasympathetic submandibular glands has been proposed, which
fibers that run through the tympanic plexus has the benefit of avoiding neck scarring as well as
along the promontory, which is the bony projec- minimizing potential damage to the marginal
tion of the basal turn of the cochlea into the middle mandibular branch of the facial nerve. One review
ear. These fibers are accessed via the ear canal, in of 77 adult patients undergoing this procedure for
which the tympanic membrane is raised, and the sialadenitis demonstrated similar surgical success
nerve fibers sectioned using either cold instru- rates between the two approaches (trans-cervical
mentation (e.g., otologic rasp or drill) or a laser. and trans-oral). However, the trans-oral approach
The risks of this surgery are altered sense of taste, was associated with a much higher rate of tempo-
as well as the possible risk of inner ear damage rary (resolving within 6 weeks) lingual (70%) and
causing sensorineural hearing loss; long-term fol- hypoglossal nerve (74%) injury causing tongue
low-up studies have shown that sialorrhea usually numbness and dysarthria, respectively (Hong
returns to preoperative baseline levels within and Yang 2008). It should be noted that trans-
6 months after this procedure. This procedure oral dissection is usually more difficult and there-
has therefore been largely abandoned (Mullins fore more time-consuming compared to the exter-
et al. 1979). nal approach.
The next set of surgical options revolves A recent meta-analysis of all the literature
around the reduction of salivary output from the regarding the different surgical treatment op-
submandibular and parotid glands. This is usually tions for sialorrhea demonstrated that bilateral
accomplished by way of submandibular and/or parotid duct ligation in conjunction with bilateral
parotid duct ligation, not infrequently in com- submandibular gland excision had the highest
bination with submandibular and/or sublingual reported rate of success (87.8%, k = 8 studies,
gland excision. Ductal ligation is usually ac- p < 0.001), with success usually defined by a
complished by first cannulating the ducts (the subjective grading scale particular to each study
submandibular duct, or Wharton’s duct, and/or (either an ordinal scale such as the TDS or a binary
the parotid or Stensen’s ducts) with lacrimal pro- response of “drooling was/was not significantly
bes or flexible angiocatheters and then dissecting improved”). The procedure with the lowest rate of
along the path of the duct to fully expose the reported success was 4-duct ligation of the sub-
duct from any surrounding neurovascular struc- mandibular and parotid ducts (64.1%, k = 4 stud-
tures (e.g., lingual nerve) before performing suture ies, p = 0.001). Overall, across all techniques, the
ligation. The sublingual glands are usually acces- mean success rate was 81.6% (95% confidence
sible trans-orally for excision, unless precluded by interval of 77.5–85.7%) (Reed et al. 2009). This
patient anatomy (craniofacial malformations such suggests that sialorrhea surgery results in a reduc-
as micrognathia or trismus), in which case an tion in the degree/severity of drooling, regardless
external trans-cervical approach is indicated. The of technique.
sublingual glands are often quite intimately asso- However, there is some evidence that manage-
ciated with the submandibular ducts, and excision ment of the submandibular glands alone is ade-
of these glands may sometimes be required during quate for reducing baseline salivary production,
submandibular duct ligation due to bulkiness. given that the parotid glands only contribute pri-
The submandibular glands are generally acces- marily to stimulated saliva production during gus-
sible via the trans-cervical approach. The mar- tatory activities. Over a 30-year period at a
ginal mandibular branch of the facial nerve must pediatric Drooling Control Clinic at Toronto Hos-
be protected during this procedure, as it usually pital for Sick Children, it has been demonstrated
runs in the fascia investing the gland. It is also that only 5% of children required additional
lateral to the lingual and hypoglossal nerves, parotid duct ligation after submandibular duct
and the facial vessels are oftentimes ligated as ligation (Crysdale et al. 2006).
part of the surgical dissection. More recently, a Several surgical procedures aim to divert sali-
trans-oral approach for removal of the vary flow to the posterior portion of the oral cavity
806 C. Tsang et al.
and oropharynx. This is most often accomplished necessitates its simultaneous removal at the time
by relocating the ducts of the major salivary of surgery; previous literature had shown that
glands (parotid and submandibular). Generally, ranula (a salivary pseudocyst in the floor of
the principle is the same for both anatomic sites mouth, usually involving the sublingual gland)
(Figs. 2 and 3). The ductal papilla is identified and formation was as high as 13% after submandibu-
excised in continuity with a small island of sur- lar duct relocation and that number dropped to
rounding mucosa. The duct is then dissected in a zero at a 5 year follow-up in one study (Webb
retrograde fashion and tunneled under a mucosal et al. 1995). The overall complication rate for
bridge to be sutured into its new position, usually submandibular duct ligation is now roughly 10%
the ipsilateral tonsillar fossa, with the original and includes such sequelae as airway obstruc-
defect closed primarily without need for any adja- tion from floor or mouth/tongue swelling and
cent tissue rotation (Kitsko and Mehta 2014). injury to the lingual nerve. Additionally, it
There are several complications that may be should be noted that parotid duct relocation
associated with ductal relocation surgery. In the alone has been largely abandoned in favor of
case of submandibular duct relocation, the inti- parotid duct ligation, given the higher success
macy of the sublingual gland to the duct usually rates and decreased operative time of the latter;
Fig. 2 Normal trans-oral anatomy of the salivary ducts. (Used with permission by Steven P. Cook, MD)
Fig. 3 Submandibular duct

re-location as viewed
through the oral cavity.
(Used with permission by
Steven P. Cook, MD)
furthermore, parotid duct relocation was associated he/she can produce an effective cough), and the
with a complication rate as high as 35%, including tracheostomy tube offers an access point for
ductal stenosis, wound breakdown, and septic par- flexible suction to be passed by parents or the
otitis. That being said, a recent study demonstrated primary caregiver. It should be noted, however,
the efficacy of quadruple duct diversion in a series that a tracheostomy does not prevent aspiration,
of 12 pediatric patients with CP, with at least a but can potentially decrease the risk or frequency
1-point improvement across all patients using a through pulmonary hygiene. The potential com-
modified TDS at an 18-month median follow-up plications of pediatric tracheostomy are very well
(Celet Ozden et al. 2012). documented and include local soft tissue infec-
Most children managed surgically have cli- tions, bleeding, tracheal stenosis, and fistula
nical improvement. Those with refractory sia- (tracheo-cutaneous and tracheo-innominate)
lorrhea, particularly when recurrent or chronic formation.
aspiration is a significant problem, may then be TED and LTS take this a step further, by sur-
considered for a tracheostomy, tracheo-eso- gically separating the larynx from the rest of the
phageal diversion (TED), or laryngotracheal sep- trachea (Fig. 4). The trachea is transected through
aration (LTS). A tracheostomy can provide a the cervical segment and is either closed as a blind
means for effective pulmonary toilet, as the pouch (LTS) or diverted into the cervical eso-
patient can clear his/her own secretions (provided phagus (TED). Both techniques have similar
Fig. 4 Sagittal view demonstrating the differences diversion (TED). (Used with permission by Steven
between (clockwise from top): tracheostomy, laryngo- P. Cook, MD)
tracheal separation (LTS), and tracheo-esophageal
808 C. Tsang et al.
success rates as far as reducing the frequency of ▶ Medical Management of Sialorrhea in the Child
suctioning and incidence of aspiration pneumo- with Cerebral Palsy
nias. That being said, one advantage of LTS ▶ Palliative Care for Individuals with Cerebral
over TED is the lack of a second suture line Palsy
at the tracheo-esophageal anastomosis, which ▶ Surgical Management of Tracheostomies and
reduces the risk for potential wound breakdown/ Tracheal Diversion in Children with Cerebral
fistula formation. In both procedures, there are Palsy
several not insignificant risks, ranging from fistula
formation and stomal stenosis to tracheo-in-
nominate fistulas. In a large series of 56 children References
who underwent LTS, every child had a signifi-
cant decrease in the number of pneumonias Bushara KO (1997) Sialorrhea in amyotrophic lateral scle-
after surgery (4.6 admissions/year preoperatively, rosis: a hypothesis of a new treatment: botulinum toxin
a injections of the parotid glands. Med Hypotheses
0.73 admissions/year postoperatively); the most
48(4):337–339
common complication was a transient fistula Celet Ozden B, Aydin A, Kuvat SV et al (2012) Quadruple
between the laryngotracheal pouch and the skin salivary duct diversion for drooling in cerebral palsy.
(11%), all but one of which resolved with wound J Craniofac Surg 23(3):738–741
Cook SP (2009) Laryngotracheal separation in neurologi-
management, but no children in that study devel-
cally impaired children: long-term results. Laryngo-
oped a tracheo-innominate fistula (Cook 2009). scope 119(2):390–395
Another study observed that out of 40 patients Crysdale WS, McCann C, Roske L et al (2006) Saliva
who underwent either TED or LTS, two ended control issues in the neurologically challenged: a
30-year experience in team management. Int J Pediatr
up developing tracheo-innominate fistulas, both
Otorhinolaryngol 70(3):519–527
of which required emergent surgical ligation and Daniel SJ, Kanaan AA (2015) Chapter 201: salivary gland
subsequent endovascular embolization (Takano disease in children. In: Flint et al (eds) Cummings
et al. 2015; Hara et al. 2014). Otolaryngology – Head & Neck Surgery, 5th edn.
Elsevier Saunders, Philadelphia, pp 3117–3118
Eiland LS (2012) Glycopyrrolate for chronic drooling in
children. Clin Ther 34(4):735–742
Conclusion Fairhurst CBR, Cockerill H (2011) Management of
drooling in children. Arch Dis Child Educ Pract Ed
The drooling child with CP can be challenging 96(1):25–30
Garnock-Jones KP (2012) Glycopyrrolate oral solution: for
from a management perspective. Each child may
chronic, severe drooling in pediatric patients with neu-
exhibit different responses to the various inter- rologic conditions. Paediatr Drugs 14(4):263–269
ventions, and as such, there does not exist a stan- Greensmith AL, Johnstone BR, Redi SM et al (2005)
dardized treatment protocol for this condition Prospective analysis of the outcome of surgical man-
agement of drooling in the pediatric population. Plast
(Fig. 2). No one treatment guarantees success.
Reconstr Surg 116(5):1233–1242
Management of sialorrhea necessitates a multi- Hara H, Hori T, Sugahara K et al (2014) Effectiveness of
disciplinary approach, with input from the family, laryngotracheal separation in neurologically impaired
caregivers, physical therapists, speech, and lan- pediatric patients. Acta Otolaryngol 134(6):626–630
Hong KH, Yang YS (2008) Surgical results of the intraoral
guage pathologists, in addition to specialists
removal of the submandibular gland. Otolaryngol Head
from pulmonology, neurology, otolaryngology, Neck Surg 139(4):530–534
and gastroenterology, among others. Inga CJ, Reddy AK, Richardson SA et al (2001) Appliance
for chronic drooling in cerebral palsy patients. Pediatr
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Jongerius PH, van den Hoogen FJ, van Limbeck J et al
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▶ Dental Hygiene for Children with Cerebral Kitsko DJ, Mehta D (2014) Chapter 72: The management
of drooling (sialorrhea). In: Bluestone et al (eds)
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ment of sialorrhea with glycopyrrolate: a double- Stern Y, Feinmesser R, Collins M et al (2002) Bilateral sub-
blind, dose-ranging study. Arch Pediatr Adolesc Med mandibular gland excision with parotid duct ligation for
154(12):1214–1218 treatment of sialorrhea in children: long term results. Arch
Montgomery J, McCusker S, Lang K et al (2016) Manag- Otolaryngol Head Neck Surg 128(7):801–803
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Auditory Rehabilitation in Children
Kiley Trott, Amy Powell, Yell Inverso, and William J. Parkes
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 812
Diagnosis of Hearing Loss . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 812
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 812
Conventional Amplification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 812
Cochlear Implantation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 813
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 817
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 817
Abstract
A number of risk factors for sensorineural
hearing loss (SNHL) overlap with known
causes of cerebral palsy (CP). Up to 39% of
K. Trott patients with CP also have some degree of
Department of Otolaryngology – Head and Neck Surgery,
Thomas Jefferson University Hospital, Philadelphia, PA, hearing loss. During the neonatal and infant
USA periods, acute care needs often take precedence
Nemours/Alfred I. DuPont Hospital for Children, and may even preclude definitive diagnosis
Wilmington, DE, USA and intervention. Once these children are med-
e-mail: kiley.trott@jefferson.edu ically stable, it can be difficult to monitor their
A. Powell hearing loss with age-appropriate behavioral
Outpatient Therapy Services, Nemours/Alfred I. DuPont testing. Auditory rehabilitation in these chil-
Hospital for Children, Wilmington, DE, USA dren can also be challenging. This chapter
e-mail: amy.powell@nemours.org
will review some of the aforementioned diffi-
Y. Inverso culties in more detail and provide insight into
Nemours/Alfred I. DuPont Hospital for Children,
Wilmington, DE, USA the comprehensive approach that is necessary
e-mail: yell.inverso@nemours.org to optimize audition in these children.
W. J. Parkes (*)
Division of Otolaryngology, Nemours/Alfred I. DuPont
e-mail: william.parkes@nemours.org

https://doi.org/10.1007/978-3-319-74558-9_64
812 K. Trott et al.
Keywords A hearing assessment can be divided into

Cerebral palsy · Cochlear implant · Hearing two main categories, electrophysiologic and
loss · Sensorineural · Auditory rehabilitation behavioral. For infants or older children who
are otherwise unable to complete behavioral
hearing assessments, electrophysiologic testing
Introduction can be completed. Commonly, the cutoff for an
unsedated assessment to be successful is 6 months
A number of risk factors for sensorineural hearing of age. Infants older than 6 months tend to be too
loss (SNHL) overlap with known causes of cerebral alert for testing, even when asleep. If sedation is
palsy (CP). Examples include congenital infections necessary, this is often postponed to be completed
(i.e., cytomegalovirus), prematurity, low birth in conjunction with another sedated procedure.
weight, neonatal hyperbilirubinemia, severe This can create a delay in the initial diagnosis of
hypoxic-ischemic insults, and neonatal meningitis a hearing loss. Traditional behavioral testing of
(Ashwal et al. 2004; Sano et al. 2005). Addition- hearing in young children uses operant condition-
ally, there are genetic conditions that have variable ing toward sound and the visual reinforcement
incidence in the general population and, therefore, of this conditioning. The audiologist relies on a
could occur in the CP population without a direct patient’s ability to turn their eyes or head toward
relationship. According to a large 2018 review, up the direction of a sound. In children with CP,
to 39% of patients with CP also have some degree the necessary motor skills to engage in these
of hearing loss (Weir et al. 2018). Auditory reha- techniques may be delayed, thereby confounding
bilitation in these children can be challenging. Dur- results for many months.
ing the neonatal and infant periods, acute care
needs often take precedence and may even preclude
definitive diagnosis and intervention. Once these Treatment
children are medically stable, it can be difficult to
monitor their hearing loss with age-appropriate Conventional Amplification
behavioral testing. Similarly, clinical progress
with auditory prostheses can be hard to gauge. Once a hearing loss is diagnosed and confirmed,
This chapter will review some of the aforemen- the focus for professionals shifts to ensuring
tioned challenges in more detail and provide insight appropriate intervention. In the absence of proper
into the comprehensive approach that is necessary treatment, hearing loss in children with cerebral
to optimize audition in these children. palsy can lead to difficulties in the development of
language and ultimately impair social and per-
sonal growth. In cases of conductive hearing loss
Diagnosis of Hearing Loss (i.e., otitis media), medical or surgical interven-
tion is often indicated. Amplification is necessary
For any individual with a hearing loss, early diag- for hearing losses that are not conductive in
nosis is the key to early intervention. The critical nature. Hearing aids, which are synonymous
window for the development of speech and lan- with conventional amplification, are technologi-
guage is birth through 3 years of age. Even during cal devices that are prescribed and fit by a licensed
the 1st year, when speech output is limited, the audiologist. Hearing aids are small, usually digital
building blocks of language are being laid through devices that are worn on or in the ear. Audiologists
incidental learning. In children with CP, there are use the thresholds obtained in audiometric testing
often barriers to prompt diagnosis and treatment to set the parameters of hearing aids. In children
of hearing impairment. Frequently, coexisting who are unable to participate in this type of behav-
medical issues may take precedence over hearing ioral testing, thresholds extrapolated from their
loss. In addition, it can be difficult to obtain accu- auditory brainstem response (ABR) testing can
rate hearing thresholds in this population. be used. Hearing aids receive sounds through a
55 Auditory Rehabilitation in Children with Cerebral Palsy 813
microphone and, after processing, amplify them behind the ear) and an internal component that
based on the needs prescribed by the patient’s communicate transcutaneously. The internal
audiogram. Hearing aids have become highly device is activated by a CI audiologist approxi-
sophisticated and are capable of overcoming the mately 1 month after it is implanted. Initial stim-
loss to volume experienced by children with mild ulation should result in an auditory percept, but
to severe hearing loss. the brain must learn how to use that percept over
In the aforementioned review of children with time. This process typically requires intensive
CP, 7% were assisted with hearing aids (Weir et al. rehabilitation with both audiology and speech
2018). This is likely lower than the percentage and language pathology.
aided without a comorbidity such as CP. The Historically, patients with CP were not felt to
most significant limiting factor for success with be good candidates for cochlear implantation.
hearing aids is the placement of the devices. For Reasons included more pressing medical issues,
most children, behind-the-ear (BTE) hearing aids practical difficulties with using the technology,
are more appropriate than in-the-ear (ITE) hearing behavioral barriers to rehabilitation, and the
aids because ear molds need to be updated guarded prognosis with respect to speech and
over time as the ear canal grows. In children language outcomes. Candidacy criteria have
who are reliant on a wheelchair and have difficulty evolved over time, however, and evidence is
maintaining head control, however, acoustic emerging that cochlear implantation may have
feedback can become an issue with BTE aids. a positive impact on this population of children
Feedback is caused when some of the amplified (Daneshi and Hassanzadeh 2007; Bacciu et al.
sound leaks from the ear canal and is picked up by 2009; Steven et al. 2011). Unfortunately, this
the hearing aid microphone and then re-amplified. knowledge is not necessarily pervasive, and
This re-amplification occurs more commonly many potential CI candidates with CP are never
when aids rest in close proximity to the headrest referred to a CI center for an assessment.
of the chair. If this feedback is not able to be In the United States, CIs are FDA-approved for
overcome with digital feedback suppression and use in children under age 2 with bilateral profound
an ITE aid is not an option, one can consider the SNHL and in children over age 2 with bilateral
use of a bone conduction hearing aid on a severe to profound SNHL. These audiometric
softband. A bone conduction hearing aid can be criteria only represent one component of what is
worn in the center of the forehead of a patient (i.e., truly a multidisciplinary candidacy assessment.
as far from the headrest as possible). While this is CI candidates meet with care providers from audi-
not the traditional use for this device (primarily ology, speech and language pathology, otolaryn-
used for maximal conductive hearing loss or gology, and social work.
single-sided deafness), this creative option will
send amplified sound directly through the bone Candidacy Assessment with Audiology
to the cochlea of both ears. The decision to perform a CI candidacy assess-
ment is appropriate when conventional hearing
aids do not seem to be providing meaningful
Cochlear Implantation auditory access. The primary purpose of the audi-
ological assessment is to confirm that a patient has
In children with significant SNHL and no percep- the hearing loss characteristics of a CI candidate.
tible benefit from conventional amplification, As part of this evaluation, the audiologist must
cochlear implantation can restore audition and also verify that the child’s aids have been fit prop-
promote the development of listening and spoken erly, assess the family’s ability to care for their
language. A cochlear implant (CI) works by child’s technology, and attempt to gauge the fea-
converting an acoustic signal to an electrical sig- sibility of programming a CI postoperatively.
nal that is then transmitted directly to the cochlear The audiological candidacy assessment itself
nerve. There is both an external component (worn consists of many of the same tests employed to
814 K. Trott et al.
establish the initial hearing loss diagnosis. The implantation. Some children with cerebral palsy
primary difference in a CI candidacy evaluation may not have developed a formal communication
is that the majority of testing is completed while system. As such, a more comprehensive develop-
the child is wearing appropriately fit hearing aids. mental evaluation is often necessary to determine
The amount of additional testing that is completed their current levels.
will vary based on the behavioral abilities of the Standardized assessments of receptive and
child. In its purest form, it is an evaluation during expressive language are commonly used to deter-
which we determine if, without the use of a CI, the mine age equivalencies. Often, these assessments
patient’s hearing aids are able to achieve audibility are standardized on children without any disabil-
and comprehension levels adequate for the devel- ity (Bradham and Houston 2015). An example is
opment of speech and language. In order to do so, the Preschool Language Scale-5 (PLS-5). This
more advanced electrophysiologic measures may assessment can be very difficult for children with
be necessary to determine how much of the ampli- cerebral palsy regardless of the severity of their
fied signal is making it to the auditory cortex using hearing loss. When motor or cognitive delays
their hearing aid technology. Cortical Auditory prevent the use of standardized assessments,
Evoked Potential (CAEP) testing is performed in parent report measures such as the Receptive-
an awake patient but does not require active par- Expressive Emergent Language Test-3 (REEL-3)
ticipation in the listening task to record a response. can be useful. Ultimately, informal observation
The P1 evoked potential has been shown to be may be the best tool for evaluating the communi-
a reliable biomarker for assessing the maturity cation skills of children with additional disabil-
of the central auditory system. Completing this ities. It is important to look at the way in which
assessment in the aided and unaided conditions these children are communicating: Do they
can afford the audiologist additional insight into respond to any sounds in their environment
whether or not the hearing aids are conferring a (such as someone calling their name), are they
benefit. using any signs/gestures, are they attempting to
Finally, the audiologist must gauge the likeli- vocalize, do they engage in joint attention, and do
hood that a candidate will be able to participate they have turn taking skills?
in the postoperative programming (mapping) Oral motor impairment and dysarthria can have
of the device(s) to ensure adequate and comfort- a major impact on the development of spoken
able access to sound. Encouraging signs include language for children with cerebral palsy. If they
appropriate eye gaze toward stimuli, a startle are followed by a speech and language pathologist
response at a suprathreshold level, and interest in who specializes in feeding, their input is invalu-
the conditioned play used to demonstrate that a able. Gathering information regarding their feed-
stimulus was detected. If a child with CP is unable ing skills and their oral motor abilities can help to
to participate in behavioral audiometry, the map- predict future outcomes with spoken language
ping process for a CI will be altered as both utilize development.
similar techniques. Though the lack of consistent
behavioral responses would not rule a patient out Candidacy Assessment with
for implantation, the audiologist would need to be Otolaryngology
prepared to use alternative techniques such as As part of the medical evaluation, imaging of the
electrophysiologic testing. brain and internal auditory canals is necessary in
order to delineate the inner ear anatomy, confirm
Candidacy Assessment with Speech the integrity of the cochlear nerves, and assess the
and Language Pathology auditory cortices. In children with CP resulting
The goal of a speech and language assessment from meningitis, it is important to rule out
prior to cochlear implantation is to determine cochlear ossification, which can be a sequela of
present levels of communication and to the meningitis. Though the presence of ossifica-
identify positive prognostic indicators following tion does not necessarily preclude implantation,
surgical technique is significantly altered, and out- adaptation to novel stimuli. It is also well-known
comes are known to be poorer. In the CP popula- that a child’s overall developmental potential will
tion, imaging studies will usually require general influence auditory rehabilitation ability. Several
anesthesia and are ideally combined with confir- studies have found that deaf children with addi-
matory ABR testing whenever applicable to min- tional handicaps have lower perception scores and
imize the anesthetic exposure. The potential need language development after cochlear implantation
for postoperative magnetic resonance imaging as compared to children without multiple disabil-
(MRI) must also be considered. The internal com- ities (Pyman et al. 2000; Waltzman et al. 2000;
ponent of a CI contains a magnet that can be Hamzavi et al. 2000; Holt and Kirk 2005;
problematic in a scanner. There are presently Berrettini et al. 2008). A 2007 literature review
three manufacturers of FDA-approved cochlear performed by Edwards on pediatric cochlear
implants, and the guidelines regarding MRI safety implantation in children with complex needs dem-
differ across the devices. Additionally, the internal onstrated that cognitive impairment was a strong
component of an implant will create an artifact predictor of outcomes (Edwards 2007). In 2013,
that can obscure a view of the adjacent brain. Byun et al. reviewed post-implantation perfor-
Assuming that no anatomical or medical con- mance of prelingual deaf children with CP and
traindications to surgery are uncovered, the most found that the subset of children with performance
important consideration during the medical eval- comparable to age- and sex-matched control CI
uation is the duration of auditory deprivation. It is recipients had less severe motor disabilities,
well established that prolonged periods of higher social quotients, and stronger cognitive
profound SNHL result in reorganization of the abilities (Byun et al. 2013). With this in mind,
auditory cortices that will negatively impact the consultation with neuropsychology or develop-
potential benefit of a CI (Litovsky and Gordon mental pediatrics can provide valuable insight
2016). This fact is especially relevant in the during the counseling process.
CP population given that historical misconcep- Even when the development of listening and
tions may contribute to significantly delayed spoken language is not felt to be realistic, cochlear
presentations. implantation in deaf children with additional dis-
ability can still have a positive impact on quality
Candidacy Assessment with Social Work of life (Waltzman et al. 2000; Hamzavi et al. 2000;
Involvement of social work is important for any Fukuda et al. 2003; Wiley et al. 2005; Berrettini
family moving through a CI candidacy assess- et al. 2008). Simply restoring sound awareness
ment because of the rehabilitative commitment can lead to increased connectivity and interest
that follows surgery. For families with disabled with the child’s environment and enhance their
children, this component of the evaluation is even social interactions.
more critical. Preexisting emotional, social, and
financial stressors can be exacerbated over the Intraoperative Considerations
course of rehabilitation and must be explored to Typically, any cervical spasticity dissipates under
ensure adequate support is provided. general anesthesia, so standard positioning for
otologic surgery (shoulder roll with head turned
Preoperative Counseling to the opposite side) is feasible. When planning
Once the CI team has determined that a child is a incision and device location, consideration needs
candidate for surgery, it is imperative that realistic to be given to preoperative neck strength and
expectations are set with respect to outcomes. As whether or not a head support is used if wheel-
detailed previously, one of the key factors in post- chair bound. Postoperatively, the patient’s head
implantation performance for any child is the posture, as well as the frequency and direction
duration of pre-intervention auditory deprivation of head motion, can impact device comfort and
(Nikolopoulos et al. 1999). Younger infants pos- stability (Ray et al. 2006; Steven et al. 2011).
sess greater neural plasticity, allowing for faster In order to avoid constant contact with supporting
816 K. Trott et al.
surfaces and associated displacement forces, Postoperative Rehabilitation

the internal component of the device can be placed Mapping is a term that is commonly used to
in a more vertically oriented position post- describe the programming of a patient’s cochlear
erosuperior to the mastoid cavity. implant to their individual needs. Once sound
As the majority of hearing loss in children enters the microphone of a CI, it is processed and
with CP is acquired, the temporal bone anatomy digitized to electrically stimulate the electrode
is typically normal, so the surgical approach is array. During a mapping session, programs are
expected to be straightforward. One exception created to optimize the cochlear implant user’s
would be in a child with a history of meningitis access to sound by adjusting the input to different
and subsequent cochlear ossification. In these electrodes on the array. The input must not only be
cases, a drill-out of the cochlea and the use of audible but also comfortable. Though active patient
special electrode arrays may be necessary. participation is ideal during these sessions, it is not
always feasible. The patient’s ability to participate
Complications in their mapping is dependent on their overall abil-
Surgical site infections after cochlear implantation ity to communicate and comprehend the process. In
occur in 1–12% of patients (Cunningham et al. infants and very young children, objective mea-
2004; Hopfenspirger et al. 2007; Rubin et al. sures are combined with behavioral observation
2010). Incisional infections can lead to wound until the child is old enough to offer their feedback.
breakdown, dehiscence, and even device exposure. In patients with CP, the use of subjective tools and
Perioperative and postoperative antibiotics are indi- observation can be used long term if necessary.
cated to mitigate this risk. Caretakers must be espe- Many patients with CP will establish a relationship
cially vigilant when the incisions and underlying with their audiologist through which they create a
devices are in contact with supporting surfaces, system for responding to the signals. This can
such as headrests. If an abscess forms around the include using a chart and eye gaze to indicate the
device or wound breakdown results in exposure, level of the sound, or if the patient uses an aug-
then explantation may be required. When a wound mentative communication device, a page set could
infection is suspected, the patient should be referred be created specific to the sound descriptors needed
promptly to the operating surgeon for evaluation. for successful mapping. Needless to say, there are
Acute otitis media after cochlear implantation work-arounds that CI audiologists can use to cir-
can quickly spread through the mastoid cavity cumvent the obvious barriers to traditional map-
and threaten the implanted device. Patients with ping in this patient population.
cochlear implants who develop acute otitis media Progressive mapping is paired with intensive
should be treated immediately with antibiotics speech and language therapy to advance children
and must be followed closely until resolution of with CIs through a hierarchy of auditory skills.
the infection. Watchful waiting for symptoms of The first step is sound detection, followed by
acute otitis media is not indicated when a cochlear discrimination (the ability to distinguish different
implant is in place. sounds). Later, the hope is that children with CIs
There is also a risk of ascending infection via will actually identify sounds (i.e., attach meaning)
the cochlea after cochlear implantation. Because and eventually develop the comprehension of
of this, there is an increased incidence of menin- connected speech (sentences and conversations).
gitis in children with cochlear implants compared Typically, the goal of auditory verbal rehabili-
to the general population (Reefhuis et al. 2003). tation is the development of spoken language.
In addition to routine vaccination against This may be unrealistic in children with CP who
Haemophilus influenza type B and pneumococ- have significant dysarthria. Instead, a focus
cus, children with cochlear implants older than on alternative forms of expressive language may
2 years of age should also receive the polyvalent be more appropriate. Sign language is an
pneumococcal vaccine indicated for high-risk option for some but could prove to be equally
groups. “unintelligible” in children with more significant
motor delays. In these cases, a referral to a speech References

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doi.org/10.1542/peds.2010-1427 2005.01.011
Upper Airway Obstruction in the Child
with Cerebral Palsy: Indication for 56
Adenotonsillectomy
Brian Swendseid and Heather C. Nardone
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 820
Prevalence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 820
Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 821
Impact on Quality of Life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 821
Diagnostic Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 822
Treatment of OSA in CP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 822
Tonsillectomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 823
Additional Surgical Interventions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 824
The Role of Tracheostomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 825
Postoperative Management and Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 825
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 826
Abstract disorder. In addition to the many known health

Children with cerebral palsy have a high prev- consequences, obstructive sleep apnea in this
alence of obstructive sleep apnea given their population is associated with poor quality of
poor neuromuscular control in addition to life for patients and their families. Adenoton-
airway abnormalities characteristic of the sillectomy, possibly in combination with other
surgeries to address upper airway obstruction,
may be beneficial for those with moderate-to-
B. Swendseid
Department of Otolaryngology, Thomas Jefferson
severe obstructive sleep apnea and those
University, Philadelphia, PA, USA failing conservative management. Poly-
e-mail: bps41@case.edu somnogram is an important diagnostic tool
H. C. Nardone (*) useful in preoperative planning and in moni-
Division of Pediatric Otolaryngology, toring resolution.
Nemours/Alfred I duPont Hospital for Children,
Wilmington, DE, USA
Otolaryngology and Pediatrics, Thomas Jefferson
e-mail: heather.nardone@nemours.org

https://doi.org/10.1007/978-3-319-74558-9_66
820 B. Swendseid and H. C. Nardone
Keywords (Newman et al. 2006). Several studies have

Cerebral palsy · Obstructive sleep apnea · employed the use of a validated questionnaire,
Upper airway obstruction · Pediatric · either the Pediatric Sleep Questionnaire (PSQ) or
Adenotonsillectomy the Sleep Disturbance Scale for Children (SDSC),
as a screening tool to help identify children with
CP at increased risk for OSA. For instance, New-
Introduction man et al. used the SDSC to determine the fre-
quency of sleep disturbance in children with CP
Sleep-disordered breathing (SDB) is common and found 14.5% to have SDB (Newman et al.
in the pediatric population, affecting approxi- 2006). In another study, Koyuncu et al. used the
mately 12% of children. It is defined by an abnor- Sleep-Related Breathing Disorder Scale of the
mal respiratory pattern during sleep and includes a PSQ to screen for OSA in healthy children and
spectrum of disorders ranging from snoring to those with CP. 18.1% of those with CP had scores
obstructive sleep apnea (OSA) (Roland et al. concerning for SDB, versus 7.4% of the controls
2011). OSA is defined as SDB plus an abnormal (Koyuncu et al. 2017). Lastly, Garcia et al. used
polysomnogram, showing partial or complete, the PSQ to screen for OSA in those children
intermittent upper airway obstruction that disrupts with CP versus a comparison group without CP
normal ventilation and sleep patterns. During and demonstrated increased PSQ scores in 58% of
the nighttime, children with OSA can experience those with CP, versus 27% in the comparison
snoring, mouth breathing, restless sleep pattern, group. The presence of both CP and epilepsy
pauses and gasping noises during sleep, and fre- increased the percentage of those with a positive
quent awakenings. Daytime symptoms can PSQ to 67% (Garcia et al. 2016). This is an impor-
include excessive daytime sleepiness, hyperactiv- tant finding, as approximately one-third of chil-
ity/difficulty focusing, behavioral concerns, and dren with CP, particularly those children with
poor school performance. OSA affects 1.2–5.7% more severe forms of CP, also have epilepsy
of children, (Marcus et al. 2012) and as many (Garcia et al. 2016).
as 40% of children referred to a sleep clinic Results are conflicting as to whether those
or otolaryngologist for evaluation of sleep- children with more severe forms of CP are at
disordered breathing will be diagnosed with increased risk for OSA. In Garcia’s study,
OSA (Tunkel et al. 2008; Sterni and Tunkel increased GMFCS level, which classifies the
2003). Adenotonsillar hypertrophy is the most degree of gross motor impairment with a higher
common risk factor associated with pediatric level indicating worse function, correlated with
OSA. Other risk factors include obesity, craniofa- increased PSQ scores. Thus, children with more
cial syndromes, and neuromuscular disorders, severe CP were at more risk for OSA (Garcia et al.
such as cerebral palsy (Marcus et al. 2012). 2016). However, this finding is in contrast to the
Untreated OSA is associated with various health findings from Koyuncu, in whose study no signif-
consequences, including neurocognitive distur- icant relationship between SDB and level of
bances, behavior problems, cardiovascular disor- motor dysfunction was detected (Koyuncu et al.
ders, failure to thrive, and systemic inflammation 2017).
(Marcus et al. 2012; Bhattacharjee et al. 2010; Interestingly, in Garcia’s study, only 8% of
Ye et al. 2010; Mitchell 2007). those with CP had been previously diagnosed
with OSA or had mention of symptoms of sleep
disturbance in their medical record, versus 58%
Prevalence identified by the PSQ, suggesting that OSA may
be under-recognized in children with CP (Garcia
Studies suggest that upper airway obstruction, et al. 2016). Being aware that children with CP
whether while awake and/or during asleep, is have an increased likelihood of OSA is critical.
more common in children with cerebral palsy Using a validated questionnaire to screen for OSA
56 Upper Airway Obstruction in the Child with Cerebral Palsy: Indication for Adenotonsillectomy 821
is a reasonable, cost-effective way to identify chil- and/or flexible nasopharyngolaryngoscopy

dren with CP who are at increased risk and for (NPL) in the office. The likelihood that
whom a polysomnogram, the gold standard for adenotonsillar hypertrophy contributes to the
OSA diagnosis, is warranted. OSA seen in CP children remains unclear, as
studies examining the topic are limited to small
case series examining children with varying
Etiology degrees of CP. In one series of nine children
with severe CP and upper airway obstruction,
The cause for the increased risk of OSA in chil- five out of nine (55.6%) were found to have
dren with CP is multifactorial and can include adenotonsillar hypertrophy (Kotagal et al.
causes of upper airway obstruction typically 1994). In another case series reported by Wilkin-
seen in the general pediatric population, such as son et al., eight children presented with severe CP
adenotonsillar hypertrophy (Fig. 1). However, and upper airway obstruction while awake. Flex-
children with CP often also have abnormal neu- ible NPL performed while awake showed pha-
romuscular control of the upper airway, which ryngeal collapse without anatomical obstruction
can manifest as generalized pharyngeal hypoto- (adenotonsillar hypertrophy), in the majority (six
nia, laryngomalacia, and glossoptosis. Determin- out of eight or 75%) (Wilkinson et al. 2006).
ing the site(s) of upper airway obstruction is
important to help guide decision-making in
regard to therapeutic options (Fig. 2). Impact on Quality of Life
Adenotonsillar hypertrophy can easily be
detected either through clinical examination OSA significantly affects the quality of life
(QOL) of both children with CP and their par-
ents. Sandella examined the impact that sleep
disruption has on quality of life (QOL) for chil-
dren with CP. In those with CP, excessive day-
time sleepiness predicted a lower physical
quality of life. The authors speculate that feeling
sleepy during the daytime can exacerbate
existing physical limitations, underscoring the
importance of considering sleep difficulties
when providing medical care to children with
CP (Sandella et al. 2011). Other studies demon-
strate an improvement in both child and care-
giver quality of life after treatment of OSA in
children with CP. Children with more severe CP
(GMFCS level 5) who had undergone treatment,
either adenotonsillectomy or CPAP, were com-
pared to a group with CP who did not receive
treatment. After treatment, parents reported a
decrease in their child’s sleep disturbance,
improvement in daytime functioning, and a
reduction in the parent’s concern about their
child. Improvements were not limited to
improvement in the child’s QOL, as an improve-
ment in the parent’s QOL was also found, in
their perception of social support (Hsiao and
Fig. 1 Tonsillar hypertrophy Nixon 2008).
Fig. 2 Levels of upper

airway obstruction
surgical intervention and need for further surgery

Diagnostic Considerations
and/or CPAP (Roland et al. 2011). Finally,
patients with CP frequently suffer from central
For all pediatric patients with CP for whom
apneas in addition to obstructive apneas, due to
OSA is suspected, consideration should be given
dysregulation of respiratory centers in the medulla
to treating with adenotonsillectomy. In typically
oblongata. PSG provides key information as to
developing children with low surgical risk, a
what contribution obstructive versus central
clinical picture of SDB with parent-reported snor-
apneas play in a child’s sleep disturbance (Biavati
ing, restless sleep pattern with nighttime awaken-
et al. 1997). Polysomnography is the gold stan-
ings and witnessed pauses and gasping noises
dard for diagnosing and quantifying OSA in chil-
during sleep, can be sufficient to allow the pedi-
dren (Roland et al. 2011). OSA severity is graded
atric otolaryngologist to proceed to the operating
based on the apnea-hypopnea index (AHI) and the
room without further diagnostic workup. In
oxygen saturation nadir. Mild OSA is defined as
children with cerebral palsy, further diagnostic
AHI > 1 and 5, moderate is >5 and 10, and
workup with polysomnogram prior to surgery is
severe is >10 or oxygen saturation nadir <80%
advised. Children with CP are at increased risk for
(Mitchell 2007).
perioperative complications (Biavati et al. 1997).
Obtaining a PSG prior to surgical intervention in a
high-risk child confirms the diagnosis and the
need for surgery and defines the OSA severity, Treatment of OSA in CP
allowing for proper perioperative planning, such
as postsurgical monitoring in the intensive care Given the high prevalence of OSA in children
unit. As persistent OSA is more likely in high-risk with CP and its negative effect on their health
patients, the PSG also provides a baseline for and quality of life, intervention is recommended
comparison, as a postoperative PSG will com- when moderate-to-severe OSA is identified. Con-
monly be obtained to assess the success of servative medical treatment can include CPAP/
BiPAP. When tolerated, these treatments can help children aged 15 years and younger (Cullen
promote continuous sleep, minimize daytime et al. 2009).
symptoms, and improve both patient and care- Tonsillectomy is performed using various tech-
giver quality of life. Unfortunately, compliance niques. Traditional tonsillectomy is accomplished
with these therapies is poor among CP patients, via sharp dissection or monopolar electrocautery
leading many families to seek out surgical inter- to completely excise the tonsil with its surround-
ventions (Magardino and Tom 1999). Mild cases ing capsule. In 2002, Koltai first described
of sleep apnea can often be observed unless com- intracapsular tonsillectomy using a powered
plications develop. microdebrider, whereby the bulk of the tonsil
tissue is removed while preserving a small rim of
tonsil tissue and the tonsillar capsule (Fig. 3)
Tonsillectomy (Koltai et al. 2002). Powered intracapsular tonsil-
lectomy and adenoidectomy (PITA) have been
Dysfunction in neuromotor control is thought shown to be an effective technique for treatment
to be the underlying cause of upper airway of OSA in children. Studies revealed a reduction
collapse during sleep. In many children, this in postoperative AHI (Tunkel et al. 2008) along
dysfunction is further exacerbated by airway with less postoperative pain and faster resumption
narrowing associated with adenotonsillar hyper- of normal diet and activity as compared to the
trophy (Mitchell 2007; Marcus et al. 2005). traditional tonsillectomy (Koltai et al. 2003;
Enlarged upper airway tissue causes anatomic Reilly et al. 2009; Du et al. 2010; Lister et al.
narrowing of the upper airway and increases pha- 2006; Derkay et al. 2006). Children undergoing
ryngeal resistance, resulting in further episodic PITA have lower rates of postoperative bleeding
airway narrowing and collapse. The American and readmission for dehydration, as compared to
Academy of Pediatrics recommends adenoton- those who undergo traditional tonsillectomy
sillectomy as the first line of treatment for patients (Solares et al. 2005).
with OSA resistant to medical therapy (Marcus Adenotonsillectomy improves OSA in the
et al. 2012). In the United States, 530,000 cases of majority of children; however, abnormal postop-
tonsillectomy with or without adenoidectomy are erative PSG studies have been reported in
performed annually, making it the second most approximately 20–40% of cases (Mitchell and
common ambulatory procedure performed in Kelly 2004, 2005; Tauman et al. 2006;
Fig. 3 Intracapsular
tonsillectomy
Guilleminault et al. 2004). A severely elevated airway. Uvulopalatopharyngoplasty (UPPP),

preoperative AHI is the most frequently reported septoplasty, turbinectomy, tongue base suspen-
risk factor for persistent elevation of AHI post- sion (TBS), tongue base reduction, and trache-
tonsillectomy. Age, body mass index (BMI), and ostomy have been employed in the management
presence of asthma (in nonobese children) are of OSA.
other reported risk factors (Bhattacharjee et al. Studies have assessed the effect of combined
2010; Mitchell and Kelly 2005; Tauman et al. procedures to address OSA in children with CP
2006). Definitive data regarding the efficacy of with encouraging results. Kosko and Derkay
adenotonsillectomy in patients with CP is reported a series of 15 children with severe neu-
lacking. However, many studies have shown ben- rologic impairment who received adenoton-
efit for a substantial percentage of patients. A sillectomy and UPPP. Twelve of these patients
series of 25 patients with CP treated with (80%) had relief of OSA, as measured by poly-
adenotonsillectomy found that 74% had symp- somnogram showing AHI dropping from a mean
toms improvement and required no further sur- of 8.0 to 2.5 (Kosko and Derkay 1995).
gery at a mean follow-up of 34 months Kerschner reported 15 neurologically impaired
(Magardino and Tom 1999). Another series com- children with OSA who also received adenoton-
pared subjective assessments completed by par- sillectomy and UPPP. This study found a similar
ents of CP patients treated for OSA (seven out of rate of improvement immediately after surgery
ten by adenotonsillectomy, three out of ten by (86.7%), with a slightly lower rate of sustained
CPAP) to nine controls. Parents reported decrease improvement at a mean follow-up time of
in overnight sleep disturbances, improvement in 5 years (62%). Improvement was documented
daytime performance, and improved parental with postoperative PSG, which also showed an
quality of life due to less worry about their child’s increase in average oxygen nadir from 65% to
sleep (Hsiao and Nixon 2008). While results in 85% (Kerschner et al. 2002). Another study
the aforementioned studies are encouraging, it is suggested performing a tongue base suspension
important to note that the effectiveness of in addition to adenotonsillectomy and UPPP,
adenotonsillectomy in alleviating OSA was not particularly in patients with more severe OSA
evaluated by using objective measures, namely, a or glossoptosis as seen on examination or sleep
posttreatment polysomnogram. Across all endoscopy (Hartzell et al. 2013). The authors
patients, post-adenotonsillectomy AHI normal- found improvement in AHI from 27 to 10.7 in
ized in only 25% (Tauman et al. 2006). Given the group receiving all three interventions, as
multiple sites of anatomic airway collapse well as improvement in AHI from 6.8 to 1.8 in
observed in children with CP who have OSA, the group receiving adenotonsillectomy and
rates of objective residual disease are likely to UPPP alone. Finally, a study examined 18 chil-
be higher, although studies to verify this have dren with CP who failed medical therapy and
not been performed. were treated with multilevel airway surgery.
83.3% were free from subsequent tracheostomy
at 30 months, and 84.5% showed improvement
Additional Surgical Interventions in their AHI, from an average of 3.61 to 0.67
(Cohen et al. 1997).
Sleep apnea can be caused by obstruction at Together, these studies provide an encourag-
multiple levels of the upper airway, and thus ing picture of the success rate of surgical inter-
the specific anatomic level or levels of vention for OSA in children with CP. However,
collapse can vary from child to child. For this the data is limited to small series of patients with
reason, several additional surgical approaches varying severities of CP, with each study exam-
have been proposed as stand-alone procedures ining a different array of airway interventions
or in conjunction with adenotonsillectomy and using differing methods to evaluate surgical
to target different portions of the collapsing success.
The Role of Tracheostomy tracheostomy. From these studies we can con-

clude that adenotonsillectomy may help prevent
For patients with OSA resistant to or recurrent need for tracheostomy in CP patients, although
after surgical intervention, difficult-to-manage some, particularly older children, may eventually
secretions, and/or respiratory decompensation, require a trach, as the severity of airway obstruc-
consideration should be given to tracheostomy. tion tends to increase with age, with upper airway
In the setting of severe OSA, bypassing the areas collapse becoming more multilevel and not lim-
of upper airway collapse via tracheostomy can be ited only to adenotonsillar obstruction. This high-
lifesaving (Cohen et al. 1997). It can also provide lights the need for high suspicion and early
an avenue for improved pulmonary toilet for diagnosis in younger patients and increased
patients with tenacious secretions. However, tra- awareness for possible treatment failures with
cheostomy can negatively impact a child’s quality time. Unfortunately, the literature does not pro-
of life and further impair their ability to commu- vide us with information beyond the 3-year fol-
nicate. There is increased risk for adverse events low-up range, so the long-term need for
and even mortality related to having a tracheos- tracheostomy may be higher than the literature
tomy tube. Having a tracheostomy also requires values suggest.
additional medical training and places financial
and emotional strain on caregivers and may ulti-
mately result in institutionalization of patients Postoperative Management
(Magardino and Tom 1999). For these reasons, it and Complications
is often in the best interest of the child and family
to avoid or delay tracheostomy placement when The optimal postoperative management for ton-
feasible. sillectomy and adenoidectomy has been the
Surgical interventions aimed at relieving ana- subject of some debate. In older children without
tomical obstruction of the upper airway represent comorbidities and mild sleep apnea, adenoton-
an approach to avoid tracheostomy. Three studies sillectomy is often performed on an outpatient
support a low rate of tracheostomy following such basis. Complication rates in these patients are
surgical intervention in this patient population. low, approximately 0.2–8.3% (Rodman et al.
In 25 CP patients treated with adenotonsillectomy, 2013). Various studies have sought to characterize
only 16% required tracheostomy, at a mean factors that predict postoperative complica-
follow-up time of 34 months (Magardino and tions following adenotonsillectomy. Overall,
Tom 1999). In a second study, only 17% of CP higher rates of complications and unplanned
patients treated with multilevel surgery required readmissions are found when adenotonsillectomy
tracheostomy at 30-month follow-up (Cohen et al. is performed for OSA versus other causes
1997). Thirteen percent of neurologically (9.8% vs. 6.5%) and for those under 3 years of
impaired patients in another study required trache- age versus those over 3 (10.7 vs. 2.3) (Rodman
ostomy after adenotonsillectomy and UPPP, et al. 2013). Severity of OSA influences postop-
(Kosko and Derkay 1995) with unclear duration erative complications, with AHI > 10, respiratory
of follow-up. Conversely, one study paints a disturbance index >40, and oxygen saturation
bleaker picture, concluding that 64% of children nadir <70% correlating with higher rates of com-
with CP treated with adenotonsillectomy ulti- plications (Rodman et al. 2013).
mately required tracheostomy due to lack of sig- Cerebral palsy has been linked to higher
nificant improvement, at an average postoperative rates of postoperative complications following
time of 1.9 years (Kontorinis et al. 2013). adenotonsillectomy, due to poor muscle tone, ana-
This study also showed that the likelihood of tomical abnormalities, and poor brain stem
needing tracheostomy after sleep apnea surgery coordination. Respiratory complications are com-
correlated to more advanced age, with all children mon and can include airway obstruction and
over the age 14 years ultimately requiring desaturations, requiring intervention in the form
of supplemental oxygen, placement of nasopha- Cross-References

ryngeal airway, and even unplanned intubation
(Biavati et al. 1997). Biavati et al. found CP to ▶ Medical Management of Tracheostomy in the
be the comorbidity that most increased the likeli- Child with Cerebral Palsy
hood of having a complicated postoperative ▶ Obstructive Sleep Apnea in Children with
course, with an odds ratio of 6.8. The comorbidity Cerebral Palsy
next most likely to result in postoperative compli- ▶ Surgical Management of Tracheostomies and
cations was seizure history with an odds ratio Tracheal Diversion in Children with Cerebral
of 5.2, an important finding as well, given that Palsy
seizures are not uncommon in CP patients
(Biavati et al. 1997).
CP is also associated with higher rates of
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Surgical Management
of Tracheostomies and Tracheal 57
Diversion in Children
with Cerebral Palsy
Richard Schmidt, Christopher Tsang, and Patrick Barth
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 830
History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 830
Natural History and Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 831
Indications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 831
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 831
Tracheostomy Technique . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 831
Diversion Techniques . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 833
Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 834
Complications After Tracheostomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 834
Immediate Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 835
Complications of Tracheal Diversion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 837
Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 838
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 838
Abstract
Children with cerebral palsy are most likely
to have a tracheostomy placed for upper air-
way obstruction, although it may also aid in
R. Schmidt (*) · P. Barth
Division of Pediatric Otolaryngology, Nemours duPont
pulmonary toilet. The tracheostomy proce-
Hospital for Children, Wilmington, DE, USA dure is most safely performed in the operating
Department of Otolaryngology, Sidney Kimmel Medical
room under general, endotracheal anesthesia.
College of Thomas Jefferson University, Philadelphia, PA, Initial postoperative care occurs in an inten-
USA sive care unit until the first tracheostomy
e-mail: rschmidt@nemours.org; tube change, usually on postoperative day
patrick.barth@nemours.org
5. However, a large percentage of children
C. Tsang who receive a tracheostomy experience one
Surgery, Nemours Alfred I. DuPont Hospital for Children,
or more complications. Complications are clas-
Wilmington, DE, USA sified as immediate (occurring during surgery),
e-mail: Christopher.Tsang@nemours.org

https://doi.org/10.1007/978-3-319-74558-9_225
830 R. Schmidt et al.
early (occurring prior to the first tracheostomy obstruction even while awake. In particular,
tube change), or late (occurring after the first children with severe neuromotor impairment
tracheostomy tube change) with late com- are at increased risk for this condition. Flexible
plications being by far the most common. nasopharyngolaryngoscopy (NPL) may be
While most complications are minor, acciden- performed to assess the airway, and this typi-
tal decannulation, tube obstruction, and bleed- cally demonstrates pharyngeal wall collapse
ing from a tracheo-innominate fistula can be similar to that seen in children with OSA (Wil-
life-threatening. The surgical technique for tra- kinson et al. 2006).
cheostomy should include the use of stay
sutures and stomal maturation sutures as
these help to minimize immediate and early History
postoperative complications. Children, partic-
ularly those who have already received a tra- Asclepiades of Bithynia, a Greek physician who
cheostomy, with significant difficulties lived around 100 BC, is credited with the first
maintaining pulmonary hygiene or with recur- description of a tracheostomy, but Paul of Aegina
rent aspiration pneumonia may benefit from a is believed to have performed the first success-
procedure to separate the airway from the ful tracheostomy in the seventh century AD
digestive tract. Two such procedures are the (Yapijakis 2009). His description of the procedure
laryngotracheal separation and tracheoe- is remarkably consistent with modern techniques:
sophageal diversion. “[B]ending the patient’s head backwards, so as to
bring the windpipe better into view, we are to
Keywords make a transverse incision between two of the
Cerebral palsy · Tracheostomy · rings, so as that it may not be the cartilage,
Laryngotracheal separation · Surgical which is divided, but the membrane in between
technique · Complications the cartilages. . .” (Gurunluoglu and Gurunluoglu
2003). By the nineteenth century, the procedure
was more common. Armand Trousseau, among
Introduction others, performed tracheostomy to treat patients
suffering from dyspnea caused by diphtheria
Although cerebral palsy (CP) is considered a non- (Dal'Astra et al. 2017).
progressive disorder of motor function; symp- For much of its history, tracheostomy was used
toms of airway compromise often worsen as to treat acute upper airway obstruction, often as-
these children age. Poor neuromuscular tone is sociated with infectious diseases. With the advent
likely the reason for this progression. As the of vaccines against Haemophilus influenzae and
child grows and gains weight, hypotonic muscles Corynebacterium diphtheriae in the twentieth
of the upper aerodigestive tract are unable to pro- century, once-common causes of acute upper air-
vide the tonal support necessary to maintain way obstruction all but vanished (de Trey et al.
patency of the pharynx and larynx (Kontorinis 2013). However, improved management of
et al. 2013). Laryngopharyngeal reflux (LPR), chronic life-threatening conditions in the second
craniofacial malformations, and poor oropharyn- half of the twentieth century, particularly better
geal secretion management contribute to airway intensive care protocols, endotracheal intubation,
obstruction as well (Karkos and Papouliakos and mechanical ventilation gave rise to a com-
2014; Cohen et al. 2002). pletely new set of indications for the procedure.
Upper airway obstruction in children with CP Today, chronic upper airway obstruction, pro-
often manifests as obstructive sleep apnea longed mechanical ventilation, and poor pulmo-
(OSA) (Garcia et al. 2016). However, a certain nary toilet are the most common indications for
subset of these children will have upper airway pediatric tracheostomy.
57 Surgical Management of Tracheostomies and Tracheal Diversion in Children with Cerebral Palsy 831
Natural History and Pathophysiology drastic procedure than a tracheostomy. There are
several diversion procedures, namely, tracheo-
Indications esophageal diversion (TED) or laryngotracheal
separation (LTS). These two procedures describe
The most common indication for tracheostomy techniques by which the larynx is surgically sep-
in children with CP is upper airway obstruction. arated from the rest of the trachea (Fig. 3).
Some children also require the procedure to
improve pulmonary toilet. Although tracheos-
tomy has a long and sometimes ignoble history, Treatment
improved surgical technique and improved peri-
operative and postoperative care in recent decades Tracheostomy Technique
have made it a very safe procedure (Wilcox et al.
2016; Goldenberg et al. 2000). Nonetheless, one The ideal setting for pediatric tracheostomy is
should not lose sight of the profound impact a in the operating room with an oral endotracheal
tracheostomy will have on the child and his/her tube in place and continuous cardiopulmonary
caregivers. It may alter the type and location of monitoring under the supervision of a pediatric
therapy that the child can receive and may even anesthesiologist. With the child supine and under
necessitate moving from home into a skilled nurs- general anesthesia, we perform a midline skin
ing facility. For these reasons and others, all mem- incision. Our group is divided (as is the literature)
bers of the care team should participate in the as to whether a horizontal incision made just infe-
decision to perform a tracheostomy. Likewise, a rior to the cricoid cartilage or a vertical incision is
tracheostomy should only be performed after best. Proponents of the horizontal incision believe
other, less invasive measures are unsuccessful. that the scar will be less unsightly if the child is
While detailed discussion of the management decannulated, while proponents of the vertical
of upper airway obstruction in children with CP incision believe that it allows for improved access
is beyond the scope of this chapter, it is important to the trachea and more effective maturation of the
to note many options are available precisely stoma using our standard maturation technique.
because none is universally effective. Medical As the procedure proceeds deep to the skin, we
management of reflux and nonsurgical therapy recommend removing a core of subcutaneous adi-
to decrease salivary secretions are often used as pose tissue until the fascia of the strap muscles is
first-line therapy for airway symptoms (Karkos readily identified. Regardless of the type of skin
and Papouliakos 2014). Positive airway pressure incision employed, dissection now proceeds in a
(PAP) is effective but often poorly tolerated (Haw- vertical direction to avoid undue trauma to the
kins et al. 2016). Adenotonsillectomy will im- strap muscles and injury to nearby vascular struc-
prove symptoms in a majority of children with tures, particularly the anterior jugular veins. We
CP who also have OSA (Magardino and Tom separate the strap muscles along their midline
1999). However, the benefit appears to be short- raphe and retract them laterally out of the opera-
lived in many children. Kontorinis and colleagues tive field. At this time, the cricoid and upper
found that 64% of children with CP initially tracheal cartilages are identified. If the thyroid
treated with adenotonsillectomy ultimately re- isthmus is encountered, it can be either divided
ceived a tracheostomy with an average interval (typically using either electrocautery or suture
of 1.9 years (range 0.5–3.5) between procedures ligation with nonabsorbable suture) or retracted
(Kontorinis et al. 2013). out of the way. We prefer to divide the thyroid
It should be noted that children with signifi- isthmus as this maneuver reduces the risk of future
cant difficulties maintaining pulmonary hygiene stomal occlusion and chondritis, although it
or with recurrent sequelae from chronic aspiration increases the risk for short-term tracheostomal
(e.g., pneumonia) may benefit from an even more bleeding (Kremer et al. 2002).
Fig. 1 Location of
tracheostomy incision
Once the upper trachea is exposed, we place Next, maturing sutures with braided absorb-
two stay sutures into the anterolateral aspects of able suture (e.g., Vicryl) are placed to secure
the trachea on either side of the planned tracheot- the dermis to the anterolateral tracheal wall
omy incision. A nonabsorbable suture such as (Fig. 2a, b). Care must be taken in placing these
Prolene is ideal for this purpose. These sutures sutures so that subcutaneous fat is not pulled
are placed through the third and fourth tracheal into the surgical field. Rather, these sutures should
cartilages, but ideally not into the lumen of the prevent structures from migrating over the inci-
trachea itself. They are inserted in a vertical para- sion in the event of an early, accidental de-
median orientation so that they will straddle the cannulation. Maturing sutures also make the
soon to be created midline tracheal incision. If creation of a false passage by inadvertent insertion
properly placed, these sutures may be used for of the tracheostomy tube into the soft tissue ante-
retraction and stabilization of the trachea for the rior to the trachea less likely. Moreover, there is
remainder of the procedure, as well as postopera- evidence that maturing sutures actually decrease
tively at the bedside in case of accidental dis- the risk of both accidental decannulation and
lodgement or decannulation. return trips to the OR for tracheostomy-related
We incise the trachea through the exposed complications (Park et al. 1999). Although less
tracheal rings vertically in the midline with either of an issue in children with CP, who will likely
a #11 or #15 blade (Fig. 1). The goal of this tech- require a tracheostomy for the remainder of their
nique is to protect (as much as possible) the struc- lives, there is a theoretical concern that maturing
tural integrity of the trachea. In adult sutures will lead to an increased incidence of
tracheostomies, the airway is usually entered some- a persistent tracheocutaneous fistula after de-
what differently; either the central portion of the cannulation. However, the literature does not sup-
tracheal ring is excised to create a tracheal window port this concern (Colman et al. 2010).
or an inferiorly based Bjork flap is created. How- At this point in the procedure, we request that
ever, using an animal model, Fry and colleagues the anesthesiologist begin withdrawing the endo-
demonstrated that a vertical incision resulted in tracheal tube (ETT). Once the ETT is just above
no significant increase in airflow resistance after the tracheostomy incision, withdrawal is halted.
decannulation when compared to controls (i.e., The ETT remains in this position until the com-
unoperated subjects). In contrast, inferiorly based pletion of the procedure, including securing of the
flaps and “H”-type incisions both resulted in tracheostomy tube. This technique allows for easy
increased airflow resistance when compared to reintubation in the event of difficulty inserting the
the control animals (Fry et al. 1985). However, tracheostomy tube. Next, the tracheal incision is
older children who are essentially adult-sized may gently dilated with a hemostat, and the tracheos-
require a Bjork flap, especially if the trachea is tomy tube is inserted. The anesthesia circuit is
relatively deep compared to the skin. connected to the tracheostomy tube, and the
Fig. 2 (a and b) Maturing sutures with braided absorbable suture (e.g., Vicryl) are placed to secure the dermis to the
anterolateral tracheal wall, courtesy of Dr. Steven Cook
presence of end-tidal CO2 is confirmed. A mem- technically difficult will have the first change per-
ber of the anesthesia team will also auscultate for formed in the operating room. This may include
bilateral breath sounds. Finally, the tracheostomy patient characteristics such as a thick neck/deep
tube is secured with a Velcro collar, and the stay tracheostomy tract, abnormal tracheal anatomy,
sutures are secured to the chest wall with adhe- presence of large-caliber blood vessels in the sur-
sives; these stay sutures are usually labeled “Left” gical field, or craniofacial abnormalities (e.g.,
and “Right” to avoid confusion in case of emer- Pierre Robin sequence, macroglossia, etc.). If
gencies. At this time, the ETT is completely the change is performed without difficulty and
removed. the stoma appears to be healing well, the stay
We monitor the child in the pediatric intensive sutures are removed, and further tracheostomy
care unit (PICU) after surgery, until at least first changes are delegated to nursing and respiratory
tracheostomy tube change, which is performed by personnel.
members of the otolaryngology team. Most com-
monly, the first tube change is performed at the
bedside on postoperative day 5, although this can Diversion Techniques
vary depending on various factors, including
patient nutrition, local infection, bleeding risk, or After the patient is endotracheally intubated,
need for further procedures. If there is evidence the skin is incised in a horizontal fashion down
that the tract between the patient’s skin and tra- to the strap musculature. These muscles are
chea is not well-formed, then the first change may either retracted or divided so as to expose the
be delayed until adequate wound healing has entire larynx and cervical trachea. The trachea is
occurred. Additionally, individual patient charac- transected through the cervical segment and is
teristics may necessitate a change in timing and/or either closed as a blind pouch resulting in a
venue for the change. For example, children laryngotracheal separation (LTS) or diverted into
whose anatomy makes them difficult to intubate the cervical esophagus resulting in a tracheoe-
or those whose tracheostomy procedure was sophageal diversion (TED) (Fig. 3). Care is
Fig. 3 Tracheal diversion techniques
taken during this portion of the procedure to with tracheostomy tubes will experience more
properly identify and preserve the cervical than one complication (Wilcox et al. 2016).
esophagus. It may also be beneficial to identify These facts are not surprising given the nature of
the recurrent laryngeal nerves, which run in the the procedure, which results in an indwelling for-
tracheoesophageal grooves on either side and eign body, in a non-sterile location, exposed to
innervate the intrinsic laryngeal musculature, both the skin and respiratory pathogens and sub-
including the vocal cords. This way, if the projected to considerable movement against native
cedure were to be reversed in the future, it may be tissues. The overall mortality rate for pediatric
possible for the child to phonate to a certain tracheostomy has been reported to be over 40%
degree. (Wilcox et al. 2016; Kremer et al. 2002). Most
of these deaths were attributable to the children’s
underlying medical problems, however, and the
Complications tracheostomy-specific mortality is likely less than
4% (Wilcox et al. 2016). In this section we will
Complications After Tracheostomy take an in-depth look at complications after tra-
cheostomy. Tracheostomy complications are
Unfortunately, complications of tracheostomy are usually classified as immediate, early (occurring
quite common. As many as 77% of children with a within the first week or prior to the first tracheos-
tracheostomy will experience a complication, tomy tube change), or late (occurring after the
most often after the first tracheostomy tube first week or tracheostomy tube change) compli-
change (Carr et al. 2001). A majority of children cations (Table 1).
Table 1 Complications of tracheostomy Airway fire is a dreaded complication of head

Early and neck surgery. It can occur any time there is an
Hemorrhage open airway circuit and a spark source such as
Tube dislodgement/obstruction electrocautery. These two conditions exist during
Interstitial air, pneumothorax, pneumomediastinum every tracheostomy, so special care must be taken
Infection to avoid fire. In particular, we will have our anes-
Late thesia colleagues lower the partial oxygen content
Granulations (FiO2) to below 30% prior to incising the trachea
Infection (tracheitis) and are careful to avoid using electrocautery once
Accidental decannulation/tube obstruction the trachea has been opened.
Hemorrhage/tracheo-innominate fistula
Tracheocutaneous fistula
Early Complications
Tracheal stenosis
Bleeding in the early postoperative period is most
likely from the cut edge of the thyroid gland or
Immediate Complications from inadvertent trauma to the strap muscles
during surgical dissection. Often such bleeding
Intraoperative complications include bleeding, is self-limited and requires no treatment. Occa-
injury to adjacent structures including the cricoid sionally, application of absorbable hemostatic
cartilage and esophagus, loss of the airway, pneu- sponges to the wound is necessary. Rarely, these
mothorax, and airway fire (Goldenberg et al. bleeds require control in the operating room.
2000; Tantinikorn et al. 2003). Bleeding is usually Accidental decannulation (tube dislodgement)
from the anterior jugular veins, the strap muscles, can occur as either an early or a late complication;
or the thyroid gland and can be minimized by however, dislodgement prior to the formation of a
careful dissection in the midline, thereby avoiding well-healed stoma is much more likely to result in
injury to these vascular structures. Meticulous difficulty reinserting the tube. In a child with
hemostasis during dissection is critical to this significant upper airway obstruction or respiratory
endeavor. Similarly, careful dissection and inser- compromise, dislodgement must be recognized
tion of the tracheostomy tube as well as a thor- quickly, or it can lead to respiratory compromise
ough knowledge of the relevant anatomy should followed by cardiac arrest. Indeed, accidental
allow the surgeon to minimize the risk of injury to decannulation and tube obstruction are the most
adjacent structures. To avoid losing control of commonly identified causes of tracheostomy-
the airway during the procedure, we leave the related death in children (Wilcox et al. 2016).
ETT in the upper trachea until the surgery is They are also among the most common compli-
completed and the tracheostomy tube is secured. cations, comprising over 50% of both early and
This is particularly important in patients whose late serious complications (Corbett et al. 2007;
anatomy may make emergent reintubation diffi- Simma et al. 1994).
cult or impossible. If the tracheostomy tube is discovered to be
Pneumothorax is an uncommon but real risk of dislodged in the early postoperative period
the procedure. This may result either from high (or becomes plugged and needs to be removed),
ventilatory pressures or from accidental injury to it will need to be replaced, or the child will need
the pleura and/or lung apices from surgical dis- to be reintubated. Replacement is ideal, but re-
section. In children, the lung apices extend into intubation or insertion of an ETT into the trache-
the neck more commonly than in adults. If there is ostomy stoma may be lifesaving. The stay sutures
a sudden change in ventilatory parameters during should be used to control the trachea during
the procedure, a chest X-ray should be obtained. replacement, and excellent lighting, preferably
If a pneumothorax is detected in this setting, it from a headlight, is important. Occasionally,
should be treated appropriately with chest tube the tube can be reinserted over a flexible la-
placement. ryngoscope using a Seldinger technique.
Division of the thyroid isthmus and maturation of Peristomal granulations occur externally, while
the stoma should make re-insertion of the tube suprastomal granulations occur internally. The
easier (Park et al. 1999). etiology for both entities is believed to be a for-
Interstitial air, pneumothorax, and pneumome- eign body reaction to the tracheostomy tube.
diastinum all have similar pathophysiology: an Because they are so common and often of no
opening in the airway that allows air to escape clinical consequence, many authors consider
and dissect through body tissues but not escape granulations to be sequelae of the procedure rather
adequately through the skin incision. Frequently than complications (Parrilla et al. 2007). Granula-
cited causes include injury to the lung apices, tions should be treated if they bleed, interfere
air escaping through the tracheal incision and with tracheostomy tube changes, or cause airway
dissecting through the subcutaneous or deeper obstruction. Treatment options for peristomal
spaces, or rupture of an alveolar bleb. Oftentimes granulations include topical antibiotic/steroid
these are asymptomatic and only discovered combinations, silver nitrate cautery, or excision.
because chest X-rays are routinely performed Symptomatic suprastomal granulations require
postoperatively. Conservative therapy will fre- excision via a trans-laryngeal or combined trans-
quently suffice although a pneumothorax may laryngeal/trans-stomal approach.
require a chest tube for treatment. Children with long-standing tracheostomy
Infection at the tracheostomy site is not as tubes are frequently colonized with Pseudomonas
common as one would expect considering that aeruginosa, Staphylococcus aureus, or both. Col-
the wound is often bathed in respiratory secre- onization alone should not prompt treatment,
tions. This is likely due to standardized nurs- unless signs of infection are present (Dal'Astra
ing protocols for tracheostomy care and the et al. 2017). If signs of soft tissue infection,
neck’s excellent blood supply. If infection chondritis, perichondritis, and/or tracheitis are
occurs, cultures should be obtained and used present, then cultures may be obtained to better
to direct systemic and/or topical antimicrobial direct antimicrobial therapy.
therapy. Tracheostomy tube obstruction and acci-
dental decannulation are among the most fre-
Late Complications quent serious late complications. In an audit of
Late complications after tracheostomy are up to over 100 children who underwent tracheostomy at
six times more common than early complications, a large children’s hospital in the United Kingdom,
with a majority of patients experiencing more than 50% of the late complications were either tube
one (Wilcox et al. 2016; Carr et al. 2001). The obstruction or accidental decannulation (Corbett
most common late complications are peristomal et al. 2007). A similar survey of almost 150
or suprastomal granulations, infection (tracheitis), patients at a children’s hospital in the United
tube obstruction or accidental decannulation, sto- States found that 16% of all patients with trache-
mal bleeding, and persistent tracheocutaneous ostomy experienced at least one of these two
fistula after decannulation. Less common compli- events (Carr et al. 2001). Reviews of the in-
cations include subglottic or upper tracheal steno- ternational literature have found similar rates
sis (often related to prolonged intubation prior to of obstruction and accidental decannulation
tracheostomy), tracheoesophageal fistula, and (Dal'Astra et al. 2017). Moreover, these are the
tracheo-innominate fistula (TIF). Persistent complications most often resulting in patient
tracheocutaneous fistula and subglottic or upper death, underscoring the importance of prevention
tracheal stenosis are relevant for the child who and, failing that, rapid diagnosis and treatment
has been or is undergoing evaluation for de- (Kremer et al. 2002).
cannulation and will not be discussed further Diligent tracheostomy tube care, including the
here. Stomal bleeding and TIF will be covered use of humidification to prevent tenacious secre-
together as the key to managing the latter is not tions from clogging the tube and judicious use of
to confuse it with the former. suctioning, may help to minimize tracheostomy
tube obstruction. Too infrequent suctioning may massive bleed, highlighting the importance of
lead to tube occlusion; however, suctioning tracheoscopy for tracheal bleeding (Joshi et al.
beyond the distal end of the tube may lead to 2007).
mucosal injury, bleeding, and tube occlusion The etiology of TIF is believed to be related to
with dried blood. Selection of the proper length chronic repetitive trauma on the anterior tracheal
and diameter of the tube will protect against acci- wall caused either by the tip of the tracheostomy
dental decannulation, as will an appropriately tube or its cuff. Repetitive trauma then leads to
tightened tracheostomy collar. For these reasons, inflammatory changes to the tracheal wall and
adequate training of all individuals who will be adjacent innominate artery. The resultant tissue
caring for a child with a tracheostomy, whether at necrosis leads to fistula formation (Goldenberg
home or in a facility, is important. et al. 2000; Miyake et al. 2013).
Caregivers must be trained in the diagnoses Children are more at risk for TIF formation
and management of tracheostomy tube problems than are adults, and children with neuromuscular
such as obstruction or accidental decannulation. disease appear to be at even higher risk (Das et al.
To this end, training in emergency tracheostomy 2012). Contributing factors to TIF formation in
tube changes and pediatric basic life support this population include distortion of the normal
(BLS) is critical for caregivers prior to patient anatomical relationship between the trachea and
discharge from the acute care facility. mediastinal vessels due to scoliosis as well as
Bleeding from the tracheostomy is appropri- frequent involuntary movements secondary to sei-
ately a concern for caregivers. Although the vast zures (Byard and Gilbert 2011).
majority of these episodes are from benign In the event of a massive bleed, intubation
sources such as tracheitis or suction trauma, one through the tracheal stoma with an endotracheal
must always consider tracheo-innominate fistula tube and inflating the cuff to tamponade the artery
(TIF) in the differential diagnosis of such bleeds. may be lifesaving. Definitive treatment is to
Bleeding from external, peristomal, granulation surgically repair or reposition the innominate
tissue is usually obvious as the bleeding will be artery through a sternotomy, although endo-
light and around, rather than through the tube. vascular stenting has also been reported (Miyake
Silver nitrate cautery is often effective in treating et al. 2013).
such bleeds.
A more thorough investigation is required for
bleeding through the tracheostomy tube to evalu- Complications of Tracheal Diversion
ate for signs of a TIF. Flexible endoscopy through
the stoma with the tube withdrawn is essential. With respect to the diversion techniques, both
Endoscopic evaluation of the trachea is performed procedures have similar success rates as far as
to assess for evidence of erosion or granulation reducing the frequency of suctioning and inci-
tissue, with particular attention to the anterior dence of aspiration pneumonia. One advantage
tracheal wall and carina. If significant clots or of LTS over TED is the lack of a second suture
bleeding is noted, further investigation with rigid line at the tracheoesophageal anastomosis, which
endoscopy in the operating room and/or angiog- reduces the risk for potential wound breakdown/
raphy is required. fistula formation. In both procedures, there are
Although TIF is a rare complication of trache- several not insignificant risks, ranging from
ostomy, occurring somewhere between 0.1 and fistula formation and stomal stenosis to tracheo-
1% of patients (Joshi et al. 2007), it carries an innominate fistulas. In a large series of 56 children
80–90% mortality rate (Goldenberg et al. 2000). who underwent LTS, every child had a significant
Affected patients often present with massive decrease in the number of hospital admissions for
bleeding resulting in dire outcomes. However, pneumonia after surgery (4.6 admissions/year
up to one third of these patients may present preoperatively, 0.73 admissions/year postopera-
with a “sentinel” bleed days to weeks before a tively). In this series, the most common
complication was a transient fistula between the References

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Part XII
Genitourinary
Toilet Training and Bladder Control
Puneeta Ramachandra and T. Ernesto Figueroa
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 844
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 844
Normal Toilet Training and Voiding Review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 844
Voiding Issues in Upper Motor Neuron Versus Lower Motor Neuron Lesions . . . . . . . . 844
Factors Influencing Toilet Training in Children with CP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 845
Effect of Constipation on Voiding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 846
Summary of Toilet Training . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 846
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 846
Urologic Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 846
Noninvasive Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 847
Invasive Testing: Urodynamic Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 847
Treatment Options . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 848
Environmental Modification and Communication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 848
Bowel Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 848
Medications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 849
Bladder Catheterization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 849
Selective Dorsal Rhizotomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 849
Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 849
Upper Urinary Tract Deterioration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 849
Changes in Adulthood . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 850
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 850
Abstract
Patients with cerebral palsy often have changes
P. Ramachandra (*) · T. E. Figueroa to their urinary tract function. This can lead
Division of Pediatric Urology, Department of Surgery,
Nemours/Alfred I. DuPont Hospital for Children, to significant morbidity over a lifetime. The
Wilmington, DE, USA etiology of urinary tract dysfunction is multi-
Department of Urology and Pediatrics, Sidney Kimmel
factorial and complex. Understanding and
Medical College of Thomas Jefferson University, managing urinary tract symptoms can have
Philadelphia, PA, USA a huge impact on health and quality of life for
e-mail: Puneeta.Ramachandra@nemours.org; patients and caregivers.
T.Figueroa@nemours.org

https://doi.org/10.1007/978-3-319-74558-9_56
844 P. Ramachandra and T. E. Figueroa
Keywords sacral spinal cord, and peripheral nervous sys-

Toilet training · Urinary tract · Urodynamics · tem. Readiness for toilet training depends on
Incontinence · Constipation behavioral, physiologic, and developmental
criteria rather than the child’s chronologic age.
These criteria include physical abilities (e.g.,
Introduction ability to get to a toilet, undress, and sit with
stability), cognitive abilities (e.g., expressing
Cerebral palsy (CP) represents a group of chronic, and vocalizing need to eliminate), and voluntary
nonprogressive motor disorders resulting from control of sphincter mechanisms. In addition, the
perinatal or postnatal central nervous system child needs to be able to be conscious of bladder
insult. The cerebral injury, classified as an upper filling, be able to inhibit reflex bladder contrac-
motor neuron lesion, removes normal inhibitory tions, and start voiding voluntarily in a socially
control over the micturition center in the pons but appropriate manner.
may also affect other areas of the nervous system
(Decter et al. 1987). In addition to motor distur-
bances, patients are often affected by disturbances Voiding Issues in Upper Motor Neuron
in cognition, communication, sensation, and other Versus Lower Motor Neuron Lesions
medical comorbidities. Over half of children and
adults with CP experience at least one lower uri- In very broad terms, neurogenic bladder dys-
nary tract symptom (Samijn et al. 2017a). While function can be categorized as upper motor neu-
urinary incontinence is the most frequent com- ron (UMN) versus lower motor neuron (LMN)
plaint in patients with CP, other symptoms such dysfunction. UMN bladder describes the pattern
as urinary tract infections (UTIs) or difficulty of micturition due to an injury to the suprasacral
emptying the bladder can also occur. Since CP is nervous system including the brain. Lesions
a life-long condition, the morbidity of urinary above the pons such as cerebral injury fall into
tract dysfunction is significant. Understanding the UMN lesion group. It is usually characterized
and managing urinary tract symptoms can help by detrusor overactivity (uninhibited bladder
improve health and quality of life for patients contractions) during filling and subsequent
and caregivers. decreased bladder capacity, with or without
detrusor sphincter dyssynergia (DSD). On the
other hand, LMN bladder results from damage
Natural History to the sacral spinal cord or peripheral nerves in
the pelvis. LMN dysfunction consists of
Normal Toilet Training and Voiding acontractile or flaccid bladders (Wein 2012).
Review CP is the result of an injury to the brain;
therefore, upper motor neuron dysfunction
Toilet training represents an important develop- would be expected. In reality, the dysfunction
mental milestone for children and parents. The of the lower urinary tract in children with CP
definition of successful toilet training varies by can be quite varied; thus the urological abnor-
culture but usually involves achieving conti- malities can span the spectrum from normal
nence of the bladder and bowel with ability to voiding, to urinary incontinence or urinary
express the need to eliminate. In the USA, most retention.
developmentally normal children are toilet Children with CP exhibit a range of symp-
trained between 24 and 48 months of age toms and findings during lower urinary tract
(Stadtler et al. 1999). Normal micturition evaluation and can have UMN, LMN, or mixed
involves complex interactions between the upper and lower motor neuron lesions. In an
brain, pontine micturition center (PMC) in the early study of urodynamics (UDS) in 57 children
brain stem, the sacral micturition center in the with CP, Decter et al. (1987) found that 86% of
58 Toilet Training and Bladder Control in Children with Cerebral Palsy 845
patients exhibited the expected picture of upper Factors Influencing Toilet Training
motor neuron lesion including uninhibited blad- in Children with CP
der contractions, DSD, hyperactive sacral
reflexes, decreased bladder capacity, hypertonic- Few studies have been done to guide expectations
ity of the pelvic floor, and lack of voluntary for toilet training in children with CP. In 2001,
control. Surprisingly, 11% of children demon- Roijen et al. performed a review to investigate
strated incomplete lower motor neuron lesions the development of bladder control and identify
including acontractile bladders, suggesting that risk factors for not achieving urinary continence.
the neurologic insult in CP could involve the This study, which included 459 participants ages
spinal cord as well. Samijn et al. (2017a) 4–18 years, demonstrated that 70% of patients
performed a systematic review of studies were able to achieve continence but were delayed
examining lower urinary tract symptoms compared to typically developing children. The
(LUTS) and urodynamic findings in patients vast majority of continent participants (97%)
with CP. The paper included 15 articles with achieved daytime continence followed by noctur-
urodynamic findings and noted that abnormal nal continence, and most achieved nocturnal
urodynamics was found in 84.5% of patients on continence within a year following daytime con-
average. Neurogenic detrusor overactivity tinence. This is similar to expected toilet training
(NDO) was the most commonly observed in typically developing children. If daytime con-
urodynamic abnormality with an average tinence was achieved after age 8 years, there was a
prevalence of 59% across 14 studies. significantly longer delay to gaining nocturnal
Reduced bladder capacity was found in 73.5% continence. 23.5% of the patients had persistent
of patients, while DSD was noted in 11% of urinary incontinence. Importantly, the study
patients. showed that patients with spastic quadriplegia
Hypertonicity of the pelvic floor, or inability and low intellectual capacity gained continence
to voluntarily control the pelvic floor related to at a later age and had lower probability of gaining
spasticity, can cause difficulty urinating in some continence overall. The combination of low
patients with CP. This complaint seems to occur intellectual capacity and spastic quadriplegia had
more often as patients age (Karaman et al. 2005). a bigger influence on continence than either factor
It has been suggested that patients with difficulty alone. Patients with hemiplegia have a lower rate
urinating may progress to urinary retention in of LUTS and abnormal urodynamic findings, pos-
adult life (Mayo 1992). sibly due to plasticity of the central nervous sys-
LUTS have be documented across the tem, where the unaffected side assumes more
lifespan of patients with CP. Urinary tract symp- bladder control during development (Murphy
toms have been demonstrated in CP patients of et al. 2012).
all educational and functional levels. Symptoms Studies have also shown the influence of
and clinical presentation can vary, and several gross motor functional impairment on continence.
studies have attempted to clarify this topic via Recently one study found that children with Gross
questionnaires, interviews, and medical records. Motor Function Classification System (GMFCS)
Urinary incontinence is the most commonly level 4 and 5 had significantly higher odds
observed symptom in many studies, but the of having urinary incontinence (Samijn 2017b).
exact incidence is difficult to determine. Urinary Higher GMFCS level is associated with decreased
incontinence, urgency, and frequency are more ambulation and need for external mobility aids.
prevalent in children with CP compared to Children with impaired mobility would take lon-
healthy children (Ozturk et al. 2006). Other com- ger to reach a toilet. Those with impaired manual
mon symptoms are difficulty urinating, urinary skills would have difficulty undressing at the toilet
hesitancy, nocturia, nocturnal enuresis, urinary as well. This can be especially challenging given
tract infection (UTI), urinary retention, and that sudden urgency to urinate is common in the
upper urinary tract dysfunction. setting of neurogenic detrusor overactivity.
Expressing the need to urinate and desire to toilet trained. Toilet training may occur later in
achieve continence is also an important factor. these patients than in typically developing chil-
Arguably, communication ability is more impor- dren. Success in toilet training depends on intel-
tant than motor ability for some patients. Murphy lectual capacity, degree of motor impairment,
et al. (2012) studied 214 children and adults and ability to communicate. Lower urinary tract
with bladder symptoms across all GMFCS levels symptoms, especially urinary incontinence, are
who had the ability to answer yes/no questions. common. Referral to a urologist should be initi-
The patients all underwent urodynamic testing ated if there are lower urinary tract symptoms,
to characterize their bladder function and a “Func- history of UTIs, or spontaneous bladder control
tional Toileting Review” to better understand has not occurred by age 8 years.
their toileting process and environment. Manage-
ment was individualized based on findings and
included medications, management of constipa- Treatment
tion, behavioral modification, and bladder empty-
ing with intermittent catheterization. The authors The question of whether urologic evaluation is
concluded that functional communication and necessary for every patient with CP is controver-
modification of environment, equipment, and sial. Most children with CP are referred to a pedi-
staffing were essential in maintaining continence atric urologist if they have urologic symptoms or
despite severe physical impairment. If the patients urinary tract infection (UTI). There is a real con-
were able to reliably communicate their need to cern that voiding dysfunction or UTIs predispose
toilet and someone was able to assist, continence to upper urinary tract deterioration. There is also
could be achieved. a concern about progression of bladder dysfunc-
tion and upper urinary tract deterioration in
adulthood.
Effect of Constipation on Voiding
Chronic constipation is common in patients Urologic Evaluation

with CP and results from many factors including
immobility, slow colonic transit time, poor feed- Appropriate urologic evaluation begins with
ing, insufficient fluid intake, and chronic dehydra- a thorough history and physical examination.
tion. Constipation is known to cause painful Careful history should include information
muscle spasms, irritability, poor appetite, and sub- about incontinence of urine and feces, daytime
sequent growth impairment. Constipation can and nighttime continence, urinary urgency, fre-
also lead to reduced bladder capacity, detrusor quency, ability to initiate voiding, dysuria,
instability, urinary tract infections, and urinary hematuria, history of urinary retention, and
retention. Treatment of constipation depends on UTIs. The clinician should also inquire about
severity of symptoms. While some patients may intellectual capacity and the ability to communi-
respond to simple increased fiber and fluid intake, cate needs. Information regarding use of diapers;
others may require bowel cleanouts and daily use of restrooms either voluntary or with assis-
bowel regimens. The primary goal of bowel man- tance; and any prior efforts to achieve toilet
agement is attaining predictable, soft, formed training should be gathered. In addition, the
bowel movements with minimal incontinence. evaluation should include an assessment of uri-
nary behavior following orthopedic surgical
intervention. The subtype of CP is also impor-
Summary of Toilet Training tant, as patients with spastic quadriplegia tend to
have more urologic problems, whereas patients
In summary, over 50% of children with CP will with hemiplegia tend to have fewer symptoms
achieve urinary incontinence and be able to be (Murphy et al. 2012).
Depending on the degree of urinary due to the low incidence of structural abnormali-
continence, a voiding diary obtained at home ties (Brodak et al. 1994). However, in another
documenting the amount of voided urine and study, although the incidence of UTI was only
time of urination can assist the urologist in esti- 10% of the study population, 83% of those with
mating functional bladder capacity. This useful UTI had structural changes of the upper urinary
tool can only be applied to those children who tract (Decter et al. 1987). In a third study of
have some degree of urinary continence. Patients 33 children with CP from Turkey, 4 children had
who void involuntarily into diapers after the evidence of upper urinary tract deterioration on
expected age of toilet training (approximately ultrasound. Clinical symptoms of urinary reten-
4 years old) are more challenging to assess. The tion, hesitancy, and interrupted voiding as well as
voiding pattern in these children can be rather culture-proven febrile UTI correlated positively
normal and benign as a coordinated pattern with upper tract findings (Gündoğdu et al. 2013).
(detrusor contraction and urinary sphincter relax- Since ultrasound is a noninvasive imaging modal-
ation) or abnormal and potentially damaging as a ity, it would be reasonable to obtain in the setting
dyssynergic pattern (urinary sphincteric contrac- of a urinary tract infection.
tion at the time of detrusor contraction). Although Noninvasive urologic testing can include the
not every patient with CP who voids involuntarily use of uroflowmetry with or without pelvic floor
into the diaper needs urological investigation, electromyography (EMG) and measurement of
the occurrence of UTI, urinary retention, postvoid residual urine volume. In order to per-
hydronephrosis, urinary calculi, and bladder wall form a uroflow test, the patient must be able to
thickening by ultrasound mandate careful urologi- void voluntarily. Uroflowmetry demonstrates the
cal investigation. rate of urine flow and pattern of micturition.
A careful physical examination should docu- Adding EMG data can show external urinary
ment dependency on wheel chair or other assistive sphincter contraction during attempted micturi-
devices, abdominal distension or palpable stool tion. An interrupted or staccato urine flow pattern
content, upper and lower extremity spasticity, with EMG activation during voiding suggests
any perineal skin abnormalities due to inconti- detrusor sphincter dyssynergia and warrants fur-
nence, Tanner stage, and appearance of the geni- ther workup. Measuring postvoid residual volume
tals. In boys, the exam should also include the provides a good measure of the patient’s ability to
circumcision status and the position of the testes. empty his or her bladder. A chronically elevated
Undescended and secondarily ascended testes are postvoid residual volume could predispose
common in boys with spastic CP. patients to UTI. During the uroflowmetry, the
urologist can observe the patient void, standing
or sitting, to determine physical impediments to
Noninvasive Testing micturition.
The initial step in the assessment of CP patients

with urinary symptoms is the urinalysis and if Invasive Testing: Urodynamic Studies
suspicious for UTI, a urine culture. The next step
in a urologic evaluation is usually a renal and The next step in the evaluation of urinary tract
bladder ultrasound to assess the upper urinary dysfunction involves urodynamic testing or com-
tract. This may be especially warranted in patients plex cystometrogram with pelvic floor electromy-
with a history of UTI. In one study of 90 patients ography. This test consists of placing a catheter
who were evaluated with renal ultrasound pro- into the bladder to measure intravesical pressures
spectively, only 7 had any structural renal or blad- while filling the bladder with fluid. A second
der anomalies. None of the seven had a history pressure-sensing catheter is placed into the rectum
of UTI. The authors concluded that screening to measure intra-abdominal pressures. Subtracting
asymptomatic patients with CP is unwarranted intra-abdominal pressure from intravesical
pressures results in an estimate of pressure gener- optimize the opportunity for socially acceptable
ated by the detrusor muscle of the bladder. Patch urinary continence.
electrodes are placed on the perineum to measure
pelvic floor muscle activity.
There are two main phases of the study: filling Environmental Modification
phase and voiding phase. During bladder filling, and Communication
careful observations are made regarding presence
of uninhibited detrusor muscle contractions (neu- Physical access to a toilet can be a major barrier to
rogenic detrusor overactivity), bladder capacity, continence in patients with limited mobility.
urinary leakage, and appropriate sensations of When feasible the patient’s environment should
bladder filling. During the voiding phase, the be modified so that he or she can reach a toilet
strength of the detrusor contraction, pelvic floor quickly. Positioning aids to help the patient sit or
muscle activity, and ability to empty is noted. stand at the toilet are helpful as well. The ability to
Normally, the pelvic floor is completely relaxed undress and redress should be taken into account.
during micturition. Videofluoroscopy images of Clothing that is easy to remove and handle is
the bladder can also be obtained if an X-ray useful. The ability to communicate the need to
machine is available. These images can show the urinate voluntarily is essential to achieve toilet
contour of the bladder during filling and voiding, training. Timed voiding, offering regularly sched-
the presence or absence of vesicoureteral reflux of uled visits to the bathroom to void volitionally
urine, and the shape of the bladder neck and can, be helpful with some patients who are conti-
urethra during voiding. nent of urine but require assistance with
ambulation.
Treatment Options
Bowel Management
Treatment of bladder dysfunction depends on the
findings of the evaluation and should be tailored Aggressive management of constipation to treat
to each individual. Any therapy should address both symptoms of constipation and bladder
not only the anatomy and pathology of the urinary dysfunction in children with CP is an integral com-
tract but also the environmental and social barriers ponent of the management of urinary tract dysfunc-
in the toileting process. tion. The etiology of constipation is multifactorial
An important step in the urological manage- in children with CP, resulting from neurologic fac-
ment of CP patients is the determination of tors, immobility, medication side effects, and diet.
the patient’s likelihood to achieve toilet training Constipation can lead to painful muscle spasms,
or voluntary urination. Many factors can affect encopresis due to fecal impaction in the rectum,
this process, including UMN lesion, cognitive and bladder dysfunction including urinary reten-
and expressive difficulties, physical impedi- tion, urinary incontinence, and UTI. An individu-
ments, constipation, spasticity, and medication alized approach should be taken to allow the patient
side effects (e.g., anticholinergic agents for to have predictable regular stools. Adequate fiber
sialorrhea). Treatment should be reserved for and fluid intake should be assessed and augmented
patients with symptomatic urinary tract dysfunc- as needed, followed by the addition of laxatives and
tion (uncoordinated voiding, UTI, urinary reten- stool softeners. Optimizing the gastrocolic reflex by
tion) or for those patients who have achieved or directing the child to defecate after one of the meals
are likely to achieve toilet training but who strug- of the day on a routine basis should be part of the
gle with urinary incontinence. A thoughtful, approach to manage constipation. Referral to a
stepwise approach is necessary to minimize the gastroenterologist for refractory bowel issues
deleterious effects of bladder dysfunction and to should be considered.
Medications or in acute or chronic urinary retention. Lifelong

CIC can be done safely without sterile technique
Anticholinergic Medications at an interval that depends on the patients’ and
Anticholinergics are considered the first-line treat- caregivers’ needs. Patients require adequate
ment for bothersome urinary urgency, urinary manual dexterity and mobility to perform self-
frequency, urge incontinence, overactive bladder, catheterization. Indwelling bladder catheters can
and neurogenic detrusor overactivity. These med- be placed via the urethra or via a suprapubic
ications work by relaxing the smooth muscle approach and should be changed periodically
of the bladder thereby decreasing uninhibited to decrease the risk of UTIs. All patients who
contractions, increasing bladder capacity, and undergo repeated bladder catheterization will
relieving bothersome symptoms. Common side become colonized with bacteria but usually do
effects include constipation, urinary retention, not need to be treated for asymptomatic
dry mouth, and blurred vision, among others. In bacteriuria.
pediatric patients, the most commonly used
medication in the class is oxybutynin, which is
available in both immediate-release and extended- Selective Dorsal Rhizotomy
release formulations and comes as a liquid, pill,
topical gel, or transdermal patch. A more drastic approach to carefully chosen
Any CP patient taking anticholinergic medica- patients is the selective dorsal rhizotomy, a neu-
tions should be monitored for worsening consti- rosurgical procedure performed on patients with
pation, which is already highly prevalent in this spastic CP where the L1 to S2 nerve roots are
group. Fiber supplements or stool softeners selectively divided to reduce afferent sensory
should be considered. Patients should also be input thereby decreasing muscle spasticity. Lim-
monitored for urinary retention or worsening ited data with small numbers of patients in each
postvoid residual urine volumes. study suggest that this procedure can improve
bladder function (Chiu et al. 2014; Houle et al.
Desmopressin 1998).
Desmopressin, an analogue of antidiuretic Selective dorsal rhizotomy has also been
hormone, is an option to treat patients with pri- shown to potentially worsen or result in neuro-
mary nocturnal enuresis, in the absence of diurnal genic bladder or bowel complications. In one case
incontinence or detrusor overactivity. An oral series of 158 patients who underwent the proce-
dose is administered at bedtime with limited dure, 12.7% had postoperative urinary or bowel
fluid intake from 1 h before administration until symptoms including urinary incontinence, urinary
the next morning. After starting the medication, urgency, failure to toilet train, and fecal soiling
patients should be monitored for hyponatremia. (Steinbok and Schrag 1998). Changes to surgical
Specific efficacy in patients with CP has not been technique (less sectioning of S2 dorsal root or use
documented in the literature, and it would be of pudendal monitor) may result in fewer urologic
ineffective in patients with combined diurnal complications.
incontinence and nocturnal enuresis.
Complications
Bladder Catheterization
Upper Urinary Tract Deterioration
Clean intermittent catheterization (CIC) of the
bladder or indwelling bladder catheter both facil- Bladder dysfunction has the potential to cause
itate bladder emptying. These are especially use- upper urinary tract deterioration in the long term.
ful in patients with flaccid, underactive bladders In patients who have neurogenic bladder due to
spinal cord injury or spina bifida, there is clear medications, and spinal surgery. At least some of
evidence that the upper urinary tract deteriorates the patients had never had urologic evaluation in
when bladder pressures are consistently elevated childhood. This raises the concern that silent or
or when detrusor sphincter dyssynergia occurs. undiagnosed bladder dysfunction in childhood is
Recurrent febrile UTIs also potentially result in progressive. Evaluating and addressing urinary
kidney damage. A few studies have shown a sim- issues in childhood may prevent problems in
ilar correlation between upper urinary tract adulthood.
pathology and febrile UTI or detrusor sphincter To summarize, lower urinary tract symptoms
dyssynergia in CP patients (Decter et al. 1987; and bladder dysfunction are common in patients
Gündoğdu et al. 2013). However, identifying with cerebral palsy. Referral to a pediatric urolo-
other urodynamic parameters and risk factors for gist is important for any child with symptoms,
upper tract deterioration remains difficult due to especially history of urinary tract infection. Uro-
small numbers of patients in each study. As stated logic evaluation and intervention are important to
earlier, given the limited evidence available and the improve quality of life and prevent deterioration
ease of obtaining renal ultrasounds, any patient of the urinary tract with age.
who has a history of febrile UTIs or evidence of
detrusor sphincter dyssynergia should have imag-
ing of the upper urinary tract. The social stigma of
Cross-References
urinary incontinence in patients with incomplete
toilet training cannot be overemphasized. While
▶ Aging with Cerebral Palsy: Adult Musculoskel-
some of the more compromised CP patients who
etal Issues
remain diaper-dependent with physiologic invol-
▶ Dorsal Rhizotomy for Spasticity Management
untary voiding throughout life are “socially accept-
in Cerebral Palsy
able,” the more functional patient who is toilet
▶ Neurogenic Bladder in Cerebral Palsy: Upper
trained but struggles with daytime urinary inconti-
Motor Neuron
nence faces a significant social barrier. Correcting
the factors leading to incontinence in these patients
can be extremely helpful in the social integration of
References
these patients.
Brodak PP, Scherz HC, Packer MG (1994) Is urinary tract
screening necessary for patients with cerebral palsy?
Changes in Adulthood J Urol 152(5 Pt 1):1586–1587
Chiu PK, Yam KY, Lam TYet al (2014) Does selective dorsal
rhizotomy improve bladder function in children with
Studies regarding bladder symptoms and function cerebral palsy? Int Urol Nephrol 46(10):1929–1933
in adults with CP are scarce. Even more difficult to Decter RM, Bauer SB, Khoshbin S et al (1987)
characterize is how lower urinary tract symptoms Urodynamic assessment of children with cerebral
evolve from childhood to adulthood. One study palsy. J Urol 138(4 Pt 2):1110–1112
Gündoğdu G, Kömür M, Avlan D et al (2013) Relationship
postulated that neurogenic detrusor overactivity of bladder dysfunction with upper urinary tract deteri-
with low bladder capacity in childhood could oration in cerebral palsy. J Pediatr Urol 9(5):659–664
decompensate into neurogenic underactivity with Houle AM, Vernet O, Jednak R et al (1998) Bladder func-
age (Murphy et al. 2012). In another study, several tion before and after selective dorsal rhizotomy in chil-
dren with cerebral palsy. J Urol 160(3 Pt 2):1088–1091
subjects presented for evaluation only in the second Karaman MI, Kaya C, Caskurlu T (2005) Urodynamic
or third decade of life with previously undiagnosed findings in children with cerebral palsy. Int J Urol
voiding symptoms. Unlike studies in children, 12(8):717–720
adults had more urinary retention and decreased Mayo ME (1992) Lower urinary tract dysfunction in cere-
bral palsy. J Urol 147(2):419–420
voiding frequency, possibly due to chronic over- Murphy KP, Boutin SA, Ide KR (2012) Cerebral
distension of the bladder, prostatic enlargement palsy, neurogenic bladder, and outcomes of lifetime
with age, pharmacological effects of antispasmodic care. Dev Med Child Neurol 54(10):945–950
Ozturk M, Oktem F, Kisioglu N et al (2006) Bladder and Stadtler AC, Gorski PA, Brazelton TB (1999) Toilet train-
bowel control in children with cerebral palsy: case- ing methods, clinical interventions, and recommenda-
control study. Croat Med J 47(2):264–270 tions. American Academy of Pediatrics. Pediatrics
Roijen LE, Postema K, Limbeek VJ et al (2001) Develop- 103(6 Pt 2):1359–1368
ment of bladder control in children and adolescents Steinbok P, Schrag C (1998) Complications after selective
with cerebral palsy. Dev Med Child Neurol 43(2): posterior rhizotomy for spasticity in children with cere-
103–107 bral palsy. Pediatr Neurosurg 28(6):300–313
Samijn B, Van Laecke E, Renson C et al (2017a) Lower Wein AJ (2012) Pathophysiology and classification
urinary tract symptoms and urodynamic findings in of lower urinary tract dysfunction: overview. In:
children and adults with cerebral palsy: a systematic Kavoussi LR, Novick AC, Partin AW, Peters CA
review. Neurourol Urodyn 36(3):541–549 (eds) Campbell-Walsh urology, 10th edn. Saunders
Samijn B, Van den Broeck C, Deschepper E et al (2017b) Elsevier, Philadelphia, pp 1834–1846
Risk factors for daytime or combined incontinence in
children with cerebral palsy. J Urol 198(4):937–943
Neurogenic Bladder in Cerebral Palsy:
Upper Motor Neuron 59
Hong Truong and Ahmad H. Bani Hani
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 854
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 854
Normal Bladder Function . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 854
Lower Urinary Tract Dysfunction in Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 856
Pathogenesis of Urinary Tract Symptoms in Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . 857
Diagnostic Work Up and Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 859
Work Up of Urological Symptoms in Children with Cerebral Palsy . . . . . . . . . . . . . . . . . . . 859
Treatment of Lower Urinary Tract Symptoms in Children with Cerebral Palsy . . . . . . . 862
Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 867
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 867
Abstract motor, mental, cognitive, and neurological dis-

Although most children with cerebral palsy can abilities associated with cerebral palsy. While
eventually develop total urinary control, more routine urological evaluation in children with
than 50% of them suffer from a spectrum of cerebral palsy is not indicated as in the case in
lower urinary tract symptoms. The severity of children with spinal dysraphism, physicians
urinary symptoms depends on the extent of who care for children with cerebral palsy
should be familiar with urological manifesta-
tions of the disorder and refer children with
H. Truong
Department of Urology, Thomas Jefferson University
voiding complaints for urological work
Hospital, Philadelphia, PA, USA up. Common lower urinary tract complaints
e-mail: hong.truong@jefferson.edu in children with cerebral palsy include delay
A. H. Bani Hani (*) in toilet training, urinary incontinence, urinary
Division of Pediatric Urology, Nemours/Alfred I. duPont frequency, urgency, hesitancy in voiding,
Hospital for Children, Wilmington, DE, USA incomplete emptying, and recurrent urinary
Department of Urology and Pediatrics, Sidney Kimmel tract infections. Urodynamic studies in select
Medical college-Thomas Jefferson University, cerebral palsy patient populations demonstrate
e-mail: abani@nemours.org; Ahmad.banihani@
detrusor overactivity, reduced bladder capac-
nemours.org ity, detrusor-sphincter dyssynergy, and rarely

https://doi.org/10.1007/978-3-319-74558-9_57
854 H. Truong and A. H. Bani Hani
impaired bladder compliance and upper uri- palsy often do not ask or screen for existing
nary tract deterioration. In this chapter, we urinary symptoms, leading to under-referral of
discuss the physiology of bladder function, patients with voiding complaints for urological
urological presentations, diagnostic work up, evaluation and treatment (Yıldız et al. 2017).
and management of children with cerebral Problems related to the genitourinary tract are
palsy. among the most common reasons that young
adults with cerebral palsy require hospital
Keywords admission (Young et al. 2011). A large propor-
Neurogenic bladder · Detrusor · Urodynamic · tion of adult patients with cerebral palsy reported
Uroflow · Voiding diary · Vesicoureteral voiding symptoms causing interference with life,
reflux · Chronic kidney disease · requiring them to plan their activities around
Hydronephrosis · Botulinum toxin bladder symptoms and toilet availabilities
(Marciniak et al. 2014; Yıldız et al. 2017).
While cerebral palsy is not associated with pro-
Introduction gressive neurologic deficit, striated muscle spas-
ticity may worsen with age, leading to significant
Essential to bladder control and urinary conti- problems with bladder emptying that may
nence is physical maturation of the bladder and increase the risk for urinary tract infections.
the cortical pathways that regulate the micturition Lower urinary tract dysfunction has an increas-
center located in the brainstem. During bladder ingly important role in the health of children with
filling, afferent signals are transmitted through the cerebral palsy as they mature into adulthood.
spinal cord by autonomic pathways that converge Managing urologic problems in patients with
in the pontine micturition center, where the mic- cerebral palsy has the potential to improve their
turition reflex is constantly inhibited by cortical quality of life and participation in care and activ-
signals until the appropriate time for voiding. ities of daily living.
Children with cerebral palsy suffer from central The objectives of this chapter are to familiarize
nervous system insult during fetal or neonatal physicians treating cerebral palsy patients with
periods. The cerebral insult removes inhibitory normal bladder physiology and neurological
control over the pontine micturition center impacts of central nervous system insult on the
(Fig. 1). lower urinary tract, common lower urinary tract
Urodynamic studies of children with cerebral symptoms affecting children with cerebral palsy,
palsy demonstrated decreased volitional bladder and the evaluation and management of these chil-
control and uninhibited detrusor contraction con- dren. We also discuss the long-term urologic com-
sistent with upper motor neuron lesions (Decter plications and side effects of medications
et al. 1987). It has been hypothesized that patients commonly used to treat voiding problems in chil-
with cerebral palsy also suffer hypoxic injury to dren with cerebral palsy.
the spinal cord, causing lower motor neuron
lesions leading to external urinary sphincter dys-
function (Decter et al. 1987). Over half of children Natural History
with cerebral palsy experience at least one lower
urinary tract symptom (Silva et al. 2009). The Normal Bladder Function
most common urological complaints in patients
include urinary incontinence, frequency, and The bladder is a unique pelvic organ that has dual
urgency. function: storage and emptying of urine. The wall
While lower urinary tract symptoms are com- of the bladder consists of three main layers:
mon in children with cerebral palsy, it is often mucosa, detrusor muscle, and adventitia. The
overlooked, thus affecting patients’ quality of detrusor muscle consists of a meshwork of smooth
life. Physicians caring for patients with cerebral muscle fibers arranged into a single functioning
59 Neurogenic Bladder in Cerebral Palsy: Upper Motor Neuron 855
Fig. 1 Efferent and

afferent signals
Cerebrum
(Voluntary Voiding Activity)
Pontine Micturition
Center
(Coordinated Voiding)
T10
Efferent T11 Afferent
T12
L1
Spinal L2
Cord
L3
L4
L5
S1
Sacrum
S2
Sacral S3
Nerve
S4 Detrusor
Muscle
Bladder
Pelvic Floor
External Muscle
Sphincter Urethra
Muscle
unit. The latter has the ability to elicit nearly The delicate and precise synergy seen in the
maximum active tension over a wide range of bladder-sphincter complex is achieved by central
length allowing the bladder to fill with urine somatic and autonomic nervous system as seen in
from the upper tracts at low pressure, a term we Fig. 1. Three sets of peripheral nerves (sacral
refer to as “bladder compliance.” Moreover, the parasympathetic pelvic nerve, thoracolumbar
concomitant activity of the detrusor muscle and sympathetic hypogastric nerve, and sacral somatic
the bladder outlet (i.e., bladder neck, proximal pudendal nerve) act together to control the blad-
urethra, and external striated sphincter) allows der-sphincter complex.
the bladder to store urine and act as a reservoir. During the first 2 to 3 years of life, there is a
In the filling phase, the combination of a relaxed progressive evolution from indiscriminate infan-
detrusor muscle and a competent (closed) bladder tile voiding pattern to a more socially conscious
outlet allows for a slow filling of the bladder to its and voluntary adult pattern of micturition. In addi-
functional capacity. Once that is achieved, relax- tion to an intact nervous system, three prerequi-
ation of the bladder outlet followed by synchro- sites are needed to achieve the full potential of the
nous detrusor contraction as a single unit results in bladder as an ideal reservoir: progressive increase
the classic funneling effect that opens up the blad- in functional bladder capacity with age, matura-
der outlet allowing voiding. tion of voluntary control over the external urethral
sphincter, and development of direct volitional Stutzle 1977). The median age for achieving uri-
control over the bladder-sphincter complex so nary continence in cerebral palsy children with
that the child can voluntarily inhibit or initiate high intellectual capacity, as defined by IQ > 65,
the micturition reflex. and diplegia or hemiplegia is 3.6–4.1 years
Progressive increase in bladder capacity with (Roijen et al. 2001). These children have good
age is an important step in achieving an ideal probability (85–92%) of becoming continent
urinary reservoir that would accommodate an before their eighth birthday (Roijen et al. 2001).
increase in urinary volume production at the Children with low intellectual capacity, IQ < 65,
same time allowing decrease in voiding fre- and tetraplegia achieve bladder control at much
quency. The most common formula used to pre- later age, from 10.1 to 13.2 years (Roijen et al.
dict bladder capacity was described by Koff for 2001). Similar to neurologically normal children,
children <16 years of age: bladder capacity children with cerebral palsy achieve daytime con-
(ml) = [age (years) + 2] 30 (Koff 1983). tinence first, followed by nocturnal continence
As most formulas use age for calculating esti- during the subsequent year.
mated bladder capacity, they assume the child to Studies report that lower urinary tract symp-
have normal body habitus. Children with cerebral toms are common in children with cerebral palsy.
palsy usually have smaller than expected body An average of 55.5% of patients with cerebral
habitus and it is in those that a more applicable palsy experience one or more symptoms (Silva
formula of 7 ml/Kg of body weight is more suited et al. 2009). Urinary incontinence is the most
(Fairhurst et al. 1991). common lower urinary tract symptom in children
Bladder compliance describes the ability to with cerebral palsy. The reported prevalence
distend the bladder with low pressure. It is calcu- ranges widely from 23% to 93% in the literature
lated by dividing the change in bladder volume (Roijen et al. 2001; Richardson and Palmer 2009;
(ΔV) by the change in bladder pressure (ΔP). Murphy et al. 2012; Gündoğdu et al. 2013). The
Bladder compliance should be greater than higher incontinence rate may be an overestimate
10 ml/cm H2O pressure. Normally the bladder is when studies did not control for functional incon-
highly compliant. A stiff bladder, often called tinence in younger children. The true prevalence
poorly compliant bladder, will store urine at high of urinary incontinence in patients with cerebral
pressures leading to a progressive deterioration of palsy is likely about 35–45% (Gündoğdu et al.
renal function. 2013).
Urinary urgency and frequency are more prev-
alent in children with cerebral palsy compared to
Lower Urinary Tract Dysfunction their healthy age-matched counterparts (Reid and
in Cerebral Palsy Borzyskowski 1993; Samijn et al. 2017). The
average prevalence of urinary urgency and fre-
In the same way that the area and degree of brain quency in children with cerebral palsy is reported
damage affect the severity of motor and cognitive at 38.5% and 22.5%, respectively (Samijn et al.
disabilities in children with cerebral palsy, they 2017). Similar high prevalence of urinary fre-
cause a wide spectrum of lower urinary tract quency and urgency have also been reported in
symptoms and disorders. Most children with cere- adult patients with cerebral palsy at 48.7% and
bral palsy will develop total urinary control. How- 20.5%, respectively (Yıldız et al. 2017). About
ever, these children often achieve urinary half (45.7%) of patients in a cross-sectional
continence later than their age-adjusted normal study of adult patients with cerebral palsy by
peers do. The median age for attaining daytime Yildiz et al. reported frequent sensation of urinary
and nighttime continence in normal children is urgency and about 20% of the adult patients
3.5 years and 4 years, respectively (Jansson et al. reported constant sensation of urgency, which sig-
2005) with 91% of children achieving complete nificantly affected their quality of life (Yıldız et al.
bladder control by the age of 6 years (Largo and 2017). Nocturia (excessive urination at night) is
reported in 8.3% of children (Ersöz et al. 2009) chronic kidney disease in neurologically normal
and 62.5% of adult patients with cerebral palsy children in the urologic literature. While the
(Yıldız et al. 2017). degree of motor and cognitive disabilities is
Urinary hesitancy (difficulty initiating closely associated with lower urinary tract symp-
voiding) is reported at an average of 24% among toms in children with cerebral palsy (Roijen et al.
all patients with cerebral palsy and 16.5% in chil- 2001; Gündoğdu et al. 2013), it does not correlate
dren alone (Samijn et al. 2017). The prevalence of with risk of upper urinary tract deterioration
acute and chronic urinary retention has not been (Gündoğdu et al. 2013).
well reported. One study involving adult patients
with cerebral palsy reported 23% require intermit-
tent catheterization for urinary retention, presence Pathogenesis of Urinary Tract
of hydronephrosis on renal ultrasound, and refrac- Symptoms in Cerebral Palsy
tory lower urinary tract symptoms (Goldfarb et al.
2016). In our clinical practice, we have encoun- Essential to bladder control is physical maturation
tered adolescent cerebral palsy patients who pre- of the bladder and nervous systems. These are
sent with acute urinary retention requiring required for an individual to be conscious of blad-
emergent bladder drainage. der filling, to inhibit bladder reflex contractions,
Children with cerebral palsy and lower urinary and to start voiding. Furthermore, the individual
tract symptoms are prone to have recurrent urinary needs the mental drive and the physical capacity
tract infections. The incidence of urinary tract to reach an appropriate place to void as well as the
infections in children ranges from 12.1% to ability to undress.
56.7% (Gündoğdu et al. 2013; Silva et al. 2009). Control of micturition, the phases of bladder
Risk factors for urinary tract infections include filling and emptying, is performed by the intricate
voiding dysfunction and constipation, both of coordination between the peripheral nervous sys-
which are common findings in children with cere- tem (autonomic and somatic) and cortical path-
bral palsy. ways. In children, urinary continence develops
The literature does not support any evidence with maturation of the cortical pathways that reg-
that children with cerebral palsy are at risk of ulate the micturition center located in the
upper urinary tract deterioration and nephropathy. brainstem (pontine micturition center). During
Unlike in children with spina bifida or tethered bladder filling, afferent signals are transmitted
cord syndrome, children with cerebral palsy have through the spinal cord by autonomic pathways
safe and more stable bladder storage profiles. that converge in the pontine micturition center,
Studies that assessed the risk of upper urinary where the micturition reflex is constantly inhibited
tract deterioration had different definitions of by cortical signals until the appropriate time for
upper tract disease, including bilateral voiding. Cerebral dysfunction, as in the case of
hydronephrosis, impaired bladder compliance, children with cerebral palsy, may lead to loss of
bladder thickness, and high detrusor leak point this inhibition resulting in uninhibited detrusor
pressure of more than 40 cm water (Brodak et al. overactivity and voiding dysfunction. Further-
1994; Silva et al. 2009; Murphy et al. 2012; more, cerebral injury in children with cerebral
Gündoğdu et al. 2013). These studies did not palsy can lead to cognitive impairment and learn-
find any statistically significant prognostic factors ing disability, both of which can affect the child’s
that place children with cerebral palsy at risk of ability to have conscious control over their
nephropathy. Gundogdu et al. observed that high bladder.
grade vesicoureteral reflux, febrile urinary trac- It is difficult to decipher the underlying etiolo-
tion infections, and untreated detrusor sphincter gies of lower urinary tract symptoms in children
dyssynergia are clinical indicators of upper tract with cerebral palsy based on history and physical
deterioration (Gündoğdu et al. 2013). Interest- examination alone. Previous studies have used
ingly, these are also well-accepted risk factors of urodynamic findings to correlate with reported
voiding patterns to understand the nature of lower Observed bladder capacity is lower than
urinary tract symptoms associated with cerebral expected bladder capacity based on ages and
palsy and how to manage voiding dysfunctions in weights in 42–93% of children with cerebral
children with cerebral palsy. We discuss more palsy (Ersöz et al. 2009; Silva et al. 2009;
about the methodology and interpretation of Gündoğdu et al. 2013). About half of these chil-
urodynamics testing in the next section. dren have observed bladder capacity at or below
Up to one third of children with cerebral palsy 50% of the expected bladder capacity (Ersöz et al.
and lower urinary tract dysfunction have normal 2009; Karaman et al. 2005). Proposed etiologies
urodynamic studies (Silva et al. 2009). of reduced bladder capacity in children with cere-
Urodynamic findings of upper motor neuron bral palsy include neurogenic detrusor overactiv-
lesion of the bladder result from loss of inhibitory ity, urinary incontinence, and restricted fluid
cerebral cortical control over the pontine micturi- intake caused by swallowing problems and insuf-
tion center, resulting in lack of volitional bladder ficient hydration leading to poor bladder cycling
control in a patient who can understand com- and growth (Ersöz et al. 2009; Karaman et al.
mands, uninhibited detrusor contractions (also 2005). The combination of detrusor overactivity
known as neurogenic detrusor overactivity), and reduced functional capacity account for most
small bladder capacities, and neurogenic detrusor cases of urinary incontinence, urinary urgency,
underactivity. Upper motor neuron lesion effects and frequency in children with cerebral palsy
on the external urinary sphincter include hyperac- (Reid and Borzyskowski 1993).
tive sacral reflexes, causing sphincter hyper- Detrusor-sphincter dyssynergia is a term used
reflexia, and the inability to relax the external to describe involuntary contraction of the external
striated sphincter during voiding, a condition sphincter during voiding. The overall prevalence
known as detrusor-sphincter dyssynergia. of detrusor-sphincter dyssynergia in patients with
Urodynamic abnormalities and their cerebral palsy is about 11% to 12% (Karaman
corresponding lower urinary tract symptoms are et al. 2005; Cotter et al. 2016). Patients with
summarized in Table 1. isolated cerebral cortical lesion, as in patients
Neurogenic detrusor overactivity and reduced with classic cerebral palsy, are expected to have
bladder capacity are the most common coordinated sphincter activity. Detrusor-sphincter
urodynamic findings in children with cerebral dyssynergia in cerebral palsy can result from
palsy. The average prevalence rate of neurogenic hyperactive sacral reflexes and pelvic floor muscle
detrusor overactivity is 59% (Samijn et al. 2017), spasticity, causing sphincter hyper-reflexia and
ranging from 35% to over 80% (Decter et al. the inability to relax striated skeletal muscles of
1987) (Silva et al. 2009; Murphy et al. 2012; the external sphincter during voiding (Decter et al.
Gündoğdu et al. 2013). Neurogenic detrusor over- 1987; Drigo et al. 1988). Another mechanism may
activity can account for symptoms of urinary be suprasacral spinal cord injury at birth. Decter
incontinence, urinary frequency, sensory urgency, et al. observed 50% of patients with detrusor-
and urge urinary incontinence in children with sphincter dyssynergia had a history of perinatal
cerebral palsy (Reid and Borzyskowski 1993). cyanosis, when the spinal cord may be at
Table 1 Common urodynamic findings and lower urinary tract symptoms in patients with cerebral palsy
Incontinence Frequency Urgency Hesitancy Intermittency Retention
Detrusor overactivity + + +
Detrusor underactivity +/ + + +
Reduced bladder capacity + + +
Sphincter hyper-reflexia + + +/
(detrusor sphincter
dyssynergia)
risk for anoxic injury (Samijn et al. 2017). The last ideally from both the children and their parents/
proposed mechanism of detrusor-sphincter guardians. Urinary history should focus on symp-
dyssynergia is that children with cerebral palsy toms related to both the storage and emptying
develop pelvic floor overactivity as a voluntary phases of urine. Symptoms such as urinary fre-
reaction to detrusor overactivity and incontinence quency, urgency, urge incontinence, infrequent
(Bross et al. 2007). Detrusor-sphincter urination, and hesitancy to initiate void can be
dyssynergia can lead to urinary hesitancy, inter- elicited during office visit. Clear distinction
mittency (interrupted voiding), and urinary reten- should be made between continuous and intermit-
tion. Even though cerebral palsy is a tent incontinence and between daytime and night-
nonprogressive neurologic dysfunction, general- time urinary leakage. Toilet behavior and
ized spasticity and thereby tonic external urinary subjective quantification of urinary stream are
sphincter spasm may continue to worsen with age. important parameters. Physicians should ask
Although rare, detrusor underactivity has been about holding maneuvers such as squatting, hold-
reported in patients with cerebral palsy at a rate of ing genital area, or leg crossing as these are com-
about 6% (Murphy et al. 2012; Cotter et al. 2016). mon in children with voiding dysfunction. Bowel
These patients were previously continent earlier in dysfunction can coexist in children with lower
their life. Urodynamic findings in these patients urinary tract symptoms in the form of constipa-
include large maximum bladder capacity and flac- tion, encopresis, and fecal impaction. The rectum
cid (hypotonic) or acontractile bladder, suggesting and bladder have close anatomic proximity and
that detrusor underactivity develops as a sequela share the same parasympathetic S2 to S4 and
of chronic urinary retention (Murphy et al. 2012; sympathetic L2 to L4 innervation. Therefore,
Cotter et al. 2016). Patients with detrusor under- stooling behavior should be noted during history
activity can present with urinary retention with or taking of children with lower urinary tract
without hydronephrosis and acute renal failure, or symptoms.
overflow incontinence. Medical history in children should start with
obstetric history, including prenatal
hydronephrosis, oligohydramnios, fetal distress,
Diagnostic Work Up and Treatment anoxia, prematurity, etc. Developmental mile-
stones, cognitive disability, and physical limita-
Work Up of Urological Symptoms tion should be noted. If applicable, information on
in Children with Cerebral Palsy toilet training and ages at which daytime and
nighttime continence is achieved should be
Routine urinary tract screening, in the absence of obtained. History of previous urinary tract infec-
voiding symptoms or urinary tract infection, is not tion, medical conditions, and relevant surgeries
usually recommended in children with cerebral should be queried.
palsy due to low incidence of upper tract abnor- A two-day voiding diary and one-week
malities (Brodak et al. 1994). On the other hand, stooling diary (Fig. 2) provide objective mean of
children with lower urinary tract symptoms assessing a child’s voiding and stooling behavior.
should be referred to a pediatric urologist for The chart gives urologists information about a
further evaluation. Initial assessment of children child’s voiding frequency, total voided volume in
with cerebral palsy and lower urinary tract symp- 24 h, average voided volume, distribution of urine
toms should consist of a detailed and structured volume over day and night, incontinence episode,
history, a voiding and stooling diary, and a phys- and fluid intake. A one-week stooling diary,
ical examination. Bedside bladder scan for post- including the Bristol Stool Form Scale, informs
void residual may also be done at initial evalua- physicians of a child’s stooling frequency and
tion to rule out significant urinary retention. stool consistency. The voiding and stooling diary
History taking in children with lower urinary can be used for both diagnostic purpose and mon-
tract symptoms should be detailed and structured, itoring of treatment success.
Physical examination in children with lower dimple, abnormal or asymmetric gluteal fold,
urinary tract symptoms includes a general pediat- hairy tuft or subcutaneous lipoma. Physicians
ric examination. Abdominal exam should rule out should give a special attention to a child’s level
costovertebral tenderness and retained stool/fecal of mobility and gait if applicable. The child’s
impaction. The lumbosacral region needs to be underwear needs to be evaluated for dampness
evaluated for cutaneous manifestation of occult or fecal soiling. Genitourinary examination com-
spinal cord lesion such as the presence of a sacral prises of inspection of the position of urethral
VOIDING DIARY – DAY 1
DATE:
TIME VOLUME OF FLUIDS VOLUME OF URINE UNDERWEAR IS: URGENCY

(oz.) (oz.)
1 DRY DAMP WET YES NO
Fig. 2 (continued)
STOOL DIARY*
DAY 1DATE:
NO TYPE 1 TYPE 2 TYPE 3 TYPE 4 TYPE 5 TYPE 6 TYPE 7
STOOL
SEPARATE SAUSAGE- LIKE A SAUSAGE LIKE A SAUSAGE SOFT BLOBS FLUFFY PIECES WATERY, NO
HARD LUMPS SHAPED BUT BUT WITH OR SNAKE, WITH CLEAR CUT WITH RAGGED SOLID PIECES
LIKE NUTS LUMPY CRACKS SMOOTH AND EDGES EDGES, A
SOFT MUSHY STOOL
SUNDAY
COMMENTS:
MONDAY
COMMENTS:
TUESDAY
COMMENTS:
WEDNESDAY
COMMENTS:
THURSDAY
COMMENTS:
FRIDAY
COMMENTS:
SATURDAY
COMMENTS:
Fig. 2 Voiding (a) and stooling (b) diary
meatus, rash, leakage of urine, and pooled urine in may be present, and medical renal disease
the vagina. manifested with proteins or deformed red blood
A urine analysis and microscopy during office cells in urine.
visit can rule out other medical causes that can A screening renal and bladder ultrasound is not
contribute to urinary symptoms such as a urinary routinely indicated in children with cerebral palsy
tract infection, diabetes insipidus, in which urine and lower urinary tract dysfunction (Silva
specific gravity will be low (normal range is et al. 2010; Brodak et al. 1994). Bladder wall
1.001–1.003), diabetes mellitus where glycosuria thickness on ultrasound does not correlate with
the presence of bladder dysfunction or inconti- between the bladder and sphincter activities dur-
nence (Silva et al. 2010). If the child has a history ing filling and voiding phases of the study.
of febrile urinary tract infection, a renal ultrasound As previously discussed in this chapter, about
is indicated to assess the upper urinary tracts, one third of children with cerebral palsy and lower
presence of renal scarring, and any other anatom- urinary tract symptoms have normal urodynamic
ical abnormalities such as renal duplication, findings (Silva et al. 2009). Common etiologies of
ectopic ureter and ureterocele. It is also important lower urinary tract symptoms found on
to assess the bladder before and after voiding to urodynamics include detrusor overactivity,
assess residual urine volume noninvasively. Chil- reduced bladder capacity, and detrusor sphincter
dren with hydronephrosis or renal scarring on dyssynergia (Reid and Borzyskowski 1993;
initial ultrasound or those with recurrent febrile Karaman et al. 2005; Ersöz et al. 2009).
urinary tract infections need to undergo further In rare cases, children with cerebral palsy may
work up with voiding cystourethrogram to rule have detrusor underactivity and impaired bladder
out vesicoureteral reflux and warrant referral to compliance (Murphy et al. 2012; Cotter et al.
pediatric urologists (Roberts 2012). 2016). Conceptually, these urodynamic findings
In highly selected group of patients such as and diagnoses are classified as either failure of
those with complex lower urinary tract symp- urine storage or emptying at the level of the blad-
toms, failure of medical therapies, urinary reten- der versus bladder outlet as demonstrated in
tion, and upper tract at risk, further work up with Table 2.
video urodynamic study may be needed to define
precisely the function of the lower urinary tracts.
Video urodynamic study is a minimally invasive, Treatment of Lower Urinary Tract
interactive diagnostic study of urinary storage Symptoms in Children with Cerebral
and emptying. In this study, two catheters with Palsy
pressure recording devices are placed in the
bladder and rectum or vagina in females. The In children, it is imperative to diagnose and treat
bladder catheter will measure intravesical pres- any constipation prior to moving forward with any
sure [Pves] (which is in turn the sum of detrusor treatment of urinary incontinence as constipation
pressure [Pdet] and intra-abdominal pressure may induce or exacerbate lower urinary tract
[Pabd]). The rectal or vaginal catheter measures symptoms. After bowel dysfunction has been
the intra-abdominal pressure [Pabd]. A computer addressed, the treatment course will depend on
software will deduct the intra-abdominal pres- lower urinary tract symptoms and video
sure from the intravesical pressure to give us urodynamic findings if applicable.
indirectly the detrusor pressure (Fig. 3). The In children with cerebral palsy and urinary
video component of the study refers to the use incontinence, patient’s mental acuity and age
of fluoroscopy during bladder filling and empty- play an important role in the management deci-
ing which gives invaluable information on the sion. Since most children with cerebral palsy have
shape and contour of the bladder wall, status of delayed toilet training compared to their neuro-
the internal and external sphincter competency, logically normal peers, urinary incontinence may
and presence or absence of vesicoureteral reflux be physiologic if the patient has not achieved
(Fig. 4). Electromyography is also performed bladder control. Physiologic urinary incontinence
during the filling and emptying of the bladder due to impaired cognitive maturation will require
by attaching electrodes in the perineal area. time and patience from both parents and the
These electrodes study the electronic potentials treating physician.
produced by the depolarization of striated exter- In setting of urinary incontinence after patient
nal sphincteric muscles of the perineum which has been fully potty-trained, it is important to
will provide information on the coordination address any associated problems such as urinary
tract infections, psychological stressors, and The second line of treatment of urinary inconti-
bowel dysfunction. nence includes oral anticholinergic and beta-3 ago-
The first line of treatment of urinary inconti- nist classes of medication. Anticholinergic
nence due to overactive bladder includes behavior medication reduces urinary incontinence and fre-
modifications such as timed voiding, double quency by inhibiting bladder contractions. Studies
voiding, and dietary modification to reduce food in children have shown that anticholinergic medica-
and fluids that may act as bladder irritants such as tions, including oxybutynin (Youdim and Kogan
carbonated drinks, coffee, tea, and fruit juices 2002; Cartwright et al. 2009), tolterodine (Reinberg
high in sugar content. It is important to provide a et al. 2003), tropsium (Lopez Pereira et al. 2003),
note to the child’s school in order for school staff solifenacin (Bolduc et al. 2010), and fesoterodine
to set up a timed voiding program while the child (Malhotra et al. 2012), demonstrate sustained effi-
is at school. Studies in neurologically normal chil- cacy in children with overactive bladder symptoms
dren with lower urinary tract dysfunction have (Palmer 2016). Oxybutynin is the most commonly
shown a simple voiding program alone effectively used anticholinergic medication in pediatric patients
improves symptoms in 45–55% of patients (Allen (Kinlaw et al. 2017). Oxybutynin is available in
et al. 2007; Thom et al. 2012). timed-released tablet, liquid, gel, and patch forms.
Fig. 3 (continued)
Fig. 3 Urodynamic tracing showing detrusor overactivity (a and b)
Selective beta-3 adrenergic receptor agonists tolerate two anticholinergic medications were
reduce bladder overactivity and urinary inconti- placed on mirabegron, 90% achieved greater
nence by relaxing the detrusor smooth muscle. than 50% reduction in incontinence symptoms,
The only beta-3 adrenergic receptor agonist and 22% achieved complete dryness (Blais et al.
available for overactive bladder is mirabegron. 2016). A different study placed children on com-
There are two off-label studies of mirabegron as bination of mirabegron and an anticholinergic
monotherapy and combination therapy in chil- medication, including solifenacin, oxybutynin
dren with refractory overactive bladder (Blais ER, and fesoterodine ER. Overall success rate
et al. 2016; Morin et al. 2017). Children with of combination therapy was 94% of children
overactive bladder who failed or could not achieving at least 75% improvement in
the cells from releasing acetylcholine neurotrans-

mitter, and thereby inhibiting contraction of the
detrusor muscle. Botulinum toxin is injected
directly into the bladder detrusor muscle via trans-
urethral cystoscopic approach during outpatient
procedure and, in adults, office procedure under
local anesthetic. Intradetrusor botulinum toxin has
been shown to be efficacious in children with
overactive bladder refractory to oral medical ther-
apies (Marte et al. 2010; Blackburn et al. 2013). In
an initial study of 100 units of botulinum-A toxin
injection in children with reduced bladder capac-
ity and refractory overactive bladder, 60% of chil-
dren achieve complete response after one
injection, with 89% of those retain durable effect
after one year of follow up (Hoebeke et al. 2006).
Neuromodulation inhibits detrusor contraction
by blocking the afferent limb of the sacral reflex
arc (Palmer 2016). Percutaneous tibial nerve stim-
ulation and parasacral transcutaneous electrical
neurostimulation have been used successfully in
children with both overactive bladder and dys-
Fig. 4 Cystogram showing abnormal bladder contour and
bilateral vesicoureteral reflux functional voiding (Palmer 2016). However,
these approaches require time commitment from
Table 2 Voiding dysfunction conceptual framework
parents, which can be challenging in children with
based on urodynamic findings cerebral palsy. Implantable sacral neuromodulator
Failure to store Failure to empty
into the posterior S3 foramen is FDA approved
Due to the Reduced Detrusor underactivity
for urge incontinence, urinary frequency,
bladder bladder capacity (atonic bladder) and non-obstructive urinary retention. The uro-
Detrusor logical experience with implantable sacral
overactivity neuromodulators in children is limited but favor-
Due to the Intrinsic Detrusor sphincter able. Children with urinary incontinence, fre-
outlet sphincter dyssynergia
deficiency Bladder outlet quency, and urgency have a reported 40%
Fistula obstruction complete response and 33–88% partial response
(e.g., enlarged prostate rates (Groen et al. 2012; Dwyer et al. 2014). The
in older men) reoperation rate for device exploration for any
Urethral stricture
cause was 27–35% in these two series.
Sphincter hyperreflexia and detrusor-sphincter
incontinence symptoms with 34% achieving dyssynergia are more challenging to manage in
complete dryness (Morin et al. 2017). children with cerebral palsy than urinary fre-
The third line of treatment of urinary frequency quency and urgency. Although cerebral palsy
and incontinence in children include intradetrusor does not have advancing neurologic dysfunction,
botulinum toxin injection and neuromodulation. striated sphincter spasm continues to worsen with
Botulinum toxin is a neurotoxin produced by age. Symptoms of detrusor-sphincter dyssynergia
Clostridium botulinum. There are seven subtypes include urinary hesitancy, incomplete emptying,
of botulinum toxin, of which onabotulinum toxin urinary retention, and in severe cases
A (Botox ®) is most commonly used. Botulinum hydronephrosis and obstructive nephropathy. As
toxin cleaves SNARE complex proteins, prevents in the case of urinary incontinence and frequency,
detrusor-sphincter dyssynergia in children with injection directly to the external urethral sphincter
cerebral palsy should be treated sequentially via transurethral and perineal approach.
with behavioral modification, followed by oral Intrasphincteric botulinum injection has been
therapy, intermittent catheterization, and finally shown to improve postvoid residuals, sphincter
invasive surgical intervention. synergism during voiding, and voiding pressure
Behavior modifications for detrusor-sphincter on urodynamics in both adult patients with spinal
dyssynergia include the use of pelvic floor bio- cord injury (Schurch et al. 1996) and children with
feedback training. Biofeedback therapy involves refractory voiding dysfunction (Vricella et al.
electromyography tracing of pelvic floor muscle 2014). In both studies, a total of 100 units of
contraction and relaxation in the form of an ani- botulinum-A toxin were injected at four spots
mation with a soundtrack tailored for children. It around the external sphincter, typically 3, 6,
is labor and time intensive and requires motiva- 9, and 12 o’clock positions (Schurch et al. 1996;
tion and commitment from both affected children Vricella et al. 2014).
and their families. Pelvic floor muscle training Male patients with detrusor-sphincter
using interactive animated computer game has dyssynergia who fail oral therapies and botulinum
been effective in neurologically normal children toxin injection or are intolerant of intermittent
(McKenna et al. 1999). Pelvic floor muscle train- catheterization may ultimately need external
ing may be difficult and less effective in those sphincterotomy (transection of the external
children with cerebral palsy who also have cogni- sphincter via cold knife or laser utilizing the cys-
tive impairment and chronic tonic spasticity. toscope). The goal of external sphincterotomy is
Several oral medications have been used to to protect the upper tract and improve bladder
reduce tone in children with cerebral palsy, includ- emptying by mechanically impairing the external
ing baclofen, benzodiazepines, dantrolene, alpha2- sphincter to reduce bladder outlet obstruction. The
adrenergic agonists, and gabapentin. Although they long-term success rate of external sphincterotomy
can decrease spasticity, most of these medications is 32% complete resolution of sphincter hyper-
have strong sedating side effects and are not well reflexia during voiding and 65% avoidance of
tolerated in children (Krach 2001). Baclofen is an further need for surgical intervention (Pan et al.
analogue of gamma-aminobutyric acid (GABA), the 2009). It is important to note that several studies
main inhibitory neurotransmitter in the central ner- have shown that patients may need revision exter-
vous system. Baclofen relaxes the external urethral nal sphincterotomy for late failure as defined by
sphincter by suppressing the pudendal-to-pudendal recurrent detrusor-sphincter dyssynergia, elevated
nerve reflex through the spinal cord presynaptic postvoid residual, and upper urinary tract dilation
hyperpolarization (Leyson et al. 1980). Oral baclo- (Pan et al. 2009; Vainrib et al. 2014).
fen has been shown to improve urinary hesitancy Patients with urinary retention, often second-
and bladder emptying in 73% of patients of detrusor- ary to detrusor-sphincter dyssynergia and detrusor
sphincter dyssynergia after stroke (Leyson et al. undercontractility, may require catheterization for
1980). Another study of 21 female patients with bladder drainage. Children with cerebral palsy
detrusor-sphincter dyssynergia from multiple often cannot tolerate intermittent urethral cathe-
causes showed 76% improvement in clinical and terization (Goldfarb et al. 2016). In these children,
urodynamic findings on combination therapy with indwelling suprapubic catheter is recommended
baclofen and doxazosin (Kilicarslan et al. 2006). over indwelling urethral catheter due to less risk
The effectiveness of oral therapies for detrusor- of urethral injury, stricture, fistula, and scrotal
sphincter dyssynergia cannot be maintained in the abscess with the use of suprapubic catheter
long term. Most patients will ultimately need (Hunter et al. 2013). Physicians should not order
intermittent catheterization for long-term manage- screening urine cultures in asymptomatic patients
ment of their detrusor sphincter dyssynergia and with indwelling catheters due to risk of over-
rarely surgical intervention. The least invasive treating chronic bacterial colonization leading to
surgical treatment is off-label botulinum toxin antibiotic-resistant organisms.
Table 3 Side effects of commonly used medications in children with lower urinary tract symptoms
Class of medication Medication Side effects
Muscarinic receptor Oxybutynin Oral: dry mouth, constipation, heat intolerance, drowsiness (Youdim
antagonist and Kogan 2002) Transdermal patch: vasodilation, pruritus, rash,
erythema, dry skin (Cartwright et al. 2009)
Tolterodine Dry mouth, constipation, incomplete emptying, blurred vision,
dizziness, somnolence, asthenia, insomnia, nervousness, headaches,
dyspepsia, nausea, vomiting (Appell et al. 2001; Reinberg et al.
2003)a
Solifenacin Xerostomia, constipation, blurred vision, headache, insomnia,
behavior changes, incomplete emptying, UTI (Bolduc et al. 2010)
Tropsium Dry mouth, abdominal cramps, headache, dizziness (Lopez Pereira
et al. 2003)
Fesoterodine Dry mouth, constipation, dry eyes, blurred vision, nausea,
incomplete emptying (Malhotra et al. 2012)
Selective beta-3 adrenergic Mirabegron Transient abdominal colic, constipation, nausea, nasopharyngitis.
receptor agonist blurred vision, change in behavior, urinary retention (Blais et al.
2016; Morin et al. 2017)
Botulinum toxin Botulinum- Urinary retention, UTI, temporary vesicoureteral reflux, bladder pain
A toxin (Hoebeke et al. 2006; Blackburn et al. 2013)
Gamma-aminobutyric acid Baclofen Sedation, weakness, ataxia, orthostatic hypotension (Krach 2001)
(GABA) receptor agonist
a
Side effects noted from adult trial only. Pediatrie trial did not specify side effects
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Kidney Stones: Risks, Prevention, and
Management in Cerebral Palsy 60
Carlos E. Araya and Ahmad H. Bani Hani
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 872
Immobilization and Hypercalciuria . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 872
The Ketogenic Diet and Kidney Stone Risk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 873
Antiepileptic Medications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 874
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 876
Medical Management of Acute Renal Colic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 876
Surgical Management of Kidney Stones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 877
Imaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 877
Surgical Modalities for the Treatment of Kidney Stones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 877
Extracorporeal Shock Wave Lithotripsy (ESWL) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 878
Endoscopic Lithotripsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 878
Percutaneous Nephrolithotomy (PCNL) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 878
Prevention of Recurrent Kidney Stones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 878
Adequate Fluid Intake . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 878
Sodium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 878
Calcium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 878
Protein . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 880
Alkali Therapy/Potassium Citrate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 880
Diuretics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 881
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 881
C. E. Araya (*) Abstract

Division of Pediatric Nephrology, Nemours Children’s Urolithiasis is a relatively common problem
around the world. In neurologically impaired
e-mail: Carlos.Araya@Nemours.org
children and those with cerebral palsy, kidney
A. H. Bani Hani
stones represent an understudied and unique
Division of Pediatric Urology, Nemours/Alfred I. duPont
Hospital for Children, Wilmington, DE, USA challenge. Children with cerebral palsy are
at increased risk of kidney stones due to their
Department of Urology and Pediatrics, Sidney Kimmel
Medical college-Thomas Jefferson University, limited mobility, associated hypercalciuria,
Philadelphia, PA, USA and inability in some to self-regulate their
e-mail: Ahmad.banihani@nemours.org

https://doi.org/10.1007/978-3-319-74558-9_58
872 C. E. Araya and A. H. Bani Hani
water intake. Some children are exposed to calcium phosphate as the main constituent of
antiepileptic medications that have lithogenic their stones (Gnessin et al. 2011).
potential, while other children may be receiv- In the next sections, we will describe the
ing a ketogenic diet to help control their lithogenic risk factors, medical management,
epilepsy. Children with cerebral palsy pretreatment, and prevention strategies of urolithiasis
senting with kidney stones may be unable to in patients with cerebral palsy.
verbalize their discomfort and do not have
a typical clinical presentation of renal colic,
which can cause a delay in the diagnosis and Immobilization and Hypercalciuria
treatment. Conservative management includes
analgesia, hydration, and medical expulsive Multiple factors may adversely affect bone den-
therapy. Surgical treatment of kidney stones sity and metabolism in individuals with cerebral
is considered for larger stones, patients with palsy. Clearly, limited weight-bearing ambulation
persistent pain, and presence of urinary tract during skeletal growth is one of the main factors.
infection or urinary tract obstruction. The pre- Another important factor is the temporary immo-
vention strategies for recurrence of kidney bilization following orthopedic surgical proce-
stones include dietary modification and ample dures often performed on a child with cerebral
fluid administration. In some cases, alkali ther- palsy.
apy and administration of thiazide diuretics Orthopedic immobilization leads to increased
may also be helpful. bone resorption, causing hypercalciuria and an
increase in the risk of kidney stones (Andrews
Keywords and Rosenberg 1990; Muller et al. 1994). Hyper-
Kidney stones · Urolithiasis · Cerebral palsy · calciuria is common after long-term immobiliza-
Pediatrics tion and is likely explained by a reduced rate of
bone mineralization and increased loss of skeletal
calcium. In healthy subjects and after 12 weeks of
Introduction immobilization, there was a marked increase in
bone resorption (Zerwekh et al. 1998). The period
Urolithiasis is a relatively common problem of immobilization produced a small but signifi-
around the world. In pediatrics, there is a greater cant increase in serum calcium, hypercalciuria,
proportion of kidney stone patients that have iPTH suppression, and decline in serum 1,25
a well-defined underlying condition that increases (OH)2D. The increased bone resorption was fur-
their risk for the formation of stones. In neurolog- ther supported by the significant increases in the
ically impaired children and those with cerebral biochemical markers of bone resorption during
palsy, kidney stones represent an understudied the entire period of immobilization and their
and unique challenge. These children may have decrease during the reambulation period
limited mobility or are immobile with low bone (Zerwekh et al. 1998).
mineral density. Some may not be able to self- In an evaluation of 14 young adults primarily
regulate their water intake according to thirst and suffering from spinal cord injury, investigators
are usually on a fixed amount of fluid intake. They documented that despite normal serum calcium
may not be on a typical pediatric diet, with some levels, patients had significant hypercalciuria
receiving a ketogenic diet. These children are at (Stewart et al. 1982). The mean fractional excre-
increased risk of seizures or epilepsy and may take tion of calcium was elevated to three times normal
antiepileptic medications that have lithogenic and the 24-h urinary calcium excretion reached a
potential. Furthermore, these children often mean value of 314 mg despite dietary calcium
cannot verbalize renal colic pain, which can restriction. The upper limit of normal for 24-h
cause a delay in the diagnosis and treatment of urinary calcium excretion is 200 mg in females
kidney stones. The vast majority of them have and 250 mg in males. The secretion of iPTH was
60 Kidney Stones: Risks, Prevention, and Management in Cerebral Palsy 873
suppressed in these patients. The restriction anticonvulsant effect. However, as many as 7%

of dietary calcium did not cause any reduction of children develop kidney stones while receiving
in urinary calcium excretion. a ketogenic diet (Kossoff et al. 2002; Sampath
A mean increase of 2.3 times baseline values et al. 2007; Wibisono et al. 2015).
of urinary calcium was observed in 40% of There are several reasons for the increased risk
previously normocalciuric children following of kidney stones. Hypercalciuria is observed more
intermediate-term immobilization (Korkes et al. commonly while on a ketogenic diet. In a study
2006). The hypercalciuria was transient as values of 197 children with intractable epilepsy that were
returned to normal after 6 weeks and towards the started on a ketogenic diet, the urinary calcium to
end of the study. No significant abnormalities creatinine ratios were available for review in 71%
were noted in the children in the serum calcium of the cohort. The median urine calcium to creat-
or iPTH levels after immobilization. inine ratio at baseline was 0.2 mg/mg and
In another pediatric study, the nephrolithiasis increased to 0.4–0.5 mg/mg after 3–12 months
risks were compared between healthy and medi- in all patients. The mean urine calcium to creati-
cally complex children (Smith et al. 2011). The nine ratio at the time of the diagnosis of kidney
patients that were medically complex and had stones was 0.94 mg/mg (Sampath et al. 2007). In
kidney stones were noted to have a lower a case-control study, the prospective evaluation
Z-score on bone mineral densitometry. However, of children initiating a ketogenic diet revealed
the rates of hypercalciuria were similar in those that almost 40% of the cohort had elevated fasting
considered medically complex (2/7) and those urine calcium to creatinine ratio at baseline. This
considered neurologically intact (7/24). increased to 75% of the cohort after 6 months on
The above data supports the observation that a ketogenic diet (Furth et al. 2000).
limited weight-bearing ambulation and therapeu- Children on a ketogenic diet are also more likely
tic immobilization following orthopedic proce- to experience hypocitraturia. Citrate is an inhibitor
dures in cerebral palsy patients can lead to the of calcium oxalate and calcium phosphate crystal-
development of hypercalciuria. However, the lization. Citrate is freely filtered by the glomerulus
hypercalciuria secondary to immobility is likely and reabsorbed in the proximal tubule. Citrate com-
a transient phenomenon and by itself is unlikely to bines with urinary calcium to form a soluble com-
be a major risk factor for the formation of kidney plex resulting in less free calcium to combine with
stones. oxalate, decreasing its urinary supersaturation. It
also acts as an inhibitor of calcium oxalate aggre-
gation (Hess et al. 1993; Pak 1987). In acidosis-
The Ketogenic Diet and Kidney induced hypocitraturia, there is an enhanced prox-
Stone Risk imal tubular reabsorption of citrate which increases
the available urinary free calcium; the lower citrate
Epilepsy can happen frequently in patients with has less effect on crystallization inhibition
cerebral palsy with a reported frequency that (Copelovitch 2012).
ranges from 25% to 41% (Christensen et al. Uric acid stones have been reported in patients
2014; Novak et al. 2012). The ketogenic diet on a ketogenic diet, but hyperuricosuria is not
uses a high fat, adequate protein, a common metabolic abnormality for these
low-carbohydrate diet as part of the non- patients (Furth et al. 2000). However, urine pH
pharmacological treatment of intractable epilepsy is a major determinant of uric acid supersatura-
or poorly controlled epilepsy in patients receiving tion. At an acid urinary pH, there is a greater
at least two antiepileptic medications. With a supersaturation with respect to uric acid and a
ketogenic diet, fatty acid oxidation is stimulated greater propensity for stone formation. Since
and the ketone bodies, acetoacetate and patients on the ketogenic diet have a lower urinary
b-hydroxybutyrate, produced in the liver cross pH, this may explain the lower uric acid solubility
the blood-brain barrier producing an and propensity to form crystals.
Lastly, children with cerebral palsy and on The severity of the acidosis is increased if there
a ketogenic diet are generally prescribed a are other factors present that predispose to met-
“fixed” daily fluid intake based on a calculation abolic acidosis such as concurrent use of a keto-
of their requirements. Fluid intake in some cases genic diet (Sheth 2004).
is targeted at 80% of the estimated daily needs. The biochemical profile of patients treated with
Furthermore, some of these children are unable topiramate reflects the effect of the medication on
to self-regulate their water intake based on carbonic anhydrase enzymes in the renal proximal
their thirst resulting in low urinary volumes tubules. There is a reduction in serum bicarbonate
which can increase the risk for stones. Because levels, profound dose-dependent hypocitraturia,
increased fluid intake does not diminish the effi- elevated urine pH, and hypercalciuria with an
cacy of the ketogenic diet in controlling seizures increase supersaturation for calcium phosphate
and blood ketone levels, hydration with larger (Vega et al. 2007).
amounts of water should be encouraged to Reports of the prevalence of kidney stones in
prevent the formation of kidney stones children taking topiramate have shown variable
(Furth et al. 2000). results. In the short-term clinical studies that led
to its approval by the Food and Drug Adminis-
tration (FDA), 1.5% of topiramate-treated adult
Antiepileptic Medications patients developed kidney stones (Topamax
Package Insert 2009). Studies that involved the
Medication-induced nephrolithiasis accounts for use of topiramate in children without epilepsy
1–2% of the total number of stones analyzed at have shown lower prevalence of stones (Lewis
specialized laboratories. Two main mechanisms et al. 2009). There are no specific data evaluating
are involved in the formation of medication- the use of topiramate in children with cerebral
induced stones: directly, with the medication itself palsy and the associated risk of kidney stones.
or its metabolites being total or partial compo- However, when reviewing the studies that
nents of the stone, or indirectly, by inducing the involved children with epilepsy or children on
formation of the stone through its metabolic longer-term use of topiramate, the prevalence of
effects. Topiramate and zonisamide are the two stones was higher. During long-term treatment in
main antiepileptic medications that have been an open-label extension study of 284 pediatric
shown to induce the formation of kidney stones patients 1–24 months old with epilepsy, 7%
primarily due to the inhibition of carbonic developed kidney or bladder stones (Topamax
anhydrase. Package Insert 2009). In a series of 96 children
treated with topiramate for at least 1 year, the
Topiramate prevalence of asymptomatic kidney stones
Topiramate has multiple mechanisms of action detected by ultrasound was 5.2% (Mahmoud
including the blockade of voltage-dependent et al. 2011). All children with a normal baseline
sodium channels, enhancement of ultrasound were included in the study. The rea-
γ-aminobutyric acid receptor activity, inhibition son for performing the baseline ultrasound was
of glutamate receptors, and inhibition of not mentioned by the investigators. The median
carbonic anhydrases (Ben-Menachem et al. time in months for ultrasound evaluation at
2008). Treatment with topiramate causes a mild follow-up for all children was 14.2 months
hyperchloremic, non-anion gap metabolic acido- (interquartile range 10.1–22.8) and 21.2 months
sis with a reduction in serum bicarbonate levels (17.9–32.8) for children with kidney stones. The
in 32–44% of adults and 67% of children (Sheth investigators concluded that long-term use of
2004). The bicarbonate reduction can be mild to topiramate may result in increased incidence of
moderate, averaging 4 mEq/L at daily doses kidney stones and that baseline and follow up
of 400 mg in adults and 6 mg/kg/day in children. kidney ultrasound evaluation should be
considered. Data on topiramate dosing was not crystalluria and the withdrawal of the medication
available for comparison between stone formers causes decrease of the crystalluria (Go 2013). The
and non-stone formers. urinary pH does not change after the addition or
In a cohort of outpatient topiramate-treated withdrawal of zonisamide, demonstrating that
children without known history of stones, the a change in the urinary pH is not the cause of the
prevalence of asymptomatic kidney stones crystalluria and that the kidney stones caused by
detected by ultrasound was 4.8% (Corbin Bush zonisamide are not the result of alkalinization of
et al. 2013). The stones were radio-opaque on the urine.
abdominal radiograph, and stone analysis demon- The first report of kidney stones with the use of
strated calcium phosphate composition. The most zonisamide was in a safety and efficacy historical-
striking feature was hypocitraturia, with 93% of controlled, open-label multi-centered clinical trial
patients demonstrating a low citrate to creatinine (Leppik et al. 1993). In this study, four partici-
ratio. Hypercalciuria was seen in 51% of the study pants (3.7%) developed kidney stones and were
group and was noted in both ambulatory and withdrawn from the study 250–477 days after
immobilized patients. There was no association starting zonisamide. Three short-term placebo
between the dose of topiramate and degree of controlled studies were completed in adult
hypocitraturia or hypercalciuria (Corbin Bush patients with refractory epilepsy. Suspected kid-
et al. 2013). ney stones were reported in 4 of 203 participants
In a retrospective review of nonambulatory and of one of the US studies (Faught et al. 2001). All
neurologically impaired individuals in a long- patients had ultrasound examinations before, dur-
term care facility, stone fragments were evident ing, and after the study. Three of the patients had
in the diapers of 13 of the 24 children on normal follow-up ultrasounds at 4, 6, and
topiramate (Goyal et al. 2009). Radiologic confir- 12 months, and one had no evidence of a stone
mation of the stone was achieved in 7 of the at a 2-month follow-up. None of these patients
13 patients with ultrasound or computed tomog- discontinued zonisamide during the study period.
raphy. In four patients, stones were not evident The incidence of symptomatic kidney stones
with imaging and two of the patients did not increased with long-term treatment. When all long-
undergo testing. All of the patients were receiving term studies were pooled, 15 of 549 (2.7%) patients
a fixed dietary and fluid intake, but none were on a developed kidney stones (Faught 2004). The per-
ketogenic diet. Spot urine chemistries revealed centage of patients affected varied by each study
hypercalciuria in the topiramate-treated patients from 1.6% to 4.9%. Two patients discontinued the
who developed stones compared to stone-free medication due to the kidney stones.
patients (Goyal et al. 2009). Kidney stones may develop rapidly while on
The above studies suggest that this subpopula- zonisamide treatment during episodes of dehy-
tion of patients has a higher frequency of stone dration. Severe, bilateral, obstructing calculi
formation when exposed to medications such as were reported in a 10-year-old female patient
topiramate. soon after being admitted with a ventriculo-
peritoneal shunt infection and dehydration
Zonisamide (Sato et al. 2013). A right-sided percutaneous
Zonisamide is an antiepileptic that stabilizes neu- nephrostomy and left-sided ureteral stent were
ronal membranes by blocking voltage-sensitive placed due to presence of acute kidney injury. A
sodium channels and reducing voltage-dependent CT scan 3 weeks prior to the admission did not
calcium channel currents. Zonisamide is also reveal any kidney stones. The stones were com-
a weak carbonic anhydrase inhibitor and seems posed of calcium phosphate. This report under-
to induce a lower incidence of kidney stones when scores the risk of rapid stone formation while on
compared to topiramate. In children and young zonisamide treatment during a period of acute
adults, zonisamide has been shown to cause illness with dehydration.
Treatment drink, then parenteral fluid hydration is used to

restore euvolemia and maintain a high urine
Medical Management of Acute Renal flow rate.
Colic Medical expulsive therapy, which is the use of
alpha-adrenergic blockers or calcium channel
The management of an acute symptomatic stone blockers, that promote or facilitate ureteral
episode is directed towards pain control and stone passage is frequently prescribed. The pro-
facilitating passage of the stone. In some cases, posed method of action of medical expulsive
outpatient medical management is sufficient. therapy is by selective relaxation of ureteric
However, hospitalization may be necessary if the smooth muscle, causing reduction of the sponta-
pain is severe; there is inability to remain hydrated neous contractions of the ureter and dilation of
or take analgesics orally due to emesis; there is an the ureteral lumen allowing stones to pass (Par-
associated urinary tract infection; and there is sons et al. 2007). In adults, studies suggest that
urinary tract obstruction or the patient has a soli- treatment with alpha-adrenergic blockers for up
tary kidney. to 4 weeks, in addition to conservative therapy,
The typical adult presentation of severe acute may facilitate spontaneous stone passage in
onset flank pain that radiates to the groin is patients presenting with ureteral stones greater
uncommonly seen in children. Young children than 5 mm and less than 10 mm in diameter
may complain of vague or nonspecific abdominal (Wang et al. 2017). In pediatrics, there have
pain and irritability (Bartosh 2004). Gross hema- been four systematic reviews, three of which
turia is seen in up to 50% of patients and micro- conducted meta-analyses, looking at the rate of
hematuria in up to 90% of children with stones stone passage with medical expulsive therapy
(Bartosh 2004). Lower urinary tract symptoms (Greeves et al. 2018). The data suggests that
such as dysuria, frequency, or urinary retention the use of alpha-adrenergic blockers improves
can be seen in up to 10% of distally located stones the rate of stone passage when compared to
(Bartosh 2004). Urinary tract infection at the time conservative therapy alone (OR 1.8–4) (Greeves
of urolithiasis diagnosis is more common in et al. 2018). The studies were limited to stones
patients less than 5 years of age (Bartosh 2004). less than 12 mm in size. No randomized trial has
Children with cerebral palsy may be unable to evaluated the efficacy of this treatment in chil-
verbalize their discomfort and may display irrita- dren. Side effects of medical expulsive therapy
bility, intolerance to feedings, or emesis. were reported to be minimal. Only one out of
Pain associated with the passage of a stone is 175 patients (0.6%) who received alpha-
often severe and should be treated promptly with adrenergic blocker treatment withdrew from
nonsteroidal anti-inflammatory or narcotic medi- treatment due to adverse effects (Velazquez
cations. Intravenous ketorolac is considered a first et al. 2015). The most commonly reported side
line agent for pain management in children with effect was somnolence, reported in one study to
renal colic as it has been found to be both safe and be experienced by 24.2% of the treatment group
effective (Eberson et al. 1999; Gonzalez and versus 17.9% of the control group.
Smith 1998). Other analgesics such as narcotics Treatment with alpha-adrenergic blockade in
or acetaminophen can be added if pain is not fully children appears to increase the rate of stone
controlled with the anti-inflammatory medication. expulsion and is generally safe. However, the
Antiemetic treatment is frequently provided studies included are of low quality and include
for patients with nausea and emesis associated a low number of patients. Given the above, it
to severe pain. The serotonin antagonist, would be reasonable to provide patients with
ondansetron, is the most commonly prescribed ureteral stones with medical expulsive therapy if
antiemetic medication in children followed by there is no obvious advantage to immediate stone
metoclopramide and promethazine (Mee et al. removal (i.e., acute kidney injury or obstructed
2011). If the patient is vomiting and/or unable to solitary kidney).
In general, stones that are 3 mm or less in size Limitations of RBUS include less sensitivity and
tend to pass spontaneously (Van Savage et al. specificity in detecting stones in comparison to CT
2000). The bigger the stone, the more likely scans, operator dependent and inability to detect
a surgical intervention will be required. stones within the ureter except if the stone is lodged
Conservative management is inappropriate in at the distal end of the ureter towards the bladder.
the following scenarios: Despite the aforementioned limitation, RBUS
should be the first line imaging study performed
– Failure to thrive secondary to kidney stones in children with suspected kidney stones, and it is a
– Persistent pain great screening tool nonetheless.
– Persistent nausea and vomiting Unenhanced CT scan is considered the gold
– Presence of fever standard imaging study for kidney stones given
– Urine analysis that suggests a urinary tract its high sensitivity and specificity in detecting
infection kidney stones independent of their location
– Presence of ureteral obstruction (Heneghan et al. 2003). Because children with
kidney stones have an increased lifetime risk for
recurrent stone formation, it is crucial that we limit
Surgical Management of Kidney Stones their radiation exposure by only obtaining CT
scan in situations that we know will influence
Surgical management of kidney stones has the choice of surgical modality. Kuhns and asso-
improved dramatically in the last two decades. ciates estimated the lifetime calculated risk in
Many of the technological advancements mir- children who underwent a single CT scan for
rored the expansion of minimally invasive surgery stone disease workup. For children 10 years or
in general, including the development of smaller younger at the time of the examination, about
and more durable endoscopic equipment. In this three radiation-induced cancers are predicted for
section, we will discuss the use of imaging studies every 1000 naturally occurring cancers, and for
as well as the different surgical options used in the children 15 years old, about two radiation-
treatment of kidney stones. induced cancers are predicted for every 1000 nat-
urally occurring cancers (Kuhns et al. 2011).
Imaging
Surgical Modalities for the Treatment
Imaging provides important information about of Kidney Stones
the kidney stones and anatomy of the urinary
collecting system. Size, shape, location of the Fortunately, several surgical modalities are avail-
stones within the collecting system, and presence able to the pediatric urologist when it comes to the
or absence of congenital abnormalities in the treatment of children with kidney stones. These
urinary system can affect the decision-making and modalities range from the least invasive use
choice of surgical treatment offered. The two most of extracorporeal shock wave lithotripsy
commonly used imaging modalities are renal and (ESWL) to the most invasive open surgical stone
bladder ultrasound (RBUS) and unenhanced heli- extraction. The increasing incidence of kidney
cal computed tomography (CT scan). stones in children and the increasing demand put
RBUS is the most widely used imaging modal- on pediatric urologists to treat stone disease were
ity for children presenting with kidney stones. It has paralleled by advancement in the technology of
the distinct advantage of no associated ionizing minimal invasive endourological procedures
radiation. Ultrasound, often combined with a plain facilitated by making smaller and more durable
abdominal x-ray, can detect stones in the kidneys or instruments. We will describe several of these
bladder and reveal if any degree of dilatation is minimal invasive surgical techniques used in the
present within the collecting urinary system. pediatric population.
Extracorporeal Shock Wave Lithotripsy calyx, cystine, or struvite stones, and anatomic
(ESWL) kidney abnormalities impairing urinary drainage
and stone clearance. Large retrospective studies
ESWL is based on delivering shock waves of PCNL have demonstrated high efficacy rates
from outside the body which is then targeted at a approaching 95% (Shokeir et al. 2006). Complica-
kidney stone to fragment it into smaller pieces tions related to the use of PCNL include bleeding,
(Fig. 1). The ideal candidates for ESWL are the delayed renal hemorrhage, sepsis, pneumothorax,
ones with stones smaller than 15 mm in diameter and injury to organs adjacent to the kidney.
with favorable anatomic position in the middle or
upper pole renal calyces. Success rates varies in
the literature from 68% to 92% (Straub et al. Prevention of Recurrent Kidney Stones
2010). Complications are minimal and range in
severity from hematuria and ecchymosis to ure- Adequate Fluid Intake
teral obstruction from passing larger fragments to
sepsis. Ample fluid intake is the most important component
in kidney stone prevention. The exact
fluid prescription is not known. However, most
Endoscopic Lithotripsy clinicians recommend that the intake of fluids be at
least the calculated maintenance requirements and
In this modality, an ureteroscope (Figs. 2, 3, and 4) 2–2.5 l per day in adolescents (Copelovitch 2012).
is advanced through the ureteral orifice all the way The amount of fluid requirement will be greater in
to the renal collecting system. Stones can then be situations where there are higher water losses such
fragmented using a holmium:YAG laser and then as fever or diarrhea. In children with cerebral palsy
retrieved with various instruments such as endo- and swallowing difficulties, a gastrostomy tube may
scopic baskets. Significant advances in miniaturi- be required to deliver the appropriate amount of
zation and durability of pediatric endoscopic daily fluids. For children on a ketogenic diet that
equipment made ureteroscopic laser lithotripsy a are fluid restricted, liberalization of fluid intake
more attractive option in young children. Stone- may be beneficial since increasing fluid
free success rates approaching 98% have been intake does not diminish the efficacy of the
reported (Minevich et al. 2005). Complications ketogenic diet in controlling seizures, but
related to the use of endoscopic equipment include hydration with larger amounts of water may
ureteral perforation, ureteral stricture, ureteral avul- prevent the formation of kidney stones (Furth et al.
sion, and sepsis. 2000).
Percutaneous Nephrolithotomy (PCNL) Sodium
In this technique, the renal collecting system is High sodium intake is known to promote hyper-
approached from the back of the patient. Under calciuria. Limiting the sodium in the diet to
fluoroscopic or ultrasound guidance, a needle is 2–3 mEq/kg/day is recommended for patients
inserted percutaneously into the collecting system. with hypercalciuria or calcium-containing stones
A guide wire is then inserted into the ureter (Copelovitch 2012).
followed by serial dilatation of the tract to allow
the passage of a nephroscope into the collecting
system. Ultrasonic probe or laser fiber can then be Calcium
used to fragment the stone into smaller pieces
(Fig. 5). Relative indications for PCNL include Low calcium diets should be avoided. A low
stones larger than 15 mm in diameter, stones in calcium diet will enhance intestinal absorption
less than favorable location such as a lower pole of oxalate (Habbig et al. 2011). Also, a low
Fig. 1 Extracorporeal
shock wave Lithotripter
Fig. 2 Pediatric
cystoscope
Fig. 3 Pediatric semirigid

ureteroscope (4.5 Fr tip)
calcium diet was found to be less effective than 2002). The recommended dietary calcium
a normal calcium diet, low sodium diet, and intake in children with kidney stones is appro-
low protein diet in preventing calcium-containing ximately 100% of recommended daily
stones in adults with hypercalciuria (Borghi et al. allowance (RDA).
Fig. 4 Flexible
ureteroscope
Fig. 5 Pediatric mini-

percutaneous
nephrolithotomy
endoscopic set
Protein intake for children with kidney stones should be

approximately 100% of the RDA for age to supply
Excessive dietary protein intake causes an adequate substrate for linear growth.
increased acid load which promotes skeletal cal-
cium loss, hypercalciuria, hypocitraturia, and low
urinary pH facilitating the formation of calcium Alkali Therapy/Potassium Citrate
oxalate stones (Copelovitch 2012). Vegetable and
dairy protein sources do not seem to carry the Treatment with potassium citrate has been shown to
same lithogenic risk. The consumption of exces- reduce the risk of stone formation in patients
sive amounts of dietary animal protein also results receiving a ketogenic diet. In a study that included
in increased uric acid production and may con- 197 children with intractable epilepsy on the keto-
tribute to uricosuria (Tasian and Copelovitch genic diet, urinary calcium to creatinine ratios were
2014). Therefore, the recommended protein measured at baseline and every 3–6 months
(Sampath et al. 2007). Potassium citrate treatment Cross-References

was started if the urine calcium to creatinine ratio
was greater than 0.20 mg/mg. The prevalence of ▶ Epilepsy in the Child with Cerebral Palsy
kidney stones was 3.2% for those started on ▶ General Nutrition for Children with
potassium citrate preventively compared with Cerebral Palsy
10% for those who were not (Sampath et al.
2007). As a result of the above findings, the same
investigators empirically began potassium citrate,
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Undescended Testis in Boys
Julia Spencer Barthold and Jennifer A. Hagerty
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 886
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 886
Prevalence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 886
Associated Risk Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 886
Treatment and Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 888
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 889
Abstract gestational age, hearing impairment, singleton

Cryptorchidism, or undescended testis, is the birth, incontinence, and intrauterine growth
most common male reproductive birth defect restriction (IUGR) but not with brain
presenting postnatally or in childhood. The malformations, hydrocephalus, intellectual
etiology is unknown, but the risk is increased disability (ID), gastrostomy use, or vision or
in many syndromic disorders, including cere- speech impairment. The association with spas-
bral palsy (CP). The frequency has been ticity and with presentation later in childhood
reported to be 41–54%; however, a recent in this population suggests that an “acquired”
larger series suggests that 29% of boys with presentation is common, possibly due to
CP have undescended or retractile testes, cremaster muscle spasticity. However, the
approximately tenfold greater than the general association with other congenital anomalies
population. Cryptorchidism risk in CP is inde- suggests that genetic causes may also contrib-
pendently associated with the severity of spas- ute significantly to co-occurrence of cryptor-
ticity, other congenital anomalies with or chidism with CP. In the general population,
without known genetic defects, reduced cryptorchidism is associated with increased
risk of subfertility and testicular malignancy,
but the level of these risks in the CP population
J. S. Barthold (*) · J. A. Hagerty is not defined. Undescended testes are also at
Nemours Biomedical Research and Department of higher risk for torsion, which may be difficult
Surgery, Division of Urology, Nemours/Alfred to diagnose in patients with ID. Except in high-
I. DuPont Hospital for Children, risk, complex patients, surgical correction is
Wilmington, DE, USA
e-mail: Julia.Barthold@nemours.org; indicated.
Jennifer.Hagerty@nemours.org

https://doi.org/10.1007/978-3-319-74558-9_59
886 J. S. Barthold and J. A. Hagerty
Keywords We recently reviewed a large database of

Undescended testis · Cryptorchidism · almost 3000 children with the established diagno-
Cremaster muscle · Retractile testis sis of CP at our institution, for whom testicular
position was documented in 776 males followed
until at least age 7 (Barthold et al. 2018). In this
Introduction extensive CP population, the prevalence of crypt-
orchidism was 24%, about tenfold higher than the
Cryptorchidism, or undescended testis, is a com- general population but lower than identified in
mon reproductive anomaly characterized by fail- previous reports that focused solely on institution-
ure of the testis to descend into the scrotum. The alized, frequently older individuals. The preva-
specific causes of isolated cryptorchidism are cur- lence of retractile testes in this population among
rently unknown, but there is evidence to suggest boys who never developed true cryptorchidism
that susceptibility is complex and dependent on a during follow-up was 5%. When the affected
combination of genetic and environmental factors side was clearly documented, the condition was
(Barthold et al. 2016). Cryptorchidism is a com- bilateral in 114 of 166 (69%) and 24 of 36 (66%)
ponent of hundreds of recognized syndromes, as of undescended and retractile cases, respectively,
defined by inclusion in the clinical synopsis for much higher than the prevalence of bilaterality
over 400 syndromes included in Online Mende- (25–30%) in boys with nonsyndromic cryptorchi-
lian Inheritance in Man (OMIM, http://omim. dism. Prior scrotal position was documented in
org). Similarly, almost half of the recognized syn- 20% of subsequently cryptorchid testes, and the
dromes identified in cerebral palsy (CP) patients average age at diagnosis was 5.8 years, suggesting
in one series are known to include cryptorchidism that testicular ascent may be common in the CP
as a component (Garne et al. 2008). An associa- population. In a comparison of these data and
tion between CP and cryptorchidism has been those for acquired, nonsyndromic cryptorchidism,
known for many years. However, the small case we found that bilaterality was more common in
series on which these observations were based CP cases but that milder phenotype (77% of testes
were insufficiently powered to determine the distal to the external ring) and the prevalence of
nature of the association. associated inguinal hernia (56%) were similar to
the frequencies we reported for uncomplicated
cases of testicular ascent (79% and 46%, respec-
Natural History tively) (Barthold et al. 2012).
Prevalence
Associated Risk Factors
Historically, studies that directly assessed the
prevalence of cryptorchidism in males with CP In single-variable analyses of our population, CP
focused on institutionalized, frequently older indi- comorbidities significantly associated with crypt-
viduals and the co-occurrence of intellectual dis- orchidism included quadriplegia, congenital
ability (ID). In a report of 148 institutionalized anomaly and/or genetic defect, intrauterine
individuals with ID, 44 (30%) had cryptorchi- growth restriction (IUGR), postnatal death, brain
dism, and the majority of these (82%) also had malformations, seizures, gastrostomy, absent
CP (Cortada and Kousseff 1984). Overall, crypt- bladder control, intellectual disability and hear-
orchidism was present in 36 of 88 (41%) and 21 of ing, and speech or visual impairment (Table 1,
39 (54%) severely disabled males with CP in Barthold et al. 2018). For the majority of these,
2 studies (Cortada and Kousseff 1984; Rundle there was a strong ordinal trend when comparing
et al. 1982). Similarly, a multivariable CP risk scrotal, retractile, and undescended testes within
ratio of 20.9 was reported in a perinatal cohort the CP population. In a stepwise multivar-
that included 385 cryptorchid boys (Depue 1988). iable analysis, we found independent positive
61 Undescended Testis in Boys with Cerebral Palsy 887
Table 1 Frequencies (%) of clinical characteristics in boys with cryptorchidism or retractile testes and CP
Variables (# cases) Descended Retractile Undescended p Valueb
(553) (38) (185)
Diagnosis
Quadriplegic 32.5 47.4 70.3 <0.001
Hemiplegic 42.1 39.5 24.3
Diplegic 25.3 13.2 5.4
Movement disorder 6.7 5.3 6.5 0.94
Death 2.0 5.3 6.3 0.009
Gestational age < 37w 55.4 57.9 53.6 0.85
Multiple birth 14.0 13.2 8.7 0.18
Intrauterine growth restriction (IUGR) 15.6 21.6 25.1 0.015
Congenital anomalya and/or genetic defect 8.3 15.8 20.3 <0.001
Brain malformation 8.1 10.5 14.3 0.049
Gastrostomy 21.7 31.6 51.4 <0.001
Absent continence 33.0 43.2 68.5 <0.001
Seizures 43.8 50.0 58.9 0.002
Hearing impairment 8.0 7.9 25.4 <0.001
Visual impairment 30.7 47.4 45.1 0.001
Abnormal speech 41.2 50.0 67.0 <0.001
Intellectual disability
None/mild 51.5 36.8 21.6 <0.001
Moderate 29.8 31.6 36.8
Severe/profound 18.6 31.6 41.6
a
At least one non-CNS congenital anomaly in addition to cryptorchidism
b
Results of chi-square analysis
associations of cryptorchid or retractile testes with Table 2 Stepwise logistic regression model of
quadriplegia, syndromic features/known genetic comorbidities associated with cryptorchidism in boys
disease, selected functional deficits including with CP
abnormal hearing and absent bladder control, Variable OR (95% CI) p Value
and with non-CNS congenital anomalies in Diagnosis
males with CP (Table 2). These data suggest a Diplegia Reference
stronger association of cryptorchidism with spas- Hemiplegia 1.8 (0.95, 3.4) 0.07
ticity than with ID and do not support the theory Quadriplegia 4.0 (2.0, 7.8) <0.001
that abnormalities of the hypothalamic-pituitary- Congenital anomaly 2.5 (1.4, 4.3) 0.001
and/or genetic defect
gonadal axis due to brain injury are the major
Gestational age 0.96 (0.93, 0.99) 0.015
cause of cryptorchidism in CP (Depue 1988).
Hearing impairment 1.9 (1.1, 3.1) 0.016
Alternatively, a role for muscle spasticity in
Multiple birth 0.53 (0.29–0.96) 0.036
the etiology of cryptorchidism in boys with CP Absent continence 1.6 (1.0, 2.6) 0.038
has also been suggested. In a longitudinal study Intrauterine growth 1.5 (0.96, 2.3) 0.079
comparing 50 infants and children with CP and restriction (IUGR)
age-matched controls, testicular position was Variables included in the model: race, diagnosis, movement
higher and remained static in CP cases, while testes disorder, death, birth weight, gestational age, multiple
of normal children were lower and became more birth, intrauterine growth restriction (IUGR), congenital
anomaly (non-CNS in addition to cryptorchidism) and/or
dependent with age and linear growth (Smith et al. genetic defect, postnatal injury, hydrocephalus,
1989). Based on these data, the authors theorized gastrostomy, absent continence, seizures, hearing impair-
that progressive cremaster muscle shortening is the ment, visual impairment, abnormal speech, and intellectual
cause of cryptorchidism in the CP population, a disability
theory also proposed in the non-CP population. A Table 3 Stepwise logistic regression model of
later age at diagnosis may also be related to deferral comorbidities associated with CNS and/or non-CNS con-
genital anomalies or genetic defect in boys with CP
of testicular exams in these complex patients or
potential uncertainty regarding indications for sur- Variable OR (95% CI) p value
gery (Harper et al. 2010; Springer et al. 2013). Intellectual disability (ID)
Recent studies indicate that congenital anoma- None/mild Reference
Moderate 2.1 (1.2, 3.4) 0.004
lies and genetic defects are more common than
Severe/profound 1.9 (1.3, 3.1) 0.019
previously recognized in CP (Fahey et al. 2017;
Undescended or retractile 2.0 (1.3, 3.1) 0.002
MacLennan et al. 2015; Nelson and Blair 2015). testis
Interestingly, we found that cryptorchidism is Gestational age 1.1 (1.1, 1.2) <0.001
more likely to occur in cases of CP associated Postnatal injury 0.4 (0.2, 0.8) 0.006
with other congenital anomalies and with IUGR, Intrauterine growth 1.5 (0.93, 2.4) 0.09
a known strong risk factor for both nonsyndromic restriction (IUGR)
cryptorchidism (Barthold et al. 2016; Gurney Variables included in the stepwise logistic regression
et al. 2017) and for CP (Jacobsson et al. 2008; model: race, diagnosis, movement disorder, death, birth
weight, gestational age, multiple birth, intrauterine growth
Blair and Nelson 2015). Similarly, our data
restriction (IUGR), postnatal injury, hydrocephalus,
suggest that cryptorchidism and IUGR are inde- gastrostomy, absent continence, seizures, hearing impair-
pendently associated with the occurrence of other ment, visual impairment, abnormal speech, intellectual dis-
congenital anomalies in cases of CP (Table 3; ability, and undescended or retractile testis
Barthold et al. 2018). However, we found several
differences in the patterns of comorbidity associ- ID and more profound functional impairment in
ated with cryptorchidism and other congenital univariable and multivariable models, respec-
anomalies in our CP population. In addition, the tively (Samijn et al. 2017).
presence of other congenital anomalies, unlike Although the etiology of CP and associated
cryptorchidism, did not correlate with the pattern cryptorchidism remains unclear and is likely
of spasticity, as others have found (Rankin et al. multifactorial, our results suggest that a subset
2010). Singleton birth was retained as an indepen- of males with CP present with a spectrum
dent risk factor in the final model for cryptorchi- of congenital anomalies that more commonly
dism but not for congenital anomalies. We also include cryptorchidism. Such cases may be
found that cryptorchidism risk in CP cases was caused by underlying genetic defects that also
inversely related to gestational age, as it is in the increase the risk of IUGR. In other boys with
non-CP population (Barthold et al. 2016; Gurney CP, the testes may fail to descend following pre-
et al. 2017). In contrast, full-term birth is more term birth due to local factors such as cremaster
common in children born with CP and associated muscle spasticity and/or inguinal hernia.
congenital anomalies (Nelson and Blair 2015;
Rankin et al. 2010).
Other independent associations that are Treatment and Complications
observed for cryptorchidism in CP include hear-
ing deficit and absent bladder control. The Given not only their increased risk of unde-
reported prevalence of hearing loss in 685 children scended testicles at birth but also risk for testicular
with CP mirrors that which we found in our pop- ascent, boys with CP should undergo scrotal
ulation (12%), and in univariable analyses, was exams to evaluate testicular position at least
associated with quadriplegia, ID, movement dis- yearly until onset of puberty. To best determine
orders, visual impairment, and seizures (Reid the position of the testes, boys should be exam-
et al. 2011). A study of 79 children with CP and ined in the supine and, if possible, sitting cross-
urinary incontinence found associations with ID, legged and standing positions. Abduction of the
severity of spasticity, movement disorder, and thighs, if feasible, assists with inhibition of the
issues related to speech and swallowing and with cremasteric reflex. A thorough exam should
61 Undescended Testis in Boys with Cerebral Palsy 889
include documentation of testicular palpability, difficult to diagnose promptly in this population

position, mobility, size, and possible associated (Ghalige et al. 2014). An alternative to correction
findings such as hernia, hydrocele, and hypospa- is removal of the testicle. This may be considered
dias. Patient distraction, a warm room and hands, in those with a normal contralateral testicle who
and repeated exams also help to localize the testis also have a very short vas deferens or vessels,
and to limit cremaster muscle activity and resul- hypoplastic testicle, or are postpubertal (Kolon
tant difficulty in determining testicular position. et al. 2014). Given the negligible difference in
Sustained gentle traction on the cord can help to surgical complexity and the high success rate of
inhibit the cremaster reflex and allow a retractile correction, removal of the cryptorchid testicle
testis to remain at least temporarily in a stable would not otherwise be recommended.
scrotal position. There is no role for scrotal ultra-
sound in the diagnosis of cryptorchidism, since it
does not improve diagnosis beyond the standard References
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in children with cerebral palsy: a population-based record
Gynecological Issues in Girls and
Young Women with Cerebral Palsy 62
Beth I. Schwartz and Chelsea Kebodeaux
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 892
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 892
Puberty and Menstruation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 892
Sexuality in Young Women . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 893
The Office Visit . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 894
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 895
Menstrual Suppression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 895
Contraception . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 900
Preventative Health and Screening . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 900
Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 901
Pregnancy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 901
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 902
Abstract
Girls and young women with cerebral palsy
face more difficulties than their nondisabled
peers. In particular, reproductive health issues
can be more complicated for adolescents with
B. I. Schwartz (*) disabilities. This can be an area of significant
Department of Obstetrics and Gynecology, Thomas apprehension and frustration for young women
Jefferson University, Philadelphia, PA, USA and their families. Medical providers often
Division of Adolescent Medicine and Pediatric have limited training and comfort caring for
Gynecology, Department of Pediatrics, Nemours/A.I. young women with disabilities, especially
duPont Hospital for Children, Wilmington, DE, USA with gynecologic issues in this population. As
e-mail: beth.schwartz@jefferson.edu;
beth.schwartz@nemours.org a result, adolescents with disabilities, and with
cerebral palsy in particular, are less likely to
C. Kebodeaux
Department of Obstetrics & Gynecology, Christiana Care receive education about reproductive health. In
Health System, Newark, DE, USA addition, confidentiality, a key tenet of adoles-
e-mail: chelsea.kebodeaux@gmail.com; cent health care, is often overlooked in this
chelsea.a.kebodeaux@christianacare.org

https://doi.org/10.1007/978-3-319-74558-9_60
892 B. I. Schwartz and C. Kebodeaux
population. This chapter aims to provide edu- bleeding can be challenging. The risk of preg-
cation about reproductive health for young nancy in girls with special needs can also be
women with cerebral palsy, with a focus on quite concerning to parents.
menstrual management and contraceptive Unfortunately, parents of children with disabil-
options. ities are less likely to be counseled regarding
puberty. It is important to provide anticipatory
Keywords guidance prior to the onset of puberty and to
Cerebral palsy · Gynecology · Reproductive address the concerns of both the child and parents
health · Menstrual suppression · Contraception early in development. In girls with cerebral palsy,
puberty begins earlier but ends later. The median
age of menarche for all girls in the United States is
Introduction 12 to 13, and girls with cerebral palsy experience
the onset of menses approximately 1.3 years later
Gynecologic health is often an area of great uncer- (Worley et al. 2002). Therefore, while girls with
tainty for girls with cerebral palsy and their families cerebral palsy may present with thelarche (breast
and providers. There may be concerns about how development) or adrenarche (pubic hair develop-
the hormonal changes of puberty will affect their ment) earlier than their peers, menarche, complete
bodies, associated medical conditions, and emo- Tanner stage 5 development, and achievement of
tions or behaviors. Menarche may also cause diffi- final adult height are often delayed.
culty due to challenges with hygiene, fear of abuse, For girls, menstruation is both an important
or apprehension about future pregnancy. Early milestone of adolescence and a medical indicator
exposure to gynecologic care can provide an of well-being and normal development. An under-
opportunity to offer education about reproductive standing of the normal adolescent menstrual cycle
health to girls with cerebral palsy and their families, is needed. Typical cycle lengths are 21 to 45 days.
including routine preventative healthcare, discus- Anovulatory bleeding leading to irregular cycles
sion about sexuality and sexual health, and men- is common in all teenagers, especially in the
strual management and contraceptive options. 2–5 years following the first period, but it is
Girls can also be reassured that pelvic exams are abnormal to have two periods more than 90 days
rarely necessary until adulthood. This chapter apart at any time (ACOG 2015, 2016). If periods
focuses on gynecologic health concerns specific are abnormal, onset of breast development has not
to girls and adolescents with cerebral palsy, includ- occurred by age 13, or menarche by age 15, eval-
ing pubertal changes, menstruation, sexuality, uation may be indicated. It is important to dis-
menstrual management and contraceptive options, cover abnormalities in pubertal development in a
and pregnancy. timely fashion, as an underlying endocrinologic
disorder may be the cause.
In addition to a clinical assessment of men-
Natural History strual cycles, it is important to address practical
concerns regarding menstruation. Girls and their
Puberty and Menstruation parents often have significant concerns regarding
the practicality of dealing with menses, and antic-
Puberty can be a source of anxiety for all parents ipatory guidance can be very helpful. In teenagers
but especially for parents of children with special with developmental delay, it may be difficult to
needs. There is often concern that hormonally explain the concept of “normal blood” (Quint
mediated mood changes will be difficult to navi- 2014). Even with normal menstrual duration and
gate or cause behavioral deterioration. For girls flow, maintaining hygiene may be challenging for
who need significant assistance with activities of girls with cerebral palsy. In those with contrac-
daily living, the logistics of managing periods and tures and limited manual dexterity, menstrual
62 Gynecological Issues in Girls and Young Women with Cerebral Palsy 893
products may have to be changed by caregivers, Sexuality in Young Women

which can be uncomfortable for both adolescents
and their caregivers. Girls and parents can be Sexuality is an important topic to address with all
reassured that those who can care for themselves adolescents and is especially important to discuss
in the bathroom without assistance can usually in those with disabilities due to societal and pro-
learn to use menstrual products appropriately. vider misconceptions. Girls with disabilities are
Pain with periods is a common complaint for often considered asexual and are rarely educated
many adolescents. Parents of girls with cerebral about sex, but this does not mean that they do not
palsy may be concerned regarding how they may have sexual thoughts and desires and are not sex-
manifest pain with periods, especially if they are ually active (Quint 2014). Although research is
nonverbal. This may result in mood and behavior limited in this area and is mainly based on survey
changes, which is a significant concern among data, the overwhelming evidence is that adoles-
parents of girls with cerebral palsy. In adults cents with cerebral palsy are interested in sexual
with developmental delay, 18% were noted to activity and do become sexually active. Unfortu-
have mood changes associated with menses, nately, teenagers with CP often experience a com-
many of which improved with pain medication plete lack of education regarding sexual health. In
(Quint 2014). Parents may be concerned or a cohort study of young adults with cerebral palsy
express frustration regarding mood changes that of average intelligence, 90% reported sexuality
lead to behavior problems at school or at home. had never been discussed with them, although
Prospective charting of mood and behavior the majority had some sexual experience before
changes for at least a few cycles is important to reaching their twenties and most had engaged in
rule out underlying medical or psychiatric disor- sexual intercourse (Wiegerink et al. 2011). Rela-
ders prior to treating for a menstrual-associated tionships and sexuality are two factors that con-
disorder. Hormonal medication and selective tribute substantially to quality of life for
serotonin reuptake inhibitors (SSRIs) may be con- adolescents with cerebral palsy, and sexual health
sidered, but consultation with a psychiatrist or should be included in discussions about social
neurologist is needed in patients with complex development (Sellwood et al. 2017). In qualitative
medical history or on multiple medications. Par- studies, teenagers expressed frustration that health
ents should be reassured that they know their child care providers do not ask straightforward ques-
and that pain should be treated adequately prior to tions regarding sexual activity. They also
treatment of mood and behavioral disturbances. expressed interest in disability-specific sexual
Girls with cerebral palsy are more likely to health information (East and Orchard 2014).
have a concomitant seizure disorder, which can The main difference in sexuality among young
both affect and be affected by the menstrual cycle. adults with cerebral palsy found in a study
Seizures can be temporally associated with men- conducted in the Netherlands was that sexual
ses or increase in frequency around menses, debut occurred approximately 2 years later com-
which may require the addition or adjustment of pared to their peers. This may be related to emo-
antiepileptic medications. The menstrual cycle tional inhibition and complex issues with body
and seizure timing and frequency should be image. In addition, physical problems with inter-
assessed in all adolescents with a seizure disorder. course are present in about 80% of people with
Some antiepileptic medications can lead to men- cerebral palsy. The most common obstacle is spas-
strual irregularities through elevations in prolac- ticity. Difficulty with positioning, impaired man-
tin, weight gain, and increased risk for polycystic ual ability, fatigue, and anorgasmia are also
ovarian syndrome (Herzog and Schachter 2001). common (Wiegerink et al. 2011). Women were
Although medications may be the cause of irreg- more likely than men to report problems with
ular menses, an evaluation is still indicated to rule physical fatigue. Despite these issues, both
out other causes. women and men with cerebral palsy are able to
have satisfying sexual lives. It is important to In addition to normal sexuality, sexual abuse
acknowledge sexuality as part of normal adoles- awareness and prevention should be discussed
cent development. Addressing sexuality is even with girls and their families. Unfortunately, the
more vital in this population, as patients may risk of dating violence among disabled high
significantly benefit from education and assis- school girls is nearly tripled compared to their
tance to improve sexual health and function. able-bodied peers (Mitra et al. 2013). Girls are
The most important aspect of addressing sex- also exposed to caregivers who may take advan-
uality in teenagers is confidentiality. Whenever tage of power dynamics. Young girls with disabil-
feasible and appropriate, confidential time with ities are often rewarded for their compliance and
the patient alone should be included in the visit. amiability, which increases their susceptibility to
First, providers should assess the adolescent’s exploitation. Warning signs of abuse may include
knowledge about anatomy and sexual health. regression of milestones or sudden use of sexually
Then sexual experience can be addressed. It is explicit language or behaviors. History and risk of
also important to acknowledge and address par- abuse should be assessed at every visit. Girls
ents’ concerns and fears regarding this area. should be counseled regarding abuse in a devel-
Parents may not even consider the sexuality of opmentally appropriate way.
their child or may be most concerned about
abuse. Alternatively, they may desire reassur-
ance that their child is able to have a fulfilling The Office Visit
intimate and sexual life in the future. Caregivers
are often in control of a patient’s access to History
healthcare providers and services, so it is impor- All young women and their families should be
tant for providers to use routine visits to explore questioned about the onset, timing, and pattern
sexual health as an aspect of normal of pubertal development to allow education
development. about normal pubertal development and the
Routine screening and contraceptive counsel- expected onset of menstruation. Once menarche
ing should also be provided. Sexually transmitted has occurred, a full menstrual history should be
infections (STIs) may be underdiagnosed or mis- obtained, including age at menarche, frequency,
taken for urinary tract infections, especially if pro- duration, and flow of menses. Information about
viders assume that a patient is not sexually active. associated pain and symptoms should be elicited
Therefore, it is important to offer routine screen- as well. Periods may affect the ability of young
ing for sexually transmitted infections and access women with physical limitations to be indepen-
to contraception (ACOG 2016). As for all adoles- dent (Quint 2014). The effects of periods on
cents, condom use should be encouraged for con- hygiene, mobility, moods, and behaviors should
traception and prevention of sexually transmitted be explored with the patient and her family. The
infections. Latex allergies are more common in menstrual history should be treated as a vital sign
adolescents with disabilities, so adolescents in adolescents (ACOG 2015). This helps allow for
should be counseled they may have a reaction. education about normal and abnormal menstrua-
Although latex-free condoms may not be as effec- tion. Identification of abnormal menses may indi-
tive at preventing pregnancy or protecting against cate undiagnosed health problems and lead to
STIs, they should still be used for those with latex earlier diagnosis and treatment. In addition, this
allergies. Girls with manual dexterity issues may opens the door for a discussion about possible
also have trouble manipulating barrier methods, menstrual management.
leaving them more vulnerable to sexually trans- The medical history of young women with
mitted infection (ACOG 2005). Contraception cerebral palsy should also include an assessment
should be discussed with all adolescents who are of the patient’s knowledge about reproductive
considering sexual activity or who are already health, her risk for physical or sexual abuse, and
sexually active. Contraceptive options are her ability to consent to sexual activity. Regard-
discussed in detail below. less of age, developmentally appropriate language
should be employed in girls with developmental to common adolescent complaints of irregular,

delay to discuss these concepts. Whenever it is heavy, or painful periods or related to issues spe-
appropriate and feasible, visits should include a cific to cerebral palsy. Menstrual management is
confidential portion with one-on-one time with indicated for periods that are heavy enough to
the patient to discuss issues of sexuality, sexual cause anemia or iron deficiency or painful enough
activity, and assess for abuse. to cause absences from school or activities. Addi-
tional indications in girls with cerebral palsy may
Physical Examination include issues with hygiene, exacerbation of con-
A full physical examination should be performed comitant medical disorders (such as seizures), or
when indicated. If a patient complains of heavy menstrually associated mood and behavioral dis-
menses, she should be evaluated for pallor, pete- turbances. Adolescents with physical disabilities
chiae, or ecchymoses. Attention to any possible or developmental delay may require assistance
signs of abuse is crucial if the history raises any with hygiene, which may contribute to a desire
concerns. Tanner staging of the breasts and pubic to manipulate menses.
hair is indicated for premenarchal girls to evaluate It is important to assess how menses affect the
the timing of pubertal progression and expected patient’s quality of life and to investigate the rea-
menarche. It is also a necessary part of the evalu- sons and motivations for the request for menstrual
ation of primary amenorrhea. manipulation, especially when it is coming from
A pelvic examination is usually not necessary the caregiver. The patient and family’s goals for
until age 21, as Pap testing is not indicated until menstrual management should also be assessed.
this age, regardless of sexual activity (ACOG Goals include predictable menses, reduction in the
2014a, b). As such, a pelvic examination is indi- duration or frequency of menses, and a decrease in
cated only for specific situations, such as persis- menstrually associated symptoms. The ultimate
tent abnormal bleeding that does not respond to goal of menstrual management is optimal sup-
usual medical interventions, vaginal discharge, pression, defined as a reduction in the amount
concern for a foreign body, or evaluation of pos- and total days of blood flow (ACOG 2016).
sible sexual abuse. For most of these situations, an Some patients and families prefer regular, predict-
external genitourinary examination is sufficient. able, improved periods, while others seek com-
Urine testing and vaginal swabs can be used to plete amenorrhea. It is very important to discuss
evaluate vaginal discharge and to screen for vag- realistic expectations with patients and their fam-
inal or sexually transmitted infections. A specu- ilies, as complete amenorrhea is very difficult to
lum or bimanual exam is not necessary for this. If achieve and should not be promised.
an internal examination is needed and the patient The American College of Obstetricians and
cannot tolerate it in the office, an examination Gynecologists (ACOG) recommends combined
under anesthesia may be performed. There may oral contraceptives and office placement of
be challenges in positioning young women with levonorgestrel intrauterine devices (IUDs) as
cerebral palsy for these examinations. The posi- first-line treatments for menstrual management
tioning should be varied according to their phys- for women with disabilities, depending on patient
ical limitations and contractures and may require characteristics, associated medical comorbidities,
extra staff or special equipment for assistance. and preferences. Second-line options include pro-
gestin-only pills, depot progestin formulations,
and IUDs when placement under anesthesia
Treatment is necessary. Hormonal implants are not typically
recommended for menstrual management.
Menstrual Suppression Endometrial ablation is not recommended for
adolescents, and hysterectomy should only be
Many young women with cerebral palsy and their considered as a last resort.
families and caregivers may be interested in men- Menstrual manipulation and suppression is not
strual regulation or suppression. This may be due indicated prior to menarche. Waiting until the
completion of pubertal development allows for Hormonal Treatment

the attainment of full adult stature. It also confirms A summary of all hormonal treatment options is
a patent reproductive outflow tract. In addition, seen in Table 1.
menses are often tolerated better than expected.
Estrogen-Containing Methods
Nonhormonal Treatment Menstrual management medications that contain
Some patients and their families are interested in estrogen come in multiple forms, including pills,
trialing nonhormonal options prior to starting hor- transdermal patches, and intravaginal rings. All
monal medications. They may perceive these to contain a combination of an estrogen and a pro-
be safer and to have less interaction with their gestin in varying doses. Benefits of these methods
other medical conditions or medications. The include regular, predictable periods with shorter
two most common categories of medications are duration, lighter flow, reduction in dysmenorrhea,
nonsteroidal anti-inflammatory medications and and improvement in menstrually related symp-
antifibrinolytics. toms and moods. Different formulations and
Nonsteroidal anti-inflammatory drugs doses can be used to avoid or limit side effects.
(NSAIDs) include ibuprofen, naproxen, and They can also be used in extended cycle or con-
ketorolac. Many are available over-the-counter, tinuous forms to decrease menstrual frequency
but some formulations and strengths are only and associated symptoms, although this may
available by prescription. They may be used to result in breakthrough bleeding. Breakthrough
achieve a moderate reduction in menstrual flow, as bleeding or spotting typically decreases over
well as a significant decrease in dysmenorrhea, time but may be very bothersome to patients.
and possible improved menstrually related mood There may be special considerations for use of
and behavior changes. Quint et al. (1999) found these medications in patients with cerebral palsy.
that 65% of adults with developmental delay had First, some patients may have relative or absolute
cyclic behavior changes that were responsive to contraindications to these medications. Those
NSAIDs. These medications may also improve with hypertension and migraines with aura should
menstrually related headaches and GI symptoms, not use medications that contain estrogen. There is
which are often mediated by prostaglandin a theoretical increased risk of VTEs in patients
release. However, they will not improve men- with impaired mobility. As estrogen also increases
strual regularity and some other menstrually the risk of VTE, some patients and providers are
related symptoms. nervous about using estrogen-containing medica-
Antifibrinolytics work by inhibiting fibrino- tions in this population. This may be especially
lysis. Tranexamic acid is FDA approved for true with the transdermal patch, which has
adults with menorrhagia. It significantly reduces conflicting evidence on whether there is an
menstrual duration and flow. It is also desirable increased thrombosis risk given its higher sys-
for some patients because it is only taken during temic estrogen absorption but lower peak estrogen
the first 5 days of menses. There is a theoretical concentrations (Schreiber and Barnhart 2014).
increased risk of venous thromboembolic events However, although there is an increased risk of
(VTE) due to its mechanism of action, though no thrombosis in elderly individuals who are
actual increase in VTEs has been seen even in wheelchair-bound and in others with new onset
high-risk patients (Lindoff et al. 1993). How- of prolonged immobility, such as recent surgery or
ever, this listed contraindication may limit its long air travel, the risk may actually be lower in
use in patients with cerebral palsy who have those who have had decreased mobility since
decreased mobility or are nonambulatory. In childhood (Lohiya et al. 2006). There is no con-
addition, it has not been tested or approved in vincing data against the use of these medications
adolescents, although it is often used off-label in in adolescents and young women with impaired
this population, especially in those with bleed- mobility who do not have other risk factors for
ing disorders. thrombosis. Despite the fact that there is no
Table 1 Summary of hormonal menstrual management options

Method Advantages Disadvantages Contraindications
Combined estrogen/progesterone
Pills Easily reversible Daily pill Absolute:
Patches Regular, predictable periods Possible mild temporary side effects: High blood
Rings (monthly or less frequent) nausea, headaches, breast soreness, pressure
Decreased flow, cramping, and irregular bleeding Migraines with
other menstrually related More serious side effects: high blood aura
symptoms (e.g., headaches, pressure, changes in cholesterol, Personal history of
nausea) interaction with other medications thrombosis
Improved acne Very serious but rare side effects: Personal history of
Decreased ovarian and endometrial increased risk of thrombosis or stroke a thrombophilia
cancers (1/1000) Relative:
Patch or ring can be used for Immobilization
convenience or if cannot tolerate Strong family
oral medication history of
thrombosis or
thrombophilia
Progesterone only
Pills Easily reversible Daily pill
Dose can be adjusted to achieve Possible weight gain
amenorrhea Increased acne
Worsened moods
Injection Every 11–13 weeks Irregular, unpredictable bleeding in Osteoporosis
Decreased flow, cramping, and the first few months that will improve Other risk factors
other menstrually related Possible weight gain, headaches, for bone density
symptoms worsened moods loss
High rates of amenorrhea Reversible bone density loss
Raises the seizure threshold for
those with epilepsy
Implant Lasts for 3 years Irregular, unpredictable bleeding that Not recommended:
Decreased cramping and other may not improve Only 20%
menstrually related symptoms Possible weight gain, headaches, amenorrhea
worsened moods
Requires a simple procedure
Levonorgestrel Lasts for 5 years Irregular, unpredictable bleeding, and
intrauterine Decreased flow and cramping cramping in the first few months that
device (IUD) Minimal systemic hormones and will improve
side effects Requires a pelvic exam and
No interactions with other procedure (can be placed under
medications sedation)
Risk of expulsion (~5%)
Rare risk of pelvic infections and
uterine perforation
absolute contraindication to estrogen-containing estrogen-containing medications have not been

medications, concerns about thrombosis among associated with increased seizure activity
families and medical providers may still limit (ACOG 2016). This is likely because it is fluc-
their use in nonambulatory patients. tuations in estrogen levels that affect seizures,
Second, there may be interactions of and the steady levels in most medications pre-
estrogen-containing medications with other vent these fluctuations. Additionally, the activity
medical problems or medications that are com- of progestins in combined hormonal contracep-
mon in this population. Although estrogen is tives acts as an anticonvulsant (Foldvary-
typically thought of as a proconvulsant, Schaefer et al. 2004).
There are notable interactions with some com- is not always achievable, and breakthrough
monly used antiepileptic drugs. These medica- bleeding is common. Possible side effects of
tions (phenytoin, carbamazepine, primidone, progestin-only medications are weight gain due
topiramate, oxcarbazepine, barbiturates) are also to increased appetite, acne, worsened moods, and
metabolized by the cytochrome P450 system and dyslipidemia.
can cause decreased efficacy of hormonal medi-
cations, including all estrogen-containing medica- a. Pills
tions, as well as progestin-only pills and the Progestin-only contraceptive pills, some-
hormonal implant. This interaction can cause an times referred to as the “minipill,” have only a
increase in breakthrough bleeding or other symp- 20% rate of amenorrhea with high rates of
toms and a theoretical increased risk of contracep- breakthrough bleeding. They do not reliably
tion failure. If breakthrough bleeding occurs or suppress ovulation, so dysmenorrhea or other
patients are sexually active, a pill with an estrogen menstrually related symptoms may not be ade-
dose of at least 30 mcg should be used. It is quately improved. In addition, the pills need to
important to note that hormonal contraception be taken at the same time daily, and adherence
does not decrease the efficacy of these anti- to this strict regimen impacts bleeding patterns
epileptic medications. The only exception is and efficacy.
lamotrigine, as estrogen-containing medications Oral progestins can also be used in higher
can decrease its serum concentration. This can doses to better achieve amenorrhea. Norethin-
result in worsened seizure activity when drone acetate is commonly used for menstrual
lamotrigine is used as monotherapy for seizure suppression in girls and young women with
control. The use of concomitant estrogen- special needs. There are limited data on this
containing medications is not contraindicated, medication, but amenorrhea rates of almost
but lamotrigine levels need to be monitored and 100% have been reported in those using it for
adjusted appropriately. pain control for endometriosis (Kaser et al.
Third, the route of administration should be 2012). Oral medroxyprogesterone acetate has
carefully considered in patients with cerebral also been used for menstrual suppression, but
palsy. For girls who cannot swallow pills, there this is usually used for acute bleeding rather
are chewable oral formulations of combined oral than for long-term use.
contraceptive pills. The pills can also be crushed b. Injection
and mixed with food or administered via G-tube. Depot medroxyprogesterone acetate
Transdermal patches may be a desirable alterna- (DMPA) is administered as an intramuscular
tive due to easier administration. However, they injection every 11–13 weeks. Benefits
are sometimes (inadvertently or deliberately) included improved bleeding, increased con-
removed by girls with disabilities. Patches venience, and lack of interaction with anti-
should be placed out of reach, such as on the epileptic medication. DMPA results in high
upper back, to avoid this. The vaginal ring may rates of amenorrhea that increase with time.
present difficulty with placement in young Amenorrhea rates of over 50% at 1 year and
women who have mobility issues or contractures 70% at 2 years have been reported (Pfizer
and create intimacy concerns and a violation of 2017). However, initial irregular bleeding is
privacy if placed by a caregiver. Thus, it is often common. It only requires four injections a
not an ideal option for patients with cerebral year, which is very convenient for patients.
palsy. DMPA has also been shown to raise the sei-
zure threshold and does not interact with any
Progestin-Only Methods antiepileptic medications. Although a meta-
Unlike estrogen-containing methods, which result analysis found limited evidence of weight
in regular periods, the typical goal of progestin- gain with this method, some patients on
only methods is amenorrhea. However, this goal DMPA gain significant weight. If patients
are nonambulatory, even small increases in d. Intrauterine device

weight can interfere with wheelchair transfers Although the use of intrauterine devices
(Quint 2014). There is also concern about the (IUDs) was previously limited to adult
effects of long-term use of DMPA on bone women who have had at least one child, they
mineral density, which led to a 2004 FDA are increasingly being used in adolescents and
black box warning. Although a decrease in nulliparous women. Hormonal (levonorges-
bone density of 2.7–4.1% in adolescents on trel) IUDs have great potential for use in
DMPA was seen, bone density has been young women with special needs for multiple
shown to return to preexposure levels after reasons. First, they are convenient, with
discontinuation, regardless of the duration of approval for 5 years for contraception. Second,
use (Scholes et al. 2005). However, patients hormonal IUDs result in a significant decrease
with disabilities who have limited mobility in bleeding days and overall blood loss with an
have lower baseline bone mineral density, amenorrhea rate of about 50% at 1 year
and many have both low bone density and (Hildalgo et al. 2002). As with DMPA, there
fragility fractures, resulting in a diagnosis of is frequent initial irregular bleeding that
osteoporosis. Antiepileptic and other medica- steadily improves with time. Unlike other
tions may also be additional risk factors for methods, the IUD’s actions are almost
bone density loss in this population. Some completely localized, with minimal systemic
girls with cerebral palsy begin treatment for absorption, side effects, or interactions with
osteoporosis in childhood, and the effect of other medications or medical problems. A
DMPA for these girls is not known. The ben- drawback is that IUDs often require placement
efits and risks should be considered and under anesthesia in adolescents with disabil-
discussed prior to prescribing DMPA for ities due to inability to tolerate or to obtain
young women with cerebral palsy. Routine adequate positioning for office placement. To
bone density testing is not recommended for ameliorate the risk of anesthesia, IUD place-
adolescents on DMPA. There are no recom- ment can sometimes be coordinated with other
mendations specific to adolescents with dis- examinations or procedures under anesthesia.
abilities or who have other risk factors Common concerns about IUD use in ado-
(ACOG 2016). lescents include an increased risk of infection
c. Implant and pelvic inflammatory disease, but this is
The etonorgestrel implant is a 4 cm rod that only caused by ascending sexually transmitted
is implanted subdermally in the upper arm. It is infections in the first 20 days after insertion.
very convenient, as it lasts for 3 years before Infection screening can be performed at the
requiring removal. It significantly decreases time of insertion. Expulsion rates have been
dysmenorrhea, but its bleeding pattern may reported as higher in nulliparous women, but
not be ideal for patients with cerebral palsy low rates (2–11%) have been reported in young
who are seeking menstrual suppression. women with disabilities (Kirkham et al. 2013,
The amenorrhea rate is only about 20% Pillai et al. 2010, Savasi et al. 2014), though
(Darney et al. 2009). Common complaints of this is based on limited data. There is no dif-
unscheduled and irregular bleeding may not ference between adolescents and adults in the
improve with time, as the bleeding pattern in risk of uterine perforation, which is about
the first 3 months is highly predictive of the 2/1000. Due to the excellent bleeding and
future bleeding pattern. The implant may also safety profiles, ACOG recommends that this
interact with antiepileptic drugs in the same method be considered for all adolescent
way as oral medications. Placement requires a patients.
high level of cooperation. A patient who is not Patients and their parents should be edu-
able to tolerate or remain still for insertion may cated on expected changes in bleeding pat-
require sedation. terns. They should report any changes in
bleeding or discomfort after the initial post- Contraception

insertion period to their providers. If a patient
cannot tolerate an exam to check for proper In general, adolescents should be counseled
IUD positioning, an abdominal ultrasound to regarding contraception as discussed for men-
evaluate positioning can be obtained. strual suppression, but counseling may be modi-
fied based on the goals of treatment. While the
Surgical Treatment contraceptive implant is not the most effective
Although some families of girls with cerebral option for menstrual suppression, it is the most
palsy may request surgical options for menstrual effective reversible contraceptive option. Long-
suppression, ACOG (2016) does not recommend acting reversible contraception, which includes
these options. Surgical options have increased both implants and IUDs, should be recommended
morbidity compared to the many other effective as the most effective methods to prevent
options and should be used as a last resort or not unintended pregnancy (ACOG 2012). The vagi-
at all. nal ring may be more acceptable to a sexually
active woman with a stable partner who could
Endometrial Ablation help with insertion and removal compared to a
Endometrial ablation is a surgical procedure woman who does not have a sexual partner to
during which the uterine lining is destroyed. provide this assistance. Emergency contraception
The amenorrhea rate with this method is only should also be made available in addition to birth
about 33%, and there are high reoperation rates control. Girls with cerebral palsy may have sig-
of up to 22%. The failure rate is much higher in nificant transportation difficulties and may have
women under age 45, and the procedure has more difficulty obtaining emergency contracep-
never been studied in adolescents. Although it tion if their parents are not aware of their sexual
is not considered a sterilization method, it does activity.
result in decreased fertility. If a pregnancy Although some families may desire permanent
occurs after an ablation, it is considered a high- sterilization for contraception, this request should
risk pregnancy. For all of these reasons, ACOG be treated similarly to hysterectomy, as it raises
recommends against use of this procedure in ethical concerns due to its irreversible nature and
adolescents, including adolescents with issues with consent. In addition, it does not help
disabilities. with menstrual management and does not prevent
abuse.
Hysterectomy
Hysterectomy is not recommended for menstrual
suppression due to its irreversible nature and Preventative Health and Screening
potential risk for morbidity and mortality. In addi-
tion, although many families request this for both The American College of Obstetricians and Gyne-
menstrual suppression and permanent steriliza- cologists recommends that a girl’s first visit for
tion, it does not protect against abuse or sexually screening and reproductive health care services
transmitted infections. It also does not stop the occur between ages 13 and 15 (ACOG 2014a).
hormonal or behavioral effects of menses, unless The provider should discuss and provide anticipa-
the ovaries are also removed, which is not tory guidance regarding pubertal development,
recommended. There are also significant concerns normal menses, sexually transmitted infections,
due to the ethics of consent. Therefore, ACOG sexual orientation and gender identity, and sexual
recommends consideration of hysterectomy only assault prevention. A specialist provider, such as
after all other reasonable alternatives have been an adolescent medicine pediatrician, pediatric
attempted and considered. The hospital Ethics gynecologist, or obstetrician/gynecologist famil-
Committee should be involved with these iar with treating adolescents and/or women with
requests. disabilities may be the best provider to conduct
this visit. Girls with special needs and their (ACOG 2014b). Urine screening can be employed
parents may have specific questions or needs if a pelvic exam is not otherwise indicated or if the
regarding menstruation, hygiene, menstrual sup- exam is unable to be tolerated due to contractures
pression, contraception, and fertility. Guidance or spasticity. Adolescents may prefer to self-
regarding recommended health maintenance and collect a vaginal swab if they are physically able
cancer screening is important, as women with to do so.
physical disabilities are more likely to underesti- The use of sedation or anesthesia may be con-
mate or lack awareness of their risk for gyneco- sidered in women who are unable to tolerate
logic cancer and thus are less likely to receive breast or pelvic exams due to physical limitations
screening (ACOG 2005). or discomfort. To minimize the risk of anesthesia,
Prevention of cervical cancer has two compo- this should ideally be coordinated with other nec-
nents: vaccination and screening. Human papil- essary exams or procedures, such as dental work.
loma virus (HPV) vaccination should be offered These may also be spaced to every 3 years if
to all young women ages 9 to 26, regardless of screening is normal.
sexual activity (ACOG 2014b). It is typically
recommended at ages 11–12. In girls with disabil-
ities, initiation of HPV vaccination is encouraged Complications
as early as possible due to the unfortunately high
risk of sexual assault in this population. Screening Pregnancy
by cervical cytology (Pap test) should begin at age
21, regardless of sexual activity. In general, research on pregnancy in patients with
Breast cancer screening includes the clinical cerebral palsy is limited. Fertility is thought to
breast exam and mammography. Clinical breast be normal for most women with disabilities,
exams should begin at age 21. There are some although one small study implied that increasing
variations in recommendations for mammogra- disability is associated with lower conception
phy. The American Cancer Society recommends rates. Pregnancy outcomes are generally consid-
annual mammography screening from age 45 to ered favorable, but degree and types of risks
70 for average risk women; it may be offered depend on the patient’s severity of impairment
starting at age 40 (Oeffinger et al. 2015). In and the extent of contractures, spasticity, and
order to support women undergoing mammogra- other visual, auditory, or intellectual impairments
phy, it is important to inform patients about the (Signore et al. 2011).
physical requirements of the test. There are spe- Preconception planning is important for all
cial equipment and positioning available that may patients and is even more important for patients
be used for women with physical limitations. with cerebral palsy. Preconception planning
Standing is not required to undergo mammogra- improves pregnancy outcomes, but unfortunately
phy. Recommendations of facilities that are more is often neglected due to providers’ negative atti-
accommodating of women with disabilities are tudes toward women with disabilities who desire
useful. If a woman is unable to undergo a mam- pregnancy (Thierry 2006). Preconception
mogram, breast ultrasound may be used, but it is counseling should include identification of medi-
important to be aware that ultrasound is not as cal problems and behaviors that may affect preg-
effective as mammography for detecting micro- nancy outcomes. Women with disabilities are
calcifications, which may indicate the earliest more likely to have pregnancy risk factors, includ-
stages of breast malignancy (Poulos et al. 2006). ing obesity, diabetes, asthma, smoking, inade-
Sexually transmitted infection screening, quate exercise, and lack of social support (Mitra
including for chlamydia, gonorrhea, and HIV, et al. 2016). Counseling regarding weight loss,
should be offered to all sexually active adoles- improved diabetic control, smoking cessation,
cents annually until at least the age of 26 and and increased exercise prior to pregnancy can
beyond then based on patient risk factors decrease the risk of miscarriage, birth defects,
preterm birth, and other poor pregnancy out- correlated with an increased risk of prematurity
comes. Antenatal medications should be and low birth weight. Extrapolating this connec-
reviewed, and patients should be referred to a tion, it may be reasonable to offer growth ultra-
maternal-fetal medicine specialist for consulta- sounds to screen for fetal growth restriction in
tion, optimization of health, and discussion of women with cerebral palsy.
the benefits and risks of their current medication Although the data on thrombotic events in
regimens. pregnant women with cerebral palsy are too lim-
Pregnancy may increase physical challenges ited to show an increased incidence, pregnant
for women with cerebral palsy. Weight gain and women are at an overall increased risk of throm-
change in body habitus may pose special limits on bosis. There is not enough evidence to recom-
women with impaired mobility. In ambulatory mend thrombosis prophylaxis in pregnant
women, changes in their center of gravity and women with decreased mobility, but thrombosis
weight distribution may increase the risk of falls awareness and prevention should be at least
or require the use of assistance devices. Some discussed with pregnant women with cerebral
women may have to use a wheelchair for the palsy.
first time during pregnancy (Signore et al. 2011). Labor and delivery is usually uncomplicated
In wheelchair-bound women, pregnancy weight for women with cerebral palsy. In small studies,
gain may limit their ability to transfer indepen- there are no reports of spasticity or contractures
dently or propel their chair. It may also increase causing issues during labor and delivery. The
the risk of decubitus ulcers, especially if other risk cesarean delivery rate may be higher than for the
factors are present. Women should be counseled general population, although the etiology is
to avoid excessive gestational weight gain and to unclear (Signore et al. 2011). Women with cere-
continue range of motion exercises throughout bral palsy should not undergo primary cesarean
pregnancy. Consultation with a physical therapist section, except for obstetric indications.
may be indicated early in pregnancy to ameliorate In the postpartum period, breastfeeding sup-
these risks. port should be offered. Assistive devices that
Women with decreased respiratory reserve due improve positioning to optimize comfort and
to contractures or weakness may have increased support should be provided. Postpartum depres-
shortness of breath and pulmonary complications sion may be more prevalent in women with dis-
during pregnancy. Genitourinary issues may also abilities, and women should be screened and
be heightened. Women may experience inconti- counseled appropriately early in their postpartum
nence, an increased need for catheterization, or the course. The risk of thrombosis is highest during
inability to perform self-catheterization due to the this period, and women should be counseled
gravid uterus. Although limited data do not show accordingly.
an increased rate of urinary tract infections in
pregnant women with cerebral palsy, there is a
theoretically increased risk in pregnant women Cross-References
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There are no known neonatal risks related to
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Part XIII
Pulmonary
Bronchopulmonary Dysplasia
and Cerebral Palsy 63
Frances Flanagan and Anita Bhandari
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 908
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 908
Definition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 908
Incidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 908
Pathology of BPD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 909
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 910
Prevention of BPD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 910
Postnatal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 911
Treatment of Established BPD . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 912
Immunizations and RSV Prophylaxis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 912
Outcome/Prognosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 913
Respiratory Outcomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 913
Neurodevelopmental Outcomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 913
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 913
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 914
Abstract bronchopulmonary disease (BPD) has

Advances in perinatal care have dramatically remained largely unchanged if not slightly
improved the outcome of preterm infants increased over this time period, likely due to
over the last few decades. Incidence of the increased survival of extremely preterm
infants. BPD is a multifactorial disorder and
infants frequently undergo treatment with var-
F. Flanagan ious pharmacological agents, many of which
Division of Pulmonary and Respiratory Diseases, Boston lack efficacy in studies to date. BPD is an
Children’s Hospital, Boston, MA, USA
e-mail: frances.flanagan@childens.harvard.edu independent risk factor for neurodeve-
lopmental delay and cerebral palsy (CP) in
A. Bhandari (*)
Department of Pediatrics, Division of Pulmonary children. Therefore, the presence of CP needs
Medicine, Children’s Hospital of Philadelphia, to be considered when treating patients
Philadelphia, PA, USA with BPD.
e-mail: bhandaria@email.chop.edu

https://doi.org/10.1007/978-3-319-74558-9_67
908 F. Flanagan and A. Bhandari
Keywords defined as having moderate BPD. Those infants

Cerebral palsy · Bronchopulmonary requiring >30% FiO2 or positive pressure venti-
dysplasia · Chronic lung disease · Prematurity lation are defined as having severe BPD (Jobe and
Bancalari 2001) (Table 1). Infants born
>32 weeks’ gestation follow the same severity
Introduction criteria but are assessed at >28 but <56 postnatal
days or at discharge home whichever occurs
Advances in perinatal care have dramatically earlier.
improved the outcome of preterm infants over CP occurs more frequently in children with
the last few decades. Despite this, the incidence BPD. CP is defined as motor impairment that
of Bronchopulmonary Disease (BPD) has limits activity and is attributed to
remained largely unchanged if not slightly non-progressive disturbances during brain devel-
increased over this time period, likely due to the opment of fetuses and infants.
increased survival of extremely preterm infants.
BPD is a multifactorial disorder and infants fre-
quently undergo treatment with various pharma- Incidence
cological agents, many of which lack efficacy in
studies to date (Stoll et al. 2015). BPD is an The risk of development of BPD is inversely
independent risk factor for neurodevelopmental related to the birth weight and gestational age of
delay and cerebral palsy (CP) in children. There- the neonate at birth. It occurs in 46% of surviving
fore, the presence of CP needs to be considered infants with a birth weight between 500 g and
when treating patients with BPD. This chapter 750 g, in 36% of infants weighting 751–1000 g,
will discuss the natural history, treatment options, in 14% of infants weighting 1001–1250 g, and in
and outcomes for children with Cerebral Palsy 6% of infants with a birth weight of 1251–1500 g
and Bronchopulmonary Dysplasia. (Fanaroff et al. 2007). BPD has repeatedly been
shown to be independently associated with CP
(Isayama et al. 2017). In one study of infants
Natural History with a very low birth weight (VLBW <1500 g),
15% of survivors with BPD had CP compared
Definition with 3–4% in comparable patients without BPD
(Skidmore et al. 1990). Patients with BPD who
The definition of bronchopulmonary dysplasia require mechanical ventilation at 36 weeks PMA
(BPD) remains “a moving target” since its original
description by Northway et al. in 1967 due to
novel respiratory approaches and the management Table 1 Severity definition of BPD
of the preterm infant (Northway et al. 1967). The Severity of
National Institutes of Health proposed a definition BPD
of BPD in 2001 which remains the consensus None O2 treatment <28 days and breathing
room air at 36 weeks PMA or discharge
definition for infants born <32 weeks gestation. home, whichever comes first
To enable a severity-based classification of BPD Mild O2 treatment at day 28 and breathing
in this group of extremely preterm infants, all room air at 36 weeks PMA or discharge
infants born at less than 32 weeks still requiring home, whichever comes first
supplemental oxygen at 28 days of life undergo a Moderate O2 treatment at day 28 & receiving <30%
O2 at 36 weeks PMA or discharge home,
respiratory support assessment at 36 weeks post-
whichever comes first
menstrual age (PMA). Infants breathing room air Severe O2 treatment at day 28 & receiving >30%
at 36 weeks’ PMA are defined as having mild O2 or nasal CPAP / HFNC / mechanical
BPD. Infants needing <30% fraction of inspired ventilation at 36 weeks PMA
oxygen concentration (FiO2) supplementation are Jobe and Bancalari (2001)
63 Bronchopulmonary Dysplasia and Cerebral Palsy 909
(i.e., severe BPD) were recently reported to have a extremely premature (<28 weeks) and more
sixfold increased risk of quadriparesis and a four- likely to be exposed to gentler modes of ventila-
fold increased risk of diparesis (Van Marter et al. tion. Histological findings in “old” BPD include
2011). In addition to CP, patients with BPD can extensive airway disease, areas of overinflation
have specific movement disorders, exhibit poor and fibrosis, pulmonary arteriolar
gross and fine motor skills, and have more visual muscularization, and interstitial and alveolar
and auditory problems then preterm children edema. This is in contrast to “new” BPD pathol-
without BPD (Doyle and Anderson 2009). ogy, which is characterized by impaired alveolar-
capillary development with larger, simplified
alveoli, increased interstitial fibrosis along with
Pathology of BPD abnormal pulmonary vasculature with decreased
branching and pre-capillary arteriovenous anasto-
In the BPD literature, authors often talk about moses (Coalson 2003).
“old” BPD and “new” BPD. “Old” BPD refers Simply put, old BPD reflects the response of
to changes seen in the lungs of patients before the premature lung to barotrauma, volutrauma,
surfactant was routinely used, and since this ther- and oxygen toxicity, whereas new BPD reflects
apy dates back to the late 1980s and early 1990s, abnormal or even restricted lung growth.
babies with “old” BPD were more likely to be There are many factors implicated in the devel-
larger preterm babies, more likely to have opment of BPD (Fig. 1) including chorioam-
received aggressive mechanical ventilation and nionitis. Chorioamnionitis is a perinatal
have been exposed to high oxygen concentrations. condition which is characterized by inflammation
“New” BPD infants are more likely to be of fetal membranes and has interestingly been
Fig. 1 Pathogenesis of “new” BPD This figure shows multiple factors that impact development of BPD. Bhandari and
Bhandari. Pediatrics 2009 (123) 1562–73
implicated both in the development of BPD and regional ventilation and perfusion in addition to
CP in preterm infants. With respect to CP, data reducing radiation exposure (Bhandari and
suggests an association of clinical chorioam- McGrath-Morrow 2013).
nionitis with development of CP in preterm
infants (Shi et al. 2017), whereas the data is
conflicting regarding its role in the development Treatment
of BPD. Others have reported that chorioam-
nionitis does not increase the risk of neurodeve- Various modes of ventilation, drug therapies, and
lopmental disability in premature infants with nonpharmacological therapies have been devel-
BPD (Bashir et al. 2016). oped to help prevent BPD and mitigate its effects
once established. Unfortunately, many of these
Radiology therapies have not delivered their expected out-
Radiology is no longer included in the definition come. Most therapies continue to lack evidence
of BPD. However it can be useful to help predict and hence remain institution or physician specific.
the severity and to guide ongoing management of Despite the increased coexistence of BPD with
children with BPD. Chest CT has been shown to CP, most therapies and management options do
be more sensitive than chest x-ray (Figs. 2 and 3) not change depending on the presence or absence
in assessing pulmonary damage in children with of CP and have no impact on neurodevelopmental
BPD. outcomes once BPD is established.
Multiple parenchymal abnormalities are found
on imaging of children with BPD including,
multifocal hyperlucent areas, linear and sub- Prevention of BPD
pleural opacities, bronchial wall thickening, bul-
lae and bronchiectasis (Tonson la Tour et al. Antenatal
2013). Newer modalities, including hyper- Gluocorticoids accelerate surfactant production
polarized gas magnetic resonance imaging and hence lung maturation. A single short course
(MRI) scans and arterial spin labelling are prom- of maternal antenatal glucocorticoids is now the
ising, as they are also helpful in the assessment of gold standard of care for women between 24 and
Fig. 2 Chest X-ray of a patient with BPD

Reproduced with permission from Vineet Bhandari (2018). Fig. 3 Chest CT scan of a patient with severe BPD
Chest X-ray of a premature baby on mechanical ventilation Chest CT and angiogram of an infant with severe BPD
shows haziness and increased interstitial markings in both showing mild hyperinflation, marked bilateral interstitial
ling fields thickening, and presence of subpleural and paraseptal cysts
34 weeks gestation with risk of preterm labor. Vitamin A

Despite its effect on reducing neonatal mortality Vitamin A plays an integral role in the regulation
and the incidence of respiratory distress syndrome and growth of cells, including maintaining the
(RDS), antenatal steroids have not been shown to integrity of the epithelial cells lining the respira-
decrease the risk of BPD (Roberts et al. 2006). tory tract. Supplementary intramuscular Vitamin
A has been shown to result in a modest improve-
ment in incidence of BPD, but the need for
Postnatal repeated intramuscular injections limits its use
(Tin and Wiswell 2009).
Surfactant Therapy
Premature lungs lack surfactant, resulting in poor Oxygen Therapy
lung compliance and ultimately increased work of Oxygen supplementation is the most commonly
breathing and respiratory failure. Hence many of used drug in infants with RDS and BPD, with an
these patients require exogenous surfactant. Sur- ultimate goal of providing adequate tissue oxy-
factant therapy is now standard of care for prema- genation while avoiding oxidative stress and oxy-
ture infants with RDS requiring supplemental gen toxicity. Hyperoxemia has long been
oxygen and respiratory support. Current practices identified as being toxic to the pulmonary epithe-
involve administering surfactant via the lium. Thus far, no optimal target Sp02 has been
intratracheal route (whether via tracheal intuba- identified in preterm infants predischarge, as a fine
tion in an already intubated baby or via the balance between hypoxemia and hyperoxemia
INSURE method, which combines intubation, remains. Current AAP guidelines recommend a
surfactant treatment, then rapid extubation back Sp02 alarm limits of 89–96%, while awaiting
to noninvasive support). Surfactant replacement further study results (Manja et al. 2017). Most
therapy has also been shown to reduce mortality institutions aim to maintain O2 saturations
and RDS but has not been shown to reduce the >92% post discharge home and while weaning
risk of developing BPD. off O2 therapy (Abman et al. 2017) and > 94% if
there is evidence of pulmonary hypertension.
Caffeine
Caffeine is one of the therapies which have been Corticosteroids
associated with decreased risk of developing The use of systemic corticosteroids in the postna-
BPD. Additionally, it is used to reduce the fre- tal period remains controversial. Despite studies
quency of apnea and the need for prolonged sup- showing a reduction in the incidence of BPD, a
plemental oxygen, continuous positive airway reduction in intubation time, a decrease in the
pressure, and mechanical ventilation (Schmidt need for a later course of systemic steroids and
et al. 2006). In fact, in patients with a birth weight home oxygen therapy, their clear association with
of 500–1250 g, caffeine has been shown to a poor neurodevelopmental outcome and signifi-
increase the rate of survival without cant short-term side effects including hyperglyce-
neurodevelopment disability at 18–21 months mia and hypertension has limited their use to a
PMA and to decrease the incidence of CP and case to case basis (Fok 2009; Doyle et al. 2017;
cognitive delay and may improve motor function Barrington 2001). The use of steroids is restricted
at 5 years of age (Schmidt et al. 2007). Follow up to a short course of dexamethasone (DART pro-
of patients at 11 years of age showed no associa- tocol) for infants who continue to require invasive
tion of caffeine therapy with a decrease in aca- respiratory support at 3–4 weeks postnatal age
demic, motor, and behavioral impairments when with a risk of BPD exceeding 50%, to facilitate
all were combined, although it was associated extubation.
with a reduced rate of motor impairment (Schmidt Due to the neurodevelopmental complications
et al. 2017). of oral steroids, clinicians have trialed the use of
inhaled steroids. The majority of clinical trials of in specific biomarkers of BPD, the aim is to
early and late inhaled corticosteroids in the neo- develop specific therapies tailored towards reduc-
natal population have shown no reduction in BPD ing non-eosinophilic inflammation (Malleske
or death compared to systemic corticosteroids; et al. 2017).
however, long-term neurodevelopment data is However, in patients with BPD and CP where
awaited. Novel use of surfactant as a vehicle for impaired neurological status can lead to impaired
intratracheal corticosteroid instillation has shown airway clearance, albuterol is frequently used as
to reduce the risk of BPD and death without part of airway clearance rather than for treatment
increasing long-term developmental problems, of bronchospasm.
but further studies are required to confirm these
findings (Yeh et al. 2016). Nutrition
Infants with BPD have additional nutritional chal-
lenges compared to their non BPD counterparts,
Treatment of Established BPD due to their increased metabolic demands,
increased work of breathing, additional stresses,
Diuretics and often chronic steroid and diuretic use. As with
Despite the long-held belief that infants with BPD any infant, the goal of nutrition in patients with
are unable to tolerate excessive fluid intake and BPD and CP is to supply adequate nutrition to
tend to accumulate lung fluid, diuretics have not meet the patient’s specific needs to allow them to
been shown to reduce mortality, the duration of grow and develop. Due to additional nutritional
invasive or noninvasive ventilation, oxygen use, requirements, infants with BPD often require
or the length of hospital stay (Donn 2017). The increased caloric intake >130 kcal/kg/day espe-
long-term use of diuretics also comes with a sig- cially during the acute phase. This often proves
nificant risk of hyponatremia, hypokalemia, hypo- problematic due to fluid balance issues and hence
chloremia, calciuria, and a contraction alkalosis. feeds are often fortified in the initial period.
In fact, contraction alkalosis can ultimately lead to Depending on the gestational age, patients with
nephrocalcinosis and osteopenic bone disease, BPD may initially be fed by a nasogastric tube,
potentially altering chest wall compliance and but once they have developed a coordinated suck
hence worsening BPD (Donn 2017). Despite and swallow reflex and their respiratory status has
this, diuretics remain the most commonly utilized stabilized, oral feeds can be initiated. Preterm
medications for BPD long term. The duration of infants often have oral aversion and are at risk
diuretic therapy remains institution and physician for aspiration. In children with BPD and CP, swal-
specific. low dysfunction often coexists with oral aversion,
increasing the risk of aspiration even further.
Bronchodilators Hence, evaluation and ongoing therapy with
Despite the evidence of airflow obstruction in experienced occupational and speech therapists
children with BPD, bronchodilators such as albu- is highly recommended (Abman et al. 2017).
terol have only shown limited success in this
population. On average, only one third of child-
hood survivors of BPD respond to bronchodilator Immunizations and RSV Prophylaxis
therapy, as measured by pulmonary function test-
ing (PFT), and the response can diminish over Vaccination programs worldwide have shown
time. This is likely due to a different pathophysi- great benefit in decreasing morbidity, hospitaliza-
ology of airflow obstruction in children with BPD tions, and death. Patients with BPD are known to
compared to term born children with asthma. be at highest risk of severe complications from
Children with BPD often display fixed obstruction developing vaccine-preventable illnesses.
due to irreversible structural airway changes and Palivizumab prophylaxis has been shown to
neutrophilic inflammation. With further research reduce wheezing episodes and hospitalizations
during the first 2 years of life in children born may lead to progressively impaired peak lung
extremely prematurely. However, it has not function in adulthood (Fortuna et al. 2016). The
shown benefit in pulmonary outcome at school majority of children with BPD participates in rou-
age (Prais et al. 2016). tine physical activities of daily life without symp-
The current AAP and CDC vaccination sched- toms; however, concern of reduced exercise
ule recommendation is to proceed with routine capacity remains in this patient population (Gib-
vaccinations including influenza vaccination son and Doyle 2014).
(after 6 months) as per the patient’s chronological Patients with CP are often unable to perform
age (ACIP 2017). The AAP recommends spirometry, hence obstructive airway disease is
palivizumab prophylaxis for all infants who are treated empirically in this population and drug
younger than 12 months at the start of the RSV doses and frequency of administration are often
season who meet one of the following criteria: titrated based on clinical response.
infants born <29 + 0 weeks gestation, infants
born <32 weeks gestation who have BPD, or
infants with hemodynamically significant congen- Neurodevelopmental Outcomes
ital heart disease. Palivizumab prophylaxis is
occasionally considered in the second year of Extremely preterm infants with BPD exhibit an
life in patients with BPD if they are receiving initial developmental lag compared to their pre-
respiratory support (including mechanical venti- term counterparts without BPD. Non-oxygen
lation, supplemental oxygen, or respiratory med- dependent children with BPD generally catch up
ications) or if they have received respiratory developmentally by 2 years of age, whereas those
support during the 6 month period before the discharged home on oxygen have been reported to
start of the second RSV season (AAP 2014). The catch up by 4 years of age (Moon et al. 2007).
recommendations remain the same for patients Infants with severe BPD are at a significantly
with CP and BPD. higher risk for developing quadraparesis and
diaparesis (Van Marter et al. 2011).
Outcome/Prognosis
Conclusion
Respiratory Outcomes
Despite major improvements in the care and out-
Children with BPD are at increased risk of hospi- come of extremely preterm infants over the last
talizations in the first 2 years of life. Although few decades, BPD (especially severe BPD)
children >8 years seldom require hospitalization, remains a challenging disease to treat and presents
they continue to exhibit respiratory symptoms and several challenges to clinicians. Its effects can be
require ongoing respiratory medications (includ- seen not only in the lungs of these infants but also
ing inhaled steroids and bronchodilators) due to in many other organ systems. BPD is a risk factor
ongoing small airway dysfunction (Bhandari and for the development of CP, with a significant
McGrath-Morrow 2013). increase in rates of CP in patients with severe
With regard to pulmonary function, children BPD. Infants with severe BPD are at a signifi-
born extremely prematurely have been noted to cantly higher risk for developing quadriplegia
have significant airflow limitation compared to and diplegia. BPD survivors continue to exhibit
their term gestation counterparts when examined more respiratory morbidity requiring various
at 8 and 12 years of age, which is particularly respiratory medications and often
pronounced in the BPD population. In addition, rehospitalization, especially in early childhood.
children with BPD have shown declining lung Hence, survivors of BPD require close monitoring
function between the ages of 8 and 12 years, indi- throughout childhood and likely into adulthood.
cating an abnormal airway growth trajectory that Reducing the rate of BPD and identifying new
specific targeted therapies for established BPD Donn SM (2017) Bronchopulmonary dysplasia: myths of
remains one of the biggest challenges for neona- pharmacologic management. Semin Fetal Neonatal
Med 22:354–358
tologists and pediatric pulmonologists. Doyle LW, Anderson PJ (2009) Long term outcomes of
bronchopulmonary dysplasia. Semin Fetal Neonatal
Med 14(6):391–395
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(> 7 days) systemic postnatal corticosteroids for pre-
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with Cerebral Palsy definition of bronchopulmonary dysplasia effect of
▶ Speech, Language, and Hearing Practice Ele- changing panoply of respiratory support for preterm
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Cerebral Palsy sia. Am J Respir Crit Care Med 163(7):1723–1729
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dysplasia. Semin Perinatol 37:132–137 corticosteroids for accelerating fetal lung maturation
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Shi Z, Ma L, Luo K et al (2017) Chorioamnionitis in the Van Marter LJ, Kuban KCK, Allred E et al (2011) Does
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Asthma in a Child with Cerebral Palsy
64
Katherine A. King and Dawn Selhorst
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 918
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 918
Pathophysiology for Asthma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 918
Natural History of Risk Factors for Respiratory Illness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 919
Diagnostic Observations and Dynamic Imaging Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 919
Role of Historical Information to Treat Asthma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 920
Treatment for Asthma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 920
Complications of Treatment for Asthma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 920
Measurable Parameters for Asthma Symptoms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 921
Validated Surveys as a Diagnostic Tool for Asthma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 922
Laboratory Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 923
Limitations of Functional Respiratory Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 923
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 923
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 924
Abstract
There are several medical challenges for a fam-
ily with a child with cerebral palsy, which
K. A. King (*) include the clinical management of respiratory
Sidney Kimmel School of Medicine, Thomas Jefferson diseases, such as asthma, aspiration pneumo-
University, Philadelphia, PA, USA nia, obstructive airway, and progressive restric-
Pulmonary Division, Nemours Alfred I. duPont Hospital tive lung disease. The clinical symptoms of
for Children, Wilmington, DE, USA asthma include spastic coughing, wheezing,
e-mail: Katherine.King@nemours.org
diminished breath sounds, and multifocal
D. Selhorst rhonchi. Diagnostic studies may include chest
Respiratory Care Department, Nemours Alfred I. duPont
Hospital for Children, Wilmington, DE, USA X-ray, nuclear imaging studies for reflux, and
e-mail: dawn.selhorst@nemours.org selected laboratory studies for IgE antibodies
https://doi.org/10.1007/978-3-319-74558-9_68
918 K. A. King and D. Selhorst
to allergens. The clinical history should and baseline immunology tests are helpful to edu-
include questions from the Asthma Predictive cate both the patient and their family about trig-
Index to determine the children’s risk for gers for asthma symptoms. Depending on the
asthma and the Asthma Control Test™ to neurocognitive development, and motor coordi-
report current respiratory symptoms exempli- nation skills of the child with cerebral palsy, mod-
fied by cough, dyspnea, and congestion. The ified spirometry techniques can be useful to
final assessment of the asthma diagnosis demonstrate the reversible obstructive disease
should reference the National Asthma Educa- process.
tion and Prevention Program to assess the
impact of the asthma symptoms upon the
child’s respiratory system. The diagnostic Natural History
assessment of asthma in a child with cerebral
palsy reflects the in-depth process of collecting Pathophysiology for Asthma
clinical and historical information in order to
determine the appropriate treatment to control Asthma exacerbations result from both an acute
the asthma symptoms. Proactive medical man- constriction of bronchial airways and from
agement for asthma can improve aerobic con- induced inflammatory response of multiple fac-
ditioning and decrease the risk of worsening tors within the lung that combine to increase the
respiratory disease. patient’s respiratory work of breathing. The
inflammatory cellular infiltrate composed of
Keywords eosinophils, mast cells, lymphocytes, and peptide
Asthma · Cerebral palsy · Asthma predictive mediators released into the airway milieu combine
index test (API) · Asthma control test with epithelial cellular response to diminish the
(ACT™) · National asthma education for airway flow. The pathophysiology of an asthma
prevention program (NAEPP) exacerbation upregulates the lung’s immune
response to the exposure to aeroallergens, air pol-
lutants, and respiratory viruses. There are specific
Introduction cellular pathways modulated by intracellular mes-
sengers, which are the subject for novel immuno-
The purpose of this chapter is to encourage phy- therapies. Mast cells, eosinophils, T2 helper cells,
sicians to investigate the etiology of recurrent and selective interleukins (IL-4, IL-13, and IL-5),
wheeze and cough in children with cerebral and immunoglobulin IgE are integrated into the
palsy. A procedural process for the evaluation of pro-inflammatory cascade. Steroids, leukotriene
asthma includes the information from validated receptor antagonists and engineered monoclonal
patient surveys and evidence-based guidelines to antibodies targeting T –helper type 2 cell interleu-
determine the severity of the asthma symptoms kins (IL-4, IL-13 and IL-5) exemplify anti-
and to optimize medical management. This chap- inflammatory medications. The current practice
ter will review the available diagnostic tools that to administer antibodies to the allergy-relevant
together establish the diagnosis and guide the immunoglobulins (IgE) and antibodies to
appropriate therapeutic interventions. After the interleukin-5 (IL-5) are effective treatment for
evaluation of the risk for aspiration pneumonia asthma symptoms experienced by patients with
and determination of the Gross Motor Function moderate to severe asthma respiratory disease
Classification System (GMFCS), use the Asthma (Fanta 2009; Parameswaran 2014). The medica-
Predictive Index (API) for asthma and the asthma tions used to treat asthma are classified as a con-
guidelines from the National Asthma Education troller or a rescue medication. The controller
and Prevention Program Expert Panel Report medications downregulate the inflammatory
(Huffaker and Phipantanakul 2014; NAEPP- immune response. The rescue medications relieve
EPR-3 2007b). The use of lab work for allergies the airway constriction. The proactive approach of
64 Asthma in a Child with Cerebral Palsy 919
using both a daily controller drug and a rescue Overall, the risk of hospitalization was higher
drug at home will decrease the number of emer- for children with cerebral palsy who demonstrate
gency room visits and hospitalizations for asthma daily respiratory distress with eating meals,
in children with cerebral palsy. uncontrolled seizures, difficulty with oral secre-
tions, and worsening kyphoscoliosis, in addition
to asthma and higher levels on the GMFCS
Natural History of Risk Factors (Blackmore et al. 2016). The authors propose
for Respiratory Illness that caregivers and physicians should initiate
medical care for respiratory disease early in child
The impact of the disability of cerebral palsy upon development, along with the continual assessment
the respiratory system can be recognized early in of the child’s oral and motor skill sets (Seddon and
life by both the family caregivers and physicians Khan 2003; Blackmore et al. 2016).
(Marks 2008; Seddon and Khan 2003). In The child with cerebral palsy and asthma will
Australia using the Cerebral Palsy Registry and demonstrate common asthma symptoms such as a
selected clinical parameters, patient charts were recurrent cough and recurrent wheezing. These
reviewed with the purpose of developing a sup- symptoms are also associated with uncontrolled
portive procedural process for the management of gastric reflux and silent aspiration. These patho-
the respiratory disease in children with cerebral logic events, combined with the restrictive lung
palsy. The study reports that 58% of participants volume, as seen with kyphoscoliosis, will increase
have daily symptoms of cough and wheeze. Ten the risk for pneumonia and acute respiratory fail-
percentage of participants report obstructive sleep ure (Proesmans 2016; Blackmore et al. 2016).
apnea and 40% have dysphagia with fluids (Pro- Medications for asthma, such as inhaled steroids
esmans 2016). In summary, the age, gender, oral- and allergy medications, and chest physiotherapy
motor function, and the level of disability can improve clinical outcomes in addition to the
(as reflected in the Gross Motor Functional Clas- appropriate antibiotics (Blackmore et al. 2016).
sification System (GMFCS)) contribute to the risk
for the recurrent respiratory symptoms and asthma
(Seddon and Khan 2003). Diagnostic Observations and Dynamic
Respiratory illness in children with cerebral Imaging Studies
palsy may present in early childhood and continue
to progress to chronic respiratory failure in ado- The awareness and education about the complex
lescence. These children will benefit from the nature of respiratory disease in a child with cere-
effort to differentiate asthma from aspiration bral palsy should be introduced early in child-
pneumonia and progressive restrictive lung dis- hood. Initial gross motor function skills such as
ease associated with kyphoscoliosis (Proesmans quality of the vocalization and head control and
2016; Marks 2008; Seddon and Khan 2003). The early core strength impacts progressive lung
Cerebral Palsy Registry in Australia listed the development. As the child grows, the clinician
parameters of the GMFCS, age, sex, oral intake, can apply the GMFCS Classes I–V. Children in
snoring, reflux, and asthma. The patient’s treat- class I and II usually have adequate oral-
ment for a respiratory-related hospitalization or pharyngeal function to swallow saliva and food,
the use of antibiotics is the measurable outcome and they are independently mobile. Those in
for analysis. The study of 470 participants con- levels III–V have a motor disability that requires
cludes that there is an increased risk of hospitali- ambulation aids such as crutches or wheelchairs,
zation for respiratory distress if the child with difficulties consuming food, and impaired protec-
cerebral palsy is an asthmatic as compared with tive airway reflexes. Those at levels of IV and V
the non-asthmatic child with cerebral palsy do not walk independently and often have
(25.8% versus 8.9% <0.001) (Blackmore et al. decreased oral intake and may have a gastrostomy
2016). tube. Some children with cerebral palsy and
impaired pharyngeal function continue to receive The guidelines integrate patient-centered care
oral nutrition despite the perception of silent risk goals to encourage parents to recognize allergy
of aspiration. triggers, learn the role of rescue and controller
Diagnostic studies are recommended to deter- asthma drugs and review an asthma action plan.
mine whether the child can use their pharyngeal The caregiver for a child with cerebral palsy can
skills to swallow food and liquids safely. Aspira- treat viral or allergic induced asthma exacerba-
tion studies (modified barium swallow and radio- tions in their own home with telephone or tele-
isotope milk scan, and liquid nuclear scan) are medicine supervision from the child’s clinician.
recommended to document silent aspiration of
fluids and foods and to demonstrate both distal
and proximal gastric reflux. The placement of a Treatment for Asthma
gastrostomy tube for nutrition in a child is often
associated with worsening gastric reflux and does One drug class used in asthma treatments is called
not prevent aspiration of oral secretions (Marks bronchodilators, which pharmacologically relax
2008; Blackmore et al. 2016). Poor oral motor the encircling smooth muscle, thus maintaining
function, observed in patients who are chronic the effective diameter of the bronchial airways.
mouth breathers and continuously pool saliva, The rescue drug is a bronchodilator and is used
combined with increased upper airway resistance proactively before a sports class or before contact
from abnormal pharyngeal tone increases the risk with allergic triggers, including cold air or ciga-
of nocturnal obstruction and silent aspiration. rette smoke (Fanta 2009). The bronchodilator
Worsening kyphoscoliosis caused by muscular (albuterol) medication is well tolerated and the
spasticity serves to impede the clearance of dose can be adjusted to prevent adverse events
mucopurulent secretions. The child with cerebral such as agitation or seizures. The length of time
palsy who has higher class of GMFCS will have for the use of the rescue medications for an asthma
an increased risk of acute respiratory failure. exacerbation is in a range of 3–5 days. Additional
medications used as quick-relief bronchodilators
include levalbuterol and ipratropium (Fanta
Role of Historical Information to Treat 2009).
Asthma
The concept of epigenetics proposes that both Complications of Treatment

intrinsic and external environmental factors mod- for Asthma
ulate the individual’s gene expression. Thus, the
evaluation of an asthmatic child includes ques- Therapies can improve the acute respiratory
tions regarding the family history, the patient’s symptoms, and daily medication for inflammation
respiratory symptoms and allergy symptoms, and and pulmonary clearance decelerate the progres-
the known allergens within the environment sion towards chronic lung disease. Historically,
(Heinle 2012; Bazzy-Asaad 2012). The National treatments used for asthma diseases, such as bron-
Asthma Educational Prevention Program chodilators and inhaled steroids, are also used for
(NAEPP) provides the templates for the physician chronic lung disease caused by genetic disorders
and explanations of the asthma symptoms for the such as primary ciliary dyskinesia and cystic
patient’s family. The procedural approach towards fibrosis. The children with cerebral palsy, who
the diagnosis of asthma was elaborated on in the have neurocognitive and/or motor skill delays,
NAEPP in 2007. The chapters are accessible for and/or multiple seizure medications, will benefit
clinical and health educators and parents. The from a personalized respiratory plan. The plan
patient handouts are written to empower patients may include chest physiotherapy, bronchodila-
to understand both the pathophysiology of asthma tors, intermittent use of antibiotics, inhaled ste-
and the guidelines for therapy (NAEPP 2007a). roids, and selective use of allergy medications.
Allergy medications both prescribed and over the The integration of the asthma classification
counter may be helpful or problematic. The pack- terminology into the asthma care plan for a child
aged propellants or mixture vehicles, such as with cerebral palsy increases the knowledge base
sugar and milk products, can interfere with the of the caregiver and standardizes the physicians’
ketogenic diet, used for the control of seizures. clinical assessment. The focus on concise mea-
Furthermore, the delivery system for the medica- surements for asthma monitoring is one of the
tions must be compatible with the child’s ability to asthma tools to advocate for ongoing patient cen-
cooperate with the caregiver. The current options tered communication. The terms “mild, moderate
for respiratory medications include a nebulizer and severe – asthma” are familiar words for
with inhaled liquid medications, dissolvable tab- patients, and summarize both the expert consen-
lets for mouth or by gastrostomy, and a preloaded sus and studies using evidence-based medicine.
inhaler used with an aero-chamber spacer with The National Institute of Health guidelines
mask (Fanta 2009; Marks 2008). enhance the exchange of medical information
among health providers and patient caregivers
(Bazzy-Asaad 2012; NAEPP 2007a; Fanta 2009).
Measurable Parameters for Asthma There are three additional categories of the
Symptoms NIH guidelines that are important for the process
of management decisions. The first and second
The National Institute of Health Asthma guidelines categories include the concepts of control of the
briefly summarized a framework for the clinic to asthma symptoms by the prescribed drugs and the
develop an optimal asthma action plan (NAEPP responsiveness of the asthma symptoms to bron-
2007a). The initial clinical assessment is the Clas- chodilators. The different pharmaceutical treat-
sification of the Severity of the asthma symptoms. ments are not universally effective across
The guideline characterizes asthma as “intermit- different ethnic and racial populations (Heinle
tent, persistent mild, moderate or severe ”. These 2012). The patient’s answers to the questions
terms are matched with the patient’s reported about control and responsiveness represent the
symptoms of cough and wheeze and quantified importance of asking the patient about his/her
per week or month. The classification is summa- symptoms during several daily activities (Heinle
rized in a visual table that is easily understood 2012; Bazzy-Asaad 2012).
(Bazzy-Asaad 2012; NAEPP 2007a). The physical The completed survey provides information
impact of the muscle spasms and the potential for about the work of breathing during daily child-
oral muscle coordination dysfunction seen in chil- hood activities and adequate sleep routines, mis-
dren with cerebral palsy associated with neuromus- sed school days, and visits to the emergency
cular skeletal challenges may limit the use of room. These lifestyle questions, in addition to
measurable clinical parameters to diagnose asthma. input from the orthopedic caregivers about the
The measurements of airway flow require the assigned GMFCS-class, the neurologist’s seizure
patient to form a tight seal on a plastic or cardboard assessment and expectations from the physical
tube which may be difficult for a patient who may therapist are necessary information to formulate
primarily breathe through the mouth. The process a pharmaceutical asthma action plan (NEAPP
to obtain a pulmonary function test (spirometry) 2007a). This integration of information within
engages both the voluntary muscles in order to the problem list and the exchange of information
inhale a deep breath, and the structural stability of amongst providers is the knowledge base for
the chest wall to exhale a deep breath. The validity anticipatory guidance for the patient and the fam-
of the results depends upon the reproducibily of the ily caregivers (Blackmore et al. 2016; Marks
patient’s attempts to successfully achieve the mea- 2008).
surable goals of duration (greater than 3 s) and The third category for anticipatory guidance
consistency of airway flow patterns, and this is for asthma monitoring is the concept of impair-
often beyond the capability of a child with CP. ment and risk. Impairment directly reflects the
frequency and intensity of the asthma symptoms. the major or minor criteria. To document a risk for
The risk concept addresses the adverse side effects asthma, the child will have three episodes of
of the asthma drugs, as well as, allergens and wheezing per year and one major or two minor
pollutants in the environment, and skeletal- criteria. The major criteria include documentation
modifying devices (such as braces) that affect by the physician of asthma in the parent and
respiratory function. Some of the identifiable eczema in the child. The minor criteria are docu-
environmental triggers are cigarette smoke expo- mentation by a physician of allergic rhinitis,
sure, seasonal temperatures changes, outdoor and wheezing apart from colds reported by the par-
indoor pollutants at the school, and the school- ents, and peripheral eosinophilia >4% (Huffaker
mates or siblings with active viral infections. The and Phipantanakul 2014). The criteria in the tem-
child with kyphoscoliosis and a baclofen pump plate have been modified as the clinical experi-
may have an additional medical problem of ence using the API has expanded. The additional
allergy-induced asthma symptoms. The presence categories in the major criteria are the addition of
of allergic-induced inflammation in both the aeroallergen sensitization and in the minor criteria
upper respiratory tract and the lower respiratory the addition of food sensitization. Patients with
airways may require additional medical care such different cultural backgrounds, which improves
as techniques for pulmonary clearance therapies patient-centered communication and optimizes
(Heinle 2012; Bazzy-Asaad 2012). The classifica- medical care (Table 1), understand the API.
tion for asthma relies on validated surveys to incor- The API and the validated survey called the
porate the patient’s own perception of how well the Asthma Control Test (ACT™) are helpful diag-
asthma symptoms are controlled (Jia et al. 2013). nostic tools for the assessment of the respiratory
symptoms. This survey documents the patient’s
reported symptoms and the caregiver’s perception
Validated Surveys as a Diagnostic Tool of the child’s asthma. The questions are written in
for Asthma an appropriate language for children and care-
givers with limited literacy skills. The ACT™
The approach towards a child with asthma starts questions are accompanied by the image of facial
with the questions in the Asthma Predictive Index expressions ranging from a sad face to a happy
(API). Specialized pediatricians (Castro- face. The visual aid of the facial expressions and
Rodriguez et al. 2000), with the purpose of iden- the use of a quantitative score make this a useful
tifying young children with asthma (Huffaker and survey for both the child and the caregiver. The
Phipantanakul 2014), developed the formatted survey is produced and distributed by Glaxo ® for
template. The immature lung of a potential asth- clinical use and is available in English and Span-
matic child, similar to the immature lung of a child ish (Jia et al. 2013). An understanding of the
with cerebral palsy, can benefit from appropriate
respiratory medications before developing
Table 1 Asthma Predictive Index. (Adapted from
chronic lung disease. A child with asthma may Huffaker and Phipantanakul 2014)
have an undiscovered allergic profile that is
Major criteria Minor criteria
revealed in the recent respiratory symptoms and
Three episodes of Three episodes of
in the family history. The API is a noninvasive wheezing/year and one wheezing/year and two
clinical tool for the early diagnosis of asthma in all major criteria minor criteria
children. This tool was studied regarding sensitiv- Asthma in a parent Allergic rhinitis in the
ity and specificity in order to achieve external reported to the physician child reported by the
physician
validation to encourage the use of the API by Wheezing apart from
general pediatricians practicing in different socio- colds reported to the
economic areas. There is a high specificity physician
reported in two large studies that includes younger Eczema in the child Peripheral eosinophilia
patients. The template creates a table labeled as reported by a physician greater than or equal to 4%
impact of familial asthma and the patient’s atopic bronchodilator. Similarly, the child can learn
response to the allergens provides a knowledge how to breathe into a Pneumatach flow measure-
base to guide both the medical and environmental ment tube that measures exhaled fraction of nitric
interventions to treat asthma. The recognition of oxide. In moderate asthmatic patients, the nitric
environmental mechanisms to modulate the oxide production is enhanced by the allergic
inherited genetic phenotype, as described in epi- immune response. The exhaled gas is not measur-
genetics, serves to personalize the medical care able in patients with bacterial pneumonia or a
plan of each child with cerebral palsy, which cystic fibrosis exacerbation. The limitation of the
should improve long-term outcomes of their technique to quantify exhaled air is the cognitive
respiratory disease. comprehension of the child and the motor skill
sets to maintain a tight seal of the lips for three
reproducible results. A study in South Korea pro-
Laboratory Studies poses that patients with cerebral palsy can practice
the necessary skill set with a peak flow meter at
There are two approaches to the recommended home to achieve repeatable flow loops within the
studies for asthma symptoms: to assess the office setting (Choi et al. 2016). Two important
patient’s immune response and to evaluate the factors are appropriate reference values for children
lung function. The initial tests include CBC, immu- and a respiratory therapist who provides both tech-
noglobulins, and postvaccine response such as the nical skills and emotional encouragement. Incen-
pneumococcal titers. The allergy-related laboratory tive spirometry exercises can improve measurable
tests are the total IgE and a screening panel for volumes for an individual child. However, the
common childhood allergies, which evaluates for quantitative measurement of an exhaled volume
an elevated IgE for common indoor and outdoor does not conclusively summarize the clinical pul-
allergens. These are house dust mites and molds monary status of the active child with disabilities.
(Aspergillus, Alternaria, and Cladosporium) and Adaptive tests for a child with disabilities to
domestic animals (cat and dog). A negative allergy measure pulmonary function include a 6-min
test in a child under 2–3 years can become positive walk exercise test with a pulse oximeter, during
as the child’s immune response continues to which measurements are taken of the distance
mature. The atopic child with positive allergy walked and the oxygen saturation. In addition,
tests has an increased risk of developing asthma the patient can practice incentive spirometry and
(Heinle 2012; Bazzy-Asaad 2012; Fanta 2009). record his best efforts or the child can blow bub-
The clinical visit concludes with a scored Asthma bles in order to coordinate the rate and depth of
Predictive Index, reviewed Asthma Control Test™, each exhalation. The rehabilitation clinic in South
education packet from the NIH Asthma Guidelines Korea introduced the incentive spirometry exer-
and a completed asthma action plan for both the cises to demonstrate that children with cerebral
family and school nurse. palsy can learn with visual feedback new skill sets
to improve their own pulmonary status (Choi et al.
2016). At home or in school, adaptive activities
Limitations of Functional Respiratory can be encouraged and asthma medications pre-
Studies scribed for the asthmatic child with cerebral palsy.
The physiologic studies for asthmatic children

include spirometry, forced exhaled nitric oxide, Summary
and incentive spirometry exercises (Choi et al.
2016). The child with cerebral palsy who is in A child with cerebral palsy and asthma can pursue
the highest functional group (GMFCS class I childhood activities, have a restful night sleep, not
and II) can learn to exhale forcibly and the exhaled succumb to respiratory infections, and participate
volume can be measured before and after a in breathing exercises with anticipatory guidance
for the caregivers. Clinicians need to monitor the (ed) Curbside consultation in pediatric asthma. Slack
cumulative loss of functional airways that are Inc., Thorofare, pp 113–116
Blackmore AM, Bear N, Blair E, Gibson N, Caris J,
compromised by chronic aspiration and impaired Langdon K, Moshovis L, Steer K, Wilson AC (2016)
mucopulmonary clearance. Factors associated with respiratory illness in children
The child’s genetic inheritance, the environment and young adults with cerebral palsy. J Pediatr
and emotional triggers all contribute to the patient’s 168:151–157
Castro-Rodriguez JA, Holberg CJ, Wright AL, Martinez
clinical history. The dynamic aspect of asthma FD (2000) A clinical index to define risk of asthma in
symptoms and respiratory disease requires a base- young children with recurrent wheezing. Am J Resp
line clinical assessment of the child’s lifestyle. Crit Care 2000:162:1403–6
The NAEPP provides explanations for the Choi JY, Dong-wook R, Park ES (2016) Change in pulmo-
nary function after incentive spirometer exercise in
symptoms of asthma during exercise and illness. children with spastic cerebral palsy: a randomized con-
The templates for asthma surveys such as the trol study. Yonsei Med J 5(3):769–775
Asthma Predictive Index and the Asthma Control Fanta CH (2009) Asthma. N Eng J Med 360
Test™ are easily accessible. The role of diagnostic (10):1002–1014
Heinle RA (2012) Who is at risk of developing asthma. In:
labwork is to identify allergies, and the role of Chidekel AS (ed) Curbside consultation in pediatric
spirometry is to monitor airway flow in asth- asthma. Slack Inc, Thorofare, pp 7–10
matics, both of which can help the physician and Huffaker MF, Phipantanakul W (2014) Utility of asthma
the family determine the asthma plan. The patient- predictive index in predicting childhood asthma and
identifying disease-modifying interventions. Ann
centered approach for the child with asthma and Allergy Asthma Immunol 112(3):188–190
additional medical and emotional needs, improves Jia CE, Zhang HP, Liang R, Jaing YQ, Powell H, Fu JJ,
the adherence to asthma therapies and the child’s Wang L, Gibson PG, Wang G (2013) The asthma
quality of life. control test and asthma control questionnaire for
assessing asthma control: systemic review and meta-
analysis. J Allergy Clin Immunol 131(3):695–703
Marks J (2008) Pulmonary care of children and adolescents
Cross-References with developmental disabilities. Pediatric Clin N Am
55:1299–1314
National Asthma Education and Prevention Program
▶ Aerobic and Anaerobic Fitness in Children and (2007a) Expert panel report 3 (EPR-3): the guideline
Youth with Cerebral Palsy for the diagnosis and management of asthma. Bethesda,
▶ Aerobic Conditioning and Walking Activity MD National Heart Lung and Blood Institute. NIH
Assessment in Cerebral Palsy publication no. 084051
National Asthma Education and Prevention Program
▶ Aspiration in the Child with Cerebral Palsy (2007b) Expert panel report 3 (EPR-3) Guidelines for
▶ Gastroesophageal Reflux in the Child with the Diagnosis and Management of Asthma Summary
Cerebral Palsy Report 2007. J Allery Clin Immunol 120(5 suppl):
▶ Upper Airway Obstruction in the Child S94–S138
Parameswaran N (2014) Anti-Interleukin-5 monoclonal
with Cerebral Palsy: Indication for antibody to treat severe eosinophilic asthma. N Engl J
Adenotonsillectomy Med 371(13):1249–1251
Proesmans M (2016) Respiratory illness in children with
disability: a serious problem. Breath 12(4):e97–e103.
https://doi.org/10.1183/20734735.017416
References Seddon PC, Khan Y (2003) Respiratory problems in chil-
dren with neurological impairment. Arch Dis Child
Bazzy-Asaad A (2012) What are the most current asthma 88:75–78
guidelines from the national institute of health and what
do I need to know about them. In: Chidekel AS
Aspiration in the Child with Cerebral
Palsy 65
Aaron Chidekel and Lauren Greenawald
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 926
Definitions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 926
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 926
Aspiration from Above . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 926
Aspiration from Below . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 927
Screening and Diagnostic Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 928
Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 929
Aspiration Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 929
Tracheobronchitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 929
Aspiration Pneumonitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 930
Aspiration Pneumonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 930
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 932
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 934
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 935
Abstract penetration of the airway by inhaled foreign

Patients with cerebral palsy are at significant material, results from poor protection of the
risk for aspiration, which leads to lung injury, upper airway, either through penetration of
chronic inflammation, and eventual increased the larynx or through the reflux of gastroesoph-
morbidity and mortality. Aspiration, the ageal contents causing airway irritation. This
commonly occurs through ineffective clear-
ance of secretions in the upper airway, oropha-
A. Chidekel (*) ryngeal dysphagia, or gastroesophageal reflux.
Division of Pediatric Pulmonology, Nemours A.I. duPont The result is aspiration pneumonitis, chemical
injury to the airway or aspiration pneumonia,
e-mail: Aaron.Chidekel@nemours.org
focal bacterial infection, tracheobronchitis, and
L. Greenawald
chronic inflammation. Imaging is nonspecific
Wilmington, DE, USA and testing is not always confirmatory of a
e-mail: Lauren.Greenawald@nemours.org

https://doi.org/10.1007/978-3-319-74558-9_69
926 A. Chidekel and L. Greenawald
diagnosis. Treatment can include various med- contents. Sialorrhea (hypersalivation) can be of
ical therapies for the improved control of secre- particular concern in this patient population.
tions and the management of reflux and can Extrinsic, noninfectious material includes oral or
extend to surgical interventions. Ultimately, a enteral tube feedings and a variety of foreign
multidisciplinary approach to management and objects. Secretions can change with viral or bac-
control of aspiration can reduce morbidity and terial pathogens; therefore, symptoms should be
mortality in this population. monitored for a new infectious source. Dyspha-
gia, a symptom defined as difficulty swallowing,
Keywords is common in the CP population and is closely
Cerebral palsy · Aspiration · Pulmonary linked to the inhalation of oral feeds, the most
compromise · Lung injury common source of aspiration in these patients.
Furthermore, aspiration of inhaled material
can be silent, without clinical symptoms or
Introduction outward signs, noted by coughing, choking,
or other changes to respiratory status. The result
The respiratory system is highly vulnerable in chil- of these episodes can manifest as generalized
dren with cerebral palsy (CP), serving as a signifi- tracheobronchitis, aspiration pneumonitis, or
cant management challenge for providers. Chronic aspiration pneumonia.
respiratory disease plays a primary role in increased Tracheobronchitis refers to the nonspecific
morbidity and mortality. A major contributor to inflammation of the airway, and it may be infec-
pulmonary compromise is aspiration, the inhalation tious or noninfectious in nature. Aspiration
of foreign material past the vocal cords. Aspiration pneumonitis is a chemical injury to the lung
syndromes have variable presentations, either parenchyma without a defined infectious source.
acutely due to immediate lung injury or as a sub- In contrast, aspiration pneumonia is a bacterial
acute, chronic inflammatory process. Similarly, infection of the lung parenchyma due to the inha-
there is wide variation in clinical presentation, rang- lation of infectious material. While the terminol-
ing from the relatively asymptomatic patient with ogy may vary, the mechanism of action and basic
silent, low-grade aspiration to those who develop evaluation of these aspiration syndromes are sim-
respiratory failure either acutely or over time. ilar, and they often require overlapping acute and
Suspected aspiration syndrome requires prompt chronic therapeutic strategies. Finally, while these
attention through diagnostic evaluation and early clinical entities significantly overlap, defining an
therapeutic management in order to decrease the etiology or even confirming a specific diagnosis
morbidity and mortality associated with the subse- can be a challenge at best but often times is
quent development of severe lung injury impossible. For example, differentiating recurrent
(Reddihough et al. 2001). viral lower respiratory tract infections from true
aspiration pneumonia during the winter months
remains an intense clinical conundrum in a med-
Definitions ically fragile child with cerebral palsy.
Aspiration is the penetration of the airway by a

foreign material below the level of the vocal Natural History
cords. Acute aspiration is the inhalation of a for-
eign material with immediate complications, Aspiration from Above
whereas chronic aspiration occurs slowly over an
extended period, leading to gradual respiratory Pediatric patients with cerebral palsy have many
decline. There are many sources of inhaled for- risk factors for aspiration when compared with the
eign material. Intrinsic, noninfectious materials healthy pediatric population. Protection of the
include nasal secretions, saliva, teeth, and gastric airway is crucial for all persons, and intact airway
65 Aspiration in the Child with Cerebral Palsy 927
defense mechanisms are critical. A normal host and results in edema of the arytenoids and epi-
has reflex stimulation in the brain that stimulates glottis. This increase in nasal and/or oral secre-
the desire for “suck and swallow.” Once this neu- tions can further increase aspiration risk and
rologic stimulus is initiated, a person protects the concerns for chronic insult, particularly when
larynx against airway penetration by an inhaled coupled with an acute upper respiratory infection.
substance through the coordination of swallowing Copious secretions can additionally fatigue the
and breathing. During this process, there is appo- swallowing mechanism and further interfere with
sition of the epiglottis and soft palate, which muscle coordination.
directs nasal and oral contents toward the esoph-
agus and away from the airway. Below the epi-
glottis, a second source of protection is the Aspiration from Below
approximation of the true and false vocal folds.
The false vocal folds create a seal, while the true Contents from the gastrointestinal tract can pene-
vocal folds close at the midline to block the pas- trate the airway, mostly through clinically signif-
sage of contents from the upper airway to the icant gastroesophageal reflux disease (GERD).
subglottic space. The strength, tone, and coordi- Patients with cerebral palsy have a higher inci-
nation of the muscles of the larynx ensure repeti- dence of GERD, as neurologic compromise can
tive and near-complete protection with each alter the innervation of the lower esophageal
defensive episode while a person is awake or sphincter and lead to low muscle tone
asleep (Zaoutis et al. 2018). (Starosvetoval et al. 2015). Low muscle tone
There are areas for deficiency in each step of this also translates to decreased motility in the stom-
complex mechanism. The bulbar reflex can be lim- ach and intestines, exacerbated by enteral tube
ited or absent with the neurologic compromise that feedings leading to more opportunity for stomach
can accompany cerebral palsy or encephalopathy. contents to reflux (Arvedson 2013). The poly-
An infant who is unable to coordinate suck and pharmacy associated with daily management of
swallow may aspirate early in life, acting as one the child’s various medical diagnoses may
of the first signs of neurologic compromise. Addi- decrease gastric motility and lead to a pH imbal-
tionally, perinatal asphyxia can lead to cranial nerve ance, thereby increasing the incidence of GERD
damage, which can include laryngeal nerve paresis for many children with cerebral palsy. Postural
or even paralysis. Furthermore, hydrocephalus and recumbency, immobility, kyphoscoliosis, and
hypoxic-ischemic encephalopathy (HIE) can lead reduced swallowing frequency are additional con-
to an abnormal anatomic shape of the skull with an tributors to the frequency, intensity, and morbidity
associated misshapen palate or pharynx. The result associated with GERD.
of this anatomic variation can be pharyngeal insuf- Simultaneous irritation of the airway and
ficiency from low muscle tone interfering with the esophagus occurs with the reflux of gastric con-
coordination of swallowing. tents to the upper level of the esophagus. Even
Like breathing, normal secretions must be distal esophageal reflux is thought to trigger ther-
managed continuously and automatically during mal receptors in the mucosa, cause broncho-
wakefulness and sleep. Anything that causes spasm, and contribute to airway inflammation
increased secretions, ranging from normal factors (Chernick and Thomas 1998). This phenomenon
such as teething to abnormal stressors such as is directly correlated with low gastroesophageal
intercurrent viral infection or gastroesophageal sphincter tone. The amount of gastric acid con-
reflux, can increase the risk of aspiration in a tents is relevant to aspiration as well. Small
vulnerable child. Once incited, secretions due to amounts of gastric acid contents irritating the
chronic aspiration may become even more abun- upper airway, known as micro aspiration, trigger
dant and difficult to manage, leading to continu- the irritant receptors and damage the cilia on the
ous and recurrent airway irritation. This disturbs mucosal surface while leading to recurrent bron-
mucociliary function of the respiratory mucosa chospasm. Aspiration of less than 1.0 ml/kg/day
can have chronic long-term deleterious effects. of refluxed contents into the nasopharynx. In
Larger amounts of greater than 1.0 ml/kg/day of infants, apnea or acute life-threatening events
gastric content aspiration at a pH of 2.5 or less (ALTE), also termed brief resolved unexpected
have been associated with pneumonia (Chernick episodes (BRUE), can be a red flag for aspiration.
and Thomas 1998). To neutralize gastric acid can The most common presenting and concerning
be equally dangerous, as patients are often asymp- symptoms are chronic congestion, cough, recur-
tomatic, yet silent and recurrent aspiration con- rent wheezing, nighttime coughing, and stridor.
tinues. This can go unnoticed for a prolonged Failure to thrive, recurrent pneumonia, sinusitis,
period and lead to further damage. acute otitis media, and visualized nasopharyngeal
Over time, when combined with dysfunctional reflux may also incur concern from medical pro-
airway defenses that accompany baseline abnor- viders to screen for underlying aspiration
mal mentation, recurrent seizures, and poor den- (Lightdale and Gremse 2013).
tition, aspiration leads to chronic inflammation of Testing to confirm a diagnosis of aspiration can
the respiratory mucosa and the lung parenchyma. be difficult, as the studies generally lack accuracy.
Coupled with the inability to breathe deeply due A positive test is obviously of concern, but tests
to limited movement or the inability to exercise may be overly sensitive or lack sensitivity. Clini-
leads to persistent de-recruitment of the lung tis- cal context and correlation are therefore particu-
sue and further increases chances for lung injury. larly critical when testing and evaluating the
Reduced cough effectiveness is an additional results. Commonly employed imaging and func-
complicating factor. Recurrent aspiration episodes tional tests are listed in Table 2. An upper GI with
accumulate irritation and inflammation leading to barium is the most common study. The compo-
permanent scarring, termed pulmonary fibrosis, nent of video fluoroscopy that assesses swallow
and ultimately respiratory failure. can provide insight into anatomic detail and struc-
tural defects, such as vascular rings or the pres-
ence of a tracheoesophageal fistula. It is
Screening and Diagnostic Testing discouraged to use a nasogastric tube during this
study, as it can affect visualized swallow and
Chronic symptoms (as listed in Table 1) and signs clarity of anatomic abnormalities. The results of
may develop with time that lead to further workup this test are limited if the patient is crying or
and testing. Silent aspiration may present without poorly positioned, both of which can further
frequent clinical symptoms but rather with recur- impair swallow function and exaggerate reflux.
rent illness or feeding intolerance. Chronic cough As a static study, it is a poor evaluation of
or coughing at mealtime can additionally be micro aspiration. In general, it is associated with
concerning, as well as gagging with feeds. Persis- a 30% false-positive test rate (Chernick and
tent nasal congestion can also suggest aspiration Thomas 1998).
Gastric scintiscan, also known as a gastric
emptying study, is a tagged feed that monitors
Table 1 The signs and symptoms common in aspiration the transit of stomach contents in the GI tract.
Symptoms of aspiration The dye is followed after oral consumption
Cough through the esophagus over a 4-h period, to
Wheezing
Increased work of breathing
Increased secretions Table 2 Commonly employed imaging and screening
Frequent emesis testing
Choking and gagging with feeds From above From below
Hypoxia Salivagram
Fever Modified barium swallow Gastric scintigraphy
Mental status change Impedance probe
additionally assess for delayed passage or empty- exposure. Secretions can also be directly evalu-
ing of material. During this time, it can also be ated from a tracheal aspirate to assess for reducing
seen if the dye enters the lungs suggesting aspira- substances or lipid laden macrophages which is
tion. This evaluation is insufficient to review the suggestive of aspiration.
anatomy and is a time-consuming process. Upper airway evaluation can also include a test
Modified barium swallow studies are called FEES, which is fiberoptic endoscopic eval-
performed with a speech therapist to assess swal- uation of swallowing. This test is performed by
low function (Rogers et al. 1994). This examina- ENT and speech. With this dynamic study, water
tion is guided by video fluoroscopy and focuses boluses of varying consistencies are administered
on the muscles and coordination of the mouth, to evaluate for aspiration into the airway. It is
pharynx, and upper esophagus. It specifically considered as an alternative to video fluoroscopy
reviews the movement of liquids of various thick- for upper airway evaluations.
ness to assess for abnormal penetration of the
larynx, as seen in Fig. 1.
Esophageal impedance probe testing has Complications
increased in popularity as an assessment, mostly
for gastroesophageal reflux as this test evaluates Aspiration Syndromes
for the presence of acidic or non-acidic gastric
contents through assessment of esophageal A high level of clinical suspicion is most impor-
pH. Episodes of GERD often occur at times of tant in the diagnosis of any aspiration syndrome.
relaxation in the lower esophageal sphincter mus- Patients with cerebral palsy may have nondescript
cle. Esophageal manometry can be employed to symptoms including fatigue, altered mental status,
measure the tone of the lower esophageal sphinc- or merely a decline in nutritional or overall health
ter and can be combined with a pH evaluation. status. Similarly, a safe feeding plan, management
To screen for aspiration from the upper airway, of GERD (if present), and attention to oral secre-
a salivagram, a nuclear medicine study that traces tions and hygiene serve as a foundation for man-
the path of saliva from the mouth to the esopha- agement of any patient at risk for aspiration.
gus, can be done. This study is easy to perform Excellent nursing care and respiratory therapy
and carries little risk outside of radiation support are critical adjuncts as well.
Tracheobronchitis
Tracheobronchitis refers to inflammation of the

main airway and bronchi. This is not necessarily
a diagnosis in and of itself, but can be a chronic
consequence of aspiration. The recurrent inhala-
tion of material leads to airway irritation and
chronic inflammation. Patients may have cough
and increased secretions with excess mucous pro-
duction by a damaged airway. Imaging may not be
helpful, as it cannot directly examine the mucosa
of the main airways; however, a bronchoscopy
can directly visualize signs of irritation or pathol-
ogy suggesting aspiration. Tracheobronchitis
is often treated with inhaled corticosteroids to
Fig. 1 Scout fluoroscopic image of an infant being pre-
sented a bottle with contrast-enhanced formula as part of a reduce inflammation, along with airway clearance
modified barium swallow study with speech pathology management (high-frequency chest wall
compression or chest physiotherapy for airway

mucous mobilization along with bronchodilation
via short acting beta-agonists) to help remove
accumulated secretions from the airways.
Aspiration Pneumonitis
Aspiration pneumonitis is the inhalation of any

foreign material such as oropharyngeal secretions
or gastric contents resulting in chemical injury to
the lung parenchyma, demonstrated in Fig. 2.
Chemical injury results from the chemical prop-
erties of the aspirated material, such as increased
acidity, which leads to inflammation. Pneumonitis
is distinguished from pneumonia, as a bronchial
lavage of the lung fluid can be sterile; there is no
underlying bacterial process.
Aspiration pneumonitis can occur acutely, for
example, with episodes of emesis or with copious Fig. 2 AP chest radiograph of aspiration pneumonitis due
secretions during a respiratory illness; however, it to inhalation of mineral oil in a young infant. Noted are
diffuse, centrally located hazy opacities
can also be a chronic process from repeated insult,
often seen with gastroesophageal reflux or dys-
phagia and repeated oral feedings. In addition to does not improve or worsens within 48 h of initial
underlying neurologic abnormalities, risk factors symptom onset. There is insufficient data to sup-
include a history of tracheoesophageal fistula, port the use of inhaled or systemic corticosteroid
presence of a feeding tube, recent endotracheal therapy in the acute setting; however, bronchodi-
intubation, awakening from recent administration lators and airway clearance devices may be help-
of anesthesia or sedation, the presence of a cleft lip ful for the removal of excess mucous and
or palate, ingestion of a foreign body, seizures, secretions produced in response to lung injury.
and poor oral hygiene. Supplemental oxygen may be necessary for hyp-
An initial phase of immediate airway irritation oxemia, and in more severe cases, endotracheal
can lead to injury of the alveoli. In the second intubation and mechanical ventilation may be
phase of lung damage, a significant amount of necessary (Cerebral Palsy and Respiratory Health
inflammation can occur which leads to cough 2017).
and tachypnea within hours of the aspiration
event. In cerebral palsy, patients may solely pre-
sent with an alteration in mental status or a Aspiration Pneumonia
depressed response to stimuli. Injury to the alveoli
can result in a decrease in surfactant, altering the Aspiration pneumonia may be difficult to distin-
balance of ventilation and perfusion, resulting in guish from community-acquired pneumonia in its
hypoxemia and even respiratory failure. Subacute clinical presentation. Acute events such as post-
pneumonitis can linger over a prolonged period extubation, misplaced feeding tubes, or choking
and present as a slow decline in a patient’s overall can be concerning for aspiration pneumonia. As a
mental and respiratory status. result, bacterial infection can develop in the lung
Treatment of chemical pneumonitis is support- parenchyma. Recent research links cerebral palsy
ive and does not require antibiotic use. Antibiotics patients who have a history of double hemiplegia,
should be considered if the patient’s condition spastic tetraplegia, and muscle hypertonicity,
or those with low tone, with an increased risk presence of infection. More severe symptoms
of more severe pneumonia (Starosvetoval et al. include respiratory distress as indicated by
2015). Aspiration pneumonia can present with a tachypnea and retractions as well as hypoxemia.
variety of symptoms, ranging from nonspecific Changes on examination can manifest as signs of
mild changes in clinical status to coughing, gag- respiratory distress associated with focal abnor-
ging, or increased secretions. Fever may be more malities on lung examination, which can include
prominent with aspiration pneumonia than pneu- decreased breath sounds, crackles, or rhonchi.
monitis, but it is nonspecific and may be absent in Diagnostic testing may be helpful but not
any of the aspiration syndromes, even in the definitive (as seen in Fig. 3), as the focal location
of pneumonia is often based on patient position-
ing. For example, supine positioning may lead to
acute pneumonia in the upper and lower lobes.
These dependent areas can also appear abnormal
with chronic changes. Additional radiographic
changes may demonstrate abscess formation or
necrotic/cavitary lesions, visualized in Fig. 4,
which could require additional treatment.
Treatment includes but also extends beyond
the recommended supportive care with aspiration
pneumonitis due to the presence of a bacterial
infection. The bacteria associated with aspiration
pneumonia are variable. The initial understanding
of the common bacteria derived from adult trans-
tracheal sampling, which revealed both aerobes
and anaerobes (Brook and Finegold 1980). The
most common bacteria include Streptococcus spe-
cies, Staphylococcus species, and Haemophilus
influenzae. These bacteria commonly originate
Fig. 3 AP chest radiographic image of right lower lobe
pneumonia attributed to aspiration in a 10-year-old female
in the upper airway. Patients in long-term care
with acute respiratory failure in the setting of static facilities and those who are frequently hospital-
encephalopathy ized can additionally grow Gram-negative
Fig. 4 CT images of a right lower lobe lung abscess in a 3-month-old male with hypoxic-ischemic encephalopathy
Table 3 Summarized Medical: from above Surgical: from above

therapeutic options for
Glycopyrrolate Submandibular gland extraction
managing aspiration
Scopolamine Parotid duct ligation
Botulinum toxin Tympanic plexus nerve ligation
Dental care Tracheal tube
Tracheoesophageal diversion
Medical: from below Surgical: from below
Thickened feeds Gastrostomy tube
Ranitidine Gastrostomy-jejunostomy tube
PPI therapy Fundoplication
Motility agents
bacteria, particularly Pseudomonas aeruginosa. Salivary medical management focuses on

Therefore, broad-spectrum antibiotics are often decreasing salivary production. Glycopyrrolate is
started empirically. Previous recommendations a commonly prescribed medication, which func-
included a combination of penicillin and tions as an antagonist to the muscarinic system.
clindamycin. Recent treatment is ampicillin com- Glycopyrrolate inhibits acetylcholine release on
bined with sulbactam or cephalosporins alone smooth muscle tissue and within exocrine glands
administered intravenously. Broadened coverage where excessive pharyngeal, tracheal, and bron-
with piperacillin and tazobactam and a combina- chial secretions are produced. Patients over the
tion of ticarcillin and sulbactam are recommended age of 12 can use tablets, currently dispensed as
in the presence of Pseudomonas, significant peri- 1 or 2 mg tablets. Pediatric patients and those who
odontal disease, or when a complicated pneumo- are gastrostomy tube-dependent receive a liquid
nia with abscess formation or necrosis is suspension. Initial dosing starts at 0.04 mg/kg two
suspected. Obtaining a true sample may be diffi- to three times daily and can be titrated based on
cult but a bronchoscopy can be helpful to obtain effectiveness to a maximum of 3 mg in adult-size
sampling. If a tracheostomy tube is in place, fre- patients (Hockstein et al. 2004). Excessive use of
quent cultures may be helpful to obtain an under- glycopyrrolate can lead to thick secretions and
standing of the patient’s bacterial flora. ultimately mucous plugging or respiratory dis-
tress, so changes in dosing should be monitored
closely. Side effects can also include urinary
Treatment retention and hypotension, considered more
common in patients with underlying neurologic
Medical management of aspiration syndromes tar- damage. An alternative or adjunctive therapy is
gets the increased production of secretions, recur- scopolamine, administered most commonly in
rent respiratory symptoms, or the irritation of transdermal form for secretion management.
gastric contents. Medical and surgical strategies This belladonna alkaloid competitively inhibits
are summarized in Table 3. muscarinic receptor sites in the parasympathetic
Respiratory support is critical, particularly dur- nervous system. The patch continuously releases
ing acute illness but also on a daily basis to help medication over the course of 3 days. The dose
dilate the airways around poorly cleared secre- is 0.006 mg/kg with a maximum of 0.3 mg per
tions and to help reduce inflammation. In turn, dose. Efficacy was recently monitored in a small
this can improve tolerance of illness. As men- subset of ten pediatric patients with cerebral palsy.
tioned previously, bronchodilator therapy and air- A significant reduction of drooling was demon-
way clearance via chest physiotherapy or strated in 50% of patients, with one third of
mechanical devices provide daily maintenance those 10 patients having a complete resolution of
for healthy airways. drooling (Lewis et al. 1994). Side effects can
include dizziness, sedation and changes in vision. tracheostomy chapter. However, its benefits
These side effects can be difficult for patients with include improved airway access for secretion
cerebral palsy to communicate, and demonstra- management and the opportunity to effectively
tion of change may be subtle. A concerning side provide mechanical ventilation.
effect is a decrease in GI motility which can lead Surgical removal of the submandibular or
to ileus or toxic megacolon in patients with parotid glands is typically delayed until conserva-
already abnormal intestinal innervation. General tive management has failed and the child has
use of anticholinergic agents has been found to reached approximately 6 years of age, as this
result in decreased temperature regulation through assures maturity of oromotor function. Decreasing
the inhibition of sweat glands, which is potentially salivary flow can be performed through removal of
dangerous as many of these patients experience the salivary glands, ligating salivary ducts, or sec-
autonomic thermal dysregulation prior to starting tioning nerves from the tympanic plexus of the
medications. middle ear that stimulate the production of saliva.
Invasive therapy to manage secretions can Most commonly the submandibular glands are
include intrasalivary injection of botulinum toxin removed as they produce a large amount of saliva
A to control sialorrhea (Krigger 2006). Botulinum (Neeraj et al. 2017). This procedure also carries
toxin is an exotoxin produced by Clostridium less risk than resection of parotid glands. Alterna-
botulinum which blocks acetylcholine at the cho- tively, parotid duct ligation is better tolerated with a
linergic, parasympathetic synapse of salivary higher success rate (Hockstein et al. 2004). Radical
glands. The result is decreased function of the surgical therapy can also include tracheoe-
salivary glands. Injection occurs into parotid or sophageal diversion, which directs the secretions
submandibular glands, with better clinical out- that bypass the protective barriers of the larynx and
comes obtained in research studies when both enter the airway to the esophagus directly, to pre-
glands are targeted. However, it is important to vent recurrent infection and lung damage from
note that this can also cause a complete or partial chronic aspiration. This procedure requires perma-
muscle paralysis in the immediate proximity of nent tracheostomy tube placement and eliminates
the injection. Injections need to be carefully the ability for speech and phonation. This surgery
performed with close monitoring of swallowing also carries significant risk, including the formation
in the chance dysfunction develops. A prelimi- of a tracheoinnominate artery fistula (Shima et al.
nary study of pediatric patients with cerebral 2010). While it does not decrease the amount of
palsy assessed 22 patients who received injec- oral and nasal secretions produced, patients have
tions, all of whom had subjective improvement experienced a decrease in the need for suctioning
in drooling without swallow dysfunction; how- and have had improved respiratory status with
ever, quantifying improvement was difficult fewer occurrences of pneumonia (Hara et al.
(Suskind and Tilton 2002). This therapy is man- 2014). It is not commonly performed in pediatrics.
aged on an individualized basis, and therapy is The therapeutic approach to complex or challeng-
limited as the effects can last weeks to months. ing cases of aspiration in patients with cerebral
Injections require sedation, which can be chal- palsy often requires a multidisciplinary plan with
lenging for some patients. Additionally, the effect the family, primary pediatrician, pulmonologist
of injections can wane over time; therefore, the and otolaryngologist, and other team members to
injections can become less efficacious. enhance outcomes.
Tracheostomy placement can be necessary in Management of gastroesophageal reflux, as
patients who have copious secretions that leads discussed in the recent clinical report published
to recurrent infection and respiratory failure with by the American Academy of Pediatrics, includes
the need for recurrent or prolonged mechanical standard medical therapy. Gastric acid secretion
ventilation. Tracheostomy carries significant risk can be one of the most damaging aspects of the
for increased morbidity and mortality with place- reflux of gastric acid secretions. Therefore,
ment, as discussed more thoroughly in the blocking acid secretions can lead to significant
improvement. H2 antagonists, particularly raniti- through improved head control, posture and muscle
dine, can block acid receptors as a first-line ther- tone, jaw stability, lip closure, control of tongue
apy. Dosing is typically 4–8 mg/kg/day divided thrusting, etc. Speech pathologists can also work
twice daily or given once a day. The side effect on oral sensations and the swallowing mechanism.
profile is minimal and it is well tolerated. If ranit- Their continued involvement in patients with cere-
idine is not sufficient, therapy often is escalated to bral palsy can be critical to airway protection
a protein pump inhibitor (PPI), the most com- (Gerber and Meyers 2016). However, this therapy
monly employed agent being omeprazole, which is time-consuming, and success is based on a min-
results in additional acid suppression by blocking imal level of cognitive function. It is generally
the action of the H+/K+ ATPase pump in the recommended that all patients receive a minimum
stomach. This medication can be administered 6-month trial of oral motor training; however, data
once or twice daily with dosing related to the on the efficacy and success of therapy is limited.
specific drug employed. There have been many Occupational and physical therapy can also help to
studies recently that link the chronic use of PPI encourage muscle movement and exercise which in
therapy to extensive multisystem side effects, turn improves lung expansion and respiratory
particularly in adults, which includes osteoporo- health.
sis, renal failure, or recurrent infection with a
change in the patient’s microbiome, resulting in
respiratory and gastrointestinal sequelae. There- Summary
fore, short-term use, close monitoring, and fre-
quent reevaluation for its necessity are generally Aspiration can be a significant source of respira-
recommended. Gastric motility can also be tory and gastrointestinal compromise, whether it
altered with medication management; a referral stems from poor management of upper airway
to a pediatric gastroenterologist for management secretions and sialorrhea or it originates from
can be helpful. reflux of gastric contents. In either case, patients
Nonmedical intervention can also include with cerebral palsy are at significant risk for recur-
changes in patient positioning for improved motility rent respiratory illness leading to a decline in
or thickening feeds to help transit to the esophagus. respiratory health, nutritional status, and ulti-
Surgical intervention with gastrostomy tubes can mately increased morbidity and mortality. Imag-
also be placed to prevent aspiration of oral feedings. ing may be beneficial in the acute setting,
These feeding tubes can feed through the stomach supported by chest radiographs, or in chronic
itself or can be extended to give feeds directly into management and screening via barium swallow
the jejunum to combat gastroparesis and refluxing of evaluation. With a variety of supportive medical
feeds. Placement of a gastrostomy tube can be asso- and surgical interventions, a comprehensive goal
ciated with fundoplication; the fundus is wrapped for the medical team is to control aspiration and
around the distal esophagus in hopes to create a stabilize respiratory and nutritional status over
muscular barrier against the reflux of gastric con- each patient’s lifetime.
tents. All surgical procedures carry some risk, and
while patients can no longer vomit, they often retch.
A fundoplication can loosen with time and patients Cross-References
can have complications including hernias and
adhesions. ▶ Assessment and Treatment of Feeding in Chil-
Additional ongoing considerations should dren and Youth with Cerebral Palsy
include adequate oral hygiene and routine dental ▶ Dental Hygiene for Children with Cerebral
evaluation to prevent gingival disease and a decline Palsy
in dentition. Speech therapy can additionally be ▶ Medical Management of Tracheostomy in the
crucial to work on oromotor training. This can be Child with Cerebral Palsy
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Medical Management of
Tracheostomy in the Child 66
with Cerebral Palsy
Jodi Gustave and Ambika Shenoy
Contents
Introduction: What Is a Tracheostomy? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 938
Natural History of Respiratory Issues in Patients with Cerebral Palsy . . . . . . . . . . . 938
Treatment: Indications for Tracheostomy Tube Placement in Patients
with CP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 940
Evaluation for Tracheostomy Placement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 941
Complications: Potential Risks of Trach Placement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 943
Care Following Trach Placement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 945
Decannulation of the Tracheostomy Tube . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 946
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 947
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 947
Abstract severe illness or chronic, recurrent respiratory

Patients with cerebral palsy (CP) may exhibit a symptoms that are progressively worsening,
variety of respiratory problems including and/or the need for escalating support over
abnormal muscle tone, restrictive lung disease, time. Common benefits of tracheostomy place-
chronic respiratory failure, upper airway ment include providing a stable airway, and
obstruction, swallow dysfunction, sleep- ensuring a pathway for adequate oxygenation
disordered breathing, impaired cough, and/or and ventilation in addition to pulmonary toilet.
difficulty clearing respiratory secretions. Tra- However, tracheostomies are not without con-
cheostomy tube placement may be considered sequences and insufficient monitoring or lack
in select patients with CP in the setting of of vigilant care can be life-threatening. Com-
mon complications following tracheostomy
tube placement may include tracheal obstruc-
J. Gustave (*) · A. Shenoy tion from mucus plugging, accidental dis-
Division of Pediatric Pulmonology, Department of lodgement, granulation tissue formation,
Pediatrics, Nemours/A.I. Dupont Hospital for Children, bleeding, or acute infection such as tracheitis.
Wilmington, DE, USA
The decision to pursue tracheostomy place-
e-mail: Jodi.Gustave@nemours.org;
Ambika.Shenoy@nemours.org ment requires careful consideration, medical

https://doi.org/10.1007/978-3-319-74558-9_70
938 J. Gustave and A. Shenoy
knowledge of the risks and benefits of such a and Hammer 2006). At this time, the placement
procedure, and candid discussion with care- of a tracheostomy tube provides a stable, perma-
givers about the lifestyle changes and exten- nent or semi-permanent way to bypass the upper
sive acute and chronic care and monitoring that airway and provide respiratory support as indi-
is required following placement. Tracheos- cated. There are several types, sizes, and brands
tomy placement in patients with CP is typically of tracheostomy tubes, each individualized
permanent, with very rare cases of patients according to specific patient needs. Some com-
who are able to tolerate tracheal decannulation monly used tracheostomy tubes used in pediatric
(removal). This chapter reviews the indications patients are pictured in Figs. 1 and 2. Figure 1
and testing available for patients in whom tra- shows two standard tracheostomy tubes, with the
cheostomy placement is being considered and one on the right known as a “flex” tube, which has
in whom decannulation may be a rare a flexible flange (outer portion of the tube) in order
possibility. to allow better movement. The one on the left is a
similar tube with a non-flexible flange. These are
Keywords both uncuffed tubes. Uncuffed tracheostomy
Tracheostomy tube · Cerebral Palsy · tubes allow airway clearance but provide no pro-
Ventilation · Upper airway obstruction · tection from aspiration. Cuffed tracheostomy
Hypertonia · Hypotonia · Obstructive sleep tubes allow for airway clearance and offer some,
apnea · Ventilator although not complete, protection from aspira-
tion. Additionally, positive pressure ventilation
can be more effective if the cuff is inflated to
Introduction: What Is a Tracheostomy? minimize air leak around the tracheostomy tube
into the upper airway. There are many different
Tracheostomy placement is the procedure by cuff styles that can be used depending on patients’
which an artificial airway is inserted through the needs (Hess and Altobelli 2014). Figure 2 shows a
anterior neck into the trachea in order to bypass cuffed tracheostomy tube with the cuff deflated
the upper respiratory structures including nasal (“down”) and Fig. 3 shows the same tube with the
passages, pharynx, larynx, and subglottic space. cuff inflated (“up”).
It is commonly used to help patients with under- Figure 4 shows the typical placement of a
lying airway or pulmonary disease to achieve tracheostomy tube in the anterior neck of a patient.
adequate oxygenation, ventilation, and pulmo-
nary toilet. Tracheostomy placement dates back
to 3600 BC in Egyptian tablets. This was a risky Natural History of Respiratory Issues
endeavor and placement was quite controversial. in Patients with Cerebral Palsy
In the early twentieth century, Chevalier Jackson
standardized the tracheostomy procedure and Cerebral palsy (CP) is a neurological condition of
postoperative management, allowing it to enter motor dysfunction. Patients with CP may exhibit
mainstream medicine (Jackson 1909). In the gross and fine motor delays, as well as speech and
mid-1900s, tracheostomies were commonly swallowing difficulties as a result of underlying
placed in the setting of upper respiratory infec- hypotonia. One of the most common respiratory
tions such as diphtheria or epiglottitis. However, issues in patients with CP is upper airway obstruc-
with the advent of routine childhood immunization, with symptoms occurring while awake,
tions, tracheostomy placement due to infectious while asleep, or both. Children may exhibit stertor
upper airway obstruction has declined. Instead, or stridor, gurgling breathing, snoring, apnea, cya-
tracheostomy placement now occurs primarily nosis, or respiratory distress. Such symptoms may
for failed extubation (with the need for prolonged be positional in nature. Additional comorbidities
mechanical ventilation) or for upper airway that can exacerbate respiratory concerns in
obstruction (congenital or acquired) (Traschel patients with CP include dysphagia with frank or
66 Medical Management of Tracheostomy in the Child with Cerebral Palsy 939
Fig. 3 Cuffed tracheostomy tube with cuff inflated

Fig. 1 Standard pediatric tracheostomy tubes. Figure on L
is standard flange and R has flexible flange
Fig. 4 Tracheostomy tube placed in a patient

Fig. 2 Cuffed tracheostomy tube. Cuff is deflated in this
figure
micro-aspiration, gastroesophageal reflux (GER), Additional issues may include sequelae from other
decreased cough effectiveness, recurrent pneumo- underlying chronic conditions such as reduced pul-
nia, prolonged respiratory infections, impaired monary reserve from bronchopulmonary dysplasia
mucociliary clearance, respiratory muscle weak- (BPD) or reduced lung growth in patients with
ness causing hypoventilation, scoliosis, obstruc- skeletal dysplasia (Seddon and Khan 2003). Thus,
tive or central sleep apnea, airway hyper- respiratory disease in patients with CP is typically
reactivity, or malnutrition (Kontorinis 2013). multifactorial. Table 1 lists some of the most
Table 1 Common respiratory issues in children with CP Table 2 Potential benefits of tracheostomy in patients
and associations with CP
Upper airway obstruction (awake or asleep) Bypass upper airway obstruction
Stertor Provide mechanical ventilatory support
Stridor Assist with pulmonary toilet
Micrognathia Allow for mobilization, transportation
Facial deformities
Macroglossia or glossoptosis
Laryngomalacia
a routine basis. This can also be a helpful option
Impaired mucociliary clearance
for complex or severe cases where noninvasive
Decreased effectiveness of cough
respiratory support/treatments or procedures have
Recurrent or prolonged respiratory infections
been attempted and failed. Chronic use of nonin-
Airway hyperreactivity
Tracheobronchomalacia
vasive positive pressure support (e.g., CPAP or
Sleep disturbances BiPAP via nasal pillows or facial/nasal mask) for
Obstructive sleep apnea prolonged periods of time may cause skin or nasal
Central sleep apnea septal breakdown. In younger children, these ther-
Hypoventilation apies may alter bony development or growth
Nocturnal hypoxia resulting in entities such as midface hypoplasia,
Gastroesophageal reflux thus further contributing to increased upper air-
Dysphagia and/or aspiration way resistance and need for support. While poor
Respiratory muscle weakness muscle tone is the main contributor to respiratory
Hypoventilation disease in CP patients, other anatomical causes
Scoliosis (for example maxillary hypoplasia, retrognathia,
Torticollis or glossoptosis) and comorbid conditions (e.g.,
laryngomalacia, dysphagia with difficulty manag-
ing secretions, or seizures) may also lead to a need
common respiratory problems in patients with for discussion about tracheostomy tube placement
CP. Each of these respiratory issues can contribute to alleviate the impact of these issues on daily life
to upper or lower airway disease and requires ded- and improve airway stability and patency
icated attention. (Table 2).
Kontorinis et al. 2013 performed a limited,
retrospective analysis of 15 pediatric CP patients
Treatment: Indications presenting to ENT clinic to determine timing of
for Tracheostomy Tube Placement tracheostomy placement. The average age at pre-
in Patients with CP sentation for tracheostomy evaluation was
approximately 8 years. All children had symp-
Placement of a tracheostomy tube may be helpful toms of upper airway obstruction and had been
in select patients with CP for a variety of reasons. treated with nocturnal and/or daytime supplemen-
It serves as a way to bypass upper airway obstruc- tal oxygen. While three patients responded to
tion to allow for airflow and appropriate gas supplemental oxygen or CPAP therapy, the others
exchange. In patients with difficulty handling required surgical interventions such as adenoton-
secretions, it can provide a way to aid in pulmo- sillectomy or supraglottoplasty. Eight patients
nary toilet and provide a conduit for regular required tracheostomy tube placement. The aver-
suctioning without traumatizing the upper airway. age age for tracheostomy placement was approx-
For children developing chronic restrictive lung imately 11.6 years, with a range of 7.5–15 years of
disease, respiratory muscle weakness, or chronic age. Of note, only four children were referred at
respiratory failure, a tracheostomy tube provides a <5 years of age, leading to speculation that
way to deliver invasive mechanical ventilation on patients with CP require chronic tracheostomy
status due to underlying hypotonia with progres- obstructive (OSA) or central sleep apnea (CSA),
sively increasing respiratory needs as they grow. nocturnal hypoxia and/or nocturnal hypo-
There are limited published studies that investi- ventilation. When OSA or CSA are discovered,
gate the timing of tracheostomy tube placement in follow-up positive airway pressure (PAP) titration
patients with CP, but discussion of potential inter- studies may be helpful to determine the optimal
vention at an earlier age may be warranted in some level of support a patient requires, particularly if
patients. they are not considered a candidate for sleep
endoscopy or surgical intervention (i.e.,
adenotonsillectomy, supraglottoplasty, etc.).
Evaluation for Tracheostomy Serum laboratory studies such as a basic or com-
Placement prehensive metabolic profile in combination with
arterial or venous blood gas may be utilized to
Careful consideration must be given in deciding evaluate for acute or chronic respiratory failure or
which patients with CP would benefit from tra- chronic hypoventilation.
cheostomy placement. Common scenarios lead- When considering tracheostomy placement, it
ing to discussion about the utility of tracheostomy is important to openly discuss indications and
procedures for patients with CP include prolonged benefits, in addition to acute and chronic risks
acute illness with failure to extubate, difficulty associated with tracheostomy status with family
weaning from mechanical ventilator support, fre- members and the extended care team. Knowledge
quent respiratory infections with difficulty han- of subjective respiratory symptoms (e.g., pro-
dling secretions, frequent hospital admissions for longed respiratory infections, muscle weakness)
escalating invasive or noninvasive ventilatory in combination with objective test results (e.g.,
support, recurrent tracheal intubations, or diffi- impaired gas exchange, OSA or CSA, respiratory
culty in managing secretions that lead to compli- muscle weakness, or impaired cough or swallow)
cations such as aspiration pneumonias. as well as failure of prior treatment modalities is
There are various testing modalities available key to prepare for discussing the possibility of
to assess for contributing factors to respiratory tracheostomy placement with a patient and their
disease in CP patients. Pulmonary function testing family. In addition to indications, risks, and ben-
may include: spirometry (if able to complete efits of tracheostomy status, it is important to
maneuvers) to assess for lower airway obstruction address the extensive education and monitoring
or bronchial hyper-reactivity, measurements of required while caring for a child with a tracheos-
respiratory muscle strength, including mean inspi- tomy. These needs result in lifestyle changes for
ratory/expiratory pressures (MIP/MEP) or if the patient and their family, particularly due to the
unable to complete such maneuvers, a measure- need for continuous monitoring of children post-
ment of negative inspiratory force (NIF) to assess operatively. The American Thoracic Society
for respiratory muscle weakness, measurement of (ATS) has standardized guidelines for the care of
total lung capacity (TLC), and diffusing capacity a child with tracheostomy, which are summarized
(DLCO). Thoracic imaging tests such as chest in Table 3 (Sherman, et al. 2000).
radiography and chest CT may be helpful in In select cases of children with cerebral palsy,
assessing for structural lung disease, i.e., recurrent chronic lung disease and ongoing severe aspiration
atelectasis, chronic mucoid impaction, bronchiec- not responsive to medical management, more
tasis, bony abnormalities, and scoliosis. extensive surgery such as tracheoesophageal diver-
Salivagram and/or modified barium swallow eval- sion or laryngotracheal separation (LTS) may be
uation in combination with Speech Therapy and considered (Hafidh 2006). While placement of a
Otolaryngology consultation can be helpful to standard tracheostomy tube with a cuff may be
assess for dysphagia and aspiration. Overnight helpful in managing secretions and decreasing the
pulse oximetry may uncover nocturnal hypoxia, risk of aspiration, it is not absolutely protective.
while Polysomnography (PSG) can diagnose Furthermore, sometimes placement of a standard
Table 3 Summary of the ATS standardized guidelines for the care of a child with a chronic tracheostomy
Care point Summary
Tracheostomy tube Size of trach tube determined by size of airway as well as underlying medical concerns
selection Uncuffed tracheostomy tubes are generally preferred over cuffed in most situations
Tracheostomy tube The most common frequency of tracheostomy tube changes is weekly, although there is no
care consensus
Suctioning Techniques should be employed to efficiently clear the airway of mucus
Clean techniques are recommended
The suction catheter should be cleaned thoroughly following each use
Depth of suctioning should be determined with premeasured technique
Humidification With upper airway bypassed by tracheostomy tube, inspired air can cause significant humidity
deficit
Gas delivered through tracheostomy tube needs to be heated and humidified
Speech development All patients with tracheostomy tube should be referred to speech department
Goals of speech pathologist are to facilitate vocal communication and swallowing
Caregiver education Home care teaching should begin before placement of tracheostomy tube and should be
individualized
All children with tracheostomy tubes should be cared for by people with tracheostomy tube
care and replacement training
All children should receive skilled home nursing for at least a transitional adjustment time
Some families will require indefinite home nursing care
Medications Other than emergency drugs, there are no indications for endotracheal administration of
medications meant for systemic effects
Some aerosolized drugs (such as inhaled corticosteroids) can be given through the
tracheostomy tube
Monitoring The best monitoring for a child with a tracheostomy tube is a vigilant and well-trained
caregiver
There is no general consensus regarding continuous monitoring of a child with a tracheostomy
tube
Clinical practice patterns vary widely in regard to home monitoring recommendations
Decannulation Tracheostomy decannulation can be considered once original need for the tracheostomy tube
procedures is no longer present
The patient needs to be able to maintain a safe and adequate airway without the tracheostomy
tube
The one-stage decannulation procedure is recommended
The patient should be monitored in a hospital setting at least 24–48 h following decannulation
There is higher risk of complications following decannulation if the airway has not been
evaluated endoscopically
Complications Possible complications of tracheostomy tube placement include intraoperative, immediate
postoperative, and late postoperative
Emergent tracheostomies generally have higher risk of complications than elective procedures
tracheostomy tube within the airway alters swallow surgeon. A 2009 retrospective study by Steven
sensation and may place the patient at higher risk Cook found that LTS was 100% effective in con-
for altered oral sensation and/or swallow dysfunc- trolling aspiration of 56 neurologically impaired
tion. LTS is a specialized procedure in which the children (Steven Cook 2009). This study found
nasopharyngeal airway is permanently separated that there was a significant decrease in hospital
from the trachea, with subsequent tracheostomy admissions for pneumonia following the surgery.
placement to maintain the airway. This procedure However, this procedure is less commonly
may be helpful in a select group of patients and performed due to its permanent and irreversible
requires in-depth discussion between the family and nature. Another important consideration for fam-
the medical care team, which may include the pri- ilies and caregivers to consider is that this results
mary care physician, pulmonologist, gastroenter- in permanent loss of voice (aphonia). In patients
ologist, otolaryngologist, speech therapist, and who undergo LTS, separate instruction on airway
emergencies is required. In case of respiratory medical equipment (pulse oximetry, ventilator

distress, these patients are not candidates for alarms) and watchful observation by a
orotracheal or nasotracheal intubation. Further- tracheostomy-trained caregiver to respond rapidly
more, in case of a cardiorespiratory arrest, they to acute changes such as accidental decannulation
require bag mask ventilation through the trache- (Table 4).
ostomy tube or over the tracheal stoma rather than The most common late-term side effects of tra-
via face mask over the nasopharynx or orophar- cheostomy tube are related to having an artificial
ynx, since there is no longer any connection airway in place that may irritate the airway mucosa
between the pharynx and the lungs. or lead to localized infection. There is greater risk of
infection with a tracheostomy tube simply because
the tube itself has no innate immunity like the upper
Complications: Potential Risks of Trach or lower respiratory tract. Furthermore, the trache-
Placement ostomy tube lacks heat and humidity naturally pro-
vided by the nasal passages of the upper airway,
While tracheostomy status provides significant making secretions more prone to drying and build-
benefits to select patients, before placement it is ing up inside the tracheostomy lumen. These prob-
also important to review the associated risks and lems are counteracted by frequently changing the
side effects of having a tracheostomy tube. Tra- tracheostomy tube, at least every 1–2 weeks
cheostomy tubes can bypass upper airway (depending on the tube and manufacturer),
obstruction or increased upper respiratory resis- suctioning the lumen regularly (at least once every
tance. Therefore, if the tracheostomy tube is acci- 8 h and as needed), and also exogenously adminis-
dentally dislodged, displaced, or obstructed, it tering heat and humidity via “mist collars” or heat
may pose a life-threatening emergency. The sever- moisture exchangers (HME).
ity of dislodgement depends on the child’s upper
airway anatomy and chronic respiratory needs.
Mortality rates in children with tracheostomies
may be as high as 42% (Kremer 2002). Overall, Table 4 Possible complications following tracheostomy
placement
tracheostomy complications may be early (within
the first 7 days of surgical procedure) or late Early: Intraoperative and up to first trach change
(7 days after tracheostomy placement)
(>7 days after tracheostomy insertion). Early
Cannula obstruction
complications commonly reported include acci-
False tract formation
dental decannulation, formation of
Localized infection
tracheocutaneous fistula/false tract, air-leak phe-
Air leak
nomena (such as pneumomediastinum, pneumo- Bleeding
thorax, and subcutaneous emphysema), airway Accidental decannulation
obstruction (most commonly from mucous), Death
bleeding, and localized infection. Late complica- Late: After first trach change (typically >7 days after
tions commonly reported include peristomal or tracheostomy placement)
subglottic granuloma formation, localized infec- Recurrent tracheitis or respiratory infections
tion/tracheitis, tracheal or subglottic stenosis, Granulomas
tracheomalacia, stomal breakdown, Suprastomal or cannula obstruction
tracheocutaneous fistula, bleeding, accidental dis- Accidental decannulation
lodgement, or death (Wilcox 2016; Itamoto et al. Subglottic stenosis
2010). Therefore, while there are clear benefits to Tracheal ulceration
tracheostomy placement, there is risk of signifi- Tracheomalacia
Persistent tracheocutaneous fistula
cant side effects. In order to reduce the risk of such
Tracheal innominate fistula/hemorrhage
adverse events, children with tracheostomy tubes
Death
require continuous monitoring through both
Granulomatous (inflammatory) tissue com- antifungal cream/ointment and suspected bacte-

monly may occur in the peristomal region (exter- rial infection may similarly be treated by an anti-
nally) as demonstrated in Fig. 5. This may be the bacterial cream or ointment. Alternatively, a
result of localized skin irritation from movement general emollient cream or ointment to the
of the tracheostomy tube, rubbing of the trache- affected area may be helpful as a skin barrier.
ostomy tube or pooled, infected secretions. Some- Another common infectious complication of a
times, external granulation may be treated (albeit tracheostomy tube is localized tracheitis as a result
off-label) with antibiotic/steroid combination of having an artificial airway in place within the
drops in combination with Otolaryngology con- normal respiratory mucosa. This is important to
sultation to determine if further surgical interven- differentiate from the airway emergency classi-
tion is required. It is important to remember that cally referred to as “bacterial tracheitis.” While
granulation tissue may form within the airway as some children may have increased secretions by
well. Airway granulomas may cause symptoms nature of having a foreign tracheostomy tube
such as bleeding with suctioning, meeting resis- within the windpipe, other children commonly
tance within the airway when suctioning, produce more mucus in the setting of localized
impaired ventilation, desaturations, aphonia, stri- infection. Classically, “tracheitis” presents with
dor, or other signs/symptoms of upper airway increased or thicker mucous secretions, possibly
obstruction not previously noted when the trache- intermittent mucous plugging of the tracheostomy
ostomy was initially placed. When concern is tube, oxyhemoglobin desaturations with need for
raised about airway granulomas, it is important increased ventilator support or supplemental oxy-
to visualize the airway via tracheoscopy and congen, and/or need for more frequent suctioning.
sult with otolaryngology to consider excision/ Tracheitis can also be a cause for emergent tra-
removal of the tissue. cheostomy change if mucous plugging
There may also be irritation of the skin at the completely obstructs the tracheostomy tube
trach site, which may be caused by a fungal or lumen and therefore the airway itself. Unfortu-
bacterial infection or generalized skin inflamma- nately, there is limited medical literature defining
tion (Fig. 6). If a fungal infection is suspected, it tracheitis and its associated signs or symptoms in
can be treated with appropriate dosing of an technology-dependent children. Similarly, there is
limited medical literature outlining the diagnostic
evaluation and treatment courses including
Fig. 5 Granulation tissue at tracheostomy stoma site Fig. 6 Irritation around the trach site
whether a systemic versus inhaled antibiotic ther- equipment and professional nursing coverage. It
apy would be more helpful in these patients. Often is important to facilitate discussion with families
times, a tracheostomy culture or tracheal aspirate about homecare needs for caregiver training, med-
is sent to the lab for analysis. Tracheitis may be ical equipment, and professional nursing support
more likely if there are increased white blood cells in accordance with the ATS guidelines referenced
on the gram stain in conjunction with increased above (See Table 3) (Sherman et al. 2000). The
colonies of bacteria, but this remains controversial recommended guidelines suggest that any child
based on expert opinion. When a diagnosis of with a tracheostomy requires continuous observa-
tracheitis is made based on clinical symptoms in tion by a trained caregiver to monitor for life-
conjunction with laboratory testing results, treat- threatening events such as tracheal decannulation,
ment consists of short-term use of inhaled or sys- ventilator disconnection, or airway obstruction.
temic antibiotic therapy. A treatment course The American Thoracic society also recommends
typically lasts between 7 and 14 days, depending that two caregivers be educated on all aspects of
on the patient’s symptoms, response, and overall routine and tracheostomy care prior to consider-
clinical course. Therapy at this time is mainly ation for discharge home. Education includes tra-
based on limited case reports in the medical liter- cheostomy care such as wound care, changing the
ature and overall expert opinion. Antibiotic choice tracheostomy tube, suctioning, troubleshooting
is empiric based on past bacterial cultures while monitors and mechanical support, and life support
awaiting new tracheostomy culture results. Gen- training (CPR). In addition, routine care such as
erally, each time tracheitis is suspected, a new medication administration, changing clothing, or
tracheal aspirate/culture is sent to the lab. Inhaled bathing needs to be reviewed. Tracheostomy
antibiotic therapy alone is not helpful if a patient tubes should be changed per manufacturer’s
has concomitant bacterial pneumonia in conjunc- instruction but typically are changed every
tion with tracheitis, as this therapy is mainly top- 1–2 weeks or in the interim in case of emergency.
ical. Typically, patients with tracheitis related to Suctioning to ensure patency of the airway should
tracheostomy status will improve and return to occur at least once every 4–8 h or more often
baseline following about 7–14 days of dedicated depending on clinical symptoms and degree of
antimicrobial treatment. secretions a child may produce. Attention to and
cleaning of the tracheal stoma and tracheostomy
ties which hold the tracheostomy tube in place
Care Following Trach Placement should occur at least 1–2 times/day. Skin should
be monitored closely for irritation or breakdown.
Aftercare for tracheostomy placement is medi- Home monitoring should be a combination of
cally complex and requires extensive education. continuous direct visualization of the child and
It is important that patients and families are aware alarms set on ventilator support and pulse oxime-
of these needs prior to making a decision to pursue try (Sterni 2016). Additionally, durable medical
tracheostomy status. The intensive care and mon- equipment (DME) companies should routinely
itoring regimen of a medically complex child with assess medical equipment in the home and ensure
tracheostomy at home requires dedicated partner- that it is functional. These companies along with
ship between the family and medical providers nursing agencies and the medical home physician
(primary care physician, pediatric pulmonologist, group should provide 24 h telephone access in
intensivists, medical equipment company, home case of emergency. Typically, extensive home
nursing, and other subspecialists). Children evaluations to ensure adequate electrical power
undergoing tracheostomy likely require several supply, telephone connection, and access into
weeks to months in the hospital following trache- and out of the home environment are also needed
ostomy placement to educate family/home care- to ensure safety of the child following discharge
givers fully on all aspects of medical care while from the hospital. These guidelines were devel-
making arrangements for home medical oped and modified to aid in transition of children
with chronic respiratory needs into the home envi- medical attention, medical equipment support,
ronment rather than institutional settings, to facil- and as much skilled nursing as possible is avail-
itate daily interactions with their family and able for tracheostomy-related matters, no matter
maintain quality of life. Residential homes or how mundane or urgent the issue that arises.
facilities do, however, remain an important option
if families or caregivers, medical equipment com-
panies, and/or skilled nursing are unable to pro- Decannulation
vide the level of intense support that the child of the Tracheostomy Tube
requires.
Home equipment for a child with a tracheos- The possibility of tracheal decannulation is
tomy often includes but is not limited to: unlikely in patients with CP. However, in some
rare cases, there are select pediatric CP patients
– Two tracheostomy tubes of appropriate size with tracheostomy status where tracheal
and one downsized tube in case of difficulty decannulation may be considered. Decannulation
replacing the tube during changes describes the process of removing the tracheos-
– Tracheostomy ties tomy tube. Consideration for decannulation, sim-
– Gauze or other medical dressings to keep skin ilar to consideration for tracheostomy placement,
dry around the tracheostoma or under ties also requires careful consideration and multi-
– Heat moisture exchanger or tracheostomy mist disciplinary input. Most importantly, there must
collar with heat/humidity to moisturize secre- be improvement or resolution in the original indi-
tions or air flow cation for tracheostomy placement, which is typ-
– Mechanical ventilator with battery in case of ically rare in patients with CP (Lee 2016). The
power outage (and back-up ventilator in case process of readying for decannulation is lengthy
of malfunction), if patient requires invasive and may take weeks to months or years. Initial
ventilation steps include weaning off mechanical ventilator
– Supplemental oxygen support while ensuring adequate gas exchange
– Pulse oximetry and growth or development during this process.
– Suction supplies – Tubing, catheter Polysomnography (PSG) may be helpful to ensure
– Ambu-bag the absence of abnormalities of gas exchange. The
– Gloves PSG is generally performed as a “capped” study,
– Syringes and sterile water (if cuffed tracheos- where a “cap” or fitted occlusive device is placed
tomy tube is in place) over the tracheostomy tube lumen to prevent air-
– Airway clearance devices: IPV, mechanical flow through it. Typically, the tracheostomy tube
insufflator/Exsufflator (if impaired cough) is “down-sized” to the smallest available to ensure
– Nebulizer or MDI adaptor for use in-line with appropriate positioning in the airway during the
tracheostomy or mechanical ventilation sleep study and to allow for airflow through the
trachea and upper airway around the capped tra-
Travel with children with a tracheostomy cheostomy tube. If patients are stable off mechan-
requires careful advanced planning. Most of the ical ventilator support and demonstrate adequate
medical equipment outlined above is required for gas exchange, the next steps aimed to ensure
the trip. Furthermore, a dedicated, tracheostomy- patency of the upper and lower airways are con-
trained caregiver (not the driver) is strongly sidered. Testing to evaluate airway protection
recommended to monitor the child continuously with reflexes such as coughing, gagging,
including during transportation to/from home or swallowing secretions, or handling secretions
school. Children also require routine visits to their often ensue next. Direct observation of the upper
primary care physician, otolaryngology, and lower airways is pursued via combination of
pulmonology, and other subspecialists for routine rigid and flexible bronchoscopy by ENT and
or urgent care. Care teams should also ensure that pulmonologists assessing airway patency,
absence of ongoing airway inflammation or air- Summary

way malacia, and absence of active infection or
granulomatous tissue. All of these entities may In summary, tracheostomy status can provide a
pose factors impeding tracheal decannulation. great deal of benefit to children with CP. It
During rigid bronchoscopy, the otolaryngologist allows them to be more mobile, and potentially
assesses for normal vocal cord mobility and the improves quality of life outside of the hospital
absence of upper airway obstruction (for example, setting. The tracheostomy tube facilitates clear-
adenoidal/tonsillar hypertrophy, granulomatous ing secretions, provides a stable airway through
tissue, or subglottic stenosis). The flexible bron- which respiratory support can be provided to
choscopy performed by the pulmonologist visual- ensure adequate oxygenation and ventilation,
izes the lower airways to assess for airway and can bypass upper airway obstruction. How-
malacia, ongoing irritation, or evidence of micro- ever, tracheostomy placement is a significant
aspiration or active infection which may be undertaking, and the decision whether or not to
concerning factors impacting the success of pursue this procedure requires careful consider-
decannulation. After these lengthy evaluations, if ation. There are significant risks to having a
CP patients are considered possible candidates for tracheostomy tube in place. These risks are
tracheal decannulation, it is strongly decreased with extensive trained caregiver edu-
recommended that this process take place in the cation and considerable continuous monitoring
hospital, typically in the intensive care unit under and vigilance. Routine follow-up care is
close monitoring for signs or symptoms of respi- required in addition to availability for urgent
ratory distress or procedural failure. Respiratory assessment if/when the need arises. A care
symptoms may be subtle initially, and thus patients team and family must decide together whether
usually require at least several nights of inpatient they are willing to undertake this process and the
monitoring. Typically, the first night or nights lifestyle changes that it entails in order to bal-
occur in the intensive care unit and subsequently ance the risks and benefits of this procedure.
take place in an area of the hospital able to manage
patients with tracheostomy tubes or reinsert the
tube (if failure is noted). Once decannulated, the Cross-References
tracheostomy typically heals slowly through pri-
mary opposition. Close follow-up with ENT or ▶ Aspiration in the Child with Cerebral Palsy
Pulmonology is strongly recommended following ▶ Asthma in a Child with Cerebral Palsy
discharge from the hospital after several nights of ▶ Bronchopulmonary Dysplasia and Cerebral
medical stability. Patients, family, home medical Palsy
equipment companies, and nursing agencies ▶ Medical Management of Tracheostomy in the
should be educated on signs or symptoms of respi- Child with Cerebral Palsy
ratory distress and upper airway obstruction and be ▶ Obstructive Sleep Apnea in Children with
advised to seek emergent medical attention should Cerebral Palsy
they occur. During this process, patients and fam- ▶ Upper Airway Obstruction in the Child with
ilies should also be educated that while tracheal Cerebral Palsy: Indication for
decannulation may be a possibility, it is not defin- Adenotonsillectomy
itive and may fail. A child with CP may have
difficulties tolerating decannulation immediately
or potentially in the future. Sometimes, tracheos- References
tomy tubes need to be replaced over time surgi-
cally. It is most important to support children with Hafidh MA et al (2006) Intractable pulmonary aspiration in
children: which operation? Int J Pediatr Otorhino-
CP in keeping with the goals they and their fami-
laryngol 70(1):19–25
lies have set and to provide them with the best Hess DR, Altobelli NP (2014) Tracheostomy tubes. Respir
quality of life as possible. Care 59(6):956–971
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Kontorinis G et al (2013) Airway obstruction in children Sterni LM et al (2016) An official American Thoracic Soci-
with CP: need for tracheostomy. Int J Pediatr Otorhino- ety practice guideline: pediatric chronic home invasive
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Kremer B et al (2002) Indications, complications and sur- Steven Cook MD (2009) Candidate’s thesis: Laryngotracheal
gical techniques for pediatric tracheostomies: an separation in neurologically impaired children: long-term
update. J Pediatr Surg 37:1556–1562 results. Laryngoscope 119(2):390–395
Lee J et al (2016) The role of polysomnography in trache- Traschel D, Hammer J (2006) Indications for tracheostomy
ostomy decannulation of pediatric patient. Int J Pediatr in children. Paediatr Respir Rev 7(3):162–168
Otorhinolaryngol 83:132–136 Wilcox LJ et al (2016) Tracheostomy complications in
Seddon PC, Khan Y (2003) Respiratory problems in chil- institutionalized children with long-term tracheostomy
dren with neurological impairment. Arch Dis Child and ventilator dependence. Pediatr Otolaryngol 154(4):
88(1):75–78 725–730
Obstructive Sleep Apnea in Children
Abigail Strang and Aaron Chidekel
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 950
Prevalence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 950
Normal Breathing During Sleep . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 950
Sleep-Disordered Breathing and OSA in Children with Cerebral Palsy . . . . . . . . . . 950
Clinical History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 951
Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 951
Treatment Options . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 952
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 954
Abstract changes including irritability, hyperactivity,

Obstructive sleep apnea (OSA) is not uncom- or poor academic performance, and cardiopul-
mon in children with cerebral palsy. Children monary disease. Untreated sleep apnea can
with cerebral palsy are at increased risk also affect the ability to adequately control
for OSA secondary to anatomic upper airway other medical conditions, such as epilepsy,
factors, craniofacial abnormalities, abnormal and cause difficulty with ability to recover
muscle tone, and underlying pulmonary and from anesthesia. The gold standard for diagno-
neurologic disease. Medications used in chil- sis of OSA is an overnight polysomnogram.
dren with cerebral palsy can also increase Treatment options include positional therapy,
risk of OSA. Consequences of untreated adenotonsillectomy and other upper airway
OSA include daytime sleepiness, behavioral surgical procedures, noninvasive positive pres-
sure therapy, and in severe cases, tracheostomy
may be required. Screening children with cere-
A. Strang · A. Chidekel (*) bral palsy for obstructive sleep apnea is impor-
Division of Pediatric Pulmonology, Nemours A.I. duPont tant for both improving quality of life and
Hospital for Children, Wilmington, DE, USA mitigating health consequences of untreated
e-mail: astrang@nemours.org; abigail.strang@nemours. sleep apnea.
org; achidek@nemours.org;
Aaron.Chidekel@nemours.org

https://doi.org/10.1007/978-3-319-74558-9_71
950 A. Strang and A. Chidekel
Keywords Normal Breathing During Sleep

Cerebral palsy · Obstructive sleep apnea ·
CPAP · Polysomnogram In general, breathing during sleep should be quiet
and comfortable. There are differences in breath-
ing during sleep compared to awake breathing
Introduction due to normal alterations in respiratory control
and muscle tone during sleep. During normal
Obstructive sleep apnea syndrome (OSA) is part sleep, ventilatory responses to hypercapnia and
of a larger group of sleep-related respiratory hypoxemia are blunted. Furthermore, in REM
disorders termed sleep-disordered breathing. (rapid eye movement) sleep, muscle tone (includ-
There is a spectrum of sleep-disordered breathing the upper airway and intercostal muscles)
ing varying in severity from primary snoring to decreases, which results in a reduced functional
classic severe obstructive sleep apnea with a residual capacity and increased upper airway
range of physiologic patterns and consequences resistance. Therefore, if children have risk factors
in between (Roland et al. 2011). OSA is defined for impaired breathing while awake (such as
by the American Thoracic Society as “a disorder crowded upper airway and chronic lung disease),
of breathing during sleep characterized by pro- these risk factors will be magnified during sleep
longed partial upper airway obstruction and/or and especially during REM sleep.
intermittent complete obstruction (obstructive
apnea) that disrupts normal ventilation and nor-
mal sleep patterns (American Thoracic Society Sleep-Disordered Breathing and OSA
1996).” in Children with Cerebral Palsy
Children with cerebral palsy are at increased risk

Prevalence for impaired breathing during sleep and OSA
secondary to anatomic upper airway factors,
The prevalence of OSA in children with cerebral craniofacial abnormalities, abnormal muscle
palsy is unclear. While the prevalence of OSA in tone, and underlying pulmonary and neurologic
all children is estimated to be between 1.2% and disease.
5.7% (Marcus et al. 2012), the proportion of chil- Children with cerebral palsy are at risk for
dren with cerebral palsy who have OSA is likely obstructive sleep apnea due to upper airway
higher than in children without cerebral palsy. narrowing, which may be caused by both ana-
Among children with cerebral palsy, OSA is likely tomic factors (such as adenotonsillar hypertrophy)
even higher in those with other co-morbidities, and abnormal muscle control. The patency of the
such as epilepsy, chronic lung disease, and more upper airway is determined by both anatomic and
severe forms of motor impairment. physiologic factors, and these can both be altered
Of note, these studies assessed rates of sleep- in children with cerebral palsy due to upper air-
disordered breathing in children with cerebral way crowding and abnormal muscle tone.
palsy using screening questionnaires rather Children with cerebral palsy and OSA have
than diagnostic polysomnogram. Therefore, it upper airway narrowing compared to healthy
is likely that the true incidence of OSA in this children (Newman et al. 2006). While an individ-
population was under-estimated. Thus, further ual is awake, there is increased upper airway tone
studies including larger populations of children and usually no clinical consequences. However,
with cerebral palsy and using objective measure- during sleep, and especially during REM sleep
ments obtained with polysomnography are as previously described, this compensatory mech-
needed in order to better understand the true anism is lost, and the airway closes despite respi-
prevalence and severity of OSA in this group ratory drive, leading to a variety of clinical
of patients. symptoms, ranging from snoring to obstructive
67 Obstructive Sleep Apnea in Children with Cerebral Palsy 951
hypopnea (partial airway closure) to obstructive Table 1 Commonly used medications in children with
apnea (complete airway closure). This decrease cerebral palsy and effect on breathing control during sleep
in airflow leads to hypoxemia and often hypercap- Potential effect on
nia, resulting in an arousal (at times followed breathing during
Class Examples sleep
by gasping), which then causes an increase in
Antispastics Baclofen " Central sleep
upper airway tone thereby restoring airway Diazepam and apnea, " OSA
patency, if only temporarily. other " OSA,
Children with cerebral palsy are at risk for benzodiazepines hypoventilation
underlying lung disease for various reasons Anti- Phenobarbital " risk of OSA
including scoliosis causing restrictive lung dis- epileptics Clonazepam " risk of OSA
Carbamazepine " risk of OSA
ease, neuromuscular weakness impairing ability Valproate " risk of OSA
to clear respiratory secretions, and risk of aspira- Gabapentin " risk of OSA
tion. Additionally, children with more severe neu- Levetiracetam No effect
rologic impairment, especially with a history of Lamotrigine No effect
Topiramate No effect
perinatal stroke or hypoxic injury, may have
Sleep aids Melatonin No effect
abnormal central control of respiration during Clonidine No effect
sleep, leading to central apnea during sleep Benzodiazepines " risk of OSA
and/or periodic breathing. Finally, medications Gabapentin " risk of OSA
that are used as part of medical treatment for Analgesics Acetaminophen No effect
NSAIDS No effect
other conditions associated with cerebral palsy, Opioids " risk of OSA
such as epilepsy or increased muscle tone, may " risk of central
increase the risk of sleep-disordered breathing, sleep apnea and
and their use should be monitored in children Hypoventilation
at higher risk for sleep-disordered breathing. See
Table 1 for a list of commonly used medications in
children with cerebral palsy which may impact adenotonsillar hypertrophy and craniofacial
breathing during sleep. abnormalities. The other common associated
physical exam findings include swollen nasal
membranes, deviated nasal septum, “adenoidal
Clinical History facies” with an elongated mid-face and mouth-
breathing, a high arched palate, overjet (overbite)
As noted above, chronic snoring is common, but a cross-bite, midface hypoplasia, retrognathia or
smaller subset of these children have obstructive micrognathia, and an enlarged neck circumfer-
sleep apnea. Parental reports of snoring are an ence (Katz and Marcus 2014).
accurate predictor of snoring on polysomnogram,
but not necessarily OSA (Preutthipan et al. 2000).
Therefore, other clinical history and exam find- Diagnosis
ings are important in identifying children who are
at risk for sleep apnea and who should undergo The gold standard for diagnosis of OSA is
further diagnostic testing. Additional historical an overnight attended polysomnogram (sleep
risk factors for OSA in a child with snoring study). In addition to determining whether OSA
include a history of witnessed apneas and restless is present or not, overnight polysomnogram can
sleep, failure to thrive, developmental delays, guide therapy by identifying the severity of sleep
poor school performance, and excessive daytime apnea present. Additionally, anesthesia and safety
sleepiness. decisions (such as need for inpatient hospitaliza-
A variety of physical exam findings have been tion after surgery or intensive care unit admission)
described in children with OSA, but many times can be more carefully considered around potential
the physical exam is normal, with the exception of surgery using data from the sleep study.
A polysomnogram can be performed in chil- pressure, depending on whether there is daytime

dren of all ages in the appropriate pediatric sleep impairment or co-morbidities present. Positional
laboratory. The American Academy of Pediatrics therapy is often useful in children with cerebral
(AAP) recommends polysomnogram as the diag- palsy, especially children with abnormal control
nostic test of choice in evaluating children with of the neck and trunk. If the patient is overweight
suspected sleep-disordered breathing (American or obese, weight loss is recommended. In mild
Academy of Pediatrics 2002). cases of OSA, medical therapy with intranasal
An example of polysomnogram montage steroids and montelukast may be trialed, espe-
typically used in pediatric patients includes elec- cially if there is chronic nasal congestion present
troencephalography, electromyogram (chin, legs), (Kheirandish-Gozal and Gozal 2008; Goldbart
electro-oculogram, measures of abdominal and et al. 2012; MacLean 2013).
thoracic excursion, pulse oximetry, end-tidal car- In terms of surgical procedures, the first
bon dioxide (ETCO2) measurement, measure- line of treatment for pediatric OSA is adenoton-
ment of nasal airflow (nasal air pressure sensor sillectomy. While adenotonsillectomy is effec-
and/or oronasal thermistor), snore volume, body tive in the treatment of OSA in the majority of
position sensor, and video and audio recording. otherwise healthy children, there are no large
A typical polysomnogram report includes mea- studies using data from polysomnogram to assess
surements of sleep architecture including sleep the efficacy of this surgery in children with
stages, respiratory events (including an apnea/ cerebral palsy, although various studies report
hypopnea index), oxygen values, ETCO2 values, symptomatic improvement based on parental
heart rate, and presence or absence of periodic observation (Hasiao and Nixon 2008; Margarido
limb movements. and Tom 1999).
The severity of the sleep apnea is typically Among all children, rates of residual sleep
determined by the apnea/hypopnea index (AHI) apnea after adenotonsillectomy are around 29%
as well as measures of abnormal gas exchange (Tauman et al. 2006) and are higher in children
(amount of time with oxygen values <92% and with obesity, age >7 years, and high pre-operative
amount of time with elevation of ETCO2 greater AHI (>20/h) (Marcus et al. 2012). Children with
than 50 mm Hg). An AHI of greater than 1 event/h cerebral palsy may be at risk for residual sleep
is generally considered positive for obstructive apnea due to other factors as well, including
sleep apnea; however, in determining a treatment abnormal muscle tone, multi-level airway
plan, other factors, such as oxygen and carbon obstruction, and underlying lung and neurologic
dioxide levels, co-morbidities, and degree of day- disease. Therefore, clinical follow-up to assess for
time impairment are also considered. resolution of symptoms is appropriate. In this
Objective measurements of the severity of group of children, consideration of a follow-up
OSA are also used in the determination of post- polysomnogram 6–8 weeks after surgery may be
operative monitoring. For example, clinical prac- considered, depending on clinical symptoms.
tice guidelines from the American Academy of If residual sleep apnea is present after
Otolaryngology-Head and Neck Surgery recom- airway procedures, or if these procedures are
mend inpatient observation for children with contraindicated or the family desires nonsurgical
severe OSA, defined as an AHI >10 events/h management, treatment with positive airway pres-
and/or an SpO2 nadir <80% (Roland et al. 2011). sure therapy should be considered as the next step
in treatment. Typically, in pediatric patients, this
therapy is started in the hospital or sleep labora-
Treatment Options tory environment so that the optimal pressure can
be titrated. However, in some cases, empiric pres-
In cases of primary snoring or mild sleep apnea, sures may be started in the home environment.
clinical observation may be considered rather than Continuous positive airway pressure (CPAP)
surgery or treatment with positive airway is administered via a nasal or oro-nasal mask
and delivers a constant pressure which increases and then gradually increase to the prescribed set-
intraluminal airway pressure, stenting the upper ting, which may improve patient comfort.
airway open (Smith et al. 1988). In adults, there If CPAP is used, a pediatric patient should
are a large number of studies demonstrating be monitored by a pediatric pulmonary or sleep
a spectrum of improvement in clinical outcomes, medicine physician at regular intervals. While
ranging from improved cognitive function, there is no established timeline for repeat poly-
decreased daytime sleepiness, improved cardio- somnography in pediatric patients using CPAP,
vascular function, and possibly decreased mortal- pressure requirements can be expected to
ity (American Thoracic Society 1994). change over time as the patient grows or in
In children, data from several large pediatric response to underlying disease process. One
studies demonstrate efficacy of CPAP in the treat- large multicenter pediatric study found that
ment of OSA (Marcus et al. 1995; Waters et al. 22% of patients required a change in CPAP
1995). These studies include a large number of pressure over the course of the study (Marcus
patients with various co-morbidities including et al. 2006).
craniofacial abnormalities, obesity, and neurolog- Side effects of CPAP use may occur and war-
ical disorders and report that CPAP was effective rant monitoring by the patient’s care team. If
and well-tolerated in more than 80% of patients. masks are ill-fitting or too tight, skin ulceration
Similar to data regarding surgical procedures, or breakdown may occur, and therefore, attention
large pediatric studies assessing objective mea- to mask fit and skin integrity is important. Tight-
sures of treatment of OSA with positive airway fitting nasal masks may cause nasal depression or
pressure are lacking in children with cerebral changes in the growth and development of the
palsy. midface and jaw, and alignment of teeth in some
One of the largest perceived obstacles to effec- cases. Nasal symptoms, ranging from dryness to
tive CPAP use in pediatric patients is adherence congestion, are common with CPAP but often
with treatment. In one study of children with OSA amenable to changes in humidification settings.
on positive airway pressure therapy, although If patients are on overnight tube feeds or have
there was clinical improvement noted in snoring, other risk factors for vomiting at night, use of an
sleepiness, AHI, and oxygen saturations, the oro-nasal mask may be contraindicated, due to
drop-out rate was approximately 1/3 of patients, risk of aspiration, especially if the patient is
and of those who used the device, adherence unable to remove the mask.
in hours per night was low at 5.3 hours/night In patients with neuromuscular weakness
(Marcus et al. 2006). Another study, including a and underlying pulmonary disease, other forms
heterogeneous group of pediatric patients, of noninvasive ventilation may be necessary
reported varying adherence, with only 31 of to control hypoventilation. Additionally, alterna-
79 of patients showing ongoing use at follow-up tive modes of positive pressure therapy may be
(O’Donnell et al. 2006). A small retrospective necessary in patients with central apnea during
study showed that adherence to pediatric CPAP sleep who need a set back-up respiratory rate.
could be improved with behavioral techniques, if In these cases, a bi-level pressure support device
the intervention was accepted by the family (BLPAP) may be necessary. See Table 2. for more
(Koontz et al. 2003). information about different modes of noninvasive
As CPAP use can be challenging in pediatric positive airway treatment.
patients, these patients should be followed at reg- If patients are not surgical candidates for OSA,
ular intervals, and compliance from device data do not tolerate noninvasive positive pressure ther-
reviewed. Often, CPAP machines can be set with apy, or if patients need positive pressure therapy
a “ramp” setting, which allows for the machine for large portions of the day, invasive ventilation
to deliver a lower amount of pressure over a set via tracheostomy may be necessary. Tracheos-
amount of time (for example, 20 min), thus allo- tomy may be necessary to clear airway secretions
wing the patient to fall asleep at lower pressures and prevent aspiration. The decision to pursue a
Table 2 Modes of noninvasive positive airway pressure for children with cerebral palsy
Mode of therapy Acronym Prescribed settings
Continuous positive airway CPAP Constant pressure setting
pressure
Bi-level airway pressure BLPAP “BiPAP ®” Inspiratory pressure (IPAP) and expiratory pressure
(EPAP)
Bi-level airway pressure with BLPAP spontaneous-timed Inspiratory pressure (IPAP), expiratory pressure
back-up rate “ST mode” (EPAP), respiratory rate
tracheostomy requires careful consideration by American Thoracic Society (1994) Indications and stan-
the family and care team. dards for use of nasal continuous positive airway pres-
sure (CPAP) in sleep apnea syndromes. Am J Respir
In summary, children with cerebral palsy are Crit Care Med 150:1738–1745
at increased risk for OSA for various reasons American Thoracic Society (1996) Standards and indica-
including abnormal upper airway anatomy, cra- tions for cardiopulmonary sleep studies in children.
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Goldbart AD, Greenberg-Dotan S, Tal A (2012)
and underlying pulmonary and neurologic dis- Montelukast for children with obstructive sleep apnea:
ease. Medications used in children with cerebral a double-blind, placebo-controlled study. Pediatrics
palsy can also increase risk of OSA. Poly- 130(3):e575–e580
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obstructive sleep apnea on quality of life in children
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positional therapy, adenotonsillectomy and other Katz ES, Marcus CL (2014) Diagnosis of obstructive
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health consequences and improve quality of life budesonide treatment for children with mild obstruc-
in these children. tive apnea syndrome. Pediatrics 122(1):e149–e155
Koontz KL, Slifer KJ, Cataldo MD, Marcus CL (2003)
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Cross-References Sleep 26(8):1010–1015
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Part XIV
Endocrine
Short Stature in Children with Cerebral
Palsy 68
Kevin J. Sheridan
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 960
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 960
Overview of Normal Growth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 960
Measurements of Growth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 961
Growth Charts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 962
Diagnosis and Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 966
Maturational Assessments of Growth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 966
Complications (Non-nutritive Factors Affecting Growth) . . . . . . . . . . . . . . . . . . . . . . . . . . 969
Growth Hormone-IGF-1 Axis: Normal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 969
Growth Hormone Axis: Assessment in Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 971
Growth Hormone Deficiency Treatment in Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . 972
Other Non-nutritive Factors in Growth Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 973
Functional Changes with Growth . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 974
Approach to Growth Problems in Children with Cerebral Palsy . . . . . . . . . . . . . . . . . . 975
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 976
Abstract metabolism, and hormones integrate with neu-

Growth in children is complex. Externally, ronal pathways and physiology in the develop-
growth is determined by changes in height, in ing brain, allowing adaptation to the
weight, and in features of physical maturation environment and future reproductive capacity.
such as body shape, body composition, and In children with cerebral palsy, assessment
secondary sexual characteristics. Internally, of growth has several challenges. Anthropo-
growth is a churning interplay of many bio- metric measurements, for example, are difficult
chemical and physiological systems. Nutrition, to obtain because of contractures and other
bodily deformities. There are also limitations
in our understanding of how maturational
K. J. Sheridan (*) descriptors of growth such as bone age, bone
Endocrinology, Gillette Children’s Specialty Hospital, mineral density, and body composition are
Saint Paul, MN, USA
e-mail: KSheridan@gillettechildrens.com
# Springer Nature Switzerland AG 2020 959

https://doi.org/10.1007/978-3-319-74558-9_73
960 K. J. Sheridan
applied to growing children with cerebral palsy development. Clinically these patterns can be
compared to their healthier peers. divided into four periods: (1) fetus (prenatal),
It is necessary for appropriate management (2) early and late infancy (1–2 years), (3) child-
of children with cerebral palsy to be aware of hood (3–10 years), and (4) adolescence (puberty).
the subtleties in the use of modified measures Growth is most rapid (i.e., changes in size and in
of growth, in the selection of appropriate body composition) in the fetus and infancy stages.
growth charts, and in the correct treatment The childhood stage, following infancy, typically
intervention. A clearer understanding of the manifests a steadier albeit slower growth in
true health challenges the child with cerebral height, weight, and body proportions. In adoles-
palsy faces leads to better risk assessments for cence another rapid burst of growth occurs in
surgical readiness and long-term health needs. body size, body composition, and physicality. In
The overarching goal is an improvement in the all stages of growth, adequate macronutrient and
quality of life for these children as they grow micronutrient intake, efficient absorption and uti-
into adulthood. lization of these nutrients, and a robust and well-
coordinated hormonal regulatory system are
Keywords necessary.
Growth patterns · Measurements · Charts · Each period of growth differs in the expression
Growth hormone · Body composition of certain genes, which affects tissue growth and
organ maturation. Secretion of specific hormones
will effect metabolic changes upon the internal
Introduction biological milieu in terms of organ size, structure,
and function.
Growth in children is complex. Externally, growth It would be impossible to fully review these
is determined by changes in height, in weight, and factors for each stage of growth. Instead, a brief
in features of physical maturational such as body review of some of the more important aspects of
shape, secondary sexual characteristics, and body growth relevant to children with cerebral palsy
composition. Internally, growth is a churning will be presented. This will also address how the
interplay of many biochemical and physiological external manifestations of growth are assessed
systems. Nutrition, metabolism, and hormones and used to differentiate “normal” from “dysfunc-
integrate with neuronal pathways and physiology tional” growth.
of the developing brain, allowing adaptation to the
environment and future reproductive capacity.
This chapter will discuss these influences in Natural History
both typically growing children and in children
with cerebral palsy. Overview of Normal Growth
Growth is not a smoothly continuous process.
It is discrete with periods of more rapid change Adequate macronutrient and micronutrient intake
alternating with periods of relative stasis. This are the most important determinant of growth,
occurs throughout the years of the developing apart from preordained genetic influences. Classi-
individual into adulthood. Even in adults there cally, it is the most likely cause of poor growth in
are changes in body composition and function chronically ill children or those with developmen-
which, although not usually considered a part of tal challenges such as cerebral palsy. As new
“growth,” nevertheless are necessary for the envi- techniques to better assess and provide appropri-
ronmental adaptation and reproductive potential ate nutrition have developed over the last few
of the individual. decades, other non-nutritive causes of poor
Superimposed on these short-term growth growth in children with cerebral palsy have
fluctuations are longer periods of growth with emerged. The following is a brief review of
patterns unique to stages of childhood some of these non-nutritive factors.
68 Short Stature in Children with Cerebral Palsy 961
For adequate growth to occur, the internal hor- also has a permissive effect on growth hormone
monal and metabolic milieu must be optimal. secretion.
Inflammatory diseases, infections, and neuropa- The sex steroids are secreted in the fetus and
thologies can all significantly alter this by limiting have implications for the maturation and develop-
nutrient utilization and transport. Abnormalities ment of secondary sexual characteristics in the
in non-volitional energy expenditure may occur male and female. The effect of estrogens and
in movement disorders, seizures, and spasticity. testosterone on growth during the childhood
The metabolic impact on cardiac, skeletal, and years is minimal. The resurgence of these hor-
smooth muscle activity and morphological mones in adolescence and their influence on
changes in the skeletal system may lead to dys- growth hormone secretion result in major physical
functions in cardiovascular, pulmonary, and gas- changes in body size, body composition, and sex-
trointestinal systems. ual differentiation in the adolescent.
Once these stressors are addressed, hormonal Throughout this time, however, external (i.e.,
regulation becomes the next most important fac- physical) assessments of growth are primary tools
tor influencing growth. The somatotropin or for clinicians and parents to determine adequate
growth hormone (GH)/insulin-like growth growth. Therefore, periodic measurements of
factor-1 (IGF-1) axis and the thyroid-stimulating body size (e.g., weight, height, body proportions)
hormone (TSH)/thyroxine (T4) axis are major and assessments of maturational changes (e.g.,
hormonal regulators of growth throughout child- bone age and pubertal Tanner staging) occurring
hood even into adulthood. Sex hormones (estro- throughout growth require as much accuracy and
gens and androgens) become increasingly precision as possible. This, at times, may be chal-
important in adolescence. They are also determi- lenging even in the typically growing child. It
nants of body composition throughout depends upon the child’s cooperation and the
adulthood. measurer’s expertise. It is more difficult, yet
Growth hormone secretion is regulated in the more important, when children with chronic ill-
hypothalamus and pituitary by multiple neurolog- nesses (e.g., cerebral palsy) are involved.
ical pathways. The secretion of GH varies in Much has been published over the years about
amplitude and frequency from the fetal period how to obtain consistent, reliable, and meaningful
through adolescence. measurements. Recommendations for obtaining
Growth hormone secretion is first detected in these measurements are not, however, always
the fetus at 9 weeks of age. Its importance for fetal followed, even for typically growing children.
growth and early infancy is much less than in later Children with challenging body shapes (e.g., in
infancy and childhood. Significant increases in syndromes, neuromuscular diseases, contractures,
the amount and frequency of growth hormone movement disorders, and other dysmorphologies)
secretion are subsequently seen in adolescence, present greater difficulties in obtaining accurate
accompanied by major changes in the physical and precise measurements.
appearance of the body. Some of this growth
hormone secretion is facilitated by the rising
levels of sex steroids from the maturing gonads. Measurements of Growth
Growth hormone secretion wanes throughout
adulthood but remains important for lifelong opti- Pre-gestationally, the fetus can be measured by
mal body composition. ultrasonography from which are obtained crude
Thyroid hormone likewise is critical for nor- “external estimates” of adequate growth prior to
mal growth and development prenatally and birth.
through infancy, childhood, and adolescence. In the postnatal infant and up to 2 years of age,
The changes in thyroid hormone secretion are length, weight, and occipital frontal head circum-
not as dramatic during these growth periods as ference measurements are the most useful deter-
they are for growth hormone. Thyroid hormone minants of growth. Sitting heights, arm spans, and
962 K. J. Sheridan
other body proportion assessments are supportive. Equations are then used wherein the segment
Precision and accuracy can be approached using a measured is the variable and an “expected” height
standardized length assessment technique. The from that measurement is calculated (Chumlea
use of a rigid headboard and movable foot board et al. 1994; Stevenson 1995). One must remem-
while attending to the “Frankfurt” plane ber, however, that only the growth of that segment
(an anatomic position in which a line connecting is measured and extrapolated to the rest of the
the outer canthus of the eyes and the external growing bones (in children).
auditory meatus is perpendicular to the long axis The equations were first developed from a
of the trunk) is recommended. large cohort of children using data from the
In childhood, that is, after 2 years of age, National Health and Nutrition Examination
standing heights are obtained using this same Surveys I, II, and III, which included 13,821 chil-
Frankfurt plane with the child’s feet together and dren (Chumlea et al. 1994). In growing children
the heels, buttocks, and occiput of the head touch- without cerebral palsy, these equations should
ing a perpendicular wall or measuring implement. closely predict their actual measured height.
This improves both accuracy and precision of the Knee heights, tibia lengths, and upper arm
measurements. A “Harpenden” stadiometer is ide- lengths were also used to measure individual
ally used for these measures as it requires less bone growth in a subset of children with cerebral
calibration and is less subject to mechanical palsy. The calculated statures (estimates of a “vir-
wear. Three heights should ideally be obtained tual” height assuming they were otherwise
and not vary more than 0.3–0.5 cm before an healthy) were plotted on standard growth charts.
average is calculated. A minimum of 3 months This “virtual” height can be plotted more readily
and ideally 6 months should occur between suc- on standard growth charts for easy visualization
cessive measurements. but is not meant to give a true height or length in
This holds true in the adolescent years as well. that child (Stevenson 1995).
(Sperling 2002, p. 212).
These measurements can then be plotted on
growth charts, which are based on an age- and Growth Charts
sex-matched patient population.
Children with cerebral palsy have varying In most primary care clinics (in North America
degrees of spasticity and deformities due to con- and elsewhere), children are measured for height,
tractures and abnormal bone shape. This makes weight, body mass index, or weight for height
attainment of acceptable heights or lengths diffi- which is then plotted on standardized growth
cult. Measuring lengths by a “top-to-bottom” or charts. The Center for Disease Control and Pre-
“bottom-to-top” segmental approach (e.g., from vention (CDC) recommends growth charts devel-
head to lower leg or the reverse) is inaccurate oped by the World Health Organization (WHO)
and imprecise, unless radiographs are used to for children ages 0–2 years. For children ages
define the beginning and end of each segment. 2–20 years, the CDC recommends using the
This is not practical in the clinical setting. National Center for Health Statistics (NCHS)
Individual body segments are useful in growth charts adopted in 2000 and based upon
assessing length growth, as they are not affected cross-sectional data from the NCHS (introduced
by joint contractures. Such examples include tibia in 1977). These were based upon (1) private infant
lengths (lower end of the lateral malleolus to data collected in the early 1900s which included
upper protrusion of the tibia condyle), knee formula-fed babies and (2) government-collected
heights (heel to above the knee in a 90-degree data from older children (ages 2–18) from the
flexed position), and upper arm lengths (lower National Health and Nutrition Examination Sur-
lateral epicondyle to proximal end of the veys in the 1960s through the 1990s. From these
humerus). These are measurements easily charts, Z-scores (i.e., age-adjusted standard devi-
obtained in typically growing children and adults. ations) can be obtained for height, weight, and
body mass index (BMI). Z-scores facilitate growing children, many will fall far below the
growth comparisons among different populations. expected channels. This can blur any ability to
These charts are limited by their ability to distinguish additional growth insults (such as hor-
satisfactorily define growth below the third per- monal deficiencies, chronic inflammatory states,
centile or above the 97th percentile. It is charac- and catabolic stresses) from the already
teristic of many children with cerebral palsy to compromised growth due to the neuromuscular
grow at or below the third percentile. To better insults.
understand these growth patterns, charts have However, there is disagreement among clini-
been constructed specifically for children with cians and researchers as to the usefulness of such
cerebral palsy. “cerebral palsy-specific” growth charts. There is a
The cross-sectional data from these CDC clinical distinction made between “prescriptive”
charts work well in infancy and childhood before and “descriptive” growth charts. “Descriptive”
the variable times of pubertal onset. However, growth charts based upon subsets of children
since puberty begins at different ages in normally with particular health issues recount or describe
growing children, cross-sectional data lead to a growing subset, whereas “prescriptive” growth
greater variance. charts present optimal growth patterns of a child
Longitudinal growth charts have been devel- without additional health challenges. This distinc-
oped to accommodate this variability and in fact tion and its ongoing debates raise difficult but
are better for adolescent growth assessment (Tan- interesting questions as to how to provide the
ner and Davies 1985). best care for children with cerebral palsy.
Weight growth charts can be used to study For the typically growing child, the terms have
short-term health challenges a child may experi- no real meaning as they are one and the same,
ence (e.g., acute short-term illnesses, nutritional unless one assumes that a prescriptive growth
compromises). In contrast, the height growth chart will better account for ethnic, cultural, and
charts are used to assess chronic illness, hormonal economic diversity. This distinction becomes
perturbations, or other metabolic aberrations of more important for children with chronic condi-
growth over longer periods. tions such as lifelong neuromuscular disease.
Recent surveys have included more ethnic and Growth charts specific for children with cere-
cultural diversity from which the population data bral palsy in North America were developed in the
are derived. latter part of the last century from which modifi-
Disease specific growth charts have also been cations and refinements were introduced over
developed for such conditions as Turner’s syn- time (Krick et al. 1996; Stevenson et al. 1995,
drome, Down’s syndrome, achondroplasia, and 2006; Kuperminc 2006; Day et al. 2007; Brooks
prematurity. Given the smaller study subject num- et al. 2011; Araujo and SIlva 2013; Wright et al.
bers and less ethnic and cultural diversity in dis- 2017).
ease specific populations, these charts may not be These attempts at defining growth, descrip-
as statistically representative of the larger popula- tively, in children with cerebral palsy had to
tion they represent. account for the following: (1) growth characteris-
In children with cerebral palsy, measurements tics dependent upon the severity of the disability,
had been obtained and used in the construction of (2) associations of poor growth with increased
growth charts for weight, height/length, and knee healthcare use and decreased social participation
height. The goal was to describe growth patterns outcomes, (3) observations that weight at different
for these children which are, ideally, controlled for levels of gross motor functioning (GMFCS class)
nutritional status. Deviations from these patterns had associated morbidities and mortality hazard
would then help address other serious ratios, and (4) effects of the neurological injury
comorbidities in the growing child. pattern (e.g., spastic quadriplegia, diplegia, hemi-
If children with cerebral palsy are plotted on plegia) on the pattern of growth (Stanek et al.
the standardized CDC growth charts for typically 2016).
964 K. J. Sheridan
Table 1 Studies-examples of cerebral palsy growth charts

Study Year(s) Measure #Subjects Ages Severity Country
Krick 1996 Wt, Ht 360 2–12 SQ USA
Stevenson 1995 Wt, Ht 172 5.4 3.5 Varied USA
KH, TL, UAL
Stevenson 2006 Wt, Ht, KH 273 2–19 III–V USA
Day 1988–2002 Wt, Ht 24,920 2–20 I–V USA
Brooks 1988–2002 Wt 25,595 2–20 I–V USA
Aruajo 2012 Wt, Ht, KH 187 2–16 “Spastic” SA
Wright 1997–2013 Wt, Ht 195 2–17 I–V UK
Wt weight, Ht height or length, KH knee height, TL tibia length, UAL upper arm length, SQ spastic quadriplegia, I–V
GMFCS level I–V, USA (United States), UK United Kingdom
The following table summarizes some of these palsy were lower on the growth charts than
studies (Table 1). were the prepubertal girls with cerebral palsy.
Krick et al., one of the earlier groups, devel-
oped growth charts for children with cerebral Other growth charts for children with cerebral
palsy. In their paper they reviewed 40 years of palsy were subsequently developed. Each had a
research studies involving growth data of chil- unique contribution to their overall applicability
dren with cerebral palsy (Krick et al. 1996). They in clinical practice. A few of these are described in
cited 14 studies from 1953 to 1993 which more detail to highlight their contributions.
addressed the growth of these children. From 1987 to 2002, Day et al. studied a large
Although these studies were few and sample population of American children with cerebral
sizes small, most characterized the growth of palsy (24,920) in the state of California (Day
children with cerebral palsy as lighter (weight) et al. 2007). The age range was 2–20 years.
and shorter (length) than their healthy peers. Anthropometric data collected from these chil-
Krick and colleagues constructed growth charts dren were used to construct weight, height, and
specific for these children, particularly for those BMI growth charts. This large cohort was also
with spastic quadriplegia. stratified according to gross motor skills and feed-
Weight and length data from 360 children, ages ing ability. They were five levels of “severity”
0–10 years with spastic quadriplegia, were used in which overlapped the GMFCS classification
the chart construction. scheme.
The following observations were made: The following groups were defined:
1. The 50th percentile for height and weight of Group 1 – walks well for 6 m (approximating
the cerebral palsy growth charts was consis- GMFCS class I)
tently less than the 10th percentile of the Group 2 – walks with support for 3 m
National Center for Health Statistics (NCHS) Group 3 – cannot walk but may move with creep-
charts for typically growing children in use at ing or crawling
the time. Group 4 – unable to move on their own; oral
2. As the children aged, the more they deviated intake but does not feed self
from the normal growth charts. For example, at Group 5 – same as group 4 but fed through G-tube
age 2 years, 5% of children were shorter than
their healthier peers, whereas at age 8 years In girls, the weight curves from group 1 devi-
10% were shorter. ated only slightly from typically growing girls
3. Compared to their sex-matched peers without across all ages, even at age 20. Although boys
cerebral palsy, prepubertal boys with cerebral showed a similar pattern at the younger ages,
their curves fell farther below the norm at older 25,545 Californian children with cerebral
ages. In group 2, boys and girls showed discrep- palsy representing all levels of GMFCS classifi-
ancies in weight from typically growing children cation were assessed. Statistical associations
at all ages, worsening as they grew older. among weight centiles and the morbidity and
Groups 3 and 4 fell even further from the norm mortality descriptors were quantified.
showing a linear adolescent growth pattern rather The new charts that were constructed helped to
than the expected exponential increase seen in identify potentially unhealthy low weight. The
typically growing children. That is, the typical goal with this approach was to help clarify
growth spurt of adolescence was not seen. This “ideal” (i.e., prescriptive) growth for these chil-
has implications for dysfunction of puberty and dren with cerebral palsy. Defining a “healthy”
GH secretion in this group. population is difficult and is subject to conflicting
The overall pattern of weight gain was similar interpretations. Growth thresholds associated with
in the more severely involved children (groups bad health is considered a more realistic clinical
4 and 5). However, those who were fed through approach. Thus “healthier” children with cerebral
a gastrostomy tube were consistently 2–5 kg palsy would be above these thresholds (Stevenson
heavier than those without a feeding tube. et al. 2006; Samson-Fang et al. 2002).
The height growth pattern paralleled that for In addition to classifying gross motor function-
weight, but the deviation from normal was sur- ality, GMFCS V was further divided into those fed
prisingly less. In general, those with a feeding with a gastrostomy tube and those fed orally.
tube consistently showed greater weight and Chronic morbidities (including diabetes
height compared to those orally fed, no matter mellitus, hypertension, congenital heart disease,
the severity of motor dysfunction. atherosclerotic cardiovascular disease, respiratory
The growth curves from this large cohort were infections, and other dysfunctions) were
compared to the earlier ones from Krick’s smaller described for each GMFCS level and for the
population of children with cerebral palsy. tube-fed GMFCS class V cohort. Comparison
There were some minor discrepancies due to between the number of chronic medical condi-
the differences in the extent and severity of the tions for children in the extreme weight quintiles
motor involvement between the two populations. (< 20th, >80th) and those in the middle three
For example, the category of spastic quadriplegia quintiles (20–40th, 40–60th, 60–80th) was
was slightly different between the two studies. In assessed statistically with t-tests. Mortality esti-
the larger Californian population, spastic quadri- mates for these weight centiles were also
plegia included children with cerebral palsy who calculated.
had some neuromuscular involvement in all four The mean number of chronic major medical
limbs regardless of the level of overall motor conditions increased moderately with the
dysfunction. Some of these subjects were there- GMFCS level. There was a notable difference in
fore less severely affected compared to Krick’s those who were fed through a gastrostomy tube in
smaller population. that the tube-fed children had twice as many major
The ability to use these weight growth curves medical conditions compared to those in the same
in this California population of children with cere- GMFCS level without a tube. It was unclear
bral palsy to assess overall health was further whether tube feeding was simply a marker for
refined in a study by Brooks et al. These investi- more medical problems in this group. In addition,
gators developed a model which superimposed children with GMFCS I–IV and V without a
morbidity and mortality statistics upon weight gastrostomy tube who had weight below the
growth curves (Brooks et al. 2011). Weight 30th percentile clearly demonstrated a greater
growth charts were then reconstructed based number of comorbidities than those who had
upon these health associations. (This was the weighed more.
same California population of children with cere- Mortality overall was 9 individuals per 1000
bral palsy.) person-years for GMFCS III–IV with weights less
966 K. J. Sheridan
than the 20th percentile and 26 per 1000 person- Patterns of healthcare use and social interac-
years in level V (tube fed). tions from the 4 weeks preceding the measure-
The modified weight growth charts which ments were described. Correlations were made
superimposed morbidity and mortality statistics among these measures. Three groups of combined
upon weight growth curves can be found at the anthropometric measurements stratified by their
following source: standard deviation from the mean were defined.
The “smaller” group averaged one standard devi-
http://www.lifeexpectancy.org/articles/newgrowth ation or less below the mean; the “middle” group
charts.shtml comprised those who were between one standard
deviation below and one standard deviation above
These modified weight charts improved the the mean; and the “larger” group was one standard
usefulness of the so-called descriptive weight deviation or greater above the mean. For each of
growth charts in these children. This improved the anthropometric measures, the “larger” group
the clinical usefulness of weight assessment for of children had better health and social participa-
at-risk individuals (Day 2017). tion than the “smaller” group of children.
Another approach linking growth charts in A common observation in all these studies was
children with cerebral palsy to important health that as children with cerebral palsy age, variance
outcome measures was explored using another from the typically growing population increases.
large registry of children involved in the North Other subtypes of cerebral palsy, e.g., diplegic
American Growth in Cerebral Palsy Project or hemiplegic cerebral palsy, may also demon-
(NAGCPP). Stevenson et al. in a cross-sectional strate differences from those with spastic quadri-
study in the early 2000s used a subgroup of chil- plegia. Height and weight of children with spastic
dren from this six-site multicentered regionally quadriplegia were consistently lower than those
based group. Anthropometric data were studied with hemiplegia and diplegia. Children with
in relation to healthcare use and social participa- hemiplegia had a greater height and weight com-
tion parameters (Stevenson et al. 2006). pared to other subtypes (Stanek et al. 2016).
273 children representing GMFCS II–IV, ages
2–18 years, were used as reference data. Growth
curves were constructed for each of six anthropo- Diagnosis and Treatment
metric measurements in these children. These
included knee height (KH), weight, upper arm Maturational Assessments of Growth
length (UAL), mid-upper arm circumference
(MUAC), subscapular skinfold thickness (SUB), Growth has an effect not only on size measure-
and triceps skinfold thickness (TR). The growth ments (weight, stature, head circumference) but
charts for each of these anthropometric measure- also on the physical features of maturation. These
ments were superimposed upon the CDC growth maturational changes are more difficult to assess
charts. The weight and length growth patterns for than changes in size measurements.
prepubertal boys and girls corroborated the earlier Bone, of course, is the most obvious body
cerebral palsy growth charts of Krick et al. Weight tissue involved in overall growth. But muscle,
and length deviated from the standard growth curves adipose tissue, and many organs (especially the
for both boys and girls up to age 10 years. There was brain and nervous system) also contribute to the
a further decline throughout adolescence. This trend growing child both in terms of weight and matu-
was similar for all the measurements studied. Knee rational change. Measuring the changes in tissue
height, however, in the prepubertal children with composition, shape, and organ interrelationships
cerebral palsy showed the greatest deviation from (e.g., due to developing neuronal and hormonal
typically growing children, which worsened interconnections) are means of assessing this
throughout the pubertal years. “growth” component.
For example, bone age determination by radi- Patterns of skeletal growth in these studies are
ography assesses predictable changes in the pres- conflicting in that they may describe skeletal ages
ence and shape of upper extremity structures that are delayed, normal, or advanced compared to
during growth with implications for other bones. the chronological age. This discrepancy between
Bone composition as calcium content and den- bone age and chronological age in some cases
sity can be measured using bone densitometry depends upon the GMFCS level of function. For
(techniques include DXA, quantitative CT, MRI, example, in more involved (i.e., severe) cerebral
ultrasound). Body composition in terms of fat and palsy, there appears to be a delay in bone age
lean body mass can be described with techniques compared to typically growing children, whereas
from DXA scans, skinfold thicknesses, and in a more ambulant cerebral palsy population, the
mid-arm circumferences, as examples. These bone ages tended to be more advanced.
techniques have been used with variable success In a group of 100 Dutch children, aged
in a typically growing child. There are more chal- 9–16 years, the skeletal age (using the Atlas and
lenges, however, in the growing child with cere- method of Greulich and Pyle) was followed over
bral palsy. 3 years (van Eck et al. 2006). This was a longitu-
dinal study examining the changes over time in
Bone Age bone age relative to chronological age and
The relationship between long bone growth (e.g., GMFCS level. Their observations did not support
stature) and bone maturation (e.g., skeletal age) is previous concerns that pubertal skeletal matura-
easily understood from our knowledge of how tion worsens gross motor functioning. There was
bone length increases in childhood. The growth a high prevalence of subjects that had more than
potential of the diaphysis depends on the progres- 1-year delay or advance in skeletal age compared
sion of ossification within the epiphysis. The to chronological age. That is, approximately
growth potential of the bone therefore can be 40–50% of these Dutch children had a bone age
assessed by the degree of ossification of the epiph- deviation. Girls had a statistically significant
yses. The shape of the long bone of the phalanges increase of 0.69 years at all time points measured
and the carpal bones of the hand also change (i.e., in the first year, the bone age was measured
predictably as a child grows. The first standards and in each subsequent year thereafter for
for skeletal age were established by Todd in 1937 3 years). There was no difference for the boys.
and later refined by Greulich and Pyle (1959). Other studies support this observation of
These are available in an atlas that describes the greater deviation in bone age from chronological
characteristics of individual bones in girls and age compared to a typically growing population.
boys at different ages (from age 2–19). They However, estimates of prevalence vary. For exam-
were based on presumably healthy North Ameri- ple, Kong et al. (1999) in children with cerebral
can Caucasian children in the early part of the palsy found 68% of their study group with a delay
twentieth century. There is minor variability in of greater than 1 year in skeletal maturation. In the
the maturational sequence in some racial and eth- above Dutch study, only 11–32% had such a delay
nic groups. Overall this has been a powerful tool in bone age. Conversely, Gollapudi et al. noted
in predicting bone growth and pubertal 94% of ambulatory children with cerebral palsy
maturation. had an advanced skeletal maturation (in fact 35%
There is disagreement, however, as to the use- were advanced more than 3 years) (Gollapudi
fulness of these bone age tools when applied to et al. 2007).
children with chronic illnesses. It is difficult to compare these studies. They
The application of the technique of bone age differed in (1) age ranges (9–16 years of age in the
has been studied in children with cerebral palsy van Eck group and 2–16 years of age in the
(Kong et al. 1999; Henderson et al. 2005, 2005; others), (2) stages of pubertal development, and
Gilbert et al. 2004; Gollapudi et al. 2007). (3) techniques of assessing skeletal maturation.
968 K. J. Sheridan
A unique contribution of the van Eck Dutch purchase of an expensive machine. Skinfold
cohort was the study design in which changes thicknesses are easier to obtain and provide no
were described longitudinally over a 3-year risk to the subject but rely upon previously devel-
period (between the chronological ages of oped equations from which are derived % body
12 and 16 years). The bone age in relation to fat. These equations were constructed from stud-
chronological age did not differ by sex (corrected ies in typically growing children.
for age and level of ambulation) or by ambulatory
ability (corrected for age and sex). Nor was there Body Composition: Skinfold Thickness
any difference between changes in bone age and Skinfold thickness is a noninvasive anthropomet-
changes in gross motor function over this period. ric measurement without exposure to X-rays that
requires only a good-quality skinfold caliper and a
Body Composition: Overview trained, experienced measurer. Slaughter et al.
Assessment of body composition can be a very published equations (now known, conveniently,
helpful measure of growth in all children. Body as the “Slaughter” equations) which are used to
composition reflects the combined effects of nutri- estimate % body fat in healthy children (Slaughter
tional status, internal hormonal and metabolic et al. 1988).
orchestration, and environmental “insults” In typically growing children, there is reason-
influencing growth. able agreement between estimates of % body fat
However, maturational growth is much more using skinfold thickness with the Slaughter equa-
difficult to assess and quantify than the more tions and the DXA method, except in some pre-
simply measured weights and lengths. It requires pubertal African-American children. Separate
assumptions about the physiological relationship equations were developed for (1) “small” individ-
between body composition and growth character- uals (whose triceps and subscapular skinfold
ized in typically growing children and the appro- thickness sums are less than or equal to 35 mm),
priateness of applying these observations to (2) “large” individuals (whose sums are
children with cerebral palsy. >35 mm), (3) males, (4) females), (5) race in
There are several techniques used to detect small males, and (6) pubertal status in small
body composition. Although bone mass and lean males.
body mass are important, it is the body fat mass Studies of the prediction of % body fat in
(e.g., expressed as % body fat) that may be the children with cerebral palsy exist. Most of these
most helpful in the clinical assessment of healthy studies were based on a small number of subjects.
growth. It is also the most labile of the body They generally agree, however, that the Slaughter
compartments. equations tend to underestimate the % body fat in
Examples of some techniques used in measur- children with cerebral palsy compared to DXA or
ing body composition include impedance plethys- deuterium dilution techniques.
mography, deuterium dilution, dual-energy Gurka et al. in 2009 studied the applicability of
absorptiometry, and skinfold thickness the Slaughter equations to children with cerebral
measurements. palsy. Seventy-one children with cerebral palsy at
Some of these techniques are used in research GMFCS level I–V (Gurka et al. 2010) and
settings and tend to be cumbersome, expensive, between the ages of 8 and 18 years were subjected
and inconvenient in a busy clinical practice. to % body fat estimates using triceps and sub-
More applicable to clinical practice is the use scapular skinfold thicknesses. These were com-
of dual-energy X-ray absorptiometry and skinfold pared to % body fat estimates obtained from DXA
thicknesses to describe body composition com- analysis.
partments (i.e., % body fat, lean body mass, and The % body fat from skinfold thickness again
bone mineral content). supported previous observations of a 0.6%
DXA is a noninvasive technique. However, it underestimation when compared to DXA
does involve X-irradiation and an upfront analyses.
A model was developed that incorporated the It is interesting that DXA assessment of body
factors which may have compromised this rela- composition is commonly used as a standard to
tionship. The following were considered impor- compare other similarly noninvasive means of
tant contributors to the differences: sex, GMFCS, obtaining body composition.
pubertal status, race, and size. Correction factors
were computed and used to modify the original
Slaughter equations. These corrections signifi- Complications (Non-nutritive Factors
cantly improved the agreement between estimate Affecting Growth)
of % body fat using the skinfold thickness and
DXA techniques. Compromises in nutrition (food availability, intake,
digestion, absorption, and utilization) and energy
Body Composition: DXA Technique metabolism (energy expenditure in movement dis-
The use of DXA in the evaluation of bone health orders and degrees of spasticity) have classically
in children with cerebral palsy is discussed more been the most likely contributors to poor growth in
fully in another chapter in this book (▶ Chap. 26, children with cerebral palsy. Over the last few
“Managing Bone Fragility in the Child with Cere- decades, however, greater use of enteral nutrition
bral Palsy”). through gastrostomy tubes and closer attention to
In addition to assessing bone mineral content nutritional needs have lessened this impact on
and bone mineral areal density, DXA has also growth. However, despite this, these children still
been used as a noninvasive and less cumbersome grow more slowly, are shorter, and attain subnor-
means of assessing body composition in children mal adult height. Thus, interest in non-nutritive
and adults with cerebral palsy. factors that affect growth has increased.
DXA exposes the individual to a very low Factors such as flexor muscle and tendon short-
level of radiation. Body composition estimates ening and spinal growth abnormalities with
from DXA are based upon the ratio of low- to kyphosis and scoliosis (which are common to
high-energy X-ray attenuation in soft tissue cerebral palsy individuals as they grow) play a
compared to bone from which can be derived role in this attenuated growth. However, they are
estimates of fat mass, fat-free mass, and bone lesser contributors to the overall effect on linear
mineral content. growth than hormonal factors.
Many studies using isotope dilution techniques Hormonal control of growth and its dysfunction
and body carcass analysis have demonstrated a are probably more important non-nutritive influ-
good correlation to the DXA technique of ences on growth in children with cerebral palsy.
assessing body composition. DXA also has excel- There has been a significant interest in the disrup-
lent reproducibility (Liu et al. 2005, p. 794). tion of pituitary-related hormonal systems such as
In 2005 Liu et al. determined correlation coef- the growth hormone-IGF-1 axis, the hypothalamic-
ficients between measurements of body composi- pituitary-thyroid axis, and the hypothalamic-
tion (fat mass, fat-free mass, and % body fat) pituitary-gonadal axis. These systems may be dam-
using body impedance plethysmography (BIP) aged in some of these brain-injured children.
compared to DXA and anthropometric skinfold
thickness assessment compared to DXA. There
was excellent correlation for fat-free mass Growth Hormone-IGF-1 Axis: Normal
among all methods. There was moderate correla-
tion when fat mass and % body fat measurements Growth hormone is secreted by the somatotroph
were undertaken. BIP correlated better with DXA cells in the adenohypophysis (anterior pituitary)
for fat mass than the skinfold anthropometry and is regulated by multiple CNS peptides, hor-
method, whereas skinfold thickness estimates of mones, neuronal pathways, and physiological fac-
% body fat were slightly better than BIA estimates tors. These factors alter growth hormone-
when compared to DXA. releasing hormone (GHRH) and somatostatin
970 K. J. Sheridan
Growth Hormone Axis

GHRH Somatostatin
Muscle
GROWTH
HORMONE
IGF BP3 Bone
IGF-1
Adipose
secretions from the hypothalamus. GHRH stimu- suppression of growth hormone by oral or inhaled
lates growth hormone synthesis, maturation, and steroids. Growth may also be affected indirectly, for
secretion from the pituitary. Somatostatin, on the example, by side effects of antiseizure medications
other hand, inhibits growth hormone secretion. on sodium, calcium, and glucose balance.
Somatostatin is secreted in a reciprocal fashion Secreted growth hormone has many effects on
with GHRH to cause the episodic (i.e., pulsatile) organ systems and metabolic pathways, usually
bursts of growth hormone throughout the day. mediated by insulin-like growth factor-1 (IGF-1),
There are many other neurotransmitter and a liver-synthesized protein. The growth hormone-
neuropeptide influences on this reciprocal rela- stimulated IGF-1 then exerts a negative feedback
tionship. Serotonin, norepinephrine, dopamine, on growth hormone secretion at the level of the
ADH, GABA, neuropeptide Y, and arginine are hypothalamus and pituitary. IGF-1 exerts its big-
a few examples. gest effect on the skeleton, particularly in chil-
Physiological factors affecting growth hor- dren, at the growth plate.
mone secretion include stress, exercise, hypogly- IGF-1 is itself transported in the plasma by a
cemia (e.g., insulin induced), hemorrhage, and binding protein that regulates its availability. The
fasting. Testing for growth hormone deficiency most abundant binding protein is IGFBP3 pro-
takes advantage of these effects. For example, duced in the liver. It is also dependent upon
arginine, dopamine, clonidine, glucagon, and growth hormone for its production. Therefore, in
insulin-induced hypoglycemia all increase growth children, a good screening assessment for the
hormone secretion. Standardized expected peak somatotropin axis would be assessing blood levels
increases of growth hormone are used to “define” of GH, IGF-1, and IGFBP3.
adequate growth hormone secretion and, in their GH secretion is first noted in the fetus at
absence, growth hormone deficiency syndrome. 9 weeks of gestation. During pregnancy and in
Many children with cerebral palsy have the first postnatal year, the influence of growth
comorbidities such as restrictive and obstructive hormone is less important compared to later years.
lung disease, seizure disorders, and dysautonomias. Growth hormone secretion in childhood is
Some of these conditions as well as the pharmaco- characterized by pulsatile bursts throughout a
logical agents used in treatment, may affect the 24-h period with the maximal number of secretory
growth hormone axis directly, for example, through bursts occurring at night (especially at the onset of
slow wave sleep, stages III and IV). Sleep distur- in IGF-1 production despite normal to elevated
bances, common in children with cerebral palsy, growth hormone levels. Once malnutrition and its
may modify these bursts. effect on growth hormone secretion are addressed,
The 24-hour secretion of growth hormone there still may be dysfunction in the somatotropin
increases throughout adolescence, begins to fall axis.
in late adolescence, and continues a slow decline Multiple studies have examined the role of
through adulthood. growth hormone and its possible dysfunction in
Normal young men experience 12 growth hor- children with cerebral palsy since the 1990s.
mone secretory bursts in a 24-h period (or approx. These studies were small in sample size and var-
0.35–0.52 mg growth hormone/m2). iable in subject characteristics and study design.
Throughout this time, however, growth hor- Generalizing to the larger population of children
mone secretion is accompanied by a parallel rise with cerebral palsy from these studies is challeng-
in IGF-1. In fasting states and obesity, growth ing. They vary in age, pubertal stage, and method
hormone and IGF-1 are inversely related, of growth hormone assessment (e.g., use of insu-
suggesting a feedback effect of IGF-1 in the hypo- lin induced hypoglycemia or pharmacological
thalamic and pituitary control of GH secretion. In agents to assess stimulated growth hormone
fasting or nutritionally compromised states, IGF-1 secretion).
is low with growth hormone normal to high, Although the prevalence of growth hormone
whereas in obesity growth hormone may be low deficiency cannot be generalized from these
while IGF-1 levels are adequate. studies, they do suggest that some form of
In general, the effects of growth hormone can growth hormone dysfunction is more likely in
be summarized as follows: children with cerebral palsy than in a healthier
population.
1. Physeal (growth plate) differentiation and In 1989 Hayashi reported four children with
epiphyseal/metaphyseal growth. cerebral palsy who had subnormal growth hor-
2. Bone mass increase accompanied by increased mone responses to clonidine and seven children
osteoblast activity and endochondral bone with inadequate response to GHRH (Hayashi
formation. et al. 1989). In 1996 Coniglio et al. reported six
3. Acute insulin-like effects in the adipose tissue, out of 10 children with cerebral palsy and growth
mediated through IGF-1, with storage of tri- failure who had abnormally low spontaneous
glycerides, followed by subsequent lipolysis. growth hormone secretion and subnormal growth
4. Increase in muscle mass and energy hormone release in response to stimulants
expenditure. (Coniglio et al. 1996).
In a group of 50 Egyptian children, ages
Growth hormone overall favors nitrogen reten- 3–11 years, Hamza et al. in 2011 described
tion and can have anti-insulin effects resulting in growth hormone deficiency in 52% of these chil-
increased glucose blood levels. IGF-1, paradoxi- dren (Hamza et al. 2011). This was based upon a
cally, may have glucose-lowering effects. lack of peak growth hormone response (i.e., at
least to 10 ng/ml) to insulin-induced hypoglyce-
mia. They also noted that 62% had lower IGF-1
Growth Hormone Axis: Assessment and IGF-binding protein-3 levels compared to
in Cerebral Palsy age-, sex-, and puberty-matched controls.
Stimulation of growth hormone by provocative
The somatotropin axis is an important hormonal testing with insulin-induced hypoglycemia is con-
component of growth in typically growing chil- sidered by many to be the “gold” standard of
dren and has also been studied in children with defining growth hormone deficiency. Deficiency
cerebral palsy. Malnutrition has a large impact on is generally defined by peak secretion of growth
this axis, which may result in a profound decrease hormone of less than 10 ng/ml.
972 K. J. Sheridan
The perception of growth hormone dysfunc- for a slightly higher risk of leukemia in a Japanese
tion in many of these children with cerebral palsy population has been discounted by wider and
led, naturally, to an interest in treatment with geographically more diverse studies (Allen et al.
exogenous growth hormone. 1997; Nishi et al. 1999).
Although the use of growth hormone to treat
deficiency is clear, it may also be beneficial (and
Growth Hormone Deficiency Treatment is, in some of these cases, approved for use) in
in Cerebral Palsy such medical conditions as Turner’s syndrome,
Prader-Willi syndrome, and children who had
Growth hormone replacement has successfully experienced intrauterine growth retardation. Idio-
restored normal growth and led to acceptable pathic short stature was previously accepted in
adult stature in children considered growth hor- many countries as an indication for treatment,
mone deficient. Growth hormone has been used although its effect on adult height varies.
since the 1950s when human pituitary extracts The most important benefit of growth hormone
were isolated and given to growth hormone- is an improvement in height growth and eventu-
deficient individuals. More than 27,000 children ally adult stature. Other benefits, however, may
were treated worldwide with this extract. Unfor- include favorable changes in body composition
tunately, in the 1980s, a causal relationship with (lower fat mass and more muscle mass), muscle
the use of these extracts and Creutzfeldt-Jakob strength, and bone mineral density and, in some,
disease (a rare and fatal spongiform encephalopa- quality of life measures.
thy) was suggested. Its use therefore was halted. Growth hormone has also been used in trials
Human recombinant growth hormone, developed involving children with cerebral palsy. These
in the 1980s, did not have this risk and is the main studies are varied ranging from case reports to
form of growth hormone in use today. small case-controlled studies. Their applicability
Immediate treatment is recommended once to the general population of pediatric cerebral
growth hormone deficiency is diagnosed. Dosing palsy children is less clear. The benefits are diffi-
is based upon multiple clinical studies and is cult to quantitate.
assumed optimal (i.e., benefits outweigh risks) In one case report in 2004, Shim et al. reported
when administered nightly at approximately their experience with three children who had cere-
0.04–0.05 mg/kg/d. Administering the growth bral palsy and who were treated over 2 years with
hormone as a daily injection is more effective growth hormone. Two of the three were growth
than other routines (such as three times a week). hormone deficient defined by lack of an adequate
Typically, there is a robust response to treat- peak response to insulin-induced hypoglycemia
ment in growth hormone-deficient individuals in (Shim et al. 2004). The third was not deficient
the first year of treatment (possibly due to “catch- by stimulation testing. However, all three were
up” growth), becoming less robust subsequently. treated with daily growth hormone injections.
Treatment is monitored with periodic measure- All experienced an improvement in their height
ments of height and height velocity, IGF-1 levels, or length standard deviation score. The benefit
and bone ages. Dosing is adjusted according to was greatest for the two children who were
these measurements and the deviation from defined as growth hormone deficient. This fur-
accepted standards. thered an interest in assessing the role of growth
Side effects are rare. Such conditions as hormone in other children with cerebral palsy.
pseudotumor cerebri (headaches, nausea, dizzi- In 2007, Ali et al., in a small pilot study,
ness), insulin resistance (acanthosis nigricans observed 12 children, ages 5–15 years, with cere-
skin changes, prediabetes, or frank diabetes), and bral palsy (GMFCS I–V) over an 18-month treat-
slipped capital femoral epiphyses (hip pain, limp) ment period with and without growth hormone
are symptomatically screened at each visit, even administration (Ali et al. 2007). Half (6) of these
though they are not common. A previous concern children were treated with growth hormone; the
others were not. All were examined at 0, 3, 6, 12, velocity were lower in the group of children with
and 18 months for length or height, weight, BMI, cerebral palsy compared to those without cerebral
quality of life measures (POCI), and blood tests palsy. This was complicated by the fact that knee
(IGF-1, IGFBP3, and other markers of bone heights were used in the children with cerebral
health). BMD by DXA scanning was also palsy and extrapolated to a virtual “standing
performed during this time. The two groups height” using equations derived from normally
were similar in ranges of age, GMFCS level, growing children in the 1990s. In the control
pubertal development, and initial anthropometrics. population, only standing heights were used.
None of these children were assessed for growth In girls, the amount of growth hormone
hormone deficiency by stimulation testing. released nocturnally, and the IGF-1 concentra-
Height SDS and IGF-1 concentrations and BMI tions were lower compared to typically growing
increased significantly in the growth hormone- girls, across the more advanced Tanner stages.
treated group but not in the untreated group. However, the pattern of growth hormone release
The researchers noted that this was a small over a nocturnal 12-h period was similar (i.e., the
preliminary study suggestive only of possible number and timing of growth hormone “bursts” as
growth hormone benefit in this population. opposed to the amplitude of the “bursts”).
Growth hormone, unfortunately, is expensive The trend in boys was similar but not statisti-
and needs to be administered by subcutaneous cally significant. Girls in this study progressed
injections. In recent years, some insurance com- from Tanner I through Tanner IV, while boys
panies have been less supportive in providing only progressed to Tanner II during the study
coverage for such treatment. This is true even for period. There were also fewer boys than girls in
idiopathic short stature, which had been an the study. This study therefore provided a better
FDA-approved indication for treatment. It is understanding of the longitudinal changes in
therefore unlikely that approval for routine use anthropometric measurements and growth hor-
in children with cerebral palsy will be forthcom- mone secretory activity in these children.
ing, without stronger clinical evidence of safety Overall the studies tend to support the pre-
and benefit. sumption that some children with cerebral palsy
Some of growth hormone’s effects, in terms of may have a disorder of growth hormone regula-
final adult stature and lifelong care, may also not tion causing their growth compromise. It is an
be desirable in those more severely affected by ongoing area of interest and active research.
their neuromuscular condition (see ▶ Chap. 69,
“Growth Attenuation for the Child with Cerebral
Palsy”). The beneficial effects on lean body mass Other Non-nutritive Factors in Growth
and bone mass may outweigh some of these neg- Disorders
ative concerns.
In 2009, Kuperminc et al. presented a study of Another extremely important hormonal system that
20 children with moderate to severe cerebral palsy affects growth is the hypothalamic-pituitary-thy-
(GMFCS II–V), ages 6–18, who were followed roid axis. Thyrotropin-releasing hormone (TRH)
longitudinally every 6 months for 3 years with from the hypothalamus stimulates maturation and
assessment of weight, knee heights, triceps skinfold secretion of TSH from pituitary thyrotrophs. TSH
thicknesses, Tanner stage, biochemical measures of then increases synthesis and secretion of thyroxine
IGF-1, IGFBP-3, and nocturnal growth hormone and triiodothyronine from the thyroid follicular
secretory patterns. These measurements were then cells. Thyroxine has a permissive effect on GH
compared to a group of 63 typically growing chil- secretion and therefore may be an even more
dren (Kuperminc et al. 2009). important “growth” factor than somatotropin.
As expected, all anthropometric measurements It is, therefore, always evaluated in growth
of weight, knee height converted to “standing disorders and is easily measured with blood tests
height,” triceps skinfold thickness, and “height” for TSH, free T4, and, if indicated, free T3.
974 K. J. Sheridan
Treatment is straight forward with thyroid hor- In many children with cerebral palsy, the
mone replacement. growth spurt may cause additional musculoskele-
The sex hormones testosterone, estrogens, tal dysfunction including progressive slumping
DHEA/DHEA-sulfate, and delta-4-androstenedi- when standing, dysfunctional changes in bone
one are less important for normal growth during shape, and gradual loss of ambulation
the prepubertal years. During adolescence, how- (Deceuninck et al. 2013).
ever, these sex steroids increase and are synergis- In one study of French children, sagittal X-rays
tic with GH effecting height, weight, and body of 119 children with cerebral palsy (including
composition changes. 17 with hemiplegia and 102 with diplegia), who
There are many other non-nutritive factors had an average age of 11.1 + 4.2 y, were com-
affecting growth in children. Having cerebral pared to 652 typically growing children (age
palsy does not, in any way, “protect” the child 12.2 + 3.1 y) in relation to specific pelvic and
from these factors. Traditionally, such causes of spine orientation parameters, kyphosis, and lordo-
abnormal growth are classified as primary sis (Deceuninck et al. 2013).
(in which there is a defect intrinsic to the growth Within this short growth period (when a puber-
plate) and secondary (in which the growth plate is tal growth spurt was likely to occur), there were
affected by extrinsic factors). These also need to problems noted in spine, pelvis, and long bone
be considered as causes of growth problems just relationships in the children with cerebral palsy
as it is in children without cerebral palsy. compared to the children without cerebral palsy.
Primary disorders include skeletal dysplasia, This therefore raised concern for risk of additional
genetic syndromes, familial short stature, disabilities and future surgical needs.
chromosomopathies (Turner’s), and IUGR. There are assumptions made, common to care
After excluding malabsorption, malnutrition, providers, about how changes in motor function
and psychosocial deprivation effects, secondary and activity may worsen during growth. Some of
causes such as endocrine deficiencies (growth these changes have been quantified to better pre-
hormone, thyroid hormone, sex hormone, vitamin dict the need for future interventions.
D dysfunction), hormone excesses (hyper- Davids et al. in 2015 reported on the relation-
cortisolemia of Cushing’s syndrome, precocious ship of strength, weight, and function with age in a
puberty with early growth cessation), hormone group of children with cerebral palsy (Davids
resistance (pseudohypoparathyroidism, vitamin et al. 2015). Motor and growth changes were
D resistance), chronic illnesses, renal failure, observed prospectively in 255 children ages
renal tubular acidosis, congenital heart disease, 8–19 from 7 pediatric orthopedic specialty hospi-
and infections are sought. tals in North America.
Since only children with spastic diplegia in this
large cohort were studied, they were more homo-
Functional Changes with Growth geneous in terms of limb involvement (GMFCS
I–III).
As previously noted, growth, especially pubertal Weight and strength improved over time (i.e.,
growth, can have a profound effect on motor as they aged). However, there was a decline noted
function and mechanics in children with cerebral when strength was normalized to weight. This
palsy. Thus, close attention to growth and how it supported the clinical impression that motor func-
may alter the physical anatomy of bone and its tion worsens with age in cerebral palsy and has a
relationship to muscle function (weakness, spas- negative impact on limb use.
ticity, etc.) becomes critical for children with Probabilities of independent ambulation and
cerebral palsy. Uncovering early dysfunction strength per weight were quantified. From this
of growth will help to preserve motor data they concluded that there was a 90% chance
function in these children (Noble et al. 2014; of independent ambulation without assistive
McFall et al. 2015). device when the strength normalized to weight
was 21 Newtons/kg. This value was 50% of that • Are calories, macronutrients, and micro-
predicted relative to a typically growing child. nutrients adequate for the age, developmental
These are just some examples of the relation- stage, and energy expenditure of the child?
ship of growth to physical changes in children • Is the diet administered in a manner which allows
with cerebral palsy which may lead to further full intake, i.e., orally or through ostomies?
disabilities as they age. • Is the gastrointestinal tract functioning nor-
mally, or is there dysmotility with gastroesoph-
ageal reflux and emesis, inadequate transit time
Approach to Growth Problems for food absorption through the small intestine,
in Children with Cerebral Palsy incomplete transit through the colon, or abnor-
mal expulsion of feces?
Growth concerns in a child with cerebral palsy can
arise whenever (1) surgical readiness assessment Nutritional compromises can easily mask other
is desired, (2) parents or clinicians perceive causes of growth delay. Once the nutritional con-
growth attenuation, or (3) routine health care cerns are explored and answered satisfactorily,
demands are not met. The first step is to plot the attention is focused on the less obvious causes of
growth parameters on an appropriate growth chart growth attenuation. The comorbidities associated
(such as those discussed above). with cerebral palsy, however, may modify the abil-
The use of an appropriate growth chart ity to identify these causes. Such comorbidities
depends upon the severity and/or ambulatory could include seizures, dysautonomia, spasticity,
status of the child. The measurements can be and the pharmaceuticals used for their treatment.
plotted on the CDC recommended growth charts In addition, there may be surgical (especially ortho-
for typically growing children if using standing pedic) interventions, skeletal fractures, and infec-
heights or “virtual heights” from knee height tions (pulmonary, skin, and genitourinary) which
conversion equations. This is at the discretion modify growth. Endogenous hormonal deficien-
of the clinician. One is not recommended over cies, such as hypothyroidism, growth hormone
the other since each has its own drawbacks and deficiency, hypopituitarism, and calcium disorders
benefits. along with iatrogenic hormone excess states such
Lengths can be used if either unable to stand or as frequent use of exogenous steroids in pulmonary
if knee heights cannot be performed. These can be diseases, are examples of conditions which occur
plotted on the standard height growth charts, more frequently in children with cerebral palsy.
being aware that a length is only an approxima- Summary Approach (Outline)
tion, not a true substitute, for height.
In the more severely involved child when con- 1. Obtain appropriate anthropometric measure-
tractures or other bony dysmorphologies prevent ments of growth
the procurement of usable heights, total body (a) Weight
lengths, or segmental lengths, then weights (b) Height, if able to stand, (using the Frank-
become more critical in assessing growth dys- furt plane)
function. Weight growth charts which incorporate (c) Length if not able to bear weight and con-
health-related measures, such as those developed tractures not extensive
by Brooks et al. (2011) and Stevenson et al. (d) Knee height or tibial segmental lengths if
(2006), may aid in identification of a truly at-risk contractures prevent adequate length mea-
child. surements (these can be converted to “vir-
As outlined in the previous sections, growth tual heights”)
disorders in children with cerebral palsy should (e) Arm span, if contractures are not
initially be addressed with careful attention to the prohibitive
nutritional status. The following questions should (f) Mid-arm circumference
be addressed: (g) Skinfold thickness
976 K. J. Sheridan
2. Plot on an appropriate growth chart Awareness of the subtleties in the use of modi-
(a) CDC recommended charts if acceptable fied measures of growth, in selection of appropriate
heights or if only lengths obtained being growth charts that incorporate health risk markers,
aware of the limitations of interpretation and in effective treatment interventions is necessary
(b) Cerebral palsy growth charts may also be for the appropriate management of these children
used for knee heights, calculated standing who differ from their healthier peers.
heights from knee heights, or lengths A clearer understanding of the true health chal-
(c) Modified weight charts should be consid- lenges that the child with cerebral palsy may face
ered for children (to address morbidity and can lead to better risk assessments for surgical
mortality concerns (e.g. Brooks et al.) readiness and long-term health needs. The over-
3. Assess body composition with bone age arching goal is an improvement in the quality of
(acknowledging the variability in delay or life for these children as they grow into adulthood.
advancement in children with cerebral palsy),
skinfold thickness protocols, or DXA
techniques Cross-References
4. Attention to nutritional health and deficiencies
5. Repeat measurements 3–6 months apart to ▶ Endocrine Dysfunction in Children with Cere-
determine height/length velocity and body bral Palsy
weight velocity ▶ General Nutrition for Children with Cerebral
6. Obtain blood tests for at-risk individuals (e.g., Palsy
poor weight or length velocity after correcting ▶ Growth Attenuation for the Child with Cerebral
nutritional problems) Palsy
(a) TSH, free T4, and free T3 (addresses pri- ▶ Managing Bone Fragility in the Child with
mary and secondary hypothyroidism) Cerebral Palsy
(b) GH, IGF-1, and IGF-binding protein-3 ▶ Premature and Delayed Sexual Maturation in
(screens for somatotropin axis Children with Cerebral Palsy
dysfunction)
(c) ACTH, cortisol, or ACTH stimulation test
(assesses hypothalamic-pituitary-adrenal References
axis)
(d) Nutrition labs – Prealbumin, albumin, Ali O, Shim M, Fowler I, Greenberg M, Perkins D,
25-hydroxyvitamin D, and complete Oppenheim W, Cohen P (2007) Growth hormone ther-
blood count apy improves bone mineral density in children with
cerebral palsy: a preliminary pilot study. J Clin Endo-
(e) Inflammatory conditions – C-reactive pro- crinol Metab 92(3):932–937. Accessed 10 2017.
tein and erythrocyte sedimentation rate https://doi.org/10.1210/jc.2006-0385
(f) Renal disease – Creatinine or cystatin C, Allen DB, Rundle AC, Graves DA, Blethen SL (1997) Risk
blood urea nitrogen, acid/base balance of leukemia in children treated with growth hormone:
review and reanalysis. J Pediatr 131(1 Pt 2):S32–S36
measures, and urinary protein Araujo LA, SIlva LR (2013) Anthropometric assessment
7. If all above is normal but IGF-1 is low or of patients with cerebral palsy: which curves are more
growth velocity is poor, refer to endocrinology appropriate. J Pediatr 89(3):307–314
for further evaluation including growth hor- Brooks J, Day S, Shevelle R, Strauss D (2011) Low weight,
morbidity, and mortality in children with cerebral
mone stimulation testing palsy: new clinical growth charts. Pediatrics 128(2):
e299–e307
In conclusion, growth assessment in children Chumlea WC, Guo SS, Steinbaugh ML (1994) Prediction
with cerebral palsy is extremely important but not of stature from knee height for black and white adults
and children with application to mobility-impaired
without pitfalls in interpretation, compared to the or handicapped persons. J Am Diet Assoc
typically growing child. 94(12):1385–1388, 1391
Coniglio SJ, Stevenson RD, Rogol AD (1996) Apparent Liu L, Roberts R, Moyer-Miller L, Samson-Fang L (2005)
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Growth Attenuation for the Child
Jonathan M. Miller and Evan Graber
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 980
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 980
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 981
Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 981
Ethical Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 982
Autonomy and Family Preferences . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 982
Beneficence, Nonmaleficence, and the Best Interest Principle . . . . . . . . . . . . . . . . . . . . . . . . . 982
Justice and Contextual Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 983
Perspective of Stakeholders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 983
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 983
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 984
Abstract larger, including transfer from bed to chair,

Approximately one-third of children with cere- diapering, dressing, bathing, and transporting.
bral palsy have moderate or severe cognitive Furthermore, the heightened burden on the
impairment. When severe cognitive impair- family can make it increasingly difficult to
ment accompanies significant physical limita- care for the child in the home environment.
tions in children with CP, the caregivers are These concerns have led some families of non-
required to provide for all of their daily ambulatory children with profound cognitive
needs. Some of these responsibilities will impairment to request growth attenuation ther-
become more difficult as the child grows apy to mitigate the impact of growth on their
ability to care for their children. Estrogen given
orally or transdermally can be used for growth
J. M. Miller (*) · E. Graber
attenuation in this population, but the ethics
Nemours A.I. duPont Hospital for Children and Sidney of this therapy continues to be debated in the
Kimmel Medical College, Thomas Jefferson University, medical community.
e-mail: Jonathan.Miller@nemours.org;
evan.graber@nemours.org

https://doi.org/10.1007/978-3-319-74558-9_74
980 J. M. Miller and E. Graber
Keywords appear in the literature. This was especially true

Cerebral palsy · Growth attenuation · for diethylstilbestrol (DES), an estrogen that was
Cognitive impairment · Estrogen therapy · used primarily in adult women to help prevent
Ashley treatment threatened miscarriage, and was also used for
GAT. It was later shown to increase the risk of
cancer in women exposed prenatally to DES
Introduction (Greenwald et al. 1971).
For years, it was thought there was a sexual
Approximately one-third of children with cere- dimorphism in which hormones contributed to
bral palsy (CP) have moderate or severe cognitive maturation and eventual closure of the epiphyses
impairment (Miller and Bachrach 2017). When more significantly in females than males. In 1994,
severe cognitive impairment accompanies signif- the New England Journal of Medicine published
icant physical limitations in children with CP, the case of a 28-year-old man who presented to an
the caregivers are required to provide for all of orthopedist with apparent osteoporosis, a height
their daily needs. Some of these responsibilities of 80.3 inches, and open growth plates on radio-
will become more difficult as the child grows graph. He was eventually found to have a muta-
larger, including transfer from bed to chair, dia- tion of the estrogen receptor (Smith et al. 1994). It
pering, dressing, bathing, and transporting. Fur- was this case that proved that estrogens, in partic-
thermore, the heightened burden on the family can ular, resulted in growth plate fusion in both males
make it increasingly difficult to care for the child and females.
in the home environment. These concerns have In 2006, Gunther and Diekema published their
led some families of nonambulatory children with experience with growth attenuation in a child with
profound cognitive impairment to request growth profound developmental disability. In this case,
attenuation therapy (GAT) to mitigate the impact a 6-year-old girl with static encephalopathy and
of growth on their ability to care for their children global developmental delay was nonambulatory,
(Gunther and Diekema 2006). nonverbal, and gastrostomy-tube dependent; mul-
tiple specialists agreed there was no expectation
for improvement in her cognitive or neurologic
Natural History function. Her family requested growth attenua-
tion so that they could continue to care for her
The idea of using sex steroids for GAT first beat home into adulthood. After consultation with
came popular in the 1950s as a treatment for the institutional ethics committee, they used high-
constitutionally tall children, especially girls. dose estrogen for growth attenuation as well
The concept was based on the observation that as pretreatment hysterectomy and removal of
children with precocious puberty had early expo- breast buds to minimize the side effects of the
sure to pubertal hormones and shorter adult height estrogen therapy. This treatment went on to be
due to early closure of the epiphyses (Drop et al. known as the “Ashley Treatment,” named after
1998). In girls, GAT involved administering vary- the described patient, as her parents were open to
ing preparations of estrogens in supraphysiologic being identified and spoke publically about their
doses in order to reduce their adult height. Data reasons for wanting to limit the growth of their
about the effectiveness of this treatment has var- child (Gunther and Diekema 2006). The article
ied, with some evidence pointing to a reduction of stimulated a great deal of controversy, much of it
2.1–10 cm of height below predicted adult height surrounding the hysterectomy and mastectomy
(Drop et al. 1998). Over time, GAT for the pur- components of the treatment, especially since
pose of treating constitutionally tall girls they are not necessary components of GAT. Ethi-
decreased in popularity as the social stigma of cal considerations of the Ashley Treatment have
being a tall woman waned. Additionally, concerns included the dignity of the patient, the benefit
about side effects of estrogen therapy started to and harm of treatment to the patient, and the role
69 Growth Attenuation for the Child with Cerebral Palsy 981
of the treatment directed toward the patient for the average on the CP-specific growth chart. There is
benefit of the parents (Bersani 2007; Allen et al. still much to learn about the impact of estrogen
2009). These issues continue to be debated today. therapy in children with medical complexity,
Since the publication of the article by Gunther including the impact on height as well as the
and Diekma and the intense public debate it gen- ultimate weight, which is arguably more impor-
erated, public interest in GAT has grown. A sur- tant than height, as well as the optimal age for
vey of pediatric endocrinologists in 2015 showed initiating therapy. Ideally, therapy intended to
that one-third had been asked to prescribe GAT for limit height should be accompanied by a focus
children with severe cognitive impairment and on nutritional intake to prevent disproportionate
the majority of these requests came from the weight gain (Allen et al. 2009).
patient’s family. Over 10% of the respondents The intended benefits of growth attenuation
had prescribed GAT, most commonly oral estro- are related to the impact of decreased height and
gen, and nearly half had withheld interventions weight on the ability of caregivers to provide
that suppress precocious puberty in order to for the activities of daily living of the child, par-
reduce linear growth (Pollock et al. 2015). A ticularly hygiene and transport, leading to an
2017 survey of pediatricians in New Zealand improved quality of life for the patient. It is easy
showed that one-quarter of respondents had been to appreciate the benefits to the family: lifting and
asked about GAT for a severely disabled child, moving the child becomes increasingly difficult
with only 3% reporting experience with prescrib- as nonambulatory children grow and caregivers
ing GAT (three pediatric endocrinologists, one get older, leading to a need for a second pair of
developmental pediatrician, and one general pedi- hands or a home health aide. Ultimately, some
atrician) (Wrigley et al. 2017). families are faced with the difficult decision to
move the child to a facility when it becomes too
difficult to maintain appropriate care at home. The
Treatment medical impact on the patient is more difficult
to document, and there are still no studies to
Little has been published on the use of GAT in evaluate the theoretical benefits of growth attenu-
children with medical complexity and even less ation. Improved mobility and easier transporta-
on children with CP. As previously stated, high- tion will enhance access to medical care. Growth
dose estrogen has received the most attention attenuation could have a potential impact on med-
for use in GAT because of historical experience ical outcomes such as pressure ulcers, aspira-
in tall adolescent girls. Testosterone has less tion pneumonia, DVTs, and facility-associated
potential because of its growth-promoting and infections.
anabolic effects.
Estrogen can be given orally, intramuscu-
larly, or transdermally. Oral options include es- Complications
tradiol (2.5–20 mg/day) and ethinyl estradiol
(0.05–0.3 mg/day) (Allen et al. 2009). Data from Estrogen therapy is associated with a number of
the literature on tall stature in girls shows a treat- potential adverse effects that must be considered
ment effect of 6 cm when treatment is initiated at a when weighing the cost and benefit for the indi-
bone age of 10 years, with decreasing impact at vidual patient. Nausea, headaches, and weight
older bone ages (Venn et al. 2008). There is one gain are common but typically mild and transient.
published study describing the growth-limiting Postmenarchal girls can experience irregular
potential in children with medical complexity bleeding and boys can develop gynecomastia
and CP (Kerruish 2016). This report of four chil- (Isaacs et al. 2011). Severe complications such
dren with profound cognitive impairment that as venous thrombosis are uncommon and may
received GAT using an estrogen patch showed be further mitigated by using patch over oral
that three of four had an ultimate height below estrogen preparations (Mohammed et al. 2015).
There are concerns about estrogen therapy and ability to travel, engage in recreational activities,
the development of malignancy (breast and and interact socially. Further, “a child who is
uterus) or infertility, but these associations are easier to move will in all likelihood be moved
unclear (de Waal et al. 1995). Furthermore, the more frequently” (Gunther and Diekema 2006).
concerns about fertility are of little consequence in The adverse effects of estrogen therapy are, to a
a child with severe cognitive impairment. Of sig- large extent, not well described in this population,
nificant importance to this decision is the fact that but when extrapolated from other uses of estrogen
there are no published studies addressing adverse for growth attenuation, the adverse effects are not
effects of estrogen therapy in medically complex known to be sufficiently severe as to outweigh the
children or in boys (Allen et al. 2009). It is potential benefits for some individuals.
unknown, for instance, whether estrogen therapy Of crucial importance to the ethical evalua-
in an immobile child with CP will yield a higher tion of GAT is the impact of short stature on
rate of venous thrombosis than in tall adolescent children with severe cognitive impairment. Chil-
girls. It is reasonable to assume that the side effect dren with severe cognitive and neurological
profile will be unique in the medically complex impairment do not derive the same benefit from
population, so this should be an area of investiga- “getting bigger,” including the personal and social
tion for researchers in the future. value, that other children experience. Therefore,
this carries less weight in the ethical analysis
than it would for a child who has greater ability
Ethical Considerations to interact with the world. There is also concern
about the patient’s inherent human dignity; every
Autonomy and Family Preferences person has the right to physical integrity, which
is threatened by growth attenuation. Violating a
Children differ from adults in that their medical patient’s integrity requires a compelling justifica-
decisions are necessarily made by a surrogate tion (Isaacs et al. 2011).
decision-maker, typically the parents. Children This decision has repercussions that go beyond
with permanent severe cognitive impairment will just the patient. The family, for example, stands
never attain decisional capacity or individual to benefit from this decision, potentially at the
autonomy and, therefore, will require a surrogate child’s expense; the child could take on the burden
decision-maker for all medical determinations. of side effects of estrogen therapy so that the
Unless there is specific reason to suspect other- family has an easier time managing the child at
wise, parents are assumed to be in the best posi- home. However, the parents’ interests in this deci-
tion to make medical decisions for their children. sion are largely aligned with that of the child, such
Parents are most acquainted with their children’s that benefits to the family extend to the child
unique needs and preferences, are well suited to (Wilfond et al. 2010).
make quality of life determinations, are directly The best interest standard is frequently ap-
impacted by the medical choices, and must live plied in beneficence/nonmaleficence ethical as-
with the consequences. sessments. However, this is problematic as best
interest is both subjective and a higher standard
than we hold parents to for any other decision. An
Beneficence, Nonmaleficence, alternative approach identifies the threshold of
and the Best Interest Principle harm that is unacceptable resulting from the deci-
sion (Shah et al. 2017). Therefore, even if the
As stated previously, the benefits of GAT for medical team does not think growth attenua-
children with CP and cognitive impairment in- tion is the best possible decision for a child, it
volve ease of caregiving and the impact of that should be considered if it provides significant
on quality of life. The benefit may go beyond potential benefit without crossing an unacceptable
ease of caregiving; families may have improved threshold of harm.
69 Growth Attenuation for the Child with Cerebral Palsy 983
Justice and Contextual Features of the child positions them to be best suited to
make this decision on behalf of the child.
There is a long history of abuses against children Opponents of GAT believed that families could
with physical and cognitive disabilities, including maintain the same quality of life if they have the
involuntary sterilization and use as research sub- appropriate resources and education to support
jects. It is of crucial importance to protect this the child. They were also worried that the intrin-
vulnerable population; nevertheless, historical sic rights and dignity of the child are violated
abuses should not preclude exploration of innova- by GAT. Finally, these parents were concerned
tive therapies for this population. about the history of abusive treatment of disabled
There is concern that proponents of GAT do not persons and the potential for a slippery slope
understand or respect children with disabilities, and whereby GAT could be applied to children with
are consequently discriminating against them by less severe disability (Kerruish 2016).
suggesting this therapy (Wilfond et al. 2010). The
counter argument states that people with disabilities
are all individuals with unique needs and differing Conclusion
social supports that are best handled in different
ways; to withhold the option of growth attenuation There is a paucity of literature on the use of GAT in
from this population would serve to eliminate a children with profound cognitive impairment and
potentially beneficial option for improving quality CP and there is much to be learned in order to
of life. Further, there is concern about making a inform the use of this modality in this population.
distinction between patients of differing levels of GAT is intended to benefit the patient and family by
cognitive impairment. As mentioned previously, allowing the child to more easily engage in activi-
children with severe cognitive impairment derive ties and potentially prevent poor health outcomes.
less benefit from “getting bigger” and have less This comes at the risk of side effects to the patient,
claim for autonomy as they will never develop as well as the risk of violating the child’s rights and
decisional capacity, so growth attenuation in this dignity. When faced with moral ambiguity (the
circumstance is not the same as in children with “gray zone”) as is the case with GAT in this popu-
less severe impairment. lation, the opinions of the parents should be given
greater emphasis. The medical team and family
should evaluate this decision in the context of the
Perspective of Stakeholders unique needs of the individual child, the family, and
uncertainty surrounding the impact of this therapy
To better inform the debate on the use of GAT given the lack of studies from which to draw. Until
in children with profound cognitive impairment, more data is available in the literature about GAT, it
Kerruish analyzed published accounts from parents is prudent to involve an institutional ethics commit-
of children who received GAT and those tee when considering GAT for a child. In this way,
who opposed treatment (Kerruish 2016). All of the the medical team can support the family to make a
parents, regardless of opinion about GAT, wanted to decision in the child’s best interests.
optimize both the health and happiness of their child.
Proponents emphasized the impact GAT had
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Palsy
Kevin J. Sheridan
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 986
Normal Pubertal Maturation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 986
Physical Assessment of Puberty . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 989
Adrenal Role in Puberty . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 990
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 991
Precocious Puberty . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 991
Diagnosis and Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 994
Diagnosis of Central Precocious Puberty . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 994
Treatment of Central Precocious Puberty . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 995
Diagnosis of Delayed Puberty . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 995
Treatment of Delayed Puberty . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 995
Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 996
Studies of Pubertal Milestones in Children with Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . 996
Studies of Pubertal Hormonal and Metabolic Changes in Children with
Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 998
Studies of Mechanisms of Pubertal Disruption in Cerebral Palsy . . . . . . . . . . . . . . . . . . . . 999
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1001
Cross-References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1001
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1002
Abstract infant, child, and adolescent and (2) the

This chapter will address the variations in hypothalamic-pituitary-adrenal (HPA) axis as
pubertal development and its altered regulation it relates to the sex steroid’s role in puberty,
in the child with cerebral palsy. abnormalities in pubertal development will be
After an overview of the (1) hypothalamic- discussed. The role of these processes in chil-
pituitary-gonadal (HPG) axis in the fetus, dren with cerebral palsy will also be addressed.
The Tanner pubertal staging system
addresses the physical manifestations of
K. J. Sheridan (*) puberty. It helps to define an expected age of
Endocrinology, Gillette Children’s Specialty Hospital, onset of these signs in boys and girls. Defining
Saint Paul, MN, USA
e-mail: Ksheridan@Gillettechildrens.com these ages is difficult in typically developing

https://doi.org/10.1007/978-3-319-74558-9_75
986 K. J. Sheridan
children, becoming even more problematic will be discussed. The role of these processes
in children with cerebral palsy. in children with cerebral palsy will also be
The accepted approaches to the diagnosis addressed.
and treatment of precocious and delayed The commonly accepted scheme for classify-
puberty will be presented as well as controver- ing different levels of motor involvement and
sies in treatment recommendations in children function in cerebral palsy is known as the “gross
with or without cerebral palsy. motor function classification system” (GMFCS).
Studies over the last 40 years concerning This clinical tool has been very useful in exploring
the timing and comorbidities in children with pubertal development in children with cerebral
cerebral palsy will be reviewed. palsy.
Without some agreement about the severity of
Keywords neurological or muscular impairment and the
Cerebral palsy · Puberty · Precocious · comorbidities that accompany these insults, it is
Delayed · Gonadotropins · Treatment difficult to draw conclusions about the expected
timing and progression of puberty in children with
cerebral palsy. Comorbidities will vary with the
Introduction severity of the cerebral palsy and further compli-
cate clinical studies.
“Cerebral palsy,” broadly defined, encompasses a A clearer understanding about the assumptions
variety of neurological insults occurring in early concerning growth and development in the care of
life (both pre- and postnatally). Associated children with cerebral palsy will improve that
comorbidities also affect growth and development care. Therefore, a critical examination of which
throughout childhood and into adulthood. assumptions have reasonable literature support,
Nutritional compromises due to an inability to which may have been formed by “expert” opin-
take in, digest, absorb, or utilize nutrients are ion, and which are individual opinions will foster
likely. There are additional metabolic disruptions better understanding.
from infections, seizures, and medications such as
steroids, anti-epileptic drugs, and psychotropic
drugs. Movement disorders such as dystonia and Normal Pubertal Maturation
athetosis are common.
Disordered neuro-regulation of hypothalamic Normal pubertal maturation implies an under-
activity may manifest as dysautonomia, appetite standing of the (1) internal “pubertal” hormonal
suppression, or abnormal antidiuretic hormone milieu which includes the inhibition and stimula-
secretion (excess or deficiency). If hypothalamic tion of hormonal secretion in the hypothalamic-
hormonal releasing factors are deficient, pituitary pituitary-gonadal (HPG) axis and the hypotha-
function is altered and may result in early or lamic-pituitary-adrenal (HPA) axis and the
delayed gonadotropin secretion and even growth (2) external manifestations of puberty, e.g., sec-
hormone deficiency. These all need to be ondary sexual characteristics and body composi-
addressed throughout the pediatric years from tion changes.
infancy to childhood to adolescence. Our understanding of how the pulsatile secre-
This chapter will address the variations in tions of sex steroids and the gonadotropins, LH
pubertal development and its altered regulation and FSH, change in amount and frequency during
in the child with cerebral palsy. the pediatric years has been facilitated by the
After an overview of the (1) hypothalamic- concept of a gonadostat. This term refers to a
pituitary-gonadal (HPG) axis in the developing negative feedback control system which can “fire
child and (2) the hypothalamic-pituitary-adrenal up” or “dampen down” the internal hormonal
(HPA) axis as it relates to the sex steroid’s role in milieu. This is a simple concept developed in the
puberty, abnormalities in pubertal development 1960s. It has been refined over the years with the
70 Premature and Delayed Sexual Maturation in Children with Cerebral Palsy 987
accumulated knowledge of genetic, paracrine, males and possible sperm and egg health in
autocrine, and endocrine regulatory factors. males and females) (Quigley 2002).
The concept is still very useful in understanding The second period of increased HPG activity
the changes that accompany puberty. occurs in early adolescence. It is necessary for
The gonadostat posits a physiologically the full reproductive potential of the adult male
defined “gonadotropin-releasing hormone and female.
(GnRH) pulse generator” in the hypothalamus. Any condition (illness, injury, genetic aberra-
It is modified by multiple neurological inputs tion, metabolic disturbance, neurological dys-
causing pulsatile GnRH secretion which itself function) that interferes with the normal early
engenders pulsatile pituitary secretion of the HPG fetal activity, the mini-puberty of infancy,
gonadotropins luteinizing hormone (LH) and the suppression of HPG activity in childhood, or
follicle-stimulating hormone (FSH). The gonado- the pubertal re-emergence of HPG function may
tropin secretions, in turn, stimulate the synthesis, affect reproductive potential and even adult car-
storage, and eventual secretion of testosterone and diovascular, muscle, and bone health.
estrogen from, respectively, the testes and ovaries.
The gonadostat feedback changes throughout Phase of Fetus and Infant Puberty
early life in a biphasic manner: (1) increased activ- Development
ity, i.e., less negative feedback inhibition, in ges- By 11 weeks of gestation, the gonadotrophic cells
tation and within the first year of life (i.e., mini- in the anterior pituitary have differentiated and are
puberty of infancy); (2) decreased activity due to capable of gonadotropin (LH, FSH) secretion.
a more sensitive negative feedback inhibition in Simultaneously, hypothalamic GnRH-producing
mid-childhood; and, subsequently, (3) increased neurons migrate to the hypothalamus and begin
activity due to another disinhibition of the to function. A peak in these hypothalamic and
gonadostat in adolescent puberty. pituitary hormones occurs at 20–24 weeks to
Thus, there are two times in an individual’s life levels not seen until later puberty.
when the HPG activity is unsuppressed and highly Both ovarian development in the female and
active (i.e., increased secretory bursts and detec- testes/genitalia development in the male are
tion in the blood of LH, FSH, and testosterone occurring now (Sperling 2002, p. 457). The
and/or estrogens): the fetal/infancy period and the female germ cells (eggs) migrate from the yolk
adolescent period. sac endoderm in the first month of gestation.
In the fetus the HPG activity is necessary for Granulosa cells and thecal cells accompany the
the development of the gonads in both males and germ cells and are responsible for sex steroid
females and for the maturation of the explicit production in the ovary and maintenance of the
secondary sexual characteristics in males. This ova. These follicles are at their greatest number at
activity abates somewhat later in gestation but birth (approximately 2,000,000) than at any other
reinvigorates immediately after birth as the nega- time in postnatal life. The production of these
tive feedback of the placental and maternal sex follicles (with their ova) is complete at birth but
hormones is lost. This mini-puberty of infancy can declines with growth due to several factors.
last several months, differing slightly in males and Toxins, placental insufficiency, and hypoxia are
females. Gonadotropin levels can increase to examples of some insults that influence their
those seen in early adolescent puberty. In older availability. The insults resulting in cerebral
infancy, central nervous system (CNS) inhibitory palsy do not have a predictable effect on these
pathways develop which results in greater nega- processes. Generally, these insults are occurring
tive feedback sensitivity of the gonadostat. after much of the early gestational HPG activity
This mini-puberty may be necessary for a has started.
pre-reproduction maturation or “imprinting” The fetal HPG activity in the male, unlike the
effect on subsequent adolescent puberty (i.e., female, is necessary to allow an “imprinting”
normal genital growth and development in effect on male genitalia for normal growth and
988 K. J. Sheridan
function. In addition, LH and FSH blood concen- old. This eventually leads to the physical appear-
trations can reach pubertal levels in secretory ance of secondary sexual characteristics.
bursts until 6 months of age in boys. Testosterone If there is any disruption in the CNS pathways
levels can increase to >100 ng/dL (equal to puber- that normally suppress gonadotropin secretion,
tal males) (Sperling 2002, p. 595). Any interfer- especially in later childhood when the negative
ence in the functioning of the hypothalamus, feedback pathways are less robust, physical
GnRH pulse generator, and pituitary gonadotro- puberty may occur. This is considered precocious
pins release or sex hormone functioning during when it occurs before the expected age in healthy
this time (such as is seen with some of the neuro- boys and girls.
logical compromise that affects children with Any pathology that disrupts the development
cerebral palsy) may have a negative impact on of these pathways such as the brain injury patterns
future sexual functioning. in children with cerebral palsy may alter the nor-
There are minor differences between boys and mal suppressive effects on puberty.
girls in age of onset, amplitude and frequency of
gonadotropin bursts, and the physical manifesta- Phase of Adolescent Puberty
tions of puberty. Hormonal changes of normal puberty, as noted
Cerebral palsy and its comorbidities can above, precede the physical manifestations. Ini-
have profound effects on sex hormone production tially GnRH from the hypothalamus is under the
throughout life, as well as on fertility potential of the influence of intra- and extra-neuronal pathways.
adult. GnRH is secreted in increasingly more frequent
and greater amplitude bursts in late preadoles-
Phase of Childhood Hormonal cence, first at night than gradually during the day.
Suppression In girls, FSH initially increases dispropor-
In older infancy, the mini-puberty regresses, tionately to LH. But as puberty progresses,
somewhat later in female than in male infants. FSH becomes less tightly regulated by GnRH
These changes are accompanied by the appear- while LH secretion increases, leading to selective
ance of estrogen receptors in the female pituitary growth and development of the ovarian follicles.
and hypothalamus and dihydrotestosterone FSH increases almost 2.5-fold during this time,
receptors in the male hypothalamus. These medi- followed by a 25-fold cyclical increase in LH. This
ate the negative feedback of estrogen and is followed by physical changes of puberty in girls,
testosterone, respectively. There are additional leading eventually to menarche and then to ovula-
central nervous system (CNS) inhibitory influ- tion with a predictable menstrual cycle.
ences of GnRH secretion that develop in late In late preadolescence, boys also begin to show
infancy. increasing spurts of LH, first at night and then
The increased sensitivity of the negative feed- during the day. The FSH changes however are
back loop leads to a relative quiescence, though less dramatic than in girls. Many factors, in boys
not complete suppression, of the male and female and girls, may be involved in the activity of the
sex hormones during mid-childhood. Testoster- hypothalamic pulse generator. For example, there
one levels are <10 ng/dL during this quiescent are changes in body fat mass, leptin, neuropeptide
period. However, some secretion can be detected Y (NPY), gallic acid, corticotrophin-releas-
with more sensitive assays. HPG dysfunction due ing factor (CRF), norepinephrine, dopamine,
to cerebral palsy and its morbidities is therefore serotonin, melatonin, gamma-aminobutyric acid
not yet manifest. (GABA), and N-methyl-D-aspartate levels.
In late childhood (e.g., age 7–10 years), there The timing of these events can vary signifi-
are increasing spurts of LH (almost doubling) and cantly among individuals. Any CNS pathology
FSH (less pronounced than LH). Thus, the inter- that affects the function of these pathways will
nal hormonal milieu differs in the prepubertal result in either early onset of puberty or, con-
10-year-old compared to the prepubertal 7-year- versely, delayed development.
Pubertal maturation and skeletal matu- staging system is uniquely applied to breast and
ration seem to have common determinants pubic hair changes in girls and external genitalia
(Sperling 2002, p. 466). Abundant clinical and pubic hair changes in boys.
evidence suggests the gonadotropin/sex hormone There are many graphic guides to the physical
axis as one of these determinants and the manifestation of the Tanner staging system in
growth hormone (GH)/insulin-like growth factor boys and girls (Marshall and Tanner 1969, 1970).
1 (IGF1) axis as another. Children with cerebral palsy are expected to go
Multiple observations confirm that there is a through the same sequence of Tanner stages. Sev-
“pubertal” bone age which is more closely asso- eral observational studies have looked at the truth
ciated with the onset of physical puberty than is of this assumption (Worley 2002). However, in
chronological age. That is, puberty and bone age these children there may be a greater variation in
are better correlated (0.82) than are puberty and the timing of physical signs due to effects of
chronological age (0.72). In girls, breast tissue nutrition, medications, and other comorbidities.
begins at an average bone age of 10.75 years and Typically the first physical sign of puberty in
in boys’ genital size increase begins at an average girls is breast tissue development (thelarche) but
bone age of 11.5. may be pubic hair development (pubarche) in
This correlation of skeletal maturation and 10% of girls (Sperling 2002, p. 480; Marshall
puberty onset depends upon many factors. Opti- and Tanner 1969).
mal nutrition is the most important. The somatic Epidemiological studies over the past 50 years
changes that precede puberty were initially have modified our assumptions of the normal age
hypothesized to be correlated with body fat to of onset of the physical signs of puberty. This has
explain the observations that weight correlated been studied in typically growing children in
better with the initiation of the pubertal growth North America and many other countries through-
spurt, peak growth velocity, and menarche than out the world (Parent et al. 2003).
did the correlation with chronological age Traditional understanding of the age of onset of
(Sperling 2002, p. 407). some pubertal physical features in girls (Tanner
Leptin was hypothesized to be the link between and Davies 1985) is shown in the following table
nutrition and the attainment of reproductive com- and diagram (Table 1):
petency. Leptin is secreted by fat cells and signals Observational studies in North America and
the hypothalamus that caloric intake and the elsewhere from the turn of the last century suggest
amount of energy stored as fat are sufficient. an earlier pubertal onset in girls than previously
But there are several other factors that also seen. Furthermore recent studies also suggest that
influence the pulse generator of GNRH in the boys may show physical signs of puberty earlier
hypothalamus. For example, neuropeptide Y, than previously seen.
GABA, N-methyl-D-aspartate, kisspeptin, and
pineal gland indoleamines (possibly) can have Table 1 Average age pubertal milestones in North Amer-
varying influences. ican girls
Pubertal stages Age (mean + -SD yr.)
Breast stage
Physical Assessment of Puberty II 10.7 1.0
III 11.9 1.0
Tanner and Marshall developed a staging system IV 12.9 1.2
for some of the characteristic physical changes of Pubic hair stage
puberty in boys and girls. It is a useful clinical tool II 11.2 1.1
to define normal pubertal progression, precocious III 11.9 1.1
puberty, and delayed puberty. IV 12.6 1.1
The prepubertal physical signs of puberty in Menarche 12.7 1.0
both sexes are defined as Tanner I. The Tanner SD standard deviation (MacMahon, 1973)
990 K. J. Sheridan
There were also differences depending upon Table 2 Approximate guide to the sequence of pubertal
the child’s ethnic origin and race (e.g., European changes in boys
white and African black). Although the timing of Physical sign Age (years)
menarche differed in these studies, it was much Testes size increase 11.5 y
less discrepant compared to the age of puberty Pubic hair Tanner II 12 y
onset (Herman-Giddens et al. 1997). Genital increase (Tanner 12.5–13 y
III–IV)
It is important to note that there are common a
growth spurt (9.5 cm/y) Variable, genital Tanner
benign variations of pubertal development. For III–IV
example, unilateral breast development preceding Vocal cord thickening 14 y
normal bilateral breast development or pubic hair Axillary hair Variable, Tanner pubic
preceding breast tissue as the first sign of puberty hair III
does not usually imply abnormality or pathology a
Accounts for 17–18% of adult height gained
in the HPG axis.
In girls, premature thelarche is breast tissue
appearing before the expected age range. The development was 10.1 years, 9.5 years, and
definition of the expected age range has changed 10.4 years, respectively (Sperling 2002, p. 595).
over the last few decades. In older studies breast Table 2 shows an approximate guide to the
tissue was considered premature before age sequence of pubertal changes in boys.
8 (Third National Health and Nutrition Examina-
tion Survey 1988–1994 NHANES III Examina-
tion Data File (CDROM Series 11, Nos 1 and 2A) Adrenal Role in Puberty
Hyattsville, MD: US Department of Health and
Human Services, National Center for Health Sta- Adrenal gland sex hormone output, with
tistics, Center for Disease Control and Prevention; increased levels of dehydroepiandrosterone
1998) and in more recent studies before age 7 in (DHEA) and DHEA-sulfate, generally occurs
girls of European background and before age 6 in close to the age of gonadarche (onset of gonadal
girls of African background (Herman-Giddens puberty). Gonadarche and adrenarche are two dif-
et al. 1997). ferent hormonal systems producing sex steroids.
Some girls present with premature breast tissue The physical changes associated with each are
in the toddler years, which may be extensions of chronologically synchronous but can be discor-
the mini-puberty of infancy, or in mid-childhood dant. Measurable blood levels of adrenal sex
which may represent a continuum of variable steroid output (i.e., DHEA-S) usually precede
negative feedback sensitivity in the HPG axis. that of the gonadal output. This occurs at about
In boys, the first physical sign of puberty is age 7–8 years in boys and 6–7 years in girls.
usually testes growth to >2.5 cm in longitudinal The androgen DHEA-S affects the
dimension or a volume > 3 ml (i.e., 4 ml or pilosebaceous unit resulting in comedones, greas-
greater). This is then followed, at various ages, iness, and body odor. This is soon overshadowed
by pubic hair (Tanner II–V), genital growth (Tan- in boys by the increased testosterone output from
ner II–V), height growth spurt, body composition the maturing testes. The androgen levels seen in
changes, voice change (laryngeal cord thicken- girls are from both the adrenals and the ovaries.
ing), axillary hair, and body odor. In boys, benign early puberty variants include
In boys, an acceptable age range for the onset of precocious pubarche and precocious adrenarche,
puberty is 11.5 years + 2.5 SD from the mean in occurring before the age of 9 years. The increase
NHANES III (1988–1994); the mean age of Tanner of sex hormone secretion from the adrenal gland
II pubic hair onset was 12 years in Caucasians, may precede gonadarche earlier than usual. This
11.2 years in African Americans, and 12.3 years does not necessarily suggest a true central activa-
in Mexican Americans. Tanner II genital tion of the HPG axis.
Natural History girls than in boys, but there is a greater likelihood

of associated pathology in boys.
Precocious Puberty Boys, like girls, can experience a benign
precocious pubarche or adrenarche. There is
The concept of “precocious puberty” implies that not however a benign premature testicular
the normal range of onset of physical puberty is enlargement in boys analogous to the benign
known and fully accepted. This, of course, is not premature thelarche in girls. In fact, early
completely true. There are some guidelines that testes enlargement in boys suggests an abnormal
may help identify those children in whom pathol- and likely central activation of the pulse generator
ogy should be investigated. Depending upon leading to a true premature puberty.
which population study one believes most The development of a “true” or “central” preco-
truly represents “normal” pubertal onset, an age cious puberty is typically isosexual as the changes
range can be chosen to define precocity or are appropriate to the sex of the child. This can occur
delay. For example, puberty onset more than 2.5 because of early activation of the HPG axis, just as if
standard deviation below the mean may be a it had occurred at the expected normal age. Typi-
guide to “precocity,” or, at the other end, 2.5 cally, this is considered “idiopathic” if an investiga-
standard deviations above the mean may be a tion does not suggest any intracranial pathology,
guide to “delay.” tumors, hormonal aberration, or other pathology.
A true or central precocious puberty implies There may be a familial tendency to this prematurity.
activation of the hypothalamic pulse generator
with increased pulsatile secretion of GnRH and Incomplete Precocious Puberty
the gonadotropins LH and FSH (first at night, then In boys, incomplete precocious puberty implies
daily), followed by pulsatile sex steroid secretion. isolated pubic hair and/or comedones and/or body
Guidelines have been published to help clini- odor and/or genital growth not accompanied by
cians decide when to investigate. testicular enlargement. In girls, incomplete preco-
For example, in girls, breast tissue occurring cious puberty is associated with isolated breast
before the age of 8 years (or before the age of growth, pubic hair, comedones, body odor, greas-
7 years in white girls and age 6 in black girls), iness, or axillary hair.
pubic hair before the age of 8 or 9 years, or menses
before the age of 9 1/2 years may suggest the need Benign Variants
to investigate (Sperling 2002, p. 483). These variants of early puberty are unlikely to
But benign early changes of puberty in girls progress to full pubertal maturation. In fact,
such as premature thelarche, premature pubarche almost 80% of those with benign variants will
(pubic hair before the expected age), and prema- not progress to a full central precocious puberty.
ture adrenarche (androgenic effects on the Thus, these variants are labelled as a benign
pilosebaceous unit with any combination of “premature thelarche” in girls and benign “prema-
pubic hair, axillary hair, body odor, acne, skin ture adrenarche” and benign “premature
greasiness) may not need investigation for reasons pubarche” in boys and girls.
cited above. Most of these children will progress The appearance of a small amount of pubic
to a full pubertal maturation at the expected hair, comedones, axillary hair, or odor occurring
age. The remainder that progresses too early may before the age of 6 years is typically accompanied
have compromised adult height as well as psycho- by increased secretion of DHEA and DHEA-
social problems. sulfate from the adrenal gland.
In boys, precocious puberty is generally The physical changes of adrenarche and
defined as any sign of secondary sexual develop- gonadarche are usually closely associated, but
ment before the age of 9 years. True precocious when adrenarche occurs earlier, it is termed “pre-
puberty however is thought to be more common in cocious adrenarche” and does not usually affect
992 K. J. Sheridan
the timing of normal central or true puberty. For In both sexes one needs to consider: sellar
example, a boy of 7 years with pubic hair Tanner or suprasellar craniopharyngiomas, meningiomas,
II would have the DHEA-S levels seen in a hamartomas, chronic inflammatory diseases,
13-year-old boy. infiltrative diseases, traumatic brain injuries,
Small increases in growth rate and skeletal congenital, or other acquired brain dysfunction
maturation can at times accompany these (as in cerebral palsy, hydrocephalus, or cerebral
early changes. This is less common in boys malformations).
than in girls. In girls, premature adrenarche The most frequent central nervous system mass
(or “exaggerated adrenarche”) may be associated to result in central precocious puberty is the
with subsequent menstrual dysfunction, glucose hamartoma of the tuber cinereum. This is usually
intolerance, and obesity (e.g., in polycystic ovar- ectopic hypothalamic tissue attached to the poste-
ian syndrome or metabolic syndrome). rior hypothalamus between the tuber cinereum
These benign variants should be considered and the mammillary bodies.
before launching into extensive investigations. Para-hypothalamic hamartomas are associ-
ated more commonly with precocious puberty
Pathological Variants than intra-hypothalamic hamartomas in which
There are rare pathological causes of isosexual seizures are the sequelae. Hamartomas are not
or contra-sexual incomplete precocious puberty. malignant and tend not to increase in size. They
These are usually gonadotropin independent and are difficult to surgically resect because of their
include severe hypothyroidism (leading to an anatomic location. They are treated only for their
unusual condition known as Van Wyk- abnormal hormonal secretions causing
Grumbach syndrome), adrenal tumors, gonadal precocity.
tumors, and hepatomas. Boys with incomplete Less benign are astrocytomas, ependymomas,
sexual precocity may have germ cell tumors, and gliomas. In boys, germinomas which
embryonal carcinomas, gonadoblastomas, rhab- secrete HCG may act like LH on the testicular
domyosarcomas, Sertoli cell tumors, Leydig cell Leydig cells, causing increased testosterone
tumors, and adrenal rest tumors. McCune- production.
Albright syndrome (a G-protein defect), familial Tumors or other CNS lesions that interfere
testotoxicosis (independent functioning of the with the normal central inhibitory pathways,
Leydig cells of the testes), and congenital adre- physiologically suppressing puberty in childhood,
nal hyperplasia are other genetic causes. Any of may cause early activation of the hypothalamic
these may present with incomplete precocious GnRH pulse generator.
puberty and may also lead to complete preco- Developmental defects associated with hydro-
cious puberty due to a poorly understood matu- cephalus or midline defects (as in septo-optic dys-
rational effect on the hypothalamic GnRH pulse plasia) that interfere anatomically with these
generator. inhibitory pathways are other causes.
Additional history may uncover iatrogenic Boys and girls with cerebral palsy can have
causes such as inhaled, ingested, or topically multiple types of brain dysfunction which affect
applied steroids (sex steroids or glucocorticoids) the timing and progression of puberty. Investiga-
or certain drugs such as steroids, antiseizure, or tion into other pathological causes should not be
antihypertensive medications. Bleeding disorders, withheld because of an incorrect assumption that
trauma, or sexual/physical abuse needs to be con- the brain injuries associated with cerebral palsy
sidered if a precocious vaginal bleeding occurs. are always causes of precocious puberty in chil-
dren with cerebral palsy.
Complete Precocious Puberty
Central or complete precocious puberty tends Delayed Puberty
to have more pathological causes in boys than At the other end of the spectrum is delayed
in girls. puberty, whose definition depends upon an
understanding of the normal range of puberty (1) dysgenetic gonads (i.e., Turner’s syndrome);
onset. The goal is to distinguish between benign (2) ovarian resistance to LH and/or FSH; (3) phys-
delays, such as variants of normal, from pathological destruction of the gonads from chemotherapy,
ical delay due to genetic or congenital abnormal- irradiation, trauma, and surgery; (4) autoimmu-
ities which affect the hypothalamic pulse nity; or (5) idiopathic premature ovarian failure.
generation of GnRH. Delay of puberty in boys is defined as no
In these children, lack of any physical physical signs of sexual maturation by approxi-
signs of puberty such as, in the male, testes mately 14 years of age. In the United States, <2%
enlargement and, in the female, breast tissue of 14-year-old boys and 0.4% of 15-year-old boys
enlargement, at an age more than 2.5 standard are prepubertal (Sperling 2002, p. 599). Therefore
deviation above the mean age of pubertal onset, using 2.5 SD above the mean, which include
sets the threshold for further investigation. 98.5% of the population, delay of puberty is
However, there may be significant overlap defined by lack of sexual development by 14 years
with a common familial tendency to start puberty of age. A testosterone level > 0.7 nM (20 ng/dL)
later. This variant is referred to as “constitutional at 0800 predicts >4 ml testicular enlargement in
delay of growth and puberty.” These children will 12 months in 77% of males and 100% of males in
usually progress to a normal adult height and 15 months (Sperling 2002, p. 599).
reproductive potential. Although this can also Also in boys, constitutional delay of growth
occur commonly in children with cerebral palsy, and puberty needs to be distinguished from
these children may not progress to their full the disorders which result in failure of the devel-
midparental height expectations. There may be opment of the hypothalamic pulse generator.
overlap of the unknown factors involved in con- This failure in its complete form has been referred
stitutional delay of growth and puberty and those to as “hypogonadotropic hypogonadism.” Distin-
due to cerebral palsy and its comorbidities. guishing between constitutional delay of growth
Delay in puberty in girls is defined as no phys- and puberty and hypogonadotropic hypo-
ical signs of puberty by age 13. In addition to the gonadism is difficult. Bone age as opposed to
possibility of constitutional delay of growth and chronological age has been suggested by some
puberty as a cause, other diseases that affect the to be a better marker of the age of puberty expec-
development and/or function of the hypothala- tation and therefore of the age when delayed
mus, pituitary, or ovaries need to be investigated. puberty should be defined. This is not widely
Functional effects on hypothalamic regulatory accepted.
inputs may be altered by malnutrition (e.g., in Like girls, hypogonadotropic hypogonadism
anorexia nervosa), malabsorption, inborn errors in boys can be caused by (1) Kallmann’s syn-
of metabolism, starvation, post-traumatic stress drome; (2) X-irradiation, infiltrative disease,
syndrome, or inability to maintain an appropriate tumors, and invasive central nervous system sur-
body composition. geries; (3) congenital disruptions from perinatal
CNS disruptions that affect the hypothalamus brain ischemia, malformations, or injuries; and
or pituitary include brain malformations, tran- (4) syndromes such as Prader-Willi, Lawrence-
scription factor deficiencies that affect hypotha- Moon-Bardet-Biedl, and others.
lamic neuronal cellular migration or maturation, Some have suggested that if normal adrenarche
and syndromes such as Prader-Willi, Laurence- occurs without pituitary gonadotropin output,
Moon-Bardet-Biedl, or Kallmann. Acquired dis- there is a greater likelihood of hypogonadotropic
ruptions may be due to traumatic brain injury, hypogonadism.
medications, surgeries, infiltrative diseases, If the pulse generator develops without any
and/or tumors. physical signs of puberty, the problem may
In addition to hypothalamic and pituitary be in the gonads and not the hypothalamus or
abnormalities, ovarian pathologies may be causes pituitary. Examples of such conditions are
of delay. Ovarian dysfunction could be due to Klinefelter syndrome, fragile X, Noonan
994 K. J. Sheridan
syndrome, mumps orchitis, chemotherapy, sur- Blood tests for LH, FSH, testosterone, and
gery, injuries, XRT, or tumors. DHEA-S should then be obtained. Depending
Another possible distinguishing feature of con- upon these investigations, the child may
stitutional delay compared to hypogonadotropic require a specific testing of the maturational
hypogonadism has been a differential response to state of the HPG axis. This usually means
a small dose of testosterone. a GnRH stimulation test, which assesses the
maturation of the gonadotropin cells in the
anterior pituitary and the ability to readily
Diagnosis and Treatment secrete preformed FSH and LH in response to
an exogenous GnRH such as Lupron, Histrelin,
Diagnosis of Central Precocious or Nafarelin.
Puberty When the hypothalamic pulse generator is acti-
vated, the intracellular stores of LH and FSH
When a precocious sign of puberty develops, one increase. An exogenous GnRH exposure (e.g., as
needs to distinguish (1) pathological from in a GnRH stimulation test) will readily release
benign causes and (2) true “central” puberty these stores of hormones. This implies a “puber-
from isolated partial puberty. These can be tal” readiness of the gonadotrophic cells.
masked by additional pituitary disease. For For example, a 100-mcg bolus of GnRH such
example, concurrent GH deficiency or thyroid as Lupron results in a rise of LH to >16 mIU/ml
hormone deficiency may mask the growth stim- from these puberty-ready pituitary gonadotrophs.
ulating effects of the precocious sex steroids. The FSH response to this stimulus in girls is less
These cases are usually referred to a pediatric useful in discrimination. Third-generation mono-
endocrinologist. clonal gonadotropin RIAs more sensitively detect
Investigation is warranted if: FSH and LH (Table 3).
The following levels have been correlated with
– More than one sign of puberty is present. initial pubertal maturation:
– Bone age advances more than 20% beyond the In central precocious puberty, one needs
height age. to exclude other pathologies such as tumors,
– Height growth accelerates. gonadotropin-independent precocious puberty,
– Signs of obesity, short stature, or acanthosis and hypothyroidism.
nigricans occur.
Table 3 LH luteinizing hormone, FSH follicle-stimulat-

The diagnosis of precocious puberty should ing hormone, GnRH gonadotropin-releasing hormone,
occur in a stepwise fashion. Investigation begins RIA radioimmunoassay
with documentation of the physical signs of Pubertal Hormone blood
puberty such as comedones, oily skin, body hormone level Other
odor, pubic hair, axillary hair, facial hair, genital Estrogens Estradiol>9 pg/ml Vaginal
growth, height growth spurt, or bone age advance- (girls) cornification
ment. Estrogen effects on breast size with simul- Testosterone 20–1200 ng/ml –
(boys)
taneous adrenal androgenic effects on hair and
Sleep- 1st increased –
acne in girls suggest a central pubertal activation. associated LH gonadotropin
Testes size increase in boys may help distinguish a Basal LH >0.6 IU/L Sensitivity
central or gonadotropin-dependent cause from a (monoclonal RIA) approx. 70%
peripheral or gonadotropin-independent cause. Basal FSH >2.0 IU/L –
Skin findings may help focus diagnoses on, for (monoclonal RIA)
example, Cushing’s syndrome, McCune-Albright Post-GnRH LH > 6.9 and FSH Sensitivity
stimulation >5.0 IU/L approx. 90%
syndrome, or neurofibromatosis.
In addition, the rise of GH and IGF1 contrib- Diagnosis of Delayed Puberty

utes to pubertal maturation.
If no signs of physical puberty is present at the
above age limits (especially bone age) and an
Treatment of Central Precocious investigation is deemed necessary, initial blood
Puberty testing for karyotype, gonadotropins (LH, FSH),
prolactin (to assess prolactinomas), and thyroid
Treatment (i.e., suppression of gonadotropin function tests could be obtained.
secretion) is easily accomplished by taking Elevated gonadotropin levels suggest normal
advantage of the observation that a prolonged development of the GnRH pulse generator imply-
(i.e., not episodic) exposure of the pituitary ing that the problem is in the gonads. Normal
gonadotrophic cell to an exogenous levels may suggest the need to pursue other
GnRH (Lupron, Histrelin, Nafarelin) results in pathology in the central nervous system.
suppression of that secretion, after an initial In a subgroup of boys with constitutional
stimulation. delay of growth and puberty, a small dose of tes-
This is continued until (1) the normal age of tosterone has resulted in a spontaneous pubertal
puberty is reached, (2) the bone age and chrono- development within months. The mild somatic
logical age are the same, or (3) the family of the maturational effects of exogenous testosterone
child with severe disabilities chooses not to inter- in these constitutionally delayed boys appear
fere with puberty in order to allow a more man- responsible for the pubertal progression. For exam-
ageable shorter adult. ple, in boys at least 14 years of age, 100 mg IM of
Adult height outcome is maximized when testosterone (as testosterone enanthate or testoster-
treatment begins at a younger age. For example, one cypionate) injected monthly for 3–4 months
adult height potential is achieved more readily in will foster testes enlargement, genital and pubic
boys less than 9 years old and testosterone levels hair growth, and other signs of normal puberty
>10 ng/deciliter compared to 11- or 12-year-old within 1–3 months. If no changes are seen by that
boys who begin treatment because of a rapidly time, then a second course of low-dose testosterone
progressive puberty leading to early closure of is given for an additional 2–3 months.
the growth plates. If there is any hypothalamic or pituitary dysfunc-
Comorbidities which may worsen when adult tion (e.g., resulting in “hypogonadotropic hypo-
height or length increases should be considered gonadism” or isolated growth hormone
in the risk versus benefit assessment of treating a deficiency), the “priming” testosterone will be
true central precocious puberty. Boys and girls ineffective.
with significant neurodevelopmental impair- A similar effect of estrogen priming in girls
ments (as in cerebral palsy, hydrocephalus, with delayed puberty is sometimes seen.
spina bifida, muscular dystrophy, seizure disor- All males and females who failed a trial of
ders) may be harmed by the continuous height or testosterone or estrogen, respectively, will need
length growth into adulthood, and therefore par- further work-up. This would include, for example,
ents may opt not to interfere with the onset of a GnRH stimulation test. Lack of response to
puberty at an early age. Difficulties in moving or this stimulation requires additional imaging and
transferring such adults may lead to greater risk genetic studies.
of fractures or other musculoskeletal injuries. On
the other hand, improved bone strength at earlier
ages due to sex steroid exposure may lessen the Treatment of Delayed Puberty
detrimental effects of an already compromised
bone due to inactivity, neuromuscular weakness, Idiopathic or other permanent causes of “hypo-
or medication exposure. gonadotropic hypogonadism” require sex
996 K. J. Sheridan
hormone replacement therapy. In boys, much Complications

lower doses of testosterone are needed, initially,
than that required for adult men. For example, The association of cerebral palsy and pubertal
50 mg per month of an intramuscular injection dysfunction is well known. Of course, many chil-
of testosterone enanthate or cypionate is started. dren with cerebral palsy also go through puberty
Comparatively, an adult replacement regimen is normally. Poor nutrition, frequent respiratory or
200 mg IM every 2 weeks. gastrointestinal infections, surgical procedures,
The dose is increased 50 mg every 6 months steroid, and other medication exposures will mod-
until the adult replacement dose is reached. Care- ulate the expected pubertal development just as it
ful attention to unwanted side effects of excess would in any child.
testosterone therapy is necessary. Side effects Puberty itself may cause a deterioration in
could include gynecomastia, priapism, or early gross motor function according to some opinions.
maturation of the physeal growth plates (limiting Detrimental changes in height, BMI, and muscle
the genetic adult height potential). contractures may accelerate with the onset and
Other androgen replacement regimens include progression of puberty. Worsening scoliosis, hip
daily administration of a gel or patch to the skin, malrotation, and personal hygiene concerns are
eventually mimicking the normal testosterone challenges faced during pubertal advancement
spike of 5–6 mg per day in adult men. The dosing (van Eck 2008).
progression using the skin applications is less well There are other problems which are common in
defined as to potential side effects and longitudi- children with cerebral palsy that may attenuate
nal effect on eventual adult height. growth and puberty. Swallowing difficulties,
More complex treatment regimens which use abnormal energy expenditure in movement disor-
gonadotropins, e.g., exogenous FSH and LH or ders, dystonia and dysautonomia, poor muscle
LH receptor stimulators, e.g. HCG, can result in tone (both weakness with spasticity and treatment
testicular enlargement and allow viable sperm of increased tone with baclofen and Botox), and
maturation and fertility in the adult. poor bone health are some examples.
In girls, estrogen replacement is accomplished When combined with a disordered develop-
by either an oral estrogen or estrogen skin patches. ment of the central nervous system in early
Dermal absorption of estrogens bypasses the liver infancy, unpredictable effects on muscle and
and decreases potential side effects of estrogens, bone, and central nervous system comorbidities
such as a thrombotic tendency. These are also (e.g., seizures), it is not surprising that pubertal
started at lower doses than that required for adult dysfunction could occur. However, it is very hard
replacement to decrease potential side effects of to predict who will experience these problems.
fluid retention, coagulability, painful breast swell-
ing and early closure of the growth plates.
One recommendation is starting a dose of Pre- Studies of Pubertal Milestones
marin (conjugated estrogens) at 0.3 mg per day in Children with Cerebral Palsy
and continuing for 6 months. At that point the
dose is increased to 0.625 mg per day for another Despite this complexity, there have been attempts
6 months. Once this adult dose is reached, proges- to characterize pubertal patterns in children with
terone (e.g., Provera) is added to induce menses. cerebral palsy.
There are many other possible regimens. Oral Over the last 100 years, published studies have
contraceptive agents which combine these hor- described associations between central nervous
mones to induce monthly menses can eventually system dysfunction and pubertal dysfunction.
be substituted. Women who desire pregnancy can However, there were no large epidemiological
also take advantage of the gonadotropin regimens studies of these associations until the late twenti-
(shots, oral meds, and pumps) as noted for males. eth century.
A landmark study of secondary sexual devel- Table 4 Comparison of patterns of sexual development in
opment in children with cerebral palsy was Caucasian boys with cerebral palsy to the general popula-
tion (years). NAGCPP North American Growth in Cerebral
conducted in the late 1990s. Worley et al. reported Palsy Project, NHANES National Health and Nutrition
sexual maturation, body composition, and other Examination Survey
anthropometric measurements in 207 children NHANES III
aged 3–18 years who had cerebral palsy (Worley NAGCPP (3–18) (8–18)
2002). This was part of a multicenter research 25% 50% 75% 25% 50% 75%
consortium study of nutrition, puberty, and health Stage ile ile ile ile ile ile
status of children with cerebral palsy. The North Genital development
American Growth in Cerebral Palsy Project Initial age 7.8 9.9 12.1 8.9 10.0 11.3
Tanner II
(NAGCPP) represented six sites including Chil-
Completed 13.9 14.7 15.4 12.7 13.4 14.2
dren’s Hospital of Philadelphia, University of age
Rochester, McMaster’s University of Ontario, Tanner IV
University of British Columbia at Vancouver, Pubic hair
and a combined site of Duke University and Initial age 9.3 10.7 12.2 11.1 11.9 12.7
the University of North Carolina. Tanner II
Children who were entered into this study had Completed 13.5 14.1 14.8 12.8 13.5 14.1
age
a confirmed diagnosis of cerebral palsy and were
Tanner IV
between the ages of 3 and 18 years. They had no
NAGCPP North American Growth in Cerebral Palsy
other known genetic or metabolic issues that Project, NHANES National Health and Nutrition Examina-
impacted growth. Cerebral palsy was character- tion Survey
ized according to a gross motor function classifi-
cation system (GMFCS).
Six hundred thirty children had cerebral palsy. completion as Tanner IV or V pubic hair and
Three hundred forty-five met age and motor inclu- genital development (Table 4).
sion criteria. Because of geographical distance from In girls, puberty onset was defined as Tanner II
the study sites and other factors, 207 were enrolled pubic hair and/or breast tissue; pubertal comple-
and underwent Tanner pubertal stage assessment. tion as Tanner IV or V pubic hair or breast tissue
Tanner staging described the pubertal matura- (Table 5).
tional features of pubic hair, breast tissue, and Girls in the Physician Research in Office
genital growth. Body composition was studied Setting (PROS) study (Herman-Giddens et al.
using subcutaneous skinfold thickness. 1997) were also compared to the NAGCPP and
The subjects were compared to two distinct NHANES III studies.
reference population groups: (1) NHANES III The mean age of puberty onset in all these
from 1988 to 1994 (females >12 years and children was 9.6 years (girls and boys). More
males 8–18 years) and (2) Physician Research than half of the girls were classified in the more
Office Settings Network (PROS-AAP) national severe GMFCS V category. The remainder
study of sexual maturity in girls (females age distributed evenly between GMFCS III and
3–12 years) (Third National Health and Nutrition IV. As expected, girls started puberty earlier than
Examination Survey 1988–1994 NHANES III boys. By age 8.6 years, 50% of the girls were at
Examination Data File (CDROM Series 11, Nos Tanner II breast or pubic hair. By age 8.9 years,
1 and 2A) Hyattsville, MD: US Department of 50% of the boys were at Tanner II pubic hair or
Health and Human Services, National Center for genital development.
Health Statistics, Center for Disease Control and However, girls with cerebral palsy tended to
Prevention; 1998) (Herman-Giddens et al. 1997). complete puberty later than did boys with cerebral
In boys, puberty onset was defined as Tanner II palsy. At age 14.4 years, 50% of boys completed
pubic hair and/or genital development; pubertal puberty (Tanner IV of V pubic hair and genital
998 K. J. Sheridan
Table 5 Comparison of patterns of sexual development in 4. White boys with CP developed pubic hair and
Caucasian girls with cerebral palsy to the general popula- genital growth earlier than in the general pop-
tion and to the PROS study (years)
ulation, but genital development in boys was
NAGCPP completed later (Worley 2002, p. 899).
(3–18) NHANES III (8–18)
25% 50% 75% 25% 50% 75%
Stage ile ile ile ile ile ile Another observation was the sexual differ-
Breast development ences in the association of body fat and puberty.
Initial age 8.1 10.1 12.1 9.6 10.3y 11.0y In white girls with CP, more body fat was associ-
Tanner II ated with advanced sexual maturation. In white
Completed 14.2 15.6 16.9 12.1 13.2 14.1 boys with CP, less body fat was associated with
age advanced sexual maturation. Whether this
Tanner IV
reflected the differences between the sex steroids
Pubic hair
on body fat composition (amount and distribu-
Initial age 6.2 8.2 10.1 9.6 10.5 11
Tanner II or tion) is unknown.
Complete age 12.1 13.2 14.4 12.1 12.9 13.6 This is a very useful study in that it attempts to
Tanner IV better describe the unique pubertal changes in
children with cerebral palsy. It only suffers from
the difficulties inherent when comparisons are
development) and at age 15.7 years, 50% of the made to more statistically powerful reference
girls completed puberty (Tanner IV or V breast populations such as in NHANES III and PROS
and pubic hair). (e.g., with a larger number of study subjects).
The sample size for black children was smaller Although firm conclusions about what consti-
than for white children (69% white). Overall 50% of tutes “normal” puberty in children with cerebral
the black children with CP (n = 43) reached puberty palsy cannot be derived from this study, it is a
using the above definitions by age 5.6 years, earlier major step forward in such understanding.
than did white children with CP who reached the
same level of maturity at age 9 years.
Comparing this study with the two referenced Studies of Pubertal Hormonal
populations obtained from NHANES III and and Metabolic Changes in Children
PROS demonstrated the following: with Cerebral Palsy
1. The mean age for onset of Tanner II breast in Using the same NAGCPP consortium population,
white girls with cerebral palsy was the same as Kuperminc et al. suggested a possible association
for those without cerebral palsy (e.g., in PROS) of the attenuated growth pattern seen in children
2. However, there was a larger range of onset of with cerebral palsy with a compromise in growth
puberty in girls with cerebral palsy. This was hormone and IGF1 function as they went through
described as a “greater proportion” of white puberty (Kuperminc 2009). Although this was a
girls with cerebral palsy having early onset of small study with 20 children with cerebral palsy,
breast development (Tanner II or greater) and a some interesting observations were made.
greater proportion with delayed onset of breast Twenty children with cerebral palsy, GMFCS
development. The greater variability in puber- III to V, ages 6–18, were compared to a reference
tal timing was thought to be secondary to the group of 63 typically growing children without
variety of central nervous system insults affect- cerebral palsy. These children were followed
ing the hypothalamic GnRH pulse generator. longitudinally every 3 months with periodic
3. Interestingly, white girls with cerebral palsy biochemical assessments for growth hormone,
completed breast development (but not pubic the GH-related proteins IGF1 and IGFBP3,
hair development) later than in the general anthropometric measurements, and bone matura-
population tion (bone age).
The following was seen: In lieu of this “value-added” information,

these children will need investigations for path-
1. Bone maturation (as assessed by bone ological causes just as would the general
age) was 10 months delayed in the children- population.
with cerebral palsy compared to There have been published studies (mostly
5 months advanced in typically growing case reports and small population studies)
children. throughout the twentieth century addressing
2. The rate of growth (estimated bone length various neurological conditions (including
velocities) was less for boys and girls with cerebral palsy) and their associations with
cerebral palsy across all stages of puberty com- precocious puberty. What classified a child as
pared to normal children. having cerebral palsy in those early years, how-
3. Secreted growth hormone and its congener ever, may be different from that used today.
IGF1 were diminished in children with cere- In 1910, an Italian publication described a
bral palsy compared to the others. syndrome they named macrogenitosomia precoce
in which precocious sexual development was
This suggested that the pattern of less associated with abnormalities of the posterior
robust growth during puberty in children with hypothalamus (Pelizzi 1910).
cerebral palsy may be related to a diminished Similar observations were made in 1925
GH-IGF1 axis. This has implications for growth (Haldeman 1925).
hormone use in this population during the
pubertal years. Growth hormone is known to
affect not only stature but also bone health, body Studies of Mechanisms of Pubertal
composition, muscle growth, and, in adults, car- Disruption in Cerebral Palsy
diovascular status.
Houlihan (2006) looking at the same study The suggestion that an anatomical disruption of
population as Kuperminc et al. reported in an the brain in children with cerebral palsy is respon-
abstract on the measurement of sex hormones, sible for interference with the normal inhibitory
estradiol, testosterone, and DHEA-S in these chil- pathways on the hypothalamus is a commonly
dren. In the children with cerebral palsy, testoster- held belief. It is a presumed cause for the pubertal
one levels were lower in boys at Tanner stages abnormalities seen in cerebral palsy. This idea that
I and II, and DHEA-S levels were lower in boys certain anatomic regions of the brain were
and girls across all Tanner stages. Interestingly, involved in normal childhood suppression of
estradiol, at all puberty stages, was similar puberty was first promulgated in the early part of
between the cerebral palsy girls and the typically the twentieth century.
growing girls. Several observations in the early 1900s pro-
Defining precocious or delayed puberty in vided support for this view. In 1925 a paper by
children with cerebral palsy is difficult. However, Horran and Bailey (1928) described associations
it is important to help differentiate more serious of pineal tumors with spasticity and other neuro-
pathologies from benign variants of pubertal logical problems.
development. In 1941 a review of 17 patients with precocious
Investigations into possible pathologies (e.g., puberty and hypothalamic tumors by Weinberger
requiring MRI/CT imaging, frequent blood test- and Grant proposed:
ing, and hormonal stimulation or suppression
tests) that would be engendered by these investi- . . .tumors in the posterior portion of the hypothala-
gations are inconvenient and uncomfortable. mus destroy some portion of the mechanisms and
neural pathways which normally serve to control or
These could be avoided if the expected pubertal inhibit the rate, character or intensity of the nerve
variations in children with cerebral palsy were impulses passing to the pars distalis of the pituitary.
better understood. (Weinberger 1941)
1000 K. J. Sheridan
Perloff and Nadine in 1950 report four cases Table 6 Classification of precocious puberty (in this
of neurologically impaired children described study)
as having congenital spastic quadriplegia with Total
signs of androgen excess but not complete Classification number (#) Males (#) Females (#)
(true) puberty. In this report, the precocity was Idiopathic 3 0 3
described as precocious adrenarche (Perloff and Uncertain 2 2 0
class
Nodine 1950).
Central 15 1 14
In 1989, Robertson et al. in a larger cohort precocious
studied 161 girls with neonatal encephalopathy puberty
and found, prospectively, variable degrees of Premature 8 2 6
early sexual maturation. The 4.3% of sexually adrenarche
precocious girls in this group was much greater Premature 4 0 4
thelarche
than (at the time) 0.6% prevalence in the general
Total 32 5 27
population. Three of the seven girls with
early sexual maturation had cerebral palsy. The
early changes included premature thelarche, Table 7 Many diagnoses were associated with these
developmental disabilities
adrenarche, and menarche. In the same study,
260 boys with neonatal encephalopathy did not Seizure disorder 14
Intellectual delay 12
demonstrate any signs of early sexual maturation
Cerebral palsy 10
by age 8 years (Robertson and Morrish 1989).
Hydrocephalus 7
Siddiqi et al. (1999) in a large 10-year retro-
Head injury 4
spective review of 15,719 patients with develop-
Myelodysplasia 4
mental disabilities at the University of Iowa Other (tumor, infection, asphyxia, etc.) 16
uncovered 32 children with precocious sexual
development. Precocity was defined according to
the ranges for the general population accepted at
that time (ages 8 years and 6 months to 13 years case-controlled study in Italy in the mid- to later
for girls and ages 9 years to 14 years for boys). 2000s (Bruzzi et al. 2017).
The earliest age of precocity was 19 months, and The study population was distributed among
the mean age of onset was 7 years and 2 months in three Italian academic centers from January 2001
boys and 5 years and 11 months in girls. They to December 2014. The total number of girls in the
observed 32 out of 15,719 children with precocity. study was only 66, distributed in a controlled
This was 20-fold greater than that expected in fashion among three groups (Group A, B, and C).
the general population (one in 10,000 per the
United States Department of Human Health and Group A - cerebral palsy and central precocious
Human Services, 1997). Fifteen of these 32 chil- puberty.
dren had central as opposed to peripheral preco- Group B - cerebral palsy only.
cious puberty (Table 6). Group C - central precocious puberty without
This study was done at a single major Midwest cerebral palsy.
regional referral center, and, therefore, its appli-
cability to the population at large is not clear Only central precocious puberty was studied.
(Table 7). It does support, however, the assump- Other forms of precocity were excluded. Most of
tion of increased frequency of early puberty in the children with cerebral palsy were also on anti-
children with cerebral palsy. epileptic drugs (AEDs).
To better understand the relationship between All children had anthropometric measure-
early puberty and spastic quadriplegia, Bruzzi ments, biochemical analyses of LH, FSH and
et al. performed a retrospective, longitudinal estradiol, Tanner staging of sexual development,
parental heights review, bone age skeletal X-rays, likelihood of a pathological cause of precocious
and comorbidity assessments. puberty (i.e., not just “early puberty” onset), and
The children with cerebral palsy were classi- (3) an increased probability of clinically relevant
fied according to GMFCS as III, IV, or V. The effects on bone and muscle health.
children with precocious puberty were usually Expert opinions, however, are needed as to the
subjected to a GnRH stimulation test to define validity and applicability of blood hormone test-
the central precocious condition. ing and stimulation testing of the HPG axis in
At the beginning of the study, there was no these children. Expert opinion is also needed to
difference in height, weight, and body mass help guide treatment regimens and recommenda-
index detected in the children with cerebral palsy. tions for daily care in these children with neuro-
A subtle observation was that basal LH, FSH, and muscular compromise.
estradiol levels were higher in children with cerebral Individual opinions from practitioners, family
palsy and central precocious puberty compared to members, and others still vary widely as to the
those with cerebral palsy alone, yet the stimulated need (1) for treatment, (2) for surgical interven-
values of these gonadotropins were the same. tions, (3) for manipulation of puberty (surgically
They also noted that at the time of central or hormonally) to modify adult care concerns (e.g.,
precocious puberty diagnosis, the children with through hysterectomies, infantilizing procedures,
cerebral palsy were shorter (using a height SDS such as the “Ashley Treatment,” or growth attenu-
corrected for midparental height SDS) than those ation procedures (Kirschner et al. 2007; Allen et al.
without cerebral palsy. 2009)), (4) for control of menstruation and men-
Basal LH and estradiol levels were higher in strual cycles in females, and (5) for controlling or
the cerebral palsy children with central precocious treating socially unacceptable sexually related
puberty compared to those without cerebral palsy. behaviors. For example, there are differing opin-
In the children who were treated for their ions about the potential benefit or harm on eventual
precocious puberty, the improvement in height adult height or length, adult bone quality, and psy-
potential was less in those that had cerebral chosexual adjustment with treatment regimens for
palsy than in those who did not. precocious and delayed puberty in childhood.
The authors concluded that the HPG axis was More multi-site studies involving centers with
less inhibited in the children with cerebral palsy sizable populations of children with cerebral palsy,
who had central precocious puberty than in those multiple disciplines caring for these children (pedi-
without cerebral palsy and that there are other atricians, complex care providers, developmental
factors which may ameliorate the benefit of sup- specialists, physiatrists, endocrinologists, and neu-
pression on eventual adult stature. rologists), and better technology for assessing
These subtle observations may be difficult to anthropometric measures of growth and develop-
generalize to the broader population because of ment are needed to help distinguish benign from
the small sample size. pathological influences on growth and pubertal
development. This not only impacts the well-
being of the developing child with cerebral palsy
Conclusion but profoundly affects their adult health.
Normal pubertal development is extremely impor-

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muscle health. ▶ Growth Attenuation for the Child with Cerebral
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Endocrine Dysfunction in Children
Hussein Elmufti and Robert C. Olney
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1004
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1004
Pituitary Gland . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1004
Thyroid Gland . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1006
Adrenal Gland . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1007
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1008
Pituitary Gland . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1008
Thyroid Gland . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1009
Adrenal Gland . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1010
Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1010
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1010
Abstract factor in the cause of cerebral palsy and may be

With a few exceptions, children and adults misdiagnosed as cerebral palsy. The diagnosis
with cerebral palsy are not at greater risk for of endocrine disorders can be a challenge in the
endocrine disorders than the general popula- setting of cerebral palsy, and special consider-
tion. However, endocrine disorders may be a ation must be made by those who provide care
to these patients. This chapter discusses the
most common endocrine disorders of the pitu-
H. Elmufti itary, thyroid, and adrenal glands, including
Division of Endocrinology, Diabetes, and Metabolism,
Nemours Children’s Specialty Care,
congenital and acquired conditions. General
Jacksonville, FL, USA guidelines for screening and treatment in
Department of Pediatrics, University of Florida,
patients with cerebral palsy are presented.
e-mail: Hussein.Elmufti@nemours.org Keywords
R. C. Olney (*) Pituitary gland · Adrenocorticotropic hormone
Division of Endocrinology, Diabetes, and Metabolism, (ACTH) · Thyroid-stimulating hormone
Nemours Children’s Specialty Care, (TSH) · Growth hormone · Luteinizing
e-mail: robert.olney@nemours.org
hormone (LH) · Follicle-stimulating hormone

https://doi.org/10.1007/978-3-319-74558-9_222
1004 H. Elmufti and R. C. Olney
(FSH) · Vasopressin · Antidiuretic hormone Natural History

(ADH) · Thyroid gland · Thyroid hormone ·
Adrenal gland · Cortisol · Aldosterone Pituitary Gland
The pituitary gland is made up of an anterior lobe,

Introduction a posterior lobe, and a vestigial intermediate lobe
and is situated within the bony sella turcica,
Endocrine disorders may play a causative role in underneath the brain and behind the orbits. The
cerebral palsy. Adrenal corticosteroids play a key dural roofing protects the gland from compression
role in cardiovascular stability during times of by fluctuant cerebrospinal fluid pressure. The
stress, including the perinatal period. Both corti- gland communicates with the brain through the
sol and growth hormone are required in the neo- pituitary stalk, which originates from the median
natal period to maintain normal blood glucose eminence of the hypothalamus (Kaiser and Ho
levels. And thyroid hormone is crucial for normal 2016). The pituitary stalk contains a portal venous
brain growth and development. Congenital system that allows blood-borne endocrine signals
absence of these hormones (singly or in combina- to reach the anterior pituitary lobe, as well as
tion) are generally diagnosed in the neonatal nerves that terminate in the posterior lobe.
period, but delayed or missed diagnosis may The anterior pituitary gland serves as the
have permanent neurologic sequelae. There are body’s “master gland” integrating data in the
also reports in the literature of undiagnosed form of brain-derived and systemic hormones to
hypopituitarism and hypothyroidism being mis- direct the function of a number of metabolic pro-
diagnosed as cerebral palsy. Hence an understand- cesses. Table 1 lists the cell types present in the
ing of these endocrine issues is important for those anterior pituitary gland, the regulatory signals
who provide care for these children so that timely received from the brain, and the major systems
diagnosis can be made and treatment started. subsequently regulated. In contrast, the posterior
Patients with cerebral palsy have the same risk lobe of the pituitary gland serves as a brain/blood
as the general population for acquired endocrine transducer where nerve cells directly secrete hor-
dysfunction, the most common of which is pri- mones into the bloodstream. Nerves arising from
mary hypothyroidism. However, the symptoms of supraoptic and paraventricular nuclei within the
hypothyroidism (and other endocrine dysfunc- hypothalamus run though the pituitary stalk and
tion) may be difficult to ascertain as the symptoms terminate in the posterior lobe. The hormones
overlap with those of cerebral palsy itself, produced are vasopressin (also called antidiuretic
resulting in possible delay in diagnosis and hormone, ADH) and oxytocin. Vasopressin acts
treatment. on the collecting ducts of the kidney to stimulate
This chapter discusses the endocrine system, water reuptake and also has vasoconstrictive
particularly the pituitary, thyroid, and adrenal sys- effects. Oxytocin acts during labor to stimulate
tems, as they relate to patients with cerebral palsy. cervical relaxation and uterine contractions and
The goal is to assist the physicians treating these postpartum to stimulate milk let down in the
patients to become familiar with endocrine dys- breast.
function and when to suspect if they might be The pituitary gland is insensitive to anoxic
present. General guidelines on screening and events and surrounding brain injury and hence
treatment are presented. Growth and bone health deficiencies are not caused by anoxia nor by cere-
are commonly affected by endocrine disorders bral palsy itself. However, the hypothalamus and
and are complex issues in cerebral palsy. some of the higher centers that ultimately control
Similarly, disorders of the timing of the onset of pituitary function can be affected in cerebral palsy.
puberty are common in children with cerebral Congenital absence of pituitary hormone pro-
palsy. Separate chapters are devoted to these duction presents as deficiency of the target organ
topics in this text. hormone. Hence, congenital TSH deficiency
71 Endocrine Dysfunction in Children with Cerebral Palsy 1005
Table 1 Hormones of anterior pituitary gland

Target Target organ
Cell types Controlling hormones Hormones released organs hormones
Corticotrophs Corticotropin-releasing Adrenocorticotrophic hormone Adrenal Cortisol
hormone (CRH) (ACTH) glands
Somatotrophs Growth hormone- Growth hormone (GH) Liver, Insulin-like growth
releasing hormone fat, bone factor-I
(GHRH) (+)
Somatostatin ( )
Thyrotrophs Thyrotropin-releasing Thyroid-stimulating hormone Thyroid Thyroxine,
hormone (TRH) (TSH) gland triiodothyronine
Gonadothrophs Gonadotropin-releasing Follicle-stimulating hormone Gonads Estrogen,
hormone (GnRH) (FSH)Luteinizing hormone (LH) progesterone,
testosterone
Lactotrophs Somatostatin Prolactin (PRL) Breast
Table 2 Pituitary hormone deficiency

Target Signs of deficiency
organ
Hormone hormone Neonatal period Later
ACTH Cortisol Hypoglycemia, hypotension, Hypoglycemia, hypotension,
cardiovascular instability, poor weight cardiovascular instability, chronic nausea/
gain or weight loss, poor feeding, vomiting
vomiting, hypotonia
GH IGF-I Hypoglycemia, micropenis Short stature, growth failure, osteopenia
TSH Thyroxine Enlarged fontanelles, hypotonia, Enlarged fontanelles, delayed fontanelle
temperature instability, jaundice closure, macroglossia, umbilical hernia,
developmental delay, short stature,
constipation
FSH and Estrogen, Micropenis (but not ambiguous genitalia) Delayed puberty, absent puberty,
LH testosterone hypogonadism
PRO – None None
presents the same as congenital hypothyroidism 252 premature infants (weight <999 g) found no
and ACTH deficiency as adrenal insufficiency. difference in the rate of cerebral palsy at 2 years,
Table 2 shows the signs present in the neonatal suggesting this is not a common problem
period of isolated pituitary hormone deficiency. (Watterberg et al. 2007). In utero, the fetus is not
Of particular concern is adrenal insufficiency due entirely dependent on the pituitary-adrenal axis
to ACTH deficiency. In neonates with perinatal for cortisol production, and hence the neonate
asphyxia or with sepsis, many of the clinical signs has some protection; however, by 2 weeks of
overlap with those of adrenal insufficiency, which age, the baby is completely dependent on this
may not be recognized, resulting in delay of treat- regulation. Hence neonates with ACTH defi-
ment. There are reports of children with cerebral ciency are at risk for adrenal crisis at a time
palsy diagnosed later in life with multiple pituitary when they are not being as closely monitored.
hormone deficiency (Uday et al. 2017), although Prolonged hypoglycemia and hypotension or
it is unknown if this deficiency played a role in shock are then risk factors for the development
the events leading to the development of of cerebral palsy.
cerebral palsy. This is also a concern in those Congenital absence of pituitary hormone pro-
born extremely premature, in whom diagnosing duction can occur in isolation or in combination
adrenal insufficiency can be difficult. A placebo- with other pituitary hormones and can occur with
controlled trial of low-dose corticosteroids in or without malformations in the region of the
hypothalamus and/or pituitary gland. By far the with low bone mineral density, osteopenia, and/or
most common syndrome of congenital pituitary osteoporosis in adolescents and adults. As
hormone deficiency is septo-optic dysplasia, also discussed in ▶ Chap. 26, “Managing Bone Fra-
called De Morsier’s syndrome (MIM 182230). gility in the Child with Cerebral Palsy,” children
Septo-optic dysplasia is a highly heterogeneous with cerebral palsy (particular non-ambulatory
condition comprising a spectrum of central patients) are already at increased risk for these
nervous system malformations that involves problems. The early identification of growth hor-
in various degrees the optic nerves, the mone deficiency can lead to appropriate treatment
hypothalamic-pituitary axis, and other midline and likely reduce this risk.
structures such as the septum pellucidum and the Screening for growth hormone problems
corpus callosum. The classic triad of this syn- should consist of an AP X-ray left hand/wrist
drome is hypoplastic optic nerves, absent septum film for bone age determination (bone ages are
pellucidum, and pituitary hormone deficiency. delayed in the children with growth hormone defi-
However, in many cases, patients have only ciency) and an IGF-I level. If growth hormone
one or two of these findings. The most common deficiency is suspected, formal growth hormone
pituitary deficiency is growth hormone, but testing is required and best done by the pediatric
panhypopituitarism is common, including diabe- endocrinologist.
tes insipidus. Because of the associated brain The most common endocrine effects of cere-
malformations, cerebral palsy is part of the bral palsy are from dysregulation of LH and FSH
clinical spectrum for this syndrome. There production, which presents as abnormal timing of
are also reported cases of dyskinetic cerebral the onset of puberty or hypogonadism. On aver-
palsy (athetoid-dystonic subtype) associated with age, the onset of puberty is earlier in children with
septo-optic dysplasia (Trabacca et al. 2012). cerebral palsy (Worley et al. 2002) and true pre-
Lack of growth in children with cerebral palsy cocious puberty is common. Delayed puberty in
is often the result of undernutrition but could also children and hypogonadism in adults (Trinh et al.
be due to impaired or deficient growth hormone 2016) with cerebral palsy also occur, both as a
secretion. Growth hormone is produced in the result of undernutrition and from pituitary defi-
pituitary gland under the regulation of the hypo- ciency. This topic is discussed in greater detail in
thalamus. Insulin-like growth factor I (IGF-I) is a ▶ Chap. 70, “Premature and Delayed Sexual Mat-
hormone primarily produced in the liver and is uration in Children with Cerebral Palsy” of this
regulated by growth hormone. Blood levels of text.
IGF-I are useful in assessing growth hormone
status, although undernutrition can also cause
low levels. Both IGF-I and growth hormone levels Thyroid Gland
were reported to be low in patients with cerebral
palsy (Kuperminc et al. 2009), and patients with The thyroid gland sits across the front of the lower
CP and growth failure who underwent growth neck, just anterior to the trachea. The thyroid
hormone secretion testing showed subnormal gland secretes thyroxine (T4) and to a lesser extent
levels of growth hormone secretion suggesting a triiodothyronine (T3), into the bloodstream. These
higher prevalence of growth hormone deficiency hormones act as overall regulators of metabolism.
(Devesa et al. 2010; Hamza et al. 2011). In Virtually all tissues contain thyroid hormone
infancy, growth hormone deficiency can be a receptors. In the cardiovascular system, thyroid
cause of hypoglycemia and must be considered hormone regulates heart rate and inotropy, in the
during evaluation of this problem. Ordinarily, gastrointestinal system it regulates rate of transit
growth hormone deficiency is not a cause of and liver metabolism, in the skin it regulates skin
hypoglycemia in older children, but this has cell turnover and growth of hair and nails, and it is
been described in children with cerebral palsy crucial for growth of the brain in infancy and
(Andersen and Lund 1995). It is also associated toddlerhood. Thyroid hormone production and
release is regulated by pituitary-derived TSH. Pri- literature still includes reports of congenital hypo-
mary (thyroid gland failure), secondary (pituitary thyroidism being misdiagnosed as cerebral palsy
TSH deficiency), and tertiary (hypothalamic fail- (Han Ze et al. 2011).
ure) hypothyroidism all present with the same The incidence of acquired primary hypothy-
signs and symptoms. roidism is not increased in patients with cerebral
In infants with extreme prematurity, the pitui- palsy, except those with chromosomal abnormal-
tary/thyroid axis is not fully functioning and tran- ities. However, it is relatively common in child-
sient hypothyroidism is frequently seen. This hood and could co-occur in patients with cerebral
transient hypothyroidism has been associated palsy. Hashimoto thyroiditis (autoimmune thy-
with an increased incidence of cerebral palsy roiditis) is the most common cause of hypothy-
(Hong and Paneth 2008). Controlled trials of roidism in areas of the world in which dietary
L-thyroxine replacement in these infants have iodine is sufficient (Brent and Weetman 2016).
shown mixed results, with some (Suzumura et al. People with chromosomal abnormalities are at
2011) showing a decrease in the incidence of increased risk for autoimmune diseases, and
cerebral palsy, while others (Uchiyama et al. Hashimoto thyroiditis is by far the most common.
2015) found no difference. A systematic review Thyroid ectopy is also a cause of acquired hypo-
has concluded that there is insufficient evidence to thyroidism. The symptoms of hypothyroidism in
support this treatment (Osborn and Hunt 2007). older children are constipation, dry skin, fatigue,
Maternal iodine deficiency (which is very rare and abnormal weight gain and, in women, heavy
in developed countries) and other maternal and frequent periods. A goiter may or may not be
thyroid disorders are also associated with an present. Screening for hypothyroidism consists
increased incidence of cerebral palsy (Hong and of a TSH and free T4 levels. Elevated TSH
Paneth 2008). levels are diagnostic of primary hypothyroidism.
As with the pituitary gland, the thyroid gland is As Hashimoto thyroiditis is the most common
resilient to anoxia or ischemia. However, hypo- cause, anti-thyroglobulin and antithyroid
thalamic (tertiary) hypothyroidism can occur. In peroxidase antibodies are often included in the
addition, congenital hypothyroidism is relatively initial screen for patients with suspected
common (incidence of 1:2000–1:4000) and may hypothyroidism.
be present coincidentally in infants with hypoxic
events. The most common cause of congenital
hypothyroidism is athyrosis or absence of the Adrenal Gland
thyroid gland. Thyroid ectopy, where the gland
forms in an abnormal location (anywhere from the The adrenal glands are located on top of the
base of the tongue to the mediastinum), disorders kidneys. The glands are made of a cortex
of thyroxine biosynthesis (dyshormonogenesis), and medulla, with the cortex serving a purely
and thyroid-blocking antibodies of maternal ori- endocrine function and the medulla serving
gin are also causes of congenital hypothyroidism. a neuroendocrine role. The adrenal cortex is
The symptoms of hypothyroidism in infants divided into three histologic zones; the zona
includes hypotonia, poor temperature regulation, glomerulosa, which makes aldosterone; the zone
and poor feeding and weight gain. These symp- fasciculata, which makes cortisol; and the
toms also occur in anoxic encephalopathy and zona reticularis, which makes androgens (Stewart
hypothyroidism must be considered by clinicians and Newell-Price 2016). Aldosterone primarily
caring for these infants. Newborn screening regulates renal handling of sodium and potassium
results cannot be relied on in this situation as and is under the control of the renin/angiotensin
most are TSH based (TSH levels can be low, system. Cortisol is a stress hormone with complex
normal, or slightly elevated in central hypo- physiologic effects. It regulates hepatic gluconeo-
thyroidism) and do not consistently identify genesis and glycogenolysis to support blood glu-
infants with central hypothyroidism. Recent cose levels and the cardiovascular system to
support blood pressure, as well as suppresses disease), infections of the adrenal glands, and
immune function and regulates bone turnover to adrenal gland hemorrhage. Patients who are
free up resources needed during the time of met- treated with glucocorticoids for other reasons are
abolic stress. Cortisol release is regulated by also at risk for adrenal insufficiency after the
pituitary-derived ACTH. medication has been stopped. Patients generally
Congenital adrenal insufficiency is a cause of present with fatigue, orthostatic hypotension, and
hypoglycemia and cardiovascular instability in chronic nausea and vomiting. Chronic elevation
the neonatal period and hence a risk factor for of ACTH results in hyperpigmentation, usually of
cerebral palsy. Central adrenal insufficiency is the gums and flexor surfaces. Often a concurrent
the result of ACTH deficiency and is discussed illness will push them into acute adrenal failure
above. The most common cause of primary adre- with hypotension/shock, hypoglycemia, and
nal insufficiency is congenital adrenal hyperplasia occasionally death. Patients with cerebral palsy
(CAH). This group of disorders are caused are not at increased risk for these disorders.
by biosynthetic defects of cortisol. The most Screening for adrenal insufficiency can be done
common of these (95% of cases, 1 in 15,000 by obtaining a cortisol level during an acute crisis,
newborns) is deficiency of the enzyme before any glucocorticoids are given. A level
21-hydroxylase (MIM 201910) and is an autoso- greater than or equal to 18 ng/mL rules out adrenal
mal recessive disorder. This enzyme plays a role insufficiency. In infants greater than 3 months of
in both aldosterone and cortisol biosynthesis. age, 8:00 am cortisol levels can be used as a screen.
In the complete absence of 21-hydroxylase (salt Diagnosis of adrenal insufficiency is done by
wasting CAH), aldosterone deficiency results in ACTH stimulation testing. For suspected central
renal salt wasting and hyponatremia and excess adrenal insufficiency, lack of ACTH stimulation
potassium reuptake, causing hyperkalemia. leaves the adrenal gland poorly responsive to an
Cortisol deficiency results in hypotension and acute increase in ACTH. Hence a small dose of
hypoglycemia. The absence of cortisol increases exogenous ACTH results in a subnormal response
ACTH levels, which drives the adrenal glands of cortisol. For testing, 1.0 mcg of ACTH(1–24)
to overproduce androgens so that girls with (synacthen, cosyntropin, Cortrosyn®) is given IV
this disorder are born with virilized genitalia. push and cortisol levels drawn at 0, 30, and 60 min.
Historically, infants with salt-wasting CAH pre- Normal adrenal function is defined as any cortisol
sented within a few weeks of birth with shock level over 18 ng/mL. For suspected primary adre-
and a high mortality rate. Survivors were at risk nal failure, a higher dose (250 mcg) of ACTH
for later development of cerebral palsy. In the (1–24) is given and cortisol levels measured at
USA, congenital adrenal hyperplasia due to 0 and 60 min. Intermediates for adrenal biosynthe-
21-hydroxylase deficiency is now included on sis are usually also measured to identify and type
the newborn screen, allowing infants to be diag- CAH. Normal adrenal function is defined as any
nosed before this occurs. Milder forms of cortisol level over 18 ng/mL.
21-hydroxylase deficiency effect only cortisol
production (simple virilizing CAH) and present
with adrenal insufficiency without the electrolyte Treatment
abnormalities. Girls present with virilization. An
even milder form (non-classic CAH) presents in Pituitary Gland
childhood as precocious adrenarche and in adult
women as hyperandrogenism. Rarer causes of Pituitary deficiency is treated by replacing
CAH and congenital adrenal hypoplasia also the target hormone. ACTH deficiency is treated
exist and can also cause adrenal insufficiency. with replacement hydrocortisone (Cortef®), 10 mg/
Acquired adrenal insufficiency is rare and can m2/day, divided three times a day. Increased doses
be caused by genetic disorders such as adreno- of two or three times this are needed during times
leukodystrophy (MIM 300100), autoimmune of acute illness or injury. Injectable hydrocortisone
destruction of the adrenal gland (Addison (Solu-Cortef®) is available in emergency kits
for use during times of stress when it can’t be given Diabetes insipidus (ADH deficiency) is
orally, such as during severe vomiting or uncon- treated with access to fluids and with
sciousness. It is important that stress coverage be desmopressin (DDAVP ®). In infants and chil-
given prior to anesthesia for any surgical proce- dren with an intact thirst mechanism, unlimited
dure. Subsequent dosing is based on body surface access to water is all that is needed to maintain
area and on symptoms of adrenal insufficiency. electrolyte balance. While they will continue to
Height must be monitored carefully as even modest have polyuria, homeostatic mechanisms will
overdosing of hydrocortisone can suppress linear trigger thirst and the child will reach equilibrium.
growth. Most children with diabetes insipidus, however,
Thyroid-stimulating hormone deficiency is are more comfortable with desmopressin to con-
treated with replacement levothyroxine at a trol the polyuria. Desmopressin can be dosed
starting dose of 10 mcg/kg/day in neonates subcutaneously, intranasally, or orally and is usu-
and 66 mcg/m2/day in infants and older children. ally given twice daily. The dose is adjusted to
In cases of severe, long-standing hypothy- allow for 8–10 h free from polyuria, with 2–4 h
roidism, rapid replacement can precipitate con- of polyuria to ensure the previous dose has worn
gestive heart failure. In these cases, we start at off before the next is given. Absorption of the
33 mcg/m2/day and gradually increase the dose. oral and intranasal preparations can be highly
Pseudotumor cerebri can also occur shortly after variable on a day-to-day basis. In children with
starting replacement. Subsequently free T4 levels intact thirst and access to water, they will com-
are monitored and the dose adjusted to keep this pensate for this variability with good results. In
within the normal range. children with acute illness and those without
Growth hormone deficiency is treated with intact thirst, hypernatremic dehydration can rap-
recombinant human growth hormone (rhGH) idly occur and be difficult to manage. In these
replacement. In infancy and early childhood, children fluid balance must be carefully moni-
rhGH is used only if hypoglycemia is a problem. tored and adjusted. In cases of desmopressin
It is otherwise started generally when the child overdosage and/or fluid overload, significant
drops below the 5th percentile on the height curve. hyponatremia can occur. Correction for this
It is dosed at 0.035–0.05 mg/kg/day. IGF-I levels must be done with great care, as too rapid a rise
should be monitored and the dose adjusted to keep in sodium level can cause pontine myelinolysis.
the IGF-I within the normal range. Potential Subcutaneous desmopressin or continuous intra-
adverse effects include pseudotumor cerebri in venous vasopressin are useful in these situations,
the first few months of treatment, slipped capital eliminating the potential variability of absorp-
femoral epiphysis, progression of scoliosis, and tion. Children with severe hypo- or hyper-
hyperglycemia. Occasionally, rhGH treatment natremia should be managed in a critical care
worsens central hypothyroidism to the point setting.
where thyroid replacement is required; free T4 Prolactin and oxytocin deficiency do occur, but
levels should be monitored after starting and on there are no associated symptoms, and no treat-
occasion during treatment. ment is necessary.
Gonadotropin (LH and FSH) deficiency is not
a problem in childhood. Hormone replacement
(testosterone for boys, estrogen for girls) is Thyroid Gland
required during adolescence when it is clear that
puberty has not started spontaneously or if Primary hypothyroidism is treated with replace-
puberty is failing to progress. Sex hormone treatment as described above for central hypothyroid-
ment has beneficial metabolic effects – especially ism. With primary hypothyroidism, the TSH is
for bone – and should not be withheld in adoles- elevated and is the most sensitive of the thyroid
cents with cerebral palsy. Treatment is long term function tests. Hence, TSH levels are monitored
and complex and best left in the hands of an regularly and levothyroxine dose adjusted to keep
endocrinologist. the TSH in the normal range.
Adrenal Gland ▶ Premature and Delayed Sexual Maturation in

Primary adrenal insufficiency is treated as ▶ Short Stature in Children with Cerebral Palsy
described above for ACTH deficiency. If aldoste-
rone deficiency is also present, then replacement
with fludrocortisone (Florinef ®) is done. Dosing
is highly variable, and infants generally require a References
higher dose, such as 0.1 mg twice daily. Regular
monitoring of blood pressure, potassium, and Andersen UM, Lund HT (1995) Hypoglycemia caused by
growth hormone deficiency. Two cases in children with
renin activity is required, and dose is adjusted to cerebral paresis. Ugeskr Laeger 157(12):1681–1682
keep these in the normal range. During stress, Brent GA, Weetman AP (2016) Hypothyroidism and thy-
fludrocortisone dosing does not have to be roiditis. In: Melmed S, Polonsky KS, Larsen PR,
increased. Kronenberg HM (eds) Williams textbook of endocri-
nology. Elsevier, Philadelphia, pp 416–448
Devesa J, Casteleiro N, Rodicio C, Lopez N, Reimunde P
(2010) Growth hormone deficiency and cerebral palsy.
Complications Ther Clin Risk Manag 6:413–418
Hamza RT, Ismail MA, Hamed AI (2011) Growth hormone
deficiency in children and adolescents with cerebral
The complications of pituitary deficiencies palsy: relation to gross motor function and degree of
are primarily related to missing the diagnoses. spasticity. Pak J Biol Sci 14(7):433–440
Infants and children with adrenal crisis (either Han Ze D, Kang L, Hui P, Gong-Wei D (2011) Clinical
undiagnosed or inadequately treated with stress analysis of misdiagnosis in 70 children with primary
hypothyroidism. Zhongguo Yi Xue Ke Xue Yuan Xue
doses) are at significant risk for cardiovascular Bao 33(1):14–17
instability and hypoglycemia. The outcome of Hong T, Paneth N (2008) Maternal and infant thyroid
this may be permanent neurologic damage or disorders and cerebral palsy. Semin Perinatol 32(6):
death. Undiagnosed or mismanaged diabetes 438–445
Kaiser U, Ho KKY (2016) Pituitary physiology and
insipidus places infants and children at risk for diagnostic evaluation. In: Melmed S, Polonsky KS,
hypernatremic dehydration or hyponatremia, Larsen PR, Kronenberg HM (eds) Williams textbook
often requiring hospitalization for adequate cor- of endocrinology. Elsevier, Philadelphia, pp 176–231
rection. Missing the diagnosis of hypothyroidism Kuperminc MN, Gurka MJ, Houlihan CM, Henderson RC,
Roemmich JN, Rogol AD, Stevenson RD (2009)
is more insidious, with potential long-term loss of Puberty, statural growth, and growth hormone release
intellectual function and short stature. in children with cerebral palsy. J Pediatr Rehabil Med
There are also complications associated 2(2):131–141
with all of the replacement therapies, including Osborn DA, Hunt RW (2007) Prophylactic postnatal thy-
roid hormones for prevention of morbidity and mortal-
adverse drug effects, underdosing, and over- ity in preterm infants. Cochrane Database Syst Rev 1:
dosing. Careful monitoring and management by CD005948
physicians with experience with these conditions Stewart PM, Newell-Price JDC (2016) The adrenal
is vital for the well-being of these children. cortex. In: Melmed S, Polonsky KS, Larsen PR,
Kronenberg HM (eds) Williams textbook of endocri-
nology. Elsevier, Philadelphia, pp 490–555
Suzumura H, Nitta A, Tsuboi Y, Watabe Y, Kuribayashi R,
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thyroxinemia and cerebral palsy in extremely preterm
infants. Pediatr Int 53(4):463–467
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Palsy Septo-optic dysplasia-plus and dyskinetic cerebral
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Cerebral Palsy Trinh A, Wong P, Fahey MC, Brown J, Churchyard A,
Strauss BJ, Ebeling PR, Fuller PJ, Milat F (2016)
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Planning in the Child with Cerebral Palsy cerebral palsy: new opportunities for intervention.
▶ Postnatal Causes of Cerebral Palsy J Clin Endocrinol Metab 101(3):1190–1197
Uchiyama A, Kushima R, Watanabe T, Kusuda S (2015) Growth and neurodevelopmental outcomes after early
Effect of L-thyroxine supplementation on infants with low-dose hydrocortisone treatment in extremely low
transient hypothyroxinemia of prematurity at 18 months birth weight infants. Pediatrics 120(1):40–48
of corrected age: randomized clinical trial. J Pediatr Worley G, Houlihan CM, Herman-Giddens ME,
Endocrinol Metab 28(1–2):177–182 O’Donnell ME, Conaway M, Stallings VA,
Uday S, Shaw N, Krone R, Kirk J (2017) Hypopituitarism Chumlea WC, Henderson RC, Fung EB,
in children with cerebral palsy. Arch Dis Child Rosenbaum PL, Samson-Fang L, Liptak GS,
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Part XV
Eyes
Testing Visual Function and Visual
Evaluation Outcomes in the Child with 72
Cerebral Palsy
Elise Ciner, Sarah Appel, Marcy Graboyes, and Erin Kenny
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1016
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1016
Vision Disorders Commonly Associated with Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . 1016
Evaluation and Treatment of Ocular and Vision Disorders Associated
with Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1018
Preparation for the Vision Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1018
Visual Skills Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1021
What Are the Primary Visual Skills that Can Be Helpful for Professionals
Working with Children with CP to Be Aware of? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1022
Color Vision . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1029
Glare Sensitivity and Dark Adaptation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1031
Vision Evaluation Outcomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1031
Complications of the Disease Process and Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1031
Treatment and Management of Identified Vision Disorders . . . . . . . . . . . . . . . . . . . . . . 1032
Integration of Recommendations into Education and Rehabilitation Plans . . . . . 1036
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1037
Abstract
Vision is an important area to evaluate in chil-
dren with cerebral palsy, playing a key role in
E. Ciner (*) learning and development throughout a child’s
Pediatric and Binocular Vision Service, The Eye Institute
lifetime. Understanding the role of vision in the
of Salus University, Philadelphia, PA, USA
e-mail: Eciner@salus.edu daily lives of children with cerebral palsy
(CP) and having knowledge of the high preva-
S. Appel · M. Graboyes · E. Kenny
William Feinbloom Vision Rehabilitation Center, The Eye lence of ocular and vision disorders associated
Institute of Salus University, Philadelphia, PA, USA with CP are essential in the medical, rehabili-
e-mail: Sarah@salus.edu; Mgraboyes@salus.edu; tation, and education profile for each child.
Ekenny@salus.edu

https://doi.org/10.1007/978-3-319-74558-9_76
1016 E. Ciner et al.
Vision disorders affecting a child’s perfor- also present challenges for eye care practitioners.
mance of vision-dependent tasks are often Children with CP may not be responsive to stan-
overlooked, undiagnosed, or unrecognized. dard testing procedures for a wide range of rea-
Evaluating the visual function of children sons. These include stress-related behaviors,
with cerebral palsy (CP) can, however, present orthopedic and neuromuscular disorders, devel-
challenges for eye care practitioners as children opmental delays, and preverbal level of develop-
with CP may not be responsive to standard ment which can impact a child’s ability to
testing procedures for a wide range of reasons. communicate during a vision assessment
As a result, erroneous labels such as severe (Dufresne et al. 2014). As a result, children may
visual impairment, “untestable,” or “blind” be erroneously labeled as having severe visual
have been applied, despite reports by parents, impairment (Salati et al. 2002; Ghasia et al.
teachers, therapists, and caregivers that these 2009; Dufresne et al. 2014), “untestable,” or
children appear to show visual responses. This “blind,” despite reports by parents, teachers, ther-
chapter discusses the common ocular and apists, and caregivers that these children appear to
vision disorders in children with CP and the show visual responses. The importance of under-
components of a clinical vision evaluation for standing a child’s visual status and its effect on
children with CP who may have widely dispa- learning and development is relevant to the child’s
rate levels of communication, cognitive, and medical, education, and rehabilitation team (Den-
motor skills. This is followed by management ver et al. 2016). This chapter will discuss the
of vision disorders and implications of assess- components of a clinical vision evaluation and
ment outcomes on overall function for the management that can be provided by eye care
child with CP. The eye care provider can con- providers from a functional perspective along
tribute important information regarding how a with the implications of assessment outcomes on
child sees, the potential for improvements in overall function for the child with CP. While ocu-
vision, and recommendations to allow educa- lar health evaluation and pathology are included
tors and rehabilitation specialists to integrate to provide a comprehensive perspective, emphasis
vision into the child’s comprehensive educa- will be on the evaluation and management of
tion and rehabilitation programs. visual skills impacted by ocular or neurologic
conditions common to CP. The model presented
Keywords in this chapter reflects the practice of the authors
Vision disorders · Visual skills and is not intended to represent a universal model
to be adopted by all providers. Vision care ser-
vices for children with CP including evaluation
Introduction techniques, areas assessed, and management may
vary between eye care providers depending on the
Understanding the role of vision in the daily lives needs of the child, training of the provider, and
of children with cerebral palsy (CP) and having local resources (Chorna et al. 2017).
knowledge of the high prevalence of ocular and
vision disorders associated with CP are essential
in the medical, rehabilitation, and education pro- Natural History
file for each child. Vision disorders affecting a
child’s performance on vision-dependent tasks Vision Disorders Commonly Associated
are often overlooked (Pennefather and Tin with Cerebral Palsy
2000), undiagnosed, or unrecognized (Dufresne
et al. 2014; Fazzi et al. 2012; da Cunha Matta et al. The importance of a comprehensive vision evalu-
2008) despite the crucial role vision can play in ation for children with CP is highlighted by the
learning and development. Evaluating the visual presence of vision disorders in up to 90% of this
function of children with cerebral palsy (CP) can population that has been widely documented over
72 Testing Visual Function and Visual Evaluation Outcomes in the Child with Cerebral Palsy 1017
the past 60 years (Breakey 1955; Duckman 1979; (Altman et al. 1966; Duckman 1979; Scheiman
Scheiman 1984; Sasmal et al. 2011; Park et al. 1984; Park et al. 2016; Fazzi et al. 2012). Children
2016; Ozturk et al. 2013; Woo et al. 2011) with are typically born with a wide range of refractive
one in 10 children diagnosed as severely visually error. “Emmetropization” or normalization takes
impaired or blind (Denver et al. 2016; Novak et al. place during the first few years of life with much
2012). CP is associated with a variety of visual of the original refractive error diminishing in mag-
disorders including strabismus, significant refrac- nitude. It has been suggested that while the mean
tive error, accommodative disorders, optic nerve refractive error of a population of children with
abnormalities, and cerebral visual impairment CP may be similar to a typical population,
among the most commonly diagnosed. These dis- emmetropization may be affected in children
orders which briefly are described below can also with CP, resulting in a higher prevalence of sig-
impact learning and visual maturation (Scheiman nificant refractive error than in other childhood
1984; Kozeis et al. 2007; Appel and Ciner 2011; populations (Sobrado 1999; Arnoldi et al. 2006,
Ozturk et al. 2013). Saunders et al. 2010). There is also a reported
Strabismus (tropia or eye turn) is the most higher prevalence of the more extreme refractive
prevalent vision disorder reported in the literature errors in the non-spastic types of CP (Saunders
in children with CP with reports ranging as high as et al. 2010; Ghasia et al. 2009). These data support
90% (Arnoldi et al. 2006; Duckman 1979; the need for careful refraction with consideration
Dufresne et al. 2014; Fazzi et al. 2012; Park toward prescribing corrective lenses if indicated.
et al. 2016; Ozturk et al. 2013; Collins 2014) and Accommodation is related to refractive error
having the highest incidence in children with and is an individual’s ability to automatically
spastic CP (Dufresne et al. 2014; Collins 2014) change the focus of the crystalline lens in each
with most studies showing esotropia more com- eye to provide a clear retinal image at different
mon than exotropia (Collins 2014). Onset of stra- distances, with an increase in focus required for
bismus is typically at birth or during infancy and near viewing. Accommodative measures are
of high magnitude and cosmetically noticeable increasingly being considered an important visual
(Lagunji and Oluleye 2007). Poor motor fusion skill to assess in children with CP (Saunders et al.
and sensory anomalies associated with strabismus 2010; McClelland et al. 2006; Pansell et al. 2014).
including amblyopia (reduced visual acuity not The association of accommodation with refractive
immediately correctable with glasses and in the error is most evident in the presence of
absence of pathology occurs due to either high uncorrected hyperopia of any magnitude, which
uncorrected refractive error or strabismus) and requires extra accommodative effort to obtain and
reduced stereopsis (binocular depth perception) maintain clear vision at all distances. Additional
are common in children with CP (Arnoldi et al. effort that is inversely proportional to the viewing
2006; Kozeis et al. 2007; Ghasia et al. 2009) along distance is required for near tasks. While most
with ocular motility disorders (Park et al. 2016). children can accommodate sufficiently to over-
Refractive error of all types and magnitude are come low to moderate amounts of hyperopia with-
also common and have long been widely reported out distress, children with CP are known to have
in children with CP (Duckman 1979; Scheiman poor accommodative skills (Scheiman 1984;
1984; Sasmal et al. 2011; Boyaci et al. 2014) with Duckman 1984; Leat 1996; McClelland et al.
the spherical refractive measures (hyperopia or 2006), which are slower and more variable
myopia) unrelated to the severity of the CP and (Duckman 1984; Pansell et al. 2014). This would
the prevalence of significant hyperopia higher make it difficult for children with CP to maintain
than in the general population (Saunders et al. clear comfortable focus when viewing nearby
2010; Kozeis et al. 2007, 2015; Arroyo-Yllanes learning materials, computers, or communication
et al. 2005). The prevalence varies by study based devices and may ultimately impact learning. Med-
on the definition of “significant refractive error” ications for seizures, depression, or anxiety may
used and has been reported as high as 50–76% also reduce accommodative responses in children
with CP (McClelland et al. 2006; Hopkins and corrected visual acuity is equal to or worse than
Pearson 1998; British National Formulary 2017). 20/70 in the better-seeing eye.
Optic disc abnormalities are reported in chil- The presence of visual-perceptual impairment
dren with cerebral palsy or cerebral visual impair- in children with CP is higher than in the general
ment (Fazzi et al. 2007; Salati et al. 2002; Ozturk population (Stiers et al. 2002; Ego et al. 2015) and
et al. 2013; Ghate et al. 2016). Optic atrophy has been suggested to be approximately 40–50%
(optic nerve pallor) is the most common optic in a review and analysis of 15 studies (Ego et al.
nerve disorder found in children with CP but can 2015). Children who were born preterm were at a
differ in etiology. Periventricular hemorrhages, greater risk for lower visual-motor skills (Fazzi
which are more common in children with et al. 2004; Pagliano et al. 2007; Ego et al. 2015).
decreased gestation periods and hydrocephalus, Regardless of the presence of other visual disor-
can cause optic atrophy (Mudgil and Repka ders, visual-perceptual skills should be considered
2000). Optic atrophy can result in a decrease in when evaluating a child with CP (Ego et al. 2015)
central vision and peripheral field, along with in addition to the visual skills presented in this
color vision and contrast problems. Cerebral chapter.
palsy may also be an associated systemic finding The associated profiles of vision disorders for
in children with bilateral optic nerve hypoplasia different types of CP, risk with prematurity, and
(Kaur et al. 2013). cerebral visual impairment have also been
Optic atrophy, temporal disc pallor, or large reported (Fazzi et al. 2007, 2012; Kozeis et al.
optic disc cupping is often the retinal manifesta- 2007; Ozturk et al. 2013). Children with tetra-
tion of cerebral visual impairment (CVI) (previ- plegia (quadriplegia) showed the highest preva-
ously referred to as “cortical” or “central” visual lence of ocular abnormalities (up to 100%) with
impairment or blindness) (Fazzi et al. 2007). CVI severe visual impairment, oculomotor dysfunc-
is defined as a decreased visual response due to a tion, eye movement disorders, and retinal abnor-
neurological problem such as periventricular malities. Children with diplegic CP showed lack
leukomalacia rather than an ocular or eye-related of stereopsis, reduced contrast sensitivity, oculo-
problem (Fazzi et al. 2007). The incidence of motor disorders, reduction in visual acuity, signif-
children with CVI is on the rise due to the increas- icant hyperopia, and strabismus. Children with
ing survival rate of infants with hypoxic brain hemiplegic CP exhibited significant refractive
injury (Philip and Dutton 2014). Imaging can be error along with visual field deficits, reduced ste-
used to support or confirm the diagnosis of CVI in reopsis, oculomotor disorders, and nystagmus
children with CP. Children with CVI may not (Fazzi et al. 2012).
display any apparent functional vision or may
demonstrate inconsistent visual responses with a
resultant diagnosis of legal blindness. Regardless Evaluation and Treatment of Ocular
of whether a child’s visual impairment is due to and Vision Disorders Associated
cerebral visual impairment or ocular disease, the with Cerebral Palsy
definition of legal blindness in the USA is impor-
tant to consider for social service purposes, and it Preparation for the Vision Evaluation
is defined as “best corrected visual acuity in the
better-seeing eye of 20/200 or worse and a resid- Preliminary Information from Caregiver
ual visual field diameter of 20 degrees or less.” In Information gathering in preparation for the vision
2007, the definition was revised to include best assessment should begin prior to the actual eval-
corrected visual acuity worse than 20/100 (indi- uation. The parent or primary caregiver is one
vidual is unable to read any letters on 20/100 line) of the richest sources of information regarding
if acuity was measured with low vision charts that the overall functioning of the child. Caregivers
contain multiple acuity levels between 20/100 and spend time with the child in a variety of settings
20/200. The term “low vision” is used when best and situations and can provide insights and
observations as to how the child responds and guide the vision evaluation. Observations about
uses vision. Due to the complexity of issues the use of vision along with questions regarding
affecting many children with CP, the child’s ocu- the impact of vision on academic achievement,
lar, medical, developmental, rehabilitation, and rehabilitation aims, and overall development are
education histories along with a list of medica- often key to shaping goals for the vision evaluation.
tions and medical alerts should be collected and Data from professionals such as occupational,
reviewed in advance of the visit in order to create a physical, or speech and language therapists might
holistic picture of the child. If there has been a include a description of the educational setting,
previous vision examination, information regard- observations of unusual head tilts or visual pos-
ing diagnoses, surgeries, treatments, medications, tures, illumination or glare issues, and current inter-
and prognosis should also be reviewed. Parents or ventions and strategies that relate to the child’s
caregivers should be encouraged to bring copies vision. Teachers and therapists should be encour-
of reports from medical specialists, educators, and aged to accompany the child to the vision evalua-
rehabilitation therapists to the examination for tion when possible. This will enable them to
review to provide the eye care provider with the provide and receive firsthand information during
most comprehensive understanding of the child. the evaluation process including strategies to
Caregivers should also be encouraged to write enhance the child’s use of residual vision, which
questions for the vision evaluation in advance of can be incorporated into the educational program.
the visit in order to guide the evaluation in a mean- In addition to a traditional clinic-based setting,
ingful way. These questions become goals for when possible, the vision evaluation might also
the visit and help the eye care specialist to target take place on-site at the child’s school. The advan-
specific concerns. Typical questions from parents tage of a community- or school-based evaluation is
may include the following: “How much can my that it is performed in an environment familiar to
child see?” “What is the best way to help my child the child and provides the eye care specialist with
function in school with the current level of vision?” direct access to educators and therapists as well as a
In order to maximize the effectiveness of the firsthand view of the environment in which the
vision evaluation, the parent or caregiver should child functions for learning and therapy.
be informed about what will take place during the
visit. Knowing ahead of time what a child will be Clinical History
asked to do in the evaluation can help the parent or The vision evaluation should begin with a com-
caregiver better prepare the child and ease some of prehensive history. A careful review of previous
the stress of the examination. For example, if a ocular, medical, and developmental history and
child has sensory issues and there will be a need to other gathered information along with goals for
occlude or cover an eye to measure vision mon- the evaluation should be completed (Ciner et al.
ocularly, the parent can practice this activity at 1996). This includes a discussion of the current
home in advance. Objects familiar to the child ocular status including how the child is observed
may be brought to the exam to be used for comfort using vision. For example, does the child respond
or as motivators along with examples of any to light either indoors or outdoors? Does the child
schoolwork for which there are visual questions. respond to facial expression? Does the child visu-
Any triggers which might upset the child during ally track toys or objects and reach out for them?
the evaluation such as loud sudden noises, fear of Does the child seem to have a preferred eye? Is
particular objects, or a dark room should be noted there sensitivity to glare or bright light either
and avoided when possible. indoors or outdoors? If a child has a seizure dis-
order, it is important to determine if there are any
Information from Educators visual stimuli that might generate a seizure such as
and Rehabilitation Therapists strobe or flashing lights.
The therapeutic team working with the child can Information regarding the cognitive and devel-
also provide a rich source of information to help opmental level of the child is also reviewed and
taken into consideration during the evaluation as which should have minimal visual or auditory dis-
this can impact the type of testing that can be used tractions and/or visual clutter that may negatively
(e.g., can the child identify shapes or colors). It is impact testing.
important to know through what means the child
communicates (e.g., looking, pointing, or verbal Ocular Health Examination
responses). If the child uses a communication The ocular health examination of a child with CP
device to respond to questions, the family should should be as extensive as the ocular health exam-
be encouraged to bring the device to the evalua- ination on any other patient with techniques and
tion where it can be incorporated into the tests available for assessment (Dufresne et al.
examination. 2014; Zambone et al. 2000; Appel et al. 1997;
It is important to understand to what degree the Ciner et al. 1996, 1999; Arnoldi et al. 2006).
child is able to move around in the environment. Although the approaches to the clinical examina-
Children with CP will vary in their ability to move tion may differ, the information gathered should
independently. Vision may play a role in goals be utilized to provide the most appropriate care
related to purposeful movement and mobility. and rehabilitation of the patient.
For example, a child may be referred for a vision When assessing the front structures or anterior
evaluation as part of an assessment for use of a segment, an eye care provider uses gross observa-
motorized wheelchair. Information that can lead tion as the starting point to the ocular health
to a better understanding of a child’s ability to see examination. By looking at eyelid symmetry and
detail, as well as the extent of peripheral vision ocular adnexa (e.g., orbit, extraocular muscles,
will add an important dimension to this process. lacrimal/tear drainage system), the clinician can
The clinical history should culminate in the examine abnormalities that may be present. Ptosis
setting of goals for the evaluation, which range and lid squint are possible gross observation find-
from diagnosis, assessment, prognosis, and man- ings for a patient with CP (Black 1982).
agement of ocular conditions to providing an A more detailed evaluation of the anterior seg-
understanding of what and how a child sees, ment utilizes a standard or portable biomicroscope
along with size of print or communication pictures (slit lamp) to magnify the ocular structures.
or icons the child should be using. Beginning with the lids, eye care providers can
In general, children should be tested in a phys- assess the presence of flaking, redness, or severe
ically comfortable environment. Fatigue, emo- meibomian gland dysfunction along with an eval-
tional distress, and illness can negatively impact uation of the palpebral (lid) conjunctiva for sig-
results. Positioning during the examination is an nificant findings such as papillae and follicles,
important area to consider. Optimal positioning which would be indicative of conjunctivitis or
allows for maximal head and eye control and inflammation or dry eye.
facilitates hand-eye coordination activities such Clarity and integrity of the cornea should be
as pointing. Positions may include propped, assessed for abnormalities such as corneal haze or
fetal, prone, supine, sitting, or standing. If a scarring. In general, a “quiet, white eye” is
child requires adaptive seating such as one with expected in patients with CP. Abnormalities
specific head and trunk support, the family should could include nevi (mole), neovascularization
be encouraged to consult with the child’s thera- (new vessel growth), or iris heterochromia (irises
pists and bring the adaptive seating when possible of different colors). The intraocular lens should be
to the examination to maximize comfort, support, examined for any obvious lenticular changes or
and attention. Many children demonstrate greater opacities that could indicate the presence of a
visual attention and stability with head or upper cataract.
trunk support. The examination should be modi- Measurement of intraocular pressures to rule
fied in any way possible to give the child every out the presence of ocular hypertension or glau-
opportunity to respond optimally to the test pro- coma can be completed with either a noncontact
cedures. Equally important is the test environment, tonometer or portable contact tonometer prior to
dilation if the child is unable to comfortably sit in can also process, understand, and act upon the
a standard exam chair to undergo standard incoming visual information. For children with
Goldmann tonometry. CP and apparently “healthy” eyes, this portion of
Children with CP should undergo an evalua- the vision evaluation can often provide answers to
tion of internal eye structures with pupillary dila- questions regarding what and how a child sees
tion at the first exam and periodically thereafter to even in the absence of well-developed communi-
allow a more complete view of the lens and inner cation skills.
ocular structures. The retinal view that is seen These “psychophysical” measures of vision
includes the optic nerve, macula, blood vessels, indicate what the world looks like to the child.
and peripheral retina. Optic nerve pallor which is When administered in an optimum environment,
more common in children with CP, optic nerve vision tests that are selected based upon the indi-
cupping indicating possible elevated intraocular vidual needs of each child can reduce variability
pressure, optic nerve hypoplasia, and papilledema and bias in order to obtain as true a measure of a
(optic nerve swelling) which may be associated child’s visual functioning as possible. While the
with elevated intracranial pressure are all clinical term “vision” is often correlated directly with
findings that should be evaluated and investigated “visual acuity” or clarity of vision, the visual
further. The macula, which is responsible for clear system is much more complex and includes
central vision, should be assessed for edema, atro- other visual factors and skills such as contrast
phy, pigmentary, or other changes, although none discrimination, binocular function and stereopsis,
of these are common in CP patients. Vessels eye movements, accommodation, color vision,
should be of normal caliber and non-attenuated. visual fields, and glare sensitivity or light/dark
Vascular dilation and tortuosity may be indicative adaptation. Each of these areas can often be eval-
of shunt malfunction in children with hydroceph- uated in children with CP regardless of a child’s
alus. The peripheral retina should be assessed for level of cognition, language, communication, or
retinal breaks, holes, or detachments and signs motor skills. While some children with CP can be
of retinopathy of prematurity (ROP) which places tested in a standard manner (e.g., reading the
a child at risk for high myopia and retinal letters on a Snellen chart and responding “which
detachment. is better – 1 or 2?”), others may require either
modifications of standard testing strategies or
alternative types of testing. These may include
Visual Skills Evaluation changing the task (e.g., pictures instead of letters),
the use of behavioral methods to determine visual
In assessing the visual skills of a child with CP, the abilities (e.g., preferential looking techniques or
eye care provider evaluates how a child’s visual monitoring of eye movements), electrophysiolog-
system receives, processes, and interprets visual ical testing, or referral for neuroimaging. In addi-
information. Beginning at the cornea, light enters tion, a child’s performance on a clinical test of
the eye and passes through to the retina where vision does not always correlate with the child’s
photoreceptors convert photons of light into elec- actual use of this vision in an academic or reha-
trical energy. After a complex series of processes bilitative setting. Ability does not always equal
occurring through the retinal layers, visual infor- function. The challenge of the educators and reha-
mation then leaves the eye and is transmitted by bilitative professionals working with a child with
way of the optic nerve to the lateral geniculate CP is to determine how best to bring a child’s full
nucleus in the midbrain and via the optic tract to ability to fruition on a daily basis in the child’s
the primary visual cortex in the occipital lobe of real-world setting.
the brain. The information is then integrated into Results of clinical vision testing can be corre-
the higher cortical areas along with feedback to lated with observational assessments and
the lower cortical areas. When this takes place, the descriptions of visual abilities by rehabilitation
child cannot only see a light, image, or picture but professionals or functional questionnaires to
assess daily visual performance in order to pro- Fortunately, the ability to test children of all cog-
vide an interdisciplinary visual assessment of a nitive, motor, and language levels has advanced
child with cerebral palsy (Ferziger et al. 2011; so that alternative measures of visual acuity can be
Ciner et al. 1996). While a comprehensive and utilized to understand what and how a child sees.
systematic review of these observational and Each of these measures has different developmen-
descriptive types of measures has been under- tal timelines, charts, and methods for testing as
taken, there is need for further validation of well as minimum thresholds for what is consid-
these measures of visual ability for predictive or ered to be within the normal or typical range based
evaluative purposes (Denver et al. 2016). upon age. The hierarchy of common clinically used
visual acuity measures includes the following:
Detection acuity is the size of the smallest
What Are the Primary Visual Skills that object a child can see. Detection of an object is
Can Be Helpful for Professionals dependent on the brightness, contrast of the object
Working with Children with CP to Be against the background, and the interest level of
Aware of? the child toward the object. It is generally an
informal, subjective assessment that provides
Spatial vision is the ability to see patterns or functional information about the child’s ability to
details of images and includes measures of visual see common items or details in educational mate-
acuity (various sizes) and contrast sensitivity (var- rials encountered during the day. Detection acu-
ious contrast levels). Both provide important ities are typically measuring visual function at
understanding of a child’s level of visual function- near viewing distances. The addition of motion
ing and can also correlate to ocular conditions or to the task may increase responsiveness and also
disease. Visual acuity is especially important for allow for testing at greater distances. However,
the determination of services a child may be eli- the visual pathway that encodes motion is differ-
gible to receive including early intervention as ent than that encoding stationary objects. Optical
well as later rehabilitation and education blur from uncorrected refractive error has also
planning. been shown to increase the size of objects used
Visual acuity. The presence of “pattern” vision for detection acuities depending on the back-
is typically assessed as visual acuity (VA) or the ground contrast (Press 1982). It is therefore
smallest detail at a specified distance an individual important to include descriptors of the character-
can see. VA has been the primary measure of istics of an object the child is responding to during
vision for more than 150 years since the advent the evaluation including size, color, brightness,
of the Snellen chart with emphasis placed on the movement, background color, and object famil-
importance of this visual skill by eye care pro- iarity to the child. There may also be inconsistent
viders, medical providers, parents, teachers, and correlation of detection acuity to standard recog-
therapists. The actual tests used for children with nition acuity. Detection acuity should therefore be
CP vary from individual to individual based on used as a supplemental measure of vision or when
several factors. In general it is desirable to admin- the child does not respond to resolution or recog-
ister a test that is the most similar to the standard nition tests.
letter chart used for adults to which a child can Resolution or grating acuity is the smallest
respond. Many children with CP are, however, spatial separation between two nearby points or
unable to read a standard letter or picture chart, lines that can be discriminated as “separate” from
resulting in labels such as “untestable” or each other. Resolution acuity can be measured
“unknown level of visual acuity.” These labels clinically at near viewing distances with a number
present a challenge to those working with children of commercially available tests that provide a
with CP as the size of visual detail that will visu- measure of spatial resolution utilizing black and
ally engage the child during an evaluation, white stripes (gratings). The width of the stripes
therapy, or educational activity is unknown. correlates to a visual acuity measure in “cycles per
degree visual angle” that can be converted to a the child is looking “preferentially” toward one
familiar Snellen equivalent such as 20/50 or side or the other. As the stripes become narrower
20/200. Resolution tests are the clinical test of on subsequent cards, a point is reached where the
choice in children who are nonverbal or unable black and white stripes “blend” into the gray
to match pictures and at risk for ocular disorders, background and the child no longer preferentially
as these tests are relatively quick to administer, looks to one side, but rather will shift gaze in a
noninvasive, and can provide repeatable results more random fashion. The last pattern that is
(Preston et al. 1987). Testing is done with a resolved by the child is recorded as the child’s
“forced choice preferential looking” (FPL) tech- visual acuity. In this manner, a reliable measure of
nique, whereby the stimulus, e.g., stripes/grating visual acuity can be obtained in many children
(e.g., Teller Acuity Cards or Lea Paddles), or with CP who would otherwise not be testable
pictures with stripes forming the edges of the with the standard charts used in typical children
pictures (e.g., Cardiff Cards) appear to the right or adults. While resolution acuities are not equiv-
or left, top, or bottom of a card that has an equal alent to a Snellen or letter chart, they do provide a
luminance gray background (Fig. 1) (Adoh et al. measure of a child’s visual resolution capabilities.
1992; McDonald et al. 1985; Morale et al. 2012). An important consideration with regard to FPL
If the child can see the black and white stripes, in acuities for children with cerebral palsy is the
the presence of normal eye movements, there is a reliance on saccadic eye movements which may
reflexive tendency for the eyes to look in that be impaired. This can lead to an underestimation
direction, and the examiner, unaware of the loca- of visual acuity if either a lack of eye movements
tion of the stripes, makes a judgment as to whether or delays in eye movement responses are not
Fig. 1 Examples of resolution charts including (a) Cardiff cards, (b) Lea grating paddles, and (c) Teller acuity cards
considered (Arnoldi et al. 2006). An equally be limited, optimum testing will include measur-
important consideration is a visual field loss ing visual acuity in each eye separately (monocu-
which may result in an underestimation of visual larly) at distance to rule out amblyopia, reduced
acuity if the child is unable to peripherally view vision in either eye, and/or unequal vision
the location of the stripes on the cards. between the two eyes. A binocular measure of
Identification (or recognition acuity) measures visual acuity at near is important to understand
the child’s ability to recognize the smallest details how a child sees in his/her habitual learning envi-
in a letter or picture and is the most common ronment with both eyes open. Many children with
method to clinically evaluate visual acuity. If a CP may lose attention for more distant measures
child is able to say, match, point to, or direct eye and can only be tested at near viewing distances
gaze at letters or pictures, this is the method of monocularly and binocularly. Examples of three
choice in the visual acuity testing hierarchy as it is different types of identification or recognition
considered most similar to the “gold standard” acuities commonly used to test children with CP
letter charts for adults and used by social service who are unable to read a standard Snellen letter
agencies in determining levels of visual impairment. chart are shown in Fig. 2.
Distance and near measures of visual acuity, Objective measures of visual acuity. Visual
when obtainable by recognition, resolution, or acuity can also be evaluated objectively with
detection methods, are important in the assess- electrodiagnostic tests if poor responses are
ment of children with CP. Because attention may obtained with clinical methods, by measuring
Fig. 2 Examples of recognition charts with optotypes for low vision visual acuity book, (b) Lea linear crowded
children with cerebral palsy unable to respond to a standard symbols, and (c) Electronic HOTV letter matching chart
Snellen or other letter type chart including (a) Feinbloom
visual evoked potentials (VEP), a subcomponent two inch icons on her communication device and
of the electroencephalogram (EEG) (Ghasia et al. wonder if they are too small or detailed for her. As
2009; Salati et al. 2002; Costa and Pereira 2014; Jen was unable to match pictures or numbers,
Westall et al. 2000). These tests require more testing with Forced Choice Preferential Looking
advanced equipment that may not be available in indicated her near visual acuity to be in the 20/70
many clinical practices. In general a visual evoked range. While this level of visual acuity is below
potential assesses the visual pathway from the her age expected level, Jen should be able to
cornea through to the visual cortex in the occipital readily distinguish the icons. There are, however,
lobe of the brain. Electrodes placed on the child’s other visual skills that may need to be considered
head measure the visual response to an alternating for Jen as well.
pattern of black and white checks or stripes on a Contrast is the brightness difference between
computer screen. Testing is generally completed the lightest and darkest parts of an object, letter, or
within a few seconds if the child is able to main- picture and evaluates a child’s ability to distinguish
tain fixation on the screen. There are various types edges and borders that are of lower contrast (e.g.,
of VEPs that can be administered depending on gray and white). While visual acuity is a measure of
the needs of the child and available equipment spatial vision under optimal high-contrast viewing
including Flash, Pattern-onset, and Sweep. The conditions (black letters or stripes on a white back-
VEP can be useful in those cases, where a measure ground), a child’s school or home environment is
of vision in a typical clinical setting provides not black and white and always includes objects
questionable results or is not obtainable. The and areas with reduced contrast. The presence of
VEP, however, only measures the central 10 of glare can also reduce the contrast of visual detail.
the visual field and may not detect a “seeing” Knowledge of a child’s contrast sensitivity level
signal that is more peripheral in the visual field. can be essential for enabling safe and independent
In the latter case, the VEP may not be able to orientation and mobility through improved lighting
provide useful visual acuity information for chil- or use of high-contrast markers in transitional areas
dren with significant central vision loss. where poor contrast commonly exists such as
Visual acuity testing with TAC versus VEP or curbs, stairs, and irregularities on surfaces. Identi-
recognition acuities may show differences and fying the presence of reduced contrast can also
inconsistencies. Clinical decisions regarding lead to recommendations to enhance contrast and
which type of visual acuity test to administer and facilitate learning by changing lighting, improving
monitor visual development with will therefore be the contrast of educational materials, and using
dependent on the type of CP, level of functioning, glare-reducing filters where appropriate. Contrast
and clinical picture for each child (Costa and sensitivity for children with CP can be evaluated
Pereira 2014; Westall et al. 2000; Dobson et al. various ways including letter or picture charts (e.g.,
1995). ETDRS or LEA symbols) and nonverbal preferen-
For children who do not demonstrate any mea- tial looking cards (e.g., “Hiding Heidi Contrast
surable pattern vision, it is helpful to identify the Cards”) depending on a child’s communication
presence or absence of “light perception” and, if and language skills (Fig. 3).
present, whether the child is able to localize and Jen’s contrast sensitivity was next evaluated
track the position of lights in the child’s visual and found to be significantly reduced. It was
field. Light perception without pattern vision may noted that several of the icons on her communi-
be helpful for orientation and mobility and can be cation device have reduced contrast that may be
a starting point for implementation of a basic making it difficult for her to identify the images.
visual skills therapy program. Changing the icon color or using a tinted filter to
Jen is a 12-year-old girl who uses a communi- improve contrast made it easier for Jen to distin-
cation device. Her previous eye exam showed her guish similar looking pictures.
eyes to be healthy, and she does not need glasses. Binocular testing includes a motor and a sen-
Jen’s therapists are not sure if she is able to see the sory component to evaluate children with CP who
cranial nerve – superior oblique palsy). Knowl-

edge regarding the fixating eye is important as it
helps parents, therapists, and teachers know when
a child is visually attending and more responsive.
Children with intermittent eye turns may maintain
eye alignment when they are alert and “on task,”
while one or the other eye may drift outward when
they are inattentive or tired.
The ability to maintain and accurately con-
verge to a near visual target such as pictures or
words in a book or on a computer screen is nec-
essary for binocular vision. Convergence can be
affected by the presence of a phoria (eye drift) or
tropia (eye turn), a child’s focusing abilities, facial
features such as widely spaced eyes (hyper-
telorism), and neurological disorders. Poor con-
vergence may be a sign of visual fatigue or
presence of diplopia with near viewing and can
result in suppression of the image to one eye,
intermittent closure of one eye, or a head turn to
avoid double vision. Medications to control seizure
activity may also decrease convergence ability.
Fig. 3 A child viewing the “Hiding Heidi” contrast chart Sensory assessment of binocularity can be
more challenging in children with CP as testing
are known to have a high prevalence of binocular often involves either subjective (verbal) or motor
disorders. The motor component or “what the (pointing) responses from the child. Sensory
parent sees” is often a cosmetic concern when a responses can include suppression of one eye,
constant or intermittent eye turn is present. An diplopia (double vision), flat fusion (images
eye drift can make it more challenging to know from both eyes are seen but not in depth), and
when eye contact with the child occurs and is stereopsis (binocular 3-D vision). Finer levels of
maintained. The sensory component or “what the stereopsis require good eye alignment, visual acu-
child sees” when the eye is turned is a functional ity better than approximately 20/80 in each eye,
concern resulting in sensory impairment. Here, good visual attention, and a motor response from
the child may be experiencing double vision, sup- the child to point to or identify a shape that
pression of information to the turned eye with appears to “float.” Matching tests with pictures
associated amblyopia, or an abnormal retina to such as the Randot preschool stereo test (RPST)
brain relationship between the two eyes (anoma- or preferential looking or pointing tests such as the
lous retinal correspondence). PASS (Preschool Assessment of Stereopsis with a
Motor assessment determines the presence of Smile) may result in greater testability in the CP
an eye turn (tropia) or eye drift (phoria) which is population with the latter used in programs such
then characterized by direction as eso (inward), as Special Olympics. Demonstration of good ste-
exo (outward), hypo (downward), and hyper reopsis indicates that the child’s visual system is
(upward), frequency (intermittent, constant, or functioning well and the eyes are aligned. (In the
alternating), identification of the fixating eye mag- absence of stereopsis, however, there remain
nitude of the turn or drift, if the deviation is monocular cues to depth including relative size,
occurring at distance and/or near, and whether a linear perspective, and motion parallax that allow
specific muscle palsy can be identified as the a child to judge relative distances and sizes of
etiology of the strabismus (e.g., palsy of the IV objects.)
Michael’s vision evaluation indicated the pres- myopia secondary to ROP will not have a clear
ence of a large intermittent left exotropia that is image beyond a few inches from their face and
present approximately 20% of the time and will have significant blur at further distances with-
increases when he is fatigued. Michael is nonver- out corrective lenses. For children with CP, the
bal, and it is not always evident where he is same concepts apply; however, many children
looking and with which eye during the school with CP may also benefit from either correction
day. Visual acuity testing indicated that he has of lower magnitudes of refractive error or modifi-
20/70 vision in his right eye and 20/200 in his cations to standard prescribing protocols. Correc-
left eye. Michael’s therapists can now monitor his tion of even low amounts of hyperopia may result
attention to educational tasks by observing his eye in better eye alignment and binocular function and
alignment and noting his right eye fixation on the improved visual attention to near tasks (Dwyer
materials. In addition, based upon his best level of and Wick 1995; Poltavski et al. 2012; Kulp et al.
visual acuity and the difference in vision between 2017; Ciner et al. 2016).
his two eyes, it is unlikely that Michael has more For example, children with an inward eye turn
than a rudimentary level of binocular vision or (esotropia) or drift (esophoria) may benefit from
stereopsis even when his eyes are straight. correction of any amount of hyperopia, even in the
Michael may also benefit from intervention to presence of lower amounts to help align an
help align his eyes and improve the visual acuity inward eye drift (Dwyer and Wick 1995). In addi-
in his left eye with amblyopia therapy (patching, tion, children with CP often have poor accommo-
exercises, or penalization therapy with drops). dative or eye focusing abilities for near viewing
Significant refractive errors are commonly distances, and lower amounts of a hyperopic cor-
seen in children with CP. The type and impact rection can help the child focus more accurately at
on function are listed in Table 1. While many near and possibly provide better attention and
children have a clinically measurable refractive concentration for learning (Arnold 2004; Simons
error, most do not require or wear glasses unless 2004). Moderate uncorrected hyperopia in chil-
the magnitude is interfering with the ability to see dren can be associated with developmental defi-
clearly or comfortably or if corrective lenses cits along with decreased reading ability, visual
improve eye alignment. The eye care provider attention, visuo-cognitive ability, and perfor-
also considers the age of the child and develop- mance on early literacy tests (Kulp et al. 2017;
mental timeline for refractive error changes when Atkinson et al. 2002, 2004; Roch-Levecq et al.
prescribing (Ciner et al. 2011; Leat 2011). When 2008; VIP-HIP Study Group et al. 2016).
moderate to high magnitudes of any refractive Accommodation or focusing measures rele-
error are present, glasses should almost always vant for children with cerebral palsy include the
be prescribed. For example, children with high accommodative amplitude (distance from the eye
Table 1 Types of refractive error in children with cerebral palsy

Refractive
error (RE) Common term Effect at distance viewing Effect at near viewing
Myopia Nearsightedness • Blur with any amount • The higher the magnitude, the more
• Dependent on magnitude reduced the reading distance
Hyperopia Farsightedness • Blur with higher magnitudes • Blur with higher magnitudes
• Extra focusing effort required for all
magnitudes
Astigmatism Distorted vision • Blur with moderate to high • Blur with moderate to high amounts
amounts
Anisometropia Unequal RE • Depends on type and • Depends on type and magnitude of
between the eyes magnitude of anisometropia anisometropia
• Blur in more myopic eye in • Blur in more hyperopic eye in most
most cases cases
when the child can no longer focus at near and CP and mild motor impairment was linked to the
blur occurs), accommodative facility (ability to side of hemiplegia and that oculomotor function
change focus rapidly and accurately from one spontaneously improved with age in these chil-
distance to another), and lag or lead of accommo- dren, even faster than for typically developing
dation (amount of under- or overfocus for reading children for some of the parameters tested (Ego
or near targets). Measuring the accommodative et al. 2014).
amplitude can be performed subjectively (child The quality and accuracy of the movements
states when print becomes blurred as it is brought (e.g., under or overshoot of the target, limitations
closer to the eyes or reports when a letter or in gaze, smoothness and accuracy of movements,
picture is readable as it is brought away from the associated head tracking, and the ability to cross
eyes from a close distance). Accommodative the midline) are factors that can be assessed with
facility is tested by the child reporting clarity of relevant high interest targets whose size can be
letters with lenses that change focus from distance based upon the results of visual acuity testing. In
to near viewing. For children who are nonverbal, children with nystagmus, it is important to iden-
the lag or lead of accommodation can be measured tify the areas of gaze that result in an increase or
objectively with tests such as Nott retinoscopy decrease in the severity of nystagmus. Children
(Saunders et al. 2010; McClelland et al. 2006), will exhibit adaptive head-turning behaviors in
whereby changes in the retinoscope reflex are order to facilitate maintenance of gaze in the
observed while the child views high-contrast pic- area where their nystagmus is least severe. The
tures at varying distances. Continuous measures placement of educational materials in that area
of accommodative response and variability over will reduce the need for these adaptive head-
time have also been measured objectively with turning behaviors. It is also important to note if
photorefraction in children with CP (Pansell the nystagmus increases in severity with patching.
et al. 2014). This “latent nystagmus” may impact on the effec-
There has been an emphasis both in the litera- tiveness of monocular patching therapy for
ture and in the clinical examination of children amblyopia. Ocular motilities can be assessed
with cerebral palsy on ocular health, visual acuity, with illuminated targets or lights in those cases
binocularity, refractive error, and associated where a measurable level of pattern vision is
accommodation disorders. Other areas however unattainable or to determine a child’s potential
are also important to the child with CP and include tracking ability with targets that are easier to view.
ocular motor skills, visual fields, color vision, Other visual findings such as central scotomas
glare sensitivity, and dark adaptation. (blind spot) or peripheral visual field loss may
Ocular motility or eye movement disorders cause a child to have difficulty initiating an eye
including nystagmus (involuntary horizontal or movement, exhibit frequent loss of fixation during
vertical oscillation of the eyes) and ocular motor ocular motility testing, or show difficulties with
apraxia (absence or lack of control of voluntary scanning during educational or rehabilitation
eye movements) are common in children with CP activities. Children with significant ocular motil-
(Fazzi et al. 2012), especially with a diagnosis of ity disorders such as oculomotor apraxia will not
CVI or periventricular leukomalacia (Jacobson dissociate head from eye movements that would
and Dutton 2000; Salati et al. 2002). Ocular motil- otherwise allow for increased range and effi-
ities in children with CP evaluate the quality and ciency. Children with CP may also exhibit gaze
extent of pursuits (smooth tracking of a moving palsies resulting in an inability to move both eyes
target), saccades (eye movements from one sta- fully either vertically or horizontally and can
tionary target to another), position maintenance result in compensatory head postures that help the
(the ability to maintain steady fixation on a target child point the eyes to a particular viewing area.
at near), and scanning of the surrounding environ- Shakira is 10 years old and uses a communi-
ment (Salati et al. 2002). A recent report demon- cation device with 30 button icons which she is
strated that eye movement deficits in children with able to see based upon the results of visual acuity
and contrast testing. An assessment of her sac- however, to consider that in cases of hemi-spatial
cadic eye movements which targets the size of the neglect, which typically result from damage to the
icons indicated that she has significant difficulties right parietal lobe of the brain, the affected indi-
moving her eyes from one point to another without vidual will turn away from a left-sided visual field
multiple losses of fixation. Although she can see deficit. Central visual field deficits or scotomas
the buttons, her facility with the communication that are associated with retinal or optic nerve
device is limited due to her poor eye movements. defects often create significant visual instability
Shakira would benefit from modifications of her as the central scotoma obscures central detail.
device and therapeutic activities to help her Individuals with central visual deficits may adopt
develop increased accuracy of her eye an eccentric viewing strategy. A child who does
movements. not look directly at visual detail may be using an
Visual fields measure the child’s peripheral or eccentric viewing position to achieve greater
side vision. CP is associated with cerebral visual stability and efficiency which can be espe-
lesions, brain injuries, or malformations that cially useful for reading or other near activities.
may affect visual field function (Jacobson et al. Visual field testing strategies for developmen-
2010; Guzzetta et al. 2001). Intracranial hemor- tally young children with CP is typically
rhages, encephalopathy, ischemia, periventricular performed by presenting high-interest visual tar-
leukomalacia, or cerebral dysgenesis may gets (based upon the child’s visual acuity) from
result in significant visual field loss, including non-seeing to seeing visual field regions, while
hemianopic, altitudinal, and quadrant visual def- the tester observes the child’s responses to the
icits. Damage to one side of the posterior brain moving target and determines the eccentricity at
may result in a field deficit on the contralateral which the child first detects the target in each field
side. A hemorrhage that occurs in the right occip- of gaze. This strategy can uncover gross periph-
ital lobe region will result in a left homonymous eral visual field deficits (Mayer 2011; Zambone
hemianopia. These central nervous disorders as et al. 2000). For developmentally older children
well as syndromes affecting the development of with CP, standard visual field testing such as
the child’s central nervous system may affect threshold or kinetic perimetry may uncover more
retinal as well as optic nerve development. Chil- subtle visual field deficits in the central or periph-
dren with associated optic nerve abnormalities or eral visual field regions. Table 2 describes exam-
retinal pathology such as ROP may also experi- ples of field loss, associated behaviors, impact on
ence central and/or peripheral visual field deficits. function, and management strategies.
Early identification of visual field deficits is
essential in the development of individualized
therapeutic programs and activities that are geared Color Vision
toward enhancing children’s use of residual vision
for learning, independent mobility, and daily The ability to see all visible colors with three
activities. In turn, observations of children during retinal cone types (trichromacy) develops by
independent mobility and other activities may approximately 3 to 4 months of age in the absence
provide the observer with significant clues about of pathology. In addition, approximately 8% of
a child’s visual field deficits that can be confirmed males and 0.5% of females have an inherited color
through examination. For example, head turns and deficiency. Knowledge of family history can help
tilts may be adaptations to visual field loss. Chil- identify if a child is at risk for an inherited color
dren with hemianopic visual field loss will typi- vision deficiency which is most typically passed
cally turn their head toward the defective visual down through the X chromosome from the child’s
field region. A child with a left homonymous maternal grandfather to the mother (who is often a
hemianopia will turn the head to the left, while a “carrier” and not affected) and onto her male
child with a lower visual field loss will tilt the head children in 50% of cases. Color vision has
downward toward the defect. It is important, shown to be impaired at a higher rate in children
Table 2 Visual field defects and management in children with cerebral palsy
Field deficit Etiology Impact on vision Visual adaptations
Management
Right Lesion at left Visual field defect Head/eye turn to • Fresnel sectoral prisms/Peli prisms
homonymous optic tract or involving right visual right • Yoked prisms for reading
hemianopia left occipital hemisphere • Orientation and mobility (O&M)
lobe When defect in • Mobility cane
occipital lobe region, • Seating to right of classroom midline
small area of central • Reading guides
visual field spared • Position materials to left of midline
Left Lesion at right Visual field defect Head/eye turn to • Fresnel sectoral prisms/Peli prisms
homonymous optic tract or involving left visualleft • Yoked prisms for reading
hemianopia left occipital hemisphere • Reading guides
lobe When defect in • O&M
occipital lobe region, • Mobility cane
small area of central • Seating to left of classroom midline
field spared • Reading guides
• Position materials to right of midline
Inferior Periventricular Visual field defect Downward head tilt • O&M
altitudinal leukomalacia, involving lower • Mobility cane
hemianopia optic atrophy visual hemisphere • Base down prisms for reading/
writing
• Position materials above midline
Homonymous Lesion at Sectoral visual field Downward head tilt • Sectoral prisms/Peli prisms
inferior parietal upper deficit in lower visual with head turn • Reading guides
quadrantanopia optic radiations hemisphere toward location of • Position materials above midline
sectoral visual field
deficit
Homonymous Lesion at Sectoral visual field Upward head tilt • Sectoral prisms/Peli prisms
superior parietal lower deficit in upper visual with head turn • Reading guides
quadrantanopia optic radiations hemisphere toward location of • Position materials below midline
sectoral visual field
deficit
360 degree Retinal disease Severe constriction Constant scanning • Fresnel sectoral prisms/Peli prisms
constriction (retinitis of peripheral visual of environment • Reverse telescope minifiers
pigmentosa, field especially when in • Reading guides
advanced unfamiliar areas
glaucoma)
Central Macular Visual field defect Eccentric viewing • Magnification strategies
scotoma disease within central visual of visual detail • Increased contrast of visual detail
Optic nerve field region • Task lighting
disease • Ambient glare reduction
• Vision services in classroom
with CP with worse performance in children with color vision. Similar to visual acuity testing, pic-
greater motor impairment (Costa and Pereira ture identification and matching as well as
2014). Color deficiencies become most relevant “pointing or looking” color vision tests are avail-
when the child begins educational or rehabilita- able. Therapists and teachers working with chil-
tive activities that may be color coded (e.g., pic- dren with CP who are engaging children in tasks
tures, blocks, balls, toys, icons, letters). While requiring color differentiation or color matching
some children with CP may be able to identify activities should be aware of any familial color
the numbers in the standard Ishihara or HRR deficiencies, especially for boys. While children
pseudoisochromatic plates for color vision test- with most types of inherited color deficiencies see
ing, many cannot, despite the presence of normal colors, the perception of color is different.
Confusion most commonly occurs between reds, Vision Evaluation Outcomes

greens, and yellows, as well as in reduced illumi-
nation, with dark or “muddy” or pastel or The most important result of an assessment of
desaturated colors. In addition, the use of medica- functional vision for a child with CP is informa-
tions such as anti-seizure medications may alter a tion about if and how the child “sees” and recom-
child’s color perception (Hilton et al. 2004). mendations for how to encourage the use of vision
for educational advancement and overall develop-
ment. It is important that this information be pro-
Glare Sensitivity and Dark Adaptation vided in a practical and understandable format so
that caregivers, educators, therapists, and others
Glare sensitivity has been documented in individ- involved in the care of the child can utilize the
uals that have experienced brain injury and stroke results in a way that benefits the child (Ciner et al.
(Beasley and Davies 2012). As cerebral vascular 2011).
accidents such as stroke and brain injury are eti- If additional vision testing is required after the
ologies for cerebral palsy, it is not surprising that initial evaluation, home practice (e.g., increasing
children with cerebral palsy may experience glare tolerance to occlusion of an eye or improving
sensitivity. Glare sensitivity is also associated attention to black and white stripes) may be
with medications such as carbamazepine that are recommended in order to habituate the child to
prescribed to control seizure activity (Hilton et al. the testing procedures and improve performance
2004). Glare sensitivity creates significant visual for future exams. Activities that incorporate the
discomfort in both outdoor and indoor environ- use of striped patterns, wearing a “pirate patch”
ments. Observation of the child in sunny outdoor and locating small objects such as a finger puppet,
environments as well as in brightly illuminated may all significantly affect the child’s responsive-
indoor environments will provide clues to the ness to the vision evaluation. Habituating the
presence of glare sensitivity and photophobia. A child to wearing glasses may be recommended
child who experiences significant glare sensitivity through a frame tolerance program that could
may adapt a downward head tilt when experienc- include both school staff and caregivers. Referrals
ing glare; demonstrate more mobility-related to other vision professionals may also be required.
issues, especially when approaching curbs, stairs, For example, a comprehensive orientation and
and other mobility-related drop-offs; and demon- mobility evaluation may be helpful for a child
strate greater difficulty in detecting visual detail, with CP who has a reduction in visual acuity or
especially low-contrast detail. field and for whom safe and independent travel is
Children who have been diagnosed with cere- a concern.
bral palsy resulting in poorer motor outcomes
have a higher incidence of optic nerve and retinal
disorders (Ghate et al. 2016; Ghasia et al. 2009). Complications of the Disease Process
Retinal disorders such as retinopathy of prematu- and Treatment
rity may lead to rod dysfunction that manifests as
dark adaptation deficits. A child with dark adap- As discussed throughout this chapter, left
tation issues will hesitate when experiencing a untreated, vision disorders common in children
change in illumination and will experience a sig- with CP such as significant refractive error often
nificant reduction in visual function until able to result in reduced vision, amblyopia, or strabismus,
adapt to the lower illumination levels. Electroret- which can in turn impact the development and
inographic procedures are helpful in detecting maintenance of associated visual skills including
photoreceptor deficits that are associated with binocularity or depth perception. For example,
increased light sensitivity as well as dark visual acuity at distance can be directly affected
adaptation. by significant myopia or astigmatism. Visual
acuity at near is also impacted by moderate to high present further mobility-related challenges to
hyperopia and poor accommodative skills. Chil- these children resulting from lowered visual func-
dren who are not seeing clearly or who are unable tion as well as significant visual discomfort. Treat-
to achieve, maintain, or change focus for a range ment and management of some common visual
of viewing distances will have difficulty discern- disorders in children with CP are described below.
ing standard educational materials at distance and
will experience challenges staying on task for near
viewing when working with standard text, a com- Treatment and Management
munication device, iPad, or computer. Children of Identified Vision Disorders
with reduced contrast sensitivity associated with
optic nerve or retinal disorders may be unable to Surgical intervention by pediatric ophthalmolo-
see lower contrast educational detail when reading gists is used to treat a number of visual deficits
or writing. Children with central or peripheral that are associated with CP. Ocular muscle relo-
visual field loss will experience difficulty when cation surgery corrects horizontal and vertical
visually tracking lines of text on a page or screen misalignment in children with strabismus. Stra-
or locating icons on a communication device. The bismus surgery can improve ocular alignment,
resulting visual instability can cause further provide better binocularity, and can be important
reduction in visual attention and difficulty acquir- for psychosocial or cosmetic reasons (Collins
ing important educational information. A child 2014; Ma et al. 2013, 2017). Muscle relocation
may attempt to compensate for visual instability is also used to reduce adaptive head-turning
with postural changes such as head turns, tilts, or behaviors in children with nystagmus. Children
bending and leaning excessively close to educa- can adapt head turns or tilts to place their eyes in a
tional materials to achieve necessary magnifica- position of gaze that reduces the severity of the
tion of visual details. While improving visual nystagmus. The goal of the surgical intervention is
processing in the short term, these adaptations to reposition the area where the nystagmus is least
may create physical discomfort and fatigue that severe or absent as close as possible to postural
reduces sustained visual attention and perfor- midline. Premature infants with CP may have
mance long term. Inadequate lighting or environ- associated retinopathy of prematurity. These
mental glare will also adversely affect academic infants are treated primarily with peripheral retinal
performance of children with light/dark adapta- ablation using laser photocoagulation as a first
tion issues. line of defense. Alternative treatments including
Vision disorders causing a reduction in visual anti-VEGF therapy, cryotherapy, or dark rearing
skills (e.g., visual acuity, binocularity, depth per- to reduce the risk of progressive disease associ-
ception, visual field, or contrast) can also be asso- ated with severe retinal changes including retinal
ciated with significant mobility-related issues. detachment are alternatives depending on the
Children with these disorders may misjudge phase of the ROP, available resources, and asso-
mobility-related drop-offs such as curbs, stairs, ciated risk factors (Chan-Ling et al. 2017). Even
and irregularities in their pathway that may with early and proper treatment, children with
cause them to trip, fall, or navigate erroneously ROP are at an increased risk for visual deficits
in a wheelchair. Children with reduced peripheral including field loss, color vision deficits, strabis-
vision may experience difficulty crossing busy mus, and significant refractive error (Hansen et al.
intersections or safely negotiating a crowded envi- 2017; Chan-Ling et al. 2017; Fielder et al. 2015;
ronment. Affected children may also not be ade- Fulton et al. 2009; Hellstrom et al. 2013).
quately able to see signs, lights, and other cues to Patching may be recommended by the eye care
navigation that are positioned at an extended dis- provider for treatment of amblyopia caused by
tance, placing them at greater risk for mobility- refractive error disparities or eye misalignment.
related injuries. Disorders such as glare sensitivity Patching the child’s better-seeing eye increases
and prolonged light or dark adaptation will the development of vision in the poorer-seeing
eye. Children with developmental delays may the child needs services that will teach safe
resist monocular patching due to tactile sensory navigation in both habitual and unfamiliar
issues. Children who have nystagmus that environments.
increases in severity with monocular patching Optical correction: When considering the pre-
will experience significantly greater visual insta- scription of corrective lenses, multiple areas
bility which can reduce the effectiveness of the should be taken into account. These include the
monocular patching therapy. In both of these impact of glasses on visual acuity, binocularity,
cases, atropine or other cycloplegic agents may accommodation, and visual comfort. For children
be used to increase the visual engagement of the with reduced visual acuity, it is also important to
poorer-seeing eye by eliminating the near- factor in the need for near magnification, glare
focusing abilities of the better-seeing eye. reduction, contrast enhancement, and protection
Vision rehabilitative services can be adminis- of the eye from injury. In cases of intermittent
tered and supported by the teacher of the visually exotropia, a correction for the full magnitude of
impaired (TVI), occupational therapist (OT), or the myopic refractive error may be helpful to
orientation and mobility (O & M) instructor in the reduce the likelihood of progression to a constant
home or school. For children with CP who have exotropia. The level of visual impairment also
severe visual impairment associated with CVI, affects prescribing strategies.
retinopathy of prematurity, or other ocular disor- For example, the eye care provider may also
ders, a basic visual skill program may be not fully correct a myopic refractive error if the
implemented by the TVI or OT that concentrates child has been diagnosed with a visual impair-
on improving visual fixation, localization, visual ment and requires a reduced viewing distance to
scanning (saccades), visual tracking (pursuits) identify visual detail. For older children who
skills, or convergence activities. The teacher or exhibit accommodative dysfunction or visual
therapist will initially use illuminated and high- impairment, incorporation of additional power
contrast visual targets that are presented within the for near in the form of bifocals will improve the
child’s area of residual vision. If visual responses child’s focus and comfort for reading and near
are inconsistent, auditory or tactile cues may be activities. In contrast, if a child has significantly
added until the child responds more consistently. reduced peripheral vision, a bifocal may create
At that point, the other sensory cues are elimi- visual blur when the child scans the lower visual
nated, and the therapy proceeds using only the region resulting in an increased risk of mobility-
visual targets. When consistent fixation, localiza- related injury. In those cases, separate near and
tion, visual scanning, and tracking behaviors are distance corrections are indicated. Table 3 lists
observed within the child’s area of residual vision, types of lenses that may be considered for children
the child is encouraged to visually track and with cerebral palsy along with reason for pre-
search for the target within the areas where there scribing, benefits, and contraindications.
was previously a reduced or absent visual Prisms: Incorporation of low amounts of
response. The TVI can also help the child effec- prisms into corrective lenses may facilitate fusion
tively use any prescribed near or distance magni- of images when viewing visual detail in the pres-
fication devices. ence of diplopia or intermittent eye turns for chil-
Children with visual impairments are at dren with CP who exhibit poor motor control.
increased risk for eye injuries resulting from Higher amounts of prism may be incorporated
contact with unseen objects in their visual into a near correction to enable a child with a
environment. They are also at greater risk for visual impairment to use both eyes for reading at
tripping or falling when encountering curbs as the reduced viewing distance that is required to
well as other mobility-related drop-offs. For achieve necessary print magnification. Prismatic
children who can walk independently or use a corrective lenses have also been used for children
wheelchair for independent mobility, an orien- who exhibit head-turning behaviors to reduce the
tation and mobility evaluation can determine if severity of nystagmus. The image displacement
Table 3 Optical options and considerations for prescribing for children with CP
Type of lenses Purpose Benefit Contraindications/negatives
Glasses • Reduced VA at distance • Improved focus and clarity • Frame intolerance
and near due to significant • Extend visual attention • Increased peripheral distortion
refractive error with higher refractive corrections
Contact lenses • Reduced visual acuity at • Improved focus and clarity • Contact lens intolerance
distance and near due to • Reduced peripheral distortion • Corneal disease
significant refractive error with higher refractive • Inability to insert, remove and
corrections maintain contact lenses
• Extend visual attention
Bifocal • Accommodative • Magnification • Reduced peripheral vision
dysfunction • Improved near focus and especially in lower visual
• Esotropia or esophoria clarity hemisphere resulting in mobility
• Visual impairment • Improved near vision comfort concerns
• Blurred near vision • Reduce near blur • Nystagmus increases on downgaze
• Improved eye alignment • Eye movement disorder with
• Provides both near and reduced downgaze
distance vision without • Reduced reading area
changing glasses
• May be used when walking
Single vision • Need for near vision • Magnification • Unable to easily switch between
for near only prescription different from • Improved focus glasses
distance • Improved near vision comfort • Should not be used when walking
• Unable to wear bifocals • Improved clarity
• Reduce near blur
• Improved eye alignment
• Increased reading area
Polycarbonate • UV protection • Reduces risk of injury • None
Protective • Protection from eye injury • UV protection
lenses • Lighter than standard lenses
Anti-reflection • Discomfort from glare • Reduces reflective glare • Increased cost of lenses
lens coating • Improves contrast
Tinted lenses • Discomfort from indoor • Light tints reduce glare • Increased cost of lenses
lighting (e.g., fluorescents) • Reduce photophobia • One tint may not work in all levels
• Enhance contrast of illumination
Transition • Discomfort from sunlight • Protection from UV • Increased cost
lenses • Comfort outdoors and indoors • Some do not become totally clear
• Reduce photophobia indoors
• Prolonged transition from tinted to
clear problematic for children with
dark adaptation issues
Polarized • Discomfort from sunlight • Reduced glare • Increased cost
lenses • Protection from UV • Need for separate pair of glasses
• Comfort outdoors for indoor use
created by the prisms reduces the need for the ability to maintain fixation and reduce loss of
compensatory head turns. place with reading or communication devices.
Prism may also be useful for children with For example, a child with a lower visual field
peripheral field loss for both near and distance deficit would typically bend toward the reading
viewing. In cases of hemianopic visual field def- material in order to superimpose the remaining
icits, low amounts of prism may be incorporated upper field over the text. Prescribing a prismatic
into a near vision correction to shift more visual correction would shift the image upward, thereby
detail into the child’s residual visual field region. reducing the need to bend over the material and
This may improve the child’s reading speed and increasing postural comfort.
For children with a hemianopic visual field for students with CP who have residual vision
defect or overall visual constriction, the place- but are unable to manipulate handheld or specta-
ment of a high-powered Fresnel (press-on) sec- cle mounted magnification devices for reading.
toral prism or Peli prism into a distance vision Lindsey is 12 years old and has reduced cen-
correction overlaps with the area of the child’s tral acuity secondary to optic atrophy. Her best-
defective field. When the child’s eyes scan into corrected visual acuity is 20/60 in both eyes along
the prism, images from the non-seeing area are with reduced contrast sensitivity. Lindsey and her
shifted into the child’s residual field, thus increas- family are going to Disney World for a family
ing awareness of potential obstacles in the vacation. They are interested in a device that
non-seeing visual region. The use of a mobility would magnify objects in the distance without
cane with the prismatic correction may also sig- her having to hold a low vision device. Lindsey
nificantly increase the child’s safety in unfamiliar benefitted from a low magnification (2.2) spec-
locations. tacle mounted telescope. Low magnification is key
Low vision devices: Visual acuity information to improving her visual acuity but not reducing
obtained during the clinical vision examination her visual field more than necessary. A spectacle
may be used to determine the degree of magnifi- mounted telescope also allows Lindsey to be
cation that is required to enable a child with cen- “hands-free” while viewing through the telescope.
tral vision loss to identify educational visual Communication devices: A child’s visual abil-
detail. Near magnification devices and other mag- ities and limitations need to be included in con-
nification strategies can enhance the use of resid- siderations for the type and setup of
ual vision and reduce visual fatigue in children communication devices. For example, a child’s
with CP and central vision loss. The prescription visual acuity can guide the stroke width and size
of these devices is individualized based upon the of letters, symbols, and other visual details
child’s visual status, educational or visual included within the device’s icons. Visual field
demands, and cognitive and motor abilities. The status can guide the optimal positioning of the
use of large print materials, hand/stand magni- communication device. Eye movement status
fiers, or magnifying reading glasses provide can also determine the positioning of the commu-
essential magnification. Video magnifiers and nication device as well as the separation between
other assistive technology strategies provide an icons and the number of icons. A child’s contrast
increased range of magnification, high-definition sensitivity ability and color preference can guide
image quality, contrast enhancement, and glare- the color and definition of the icons as well as the
reducing features such as reverse polarity presen- background brightness or color.
tation of text. Telescopic devices provide neces- Jackson was having challenges with his com-
sary magnification of visual detail at distance munication device at school. His vision exam
including information written on a classroom indicated reduced visual acuity and poor contrast
white board or the identification of street signs. sensitivity. His color vision was normal. His
For children who are unable to hold magnification device was modified with a frame providing a
devices but have adequate head control, spectacle large red border around each picture and a rec-
mounted magnification devices are also available. ommendation to increase the colors in the pictures
Text-to-speech scanners may provide visual as to help him better differentiate and identify each
well as auditory presentation of text or, if vision one (Fig. 4).
is inadequate for efficient reading, text-to-speech Environmental adaptations: Reading stands
presentation exclusively. Speed reading training and slant desks provide magnification to a child
programs that scan text and then present one word with CP and visual impairment by bringing edu-
at a time on a computer screen or tablet at variable cational materials closer. The use of bold-lined
magnification and reading speeds offer significant paper and high-contrast wide-tipped pencils and
potential for increased reading accuracy, effi- markers enhances magnification and contrast due
ciency, and speed. This is especially promising to their broader stroke widths. These adaptations
gaze and dampens on left gaze. These general

concepts also apply to positioning in a non-
traditional classroom or therapy environment.
Integration of Recommendations into

Education and Rehabilitation Plans
Data collected from the vision evaluation is often

used to address issues in education, rehabilitation,
and daily living activities for children with CP. An
enhanced understanding of visual status and how
this translates into concrete recommendations is a
fundamental outcome of the evaluation (Ciner
et al. 1996). It is also important to note that there
may be circumstances in which the use of vision
may not be the most efficient or effective way for a
child to learn or perform educational tasks. This
would include severe visual acuity and visual field
loss or the presence of a progressive ocular dis-
ease that will eventually result in severe visual
acuity and visual field loss. Multisensory
Fig. 4 Example of framing a communication device to approaches including auditory and tactile strate-
improve eye gaze
gies may also be considered to improve visual
responsiveness and help children with CP func-
would reduce the child’s need to bend over edu- tion to their fullest potential.
cational materials as well as reduce associated Vision is an important skill to evaluate in chil-
postural and visual fatigue. The use of task floor dren with cerebral palsy. The eye care provider
or desk lamps reduces ambient glare by concen- can contribute important understanding regarding
trating the light on the reading and writing mate- how a child sees, the potential for improvements
rials and away from the student’s eyes. Children in vision, and recommendations to allow educa-
who are sensitive to glare should be seated away tors and rehabilitation specialists to integrate
from outdoor windows or overhead lighting. vision into the child’s overall education and reha-
For children attending school in a traditional bilitation programs. Ocular and visual assess-
classroom, preferential seating appropriate to the ments should be a routine component of the
nature of the child’s visual impairment is critical. medical management of children with cerebral
For children with reduced central vision, front row palsy. Resulting recommendations should play
seating provides necessary magnification that an integral part in developing strategies for inter-
increases access to visual detail that is being pre- disciplinary education and rehabilitative pro-
sented to the class. For a child with a right grams for children with cerebral palsy.
hemianopic visual field deficit, seating to the
right of the classroom or therapy room enables
optimal position of classroom visual detail within Cross-References
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Strabismus Management in the Child
Jonathan H. Salvin and Dorothy Hendricks
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1042
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1043
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1043
Nonsurgical Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1044
Surgical Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1044
Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1045
Binocular Vision . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1045
Amblyopia and Visual Acuity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1045
Strabismus Surgery Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1046
Psychosocial Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1046
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1047
Abstract thorough ophthalmic examination and potential

Examining children presents unique challenges for intervention with either medical or surgical
to ophthalmologists. Examining a child with management for a multitude of ocular compli-
cerebral palsy (CP) presents even more difficul- cations seen in patients with cerebral palsy.
ties due to multiple medical issues, develop- Children with CP have a higher incidence of
mental delays or even permanent lack of strabismus than the general population.
verbal communication, and cooperation issues. Esotropia or crossing of an eye is the most
This, however, does not eliminate the need for a common type of strabismus in children with
CP. Treatment for strabismus includes medical
management, such as glasses, occlusion or
J. H. Salvin (*) · D. Hendricks
penalization therapy, and surgical manage-
Division of Ophthalmology, Nemours/A.I. DuPont ment. While surgery for strabismus in children
Hospital for Children, Wilmington, DE, USA with CP carries an increased risk of under- or
Departments of Ophthalmology and Pediatrics, Sydney overcorrection compared to the same surgery
Kimmel Medical College/Wills Eye Hospital, in typically developing children, it has still
Philadelphia, PA, USA been shown to be beneficial in decreasing
e-mail: jsalvin@nemours.org; Jonathan.Salvin@nemours.
org; Dorothy.Hendricks@nemours.org
amblyopia and improving binocularity.

https://doi.org/10.1007/978-3-319-74558-9_77
1042 J. H. Salvin and D. Hendricks
Proposed mechanisms to deal with this issue Strabismus is any misalignment of the
include adjustment of standard surgical nomo- eyes. Esotropia is the inward deviation of
grams or the use of botulinum toxin to the one eye. Exotropia is the outward deviation of
extraocular muscle, which typically has a tem- one eye. Vertical deviations, hypertropia or hypo-
porary effect. At this time, there is no consen- tropia, are the up and down deviation of one eye,
sus as to how to adjust surgical treatment for respectively. These deviations may result in
the child with CP. Successful alignment may amblyopia, poor vision development in one or
require multiple surgeries. both eyes that may be irreversible if not corrected
early. Misalignment also results in loss of binoc-
Keywords ularity and stereoacuity.
Cerebral palsy · Strabismus · Amblyopia · Treatment for misalignment is often multifac-
Esotropia · Eye muscle surgery eted, including refractive correction (glasses),
amblyopia treatment (occlusion or penalization
therapy with atropine eye drops), and surgical
Introduction correction. Surgery involves manipulating the
extraocular eye muscles to change the alignment
Children with cerebral palsy (CP) have a high of one or both eyes. Generally, earlier correction
prevalence of ocular manifestations including results in improved outcomes and vision
strabismus, amblyopia, cortical visual impair- development.
ment, nystagmus, saccade, and pursuit deficien- Strabismus is one of the most common eye
cies, as well as other abnormalities of the visual problems in childhood. It is estimated to effect
pathway (Black 1982; Breakey 1955). These 4% of the general population. The estimated prev-
patients present unique challenges to the examin- alence in CP patients, however, is between 11%
ing ophthalmologist: the patients may be difficult and 50%, making it the most common ocular
to examine due to developmental and behavioral finding in CP. Strabismus is more common in
delays; it is often unclear if intervention will be spastic-type CP than dyskinetic or ataxic CP. It
beneficial to the patient based on their cognitive is also more common in diplegic than in hemi- or
abilities; and surgical results are less predictable, quadriplegic CP (Collins 2014).
resulting in over- and under-correction at higher Esotropia is the most prevalent, as it is found in
rates than in neurologically intact children. up to 55% of patients with CP (Fig. 1), with
Strabismus Types
60
50
Percent of CP Patients
40
30
20
10
0
Esotropia Exotropia Dyskinetic Vertical (including Vertical (isolated)
DVD)
Fig. 1 Average reported strabismus types in CP patients

73 Strabismus Management in the Child with Cerebral Palsy 1043
infantile esotropia being the most common, found The Gross Motor Function Classification
in up to 20% of patients with CP. This is a rate five System (GMFCS) was designed to classify CP
times that of the general population (Jackson et al. by the level of functional capability and limita-
2006). Exotropia is reported in 30% of CP stra- tions. Levels 1 through 5 reflect increasing levels
bismus. Dyskinetic strabismus has been reported of limitation and motor impairment. At least half
in 10–23% of patients with CP (Jackson et al. of the children with CP (regardless of GMFCS
2006). These are fluctuating deviations of the level) have limited binocular vision function, with
eye in both directions (esotropia, exotropia) and 70% or more of those at GMFCS 3 or higher
frequency of the deviation. They may vary having little or no binocular fusion. Higher levels
between esotropia and exotropia and may have of strabismic amblyopia are found in children at
good control of the deviation at times where it is Levels 1 and 2; however, it is likely that children
rarely manifest and then poor control at others. at Levels 3–5 have higher rates of dyskinetic
There is not a pattern to the fluctuation as may be strabismus and poorer cognitive function, mak-
seen in cyclic strabismus. The variability makes ing measuring visual acuity more difficult.
correction a challenge for the strabismologist. Iso- GMFCS level is also found to correlate with
lated vertical strabismus is found in only 1% of afferent visual pathway pathology including
CP patients. However, dissociated vertical devia- optic atrophy and cortical visual impairment.
tion (DVD) with or without associated horizontal Strabismus, and specific types of strabismus, is
strabismus is found in up to 50% of patients. DVD found in all GMFCS levels and does not appear
is an anomalous vertical eye movement of one eye to be more significant with higher levels (Ghasia
only, without a corresponding duction from the et al. 2008).
opposite eye. It is typically seen as an upward and Vergence mechanisms, the ability to maintain
outward “floating” of one eye often manifest dur- binocular eye movements and fusion, are particu-
ing periods of inattentiveness or fatigue. larly affected in CP and highly associated with
strabismus. It remains unclear if the strabismus
causes poor vergence or vice versa or if there is
Natural History another underlying etiology for both.
The underlying etiology of most strabismus

remains unclear. Rarely, misalignment results Treatment
from cranial nerve palsies (III, IV, or VI), eye
muscle abnormalities, or eye muscle restrictive In the 1950s–1970s, little is found in the literature
processes. Strabismus often also develops in regarding strabismus treatment for children with
poorly seeing eyes from lack of visual stimulation. CP. Surgical intervention was felt to be largely
Most strabismus, however, are is due to an under- unsuccessful and to have unpredictable results.
lying breakdown of the neuromuscular control of There were also anecdotal reports of spontaneous
eye movements without a distinct neurologic resolution of strabismus or spontaneous reversal
insult. This process is not well understood. of strabismus (exotropia in previously esotropic
Periventricular leukomalacia (PVL) is a dam- patients) (Collins 2014). In addition, there was
age to the periventricular white matter caused by also the belief that due to some cognitive delays,
hypoxic ischemic events most often in premature some of the CP patients might not benefit from
children (gestational ages 24–34 weeks) (O’Keefe strabismus correction.
et al. 2001). Most children with PVL develop CP; Today, there is agreement that patients with CP
however, not all premature infants who develop gain significant visual benefits from strabismus
CP have PVL (Arnoldi and Jackson 2005). The treatment, including improvement in amblyopia,
optic pathways are often involved with the PVL stereoacuity, and binocularity, as well as psycho-
lesions therefore causing visual dysfunction, with social benefits. Improved alignment may offer
most developing strabismus. social benefits to children who may be teased for
their other sensorimotor handicaps. In children alleviate some or all of the esotropic deviation in
with CP, failure to correct strabismus may result CP patients.
in a double-negative effect, with impaired binoc- Strabismic amblyopia results from the child’s
ularity, which may exacerbate mobility and preference for one eye, typically the eye that devi-
postural dysfunction (Ghasia et al. 2011). In addi- ates more, over the other. Amblyopia manage-
tion, with technologic advancement in communi- ment involves occlusion of the better-seeing
cation devices that use gaze-directed commands, eye either with patching or with pharmacologic
improved alignment and eye movements may penalization therapy with atropine drops used to
allow successful use of these devices. blur the vision in the good eye, thus forcing the
child to use the opposite eye and improving the
vision in that eye. With equal vision, some of
Nonsurgical Treatment these children will then maintain improved align-
ment, particularly in some exotropic or vertical
Nonsurgical techniques of strabismus correction deviations.
include spectacle correction, occlusion and penal- Orthoptic convergence exercises are used to
ization therapy, and orthoptic exercises. help improve near point convergence, thereby
The human eye has the innate ability to create improving exotropic deviations. This can be
focusing power to allow for focusing on objects done at home with simple alternating distance
at varying distance to the person. This mecha- and near target focusing methods. Additionally,
nism, called accommodation, results from the there are many computer-based or internet-based
contraction or relaxation of the ciliary muscle, exercise options available, as well as in-office
which changes the shape and curvature of the optometrically guided exercise therapy programs.
crystalline lens inside the eye. The resultant These have all been shown to be effective in
change in the lens adds or subtracts refractive improving control in convergence insufficiency-
power and changes the focal distance of the eye. type exotropias, a less common variation of
When the eye accommodates, there are two deviation.
corresponding eye actions, miosis and conver-
gence. The act of convergence allows the eye to
focus on near targets. Surgical Treatment
Accommodative esotropia results from an
over-convergence mechanism which exaggerates Conventional strabismus surgery techniques are
the esodeviation of the eye. Typically, these chil- employed in CP patients as in non-CP patients for
dren are highly hyperopic and may demonstrate non-refractive types of strabismus. Generally,
anisometropia, which is an unequal refractive early surgery is preferred to allow improved bin-
error. The attempts to keep images in focus ocularity and equal visual input to the brain from
by the accommodation mechanism result in each eye. In patients with CP, surgery may be
inward deviation of one eye. In accommodative delayed due to limited examination ability in the
esotropia, appropriate hyperopic correction office to establish accurate measurements of the
relaxes the patient’s own accommodative effort deviation, instability in the deviation itself, and
and can improve alignment and vision. Some the risk of overcorrection. In some patients with
children have an additional exaggerated effect at CP, it may be felt that correcting the strabismus
near due to high accommodative convergence offers no significant functional advantages due to
to accommodation (AC/A) ratio. Bifocal correc- the severity of their cognitive limitations associ-
tion is necessary in these patients. CP patients ated with their CP. Surgery may also be delayed
may have an accommodative esotropia with because of higher-priority medical procedures and
lower degrees of hyperopia, in what would typi- high general anesthesia risk.
cally be considered the normal range of hyper- Strabismus surgery techniques include extra-
opia. Hyperopic glasses should be tried to ocular muscle recession to weaken a muscle and
resection to strengthen a muscle. Muscle transpo- Complications

sition can be used to move one muscle in place
of another palsied or otherwise impaired muscle. Binocular Vision
Surgical nomograms have been created to deter-
mine the amount of surgical adjustment to a given Sensory fusion is the ability of the brain to per-
muscle based on the angle of deviation. In neuro- ceive an image with each eye and fuse them into
logically intact patients, these nomograms offer one image. Motor fusion is the ability for the eye
long-term surgical success of 80–90% of patients alignment and eye movements to be coordinated
with a single surgery. The results of strabismus to allow for sensory fusion. Stereopsis is the abil-
surgery on developmentally delayed patients ity to use sensory and motor fusion to create the
are more variable and less predictable, with perception of a three-dimensional world. Sensory
over- and under-correction being more common, fusion, motor fusion, and stereopsis are poor in all
thus requiring additional strabismus surgery to children with strabismus but have been found to
achieve alignment success. be worse in children with CP and strabismus.
Botulinum toxin injection into the extraocular One goal of strabismus surgery is to restore
muscles has long been used as an adjunct to tra- elements of sensory and motor fusion and stereop-
ditional strabismus surgery or as a stand-alone sis. In neurologically intact children, fusion is
procedure for strabismus. It has been shown to restored in 70–90% of esotropic patients and
be effective in patients with CP as well (Ameri 50–70% of exotropic patients. In children with CP,
et al. 2015). The toxin temporarily paralyzes the this is only 50% in esotropia and 25% in exotropia.
muscle, allowing relaxation of the muscle and Stereopsis was regained in 20% of esotropic chil-
improved alignment. The toxin effects last for dren and 18% of exotropic children with CP, com-
approximately 3 months and then breaks down pared to 27–40% and 20%, respectively, in
completely. It has been shown that its effect on neurologically intact children (Ghasia et al. 2011).
strabismus can last longer than 3 months, likely The difference in outcomes may be attributed to
due to physiologic changes within the muscle neurologic disease (cortical visual impairment) but
during the time of action. Some patients require also may be due to the delay in referral and treatment
only botulinum toxin injection without further in these patients. Early intervention for congenital
strabismus surgery. It has been shown to be effec- strabismus has been shown to improve fusional and
tive as a stand-alone treatment for mild-to-moder- stereopsis outcomes. It is recommended that the
ate-angle esotropia and exotropia. It may also be eyes should be aligned before 2 years old in order
useful for paralytic (palsied) deviations and for to achieve functional fusion outcomes.
correction of small residual deviations or over-
corrections after traditional strabismus surgery.
Potential short-term side effects include ptosis Amblyopia and Visual Acuity
(from toxin effecting the levator muscle) and
overcorrections. Both of these generally resolve Amblyopia is the abnormal development of
before, if not by, the end of the 3-month effect vision in one or both eyes from poor visual input
of the toxin. It has the advantage over traditional in infancy and early childhood. Amblyopia
surgery in that no conjunctival incisions are cre- can result from a number of causes including
ated, therefore reducing postoperative infection uncorrected high refractive errors, asymmetric
rates and reducing potential scarring, leaving refractive errors (anisometropia), or strabismus.
additional muscle options for future surgery if Ptosis, corneal scarring, cataracts, or retinal pathol-
needed. It is also a considerably shorter proce- ogy can cause deprivational amblyopia. Patients
dure, therefore lessening anesthesia time. In the with CP may have neurologic impairment limiting
CP population, the temporary effect of the toxin is their visual outcomes, but superimposed ambly-
advantageous where the strabismus may be opia can potentially limit their vision further and
unpredictable and variable. should be treated to maximize their visual potential.
Measuring visual acuity and assessing for proposed. Developmentally delayed patients
amblyopia can be difficult in any preverbal or with CP may have an underlying defect in the
nonverbal child. Technologic advancement in binocularity system (potentially causing the stra-
vision screening devices has offered some bismus in the first place). Poor fusional potential
improvement in screening for amblyopia risk fac- leads to worse long-term surgical results. It is also
tors, but none of these devices directly assesses possible that the extraocular muscles of CP
visual acuity. A common method used to measure patients are abnormal and thus do not respond to
acuity in the nonverbal child is Teller Acuity typical muscle manipulation with strabismus sur-
Cards. These are cards which have graded lines gery techniques. Surgery may be delayed in
in varying patterns that measure acuity based on patients with CP due to other medical issues or
the child’s preferential looking at the pattern. delayed referral. There is also a higher rate of late
Assessing acuity by Teller Acuity Cards can be consecutive deviation (exotropia after esotropia)
time-consuming and limited in the neurologically in patients with CP adding to the late failure rate.
intact nonverbal child. The CP patient presents Adjustment of the surgical correction amounts has
additional challenges because of other abnormal- been advocated to try to improve surgical success;
ities in eye movements including saccade and however, the proper amount of adjustment
pursuit deficiency, nystagmus, and poor fixation. remains unclear. Surgical success will often
The testing results may be unreliable and inaccu- require two or more surgeries.
rately over- or underestimate their visual acuity.
Sweep visual-evoked potentials (SVEP) or flash
visual-evoked potentials can be used to assess Psychosocial Complications
visual acuity but may overestimate acuity in
suspected strabismic amblyopia (Arnoldi and Strabismus correction in patients with CP
Jackson 2006). The gold standard of testing has clear indications for visual and functional
remains as optotype testing when possible. benefits. The cosmetic value of proper alignment
should not be underestimated in this population.
These children are often faced with other disabil-
Strabismus Surgery Failure ities that create social stigmata and ridicule for the
patients and their parents. Ocular alignment can
Overcorrection is more prevalent after strabismus help promote self-acceptance and improve social
surgery in patients with CP than in other children. interactions with peers. There are benefits directly
This is seen as both an initial overcorrection with to the parents as well, who often struggle with the
a higher dose response curve to normal surgical multiple complications in their children. Strabis-
recession or resection amounts and as late over- mus correction offers improvement in one of these
correction with consecutive deviations develop- complications among so many others that may
ing sometimes years after initial surgery. not have available treatments. Parents can feel
Several recent studies have compared surgical that they are helping their child achieve improved
outcomes for infantile esotropia with bilateral vision. Improved eye movements and eye contacts
medial rectus recession (BMR) between CP are also beneficial in establishing psychosocial
patients and neurologically intact children connections with parents (Jackson et al. 2006).
(Habot-Wilner et al. 2006, 2012; Ghasia et al.
2011; Ma et al. 2013). Reported rates of under-
correction were found to be 38–42% and Cross-References
overcorrection 6–21%, versus 4–6% and 2–4%,
respectively, in controls. It has been suggested ▶ Augmentative and Alternative Communication
that the nomograms be adjusted for children with for Cerebral Palsy
CP to account for these surgical failures. Several ▶ Communication in Children and Youth with
mechanisms for surgical failure have been Cerebral Palsy
References Ghasia F, Brunstrom-Hernandez J, Tychsen L (2011)

Repair of strabismus and binocular fusion in children
Ameri A, Mirmohammadsadeghi A et al (2015) Clinical with cerebral palsy: gross motor function classification
outcomes of botulinum toxin injection in patients with scale. Invest Ophthalmol Vis Sci 52:7664–7671
cerebral palsy and esotropia. Strabismus 23(1):8–13 Habot-Wilner Z, Spierer A et al (2006) Bilateral medial
Arnoldi K, Jackson JH (2005) Cerebral palsy for the pedi- rectus recession: results in children with developmental
atric eye care team – part 1: epidemiology, pathogene- delay compared with normally developed children.
sis, and systemic findings. Am Orthopt J 55:97–105 J AAPOS 10:150–154
Arnoldi K, Jackson JH (2006) Cerebral palsy for the pedi- Habot-Wilner Z, Spierer A et al (2012) Long-term results
atric eye care team – part 3: diagnosis and management of esotropia surgery in children with developmental
of associated visual and sensory disorders. Am Orthopt delay. J AAPOS 16:32–35
J 56:97–107 Jackson J, Castleberry C et al (2006) Cerebral palsy for the
Black P (1982) Visual disorders associated with cerebral pediatric eye care team – part 2: diagnosis and treat-
palsy. Br J Ophthalmol 66:46–52 ment of ocular motor deficits. Am Orthopt J 56:86–96
Breakey AS (1955) Ocular findings in cerebral palsy. Arch Ma DJ, Yang HK, Hwang J (2013) Surgical outcomes of
Ophthalmol 53:852–856 medial rectus recession in esotropia with cerebral palsy.
Collins ML (2014) Strabismus in cerebral palsy: when and Ophthalmology 120:663–667
why to operate. Am Orthopt J 64:17–20 O’Keefe M, Kafil-Hussain N et al (2001) Ocular signifi-
Ghasia F, Brunstrom J et al (2008) Frequency and severity cance of intraventricular haemorrhage in premature
of visual sensory and motor deficits in children with infants. Br J Ophthalmol 85:357–359
cerebral palsy: gross motor function classification
scale. Invest Ophthalmol Vis Sci 49:572–580
Cortical Visual Impairment in the Child
Sharon S. Lehman
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1050
Natural History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1050
Case History . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1050
Pathophysiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1050
Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1051
Characteristics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1051
Visual Acuity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1052
Visual Field . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1052
Higher Order Deficits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1052
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1052
Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1052
Interventions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1053
Prognosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1053
Multidisciplinary Team . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1054
Complications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1054
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1054
Abstract absent or the ocular disease is not sufficient to

Cortical visual impairment (CVI) ranks as the explain the vision loss in a child with CVI.
leading cause of visual impairment in children Children with CVI display specific behaviors
in developed countries. Cortical visual impair- that are characteristic of CVI. CVI is com-
ment is bilateral vision loss associated with monly found in children with cerebral palsy.
damage to areas of the brain associated with CVI interferes with how a child accesses visual
visual function. Ocular abnormalities are information, interprets the visual information,
and responds to visual information. This can
negatively affect the child’s ability to become
S. S. Lehman (*) educated and live up to their potential. The
Nemours Children’s Health System, AI duPont Hospital
visual impairment may prevent accurate devel-
opmental testing. Accommodations can be
Sidney Kimmel Medical College, Philadelphia, PA, USA
e-mail: Sharon.Lehman@nemours.org
matched to the characteristic behaviors of

https://doi.org/10.1007/978-3-319-74558-9_78
1050 S. S. Lehman
CVI, helping the child to use vision in a more There is some controversy in terminology
efficient manner. It is imperative that concerning using the terms cerebral versus corti-
healthcare professionals screen, evaluate, diag- cal visual impairment. Some use the term cerebral
nose, and refer children with CVI for services visual impairment to mean higher level deficits
for vision. involving visual processing while others use the
term cerebral visual impairment to be a category
Keywords under which cortical visual impairment would be
Cerebral palsy · Cortical · Visual impairment · a subset (Chokron and Dutton 2016).
Pediatric Cortical visual impairment is bilateral vision
loss associated with damage to areas of the brain
associated with visual function. Ocular abnormal-
Introduction ities are absent or the ocular disease is not suffi-
cient to explain the vision loss in a child with CVI.
Cortical visual impairment is bilateral vision loss Children with CVI display specific behaviors that
associated with damage to the areas of the brain are characteristic of CVI (Roman et al. 2010).
associated with visual function (Dutton and
Jacobson 2001). It is the most common cause of
vision loss in developed countries because of the Natural History
improvements in treating prematurity and brain
injury (Solebo et al. 2017). Cerebral palsy is a Case History
nonprogressive, permanent disorder of movement
and posture due to a lesion of the fetal or infant Jessica is a 3-year-old former 24-week premature
brain (Bax 1964). It is not surprising that there infant with quadriplegic cerebral palsy. Her mother
would be some crossover of the two processes. It has concerns about how her daughter uses her
is estimated that CVI is present in up to 70% of vision. Jessica acted like she could not see when
children with cerebral palsy depending upon the she was an infant. Jessica’s vision has improved but
definition used (Fazzi et al. 2012). it takes a long time for her to respond to visual
The ability to see is an almost undeniable tasks. Jessica often becomes frustrated and gives
impetus for an infant to jump in and interact with up during activities. Jessica tends to follow red
his or her environment. The ability to perceive a objects better. She is easily distracted. Her mother
visual object, integrate it with all other available describes that a teacher frequently scolds Jessica
sensory information, decide how to react to that for not paying attention because Jessica frequently
object, and then perform the action is a very looks away from her work. Jessica seems unable to
complex activity. A defect in the sensory input see objects placed on her tray.
can cause the visually guided behavior to be inef-
ficient (Chokron and Dutton 2016). This can be
detrimental to a child’s ability to learn, have rela- Pathophysiology
tionships, and develop to their full potential. The
additional deficit caused by CVI further contrib- The eyes and optic nerves which take the message
utes to developmental and motor delays. Visual from the eyes to the brain are involved in ocular
deficit may make testing function difficult or causes of vision loss (e.g., retinal detachment
inaccurate. from retinopathy of prematurity). Visual impair-
In order to help children with cerebral palsy ment in cortical visual impairment involves dam-
and CVI, there must be a recognition of the visual age to the retrochiasmal visual pathways
disorder, diagnosis made, interventions, and including optic tracts, lateral geniculate body,
accommodations made based on characteristics optic radiations, primary visual cortex, and asso-
of CVI in order that children can make the most ciation areas. Damage results in impaired visual
of their potential. acuity and visual field defects. Damage to the
74 Cortical Visual Impairment in the Child with Cerebral Palsy 1051
connections between areas of the brain can cause Movement is a primitive visual response. Chil-
more complex perceptual deficits. Damage to the dren who appear to have very little visual response
area connecting the occipital to parietal lobes may react to a moving object brought into their
(dorsal stream) causes difficulty with finding field. Movement may again be another cue that
objects in space, visually guided behavior, and grabs the child’s visual attention.
extremity movement. Damage to the connections Children with CVI often take longer to respond
between the occipital and temporal lobes (ventral to a visual task. The reasons for this may be varied
stream) causes difficulty with recognition of and complex: difficulty with visual attention, dis-
objects, shapes, and in some cases, faces (Dutton tractions, competing stimuli, expressive delay,
and Jacobson 2001). motor delays. Children with cerebral palsy and
CVI may have particular difficulty with the appro-
priate motor response. It is imperative to give a
Etiology child the appropriate time to respond. Remind
those that interact with the child that extra time
There are multiple causes of CVI. All include is needed. One should not assume the child does
damage or structural abnormalities in the brain. not understand or lacks knowledge because they
Periventricular leukomalacia in premature infants are not responding as quickly as one would
and neonatal encephalopathy (hypoxic–ischemic expect. When this happens to children with CVI,
encephalopathy) in full-term infants are the com- they get frustrated and may eventually give up
mon causes of CVI. Other common causes trying to respond and become passive.
include hydrocephalus, structural anomalies of Children with CVI may adopt head positions
the central nervous system, central nervous sys- that allow them to use their peripheral or side gaze
tem infections, metabolic diseases, abusive head to view objects. This is not always consistent with
trauma, cardiac/respiratory arrest, seizures, and what one might expect from the anatomical dam-
hypoglycemia (Afshari et al. 2001). age the child may have in the brain. Common
patterns of traditional field loss will be discussed
below.
Characteristics Complexity presents problems for children
with CVI on several levels. They may have diffi-
The presence of characteristic behaviors is part of culty with a visual task in a complex environment
the definition of CVI. These behaviors are strong or they may have difficulty with a complex,
color preference, improved visual attention with detailed, or ornate visual object. Competing sen-
movement, latency or delayed visual response, sory stimuli may be difficult to process for chil-
visual field abnormalities, difficulty with visual dren with CVI. People who interact with the child
complexity, preference for looking at lights and with CVI should be cautioned against verbally
nonpurposeful gaze, difficulty with seeing objects distracting a child with CVI when the child is
at a distance, and atypical visual responses trying to perform a visual task.
(Roman 2007). It is unknown why children with CVI choose to
It is unclear why children with CVI demon- sometimes stare at lights and ceiling fans. The
strate affinity for certain colors, especially red and high contrast properties of the lights and move-
yellow. The bright color may be a high contrast ment of the ceiling fans may again be cues that
extra cue that helps the child locate the visual engage the child. Nonpurposeful gaze may be the
object. The color preference may be exploited in result of difficulty with sustained visual attention.
developing interventions for a child by attracting Children with CVI tend to perform better with
the child’s visual attention during educational near visual tasks. Children may get close to objects
activities using objects of the preferred color. to either magnify what they are viewing or the child
There may be several reasons why children may be trying to block out other stimuli. Distance
with CVI respond better to moving objects. objects will by default be more complex.
1052 S. S. Lehman
Atypical visual responses of children with CVI some children with CVI and cerebral palsy.
may be misinterpreted. Children with CVI fre- These deficits are seen in children who develop-
quently look away when viewing or tracking an mentally can be tested for their presence or
object. A teacher or therapist may think the child is absence. The higher order deficits may not be
not paying attention or is disinterested. It is impor- evident until a child is challenged in a formal
tant to educate those that will be interacting with the school setting (Philip and Dutton 2014). It is
child who has CVI that the looking away is how the important to continue monitoring the visual per-
child refocuses in order to be able to maintain fixa- formance of the child with cerebral palsy through
tion. Roman (2007) describes absent blink reflex and childhood. Children with significant developmen-
absent response to threat in some infants with CVI. tal and cognitive challenges cannot respond in a
way that can be interpreted when tested for the
higher order neurocognitive deficits.
Visual Acuity
Visual acuity can range from no light perception Treatment

to 20/20. In the past, it was thought that visual
acuity did not improve in children with CVI. More Diagnosis
recent studies show that there can be significant
improvement in a child’s ability to see (Matsuba A diagnosis of cortical visual impairment is made
and Jan 2006). Children with quadriplegic cere- after careful history, physical examination, and
bral palsy tend to have poorer visual acuity and consideration of neurologic impairment. A child’s
function than children with diplegic cerebral palsy profound complex medical problems and devel-
(Fazzi et al. 2012). opmental deficits may overshadow the issue of
visual impairment.
When a child with cerebral palsy is suspected
Visual Field of having visual impairment, a referral to a pedi-
atric ophthalmologist or eye care provider experi-
Visual field defects can be variable in children enced in the care of children is required. Inability
with CVI. There are some patterns in children to perform the recommended vision screening in
with cerebral palsy that are common and exami- the primary care setting is also a reason to refer the
nation should focus on verifying if a defect is child for complete eye examination. The eye
present. Accommodations can be put in place to examination will determine whether the vision
compensate for the area where the child may miss loss is ocular or neurologic or both. The assess-
visual objects. Some children with cerebral palsy ment of visual acuity and determination of diag-
may display a homonymous hemianopsia. There nosis are necessary to determine medical
will be decreased responsiveness off to the same necessity for referral for evaluation and determi-
side for each eye. Another common pattern is nation for vision services. Ongoing ophthalmo-
bilateral inferior field defects causing difficulty logic care should occur throughout the child’s life.
seeing objects on their tray unless compensations Ophthalmologic evaluation will determine the
such as teaching the child to scan or elevation of need for correction of refractive error or accom-
visual materials are made. modative insufficiency with glasses. Accommo-
dation or additional focus necessary to maintain
focus at near can be impaired for children with
Higher Order Deficits cerebral palsy more frequently than the general
population (McClelland 2006). Methods of test-
Deficits in higher order neurocognitive functions ing accommodation have some subjectivity and
such as spatial organization, visuomotor coordi- require some cooperation from the patient. It is
nation, and hand eye coordination are seen in often challenging to test accommodation in
children with significant developmental delay. their vision. Phase 2 describes a child who is
Strabismus or misalignment of the eyes is fre- using their vision and now learning to integrate
quently seen in children with cerebral palsy and their vision with other sensory cues. Phase
is discussed in ▶ Chap. 73, “Strabismus Manage- 3 describes children with better visual function
ment in the Child with Cerebral Palsy” by Salvin, who are resolving deficits. The teacher of the
JH and Hendricks, D in this textbook. Examina- visually impaired can use the data from the
tion will also assess for structural abnormalities detailed CVI Range assessment to provide a treat-
often seen in children with cerebral palsy such as ment plan for the child’s developmental and edu-
optic nerve atrophy or hypoplasia and retinal cational planning.
problems such as scarring from retinopathy of Development and validation of the question-
prematurity. naires and assessment tools continues as active
Referral for services for vision is based on research (Denver et al. 2016).
disability. Services are distributed through the
government on a state-by-state basis. Often ser-
vices are divided into services aimed at birth to Interventions
age three and then through the classroom when
children enter the educational system at age 3. The interventions are based on the characteristics
Eligibility for services varies by state. Some obtained from history and observation of the
states use a visual acuity level or visual field child’s visual behavior. The following table con-
defect for eligibility requirement. Others, in addi- tains recommendations for the patient presented
tion to visual acuity and visual field, base eligibil- above as a case history (Table 1).
ity on diagnosis with a chronic condition which
will interfere with a child’s ability to progress
educationally. Once a referral has been made, a Prognosis
functional visual assessment will be performed to
determine how a child’s visual impairment causes The level of visual impairment cannot be pre-
disability. A treatment plan with interventions will dicted by looking at an MRI. It is important to
be made for developmental and educational describe to the family of an infant with an abnor-
planning. mal brain MRI that their child is at risk for CVI
A variety of questionnaires have been devel- because of damage to the brain. It is helpful to
oped to identify whether a child has CVI (Denver review the spectrum of the disability that can be
et al. 2016). Dutton has been one of the first to use caused by CVI and to let parents know that many
a questionnaire to identify children using ques-
tions that relate to observations of caretakers upon Table 1 Interventions based on characteristics
initial assessment of a child suspected of having
Characteristic Intervention
CVI (Dutton and Bax 2010).
Latency Provide extra time to respond to
Once a child is identified as having CVI, the visual tasks
important functional information obtained can be Preference for Use red objects for activities of
used to follow resolution of symptoms and certain colors daily living or during educational
improvement of visual function. Roman (2007) tasks to interest visual attention
has developed the CVI Range, which is a clinical Difficulty with Avoid distracting patient by talking
complexity to her when she is performing visual
tool that can be used to identify children with CVI
tasks
based on the characteristics, develop interventions Atypical visual Do not punish patient for looking
based on the characteristics, and then follow that responses away intermittently when tracking
child’s progress. There are three phases that objects. It is a method of refocusing
describe in an overview where a child is on the Visual field Elevate visual material with a stand
CVI spectrum. Phase 1 describes a child who has abnormalities or mount on free arm to bring
information into patient’s view
rudimentary visual skills and is learning to use
1054 S. S. Lehman
children can obtain improvement in their visual There is current research looking at the relationship
function over time. between visual disability and classification models
Much of the negative connotation that cortical for function (Salvati et al. 2016). Neurologic
visual impairment sometimes evokes is due to the impairment, especially neurocognitive deficit,
fact that there was a misconception that visual may further complicate testing because of per-
disability associated with CVI does not improve. ceptual issues. It is imperative to factor visual
Health care providers believed that there was no disability into the performance and interpretation
hope and no way to help. Current research dem- of any developmental/functional testing that is
onstrates we can help children with CVI maxi- performed.
mize their visual abilities by leveraging their Since there is a spectrum of disability from
strengths and instituting interventions. cerebral palsy and a spectrum of disability from
CVI, each child has a separate reality. Although
there are patterns of visual impairment that one
Multidisciplinary Team might use as guidelines, each child should be
treated as an individual. Careful identification of
Care of a child with CVI involves a multi- visual impairment, ophthalmologic examination
disciplinary team made up of the patient, family, documenting visual disability, questionnaires,
and many disciplines of health care providers. observation of visual behavior, and recommenda-
Communication among the team is essential. tions from educational professionals and other
Reports from each provider should be shared health care professionals on the patient’s team
with other providers. Parents should provide should result in a treatment plan for each individ-
each provider with a list of the child’s health ual child with cerebral palsy and CVI.
care providers or the parent may be the recipient
of reports and share them with the rest of the care
team. Electronic health records and patient portal Cross-References
allowing access to their medical records can make
this process easier (Table 2). ▶ Strabismus Management in the Child with
Cerebral Palsy
Complications
References
Visual disability from CVI makes assessment using
traditional developmental testing for children Afshari MA, Afshari NA, Fulton AB (2001) Cortical visual
impairment in infants and children. Int Ophth Clinics
with cerebral palsy challenging in some cases.
41(1):159–169
Bax MC (1964) Terminology and classification of cerebral
palsy. Dev Med Child Neurol 6:295–297
Table 2 Possible multidisciplinary team members caring Chokron S, Dutton GN (2016) Impact of cerebral visual
for a child with CVI impairments on motor skills: implications for develop-
Family Educational specialist mental coordination disorders. Front Psychol 7:1471
Pediatrician Educational aide Denver BD, Froude E, Rosenbaum P, Wilkes-Gillan S
(2016) Measurement of visual ability in children with
Developmental Nurse
cerebral palsy: a systemic review. Dev Med Child
pediatrician
Neurol 58:1016–1029
Rehabilitation physician Occupational therapist Dutton GN, Jacobson LK (2001) Cerebral visual impair-
Pediatric neurologist Physical therapist ment. Semin Neonatol 6:477–485
Pediatric ophthalmologist Speech therapist Dutton GN, Bax M (2010) Visual impairment in children
Pediatric optometrist Feeding specialist due to damage to the brain. Clinics in developmental
medicine. London: Mackeith Press
Teacher of the visually Orientation and mobility
Fazzi E, Signorini SG, LaPiana R (2012) Neuro-
impaired specialist
ophthalmologic disorders in cerebral palsy: ophthalmo-
Teacher of the hearing logic, oculomotor, and visual aspects. Dev Med Child
impaired Neurol 54:730–736
Matsuba CA, Jan JE (2006) Long-term outcome of chil- Roman C, Baker-Nobles L, Dutton GN et al (2010) State-
dren with cortical visual impairment. Dev Med Child ment on cortical visual impairment. J Vis Impair 104
Neurol 48:508–512 (2):69–72
McClelland JF (2006) Accommodative dysfunction in Salvati M, Waninge A, Rameckers E (2016) Development
children with cerebral palsy. Invest Ophthalmol Vis and face validity of a cerebral visual impairment motor
Sci 47:1824–1830 questionnaire for children with cerebral palsy. Child
Philip SS, Dutton GN (2014) Identifying and characteriz- Care Health Dev 43(1):37–47
ing cerebral visual impairment in children: a review. Solebo AL, Teah L, Rahi J (2017) Epidemiology of blind-
Clin Exp Optom 97:196–208 ness in children. Arch Dis Child 102:853–857
Roman C (2007) Cortical visual impairment: an approach
to assessment and intervention. AFB Press, New York
Part XVI
Dental
Dental Hygiene for Children
Nadarajah Ganeshkumar
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1060
Goals and Environment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1060
Body Function and Structure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1060
Impact on Oral Hygiene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1060
Environmental Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1060
Personal (Family) Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1060
Technique . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1060
Early Establishment of Dental Home . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1060
Oral Hygiene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1061
Non-cariogenic Diet . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1061
Anticipatory Guidance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1062
Conditioning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1062
Regular Dental Care Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1062
New Strategies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1063
Evidence of Effectiveness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1063
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1064
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1064
Abstract importance of establishing a dental home early,

Managing dental hygiene of children with the benefits of routine dental hygiene practices
cerebral palsy is a challenging endeavor for to reduce the number of required dental expe-
the caregiver and the dental provider, and riences, and the access-to-care difficulties
these challenges vary in accordance with the faced by children with disabilities like cerebral
severity of the cognitive and physical impair- palsy and the families that care for them.
ment of the child. This chapter will discuss the
Keywords
Cerebral palsy · Oral hygiene · Dental home ·
Access to care · Caries · Gingivitis
N. Ganeshkumar (*)
Dover Pediatric Dentistry, Dover, NH, USA
e-mail: dpdganesh@gmail.com

https://doi.org/10.1007/978-3-319-74558-9_79
1060 N. Ganeshkumar
Introduction and increased burden on the caregiver in assis-

ting and providing adequate dental care to the
Children with cerebral palsy (CP), a common child with CP.
chronic pediatric motor disorder occurring in
approximately 2–2.5 per 1000 live births (Odding
et al. 2006), suffer primarily from impairment Environmental Factors
of movement and posture. They may experience
various degrees of disturbances of sensation, If access to dental care is available, parents should
cognition, communication, behavior, and percep- be encouraged to seek early establishment of a
tion. Comorbidities can include seizures and mus- dental home and regular visits to accustom the
culoskeletal problems. Severity of physical and child to a dental office environment. Acclimating
mental impairment as well as socioeconomic the child to the dental office’s unique environment
factors greatly affects the overall oral health of may enable an appropriately trained dentist and
these children and can significantly influence quality office to care for the child in the dental clinic
of life. The inability to perform personal preventive setting if the child’s disabilities are mild to mod-
dental regimens and the high reliance on caregivers erate. If the disability is severe, routine dental
for assistance for routine dental care considerably treatment may require sedation or general anes-
affects oral health outcomes. Attending to preven- thesia, which often but not always will require a
tive oral health needs becomes the responsibility of hospital setting, and this may initiate limitations
their caregivers, who play a vital role in care and with access to care, including costs involved.
supervision in all activities. Therefore, caregivers
must be included in any efforts to improve oral
health outcomes for patients with developmental Personal (Family) Factors
disabilities like CP (Minihan et al. 2014).
Early Intervention and Counseling by
Pediatric Services
Goals and Environment It is important to emphasize the need to begin early
oral hygiene regimens to parents of children with
Body Function and Structure developmental disabilities such as CP (Jan and Jan
2016). This conversation should begin when the
Most dental diseases are preventable with good child is seen for pediatric care soon after birth. Such
oral hygiene; judicious use of fluoride; and mon- instruction by the pediatrician may persuade the
itoring and maintaining a reduced-sugar, non-car- parents to initiate and persevere with appropriate
iogenic diet. The higher incidence of dental caries oral hygiene practices early. Parents should be edu-
and poor gingival health in this population cated about the limited availability of and access to
are mainly due to the patient’s diet, difficulty dental care and the resultant difficulties in treating
in performing routine oral hygiene practices dental disease when it does occur. These factors
to acceptable levels, or both. If routine oral will be more burdensome than the effort required
hygiene is practiced successfully, the need for for preventing oral disease.
dental treatment is likely to be reduced.
Technique
Impact on Oral Hygiene
Early Establishment of Dental Home
Cerebral palsy in children has an inherent impact
on daily activities, including practicing good oral As stated above, the establishment of a dental
hygiene, due to impaired movement and posture home for children with CP should be initiated at
associated with the disability. The degree of the first visit for pediatric care. Although dental
impairment will determine the extent of difficulty care for a newborn is minimal, it is necessary to
75 Dental Hygiene for Children with Cerebral Palsy 1061
use this opportunity to educate the caregiver about their ability to use dentifrices when brushing;
dental and nutritional counseling. Establishment hence, in those circumstances, it is useful to
of a dental home at year one is recommended initiate brushing practices with plain water
by the guidelines of the American Academy of or even by dipping a tooth brush in chemical
Pediatric Dentistry. However, for children with agents such as chlorhexidine as a means of
special needs, even earlier intervention will help establishing routine dental hygiene habits. A
educate the caregiver about the dental hygiene large variety of dentifrices are commercially
challenges of the growing child with CP. It should available, and attempts must be made to find
be emphasized to the caregiver that early use of a suitable dentifrice that the child with CP and
an oral hygiene regimen and non-cariogenic diet sensory difficulties can tolerate. Positioning of
will help to alleviate the need for dental treatment the child during tooth brushing (e.g., standing
and its associated difficulties. This will likely behind while assisting), use of specialized electric
reduce their care burden and might motivate or triple-sided tooth brushes, use of mouth props
them to attempt to initiate good oral hygiene for ease of access, using disclosing agents to mon-
practices even before any teeth erupt. itor and evaluate plaque removal, and judicious
use of chlorhexidine rinses are some measures
that can be used to improve oral hygiene out-
Oral Hygiene comes (Maiya et al. 2015).
The use of electric toothbrushes provides far
Children with CP have a higher mean decayed, more effective plaque control; hence, this should
missing, and filled surface (DMFS) index and be attempted early as the method of choice
higher microbial burden compared with control in children with CP and other special needs
groups (dos Santos et al. 2002). Grzic et al. (Bozkurt et al. 2004).
(2011) reported that children with CP have more
missing teeth, whereas healthy children had more
filled teeth. In addition, children with CP tend to Non-cariogenic Diet
have reduced efficiency of mastication and thus
eat foods with altered consistencies, which may One of the most effective methods to control
reduce oral self-cleansing mechanisms. Addition- dental caries is to stop cariogenic microflora
ally, other altered oral functions such as drooling, from establishing and thriving by reducing
bruxism, and mouth breathing make maintaining the intake of foods that are rich in metabolizable
good oral hygiene challenging in this population. sugars. Strong emphasis should be made by med-
Because of these factors, tooth brushing should ical professionals during routine well-child visits
be initiated once the teeth erupt and in the early about the importance of reducing sugar in chil-
stages of developing dentition. A smear of fluori- dren’s diets and the added benefit of reducing
dated toothpaste should be used, and a routine dental caries. Dental caries is a dietary disease
of brushing twice a day should be established. that will require treatment that may be difficult
Depending on the severity of the disability, this for the child with CP to obtain. Children with
will be a challenging endeavor for the caregiver. CP who have moderate-to-severe physical and
However, pediatricians and other allied medical intellectual disability may require hospitalization
professionals who routinely provide care to chil- and general anesthesia for treatment of dental
dren with CP must emphasize to caregivers that caries with the additional cost and risk associated
persistence with the oral hygiene routine will with such a scenario.
significantly benefit them and their children by Early loss of primary teeth due to dental caries
moderating their dental treatment needs if their will exacerbate the propensity for malocclusion
child develops them or eliminating them alto- that exists among children with CP. Treatment for
gether, thus reducing the burden on caregivers. malocclusion is limited because of the physical
Some children with CP may have sensory and intellectual disabilities of children with CP,
or swallowing difficulties that might preclude so it is imperative that any space lost due to dental
1062 N. Ganeshkumar
caries must be avoided by using all available dental visits, children with CP might require
preventive dental hygiene regimens, especially some mild physical restraints such as papoose
a healthy non-cariogenic diet. boards or even use of radiographic lead shields
to safely provide dental services.
Children should be treated within the limits
Anticipatory Guidance of their ability to cooperate within the context of
their disability. This will require more time and
Caregivers of children with CP must be educated effort from the dental professional to treat these
about the limitations of and lack of access to patients and will likely result in a financial burden.
dental care they are likely to face. If dental treat- Unless resources are made available to help these
ment becomes necessary, it will be an additional children, access to care will remain a challenge
burden on the caregiver if no efforts have been to the caregiver and society.
made toward establishing good oral hygiene and
diet practices early. In addition, it must be empha-
sized that the child with CP might suffer from a Regular Dental Care Management
disproportionately higher incidence of other sig-
nificant dental issues such as malocclusion, dental Dental care for children with CP places an addi-
trauma, dental developmental anomalies, enamel tional burden on the caregiver and the dental
defects, and acquisition of deleterious oral habits, provider. If care is provided in the dental clinic
all of which might be difficult to manage even in setting, it will require additional time and trained
children who do not have any disabilities. personnel to manage the child’s needs. Some-
Children with CP who have severe dis- times, additional time may be needed due to
ability and other comorbidities may require physical limitations and intellectual and behav-
hospitalizaion and general anesthesia for routine ioral constraints. Because of these limitations,
maintenance and dental treatment. Therefore, many offices cannot or will not treat such chil-
the caregiver must be aware of the opportunity dren, and community health clinics or hospital-
to seek preventive dental care if the child based dental clinics often become the venue for
undergoes general anesthesia for other medically dental treatment for these children. Most of their
necessary procedures. Unless the caregiver is dental care is likely to be covered by state and
aware of this possibility and has access to care, federal assistance programs, which will likely
the ability to obtain routine care or appropriate impose constraints about where they may seek
dental treatment will be missed. dental care for routine dental needs and, if nec-
essary, for dental treatment requirements as they
develop.
Conditioning Some routine dental care needs may require the
patient to be under some form of sedation includ-
Routine dental care for children with disabilities, ing general anesthesia, depending on the degree
including children with CP, should be attempted of physical and intellectual disability. Children
in a dental practice as the ideal choice for dental with CP with moderate-to-severe disabilities
needs. Unless children with CP are taken to a often will need treatment under general anesthesia
dental office early and often, opportunities to for comprehensive examinations, prophylaxis,
condition the child to the dental office environ- and radiographs to assess caries as well as to
ment will be missed. If it happens early, it is likely monitor developing dentition. If the child is fed
that many children, especially children with mild- through a gastrostomy tube, their experience with
to-moderate CP, will over time acquire the ability caries will be significantly reduced; however,
to cooperate adequately for oral hygiene visits and gross accumulation of calculus is common,
for most minor simple dental procedures. Because which may become an esthetic concern to the
of their motor dysfunction, if accustomed to caregiver. In these patients, periodic visits under
general anesthesia may be necessary as deter- adjunct service. Transport of these children to
mined by the dental care provider’s evaluation. a dental clinic may impose an added burden;
The high prevalence of dental trauma among chil- therefore, it might be reasonable to examine
dren with CP makes it imperative for caregivers to ways to provide at-home visits by dental
establish a dental home early, so that, if need be, hygiene services or expanded dental auxiliary
traumatized teeth can be addressed to reduce the services. In addition to providing and monitor-
pain and suffering of the child as well as to reduce ing dental hygiene services at home, these per-
the burden on the caregiver. The caregiver should sonnel can motivate and educate caregivers and
be instructed that they should request routine den- also identify subpopulations that may require
tal care if and when the child undergoes general more aggressive treatment. When coordinated
anesthesia for medical management for other with public health services, this may reduce the
comorbidities, if dental services are available. burden on the caregiver of providing timely
This requires advanced planning because it may dental care.
impose additional burdens on these institutions Alternatively, dental facilities could be
such as obtaining prior authorization because of established to care exclusively for populations
insurance and reimbursement constraints. with disabilities. Over a period of time, these
There is a higher than normal propensity for facilities could train and equip themselves to
dental developmental defects in children with CP, care for this vulnerable population, because the
such as enamel defects, congenitally missing or needs of children with CP will likely expand as
supernumerary teeth, presence of tooth wear and they age. It is unreasonable to expect that this
erosion, and prevalence of parafunctional habits population’s needs can be met by a dental pro-
such as bruxism, which may require additional vider alone, however well-trained they are, and it
monitoring or treatment. In some cases, preven- may not be financially sustainable.
tion of dental problems such as dental erosion may The development of novel health promotional
lie in treating the underlying medical condition measures, such as lectures and visual aids using
such as gastro-esophageal reflux with adequate social media such as web portals used extensively
medical management to prevent dental deteriora- by parents and caregivers, is likely to reach
tion and may require complex restorative inter- populations in need and should emphasize the
vention later if allowed to continue (Goncalves importance of good oral hygiene and the problems
et al. 2008). Side effects of medications to treat that can arise from its absence.
underlying medical comorbidities can have dele-
terious effects on gingival health if oral hygiene is
compromised. Some of these problems can be Evidence of Effectiveness
managed only empirically, with each unique situ-
ation requiring individualized management. This As a group, children with CP have higher preva-
may become frustrating for caregivers who may lence of dental caries, poor oral hygiene (Sinha
expect management and elimination of all issues et al. 2015), poor gingival health (Du et al. 2010;
as they develop but for which there may be no Guare Rde and Ciampioni 2004; Pope and Curzon
treatment modalities available even among chil- 1991), and dental development anomalies. They
dren with no disabilities due to cost and the nature occasionally acquire persistent parafunctional
of the problem. habits and suffer from frequent dental trauma
(dos Santos and Souza 2009; Miamoto et al.
2011) and malocclusion (Pini et al. 2016) when
New Strategies compared with controls, primarily because of
their compromised general health, limited access
The delivery of dental care to such a vulnerable to reasonable dental care, and the various levels
population may require different strategies, of oral hygiene awareness and abilities of their
such as providing at-home dental care as an caregivers (Santos et al. 2010). As with all
1064 N. Ganeshkumar
children with intellectual and physical disabilities, Cross-References

those with CP require early and regular oral
health care and access to services to limit severity ▶ Gastroesophageal Reflux in the Child with
of oral disease. Cerebral Palsy
The published literature about dental care ▶ General Dentistry for Children with Cerebral
for children with CP emphasizes availability of Palsy
resources and treatment, suitable training of ▶ Medical Management of Sialorrhea in the Child
professionals, and access to a clinical environ- with Cerebral Palsy
ment without physical barriers. Although these
issues are important, preventive strategies for
appropriate dental care must also be considered References
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reports of the oral health-related quality of life of chil-
management plan will result in frustration for all
dren with cerebral palsy. BMC Oral Health 12:15
and, at best, achieve only modest improvement Bozkurt FY, Fentoglu O, Yetkin Z (2004) The comparison
on the affected child’s quality of life (Abanto of various oral hygiene strategies in neuromuscularly
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General Dentistry for Children
Harvey Levy
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1068
Common Issues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1069
Similarities and Differences to Other Mental and Physical Challenges . . . . . . . . . . . . . . 1069
Risk Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1069
Quality of Life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1070
Dental Awareness and Oral Hygiene Education for Parents and Caregivers . . . . . . . . . 1070
Clinical Concerns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1071
Lip Biting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1071
Bruxism, Clenching, and Grinding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1071
Drooling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1072
Incompetent Lip Seal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1072
Dental Trauma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1073
Caries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1073
Periodontal Disease (Gingivitis, Periodontitis) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1074
GERD, Erosion, and Wear . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1074
Malocclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1075
Temporomandibular Joint (TMJ) Dysfunction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1076
Dental Treatment for Children with CP . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1076
Before Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1076
Treatment: Oral Exam and Cleaning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1082
Treatment: Complex Dental Procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1085
When Office Efforts Don’t Succeed . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1085
Oral Hygiene at Home or Institution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1087
Training for Dentist and Dental Staff . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1087
Access to Care . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1088
H. Levy (*)
Department of Surgery, Frederick Memorial Hospital,
Frederick, MD, USA
University of Maryland School of Dentistry, Baltimore,
MD, USA
e-mail: pubs@drhlevyassoc.com

https://doi.org/10.1007/978-3-319-74558-9_81
1068 H. Levy
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1088
Case Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1089
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1101
Abstract Introduction
Dental treatment is considered the greatest
unmet health need of the disabled (Kumar For children with CP, access to care remains a
et al., J Indian Soc Pedod Prev Dent 27(3): challenge. With greater knowledge and proper
151–157, 2009). Ever since its initial descrip- training, caretakers of the affected child can
tion by Dr. WJ Little in 1861 (initially known more effectively meet this challenge.
as Little’s disease) and later called cerebral CP is a group of neuromuscular disorders that
palsy (CP), it has prevented children from affect the development of movement and posture
receiving the same level of oral health care as and cause limitation in activity, affecting 2–2.5/
other children, despite the fact that it is cur- 1000 live births (Sehrawat et al. 2014), with other
rently the most common congenital neuromus- authors reporting a wider worldwide range of
cular disorder (Jones et al., J Pediatr Health 1.5–4/1000 live births (Alhashmi et al. 2017).
Care 21(3):146–152, 2007; Patton and Glick Classification includes spastic, dyskinetic/athetoid,
(eds), The ADA practical guide to patients with ataxic, or a combination of two of these. Spastic
medical conditions. Wiley-Blackwell, Hobo- CP, accounting for 50–75% of the cases, includes
ken, 2012). muscle tightness and joint stiffness. Dyskinetic
There are many reasons that children suf- (aka athetoid, dystonic), accounting for 15% of
fering from CP do not enjoy the same quality the cases (Escanilla-Casal et al. 2014), is charac-
of life, including freedom from oral discom- terized by involuntary, writhing movements.
fort, pain, and infection. The complexities of Ataxic CP makes up the remaining 5-10% of
raising a child with CP mean that oral health cases. Most cases of CP involve some degree of
often takes a back seat to the child’s other poor muscle coordination, affecting speech, gait,
needs. Dental professionals may be uncom- swallowing, muscle control of the eyes, and vol-
fortable, untrained, unable, or unwilling to untary movements of the hands.
treat these children. This chapter will address Dental practices may be ill-equipped to handle
daily proper home care as well as adequate the physical and emotional needs of children suffer-
and correct dental diagnoses, treatment plans, ing from CP. To assure greater access to care for
and successful procedures in dental care set- children with CP, this chapter will address both
tings. It will also outline unique procedures common as well as unique clinical issues. These
utilizing acupressure points to safely open and include the ability to perform routine daily oral
maintain open the mouths of children with CP hygiene at home, as well as the same quality effec-
so that dental professionals can perform ade- tive dental care afforded to all children in a dental
quate clinical exams and treatment. Clinical office or off-site facility.
cases will be presented to clarify or illustrate Reasonable modifications may include desen-
some of these points. sitization, behavior modification, chemical and
physical restraint, forced mouth opening using
Keywords manual pressure on various acupuncture points,
Cerebral palsy · General dentistry · maintenance of mouth opening with various oral
Pedodontics · Acupuncture · Mouth opening props, and modalities of treatment including oral
76 General Dentistry for Children with Cerebral Palsy 1069
sedation, injectables, or general anesthesia. Mod- issues that adversely affect their quality of life.
ifications to standard oral health care will be part Jan and Jan (2016) have correlated the following
of this discussion, including use of mechanical predisposing factors to known mechanisms:
plus pharmacologic agents, with a heightened
dental awareness on the part of the family, care- • Motor weakness and cognitive delay ➔
givers, and dental professionals. reduced oral hygiene, dependence on caregiver
and dental team
• Pseudo-bulbar palsy ➔ drooling, chewing,
Common Issues and swallowing problems
• GERD ➔ vomiting, enamel erosion, regurgi-
Common issues in children with CP include poor tation, possible aspiration
oral hygiene, bruxism, drooling, traumatic dental • Malnutrition ➔ poor calcium intake, vitamin
injuries, and malocclusion. Dougherty (2009) D deficiency
described changes in the orofacial structure in
patients with CP that may prompt parafunctional Pope and Curzon (1991) found a similar num-
habits, which in turn can cause feeding problems, ber of dental caries, but children with CP had
difficulty maintaining oral hygiene, and barriers to more extractions and unrestored teeth, fewer and
oral care access. poorer-quality restorations, worse oral hygiene
The increased risk of dental problems can result and gingival health, delayed eruption, and higher
in significant morbidity that can affect well-being levels of tooth wear. One study by Nielsen (1990)
and can negatively affect quality of life. The neu- found that the caries rate for children with CP was
rological insult, including motor and coordination lower than that of the control group.
difficulties and limited oral hygiene, results in Das et al. (2010) found no difference in the
increased risk of dental disease (Jan and Jan 2016). process of periodontal disease, prevention, or
Dental problems observed in many of these chil- treatment in children with CP vs. other children.
dren include gingival hypertrophy, enamel hypopla- The difference was the inadequate plaque
sia, dental trauma, bruxism, drooling, and class II removal. Effective oral hygiene has two require-
malocclusion. Risk factors for dental disease in these ments: motivation and manual dexterity. The
children include exposure to multiple medications, motor coordination and muscular limitations of
reduced oral hygiene, soft or cariogenic diets, peri- children with CP along with difficulty in under-
odontal disease, or feeding via gastrostomy tube standing the importance of oral hygiene led to the
(Escanilla-Casal et al. 2014). Poor oral hygiene progression of periodontal disease. Poor oral
and periodontal disease are influenced by medical hygiene led to both increased caries and periodon-
diagnosis, cognitive level, having a disabled sibling, tal disease, which affects the nutritional status of
parents’ level of education, and economic status. the child. The bleeding, swelling, and pain of
periodontal disease can make eating more difficult
and sometimes painful or untasty. Loose teeth
Similarities and Differences to Other caused by bone loss from periodontal disease
Mental and Physical Challenges can trigger pain when teeth contact
non-compressible objects or hard foods.
Only 25% of all children with CP have seen a
dentist, compared with 40% for all other children
(Stoopler 2014). Risk Factors
Cerebral palsy itself may not directly cause
dental problems. But the sum of all the associated In this chapter, we will discuss the ways in which
phenomena predisposes children with CP to CP places children at higher risk of dental
1070 H. Levy
problems and affects their medical-dental quality The burden of a reduced quality of life can also
of life. The most significant risk of dental care is affect the caregivers whose children have a high
aspiration (see “Case #5 Maria”). Aspiration decayed-missing-filled-teeth (DMFT) count,
occurs when saliva, fluid, or food goes into the manifesting as strain, isolation, disappointment,
trachea. This can happen in the dental office and environmental concerns (Rodrigues dos San-
where the patient, supine in a dental chair, is an tos et al. 2009; Santos et al. 2010a).
easy target for water, dental materials, debris, or In evaluating preschool children, Du et al.
an extracted tooth entering the lungs. In the office, (2010) determined that those with CP had lower
a throat shield should be used when a rubber dam Health and also lower Oral Health Pediatric Qual-
is not in place. Suction (high velocity evacuation ity of Life inventory scores than the control group
system) must be aggressive and thorough to pre- in all four categories of physical, emotional,
vent life-threatening aspiration (Sehrawat et al. social, and school functioning.
2014). A patient’s airway must be maintained at
all times to prevent a potentially fatal incident.
dos Santos et al. (2002) reported that children Dental Awareness and Oral Hygiene
with CP had higher frequency of decayed, miss- Education for Parents and Caregivers
ing, and filled teeth (DMFT), higher plaque score,
more Streptococcus mutans, higher Lactobacillus Dieguez-Perez et al. (2016) are some of many
counts, and lower pH and buffering capacity in the authors who urge early dental treatment and fre-
saliva, increasing the risk for dental caries. The quent home care to overcome what he observed
risk factors for malocclusion and trauma will be as poor oral hygiene in children with CP. Relative
discussed later. to other children, he observed a higher caries
incidence, worse gingival health, more dental
trauma, more parafunctional habits such as brux-
Quality of Life ism, more delayed eruption, more wear, and more
abrasion. Families and caregivers need to be
Several researchers (Abanto et al. 2012; Cardoso made aware early on that oral manifestations of
et al. 2014) have demonstrated that the more CP include malocclusion, bruxism, sialorrhea
severe the neurological damage in children with (drooling), and extensive calculus from dyspha-
CP, the higher the risk of oral disease, because of gia, pooling saliva, and possible gastrostomy
the soft consistency of the diet and the difficulty tube feeding (Patton and Glick 2012). Tell-
obtaining effective daily oral hygiene and pro- show-do is essential, as is talking to the patient
fessional oral care. The severity of dental caries directly, if they are capable of understanding.
is strongly associated with a negative quality Oral hygiene instruction and treatment plans
of life. begin with the ideal and then are modified as
Additionally, anticonvulsant drugs in the appropriate for the child’s age, abilities, and
presence of poor oral hygiene result in gingival level of comprehension and compliance (Patton
hyperplasia. Athetoid movement, motor impair- and Glick 2012).
ment, or the absence of information about dental We never assume that the parents or care-
care, or a combination, precludes effective oral givers know the basics of oral hygiene. As dental
hygiene. The harmful biofilm builds up, causing professionals, we make sure that they are aware
dental problems and decreasing the quality of proper oral hygiene with necessary modifica-
of life. tions so they can supervise or monitor the child.
It appears universally accepted that the best They may not be aware of using an electric
quality of life for these patients occurs when toothbrush, floss handle, water pick, or special
there is an integrated approach. This includes mouth rinses.
dentistry, physical therapy, speech therapy, and Given the greater likelihood of traumatic den-
caregivers working in harmony (Katz 2012). tal injuries, including avulsion of upper front teeth
from falls or accidents, a tooth-saving kit should

be available in all homes or group homes. That
would increase the chances of the dentist being
able to reimplant an avulsed tooth in a timely
manner.
Clinical Concerns
Lip Biting
Lip biting is well known in children after local

anesthesia and is clearly documented in children
with disorders like Lesch-Nyhan syndrome. For
children with severe class 2 malocclusion and a
clear overjet, the lower lip is often found tucked
between the lower incisors and the protruded
upper incisors. The lower lip then becomes red,
raw, and irritated. Drooling and incompetent lip
seal are often associated with this lower lip pathol-
ogy, as are nutritional intake concerns. Dentists,
especially orthodontists, may mitigate the prob-
lem by fabricating hard acrylic or resin lip guards
or occlusal mouth guards, similar to those used to
reduce bruxism’s harmful effects on the enamel.
Fig. 1 Lower lip bite following local anesthesia
Biting one’s lip, tongue, or cheek following local
anesthesia is also a preventable problem, with
details in a later section.
A gnathodynamometer was utilized to check max-
imum bite force and confirmed this observation.
Bruxism, Clenching, and Grinding Souza et al. (2015) found bruxism in 36.3% of
their children with CP and contend that dental
About 20% of all children appear to have some form caries and bruxism have a negative effect on qual-
of clenching, grinding, or bruxism (Fig. 1). ity of life (Fig. 2).
Researchers cannot agree on what percentages of Miamoto et al. (2011a) found that the 25% sleep
children with CP have this issue, but the consensus bruxism rate was not statistically different from
is that it is significantly higher than for the general those of the control groups and maintained that a
population, anywhere from 25% to 69.4% multidisciplinary approach yields the best success
(Alhashmi et al. 2017; Peres et al. 2007). Along for improvement. They used biofeedback, EMG,
with a higher DMFT count, there is an increase in drugs, myorelaxation plates, and night guards to
malocclusion and parafunctional habits including reduce the parafunctional sleep bruxism’s tooth
bruxism. Other than removable acrylic mouth wear, which compromises the dentition (Fig. 3).
guards, one treatment option for this would be a In evaluating children with spastic CP, Santos
fixed and secured resin protective appliance et al. (2010b) noted the oral motor function corre-
(Oliveira et al. 2011). lated with the EMG activity in all muscles tested.
Botti Rodrigues Santos et al. (2015) observed The patients with CP had motor weakness in
that for children with spastic CP, teeth grinding is jaw-closing muscles, which may compromise
associated with worsened oral motor performance. masticatory function.
1072 H. Levy
Lip position and oral seal are strongly associ-

ated with drooling (Tahmassebi and Luther 2004).
Hegde and Pani (2009) noticed that 48.7% of the
children with CP drooled, with 17.7% being
severe. The more drooling, the poorer the oral
hygiene score. Those with athetoid CP drooled
the least. Zamzam and Luther (2001) verified by
both remote surveillance and direct exams that
poor or incompetent lip position correlates with
drooling in children with CP.
Harris and Dignam (1980) reported a 73%
reduction in drooling with chin cups and special
anti-drooling practical courses. Johnson et al.
(2004) used an Innsbruck sensorimotor activator
and regulator (ISMAR) intraoral appliance to
reduce drooling and improve eating skills in chil-
dren with CP.
Fig. 2 Moderate bruxism
Maeda et al. (1990) reported that surgical sub-
mandibular duct relocation resulted in less
drooling, less odor, less time in oral care, and
improved appearance.
Inga et al. (2001) use colored bandanas to mask
the drool onto the child’s clothing. In the 1990s,
Castillo-Morales (Inga et al. 2001) developed
removable palatal plate appliances with a button
on the palate used to facilitate swallowing and
reduce drooling. The appliance resembles a
Fig. 3 Severe bruxism Hawley retainer, which is familiar to most den-
tists. This can be fixed for non-compliant patients
In addition to bruxism, other parafunctional and is most successful if the patient can swallow
habits found more frequently in children with CP on command rather than drool.
include pacifier sucking, finger sucking, biting
objects, and tongue interposition. Intervention is
recommended only if the situation is unlikely to Incompetent Lip Seal
self-correct with age (Ortega et al. 2007).
Infants who cannot create a good lip seal may not
be able to breastfeed. Infants with CP who do not
Drooling breastfeed have 3.4 times more throat infections
than those who do. Miamoto et al. (2011b) noted
Drooling is noted in 30% of children with CP but is that 18% of children with CP had poor lip seal
not associated with increased saliva flow. It is sec- compared with 5% for the control group, which
ondary to mouth opening or swallowing difficulties, was quite relevant in protecting the upper front
or both, which can lead to aspiration, skin irritation, teeth from dental trauma (Carneiro et al. 2017).
articulation difficulties, and social embarrassment. Hypotonia contributes to drooling, as does an
One of the treatments used to control drooling is open bite and inability to close lips (National
botulinum toxin injected into the parotid and sub- Institute of Dental and Craniofacial Research
mandibular glands (Alhashmi et al. 2017). [NIDCR] 2014) (Fig. 4).
Fig. 5 Fracture trauma to upper front teeth
physical and mental impairments that reduce

defensive reflexes (Miamoto et al. 2011b) (Fig. 5).
One study found that children with CP have
similar numbers of traumatic dental injuries but
receive less treatment (dos Santos and Souza
2009).
Fig. 4 Incompetent lower lip
Dental Trauma Caries
The class II malocclusion generally features flar- While not universally observed, Cardoso et al.
ing of the maxillary incisors. These upper front (2014) and most authors documented a greater
teeth are prone to fracture when accompanied by prevalence of dental caries in primary dentition
incompetent lips or struggles in ambulation and of children with CP than in nondisabled children
seizures (Alhashmi et al. 2017). The most com- (Ortega et al. 2007). Sinha et al. (2015) correlated
mon risk factors associated with this malocclu- a higher incidence of dental caries with poor oral
sion are mouth breathing, lip incompetence, and hygiene, class II malocclusion, compromised gen-
long face. The uncontrolled head movements eral health, and low dental awareness (Fig. 6).
cause the upper front teeth to strike hard objects. Observing that diseases of the mouth occur with
The absence of a good lip seal, which normally greater frequency in children with CP than in
protects the upper incisors, plus recurrent sei- control groups, Roberto et al. (2012) state that
zures and night grinding, makes the child prone dental caries constitutes a multifactorial disease
to dental injuries. Other observers (Holan et al. in which different biological, cultural, and envi-
2005) noted that children with CP had a much ronmental factors interact.
higher incidence of dental injuries even though Other factors contributing to the reportedly
they do not engage in violent sports activities. higher incidence of dental caries in this group of
Teachers, parents, and caregivers should be made children include mouth breathing, effects of med-
aware of emergency care in dealing with trau- ication, enamel hypoplasia, and food pouching
matically avulsed permanent teeth (Dubey et al. (NIDCR 2014). Many medicines reduce saliva-
2015). tion or contain sugar or both. Caregivers should be
Part of the high percentage of trauma to the encouraged to find sugar-free medicines and rinse
front teeth of children with CP is due to the with water after taking them. Alternatives to soft,
1074 H. Levy
cariogenic food and beverages are advised. Pouched

food should be removed with a finger or gauze after
every food intake.
These children need to have a specific, person-
alized protocol and means of brushing their teeth
twice daily, flossing once daily, nightly fluoride, and
sealants on all posterior teeth at risk of dental caries.
In treating caries, silver diamine fluoride has
emerged as a practical, inexpensive restorative
material. Its fluoride release coupled with its low
cost and ease of application significantly offsets the
fact that it is not as esthetic as polished composites.
These are excellent for decayed primary teeth that
will exfoliate within a few years, especially where
cost, ease of application, and durability are more
important than short-term cosmetic beauty.
Periodontal Disease (Gingivitis,

Periodontitis)
Gingival health is often poor, primarily because of

difficulties in maintaining proper oral hygiene.
Predisposing factors include poor neuromuscular
control, food pouching, and mouth breathing.
Fig. 6 Caries plus trauma
Gingival hyperplasia is often related to the use
of anticonvulsant drugs, calcium channel
blockers, or immunosuppressive drugs (Alhashmi disease. Unless the child is too uncooperative,
et al. 2017) (Figs. 7 and 8). cleaning is done at this time. If it is unsafe to
Jaccarino (2009) reports that periodontal dis- proceed, the patient is rescheduled with orders for
ease is three times higher in patients with CP than a higher level of sedation, reminder to arrive on an
in the control population, noting that poor oral empty stomach and empty bladder (or diaper/Pull-
hygiene, soft cariogenic diet, and anticonvulsant Up), and the proposed clinical procedures agreed
Dilantin are contributing factors. upon. The subsequent visit may be in the dental
In our office, all patients with special needs, office, facility, or operating room. Signatures are
including children with CP, are seen by the hygien- obtained for the informed treatment plan, physical
ist every 3–4 months. This visit focuses on evalu- restraint, and chemical restraint.
ating and cleaning the teeth and gums, following
up on prior findings, and catching any new or GERD, Erosion, and Wear
incipient pathology. Parents and caregivers are
given feedback on the child’s level of gingival Children with CP have a higher risk of dental
and periodontal health and instructed on strategies erosion, especially all molars and the upper inci-
to improve the clinical picture. Radiographic and sors (Gonçalves et al. 2008). Reports of GERD
photographic images are taken and then displayed (gastroesophageal reflux disease) range from
on our TV monitors for clarity and discussion. Six 43% to 70%, with the involuntary passage of
sites on different teeth are measured for periodontal gastric juice passing against the normal flow of
pocketing. If any are greater than 3 mm, then the the digestive tract. This rumination causes ero-
entire mouth is probed to rule out periodontal sion of teeth (Alhashmi et al. 2017). Su et al.
Fig. 9 GERD in 5-year-old child
Fig. 7 Periodontal disease with moderate calculus
Fig. 8 Periodontal disease with heavy calculus bridge
(2003) reported as many as 75% of children with Fig. 10 Malocclusion with crowding, anterior open bite,
and drooling
CP having GERD, which in turn led to dental
erosion. Shaw et al. (1998) contend that GERD
correlates with erosion more so than para- misaligned teeth. An anterior open bite with pro-
functional habits (Fig. 9). truding upper front teeth is common and often
The dentist may consult with the physician to associated with tongue thrusting (Fig. 10).
discuss medical management of the reflux. In the Class II malocclusion was the most common
dental office, patients should be seated upright for type of malocclusion at 64.2%, along with
treatment. Caregivers should be advised to rinse the increased horizontal overjet, vertical overbite,
child’s mouth with plain water or a water and baking missing teeth, anterior diastema, and incompetent
soda mixture at least four times per day to mitigate lips (Dubey et al. 2015). Most children with CP
the harmful effects of the gastric acid. It is essential are poor candidates for orthodontic correction of
that the child’s teeth are brushed twice per day and the malocclusion. A high level of behavior com-
that he or she receive a daily fluoride treatment. pliance both with daily home care and at the
dentist/orthodontist’s office is required, along
with maintenance of excellent oral hygiene.
Malocclusion Removable appliances may be dangerous, and
fixed appliances are expensive. More often than
Malocclusion in children with CP is usually a not, the offending or problematic teeth are
musculoskeletal problem rather than simply removed and not replaced. This, in turn, leads to
1076 H. Levy
role in the health maintenance of these individ-

uals. The work is not always easy, but all who
work in our practice consider it always rewarding.
Informing the child’s caregiver of what you are
about to do at every step increases success. Only
25% of children with CP have a severe form. The
remaining 75% are likely to be managed with
relative comfort in an office setting. Simple, single
direction with extra time allowed and patience
generally leads to a successful visit.
In this section I will describe what we do in our
office before we even examine the child, how we
examine them, and how we treat them, both in the
Fig. 11 Anterior open bite with incompetent, inflamed office and – when our office efforts don’t succeed
lower lip
– under IV or general sedation in an operating
room (OR).
greater speech impediment, reduced nutritional
efficiency, migration of teeth, and social embar-
rassment (Alhashmi et al. 2017) (Fig. 11). Before Treatment
Oral Drugs
Temporomandibular Joint (TMJ) To improve the chance of successful dental treat-
Dysfunction ment, we may ask that the parent or caregiver
administer an oral sedative to the child before
The frequent class II malocclusion is associated their appointment time.
with a higher incidence of TMJ problems, includ- Many sedative and hypnotic drugs have been
ing tenderness upon palpation, pain on opening or used in the past century to provide sufficient
chewing, crepitus, limited mandibular movement, relaxation so that the necessary dental work can
or luxation of the condyle. TMJ problems are be completed in the chair. Unfortunately, many of
more often found in children with CP who are these drugs proved harmful and yielded a high
male, mouth breathers, or have severe malocclu- morbidity and mortality rate. Sometimes it was
sion (Alhashmi et al. 2017). One author cites the the drug, sometimes the practitioner, and some-
frequency of TMJ signs/symptoms as 67.6% for times an idiosyncratic response of the patient. For
children with CP compared with 25% for the a myriad of reasons, many drugs that were con-
control group (Ortega et al. 2008). sidered effective in the past have been removed
from the market.
The benzodiazepines (diazepam, triazolam,
Dental Treatment for Children with CP midazolam, lorazepam, clonazepam, alprazolam)
reduce muscle stiffness and control seizures, mak-
Many general dentists refer children with CP to ing them well suited for patients with CP and
the pedodontist (pediatric dentist). But many of epilepsy. In my practice, aiming for the peak
these children are too large for the small pediatric effectiveness of the drug to coincide with the
operatory chairs or must remain in their wheel- time of the procedure on the mouth, I find that
chair or age out and outgrow the pedodontic either triazolam (Halcion) or diazepam (Valium)
office. This is where general dentists who are elixir or pill 30 min pre-op is the most effective.
properly trained, motivated, equipped to handle All of our nondiabetic patients with special needs,
the tasks and willing to accept what may be a less including children with CP, arrive in our office on
than usual and customary fee can perform a vital a 6-h empty stomach (except for medicine) and an
empty bladder (unless they are wearing a diaper or – Seizures are less likely if the child took a
pull-up). The benzodiazepines are smooth muscle preoperative benzodiazepine as a sedative and
relaxants in addition to being nonnarcotic hypnotic, anticonvulsant. Should a seizure occur, do not
sedative anticonvulsants. Urinating, defecating, insert objects between the teeth. Rather, turn
and regurgitating are common after taking benzo- the patient or the head to one side and monitor
diazepines, requiring the abovementioned regula- the airway to reduce the risk of aspiration.
tions to prevent body-content accidents, or worse,
vomit and aspiration.
Caregiver in Room
Before administering or prescribing any seda-
Many dentists, prefer not to allow the parents or
tive drugs, physically touching the patient, or
caregivers in the treatment room. Our practice is
beginning any dental treatment, we need a signed
to invite the parent or caregiver into the operatory
informed consent. The four main parts of our
room for the following reasons.
office consent form include financial agreement
for treatment plan, chemical restraint (sedation
1. If the treatment plan must be changed from, for
drugs), physical restraint (wraps, props, and phys-
example, a restoration to a pulpotomy or from
ical contact), and photographic permission
a root canal to an extraction, the power of
(photos and videos).
attorney (POA) responsible person is there to
Special precautions regarding sedation of chil-
witness, discuss, and authorize the change,
dren with CP:
since the informed consent may not have
included this unexpected new procedure.
– The airway must be carefully monitored dur-
2. The parent can witness firsthand that the child
ing, as well as after, office sedation, whether
may be screaming for no good reason other
given orally or by IV. Given the salivary
than he or she does not want to be there or
pooling with an aberrant swallowing reflex,
have that needed dental procedure performed.
the chance of saliva, water, or other material
Shrieks heard in the waiting room conjure
entering the lungs is real and can be life threat-
mental images that are dispelled if the parent
ening. Every precaution must be taken to pro-
or caregiver is in the treatment room.
tect the airway and prevent anything foreign
3. The presence of the familiar adult may prevent
from entering the lungs. See section on “Risk
abandonment anxieties. The adult continu-
Factors” for more.
ously reassures the child that everything is
– Idiosyncratic reactions to benzodiazepines
okay and no harm will come to them. This
and other agents: Hypo-responders to a drug
applies to our office as well as the first few
are rarely an emergent problem. However,
minutes in the OR, before the child is asleep.
hyper-responders may catch a health profes-
4. If dental X-rays are needed, the nonpregnant
sional by surprise, off-guard, and ill-prepared
parent can don a poncho lead apron and assist.
to handle an unexpected response. Hypoten-
5. The parent may provide one more set of hands
sion is a potential life-threatening concern. A
to help immobilize the child, while the dental
reasonable approach to prevention is to fol-
care is provided (Fig. 12).
low the dictum of “dose low and dose slow.”
It is easy to give more drugs as needed. It is
difficult or impossible to recall them once Special Operatory Chairs
administered. Also, be sure to renew basic Children with neuromotor or neuromuscular dys-
CPR for all clinical and clerical staff annually function require external support from seating
and PALS or ALS for the doctors biannually. systems to accommodate for compromised pos-
Annual drill practice in an office provides an tural control and postural deficits (Neville 2005).
opportunity to identify and correct what Pelvic stability is required for the spine so that the
might be fatal errors in an actual situation or neck is free to move. For children with CP, this is
crisis. difficult in a dental pedodontic operatory chair
1078 H. Levy
Fig. 12 Parent in office assists with treatment
Fig. 13 Patient remain in wheelchair during dental X-

and often impossible in a conventional larger rays, operatory chair off to side
adult operatory chair.
Seating solutions require a balance between the
upright anatomical symmetrical posture of 90-90-
90 of flexion of hips, knees, and ankles with the patients may require two or more assistants to
ability to function. There are anterior pelvic stabi- ensure a safe transfer in and out of the chair.
lization devices. In 1975, Cramer and Wright Straight wood transfer boards are used when the
described the effective use of beanbag chairs for wheelchair is alongside the operatory chair. If the
comfortably seating the child patient with two chairs are at 90 , we use a curved or quarter-
CP. However effective, this never caught on as a circle-arched wooden board to slide the child over
popular method of patient seating. (Levy 2016a, b; Levy and Rotenberg 2016).
In my office, we have multiple solutions for Many children prefer to remain in the comfort
solving the posture dilemma. We place chair over- of their wheelchair. To accommodate that, we use
lays to convert an adult into a pediatric chair our operatory chairs, which employ a cushion of
instantly. A lightweight portable overlay immedi- air to glide the chair across the room, allowing the
ately contours to the shape and position of the patient in the wheelchair to occupy the center of
child (Fig. 14). A mattress that conforms to the the room, permitting the dental professionals to
patient is also frequently used to provide place- perform their work with no crowding. The dentist,
ment, comfort, and support in seconds. hygienist, and dental assistant can best work on a
Smaller children may easily be transferred patient in their wheelchair if the large dental
from wheelchair to operatory chair by caregivers operatory chair is glided off to the side of the
and staff. We generally have the correct-sized room and out of the way (Fig. 13). A free educa-
body wrap already draped onto the chair. Larger tional video is available at the following link:
http://www.vivalearning.com/member/classroom. Straitjackets, restraining boards, and immobi-

asp?x_classID=3043. lization devices have been used for centuries to
restrict patients’ movements and prevent flailing
Safety Restraint and kicking. Whether these movements are vol-
“Above all, do no harm” applies to the staff as untary or involuntary, they preclude good, safe,
well as the patients. Children with CP may flail and quality dental treatment. The current trend is
their hands and kick their legs, either because they to avoid any device that may itself cause physical
are physically unable to control their involuntary injury. Yet, the restraining mechanism must pre-
movements or they are intentionally acting out in vent unwanted head, hand, feet, and torso
an attempt to escape. movements.
When children with CP attempt to move in While many outdated restraining devises and
order to help, their muscles often tense up, tools are still in use, our practice limits this nec-
increasing uncontrolled movements. Relaxation essary restraint to Velcro ®, mesh cloth, and hands.
of the patient will not halt the uncontrolled body The operatory chair or the wheelchair headrest is
movements but may reduce their frequency or the base for the first plane of movement, which is
intensity. By anticipating the child’s repetitive restricted. We assign one dental professional to
movements, one can adapt and avoid triggering immobilize the patient’s head in the remaining
aberrant muscular responses. Cradling the head five planes using both their hands and forearms.
and working slowly reduces uncontrolled move- It is crucial to immobilize the head. The goal is
ments. Avoiding sudden head turns or surprising to prevent the child from jerking his or her face
stimuli such as noises, lights, or body movements into a needle, drill, scaler, explorer, or any sharp
into uncomfortable positions will guarantee a tool. It is important to keep instruments and equip-
more successful visit (NIDCR 2014). ment out of the patient’s way and to maintain a
Some sensory tricks to suppress unwanted clear path for the patient’s potential spastic move-
movement include the following (Cerebral Palsy ment throughout the dental procedure.
Alliance): This manual restraint is often used in addition
to a piece of Velcro ® wrapped around the patient’s
– Touching the face or chin with a hand or finger forehead and the operatory headrest itself. A
– Resting the back of the head against a wall larger piece of Velcro ® is wrapped around the
– Tucking a hand under the chin patient’s knees or ankles or both, often circling
– Placing a hand behind the back part of the chair as well. A colorful,
non-threatening wrap, made of mesh and Velcro ®
that includes two cloth wrist bracelets, prevents
most children from causing disruptive movements
of limbs or torso (Fig. 15).
The wrap may be placed on the operatory chair
or onto a parent/caregiver’s lap before the child is
seated on it. Younger patients will perceive this wrap
as a comfortable snuggly often used by parents for
feeding or transport. For older children with CP, the
wrap, coupled with sedative drugs or nitrous oxide
or both, results in a 96% success rate in successfully
completing the assigned dental procedure.
Special precaution regarding safety restraints:
Helmets should only be removed when it is
deemed “safe,” such as when the child is held by
a caregiver or surrounded by pillows. Keeping the
Fig. 14 Child in small portable chair overlay hands away from the mouth where there may be
1080 H. Levy
Fig. 15 Body and legs restraint with rainbow wrap and

knee guard
sharp tools will prevent accidents. The child’s

hands may be held by a caregiver if the child is
large or strong.
Nitrous Oxide
Once the premedicated patient is seated and
restrained, we may administer a mix of nitrous
oxide/oxygen. Introduced by Wells in 1884,
nitrous oxide demonstrates a rapid onset, quick
Fig. 16 Silhouette nitrous oxide mask with mouth gag
recovery, and minimal side effects, making it an
excellent choice for patients with CP. Nitrous
oxide/oxygen leads to reduced hyperkinesis or
decreased movement during dental treatment. With four different sizes of disposable nitrous
The reduced response to pain stimuli is compara- oxide masks, the profile is so low that patients
ble to 15 mg morphine (Kaufman et al. 1982). As are now able to wear their glasses with no inter-
a result, extensive dental work can be performed, ference from the mask. Additionally, for the
while the child is sedated and quiescent. older teens with facial hair, there is no gas leak-
Yoshida et al. (2003) noted that nitrous oxide age under the nose. Two of the three sides of the
reduced the orofacial muscle tonus of children clear, disposable mask have peel-off adhesive
with CP, because of the gas’s inhibiting function strips that preclude gas escape from either side
on CNS, making it a useful adjunct during office of the nose. At the open nostril area, nitrous
dental treatment. oxide enters into the right side, and exhaled air
Jensen (2008) found the use of 70% nitrous exits the left. To make the mask appealing to our
oxide with 30% pure oxygen results in significantly children with CP, we determine their favorite
reduced movements (Sehrawat et al. 2014). My flavor or scent. We then coat the lining of the
personal observations and treatment of over mask with that scent or flavor. We also write
35,000 special-needs patients under nitrous oxide their name on the mask for them to take home
in my dental office, which included many hundreds as a souvenir of their successful office visit
of children with CP, support Jensen’s findings (Fig. 16). Nitrous oxide is typically used in
(Levy 2016a, b; Levy and Rotenberg 2016). conjunction with oral sedation drugs on chil-
The new low profile nitrous oxide mask has dren who are body wrapped and have an empty
replaced all the old masks in our office (Fig 16). stomach and bladder.
Opening the Mouth to the child is minimal. For a resistant child, a

Hippocrates was correct when he said, “before physical distraction technique may be employed
you can treat, you must diagnose.” In this context, to divert his or her attention away from the mouth-
for dental evaluations, he left out, “and before you opening procedure. This may include pressing the
can diagnose, you must be able to open the thumb fingernail at 90 to the bed of the nail or
patient’s mouth.” Whether a child is fearful from rubbing the philtrum horizontally or even a gentle
an unpleasant past experience, or a first-time but unexpected tap to the forearm. The moment
patient is afraid of the unknown, children with the physical distraction is performed, the acupres-
CP may present a challenge to a dentist. However, sure point is activated by a second person at the
this is a challenge that can always be handled with site’s proper angle and direction.
a professionalism that may even mitigate future The points that I have developed, routinely
treatment issues. employ, and now teach are the following:
Dos Santos and de Oliveira (2004) used cryo-
therapy on masseter muscle spasticity to obtain the
(A) Conception (CO or CV) -24 the mandibular
mouth opening required for oral hygiene and dental
chin button
treatment. Ice on the masseter obtained a temporary
(B) Miscellaneous Head and Neck (MHN) -18
reduction in spasticity, facilitating access to the
mental foramen or foramina
occlusal and palatal surfaces of the upper molars.
(C) Triple Warmer (Triple Burner, Triple Heater)
In our office we use a different technique,
(TW) -17 under the ear, near the TMJ
primarily based on my original research, much
(D) Governor (GV) -26 maxillary philtrum
of which is viewable on a free 1-h educational
webinar titled, “How to Open ANYONE’S
Mouth.” This video is available at the following Activation is successful only if the correct angle,
link: http://www.vivalearning.com/member/class direction, and mode of contact are used. For exam-
room.asp?x_classID=3101. ple, CO-24 must be vibrated with a knuckle at a
In over thousands of attempts to safely open 45-degree angle in and downward (Fig. 17).
the mouth of children with CP, we have been MHN-18 also requires firm vibration 45 in and
successful in the office 96% of the time. The down, be it unilateral or bilateral. TW-17 requires
other 4% were deemed not safe or potentially horizontal pressure from rear to front. GV-26 is
harmful either physically or psychologically. activated by a horizontal rubbing action (see
Those patients were examined and treated under webinar noted earlier in this paragraph). It is
safe conditions via outpatient general anesthesia
in a hospital or surgical center operating room.
More about this follows in the section on general
anesthesia (Levy 2016a, b).
The basis of successful mouth openings in the
office for uncooperative children with CP is to
precede the attempt by using benzodiazepine
drugs or nitrous oxide or both. For safety, the
child is also placed in a colorful non-threatening
body wrap made of mesh and Velcro ®. Once the
drug or nitrous oxide or both have taken effect, the
child’s head is immobilized. A dental professional
places one hand on the forehead or under the nose
to prevent unwanted downward head movement.
Then, the dentist presses one of the four
recommended acupuncture points to gently “pres- Fig. 17 Opening mouth with CO-24 pressure point and
sure” the mouth open. The momentary discomfort Open Wide Mouth Rest – horizontal
1082 H. Levy
essential that before prescribing or administering

any drugs or nitrous oxide or utilizing physical
mouth-opening techniques, proper signed
informed consents must be obtained (Levy
2011a, b).
Keeping the Mouth Open

Santos et al. (2016) found that a low intensity laser
aimed at the TMJ and muscles of mastication
increased the amplitude of mouth opening and
decreased tonus of children with spastic Fig. 18 Keeping mouth open – with mouth gag in OR
CP. Once the mouth is opened, the task is to
keep it open long enough to at least perform an For all others, we prefer to prop the second side
oral exam and preferably to complete the antici- before removing the first to prevent premature
pated dental treatment. A high level of patient mouth closure.
cooperation may not be required to perform a For the 12 anterior teeth, a bilateral mouth prop
simple oral evaluation and exam. However, if a is often used, sometimes with a lip retractor. This
needle, drill, scaler, or other sharp tool is to be device gradually forces the mouth open just like
placed in the mouth, it is prudent to assure that it the unilateral mouth gag and is found in ENT
can be done safely. Mouth props, mouth rests, catalogues.
mouth gags, or other devices sustaining oral
access are essential (Fig. 18). The tools used to
initially open the mouth may not always be the Treatment: Oral Exam and Cleaning
best ones to sustain or expand that opening.
Once we have successfully opened the child’s Every oral exam and cleaning with possible radio-
mouth by either asking, coaxing and encouraging, graphs, and every dental treatment, begins with
pinching the nose shut, or using acupressure, the our inserting a foam and wood rest. The insertion
mouth must remain open for as many minutes as it is followed by the techniques described in the
takes to complete the procedure. Whether it is a section on “keeping the mouth open.” To conduct
quick exam, an intermediate cleaning, or a length- this exam, we use several tools.
ier dental procedure, the mouth must not be allo-
wed to close at a time or manner that will cause Illuminating the Oral Field
problems or injuries. We insert a wood-covered- Many children with CP are in perpetual motion,
in-foam prop on one side of the mouth as far challenging the dental professional forced to work
posteriorly as possible. A second person then in confined conditions. The child’s head darts in
inserts an expanding mouth prop or mouth gag and out of the area illuminated by overhead fixed
on the other side, then slowly ratchets it open until operatory lights. One way to overcome that is for
maximum opening is reached. A finger is placed the operator to wear a headlight, allowing constant
on the prop’s hinge to prevent dislodgement, as illumination of the mouth by simply rotating the
the wood/foam mouth rest is removed. The dental forehead to mirror the child’s movements. We use
work is then performed on the free side that is featherweight lights, since they can be affixed to
exposed and available. One may insert a rubber one’s own glasses or to clear plastic safety glasses.
dam or other isolation tool. When the work is The rechargeable and portable light source can be
completed on that half of the mouth, the opposite used in any venue (Fig. 19).
side of the mouth is propped to its widest vertical
dimension, as the existing prop, gag, or mouth rest Illuminating Inside the Oral Cavity
is removed. For patients with TMJ, we remove Once the child’s mouth is opened and safely pro-
and reinsert every 15 min to prevent joint fatigue. pped open, we generally begin our intraoral exam
Fig. 19 Portable head light in hospital pre-op area
using a portable, lightweight, three-in-one device:

a long-handled mirror, a mouth prop, and a light
source. This device also enables us to observe soft
tissue asymmetries and has already detected sev-
eral mouth cancers (see free educational video avail- Fig. 20 Light in mouth of propped-open child with verti-
able at the following link: http://www.vivalearning. cal Mouth Rest
com/member/classroom.asp?x_classID=3042).
When one side of the mouth is fully examined, we
switch the mouth gag to the opposite side or insert
another prop on the second side before withdrawing
the first (Fig. 20).
Intraoral Photos and Video

Intraoral photos are taken of the mouth and
immediately displayed onto the TV screen in
the room. This allows us to see still images of
what were moving targets a moment ago. It also
allows us to more effectively show the parent
or caregiver what the child’s mouth looks like, Fig. 21 Intraoral camera in propped-open mouth of an
be it to educate, praise, or show areas in need uncooperative 5-year-old boy with CP using mouth gag
of attention. If the child is too animated for still
shots, we insert our video camera for intraoral
videos, knowing we can freeze frame later to the child stand up or prop his or her head in a
isolate any individual frames that will be useful wheelchair to attempt panoramic images. Our
for diagnostic, archival, communication, or panoramic X-ray machine also can take extraoral
insurance purposes. Often, we print out selected digital bitewings for children who cannot readily
images to give the family to take home as tolerate intraoral films or sensors (Fig. 22). For
reinforcement souvenirs or to communicate gaggers or uncooperative children, we may anes-
with caregivers not present (Fig. 21). thetize the mouth with a spoonful of 2% lido-
caine elixir or a topical spray. We invite any
X-Ray Imaging nonpregnant caregiver or staff member to don a
We never treat any patient without first viewing poncho lead apron and remain in the room to
the radiographs, but such images are not always immobilize the child’s head, hold the sensor or
attainable during the initial visit. We often have film, or provide comfort. Though each treatment
1084 H. Levy
Fig. 23 Dental X-rays in OR with self-developing dental

film
Fig. 22 Dental X-rays in OR
room has a wall-mounted X-ray head, we also

frequently use portable 5.5 lb. X-ray units,
which can be used in our office, in the OR,
homes, hospice centers, and other off-site facil-
ities or locations. Since the lead-aproned opera-
tor shoots the image with one hand while
holding the sensor or the patient’s head with
the other, the handheld X-ray units provide
images in less time than a wall-mounted unit.
Retakes can be instantaneous for imperfect ini-
tial images.
The 4% of cases in which radiographic images Fig. 24 Magnification loops plus light while inserting
were not successfully obtained in the office are nasal spray anesthetic
always successful when the patient is treated
while asleep in the OR (see section on “General I need an enlarged and illuminated detailed view
Anesthesia”). On the rare occasion that our sensor of the mouth. Others may prefer a magnifying
or computer is inoperable, we dare not continue lens only (Fig. 24).
the case without an adequate radiographic image.
That is when the self-developing dental film saves Isolation
the day and allows us to complete the case that The dentist needs to isolate the tooth being
session. This free-standing dental film allows us to worked on from saliva and the soft tissue of the
take excellent radiographs within 60–90 s, with- mouth, and especially in the case of children with
out delaying or canceling the case (Fig. 23). This CP, from inadvertent aspiration of fluids or foreign
is crucial whether in the OR under general anes- objects. To drill teeth or place composite restora-
thesia or out in the field at a home, institution, tions in a propped open, well-lit, clear, and dry
hospice center, dental mission work to other coun- intraoral environment, we consistently find Iso-
tries, or other off-site venues. lite ® most effective. Isolite ® is a disposable, soft-
plastic, multi-sized, easily trimmed, readily
Magnification placed mouth prop that has five levels of intraoral
My three partners and I all have different eyes and light and two levels of suction (high velocity
different preferences regarding magnification. I evacuation plus saliva ejector) (Fig. 25).
often use a headlight combined with a magnifica- Composite or sealant failures are rare when
tion lens, finding it comfortable to wear whenever Isolite ® is placed in the mouth. For gaggers, we
Fig. 26 Tetracaine and oxymetazoline nasal spray used to

anesthetize 10 upper front teeth
teeth and 64% of the upper second premolars

(St. Renatus, LLC 2016a, b, c; US Food and
Drug Administration 2016).
The most common time for any patient to bite
their locally anesthetized lip, tongue, or cheek is
right after any mouth props are removed, after the
dentist completes the procedure. While the numb-
ing effect of the anesthetic may last for many more
Fig. 25 Isolite retractor, suction, prop, and light
minutes after the procedure concludes, it is within
the first few minutes that a patient may explore the
apply 2% lidocaine viscous around the appliance. unusual sensation of biting their lip, tongue, or
For smaller mouths or mandibular tori, we cut off cheek without feeling any pain. Children with CP
any excess plastic with scissors. may be especially prone to this problem if they
don’t understand the potential harm or are not
warned. To prevent this potential self-injurious
Treatment: Complex Dental Procedures behavior, the dentist can inject phentolamine
mesylate, a vasodilator that hastens the return to
Children with CP may suffer from substandard normal sensation, in the area numbed by the local
home dental care, requiring complex dental pro- anesthetic (Fig. 27).
cedures such as restorations, crown and bridge, or
teeth extractions. In this case, after the patient is
seated, restrained, sedated, and propped, anesthe- When Office Efforts Don’t Succeed
sia is required. We start with a topical anesthetic,
followed by a local anesthetic. When the combination of oral sedation drugs,
Typically the local anesthetic is administered nitrous oxide, and restraints is applied, our suc-
with a needle, but there are other options. Tetra- cess rate in the office is 96%. For the 4% we are
caine HCL and oxymetazoline HCL, a nasal unable to safely treat in the office, we can bring
spray, can be used instead of local anesthesia for our success rate up to 100% by using either IV
the ten upper front teeth, both primary and perma- sedation or general anesthesia in an
nent. Two doses are sprayed into the one nostril operating room.
closest to the teeth being worked on For a dentist, there is nothing more efficient
(Fig. 26). This eliminates the need for any injec- and effective than treating a patient who does not
tions in 96% of the cases for the upper eight front move at all. This is especially true for children
1086 H. Levy
specialist is invited to cooperate. That is also a

perfect time for any tests to be performed that are
difficult on an awake patient. This includes blood
draw, pap and pelvic exams, chest X-ray, EKG,
and procedures by allied health professionals such
as cardiologist, ENT, or pediatrician. This is in the
true spirit of efficient, practical, successful
one-stop health care and cooperation (Levy
2016a, b).
IV Sedation
The intermediate between nitrous oxide with oral
Fig. 27 Phentolamine mesolate to reverse numbing effect
of local anesthetic drugs and intubation with general anesthesia is IV
sedation. For dentists, each state has different
with CP, who can receive the finest dental care rules and regulations for obtaining office sedation
with no psychological harm of being restrained, permits. In most states, a class 1 permit is required
no chance that their behavior might preclude for moderate office sedation. A class 2 permit is
finishing the planned treatment, and under the required for IV or deeper moderate sedation. A
safest conditions. In the OR, all the planned class 3 is required for general anesthesia. Oral
work is done in one session, without having to surgeons generally have permits that allow them
schedule multiple office visits, where case com- to monitor their own cases. Most pedodontists and
pletion is never assured. Going to the OR is the general dentists rely on dental anesthesiologists,
last, not the first, choice. The upside is the dentist nurse anesthetists, or anesthesiologists to manage
does his or her finest and most-efficient, accurate the patients’ heart, lungs, and vital signs, while the
work on a patient who cannot halt or remember dental professionals do what they do best – their
the dental treatment. dentistry. The ASDA, ADSA, private groups such
In the office, a dentist cannot guarantee that as DOCS, and many dental schools are among
any dental procedure would be completed that day organizations that help provide training for den-
as planned or hoped for. There are too many vari- tists seeking to provide anything more than mild-
ables that may preclude successful completion, to-moderate nitrous and oral office sedation.
especially given the child’s physical and behav-
ioral issues. In the hospital or surgicenter OR, all General Anesthesia
cases can be completed that same session, even if Children with CP take slightly longer to wake up
the specific procedures were modified based upon after general anesthesia. It is common for ASA III
new information from the intraoperative visual and IV patients not to go home the same day, as
exam and radiographic findings. For extractions, additional monitoring may be required to detect
we always use resorbable sutures rendering and treat complications of general anesthesia
suture removal optional rather than a possible because of their underlying disease (Escanilla-
struggle. Restorations are placed with no saliva Casal et al. 2014).
contamination or movement by the patient. In Loyola-Rodriguez et al. (2004) reported excel-
addition to stainless steel crowns, we now have lent results using sevoflurane and propofol,
composite crowns, which do not require documenting a postanesthesia recovery time of
computer-aided design/computer-aided manu- 20–40 min in children with CP.
facturing (CAD/CAM) for same day completion. In the hospital or surgical center, Versed (mid-
For immediate delivery of space maintainers or azolam) elixir is often given to any patient who
removable appliances, the absence of the child’s does not readily allow an IV to be started. It is
head movements makes the dentist’s job much mixed in a drink or squirted into their mouth with
easier. If a complex procedure beyond the skill a plastic syringe. Combative patients may also
or scope of the treating dentist is required, a require an intramuscular injection of ketamine
dental conditions or pathology, and treat them

accordingly.
If a regular toothbrush is not succeeding in
removing plaque because of the child’s
non-compliance or lack of cooperation, plan B
should include an electric toothbrush, whose bris-
tles are moving even when the caregiver’s hand is
not. If the child doesn’t accept the floss with your
fingers, try using a floss holder or sling-shot-
shaped handle. If that is not possible, consider a
water pick, being mindful of potential aspiration
concerns. One modality that has very little down-
side is 0.12% chlorhexidine (CHX) mouth rinse.
Fig. 28 Comprehensive dental care while asleep in the Maiya et al. (2015) had excellent results with daily
OR
CHX 0.2% spray in maintaining satisfactory oral
hygiene and gingival health.
IM (2–4 mg/kg), a narcolept-analgesic, which Francis et al. (1987) used CHX spray, gel, and
subdues a patient for staff to start an IV and pre- mouthwash. Although the gel was the most effec-
pare the patient for general anesthesia. Once tive in reducing plaque and gingival bleeding, the
asleep, the child is compliant, allowing the dental caregivers’ poor compliance precluded that modal-
team to perform quality dental care on a ity long term, favoring the daily spray instead.
non-moving patient (Fig. 28). Soncini and Tsamtsouris (1989) explored and
maintain that individually modified toothbrushes
OR (Operating Room) Follow-Up (IMT) are effective in improving the oral hygiene
in the Office and gingival health of children with CP. Damle
After treatment in an operating room, I always and Bhavsar (1995) also reported a marked
recommend a follow-up visit in the office, gener- decrease in plaque levels for children with CP
ally between 2 and 14 days postoperatively. All who used toothbrushes with modified handles
the tools, techniques, and tips we employ for the under supervision.
preoperative OR visit may be used for the postop- Hygienists are very creative in suggesting
erative evaluation. This brief follow-up visit may modifications to the child’s toothbrush. In our
be necessary to remove sutures; assure that office, we have used all of the following: tooth-
resorbable sutures are out; check on postoperative brush in a tennis ball, in a Styrofoam ball, in a
healing of a surgical site; confirm that there are no bicycle handle, wrapped in play dough, glued to a
high restorations; cement crowns, bridges, or Velcro ® strap, secured to a 1200 ruler, attached to
space maintainers; adjust appliances delivered in multiple rubber bands, and more (Fig. 29).
the OR; and more. The visit is also an excellent
opportunity to review and modify the child’s oral
hygiene procedures. Training for Dentist and Dental Staff
Every teacher knows that the best way to learn

Oral Hygiene at Home or Institution anything is to have to teach it. Dentists, hygien-
ists, and assistants are all obliged to teach patients
Dental care begins at home, with tooth and caregivers both proper as well as modified
brushing; flossing, fluoride, therapeutic agents oral hygiene. The techniques must be individual-
such as chlorhexidine, and alternatives such as ized and varied. Basic oral hygiene knowledge
Waterpik, water floss, and other adjunctive oral and skills are taught in the academic clinical
aids. Oral exams in the dental office are meant didactic programs. It is in the office and the field
to assess home care, evaluate any new that creativity reigns, and customized oral hygiene
1088 H. Levy
schools should better prepare graduates to meet

the demands and needs of patients with CP and
other special needs.
Casamassimo et al. (2004) noted that only 10%
of dentists saw special-needs patients often or
very often during their training. Only 25% had
any hands-on experience in school. Postgrad Gen-
eral Practice Residencies and Advanced Educa-
tion in General Dentistry programs made no
difference in terms of seeing patients with special
needs once in practice. Dentists with hands-on
experience did not consider the patient’s level of
disability or behavior as obstacles to care. I view
the primary barriers to access to care as fear and
finances. The fear factors can readily be over-
come by some professional knowledge and moti-
vation. No child should be denied dental care
because of the dentist’s level of comfort. Learning
to successfully treat children with CP is no differ-
ent than learning any other dental skill. Most state
and national dental meetings as well as dental
schools offer such workshops, in addition to
Fig. 29 OR follow-up, teaching oral hygiene online training. The unmet needs of these children
could easily be met if every dental office opened
instruction protocols are developed. Experience its doors to greet and welcome these children.
and repetition grow novices into experts, who There is much literature describing and
help train the next generation of dental health confirming the assertion that finances are a major
professionals. obstacle to seeking and obtaining dental care for
Most dental meetings and universities include these children. The articles appear similar in nature
participation courses on management of patients and conclusions yet originate from many different
with special needs. Self-study courses are avail- countries (Schultz et al. 2001; Maiya et al. 2015;
able, including YouTube and many excellent self- Vujicic 2014). In the USA, there are federal, state,
directed online programs. There is nothing more county, and private programs to assist those who
effective than a quality participation course seek either elective or urgent dental care. Other
followed by incorporation of these techniques financial resources and safety nets for needed den-
into one’s practice slowly and steadily. Though tal care include Donated Dental Services programs,
more difficult to come by, mentorships are excel- Gray Area Access programs, Missions of Mercy,
lent but require that the student clinician already Religious Coalitions, Foundations for the
have basic necessary knowledge and skills. Many Handicapped, Hospital-affiliated dental clinics
dentists are pleased to share their knowledge and (to reduce ER visits), and funds through service
experience if only asked, so consider asking. organizations and clubs.
Access to Care Conclusion
Many parents whose children with CP were on As patients in a dental office, children with CP
Medicaid perceived cost as a barrier to dental care often present challenges that require patience and
(Schultz et al. 2001). Al-Allaq et al. (2015) are creativity on the part of the dental team. Treating
some of many authors who contend that dental these patients is easily achievable if the staff is
open to working with this population and

becomes passionate about access to care. All it with her front teeth grossly flared out. She
takes is a bit of special equipment and, more was uncooperative with daily oral hygiene,
importantly, the willingness to make some adap- and needed to be sedated with oral drugs
tations to usual and customary dental office and nitrous oxide to have any office dental
protocols. care. She was wheelchair-dependent and on
An essential part of dental care for children 25 different daily medications.
with CP is preventive. Practitioners who are able On her initial office visit in 1998, in
to creatively tailor brushing and flossing proce- addition to the standard amoxicillin
dures to each patient, and who find alternative and 2 grams premedication for a cardiac condi-
effective ways for a patient to regularly practice tion, we used chloral hydrate 500 mg,
oral hygiene, reduce the need for expensive and hydroxyzine (Atarax) 20 mg, plus nitrous
possibly traumatic dental treatments. oxide/oxygen 50% to evaluate small frac-
tures on teeth #8 and #9, her upper front
central incisors. Given her unsafe thrashing
Case Studies body and hand movements, we restored her
teeth a week later with composite material
after increasing the dose to chloral hydrate 1
gm and hydroxyzine 30 mg, with nitrous
Case Study #1: Laura
70%, plus the 2 grams of amoxicillin
Laura was first seen as a 12 year old white
(Fig. C1.1).
female with CP, seizure disorder, Intellec-
tual disability, heart murmur, and combative (continued)
behavior. She had a class 2 malocclusion,
Fig. C1.1 Laura age 12, before and after composite upper front teeth repair
1090 H. Levy
Fig. C1.2 Laura age 16, before and after upper front teeth bridge placement
Four years later, at age 16, she fell down

and fractured teeth #8 and #9 again. After
monitoring for two weeks noticing they
became dark and mobile, we removed the
teeth, and prepared a fixed porcelain/metal
bridge via out-patient general anesthesia in
the hospital operating room. The family
wanted to replace the non-salvageable
teeth, but we all agreed that Laura was not
a candidate for implants or removable appli-
ances. The bridge that we prepared in the
hospital OR was cemented in our office 2
weeks later using the same sedation regime
as before. Bridge oral hygiene was
reviewed with the parents, and Laura was
placed on semi-annual dental hygiene recall
(Fig. C1.2).
(continued)
Fig. C1.3 Laura breaks 6 upper front teeth bridge
Fig. C1.4 New bridge is placed in mouth
Fig. C1.6 Laura falls and breaks second bridge
Fig. C1.5 New bridge is cemented into propped-open The same cycle repeated, whereby a third
mouth
bridge was prepared in the hospital OR
(Figs. C1.8 and C1.9) and cemented in the
office (Fig. C1.10) using the same props and
sedation
Years later, in 2009, Laura fell and frac- She has been on semiannual hygiene
tured the bridge (Fig. C1.3). Again, she was visits ever since and remains an active
taken to the OR where a new 6-unit bridge patient who is wonderfully managed by
was prepared, and also cemented in the her loving parents at home. She is still
office with maximum premed, oral seda- sedated, wrapped, and propped when
tion, and nitrous oxide (Figs. C1.4 and receiving both elective and urgent dental
C1.5). care in our office and hospital. The
Two years later, Laura fell again, break- third bridge is holding up just fine
ing the second bridge (Figs. C1.6 and C1.7). (Fig. C1.11).
1092 H. Levy
Fig. C1.7 Broken second bridge
Fig. C1.9 New bridge being prepared in OR
Fig. C1.8 Laura is in OR to have broken bridge remade Fig. C1.10 New bridge is cemented and flossed in office
Fig. C1.11 Laura with third six-unit upper front teeth

bridge
Case Study #2 Svetlana

Svetlana is a 19-year-old white female ini-
tially seen with decayed and fractured upper
front teeth (Figs. C2.1 and C2.2). She con- Fig. C2.1 Svetlana, age 19 with bandana to catch drool
stantly drools, has CP and a seizure disor-
der, is intellectually delayed, non-verbal
and wheelchair-bound. Her family wanted
us to save all teeth except for the impacted
third molars. In the OR, we placed compos-
ites and crowns on the upper front teeth, and
restored other carious teeth (Figs. C2.3,
C2.4, C2.5, C2.6 and C2.7). Two weeks
later, with Svetlana remaining in her wheel-
chair, and with her family’s support, we
cemented the two upper right incisor
crowns, and reviewed oral hygiene home
care (Figs. C2.8, C2.9, C2.10, C2.11,
C2.12 and C2.13). Semi-annual office fol-
low-ups thereafter required only simple
office cleanings (Fig. C2.14).
Svetlana does not require any sedation
other than an anticonvulsant, but requires
mouth props to prevent inadvertent clo-
sures. She always wears a towel to catch
her drool (Figs. C2.1 and C2.13).
Fig. C2.2 Four upper front teeth decayed
1094 H. Levy
Case Study #3 (Allison) anterior open bite (Fig. C3.1). She is wheel-
Allison is a 15 year old wheelchair-bound chair bound, and has a history of a spinal
female with cerebral palsy and a severe fusion. Her non-compliant behavior pre-
cludes effective daily oral hygiene. In our
office, we noticed over-retained primary
tooth #H, and assumed there may be an
impacted upper left cuspid #11. The calcu-
lus from her periodontitis was very think
and tenacious. She was unable to hold her
head still to safely have the necessary treat-
ment in our office. She is g-tube fed, which
promotes calculus build-up.
After their pediatric dentist retired it took
the family 1.5 years to find a dentist and
facility who would agree to treat Allison.
After an initial limited office exam, we
successfully treated her in the hospital OR
with a thorough dental exam, full set of
intra-oral radiographs, removal of the dan-
gerously loose baby tooth and removal of
the heavy calculus deposits (Fig. C3.2).
Exam and radiographs showed malocclu-
sion with crowding and the impacted
(continued)
Fig. C2.3 Better exam in OR shows dental caries
Fig. C2.4 Intraoral images taken in OR

Fig. C2.5 Portable handheld X-ray unit with sensor
Fig. C2.8 Svetlana returns to office for 2-week follow-up
Fig. C2.6 X-rays show decayed upper front teeth
Fig. C2.7 Crowns are prepared for upper right incisors, Fig. C2.9 Svetlana’s mouth is propped, and all OR work
composites on the left is checked in office
1096 H. Levy
Fig. C2.10 Mother assists, while we cement the crowns
Case #4 Savannah
Pt is a 19-year-old white female with a
pronounced orthodontic class 2 division 1
(Figs. C4.1, C4.2 and C4.3). She has cere-
bral palsy, is intellectually disabled, and has
had seizures since age 1. She walks slowly
on her own power, but with a spastic gait.
She is non-verbal, but uses a computer to
verbalize whatever she wants to say. She
bumped her front teeth several times, and
has a darkened upper left front tooth #9.
She has difficulty cleaning her mouth,
and cannot maintain her mouth open for
more than a few seconds at a time in a
dental office, despite her best intentions to
cooperate.
We performed a thorough visual and
radiographic evaluation plus all needed
Fig. C2.11 Porcelain/metal crowns teeth #7,8 in place dental treatment via out-patient general
anesthesia in the OR (Figs. C4.4 and C4.5).
Routine frequent office cleanings are now
upper left cuspid with the over-retained pri- performed with a mouth prop, plus 20 mg
mary cuspid (Figs. C3.3 and C3.4). Allison oral Valium and nitrous oxide to relax the
is now on a regular 3-month office cleaning mouth muscles.
cycle via Valium oral sedation in our office.
Fig. C2.12 Flossing away excess cement and instructing

family
Fig. C3.1 Allison showing severe anterior open bite, pro-

truded upper teeth, with incompetent lower lip
Fig. C3.2 Allison with widely flared upper anterior teeth

Fig. C2.13 Teaching oral hygiene to patient and family and open-bite malocclusion
Fig. C3.3 DEXIS X-ray images while asleep in OR, via

Fig. C2.14 1-year follow-up nasal intubation
1098 H. Levy
Fig. C3.4 Full series intraoral periapical images show impacted tooth #11, upper left cuspid
Fig. C4.3 Lower arch shows crowding and periodontal

disease
Fig. C4.1 Savannah age 19
Fig. C4.4 Savannah selects her favorite flavor of Lip

Smacker to line her mask
Fig. C4.2 Upper teeth show copious saliva and malocclu-

sion anterior open bite
Fig. C4.5 X-rays taken in the OR that were unattainable in an office
Fig. C5.2 Maria’s left stained teeth, crowded anterior

open bite
Fig. C5.1 Maria, age 18
Fig. C5.3 Maria’s father sits in the operatory chair, while

she remains in her wheelchair
1100 H. Levy
Fig. C5.5 Close-up of foam and wood mouth rest
Fig. C5.4 Hygienist cleans Maria’s teeth with two assis-

tants and father helping
Case #5 Maria
Maria is an 18-year-old wheelchair-bound
girl who suffered anoxic brain injury plus
cardiac arrest and septic shock as an infant
(Fig. C5.1). Her current problems include
spastic quadriplegic cerebral palsy, Lennox-
Gastout Syndrome causing intractable epi-
lepsy, Hirschsprung’s Disease, spinal fusion
for neuromuscular scoliosis, abnormal thy-
roid, anemia, esophagitis due to GERD,
hypertension, developmental delay, feeding Fig. C5.6 Maria is rewarded with a kiss from her dad
difficulty, and hip subluxation. She is g-tube
fed and has a colostomy. The severe jerky
movements of her limbs have precluded her
from having dental care, and she has been hematologist, pulmonologist and primary
on wait lists, without ever being called. She care physician, the anesthesiologists at the
has never had any dental radiographs, but only hospital in our town refused the case,
her loving and attentive father felt she might citing she was too high a risk for elective
have dental caries and periodontitis dental care.
(Fig. C5.2). Unable to obtain any dental With no other options, we treated the
X-rays in our office, we agreed to take patient in our office using oral Valium
x-rays, examine and clean her teeth in the 15 mg and continuous high velocity vac-
OR as well as restore decayed tooth #30. uum suction. The hygienist and I cleaned
Despite clearance from her neurologist,
(continued)
Botti Rodrigues Santos MT, Duarte Ferreira MC, de

Maria’s teeth and I performed a composite Oliveira GR, Guimarães AS, Lira Ortega A (2015)
restoration on tooth #30, propping the Teeth grinding, oral motor performance and maximal
opposite side. bite force in cerebral palsy children. Spec Care Dentist
35(4):170–174. https://doi.org/10.1111/scd.12106
Despite our best efforts, Maria later
Cardoso AM, Gomes LN, Silva CR, Soares Rde S, Abreu
developed lung congestion and was hospi- MH, Padilha WW, Cavalcanti AL (2014) Dental caries
talized for a month with aspiration pneumo- and periodontal disease in Brazilian children and
nia. The father did not want to tell us, adolescents with cerebral palsy. Int J Environ Res
Public Health 12(1):335–353. https://doi.org/10.3390/
fearing we would no longer be willing to
ijerph120100335
treat her in our office. Carneiro NCR, Monteiro LR, Pordeus IA, Borges-Oliveira
Maria and her father still come in for AC (2017) Oral sucking habits among children with
cleanings every 3 months. She remains in Down syndrome and cerebral palsy. Spec Care Dentist
37(4):176–180. https://doi.org/10.1111/scd.12231
her wheelchair while her father entertains
Casamassimo PS, Seale NS, Ruehs K (2004) General den-
her with her favorite i-pad songs (Fig. C5.3). tists’ perceptions of educational and treatment issues
We still have not been able to obtain any affecting access to care for children with special health
X-rays, but visual exam suggests there are care needs. J Dent Educ 68(1):23–28
Cramer JJ, Wright SA (1975) The bean bag chair and the
no further dental caries (Figs. C5.4 and
pedodontic patient with cerebral palsy. Dent Hyg
C5.5). Our Cari-Vu exam suggests no decay. (Chic) 49(4):167–168
We cannot determine impactions or other Damle SG, Bhavsar JP (1995) Plaque removing efficacy of
subgingival dental pathology, but continue individually modified toothbrushes in cerebral palsy
children. ASDC J Dent Child 62(4):279–282
to clean her teeth with bilateral high velocity
Das UM, Beena JP, Reddy D (2010) Importance of oral
suction every 3 months to prevent aspiration. hygiene habits in mentally disabled children. Int J Clin
We consider it a privilege to be able to offer Pediatr Dent 3(1):39–42. https://doi.org/10.5005/jp-
Maria and her father dental care in our office journals-10005-1052
Diéguez-Pérez M, de Nova-García MJ, Mourelle-Martínez
(Fig. C5.6). We plan to treat her in the hospi-
MR, Bartolomé-Villar B (2016) Oral health in children
tal OR when the anesthesiologists determine with physical (cerebral palsy) and intellectual (Down
it is safe enough to be considered a low risk. syndrome) disabilities: systematic review I. J Clin Exp
Dent 8(3):e337–e343. https://doi.org/10.4317/jced.52922
dos Santos MT, de Oliveira LM (2004) Use of cryotherapy
to enhance mouth opening in patients with cerebral
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Management of Skeletal Facial
Deformation and Malocclusion 77
in Cerebral Palsy
Joseph A. Napoli, Stephanie Drew, and Tim C. Jaeger
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1106
Etiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1106
Functional Deficits and Impact . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1111
Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1112
Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1113
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1117
Glossary of Terms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1117
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1119
Abstract shape of the facial bones. Malocclusion repre-

Skeletal facial deformation and malocclusion sents disharmony in the relationship of upper
are commonly found in children with cerebral and lower teeth. Malocclusions may be skeletal
palsy (CP). Skeletal facial deformations repre- or dental in nature. Thus, the cause may be
sent abnormalities in the position, size, and/or related to malposed teeth, a malposed or mis-
shapen maxilla or mandible, or a combination
thereof. These types of deformities may create
J. A. Napoli (*) functional impairment as well as problems
Division of Pediatric Plastic and Maxillofacial Surgery, with facial cosmetic appearance. The func-
Department of Surgery, Nemours/Alfred I. duPont
Hospital for Children, Wilmington, DE, USA tional deficits can be debilitating, leading to
issues with mastication, respiration, speech,
Sydney Kimmel Medical College, Thomas Jefferson
University, Wilmington, DE, USA and communication. They may also contribute
e-mail: Joseph.Napoli@Nemours.org to drooling and difficulty with oral hygiene.
S. Drew · T. C. Jaeger
Department of Surgery, Division of Oral and Maxillofacial Keywords
Surgery, Emory University School of Medicine, Cerebral palsy · Malocclusion · Dentofacial
Atlanta, GA, USA deformity · Orthognathic surgery · Distraction
e-mail: Stephanie.Drew@Emory.edu; Tim.C.
Jaeger@Emory.edu osteogenesis

https://doi.org/10.1007/978-3-319-74558-9_80
1106 J. A. Napoli et al.
Introduction of CP, a subtype that affects 70–80% of all

patients diagnosed with CP. In the athetoid and
Skeletal facial deformation and malocclusion ataxic clinical subtypes of CP, deep overbite is
are commonly found in children with cerebral more frequently noted (Carmagnani et al. 2007).
palsy. The effects of cerebral palsy (CP) on Other facial deformities, such as orofacial clefts,
dentofacial development have long been known, are also slightly more common in patients diag-
evaluated by Chalmers Lyons as early as the nosed with CP. These congenital malformations
1950s (Lyons 1956). Skeletal facial deformations occur at 2.9–4.2 times the rate seen in the general
represent abnormalities in the position, size, population (Garne et al. 2007; Pharoah 2007).
and/or shape of the facial bones. Malocclusion
represents disharmony in the relationship of
upper and lower teeth. Malocclusions may be Etiology
skeletal or dental in nature. Thus, the cause may
be related to malposed teeth, a malposed or mis- The pattern of dentofacial deformity seen in
shapen maxilla or mandible, or a combination patients with cerebral palsy has genetic, congeni-
thereof. These types of deformities may create tal, and developmental causes. Indeed, part of
functional impairment as well as problems with the evidence supporting a prenatal etiology in
facial cosmetic appearance. The functional defi- the majority (70%) of CP is the observation that
cits can be debilitating, leading to issues with congenital anomalies such as cleft lip and palate
mastication, respiration, speech, and communica- are more frequently found in children with
tion. They may also contribute to drooling and CP. Other possibilities include a common genetic
difficulty with oral hygiene. or prenatal pathogenic mechanism linking the
The exact pattern of dentoskeletal facial defor- two. To date, the association between CP and
mity that occurs in cerebral palsy seems to vary orofacial clefts remains unclear(Garne et al.
based on the patient’s classification of motor 2007; Pharoah 2007).
impairment. The less muscle control they have, Consensus is lacking regarding which
the more significant the bone deformations that factors contribute most to facial deformity and
develop. The degree of orofacial motor impair- malocclusion in patients with CP, though a prev-
ment may be objectively described with the alent explanation is classically described by
Orofacial Motor Function Assessment Scale Dr. Melvin Moss’ functional matrix theory as
(OFMFAS), a classification system that describes presented in 1962 (Moss 1962). Essentially,
a patient’s function in regard to specific orofacial Dr. Moss stated that “form following function”
motor tasks (Santos et al. 2005). As shown in will dictate the skeletal growth pattern. By this
Table 1, this system categorizes functional status hypothesis, functional alterations in orofacial
by very slight impairment, slight impairment, musculature translate to problematic patterns of
moderate impairment, and severe impairment. dental and skeletal growth (Edvinsson and
The facial skeletal deformation most fre- Lundqvist 2015; Marinez-Mihi et al. 2014;
quently encountered in patients with CP is a Carmagnani et al. 2007). The functional alter-
long face in the vertical dimension with class II ations seen most commonly in cerebral palsy
molar relationship (retruded mandibular molars), involve abnormal muscle tone, movements,
apertognathia (anterior open bite), and increased habits, and posture.
dental overjet (maxillomandibular incisal ante- Suckling is an important determinant factor
roposterior discrepancy) (Martinez-Mihi et al. of neonatal and infant facial growth. It requires
2014; Miamoto et al. 2010). See Figs. 1a–h activation of the facial musculature in order to
and 2a–d. Additionally, the maxilla may be nar- generate the negative pressure needed for effec-
row creating a “high” palatal vault (Fig. 3a, b) tive aspiration of milk from the breast. The
and possibly bilateral posterior crossbite. This lips are used to form a tight seal, while the masti-
presentation often occurs with the spastic subtype catory and tongue muscles are used to initiate
77 Management of Skeletal Facial Deformation and Malocclusion in Cerebral Palsy 1107
Table 1 Orofacial Motor Function Assessment Scale 32 to 41 implies slight impairment, and 42 implies very
(OFMFAS) by Santos et al. (2005): A score of 19 implies slight impairment
severe impairment, 20 to 31 implies moderate impairment,
1. Jaw mobility Subtotal:
a) voluntary jaw opening

yes = 2 no = 0 unable to determine = 0
b) jaw opening
midline = 2 right / left deviation = 1 inconsistent = 0
c) opening against resistance
normal / adequate = 2 weak = 1 unable to determine = 0
d) closing against resistance
normal / adequate = 2 weak = 1 unable to determine = 0
2. Voluntary jaw protrusion Subtotal:
a) yes = 2 no = 0 unable to determine = 0

b) midline = 2 right / left deviation = 1 inconsistent = 0
3. Voluntary lateral jaw movements Subtotal:
a) right
b) right
c) presence of involuntary jaw movements during jaw lateral movements
yes = 0 no = 2
4. Rapid coordinated jaw movements Subtotal:
a) tooth tap
present = 2 slow/slows with time/irregular/erratic = 1 unable P/D = 0
b) lateral jaw excursion
present = 2 slow/slows with time/irregular/erratic = 1 unable P/D = 0
5. Voluntary facial movements Subtotal:
a) show teeth
symmetrical = 2 right / left weakness = 1 unable P/D = 0
b) pucker lips
symmetrical = 2 right / left weakness = 1 unable P/D = 0
swallowing. These muscles either directly or indi- influence. As a specific example, tension in the
rectly have insertions on the periosteum through sphenomandibular ligaments during suckling
which they elicit a functional remodeling movement is found to stimulate the growth
and maturation of the skeleton. Proper skeletal of the horizontal mandibular ramus in the sagittal
growth is dependent upon this functional plane (Festila et al. 2014).
Fig. 1 (a) shows the frontal profile at repose of a 17-year- the hyperextended head posture. (d, e, f) show the patient’s
old male patient with cerebral palsy. Note the long facial dentition and malocclusion. (g) shows the lateral cephalo-
appearance and mentalis strain indicative of lip incompe- metric radiograph and retrusive lower facial growth pattern
tence. (b) shows the patient’s frontal profile with smiling. (“clockwise” growth). (h) shows the patient’s dental pan-
Note the dental crowding and apertognathia (anterior open oramic radiograph with right and left sides marked
bite). (c) shows the patient’s lateral profile at repose. Note
Aspects such as decreased perioral muscle life (Oliveira et al. 2011). This finding has been
tone, decreased masticatory muscle tone, and demonstrated in the general population as well. In
decreased tongue movement are known to cause a study of 1303 healthy 5-year-old children,
sucking difficulties (Carneiro et al. 2017). Even exclusive breastfeeding until 6 months of age
children with very mild CP may show evidence was associated with lower rates of overbite, over-
of oral-motor involvement and reduced functional jet, crossbite, and moderate to severe malocclu-
feeding skills (Wilson and Hustad 2009; Gisel sion (Peres et al. 2015).
et al. 2000). As such, these children tend to be The relationship of breastfeeding with
breastfed for a shorter period of time (Carneiro dentoskeletal alignment may have to do with
et al. 2017). Studies in children with cerebral the greater rigidity of artificial nipples on feed-
palsy have demonstrated the inverse correlation ing bottles causing altered growth patterns
between breastfeeding and development of mal- (Oliveira et al. 2011). Moreover, it has been
occlusion. In one such study, those patients who proposed that bottle-feeding is less active and
breastfed for less than 6 months or not at all had less stimulating on a child’s facial musculature.
statistically greater rates of apertognathia later in The vertical positioning of the bottle requires
Fig. 2 (a–b) show a 55-year-old male with cerebral palsy dental panoramic radiograph with generalized caries and
and intellectual handicap. (c) shows the severity of his periodontal bone loss. This patient required extraction of
dentoskeletal deformity in the sagittal plane. His mandible multiple teeth. Due to his skeletofacial deformity and air-
is hypoplastic and retrognathic; his maxilla is hyperplastic, way risk, the procedure was performed in the operating
and his dental overjet is excessive. As such, he has diffi- room under general anesthesia rather than in the office
culty incising a bolus of food. (d) shows the patient’s initial under IV sedation
Fig. 3 (a) Frontal view

showing narrow maxilla in
16-year-old female with
cerebral palsy. (b) Palatal
view of same patient
less negative pressure to produce milk. This, in Much like bottle-feeding, nonnutritive sucking
turn, leads to a functional alteration in lip tone habits can be of detriment to facial skeletal devel-
and oromandibular movement, negatively opment in patients with cerebral palsy. These are
affecting facial skeletal development (Festila defined as the sucking patterns of children not
et al. 2014). used for feeding but for psychological comfort.
Nonnutritive sucking habits commonly include Postural differences in patients with cerebral
digit sucking and pacifier use. Although nearly palsy further contribute to the skeletal development
universal in infants, most children spontaneously problem. Martinez-Mihi et al. in 2013 evaluated the
discontinue these habits in the first years of life. way patients with CP hold their heads. Based upon
When present for 24 months or more, these habits their review of 44 adult patients, they concluded
are associated with a twofold greater chance that neuromuscular functional alterations present
of apertognathia later in life (Oliveira et al. characteristic postural changes. Most commonly,
2011). Children with cerebral palsy seem to they found that their patients tend to hold their
retain these habits at a rate higher than the gen- heads in a forward hyperextended posture. Individ-
eral population. Studies have reported rates of uals who adopt a forward or hyperextended resting
nonnutritive sucking as high as 87% in children head position present a greater craniofacial angle
with CP ages 3–12 (Carneiro et al. 2017). If these versus those who adopt a flexed resting head
habits continue into the stage of skeletal matu- position. See (Fig. 4). Mechanically, this causes
rity, they become irreversible and may require stretching of the lower facial soft tissues and
orthodontic and/or surgical intervention for retrusive forces upon the skeleton. The pull of cer-
correction. vical fascia would favor posterior rotation along the
In individuals with CP, where neurologic mandibular hinge axis (also termed clockwise rota-
maturation is delayed or nonexistent, parafunctional tion given the appearance on a lateral cephalogram).
habits may develop and persist as a result of imma- Instead of growing anteriorly, the mandible grows
ture behavioral or sensorimotor patterns. Abnormal vertically. This gives the patient a long lower facial
tongue posture such as tongue thrust (anterior third, increased overjet, and apertognathia. Com-
tongue interposition) is more likely to develop and pensatory supraeruption of the molars may occur
continue until adulthood. Habitual object biting on to prevent loss of occlusal contact (Martinez-Mihi
items such as pencils, cloth, or toys is more com- et al. 2014; Fulford and Brown 1976).
mon. The relevance of these activities on the child’s Multiple causative factors have been described
skeletal development is dependent upon the specific for alterations in the sagittal dimension of growth,
mechanism of habit. Tongue thrust causes flaring but few authors have described causative factors
and protrusion of the anterior teeth with
apertognathia (anterior open bite). Chronic habitual
object biting causes malocclusion, including
apertognathia, and may cause dental trauma
resulting in damage to the teeth (Ortega et al. 2007).
Oral breathing has been found to be far
more common in patients with CP and is inde-
pendently associated with development of skele-
tal deformity and malocclusions. Oral breathing
has consequences on atypical lingual positioning.
This, in turn, affects growth patterns similarly
to habitual tongue thrust. Oral breathing seems
to occur as a compensatory means of oxygen
intake in patients who possess insufficient respi-
ratory muscle strength. It may be exacerbated
by the use of medications that further depress
respiratory strength and endurance. Among these
are benzodiazepines and antispasmodics, medica-
tions commonly used to treat seizures and spas-
ticity in CP (Castilho et al. 2017; Bakarcic et al. Fig. 4 Same patient as in 3a, b. Note neck support
2015; Martinez-Mihi et al. 2014). required
for development of asymmetry in the cerebral malocclusion (retrognathism or prognathism,

palsy patient population. Interestingly, one paper respectively) have decreased chewing efficiency.
did compare oral asymmetries with asymmetry Severe malocclusion may increase meal times
of function in the trunk and extremities of patients and lead to accidental biting of the cheek and
with CP (Haberfellner and Richter 1980). They tongue. The bolus of food that is not properly
found that patients with asymmetric muscular masticated increases the potential for choking
function had higher rates of oral asymmetry. and airway obstruction.
Furthermore, they demonstrated a concordance Temporomandibular joint disorders can
of functional preference and oral asymmetry further complicate the masticatory system of
in the majority of cases. The patient’s dominant patients with cerebral palsy. The spastic nature
side of voluntary function more commonly of CP inducing clenching and grinding habits
matched the side of aberrant oral findings than may cause pain and limit range of motion. Joint
would occur with chance alone. This result signs such as limited opening and excursive
supports the explanation that alteration of function movements, limited bite force, and noise with
drives dentoskeletal deformity formation in function occur more commonly in patients with
patients with CP. CP (Matsui et al. 2016; Bartkevicius and Santos
To add to the growth disturbances faced 2015; Miamoto et al. 2011; Santos et al. 2010;
by these patients, cerebral palsy patients have Ortega et al. 2008). The incidence of temporo-
higher rates of decay, periodontal disease, and mandibular joint pain in patients with cerebral
tooth loss (Pini et al. 2016; Sinha et al. 2015; palsy is not known as studies have been unable
Miamoto et al. 2010). When teeth are lost, occlu- to properly assess pain largely due to communi-
sal forces are redistributed to the remaining teeth. cation barriers.
Teeth also tend to migrate or supraerupt to fill Lip competence may be inadequate due to
the void left by lost teeth. Shifting of occlusal both poor muscle tone and skeletal deformation.
forces and teeth can worsen malocclusion and Drooling and spillage of food from the mouth
dentofacial deformity. will occur if the lips cannot close during eating.
Swallowing mechanics, often problematic
to begin with due to gastrointestinal dysfunction
Functional Deficits and Impact in patients with CP, may be adversely affected
by dentoskeletal deformity. The risk of aspiration
An individual’s facial appearance is one of their is great in these patients and predisposes them
most obvious characteristics and, in essence, to recurrent lung infections, including pneumonia
serves a function as one relates to other individ- and reactive airway disease.
uals. A face that deviates from the norm becomes In addition to the oromotor effects on
a stigma, and facial disfigurements are judged speech, dental and skeletal malposition may
to be among the least desirable “handicaps.” The also have a deleterious effect on speech articula-
impact of facial disfigurement can negatively tion compounding intelligibility. Patients with
impact situations such as relationships, education, apertognathia may have distortion of sibilants /s/
and employment (Cunningham 1999). Worse, and /z/ due to the tongue protrusion through
dentoskeletal deformity can be a root of social the open bite. Bilabial sounds /p/, /b/, and /m/
discrimination that leads to further negative may be impeded when unable to approximate
stereotyping of individuals with special needs the lips due to severe lip incompetence. In severe
(Rada et al. 2015). cases, where one is unable to properly close
Beyond one’s facial appearance, masticatory the lower lip against the upper teeth, production
function is also impacted by dentoskeletal of labiodental fricatives /f/ and /v/ is impaired
deformity (Schwartz et al. 2003). Patients with (Vallino and Thompson 1993).
apertognathia are unable to properly incise Airway issues are also covered elsewhere,
a bolus of food. Patients with a class II or III but relevant to this discussion on facial skeletal
deformity, in patients with severe mandibular trauma, and detrimental orofacial habits (non-
retrognathia, the hypopharyngeal airway may nutritive sucking, tongue thrust, object biting,
become obstructed by the tongue base and cause etc.)
or contribute to obstructive sleep apnea. Although cerebral palsy is a heterogeneous
group of disorders presenting with varied degrees
of spasticity, dystonia, contractures, weakness,
Assessment and coordination difficulties, multiple functional
classification systems have attempted to describe
Due to the profound developmental contribution the severity of disability in a standardized fashion
to skeletofacial deformation and due to the (Paulson and Vargus-Adams 2017). Developed
increased burden of dental disease in the cerebral by Eliasson et al. (2006), the Manual Ability
palsy patient population, the importance of Classification System (MACS) is a simple,
early dental evaluation cannot be overstated. The five-point ordinal classification system for
current recommendation from the American children 4–18 years of age that can be used to
Academy of Pediatric Dentistry is that all children classify a child’s typical use of both hands and
receive an initial dental evaluation when the upper limbs (Paulson and Vargus-Adams 2017).
first tooth erupts and no later than 12 months of See Table 2.
age (American Academy of Pediatric Dentistry The Communication Function Classification
2013). This comprehensive oral examination System (CFCS), developed by Hidecker et al.
includes an assessment of the patient’s general in 2011, is a validated assessment of everyday
health, growth, behavior, habits, facial hard communication ability. The CFCS is a five-point
and soft tissues, oral hygiene, caries risk, devel- ordinal classification system designed to be anal-
oping occlusion, and temporomandibular joint ogous to the MACS. This system assesses both
function. how information is expressed and how it is
In cerebral palsy patients of all ages, providers received (Paulson and Vargus-Adams 2017).
should assess for any concerns regarding facial See Table 3.
appearance, issues with chewing or feeding, The Orofacial Motor Function Assessment
occurrence of drooling or spillage of food, facial Scale (OFMFAS) is a measure of the degree
pain, temporomandibular joint range of motion, of orofacial motor impairment, a finding in
speech impediments, mouth breathing, obstruc- cerebral palsy that is especially pertinent to the
tive sleep apnea or poor sleep quality, dental dentofacial treatment team (Edvinsson and
Table 2 Manual Abilities Classification System (MACS)*

MACS 1 Able to handle objects easily, with the possibility of some limitations not restricting independence in daily
activities
Brushes and flosses teeth adequately
MACS 2 Decreased level of performance when handling objects; the performance may be slower and may be
impacted by asymmetric hand function. The individual remains independent in daily activities
Oral hygiene is reduced. Orthodontics and oral appliances remain good options
MACS 3 Handles objects slowly and often with limited success, requiring assistance or setup for activities. Not all
activities may be completed independently
Poor oral hygiene, possibly requiring caregiver assistance Conservative orthodontic treatment is possible
MACS 4 Needs continuous support and assistance or the use of adapted equipment to complete only a part of a daily
activity, with an inability to complete the full activity
Caregiver assistance is needed for basic oral hygiene. Limited orthodontic treatment is possible but difficult
to achieve
MACS 5 Does not handle objects and may be able to participate minimally with simple movements or may require
total assistance
Caregiver dependent for dental needs. Conventional orthodontics not advised
*A modified system, Mini-MACS, is meant for children 0–4 years of age.
Table 3 Communication Function Classification System (CFCS)

CFCS 1 Effective sender and receiver with unfamiliar and familiar partners
Communicates symptoms to the healthcare team and may participate in care-related decision-making
CFCS 2 Effective communicator, but the pace of communication is slower
Communicates symptoms to the healthcare team and may participate in care-related decision-making
CFCS 3 Effective sender and receiver with familiar partners
Communicates symptoms to family or caregivers
CFCS 4 Inconsistent sender and/or receiver with familiar partners
Has difficulty communicating symptoms such as pain
CFCS 5 Seldom effective sender or receiver even with familiar partners
Tooth or TMJ pain may first manifest as refusal to eat
Lundqvist 2015; Santos et al. 2005). This system neurologists, dieticians, and speech/language
gives a minimum score of 0 and a maximum pathologists.
score of 60 based on findings such as jaw range Therapeutic access may be complicated by a
of motion, tongue and lip movements, oral number of factors. Cooperative behavior can be
reflexes, and voluntary facial expressions. limited by intellectual disability or uncontrolled
Each of 30 subitems is graded on a Likert scale orofacial, body, and limb movements as a result
ranging from 0 (unable to perform or determine; of physical disability. Sedation may be necessary
inconsistent) to 2 (performed adequately). The to create a relatively motionless state for the
total scores are added together to give the final patient (Rada et al. 2015). In patients with severe
score out of 60. A score of 19 implies severe limitations, sedation or general anesthesia may
impairment, 20 to 31 implies moderate impair- be necessary for physical examination and record
ment, 32 to 41 implies slight impairment, and acquisition. Typical dentofacial records include
42 implies very slight impairment (Santos intraoral and extraoral photographs, dental
et al. 2005). See Table 1. impressions (or when available, intraoral scan-
The specialist managing dentoskeletal defor- ning) for fabrication of three-dimensional models
mities in a patient with cerebral palsy is advised of the dental arches, and plain or CT imaging
to carefully appraise the patient’s functional abil- radiographs.
ity in such terms, as these factors will determine When sedation is utilized, the choice of
what treatments are and are not possible for pharmacologic technique should be the simplest
a given patient and arrive at an appropriate treat- and safest available that is appropriate for
ment plan. For example, patients may not be can- the specific task to be performed for each individ-
didates for certain interventions if their mouth ual patient (Rada et al. 2015). All efforts should be
opening is limited due to spasticity, if their manual made to make efficient use of time under sedation,
dexterity precludes appliance use and good oral which may mean combining such tasks as
hygiene, or if their communication ability pre- examination, record taking, dental prophylaxis,
vents necessary feedback in regards to factors dental rehabilitation, and orthodontic or surgical
such as pain. care during the same anesthetic session. One
should avoid using sedation as the de facto tactic
to treatment but rather reserve sedation for the
Treatment most invasive procedures necessary. For example,
orthodontic appliances may be placed under seda-
Addressing the complex dentofacial deformity tion, but appliance adjustments may be made
commonly seen in CP requires a team approach. using nonpharmacological behavioral guidance
Specialists involved may include pediatri- techniques only.
cians, general or pediatric dentists, orthodon- The management of dentoskeletal deformity
tists, oral and maxillofacial surgeons, plastic in the cerebral palsy patient begins with anticipa-
surgeons, otorhinolaryngologists, anesthesiologists, tory guidance. This is the process of providing
practical, developmentally appropriate information Orthodontic management of patients with

about children’s health to prepare parents for sig- CP has been extensively documented (Castilho
nificant physical, emotional, and psychological et al. 2017; Abeleira et al. 2016; Cifter and
milestones during growth (American Academy of Cura 2016; Rada et al. 2015; Iscan et al.
Pediatric Dentistry 2013). Part of this process is 2013; Becker et al. 2004). The ability of patient
counseling parents regarding nutritive and non- and parents to cooperate for standard orthodon-
nutritive sucking habits, parafunctional habits, tic treatment in a child is challenging but even
and hygiene habits to best guide future growth more so with the addition of CP. Conservative
and ensure healthy teeth and gums. orthodontic therapy is warranted to help with
Once a dental or skeletal deformity develops, facial skeletal growth and management of mal-
the severity and implications of the deformity occlusions in the mixed dentition once the diag-
must be determined. Based upon these factors nosis of malocclusion is made. Orthopedic
and the severity of the patient’s overall disability, manipulation of the maxillary and mandibular
a treatment plan may then be established. Treat- arches is possible in some cases with extraoral
ment may be orthodontic, surgical, or both. traction (headgear) and appliance therapy to
Figure 5 shows various pathways to establish reduce the overjet of the deformation. The
a functional occlusion. No differences in the erup- twin block appliance is one such device that
tion pattern of primary or permanent teeth have uses interocclusal acrylic to slide the mandible
been described in patients with CP compared into a more anterior position during function.
to the general population, so the timing of ortho- This device may be cemented or removable
dontic and/or surgical treatment is generally depending on the patient’s hygiene, manual
similar (Sabuncuoglu and Ozcan 2014). dexterity, and other factors.
Fig. 5 Treatment algorithm for dentofacial deformity

The challenges orthodontists face when necessary for orthognathic surgery. Preoperative
treating patients with CP are related to several anesthetic considerations include the degree
unique features. It is known that many patients of spinal deformity, airway patency and reactivity,
with CP have parafunctional movements of pulmonary disease, seizure history, and neuro-
the jaw including clenching, bruxism, and object muscular status. In most orthognathic surgery
biting. The grinding of the teeth (bruxism) may procedures, nasal endotracheal intubation is nec-
be so severe that the patient may require occlusal essary to allow intraoperative verification; the
splints to protect the dentition from abnormal teeth and jaws are placed into proper occlusal
wear. Bruxing will increase the risk of failure alignment.
of orthodontic therapy because the patient may The class II skeletal pattern with or without
shear the bonded brackets from the teeth. Para- apertognathia has several variations. When the
functional habits may directly or indirectly result dental component of the occlusion develops in
in bonding failure. Patients may inadvertently such a way to “compensate” for skeletal malfor-
swallow or worse, aspirate, a bracket due to poor mation, the compensated maxillary teeth may
muscle control. Use of acrylic trays to help align have a two-plane occlusion and transverse
teeth rather than conventional braces may solve (width) deficiency. The transverse maxillary prob-
two problems; the trays may be able to be lem may be relative – caused by the position of
constructed to help protect the teeth from bruxing the maxilla as it relates to the mandible – or
while moving the dentition into alignment. Alter- absolute. The compensated occlusion of the man-
natively, metal bands firmly fixed to the teeth dible may exhibit anteriorly flared incisors and
rather than bonded brackets will avoid displaced deep curve of Spee or anterior-posterior occlusal
brackets due to bond failure. Bands for anterior curvature.
teeth often need to be specially ordered from Preparation for corrective jaw surgery is best
the manufacturer (Rada et al. 2015). done when the dentition is aligned with orthodon-
Oral hygiene is often an issue for these tic treatment to be in the best position possible
children. Permanently cemented appliances for long-term stability after the maxilla and man-
will increase the difficulty of plaque and debris dible have been surgically repositioned. This
removal. A patient’s manual abilities should be is ideally achieved and referred to as orthodontic
considered (i.e., MACS classification) prior decompensation of occlusion prior to surgery, i.e.,
to application of an oral appliance that cannot placement of teeth in their ideal (rather than com-
be removed for cleansing. The oral hygiene pensated) position within alveolar bone. If the
of patients with cemented appliances should be transverse deficiency (width) of the maxilla is
carefully monitored to prevent caries or periodon- severe, the patient may require two stages of sur-
tal disease. gery to insure adequate width by using a surgi-
Orthognathic surgery is the surgical movement cally assisted palatal expansion to achieve this
of either the maxilla, mandible, or both bones goal (Fig. 6). However, in patients with CP, it
by creating osteotomies which allow the jaws to may be best to leave the patient in crossbite to
be placed in position for improved function and obviate the need for two general anesthetics. It
appearance. These procedures may be considered may be difficult to assess facial form for surgical
for patients if the skeletal deformation can be work-up in these patients, as head position may
corrected safely with the goal to provide a better not be stable due to muscle activity.
relationship of the dentition and if the result will For patients in whom conventional orthodon-
remain stable. These osteotomies require a 6- to tics is difficult or impossible, a “surgery-first”
8-week period of healing before a functional load or “surgery-only” approach may be adopted.
can be placed to ensure stability of the osseous A “surgery-first” approach involves surgical
correction. alignment of the skeleton before orthodontic
Patients need to be carefully screened to deter- alignment of the dentition. The major limitation
mine if they are candidates for a general anesthetic of this approach is that the postsurgical occlusion
Fig. 6 (a–d) Same patient

as Fig. 3. (a) Lefort I
osteotomy (short arrows)
and mid-maxillary
osteotomy (long arrow) for
surgically assisted rapid
palatal expansion (SARPE).
(b) Palatal view showing
expansion appliance.
(c) Midline dental gap
resulting from widening of
the maxilla after SARPE.
(d) Maxillary teeth have
been realigned within the
widened maxilla closing the
dental gap. Compare this to
Fig. 3a
may be more difficult to correct than if orthodon- masseter muscles during the initial healing phases
tics had been initiated before surgery. A patient’s of the surgery. A low dose of benzodiazepine may
suitability is dependent upon their preoperative also help with the bruxing habit. Use of sturdier
occlusion (Jeong et al. 2017; Hernandez-Alfaro hardware should be considered (Bock et al. 2006).
et al. 2014; Slavnic and Marcusson 2010). How- Other risks include incomplete occlusal correc-
ever, a study by Jeong et al. showed that tion, infection, intraoperative or delayed bleeding,
the average total orthodontic treatment time avascular necrosis of bone or teeth, nerve injury
is reduced from 22 months to 14.6 months with (specifically the second and third divisions of
this approach (Jeong et al. 2017). In other cases, the trigeminal nerve) with associated numbness
a “surgery-only” approach may be able to of the lips and/or tongue, and relapse with return
improve the skeletal and dental relationships of the skeletal malalignment.
while avoiding orthodontic treatment altogether. The airway in patients with cerebral palsy
While this will not necessarily achieve ortho- must also be assessed for the possibility of
dontic perfection, this may allow for an estheti- obstructive sleep apnea. In any patient with man-
cally acceptable and functional result. dibular hypoplasia and clockwise-rotated mandi-
When orthognathic surgery is being consid- bles, there is a possibility of airway obstruction at
ered to correct a skeletal malocclusion, the the level of the tongue base associated with man-
bruxing (clenching or grinding of the teeth) habit dibular hypoplasia. The soft tissues of the base of
becomes a potential barrier to bone ossification the tongue tend to fall back while sleep occurs,
at the osteotomy sites, thereby impairing healing. obstructing the airway with a smaller lower jaw.
The sites will be under stress due to the habitual While there may be a central component to the
clenching of the jaw and may encounter hardware apnea, corrective jaw surgery could be planned
failure or malunion. Consideration should be to optimize the opening of the airway anatomi-
given to the use of medications such as botulinum cally and decrease the overall incidence of
toxin to help decrease the activation of the obstructive episodes. When the airway
obstruction is due to mandibular hypoplasia and Cross-References

is identified during infancy or early childhood,
consideration should be given to mandibular ▶ Anesthesia in the Child with Cerebral Palsy
lengthening by distraction osteogenesis (Pre- ▶ Dental Hygiene for Children with Cerebral
ciado et al. 2004). When it occurs or is identified Palsy
when the facial skeleton is mature, conventional ▶ General Dentistry for Children with Cerebral
orthognathic surgery is considered. Poly- Palsy
somnography is the gold standard to diagnose ▶ Medical Evaluation for Preoperative Surgical
obstructive sleep apnea. It is necessary to test Planning in the Child with Cerebral Palsy
patients in order to properly document this ▶ Obstructive Sleep Apnea in Children with
issue both pre- and postoperatively, enabling Cerebral Palsy
one to assess the effectiveness of the surgical ▶ Postoperative Pain and Spasticity Management
procedure. in the Child with Cerebral Palsy
Postanesthesia management of these patients ▶ Speech, Language, and Hearing Practice Ele-
requires judicious use of narcotics so that they do ments in the Management of the Child with
not have respiratory depression. A postoperative Cerebral Palsy
course of stay in a surgical intensive care unit may ▶ Upper Airway Obstruction in the Child with
also be considered. Cerebral Palsy: Indication for
Temporomandibular joint disorders en- Adenotonsillectomy
compass a wide variety of conditions, and the
treatment modalities are equally as diverse.
Importantly, orthognathic surgery should not be Glossary of Terms
offered with the expectation to correct temporo-
mandibular joint disorders. In a meta-analysis Skeletofacial deformation Abnormalities in
by Al-Moraissi et al., the effect of corrective the position, size, and/or shape of the facial bones
jaw surgery on temporomandibular joint disor- Malocclusion “Bad bite,” misalignment of the
ders was found to be impossible to predict upper and lower teeth in relation to one another
(Al-Moraissi et al. 2017). Maxilla The upper jawbone as formed by the
fusion of two maxillary bones
Mandible The lower jawbone
Summary Orofacial Motor Function Assessment Scale
(OFMFAS) Quantitative scale for the assess-
The management of skeletofacial deformity and ment of oral-motor skills in children with cere-
malocclusion in patients with cerebral palsy bral palsy
must be tailored to each patient. Management Molar A posterior tooth with a broad, flat biting
is interdisciplinary, with dentofacial orthope- surface adapted for crushing and grinding, with
dics, orthodontics, and surgery as possible treat- most adults having three per quadrant of the
ment mechanisms. The key concept in selecting mouth
a treatment approach is to match the treatment Molar class relationship Malocclusion classifi-
with the patient’s severity of deformity, motiva- cation describing the relationship of maxillary
tion, and physical and emotional limitations. first molar cusps to mandibular first molar
Proper treatment of skeletofacial deformity cusps. In a class 1 (normal) molar relationship,
and malocclusion may result in an improvement the mesiobuccal cusp of the maxillary
of the patient’s quality of life by improving first molar occludes with the buccal
speech, chewing, breathing, and communica- groove of the mandibular first molar. In a
tion. The esthetic improvement may benefit the class II (retrognathic) molar relationship,
patient as well by increasing self-esteem and the mesiobuccal cusp of the maxillary
confidence. first molar occludes anterior to the buccal
groove of the mandibular first molar. In a class Tongue thrust A behavior pattern in which
III (prognathic) molar relationship, the tongue is habitually pushed between the
the mesiobuccal cusp of the maxillary first upper and lower front teeth
molar occludes posteriorly to the buccal Craniofacial angle The degree of flexion or
groove of the mandibular first molar. extension of the skull in relation to the cervical
Apertognathia “Anterior open bite,” a type of vertebrae
malocclusion characterized by premature Clockwise rotation Clockwise description of
occlusal contact of posterior teeth and absence lower facial anterior-posterior growth pattern
of anterior occlusal contact as seen on a lateral cephalogram or right-sided
Overjet Measurement of the extent of anterior- view of a patient’s face
posterior overlap of the maxillary central Lateral cephalogram A lateral facial plain film
incisors over the mandibular central incisors radiograph
Incisor An anterior tooth with a narrow biting Supraeruption Tooth migration in an occlusal
surface adapted for cutting, with most adults direction
having two per quadrant of the mouth Retrognathism A type of malocclusion char-
Orofacial cleft Congenital malformation of acterized by abnormal posterior positioning
the lip, palate, and/or face that occurs when of the mandible relative to the facial
tissues of the face fail to properly fuse during skeleton
development Prognathism A type of malocclusion character-
Functional matrix theory Theory of skeletal ized by abnormal anterior positioning of
adaptation first presented by Dr. Melvin Moss the mandible relative to the facial skeleton
in 1962, stating, “The origin, development and Temporomandibular joint disorder Any of
maintenance of all skeletal units are secondary, several related conditions affecting the mus-
compensatory and mechanically obligatory cles of mastication and temporomandibular
responses to temporally and operationally joint
prior demands of related functional matrices.” Lip competence Ability to create a closed mouth
Sphenomandibular ligament A thin band posture of the lips at rest
of tissue that spans from the lingula of the Sibilant consonant Hissing sound made by
mandible to the sphenoid bone of the skull, directing a stream of air along the palate with
one of the two extrinsic ligaments of the the tip of the tongue
mandible Bilabial consonant Sound made by stopping
Mandibular ramus The broad, vertically ori- airflow with upper and lower lip and then
ented processes of the mandible located releasing the air
between the mandibular angle and condyle on Fricative consonant Sound produced by forcing
each side of the face air through a narrow channel created by two
Overbite Measurement of the extent of vertical articulators placed close together (i.e., tongue
(superior-inferior) overlap of the maxillary and palate)
central incisors with the mandibular central Hypopharyngeal airway The portion of respi-
incisors ratory tract bounded by the base of tongue,
Crossbite A type of malocclusion characterized lateral pharyngeal wall, aryepiglottic folds,
by lateral misalignment of one or both dental and epiglottis
arches; i.e., teeth are too close to the cheek or Obstructive sleep apnea A breathing disorder
tongue that results in repeated temporary cessation
Nonnutritive sucking habit Habitual sucking or significant decrease in airflow during sleep
used not for feeding but for psychological comfort Manual Ability Classification System
Parafunctional habit Habitual behavior or (MACS) A five-point ordinal classification
functioning of a body part in a way other than system to describe a child’s typical use
the most common use of that body part of both hands and upper limbs
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System (CFCS) A five-point ordinal classifi- Pediatr Dent 35(5):148E–156E
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Part XVII
Anesthesia Management
Medical Evaluation for Preoperative
Surgical Planning in the Child 78
with Cerebral Palsy
Emily Fingado and David Pressel
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1124
Medical Evaluation/Optimization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1124
General . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1124
Neuro/Developmental . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1125
Respiratory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1125
Gastroenterology/Nutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1126
Cardiovascular . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1126
Renal/Urologic/Genitourinary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1127
Endocrinology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1127
Hematology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1127
Psychiatric . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1127
Medications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1128
Laboratory Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1128
Miscellaneous . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1128
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1128
Case Histories . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1129
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1130
Abstract
Preoperative “clearance” by a patient’s physi-
cian is a long-established practice of question-
able benefit, particularly for overall healthy
E. Fingado (*) patients. This clearance has traditionally been
Nemours/Alfred I. duPont Hospital for Children, completed by a member of the anesthesiology
Wilmington, DE, USA team. However, as patients have increasing
e-mail: emily.k.fingado@nemours.org medical complexity, a preoperative evaluation
D. Pressel by a physician with expertise in inpatient med-
Capital Health, Trenton, NJ, USA icine and postoperative care may be beneficial
e-mail: dpressel1776@gmail.com

https://doi.org/10.1007/978-3-319-74558-9_82
1124 E. Fingado and D. Pressel
(Vazirani et al. J Hosp Med 7:697–701, 2012). Ferrari 2004). Helping the child and family/care-
A growing body of literature demonstrates giver anticipate what to expect with the upcoming
benefits for medically complicated patients in surgery is an important part of the preoperative
having preoperative evaluation and manage- evaluation.
ment of medical issues by a physician knowl- An ideal method to evaluate these children is
edgeable in the patient’s underlying disease through a co-management approach in which a
and the proposed procedure. There are well- pediatric medical provider along with members
established cases of adult programs evaluating of the surgical and anesthesiology teams collabo-
surgical patients prior to their scheduled pro- ratively evaluates the patient prior to surgery
cedure and subsequent lower mortality and (Cloake and Gardner 2016). Timing of this
shorter length of stay (Vazirani et al. J Hosp evaluation will depend on the procedure and
Med 7:697–701, 2012). These evaluations can medical complexity of the patient. The more com-
improve documentation of medical diagnoses plicated the patient or the proposed surgical pro-
and comorbidities as well as optimization cedure, the earlier the preoperative evaluation
of those comorbidities through interventions should occur (see Table 1). Concerns identified
geared toward reducing perioperative by a provider at any preoperative evaluation
risk (Wijeysundera et al. Arch Intern Med should prompt communication within a multi-
170:1365–1374, 2010). It has been demon- disciplinary team.
strated that a preoperative evaluation is
associated with a high rate of preoperative
recommendations to the family and/or care- Medical Evaluation/Optimization
giver (Rappaport et al. J Hosp Med 8:684–8,
2013). We review recommendations for preop- General
erative management in patients with underly-
ing cerebral palsy. A thorough medical evaluation, including a
complete medical history and examination, is
Keywords essential to providing comprehensive pre- and
Cerebral palsy · Preoperative evaluation · postoperative care for children with cerebral
Medical evaluation · Medical clearance palsy who are undergoing major surgery. All
aspects of a child’s medical care, medications,
and home therapies/needs should be addressed.
Introduction Any recent illnesses should be identified (upper
respiratory, urinary tract infection, etc.) as those
Children with cerebral palsy (CP) undergo sur- illnesses may impact a scheduled procedure. This
gery more frequently than their otherwise healthy will ensure that patients with cerebral palsy are
peers. The level of medical complexity and the medically optimized prior to surgery.
proposed surgical procedure should guide the
preoperative evaluation of a child with cerebral
palsy. Clearance to proceed with the surgical case Musculoskeletal
has traditionally been made by the anesthesiolo-
gist, surgeon, and family/caregiver. When pri- A discussion of a child’s musculoskeletal condi-
mary care providers (PCPs) have been asked to tions should occur during a preoperative evalua-
provide preoperative clearance, their role has tion. The type of cerebral palsy should be
been less clear. The goals for a preoperative discussed and the use of any assistive devices
evaluation should be to medically optimize noted. Any significant fracture history may indi-
patients in order to reduce morbidity and mortality cate poor bone health or vitamin D deficiency
associated with the procedure and to increase prompting screening of vitamin D, calcium,
the quality of care provided (Roizen 2000 and and magnesium levels and supplementation if
78 Medical Evaluation for Preoperative Surgical Planning in the Child with Cerebral Palsy 1125
Table 1 Timing of proposed preoperative medical evalu- problems in addition to their diagnosis of
ation in relation to the planned procedure (based on the cerebral palsy. It should be noted if the child
authors’ current practice)
has epilepsy, development delay, or underlying
Time of medical behavioral issues. Any of these may be exacer-
evaluation (in weeks prior
Planned procedure to surgical date) bated by the anesthetic used, NPO status, or post-
Posterior spinal fusion 6–8 operative pain. If a patient has epilepsy, the type
Single event multiple level 6–8 of and frequency of seizures should be noted,
procedure as well as when the last seizure occurred. The
Hip reconstruction 6–8 medications a child takes for epilepsy should
(VDRO, Dega be documented, and adverse effects of those
osteotomies, FDRO, etc.)
medications as they may pertain to the periopera-
Insertion of a baclofen 4–8
pump and intrathecal
tive period should be identified. If the surgical
catheter procedure will result in a prolonged period
Foot reconstruction 4–6 of bowel rest, consultation with the child’s neu-
Soft tissue 4 (or at the discretion of rologist will help determine the best antiepileptic
the provider) medication if the child’s routine medication can-
Miscellaneous Timing will vary based on not be used in a parenteral route. Any spasticity or
the proposed procedure
dystonia should be included in a preoperative
and institutional standards
of care evaluation as these issues may be exacerbated by
postoperative pain, and a pain management plan
should include either scheduled or as needed
indicated. Care should be taken to address the muscle relaxants.
functional status of a patient leading to surgery, A discussion with caregivers regarding
as this will allow any postoperative needs to be communication abilities of a patient with
addressed. Assessment of the child’s ability to cerebral palsy is essential in order to provide
perform activities of daily living is important, the best pre- and postoperative care. It is helpful
as their level of independent function or needs to determine how the child or young adult
may change in the postoperative period. Any indicates pain, discomfort, and comfort, as this
assistive devices or equipment may need to be information can assist in caring for a patient
adjusted postoperatively based on the type of postoperatively. It is important to recognize
surgery and rehabilitation planned. Children that a child with cerebral palsy may be of
who were ambulatory may experience some age-appropriate intellectual ability but have diffi-
temporary loss of mobility during their postoper- culty communicating.
ative convalescence, and caregivers should be
made aware of this prior to surgery. In addition,
issues such as car transport, the presence of stairs Respiratory
in the home, and bathroom use need to be
addressed. The child’s physical and occupational Many patients with cerebral palsy also have an
therapists, as well as case managers and school, underlying respiratory medical condition. This
need to be apprised of the upcoming procedure, may be independent of their cerebral palsy
and any needed equipment or modifications or secondary to their underlying neuromuscular
should be addressed. disease. Patients with cerebral palsy often have
underlying medical conditions such as poor upper
airway tone with difficulty handling secretions,
Neuro/Developmental which can lead to recurrent aspiration. Patients
may have ineffective airway clearance or an
A child with cerebral palsy may be at a higher ineffective cough and may be on an airway
risk of having other concomitant neurologic clearance regimen on a daily basis. Thoracic
cage deformities from neuromuscular scoliosis increased risk of postoperative complications

may affect their pulmonary function and can be (Cloake and Gardner 2016). Additionally, there
important, not just for intraoperative ventilation is a higher mortality rate in children with CP with
but postoperatively may result in increased risk a weight for age below the 20th percentile com-
of atelectasis, pneumonia, or difficulty with pared with those falling in the 20th to 80th
secretion management. If the child is followed percentile (Brooks et al. 2011). Optimal nutrition
by a pulmonologist, the specialist’s input can be and weight will assist in healing and recovery
sought for perioperative planning. Providers during the postoperative period. If concerns
should consider increasing the patient’s baseline regarding malnutrition or a child’s nutritional sta-
airway clearance regimen prior to surgery. An tus are identified, caloric or protein intake can
assessment of risk factors for obstructive sleep be increased, and an evaluation with
apnea (if not already diagnosed) should be taken, a registered dietician is indicated.
and if necessary, an evaluation from a pulmonol- If a patient is dependent on tube feedings for
ogist should occur prior to surgery. nutrition, it should be documented what formula
For children and young adults with home a patient receives and how these tube feeds are
oxygen requirements, it should be documented administered. Gastrointestinal reflux, delayed
what pulmonary care the patient receives at gastric emptying, and constipation are common
baseline (nasal cannula, positive pressure ventila- in patients with cerebral palsy and should be
tion, or any use of assistive technologies noted. Bowel regimens should be increased in
for enhanced pulmonary toilet), and if there is a the immediate perioperative period to assist in
sick day plan in place, it should be implemented decreasing postoperative constipation and/or
perioperatively. Certain patients can have airway obstipation related to decreased mobility after
abnormalities or limited neck mobility, and surgery and to narcotics used to treat pain.
advanced airway imaging may be indicated
(Theroux et al. 2012). Patients with significant
respiratory disease may need to be monitored Cardiovascular
postoperatively in an intensive care unit.
While less common than other comorbidities
associated with cerebral palsy, a history of heart
Gastroenterology/Nutrition disease is important to recognize prior to a patient
undergoing a general anesthetic. A cardiac history
Many patients with cerebral palsy may have asso- should include any history of arrhythmias, struc-
ciated medical issues that relate to the gastrointes- tural heart defects, or issues with hypertension
tinal tract. Children with cerebral palsy and medical or hypotension. A routine preoperative electrocar-
complexity may have difficulty with feeding or diogram or echocardiogram is not indicated in
inadequate nutritional intake leading to malnutri- those patients without history or exam findings
tion. Patients may eat a regular diet by mouth or concerning for an underlying cardiac defect
need some dietary modification in terms of texture (DiCindio et al. 2015). However, in certain
and time needed to feed, or they may require nutri- instances, preoperative assessments of cardiac
tion via an enteral feeding tube. Malnutrition can be function with electrocardiograms and echocardi-
indicated by low body mass index (BMI), low ography may be indicated. Providers should use
weight to height percentile (both of which may be their clinical judgment in determining this need.
very unreliable due to the difficulty of obtaining an If a patient has an underlying cardiac defect or
accurate height in a child with contractures due to condition that may predispose them to cardiac
their CP), or markers such as low serum albumin dysfunction, a dedicated preoperative cardiology
or prealbumin. Malnourished patients are at evaluation should be guided by the child’s cardi-
higher risk for prolonged length of stays and ologist or anesthesiologist, for example, in those
with muscular dystrophies. In patients who are endocrine disorders such as diabetes mellitus,
followed by cardiology, it is prudent to ensure diabetes insipidus, and hypo- or hyperthyroidism,
the patient has had a recent cardiac evaluation may be comorbidities for patients with cerebral
and a discussion should be had regarding the palsy. A perioperative management plan, in con-
need for cardiac specialty anesthesiology. sultation with the child’s endocrinologist, is an
essential part of perioperative planning. It may
be necessary to discuss pre-admitting a patient
Renal/Urologic/Genitourinary for intravenous fluid and electrolyte management
while NPO for a procedure. Patients with adrenal
The child with cerebral palsy may have genitouri- insufficiency will likely need perioperative stress-
nary issues particularly related to infection dose steroids. The duration of continuing the post-
and continence. Providers should identify any operative stress-dose steroids will be determined
underlying renal disease along with its manage- by the magnitude of the procedure along with any
ment. A history of urinary tract infections potential complications.
should prompt obtaining a preoperative urinalysis
and urine culture. This will allow treatment of
any urinary infection prior to surgery to Hematology
prevent unnecessary postponement or increased
morbidity from an untreated urinary tract infec- A detailed history regarding any bleeding or
tion. Providers caring for a patient with metabolic clotting disorders a child or young adult may
conditions or diabetes insipidus (central or have should be obtained as part of a routine
nephrogenic) should develop a plan for intrave- perioperative evaluation. A patient with a
nous fluid (IVF) management in conjunction with known hematologic diagnosis should have a
the patient’s subspecialist. Patients may need to perioperative management plan in place with
be admitted preoperatively for IVF and electrolyte the assistance of their specialist. If the child
management (often needing insurance prior does not have a known diagnosis but caregivers
authorization) if there are hydration or metabolic report difficulty with bleeding or clotting, a con-
concerns when a patient is NPO. sultation with a hematologic specialist should be
In female patients, a menstrual history should considered. Likewise, if there is a strong family
be taken, including whether or not the patient is history of hematologic disorders, a consultation
taking any medications for hormonal regulations may need to occur prior to a planned surgical
of her menstrual cycle. Families and caregivers procedure. Directed donor blood can be arranged
should be counseled that these medications may for patients undergoing procedures with antici-
be stopped in the perioperative period based on pated large volumes of blood loss. Families can
the risk for venous thromboembolism and the be educated regarding possible postoperative
duration of the patient’s NPO status. Education measures to reduce the risk of a deep venous
should be given that the stress of major surgery thromboembolism, such as early mobility,
may precipitate menses outside of a regular cycle sequential compression devices, and possible
or may stop the regular cycle completely for medications.
weeks to months. Post pubertal females should
be tested for pregnancy prior to surgery.
Psychiatric
Endocrinology Children and young adults with cerebral palsy

or underlying medical conditions may also have
Hormonal disorders, particularly of the a concurrent psychiatric diagnosis including
hypothalamic-pituitary axis, along with other autism, attention deficit hyperactivity disorder,
or other behavioral disorders. For these children, Laboratory Evaluation

it is important to discuss with caregivers what
may trigger behavioral outbursts and ways to Routine laboratory testing is typically not
decrease the likelihood of these occurring. This required for most patients who will be undergo-
may include the development of a behavioral ing an orthopedic surgical procedure. Data indi-
management plan, and involvement of child cates that there has been a trend to tailor
life in the preoperative area, as well as informing preoperative laboratory testing based on a
the staff who will be taking care of the patient patient’s underlying medical conditions as well
postoperatively of this management plan. Utiliza- as consideration to the type of surgical procedure
tion of ancillary services such as child life spe- (Patel et al. 1997). This may include, but not be
cialists, music therapists, and art therapists should limited to, a complete blood count, a coagulation
be considered as part of the care of a child in profile, a comprehensive metabolic profile, anti-
the perioperative period. epileptic drug levels, and a urinalysis and cul-
ture; additionally, a routine chest x-ray is not
necessary.
Medications
Miscellaneous
Patients who are undergoing a preoperative eval-
uation prior to surgery are often on multiple med-
As part of a comprehensive, co-management
ications to manage and treat their underlying
approach to preoperative evaluations, a discussion
medical conditions. These medications should be
with the family or caregivers should occur
reviewed and discussed as well as documented in
regarding what to expect in the perioperative
the medical record. Certain medications are
period. This discussion should focus on
known to increase the likelihood of postoperative
expected postoperative medical management
complications, such as the association between
that may encompass management of respiratory
valproic acid and pancreatitis. Management of
distress or failure, anemia, constipation, and feed-
these high-risk medications should be based on
ing intolerance. Approaches to pain management
careful review of the risk and benefits and include
should also be discussed and how pain will be
communication with the patient’s relevant care-
identified and treated.
givers. Other medications may be contraindicated
leading up to surgery, or surgeons may request
that these be held in the time period leading up to
surgery (most commonly NSAIDs). Depending Summary
on the patient’s underlying medical condition,
the surgery planned, and expected mobility in A growing body of literature has shown benefits for
the postoperative period, oral contraception pills preoperative evaluation for medically complex
may need to be held. A perioperative plan should patients (Rappaport et al. 2013). Perioperative
be made regarding all medications, i.e., when management is more likely to benefit medically
should the last dose of medications be given complex patients than otherwise healthy patients
prior to surgery and when can home medications (Siegal 2008). Judicious patient selection for
resume in the postoperative period. Ideally morn- preoperative evaluation should be used to optimize
ing medications can be given early the day of patients’ medical conditions prior to the challenges
surgery if they are medically necessary (anti- of major surgery. In all instances, the evaluation
epileptic drugs), though medications that are and care of a patient with cerebral palsy who will be
used for hypertension should be held on the day undergoing orthopedic surgery should be tailored
of surgery. to the type of surgery and the individual patient.
Case Histories
another preoperative evaluation and
was deemed medically optimized for his
Case 1 upcoming posterior spinal fusion (he had
The patient is a 14-year-old male with gained weight, his wound was healing
perinatal hypoxic-ischemic encephalopathy well, and he had been seen for follow-up
with resultant spastic quadriplegic cerebral by all his subspecialists). The provider had
palsy, refractory epilepsy, profound intel- a discussion with the family regarding pre-
lectual disability, chronic restrictive lung operative medical recommendations as well
disease with ineffective airway clearance, as what to expect in the perioperative
obstructive sleep apnea with CPAP depen- period, including expected postoperative
dence, dysphagia with G-tube dependence, medical management of respiratory distress
chronic constipation, a history of left or failure, anemia, constipation, and feeding
hip osteomyelitis with a chronic wound, intolerance. Approaches to pain manage-
and progressive neuromuscular scoliosis. ment were discussed as well. He underwent
When he was identified as requiring a a successful posterior spinal fusion and
posterior spinal fusion, he was scheduled recovered well from a medical and surgical
for a preoperative evaluation with a pediat- standpoint.
ric hospitalist specializing in medical
co-management.Due to his significant med-
ical comorbidities, his preoperative evalua-
tion was scheduled prior to a surgical
Case 2
date being identified to ensure he was an
The patient is a 10-year-old female with
appropriate surgical candidate from a med-
spastic quadriplegic cerebral palsy, seizure
ical standpoint. At this initial visit, a com-
disorder, gastroesophageal reflux disease
prehensive medical history was obtained,
with Nissen/G-tube dependence, moderate
medication reconciliation was performed,
obstructive sleep apnea (not on home oxy-
and the electronic health record was
gen or CPAP), and bilateral hip subluxation
updated with both; a full examination and
who was scheduled for bilateral hip recon-
review of recent laboratory and radio-
struction with her orthopedic surgeon. She
graphic data were completed. As part of
was scheduled for a preoperative evaluation
this evaluation, multiple risk factors
with a pediatrician specializing in medical
for a higher morbidity/mortality in the
co-management approximately 7 weeks
perioperative period were identified and
prior to her surgery.
were addressed. He was noted to be signif-
At this evaluation, a comprehensive
icantly underweight and was referred to a
medical history was obtained, medication
dietician. He was noted to be overdue for
reconciliation was performed, and the elec-
pulmonology follow-up, and an appoint-
tronic health record was updated with both;
ment was recommended prior to surgery.
a full examination and review of recent
In addition, an open wound was present
laboratory and radiographic data were com-
at the site of his prior osteomyelitis, indicat-
pleted. This patient had been seen by her
ing a potential for poor wound healing post-
multiple subspecialists in the weeks prior to
operatively, and he was subsequently
this evaluation; these records and any peri-
evaluated by a wound care specialist. After
operative subspecialist recommendations
he was seen by the recommended providers
were reviewed. The patient was considered
and specialists, he was again seen for
(continued)
References
medically optimized for her surgery. The
provider discussed with the caregiver pre- Brooks J, Day S, Shavelle R et al (2011) Low weight,
morbidity, and mortality in children with cerebral
operative medical recommendations as well palsy: new clinical growth charts. Pediatrics 128(2):
as what to expect in the perioperative e299–e307. https://doi.org/10.1542/peds.2010-2801.
period, including expected postoperative Epub 2011 Jul 18
medical management of pain, respiratory Cloake T, Gardner A (2016) The management of scoliosis
in children with cerebral palsy: a review. J Spine Surg 2
distress or failure, anemia, constipation, (4):299–309. https://doi.org/10.21037/jss.2016.09.05
and feeding intolerance. She underwent a DiCindio S, Arai L, McCulloch M et al (2015) Clinical
successful surgery and recovered well relevance of echocardiogram in patients with cerebral
from a medical and surgical standpoint. palsy undergoing posterior spinal fusion. Pediatr
Anesth 25:840–845. https://doi.org/10.1111/pan.12676
Ferrari LR (2004) Pre-operative evaluation of pediatric
surgical patients with multisystem considerations.
Anesth Analg 99:1058–1069. https://doi.org/10.1213/
01.ANE.0000133910.55244.0E
Patel RI, DeWitt L, Hannallah RS (1997) Pre-operative
Cross-References laboratory testing in children undergoing elective
surgery: analysis of current practice. J Clin Anesth
9(7):569–575
▶ Asthma in a Child with Cerebral Palsy Rappaport DI, Cerra S, Sharif I et al (2013) Pediatric
▶ Endocrine Dysfunction in Children with hospitalist pre-operative evaluation of children with
Cerebral Palsy neuromuscular scoliosis. J Hosp Med 8(12):684–688.
https://doi.org/10.1002/jhm.2101. Epub 2013 Nov 18
▶ Epilepsy in the Child with Cerebral Palsy
Roizen MF (2000) More pre-operative assessment
▶ Gynecological Issues in Girls and Young by physicians and less by laboratory tests.
Women with Cerebral Palsy N Engl J Med 342(3):204–205. https://doi.org/
▶ Postoperative Pain and Spasticity Management 10.1056/NEJM200001203420311
Siegal EM (2008) Debates in hospital medicine. J Hosp
in the Child with Cerebral Palsy
Med 3(5):398–402. https://doi.org/10.1002/jhm.361
▶ Psychiatric Disorders in Children with Cerebral Theroux MC, Nerker T, Ditro C et al (2012) Anesthetic
Palsy care and peri-operative complications of children with
▶ The Child, the Parent, and the Goal in Treating Morquio syndrome. Pediatr Anesth 22(9):901–907.
https://doi.org/10.1111/j.1460-9592.2012.03904
Cerebral Palsy
Vazirani et al, J Hosp Med, 7:697–701, 2012
Wijeysundera et al Arch Intern Med 170:1365–1374, 2010
Anesthesia in the Child with Cerebral
Palsy 79
Dinesh K. Choudhry and Mary C. Theroux
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1132
Surgical Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1133
Perioperative Concerns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1133
Neurologic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1133
Respiratory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1133
Cardiovascular . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1134
Gastrointestinal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1134
Fluids and Electrolytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1136
Thermoregulatory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1138
Pharmacologic . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1138
Positioning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1139
Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1139
Preoperative . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1139
Intraoperative . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1140
Postoperative . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1141
D. K. Choudhry (*)
Department of Anesthesiology and Perioperative
Medicine, Nemours/Alfred I. duPont Hospital for
Department of Anesthesiology, Jefferson Medical College,
e-mail: dinesh.choudhry@nemours.org
M. C. Theroux
Department of Pediatrics, Jefferson Medical College,
e-mail: mtheroux@nemours.org

https://doi.org/10.1007/978-3-319-74558-9_83
1132 D. K. Choudhry and M. C. Theroux
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1142
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1142
Abstract 1964; Bax et al. 2005; Maranhao 2005; Murphy

Cerebral palsy (CP) is a nonspecific, descrip- and Such-Neibar 2003; Theroux and Akins 2005).
tive term that encompasses a constellation of Prenatal cerebral insult is thought to be responsi-
symptoms due to neurologic lesion resulting ble for as high as 75% of cases and postnatal insult
from the insult to the developing brain accounts for 10–18% of the cases (Pharoah et al.
sustained early in life. Although the neurologic 1989; Palmer et al. 1995). The neurologic lesion
lesion in CP is nonprogressive, the motor dys- in children with CP is nonprogressive and hence
function due to spasticity may be progressive the term static encephalopathy is frequently used
leading to spinal deformities, joint contrac- to describe it. However, the motor dysfunction
tures, and dislocations requiring medical and due to spasticity may be progressive leading to
surgical interventions. Anesthetic care for chil- spinal deformities, joint contractures, and disloca-
dren with cerebral palsy is fraught with signif- tions requiring medical and surgical interventions
icant concerns for anesthesia provider and (Nolan et al. 2000).
careful attention to all aspects of perioperative Classification of CP is based on the character-
care is necessary. Perioperative planning and istics of neurological dysfunction (spastic, dyski-
care should include thorough preoperative netic, ataxic, and mixed) and extremity involved
assessment, attention to co-morbidities, man- (quadriplegia, hemiplegia, diplegia, and mono-
agement of chronic medications, meticulous plegia). The Swedish classification that addresses
intraoperative care to maintaining normothermia, both the movement disorder and its distribution is
and adequate replacement of fluid and blood currently the most commonly used (Table 1)
products. Postoperative assessment of pain and (Mutch et al. 1992).
its management are essential to facilitate recov-
ery and uneventful perioperative course. Table 1 Swedish classification system for cerebral palsy
Affected
Keywords Type brain site Motor disability
Cerebral palsy · Hypothermia · Coagulopathy · Spastic Lesion in Quadriplegia (27% of all
Seizures · Spine fusion (70%) cerebrum cases of CP)
Diplegia (21%)
Hemiplegia (21%)
Dyskinetic (10%)
Introduction Number of extremities
involved correlates with
level of intelligence
Cerebral palsy (CP) is a nonspecific, descriptive
Dyskinetic Basal Dystonia – twisting
term that encompasses a constellation of symp- (10%) ganglia position of torso
toms ranging from mild monoplegia with normal Athetosis – purposeless
cognitive capacity to spastic quadriplegia with movements of extremities
severe mental retardation (Wongprasartsuk and Chorea – quick, jerky
proximal movements of
Stevens 2002). Although the precise inciting extremities
event is generally unknown, the common denom- Ataxic Cerebellum Includes tremor, loss of
inator is the subtle motor impairment to profound (10%) balance, and speech
motor dysfunction resulting from the insult to the Mixed Cerebrum Includes spasticity and
developing brain sustained early in life during, (10%) and athetoid movements
cerebellum
antenatal, perinatal, or postnatal period (Bax
79 Anesthesia in the Child with Cerebral Palsy 1133
Surgical Epidemiology high-functioning adolescents and communication

difficulties may mask normal intellect. Visual
According to the epidemiologic surveys in indus- abnormalities in the form of myopia, visual field
trialized countries, the prevalence of cerebral defects, oculomotor problems, and retinopathy of
palsy is fairly static at approximately 2.5 per prematurity are observed in about 40% of children
1000 live births among normal birth weight babies (Breakey 1955). Premedication with a benzodiaz-
(Wongprasartsuk and Stevens 2002; Murphy et al. epine is frequently needed to allay their preoper-
2002; Theroux and Akins 2005; Jacobsson and ative anxiety.
Hagberg 2004). Surgical procedures are generally Approximately 30% of cerebral palsy patients
performed in children with CP primarily for the have seizure disorder and is most common in
following reasons: first, to correct the skeletal children with spastic hemiplegia and least com-
deformities that likely result from long-standing mon in children with ataxic and choreoathetoid
spasticity; second, to reduce muscle tone in the forms(Eicher and Batshaw 1993). Tonic-clonic
extremities; and lastly, to improve organ function. and partial complex seizures are frequently seen.
Considering the comorbidity known to accom- Literature indicates that CP patients with
pany cerebral palsy, these individuals frequent coexisting seizure disorder are more than twice
the operating room for major spine surgery, as likely to have a postoperative seizure than
upper and lower extremity orthopedic surgery, a noncerebral palsy epileptic patient undergoing
reconstructive femoral and/or pelvic osteotomies, surgery (Wass et al. 2012). It is therefore advisable
intrathecal baclofen pump placement, and neuro- to continue anticonvulsant therapy up until the
surgical procedures to control spasticity (selective day of surgery and reinstituted postoperatively as
dorsal rhizotomy). Impaired oral-motor and pha- soon as possible.
ryngeal function are frequently seen that lead to
poor oral intake, gastrointestinal reflux, and aspi-
ration pneumonia, necessitating surgical interven- Respiratory
tions such as feeding gastrostomy tube placement,
Nissen fundoplication, tracheostomy, and dental Respiratory compromise is frequently the cause of
rehabilitation, (Wongprasartsuk and Stevens death in children with CP and is multifactorial in
2002; Maranhao 2005; Theroux and Akins 2005; origin (Evans et al. 1990). These children have
Spiroglou et al. 2004; Lipton et al. 1999) copious oral secretions due to hyperactive sali-
vary glands coupled with impaired ability to swal-
low due to disturbed coordination of orofacial and
Perioperative Concerns palate lingual muscles. Compromised ability to
clear pharyngeal secretions leads to pulmonary
Neurologic aspiration, development of reactive airway dis-
ease, recurrent respiratory infections, and chronic
The central nervous system is one of the first lung disease. Also, these episodes of silent aspi-
organ to develop during embryogenesis and injury ration resulting in aspiration-related lung disease
during this developmental period can lead to var- are widely prevalent and are commonly associ-
ious neurologic disabilities including develop- ated with greater neurological impairment and
mental delay; cognitive, visual, and auditory developmental delay (Weir et al. 2011). Timely
impairment; spasticity and hypertonicity; epi- administration of anticholinergics and frequent
lepsy; attention deficit; and autonomic dysfunc- suctioning are beneficial in managing secretions-
tion (Stiers et al. 2002; Van Heest et al. 1993). related side effects (Wilken et al. 2008).
Intellectual disability occurs in two third of the Airway should be assessed for potentially dif-
patients with CP; however, 60% of children with ficult laryngoscopy due to temporomandibular
hemiplegia have normal intelligence. Depression joint dysfunction, jaw malocclusion, and loose
and emotional lability are common especially in teeth. However, full airway assessment may not
always be possible due to poor cooperation and and Brenn 2002). Whether hypotension is also
review of previous anesthetic records is helpful related to inability to mount an adequate auto-
for planning airway management. Oropharyngeal nomic response to stress is something we know
suction prior to intubation and endotracheal suc- less about. The etiology of CP being a hypoxic
tion after endotracheal tube placement are useful insult to the developing brain, one may wonder if
maneuvers in children with excessive oropharyn- autonomic system was impacted by the same
geal secretions. insult, even in a small measure. CP patient’s
well-known propensity to sustain hypothermia
poses the question “is there a generalized lack of
Cardiovascular adequate stress response to challenging environ-
ment in CP patients.” Thus, if due consideration to
CP is the result of a perinatal insult and is there- the above factors is not given, hypotension during
fore environmental, not genetic, in etiology and anesthetic management of CP patients may occur.
results in neuromuscular scoliosis due to imbal- It is now well recognized that the CP patients
ances in the neurologic control of flexor and lose more blood than their non-CP peers (idio-
extensor muscle groups of the spine. This etiolog- pathic scoliosis patients) when undergoing spine
ical background explains why the incidence of fusion procedures (Kannan et al. 2002). Sub-
congenital heart defects is no greater in patients optimal levels of clotting factors are the primary
with CP than in the general population. Since reason for the relative coagulopathy while dys-
prenatally, the children with CP had structurally functional platelets exposed to chronic and long-
and functionally robust cardiovascular system, term seizure medications may be contributing as
one could surmise that a significant cardiovascu- well (Theroux and Dicindio 2014) (Table 1).
lar disease associated with CP is unlikely. This Study examining phases of clotting and clot
was further corroborated by the study conducted strength using thromboelastography during spine
by DiCindio et al., where 72 patients with CP and fusion procedure found maximum amplitude sig-
scoliosis were subjected to a retrospective nificantly lower in patients with CP at early blood
study to evaluate their cardiac status prior to loss when compared with children undergoing
their scoliosis correction. All patients were evalu- idiopathic scoliosis procedure (Brenn et al.
ated by a two-dimensional echocardiogram with 2004). Additionally, subnormal calcium and mag-
M-mode and color and spectral Doppler examina- nesium levels were observed in patients with CP
tions. The investigators found that all patients with early blood loss, which could further explain
with CP in their study had normal left ventricular increased bleeding as calcium is an essential com-
function and 2/72 patients with a hemodynami- ponent of the homeostatic mechanism (Brenn
cally insignificant mitral valve prolapse which et al. 2004). The results from these studies provide
was consistent with the incidence observed in insight into why patients with CP appear to lose
general population (4–7%), but far less than the a greater amount of blood during surgery
incidence observed (13–75%) in adolescents with (Table 2).
idiopathic scoliosis (Dicindio et al. 2003, #63;
Dhuper et al. 1997; Hirschfeld et al. 1982).
Hypotension: While CP patients are not pre- Gastrointestinal
disposed to congenital cardiac disease, they do
experience hypotension more frequently under Gastroesophageal reflux disease and aspiration
anesthetic conditions than normal population. may be of concern in patients with CP especially
Factors that contribute to hypotension are related those who have greater neurological impairment
to increased sensitivity to anesthetic agents (Weir et al. 2011). A study examining 300 children
compounded by chronic under hydration espe- for oropharyngeal and silent aspiration found
cially in nonambulatory patients and those fed that 34% of patients in their study experienced
via a gastrostomy tube (Frei et al. 1997; Choudhry oropharyngeal aspiration, and 81% of those had
79
Table 2 PT/PTT and factor levels measured at baseline (Base) and again at blood loss of 25% of patient’s blood volume (EBL25). (Reproduced from Theroux and Dicindio 2014)
Anesthesia in the Child with Cerebral Palsy
Patient Base PT BL25 PT Base PTT BL25 PTT Base II BL25 II Base VII BL25 VII Base IX BL25 IX Base X BL25 X
1 10 12 29 38 90 68 43 49 70 74 58 45
2 10 15 34 67 100 46 110 30 100 37 100 57
3 12 15 28 43 85 48 64 12 100 52 100 22
4 13 14 39 48 90 55 70 70 37 52 60 39
5 13 16 30 46 100 46 80 64 74 29 57 57
Normal range for PT = 9–11 min, normal range for PTT = 23–38 min, and normal range for factor levels = 50–150%
1135
silent aspiration. Silent aspiration was signifi- and obtain repeat hemoglobin and hematocrit,
cantly associated with neurological impairment, which may be considered as the baseline hemo-
developmental delay, and aspiration-associated globin and hematocrit.
lung disease. Further, presence of a gastrostomy
tube for feeding needs was found to be a signifi-
cant independent predictor of increased frequency Musculoskeletal
of hospital admissions (Blackmore et al. 2016).
Constipation is a well-recognized non-motor Spasticity is seen in 70% of the children with CP
manifestation in CP patients, regarding which, and is one of the greatest challenges faced when
increasingly more literature is forth coming caring for these patients. Spasticity is the most
(Awan and Masood 2016; Jaramillo et al. 2016). debilitating symptom of CP which interferes
Constipation is exacerbated in many cases in with motor function and affects the quality of
the postoperative period due initially to de- their life (Delgado et al. 2010). Up to 85% of
creased gastrointestinal motility from anesthetics patients with CP suffer significantly from their
followed by opioid-induced gastrointestinal dys- spasticity (Brunstrom 2001). Brain damage in
function. Stames in 2016 described a patient with these children likely creates a relative imbalance
CP who presented to emergency room in cardiac between inhibitory neurotransmitter gamma
arrest due to abdominal compartment syndrome aminobutyric acid (GABA) and excitatory neuro-
due to massive dilation of large bowel from fecal transmitter notably glutamate, in the descending
loading (Starnes et al. 2016). His history was inhibitory neurons (Nolan et al. 2000; Albright
significant for chronic constipation for which he 1996b). Excessive stimulation of alpha motor
had multiple hospitalizations. Thus, seemingly neurons results in spasticity. Spasticity may pre-
a trivial issue such as constipation, if allowed to sent as hyperactive reflexes, clonus, weakness,
escalate uncontrolled, could result in significant and discoordination and lead to decreased range
morbidity in CP patients. of motion, functional impairment, pain, and defor-
mities. Spasticity in these children leads to flexion
and adduction to dominate over extension and
Fluids and Electrolytes abduction of the hip joints which, over time,
leads to subluxation or dislocation of the hip joints
Significant proportions of these children are (Howard et al. 1985). The incidence of hip dislo-
unable to maintain adequate nutritional state by cation in children with cerebral palsy has been
oral feeding due to poor chewing and swallowing. reported to be as high as 59% (Howard et al.
Some are dependent largely on caregivers to pro- 1985). These conditions are painful, may lead to
vide nutrition and hydration through gastrostomy imbalance while sitting, interfere with perineal
or nasogastric tube. Their oral intake is further hygiene, and may eventually lead to decubitus
compromised by esophageal dysmotility, abnor- ulcers. Bilateral lower extremity procedures such
mal lower esophageal sphincter action, and spinal as pelvic and femoral osteotomies are frequently
deformity that lead to reflux. Malnutrition and needed to alleviate pain and facilitate nursing
concurrent use of laxatives may lead to electrolyte (Miller et al. 1997; Oh et al. 2007). Treatment of
imbalance and dehydration. The extent of under spasticity is directed towards increasing mobility,
hydration is often evident in their higher-than- independence, to prevent or minimize the devel-
expected hemoglobin and hematocrit preopera- opment of contractures, to improve positioning,
tively. Preoperative fasting for prolonged periods and to increase ease of care especially in severely
may further dehydrate them and despite underly- affected patients (Butler and Campbell 2000;
ing anemia, some of these children may present Gilmartin et al. 2000; Krach 2001). All triggers
with higher than expected hematocrit value due to of spasm should be addressed in CP patients
dehydration. It is imperative that such patients are including pain, excitement, cold, illness, sleep dis-
hydrated early during their intraoperative period turbance, immobility, and/or hormonal fluctuation
(Krach 2001; Gilmartin et al. 2000). Some of these was characterized by the spread of acetylcholine
well-known triggers of spasm need special atten- receptors beyond the limit of neuromuscular junc-
tion especially in the postoperative arena. tion (Fig. 1). In addition, such abnormalities were
Pertinent to the practice of anesthesia, neuro- found to a greater extent in nonambulatory CP
muscular junctions in CP patients have been patients compared to ambulatory CP patients
found to be abnormal in their distribution of ace- (Theroux and Akins 2005). Findings from this
tylcholine receptors. A study examining neuro- study are in agreement with other studies,
muscular junctions of both CP patients and which had examined neuromuscular junction
patients without CP (idiopathic scoliosis patients) indirectly via observing response to neuromuscu-
via biopsies of Erector Spinae muscle, obtained lar blocking agents. A dose response study by
during spine fusion procedures (biopsy taken the same investigative team found an increased
from motor innervation site of muscles) found sensitivity by CP patients to succinylcholine
abnormal distribution of acetylcholine receptors (Theroux et al. 1994), while another investigator
in approximately 30% of CP patients studied found vecuronium, a non-depolarizing muscle
(Theroux et al. 2002). Abnormal distribution relaxant, less potent in CP patients (Hepaguslar
Fig. 1 Distribution of
acetylcholine receptors in
the neuromuscular junction
of children who did not
have CP and children with
CP. (A-1) Normal
neuromuscular junction first
stained with
α-bungarotoxin (red) to
show the spread of
acetylcholine receptors
(AchRs). (A-2) The same
neuromuscular junction
stained with acetyl
cholinesterase (green) to
define the limits of the
junction. (A-3) The
superimposed
with both α-bungarotoxin
and acetyl cholinesterase
staining. Red staining
outside of the green
indicates spread of AchRs
outside the limits of the
from a patient with
CP. Significant spread of the
AchRs outside of the limits
of the neuromuscular
junction is seen.
(Reproduced from
Anesthesiology clinics
Theroux and Dicindio
2014)
et al. 1999). While up-regulation of acetylcholine Intraoperative measures such as humidification

receptors occurs in patients who are immobile of inspired gases, warming of intravenous fluids,
(Martyn et al. 1992; Gronert and Theye 1974, and forced air-warming blankets are useful strat-
1975; Fung et al. 1991; Martyn and Richtsfeld egies to prevent hypothermia. When actively
2006), it is not likely that this alone explains the warming, it is important to monitor temperature
abnormalities seen in the neuromuscular junctions because patients with CP may easily develop tem-
of CP patients. peratures greater than normal due to their inability
to regulate temperature when swings in ambient
temperatures occur.
Thermoregulatory
Hypothermia was identified as the commonest Pharmacologic

complication (55.1%) observed during general
anesthesia in CP patients (Wass et al. 2012) . Comorbid conditions associated with CP invari-
Hypothermia occurs earlier in the course of gen- ably leads to the need for multiple drugs for their
eral anesthesia and the temperatures as low as effective treatment. Anticonvulsant medications
33–34 C are not uncommon and far surpasses may be some of the most commonly encountered
that observed in otherwise healthy patients. All drugs in the perioperative arena. In general, their
modes of heat loss (conduction, convection, radi- interaction with anesthetic care is easily managed
ation, and evaporation) come into effect in the with awareness of the patient’s level of seizure
operating room environment. Etiology of hypo- control and the need to maintain therapeutic levels
thermia, however, is poorly understood in these in the postoperative period. Serum levels of anti-
children. Global ischemic injury sustained by convulsants are no longer routinely checked pre-
these patients in early childhood likely impairs operatively. More importantly, a plan to continue
thermoregulatory mechanisms and compromises the seizure medications postoperatively is essen-
hypothalamic function. In addition, a relative lack tial, and during major surgical procedures, a plan
of adipose tissue likely makes these children more should be in place to adequately keep the anticon-
vulnerable to heat loss (Dickerson et al. 2003; vulsant levels at a therapeutic level. It is reason-
Mitchell and Laburn 1985). Consequences of able to expect the drug levels to decrease when
mild hypothermia include increased surgical patient sustains significant blood loss during such
blood loss (mixed evidence with literature for procedures. A preoperative consultation with the
and against increased blood loss), prolonged neu- patient’s neurologist may be warranted.
romuscular blockade, delayed emergence, shiver- Relatively newer anticonvulsant, topiramate,
ing with increased oxygen requirement, increased has a known but rare side effect of causing
wound infection, and extended hospital stay acute angle glaucoma (Ho et al. 2013; Chalam
(Gorges et al. 2016; Guest et al. 2004). In view et al. 2008). The proposed mechanism of closed-
of the likelihood of these children getting hypo- angle glaucoma is choroidal effusion and forward
thermic and exposed to its potential complica- rotation of the iris-lens diaphragm (Sankar et al.
tions, special attention is necessary when they 2001). The effusion places pressure on the vitre-
arrive for major surgical intervention. Aggressive ous body and causes anterior displacement and
measures taken to prewarm these children while closure of the angle. Predicting who may develop
they are in the preoperative waiting area not only a case of acute-angle glaucoma perioperatively
allows for a better baseline temperature but also while on topiramate is not possible (Czyz et al.
facilitates venous line placement (Theroux and 2014). Having a high index of suspicion and early
Dicindio 2014). We prewarm our CP patients recognition are necessary to avoid unnecessary
scheduled for major surgeries using a forced pain and discomfort and earlier institution of treat-
air warming (Arizant Healthcare, Minnesota, ment. Another side effect following long-term
USA) system in the preoperative holding area. treatment with anticonvulsants includes a
decrease in platelet count and platelet function. peripheral (ulnar) nerves, lateral femoral cutane-
Valproic acid is a good example of such a drug but ous nerves of the thigh require special protection.
is used less commonly at present with the advent Of the peripheral nerves, the brachial plexus is
of newer drugs. Valproic acid is known to result in most vulnerable to stretch in the prone position
thrombocytopenia over a period of time, the (Warner and Martin 1997). Incidence of scoliosis
severity of which is related to serum levels of the in children with CP is significantly high (20–25%)
drug (Nasreddine and Beydoun 2008). and even more so in those with spastic CP (about
Neuromuscular blocking agents (more com- 75%) (Imrie and Yaszay 2010; Madigan and
monly known as muscle relaxants have altered Wallace 1981). CP patients requiring surgeries in
potency in patients with spastic quadriplegic CP prone position such as spinal fusion are especially
(Rose et al. 2000). Initially examined as a dose- vulnerable to corneal abrasion, optic vein
response study, succinylcholine was shown to be engorgement, and retinal ischemia. Higher inci-
more potent in patients with CP while vecuronium dence of blindness has been observed in patients
was found to be less potent in them (Rose et al. requiring complex spinal surgery in prone posi-
2000; Hepaguslar et al. 1999). Both studies had tion (Cladis et al. 2011; American Society of
enrolled a homogenous population of spastic Anesthesiologists Task Force on Perioperative
quadriplegic CP patients. Further studying motor Visual Loss 2012). The cause of scoliosis in CP
junctions of CP patients, Theroux et al. described is not entirely clear, but it is believed to be due to
abnormal spread of acetylcholine receptors where the combination of muscle weakness, asymmetric
by the spread projected over the limits of neuro- tone in paraspinous muscles, and truncal imbal-
muscular junction was found in approximately ance (Imrie et al. 2010).
30% of patients studied (Theroux et al. 2002)
(Fig. 1). Nonambulatory CP patients among the
group that was studied had significantly greater Management
number of abnormal neuromuscular junctions in
addition to greater abnormality in the spread of Preoperative
acetylcholine receptors (Theroux et al. 2005).
These studies are indicative of the need for cau- Children with CP undergo a variety of surgical
tion when using succinylcholine in CP patients. and diagnostic procedures, and in view of the
multiple issues of concern, thorough preoperative
evaluation and optimization of their status is
Positioning important for uneventful perioperative course.
Their cognitive ability, communication, and
Anesthetized patients are in general vulnerable to behavioral problems significantly influence the
positioning-related injuries because of their management plan. Child may have normal intel-
inability to feel the discomfort of certain positions ligence with good understanding despite impaired
that alters the normal mechanics (2011). Children communicative ability. Issues relating airway
with cerebral palsy, however, are even more vul- assessment, respiratory, neurologic, musculoskel-
nerable because first, they are generally malnour- etal, and thermoregulatory systems have been
ished and have reduced body fat and therefore discussed above. These children are frequently
reduced padding and protection to the pressure- receiving multiple pharmacologic agents such as
prone areas, and second, abnormalities in muscle antiepileptic drugs, antispasmodics, anticholiner-
tone in these children contributes to the develop- gics, antacids, laxatives, and bronchodilators. In
ment of scoliosis, lordosis, lower limb contrac- children with seizure disorder, anticonvulsant
tures, joint immobility, instability, and therapy should be continued up to and including
subluxation that makes positioning challenging. the day of surgery. Respiratory therapy such as
Forceful positioning may lead to nerve injury or bronchodilators and antibiotics and physiotherapy
skin breakdown. Vulnerable parts such as may be required. Discussion of the postanesthetic
pain management plan is essential with the family is a treatment modality that has gained popularity.
since inadequate pain control leads to anxiety and Among these procedures, spinal fusion, which
increased likelihood of muscle spasms. Anxiety is may be considered the most extensive surgical
common in these children and premedication with procedure, has a chapter in this textbook devoted
benzodiazepine such as midazolam is valuable. to it. Varus denotational osteotomy (VDRO) and
However, the dose may have to be tailored based pelvic osteotomy procedures may be combined
on the patients’ neurologic status, muscle tone, with soft tissue release as necessary to treat sub-
airway patency, and risk of aspiration. Most luxation and dislocation of the hip joints resulting
patients tolerate sedative premedication well and from chronic unrelenting spasticity. Such condi-
reducing the dose is preferable to omitting it alto- tions are not only painful but may cause decubitus
gether. Since the likelihood of these children get- ulcers, lead to difficult perineal hygiene and
ting hypothermic is high, prewarming them, while loss of balance while sitting (Dhawale et al.
they are in the preoperative waiting area not only 2013; Miller et al. 1997; Oh et al. 2007). Given
allows for a better baseline temperature but also that procedures are done bilaterally and each
facilitates venous line placement (Theroux and hip would be subjected to a pelvic osteotomy as
Dicindio 2014). Preoperative fasting for pro- well as a femoral osteotomy via two separate
longed periods may dehydrate them and despite incisions, significant blood loss and postoperative
underlying anemia, some of these children may pain should be expected. Blood loss is often
present with higher than expected hematocrit underestimated in pelvic osteotomies as a signif-
value due to dehydration. It is imperative that icant amount of blood is lost on the drapes during
unduly prolonged preoperative fasting is avoided drilling and need to be assessed visually. Addi-
and fluid deficit is corrected early during their tionally, expect hemoglobin to drop by 1–2 g
intraoperative period. Airway should be assessed postoperatively, which needs to be anticipated
for potentially difficult laryngoscopy due to tem- when need for transfusion is contemplated. The
poromandibular joint dysfunction, jaw malocclu- need for transfusion is more likely if acetabular
sion, and loose teeth. However, full airway osteotomies have been performed in addition to
assessment may not always be possible due to varus femoral osteotomies. In the postoperative
poor cooperation and review of previous anes- period, emphasis is placed on adequate treatment
thetic records is helpful for planning airway man- of pain and spasm, which unless properly treated
agement. Oropharyngeal suction prior to result in a vicious cycle of pain-triggering spasm
intubation and endotracheal suction after endotra- which leads to more pain. Regional anesthesia is
cheal tube placement are useful maneuvers in highly desirable for these patients even in the face
children with excessive oropharyngeal secretions. of difficulty with the presence of kyphoscoliosis.
Intrathecal baclofen pump insertion is a proce-
dure unique to CP patients since it is a treatment for
Intraoperative spastic disease and no other patient population so
uniformly suffers from spasticity, as do CP patients.
Predominant among the surgical procedures are When oral agents which are administered with the
the procedures designed to treat the abnormalities goal to inhibit excitatory or augment inhibitory
caused by the chronic and debilitating spasticity neurotransmitters at the spinal cord (Gracies et al.
that lead to subluxation/dislocation of the hip 1997; Goldstein 2001) fail to control spasticity, use
joints, kyphoscoliosis, and gait abnormalities. of intrathecal baclofen administered continuously
Treatment of these conditions requires orthopedic via an indwelling catheter is considered. Baclofen,
intervention and patients undergo tendon transfers 4-amine-3-(4-chlorphenyl)-butanoic acid, is a mus-
and osteotomies to correct abnormal gait and cle relaxant and antispasmodic drug and has a half-
spine fusion to correct abnormal curvatures of life of 4–5 h. With a structure similar to gamma-
spine. In addition, placement of baclofen intrathe- aminobutyric acid (GABA), it binds to GABAb
cally to treat spasm via a “catheter and pump” unit receptors, which are superficially located in the
spinal cord in laminae I–IV. Baclofen by inhibiting baclofen can lead to coma and flaccidity requiring
GABAb receptors inhibits monosynaptic and poly- mechanical ventilation. A more common scenario
synaptic spinal reflexes by inhibiting release of is excessive somnolescence in the postoperative
excitatory neurotransmitters presynaptically. period prompting a careful review of the drugs
Implantation requires a two-step surgical proce- administered, often leading to the conclusion of
dure, one where a lumbar puncture is performed an over dose of baclofen. Such patients require
to introduce and advance a catheter intrathecally admission to the ICU, with or without the need for
followed by a second incision in the lower quadrant assisted ventilation until sufficient time elapses to
of anterior abdominal wall to implant the baclofen safely discharge patient from ICU.
pump. Life span of the pump varies from 3 to
7 years and pump replacement may become neces-
sary at that time. Fitting the pump in the abdominal Postoperative
wall requires that the patient be of a certain age and
size (Albright 1996a, b). It is evident from the above discussion that chil-
General anesthesia for a duration of ~1.5 h is dren with CP due to multiple organ system
necessary to place the intrathecal catheter and to involvement present with many challenges in the
implant the baclofen pump. Catheter is introduced immediate postoperative period. There are case
via a Touhy needle into the intrathecal space, reports suggesting that the likelihood of postoper-
tunneled around the flank, either subcutaneously ative complications in children with CP correlates
or under the fascia, and connected to the pump. with the severity of the preoperative comorbidities
Catheter tip is positioned based on the treatment (Lipton et al. 1999). A study by Wass and col-
goal: T8–T10 level allows for leg relaxation; leagues suggests that factors associated with
T3–T6 level allows for lower extremity and increased likelihood of adverse perioperative
some upper extremity relaxation, T5–C5 level is events include ASA physical status greater than
chosen for patients with severe upper extremity 2, history of seizures and upper airway hypotonia
spasticity and/or opisthotonic posturing (Albright (Wass et al. 2012). Emergence from anesthesia
and Ferson 2006; Albright et al. 2006). Compli- may be slower due to their underlying neurologic
cations associated with intrathecal baclofen pump impairment, hypothermia, and delayed elimina-
include mechanical ones such as catheter breaks, tion of volatile anesthetics agents and propensity
dislodgements, and kinks. While infection is an towards airway obstruction. Special attention
ever present threat (Bayhan et al. 2016; Kolaski must be paid to maintaining a patent airway and
and Logan 2007; Dickey et al. 2013; Vender et al. removal of oropharyngeal secretion. Perioperative
2006), CSF leak, both immediate and late, in the chest physiotherapy is valuable in children fol-
postoperative period may occur (Albright et al. lowing major surgical procedures and those who
2006). Postdural puncture headache may also are predisposed to respiratory complications due
occur which may be treated with a blood patch, to preexisting respiratory compromise and
in consultation with the surgeon who placed the retained secretions. When irritability on emer-
baclofen catheter. gence is seen, identifying its underlying cause
Complications from baclofen pump includes such as surgical pain, muscle spasms, urinary
baclofen overdose (Kolaski and Logan 2007), retention, or anxiety due to unfamiliar environ-
usually from accidental dosing from flushing of ment may be difficult. Bringing the parent/care-
the catheter. Mild overdose may be treated with giver who is familiar with the child’s behavior
physostigmine or flumazenil (Saissy et al. 1992) may be helpful in identifying the cause and
to facilitate emergence from anesthesia. In our reassuring to the child. Initiation of patient’s anti-
experience, we have not seen much efficacy with epileptic medications is important in a timely
the use of either physostigmine or flumazenil to fashion to prevent postoperative increase in sei-
reverse baclofen-related depression of central ner- zures. Postoperative assessment of pain and its
vous system. A severe overdose, which is rare, of management are essential to facilitate recovery
and uneventful perioperative course. Multimodal American Society of Anesthesiologists Task Force on
approach involving medications administered via Perioperative Visual Loss (2012) Practice advisory
for perioperative visual loss associated with spine
regional, oral, intravenous, and transdermal routes surgery: an updated report by the American Society of
have many benefits. Pain control is generally Anesthesiologists Task Force on Perioperative Visual
accomplished by concurrent use of an opioid and Loss. Anesthesiology 116:274–285
benzodiazepine administered intravenously or Awan WA, Masood T (2016) Role of stretching exercises
in the management of constipation in spastic cerebral
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to be paid to positioning since prolonged pressure palsy. Dev Med Child Neurol 6:295–297
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Dan B, Jacobsson B, Damiano D (2005) Proposed
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Orthop 36:305–309
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Postoperative Pain and Spasticity
Management in the Child with 80
Cerebral Palsy
B. Randall Brenn and Dinesh K. Choudhry
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1146
Epidemiology of Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1146
Pathophysiology of Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1146
Special Challenges Relating to Pain Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1147
Chronic Systemic Sources of Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1147
Pain Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1148
Multimodal Approach to Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1149
Approaches to Pain Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1151
Opioids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1152
Nonopioid Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1152
Antispasmodics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1153
Regional Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1154
Postoperative Spasticity Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1154
Monitoring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1155
B. Randall Brenn (*)

Monroe Carrell Children’s Hospital at Vanderbilt,
Vanderbilt University Medical Center, Nashville, TN, USA
e-mail: bruce.r.brenn@vanderbilt.edu
D. K. Choudhry
e-mail: Dinesh.Choudhry@nemours.org

https://doi.org/10.1007/978-3-319-74558-9_84
1146 B. Randall Brenn and D. K. Choudhry
Pain Management for Specific Procedures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1155

Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1156
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1156
Abstract Epidemiology of Pain

Children with CP may have pain associated
with their condition even prior to having sur- The etiology of pain in hospitalized children with
gical procedures. This pain is typically of CP is multifaceted and results from the inherent
musculoskeletal, neurologic, and gastrointesti- musculoskeletal deficits associated with the dis-
nal origins. Many patients have chronic medi- ease, invasive surgical interventions, and rehabil-
cal problems that need to be acknowledged as itative therapies (McKearnan et al. 2004). Pain is
potential sources of pain. It is also not uncom- experienced by up to 60% of children with CP
mon for children and adolescents with CP to who can communicate a pain self-report and may
have chronic pain syndromes. In this chapter, be as high as 73% in children who communicate
these issues along with the pain treatment via a proxy (Doralp and Bartlett 2010; Parkinson
modalities utilized following surgical proce- et al. 2013). The sources of the pain are multifocal
dures are discussed. Pain regimens and spas- including musculoskeletal (e.g., joint subluxation,
ticity management for typical procedures are fractures secondary to osteopenia), neurologic
presented. (e.g., spasticity, dystonia, hypertonia), and gastro
intestinal (e.g., gastroesophageal reflux, constipa-
Keywords tion) (Kingsnorth et al. 2015; Penner et al. 2013).
Pain management · Pain assessment · Thus children with CP may have baseline pain in
Postoperative pain · Chronic pain · Spasticity upper and lower extremities, neck and spine, hips
and pelvis, and upper and lower abdominal areas.
Existing pain must be acknowledged prior to sur-
Introduction gical procedures as they may complicate the pain
exam in the postoperative period. In addition,
Inadequate pain management in children not only various nonsurgical and surgical therapeutic inter-
leads to immediate undue stress and suffering, but ventions such as physiotherapy assist devices,
it can also influence long-term psychological, botulinum injections, major spine surgery, upper
physiological, and emotional outcomes for the and lower extremity orthopedic surgery, recon-
patient and family (Taenzer et al. 1986; Ip et al. structive femoral and/or pelvic osteotomies, and
2009). Health-related quality of life (HRQOL) is intrathecal baclofen pump placement cause sig-
becoming increasingly popular as an outcome nificant discomfort and pain (Penner et al. 2013).
measure to analyze the effectiveness of clinical
interventions in clinical practice (Solans et al.
2008), and the presence of pain has been consis- Pathophysiology of Pain
tently found to be an important factor that nega-
tively impacts HRQOL (Russo et al. 2008; The sensation of pain is an interplay of pain per-
Dickinson et al. 2007). The Study of Participa- ception, amplification, and suppression. Insult to
tion of children with Cerebral Palsy Living in the pyramidal motor system that controls volun-
Europe (SPARCLE) identified that pain was tary movements precipitates neurological disabil-
associated with lower scores across all domains ity. The pyramidal system is a two-neuron system
in children with CP aged 8–12 years (Dickinson consisting of upper motor neuron in the primary
et al. 2007). cortex and lower motor neuron in the dorsal horn
80 Postoperative Pain and Spasticity Management in the Child with Cerebral Palsy 1147
of the spinal cord. Injury to the upper motor impairment. Pain assessment tools are influenced
neuron inhibits cortical input leading to abnormal by the degree of cognitive impairment (Breau and
muscle control and weakness. In addition, the loss Burkitt 2009). In those with minimal deficits, the
of descending inhibitory input increases excitabil- self-report tools are reliable, while behavioral
ity of gamma and alpha neurons producing spas- assessments may be the only recourse in patients
ticity and involuntary muscle activity (Goldstein with profound cognitive impairment (Breau et al.
2001). Spasticity contributes to musculoskeletal 2002).
pain, contractures, and subluxation (Flett 2003). Patients with CP often have sensorineural
Soon after surgery is commenced, nociceptive impairments involving vision, hearing, and touch.
pain is accompanied and augmented by inflam- It is estimated that 40% of children with CP have
matory pain. Tissue injury associated with sur- visual impairment, including strabismus, myopia,
gery initiates a systemic reaction accompanied visual field defects, up to and including cortical
by increase liberation of inflammatory cytokines blindness (Eicher and Batshaw 1993). While
(Kehlet 1989). Inflammatory mediators are some patients have sensorineural hearing loss,
released in the wound and adjacent tissues, others can have excellent hearing. Hearing loss is
resulting in a reduction in the threshold of associated with communication difficulties that
local nerve endings (peripheral sensitization) directly impair pain assessment, while hyperacusis
leading to peripheral and central nervous system can worsen anxiety associated with an unfamiliar
sensitization leading to hyperalgesia (Watkins hospital environment. When combined with cogni-
et al. 1995). tive impairment, these losses may lead to behav-
ioral problems that affect pain assessment.
Caregivers can have difficulty ascertaining which
Special Challenges Relating to Pain behaviors indicate pain as opposed to behaviors
Management associated with the combination of impairments.
Children with CP represent a heterogeneous

group of patients that often bring a host of Chronic Systemic Sources of Pain
coexisting conditions that can affect pain manage-
ment. Damage to the developing brain may result Several systems may be involved depending
in cognitive impairment, sensorineural losses, sei- on the medical and surgical history of the child
zures, and behavioral problems. The child may with CP. Frequently gastrointestinal problems,
have additional comorbidities associated with respiratory issues, and seizure disorders are
the neonatal period, which may have resulted in exhibited chronically, which may influence pain
chronic systemic illness (Nolan et al. 2000). assessment and pharmacologic therapy.
It must be emphasized that children with CP Esophageal dysmotility is common in CP and
exhibit a wide spectrum of these issues in that may be associated with gastroesophageal reflux.
some have very little impairment, while others Drooling can be the result of overactive salivary
have considerable debility. Postoperative pain glands or pseudobulbar palsy associated with
therapy needs to be individualized based on difficulty swallowing (Sochaniwskyj et al.
these comorbidities. Pain seems to increase with 1986). Reflux in itself can cause pain and is also
age (Alriksson-Schmidt and Hagglund 2016) and associated with dystonic reactions. Reflux and
severe chronic pain syndromes (Kingsnorth et al. drooling can lead to pulmonary aspiration. Fur-
2015) have been reported. Having preexisting ther, gut motility issues and immobility can lead to
pain makes management of postoperative pain chronic constipation. All of these problems are
especially challenging in this population. potentially worsened by common pain manage-
Most patients with hemiplegia have normal ment pharmacotherapy.
intellect, while patients with quadriplegia have the Pulmonary compromise is prevalent in CP. Many
highest incidence of profound cognitive patients may have had bronchopulmonary dysplasia
due to underlying prematurity, which manifests detection and monitoring of pain (Breau and
as chronic obstructive pulmonary disease in later Burkitt 2009). Pain assessment falls into one of
life, requiring treatment with bronchodilators. three categories, physiologic assessment, pain
Aspiration as mentioned above can lead to self-report, and behavioral assessment.
pooling of secretions and recurrent respiratory Physiologic monitoring consists of heartrate,
infections and pneumonia. As some patients blood pressure, and respiratory rate monitoring.
may be wheelchair bound, a full understanding These parameters are routinely monitored in the
of their pulmonary reserve may go unknown. postoperative period but are not specific indica-
Hypoxia and hypercarbia may be exacerbated tors of pain. Self-report techniques such as the
by narcotic and sedating medications. verbal analog scales and Wong-Baker FACES
Seizure activity may occur in up to 30% of scale have been employed in patients with
patients with CP, most prevalent in patients with CP. However, they are limited to those patients
hemiplegia and quadriplegia (Eicher and Batshaw that are able to communicate. Intellectual impair-
1993). These patients may be treated with single ment is not a priori a reason not to use self-report,
or multiple anti-epileptic medications. Some anti- but it has been demonstrated that pain in and of
epileptic medications may stimulate liver metab- itself may reduce the cognitive abilities of
olism altering the pharmacokinetics of many pain patients, possibly limiting the value of self-report
medications. Local anesthetics are associated with measures in those patients who are already cogni-
lowering the seizure threshold which, combined tively impaired.
with the stress of surgery, can be a cause of The mainstays of pain assessment in patients
increased seizure activity in the postoperative with CP are behavioral techniques consisting of
period. multi-category scales, which have been validated
and are considered reliable. Crosta et al. published
an excellent review of pain scales in children with
Pain Assessment cognitive impairment (Crosta et al. 2014). Table 1
provides a summary of their evaluations of several
Pain in children with CP is poorly understood, scales in common use.
therefore, under recognized, and undertreated. The Pediatric Pain Profile (Hunt et al. 2007)
Diagnosis of pain in children is difficult due to consists of twenty items evaluated on a four-point
multiple pain etiologies and communication chal- Likert-type scale (0 = not at all to 3 = a great deal)
lenges (Penner et al. 2013). Despite the existence with a scores that can range from 0 to 60.
of a plethora of validated tools and pain scales, the It consists of several dimensions including the
assessment of pain in children is challenging. child’s pain history, baseline and subsequent
These scales have inherent limitations that they pain assessments, interventions, and clinician’s
tend to undermine the complexity of interpersonal evaluations of the child’s pain. Several studies
interactions between patient and physician, and have established that the profile is valid and reli-
they tend to neglect the psychosocial and cultural able; however, in a small study of 30 patients
determinants in pain expression and assessment undergoing surgery, results were less favorable.
(Schiavenato and Craig 2010). In a study of non- Parents evaluated patients preoperatively and then
verbal children, it was observed that even though postoperatively for 5 days but found that there was
physicians aim to correctly identify and treat pain, little difference in pain scores across the postop-
67% of the participants had moderate to severe erative days nor was there variation related to
pain, but none were receiving any treatment. This analgesic administration.
underrecognition and undertreatment of pain may The Individualized Numeric Rating Scale
limit participation and negatively impact quality (INRS) was developed to identify and quantify
of life (Stallard et al. 2001; Schwartz et al. 1999; individual patient’s pain behaviors (Solodiuk
Fauconnier et al. 2009). The key to better pain et al. 2010). Parents are interviewed about the
management is better assessment which improves way their child manifests pain and then a 0–10
Table 1 Summary of behavioral measurement checklists. (Reproduced with permission from Crosta et al. 2014)
NCCPC-PV INRS PPP r-FLACC
Reference Breau et al. 2002 Solodiuk et al. 2010 Hunt et al. 2007 Malviya et al. 2006
Scoring 27 items, Parents recall past pain 20 items scored 0–3. Five behavioral
6 categories (vocal, behaviors and rate them Profile includes pain categories scored
social, facial, 0–10. Word anchors “no history, parent description 0–2 with option for
activity, body, pain” and “worse of child “at their best” and caregiver to add
physiological), possible pain” “at their worst” behaviors
scored 0–3
Parent/ No Yes; required Yes; required Yes; not required
caregiver
input
Observation 10 min 1 min 5 min 5 min
time
Sample Nonverbal children Nonverbal children with Nonverbal children with Children with mild to
description with severe cognitive impairment, cognitive impairment, severe cognitive
cognitive ages 6–18 ages 1–18 impairment,
impairment, ages 12 children could
3–19 self-report, ages
4–21
Setting and Post-op N = 24 Post-op N = 50 Multi-setting; home, post- Post-op N = 52
sample op, in-patient N = 141
Validity Construct Construct and Content, construct, and Content, construct,
established concurrent concurrent and concurrent
Reliability Inter-rater and Inter-rater Inter-rater and internal Inter-rater and test-
established internal retest
Note: NCCPC-PV non-communicating children’s pain checklist-postoperative version, INRS individualized numeric
rating scale, PPP pediatric pain profile, r-FLACC revised face, legs, activity, cry, and consolability
scale is applied to those behaviors. In the valida- 2006). It consists of a 0–2 scale with descriptions
tion testing, there was reliability between for each level of severity of discomfort (Table 3).
researchers and parents; however, bedside nursing The patient will receive a score from 0 to 10 with
consistently scored pain lower than parents. more pain associated with higher scores. This
The Non-communicating Children’s Pain scale has been compared to the other scales and
Checklist (NCCPC, Table 2) and its postoperative seems to be well liked by both parents and nurse
version (NCCPC-PV) was validated and shown to caregivers in the acute setting.
have high interrater reliability. It consists of Behavioral scales and checklists are tools that
27 items broken into 6 subscales including can be applied over the course of an admission to
vocal, social, facial, activity, body and limb, and give a series of temporally related assessments
physiological. Similar to the Pediatric Pain Pro- providing a complete pain picture. Regardless of
file, each item is scored using a severity rating which tool is used, a team approach involving
scale from 0 to 3. This checklist has been tested parents, nursing staff, and physicians with clear
for home use and has been translated into several objectives for the postoperative period will result
languages (Breau and Burkitt 2009). However, a in the most satisfying outcomes.
criticism has been that it is lengthy and takes
considerable time to administer.
The revised FLACC (Faces, Limbs, Activity, Multimodal Approach to Pain
Cry, and Consolability) scale (r-FLACC) was spe-
cifically designed for infants and toddlers who It is well established that pain is not a simple
cannot communicate but has also been seen to be transmission of neural impulses from the periph-
accurate in CP pain assessment (Malviya et al. ery to the cerebral cortex and the signals can be
Table 2 The Non-Communicating Children’s Pain Checklist-Postoperative Version. (Reproduced with permission from
Breau et al. 2004)
0 = Not at all 1 = Just a little 2 = Fairly often 3 = Very often NA = Not applicable
Vocal
1. Moaning, whining, whimpering (fairly soft) 0 1 2 3 NA
2. Crying (moderately loud) 0 1 2 3 NA
3. Screaming/yelling (very loud) 0 1 2 3 NA
4. A specific sound or word for pain (e.g., a word cry or type of laugh) 0 1 2 3 NA
Social
5. Not cooperating, cranky, irritable, unhappy 0 1 2 3 NA
6. Less interaction with others, withdrawn 0 1 2 3 NA
7. Seeking comfort or physical closeness 0 1 2 3 NA
8. Being difficult to distract, not able to satisfy or pacify 0 1 2 3 NA
Facial
9. A furrowed brow 0 1 2 3 NA
10. A change in eyes, including: squinching of eyes, eyes opened wide, eyes frowning 0 1 2 3 NA
11. Turning down of mouth, not smiling 0 1 2 3 NA
12. Lips puckering up, tight, pouting, or quivering 0 1 2 3 NA
13. Clenching or grinding teeth, chewing or thrusting tongue out 0 1 2 3 NA
Activity
14. Not moving, less active, quiet 0 1 2 3 NA
15. Jumping around, agitated, fidgety 0 1 2 3 NA
Body and limbs
16. Floppy 0 1 2 3 NA
17. Stiff, spastic, tense, rigid 0 1 2 3 NA
18. Gesturing to or touching part of the body that hurts 0 1 2 3 NA
19. Protecting, favoring or guarding part of the body that hurts 0 1 2 3 NA
20. Flinching or moving the body part away, being sensitive to touch 0 1 2 3 NA
21. Moving the body in a specific way to show pain (e.g. head back, arms down, curls up, 0 1 2 3 NA
etc.)
Physiological
22. Shivering 0 1 2 3 NA
23. Change in color, pallor 0 1 2 3 NA
24. Sweating, perspiring 0 1 2 3 NA
25. Tears 0 1 2 3 NA
26. Sharp intake of breath, gasping 0 1 2 3 NA
27. Breath holding 0 1 2 3 NA
augmented and attenuated at many different levels moderate to severe pain, combining drugs and
(Rose 2004). Successful acute pain management techniques that target different components of
targets all of the elements in the complex system pain pathway has been found to have benefits.
of pain transduction, transmission, modulation, Such an approach is called the multimodal or
and perception (Brislin and Rose 2005). The layered approach to pain management that not
levels targeted by multimodal analgesia are dem- only provides superior analgesia but also mini-
onstrated in Fig. 1 (Gorlin et al. 2016). mizes the occurrence of drug reactions to each
Pain treatment plans that target single step in component of the regimen because a lower dose
the nociceptive pathway with a single medication of each one is required. Reduced opioid consump-
have been found to be less effective than plans that tion decreases the incidence and severity of opioid
target multiple steps by using a combination related side effects such as nausea, vomiting, con-
of analgesics (Elia et al. 2005; Morton and stipation, urinary retention, pruritus, and respira-
O’Brien 1999; Korpela et al. 1999). Although tory and central nervous system depression
opiates continue to be the main stay in managing (Korpela et al. 1999; Watcha et al. 1992).
Table 3 The Revised Face Legs Activity Cry and Consolability Scale (FLACC-R). (Reproduced with permission from
Malviya et al. 2006)
Individual behaviora
Face
0 = No particular expression or smile Pouty lip; clenched and grinding teeth; eyebrows
1 = Occasional grimace/frown; withdrawn or furrowed; stressed looking; stern face; eyes wide open –
disinterested; appears sad or worried looks surprised; blank expression; nonexpressive
2 = Consistent grimace or frown; frequent/constant
quivering chin, clenched jaw; distressed looking face,
expression of fright or panic
Individualized behavior_____________
Legs
0 = Normal position or relaxed; usual tone and motion to Legs and arms drawn to center of body; clonus in left leg
limbs with pain; very tense and still; legs tremble
1 = Uneasy, restless, tense, occasional tremors
2 = Kicking or legs drawn up; marked increase in
spasticity, constant tremors or jerking
Individualized behavior ____________
Activity
0 = Lying quietly, normal position, moves easily; regular, Grabs at site of pain; nods head; clenches fists, draws up
rhythmic respirations arms; arches neck; arms startle; turns side to side; head
1 = Squirming, shifting back and forth, tense or guarded shaking; points to where it hurts; clenches fist to face, hits
movements; mildly agitated (e.g. head back and forth, self, slapping; tense, guarded, posturing; thrashes arms;
aggression); shallow, splinting respirations, intermittent bites palm of hand; holds breath
sighs
2 = Arched, rigid or jerking; severe agitation head
banging; shivering (not rigors); breath holding, gasping or
sharp intake of breaths, severe splinting
Individualized behavior __________
Cry
0 = No cry/verbalization States, “I’m okay” or “All done”; mouth wide open and
1 = Moans or whimpers; occasional complaint; screaming; states “Owie” or “No”; gasping, screaming;
occasional verbal outburst or grunt grunts or short responses, whining, whimpering, wailing,
2 = Crying steadily, screams or sobs, frequent complaints; shouting, asks for medicine, crying is rare
repeated outbursts, constant grunting
Consolability
0 = Content and relaxed Responds to cuddling, holding, parent stroking, kissing;
1 = Reassured by occasional touching, hugging, or being distant and unresponsive when in pain
talked to. Distractable.
2 = Difficult to console or comfort; pushing away
caregiver, resisting care or comfort measures
a
Excerpts from the additional descriptions of the individual child’s pain behavior recorded by parents on the revised Face
Legs Activity Cry and Consolability (FLACC) tool during the preoperative interview. Only 21 parents added such
comments to the revised FLACC
Regional analgesic techniques supplemented with

opiates and nonopioid medications such as non- Approaches to Pain Management
steroidal anti-inflammatory drugs (NSAID),
gabapentinoids, and clonidine have proven to be Opioids, nonopioids, and regional analgesia are
effective in controlling postoperative pain the common medications used for postoperative
(Mikawa et al. 1996; Schmidt et al. 2007; pain, and antispasmodics are used to manage mus-
Choudhry et al. 2017). cle spasms. Since children with CP frequently
Opioids, α2 agonists,
TCAs, SSRIs
Descending noradrenergic
and serotoninergic
inhibitory fibers
Ascending
Local anesthetics, spinothalamic
α2 agonists Opioids, ketamine, fibers
Local anesthetics, gabapentinoids
NSAIDs
Dorsal
root ganglion Dorsal horn
Nerve Local anesthetics
endings
Primary
afferent
nerve
©2015
MAYO
Fig. 1 The pain pathway and interventions that can modulate activity at each point. (Reproduced with permission from
Gorlin et al. 2016)
undergo extensive lower extremity procedures, Less common effects include dysphoria, hallucina-
continuous epidural analgesia has become an tions, seizures, and myoclonic movements. There
indispensable modality for managing severe is significant individual variability in the side
postoperative pain. effects profile of different opioids, and switching
to a different opioid may reduce the severity of the
side effects (Quigley 2004). Morphine still remains
Opioids the most frequently administered opiate and con-
tinues to be the standard with which others are
Opioids are commonly used for the treatment compared. Morphine can be administered via intra-
of moderate to severe pain. Opioids bind to pre- venous, oral, and epidural routes. The common
and postsynaptic cell membranes in the central opioids and their dosing parameters are given in
nervous system through the specific opioid recep- Table 4.
tors resulting in neuronal inhibition by decreasing
excitatory neurotransmitter release from the
presynaptic terminals or by hyperpolarizing the Nonopioid Drugs
postsynaptic neuron (Brislin and Rose 2005).
Opioid receptors are classified as μ, ƙ, δ, and σ. Nonsteroidal anti-inflammatory drugs (NSAID)
Most commonly used opioids work through have an established role in the management
μ-mediated analgesia (Stein and Rosow 2004). of mild to moderate postoperative pain. In addi-
Side effects common to opioid agonists include tion, for moderate to severe pain, they are
respiratory depression, sedation, nausea, vomiting, a valuable adjunct and reduce opioid consump-
pruritus, urinary retention, ileus, and constipation. tion by as much as 40%. They inhibit
Table 4 Opioid drugs dosing regimens

Drug Route/age Dose /interval Special features
Morphine Infant and 50–100 mcg/kg every Most commonly used
children 3–4 h Has active metabolite – morphine-6 glucuronide
IV bolus 10–30 mcg/kg/h
Infusion 0.2 to 0.3 mg/kg every
Oral 3–4 h
Hydromorphone IV bolus 10–20 mcg/kg every 4 h Five times as potent as morphine
Infusion 3–5 mcg/kg/h Increasingly used as first line opioid
Oral 0.04 to 0.08 mg/kg Less nausea, vomiting, and pruritis
every 3–4 h
Fentanyl IV bolus 0.5–1 mcg/kg every 100 times more potent than morphine
Infusion 1–2 h No active metabolite
Intranasal 0.5 mcg/kg/h High brain penetration due to high lipid solubility
Transdermal 1–2 mcg/kg
12.5/25/50/100/mcg/h
patches
Oxycodone Oral 0.05–0.15 mg/kg every As tablet or liquid
4h 60% bioavailability
Alone or in combination with acetaminophen
Active metabolite-oxymorphone
Hydrocodone Oral 0.1–0.2 mg/kg every 4 h As tablet or liquid
Alone or in combination with acetaminophen
Active metabolite-hydromorphone
Nalbuphine IV bolus 50–100 mcg/kg every Agonist-antagonist, risk of opiate withdrawal in
Infusion 2–4 h dependent children
20mcg/kg/h
Table 5 Nonopioid drugs dosing regimen

Drug Preparation Dose Special features
Ketorolac Injectable: 0.5 mg/kg; every 6 h Nonselective COX inhibitor, NSAID
15 mg/ml Maximum 20 doses Avoid if renal dysfunction,
coagulopathy and GI bleed
Ibuprofen Tabs: 200/400/ 6–10 mg/kg; every 4–6 h NSAID, avoid if renal dysfunction,
600/800 mg Approve only for children greater
Chewable tabs: than 6 months
50/100 mg
Elixir: 100 mg/
5 ml
Acetaminophen Tabs: 325/500 mg PO: 10–15 mg/kg Centrally acting COX-3 inhibitor
Elixir: 165 mg/ Rectal: single dose 30–40 mg/kg, Cannabinoid agonist
5 ml repeat dose 20 mg/kg Analgesic and antipyretic
Suppositories Very well tolerated
Intravenous
Clonidine Transdermal 50–100 mcg patch α2 agonist, anxiolytic, and analgesic
Caudal, epidural 1 mcg/kg Sedation and hypotension
cyclooxygenase enzyme which metabolizes Antispasmodics

arachidonic acid released from tissue injury to
form prostaglandin and thromboxane which sen- Spasticity is seen in 70% of the children with CP
sitize nerve endings and vasodilate vessels, caus- and its management is an essential element of
ing pain, erythema, and inflammation. The acute postoperative pain management. Brain dam-
dosing regimens of the commonly used NSAIDs age in these children likely creates a relative
are given in Table 5. imbalance between inhibitory neurotransmitter
gamma aminobutyric acid (GABA) and excit- medications have been used in the epidurals
atory neurotransmitter notably glutamate, in the such as dexmedetomidine (Park et al. 2017) and
descending inhibitory neurons (Nolan et al. 2000; clonidine (Chalkiadis et al. 2016) that have shown
Albright 1996). Benzodiazepines are one of promise for reducing spasm with little additional
the most frequently used agents postoperatively sedation. Epidural baclofen has also been used via
to alleviate pain due to muscle spasms. the epidural route; however, it was not found to
Chronic muscle spasticity is often treated with reduce spasm in the postoperative period (Nemeth
baclofen (oral/ intrathecal) and botulinum toxin et al. 2015).
(intramuscular). Peripheral nerve blocks have become com-
monplace as the usage of portable high-definition
ultrasound has allowed the delineation of nerves
Regional Approaches to block and blood vessels to avoid. While epi-
dural analgesia is good for multilevel and com-
In contrast to patients without CP, patients with plex bony and soft tissue procedures, often a
significant spasticity preoperatively experience single limb or a combination of arm and leg
severe muscle spasm in addition to pain in the surgery (as occurs in the hemiparetic group)
postoperative period. Muscle- and tendon- may be more amenable to peripheral nerve block-
lengthening procedures can result in significant ade. Peripheral nerve blockade, specifically pop-
amplification of spasm and pain in the early liteal blocks, prior to incision, has been shown to
postoperative period. In undertreated patients, a reduce the anesthetic requirements during the
vicious cycle of pain begetting spasm begetting procedure and analgesic use in the postoperative
pain, the so-called pain-spasm cycle (Nemeth et al. period (Ozkan et al. 2017). Further expansion of
2015), is initiated requiring heavy doses of narcotics regional blockade may be beneficial in the CP
and benzodiazepines to break the cycle. While the population, as studies determine the efficacy and
mainstay of postoperative pain management was indications.
parenteral narcotics and benzodiazepines, these reg-
imens have been fraught with side effects such as
sedation and respiratory depression. As a result, Postoperative Spasticity Management
central neuraxial and regional techniques for
extremity surgery have gained favor for manage- As mentioned, patients with CP that have signifi-
ment of pain and spasm in the postoperative period. cant spasticity preoperatively are at risk for
Continuous epidural analgesia has been increased pain and spasm in the postoperative
observed to provide excellent analgesia in chil- period. This is largely due to the pain-spasm cycle
dren with CP, with fewer side effects than inter- as previously described (Nemeth et al. 2015).
mittent bolus epidural analgesia (Brenn et al. Treatment of spasticity in general consists of phys-
1998). Epidural local anesthetics provide some ical therapy techniques, oral and injected medica-
spasticity relief, but most patients require addi- tions, and surgical techniques (Tilton 2009; Chung
tional benzodiazepine for spasm. One center also et al. 2011). These are discussed in other chapters,
employed a two-catheter approach to improve and we wish to focus on those anti-spasticity tech-
spread and coverage in multilevel orthopedic pro- niques commonly employed in the postoperative
cedures, which seemed to also reduce the severity period as part of comprehensive pain management.
of postoperative spasm and diazepam administra- In the immediate postoperative period,
tion (Nolan et al. 2000). diazepam can be given by the oral, rectal, or
The agents used in the epidural include intravenous route. This benzodiazepine acts post-
bupivacaine and ropivacaine as local anesthetics synaptically on gamma amino butyric acid a
with either fentanyl or hydromorphone as the (GABAa) receptors and has a half-life of up to
narcotic component (Nolan et al. 2000; Brenn 18 h. The dosage range is 0.1–0.02 mg per kg
et al. 1998). Recently, other adjunctive given every 6–8 h. A limitation of the use of
diazepam is that it can cause considerable seda- pain management therapy. The catheter site is
tion. Still, given that it can be administered several inspected daily to ensure continued correct place-
different ways, it is the most versatile muscle ment, signs of inflammation or infection, and
relaxant in use in the postoperative period. inspect for soilage of the site from fecal or urinary
Baclofen is a GABA analogue, which inhibits sources which may result in redressing or removal
the release of excitatory neurotransmitters in the of the catheter.
spinal cord. Baclofen can be administered via the
oral and intrathecal route. It is not a common drug
used in the perioperative period because orally it Pain Management for Specific
requires several days to weeks to titrate to effec- Procedures
tive levels. However, if the patient has an intra-
thecal pump in place infusing baclofen or has one The most common orthopedic procedures
placed as part of multiple procedures, then IT performed on patients with CP are multilevel
baclofen can be effective in combatting spasm in lower extremity soft tissue (typically multiple ten-
the postoperative period. Baclofen is associated don lengthenings), multilevel bony and soft tissue
with several side effects including sedation, nau- (including femoral and pelvic osteotomies), and
sea and vomiting, confusion, and hypotension complex posterior spinal fusions (Theroux and
(Chung et al. 2011). DiCindio 2014). The anesthetic management of
these three types of procedure is covered else-
where in the text, and our goal here is to focus
Monitoring on the distinct multimodal pain management reg-
imens and issues for each.
Monitoring postoperative patients with CP has Patients that undergo soft tissue procedures in
particular nuances. In addition to the standard our institution receive a single-shot caudal or
postoperative monitoring, additional measures epidural intraoperatively. In the postoperative
need to be taken to ensure a safe recovery period period, the pain management consists of intermit-
to account for the degree of preoperative cardio- tent intravenous opioid, typically morphine with
respiratory compromise, the complexity of the scheduled ketorolac and scheduled diazepam for
procedure, and the potential side effects from the muscle relaxation for the first 24 h. Adjunctive
medications that are being administered. medications include ondansetron and diphenhy-
Patients managed by our pain service after dramine on an as needed basis. One subgroup
orthopedic procedures are placed on full cardiore- of patients, those that undergo repair of rectus
spiratory monitoring, including standard vital signs femoris muscle have significantly severe postop-
(HR, RR, and NIBP), ECG, and pulse oximetry. erative spasm. In these patients, a continuous
Typically the standard vital signs are recorded epidural catheter infusing ropivacaine and
every 4 h, while the ECG and pulse oximetry hydromorphone has been shown to provide better
are continuously monitored. Pain assessment is pain and spasm control (Brenn et al. 1998).
performed at least every 4 h and more frequently A continuous epidural either at the lumbar or
as needed to ensure that pain therapy is optimal. caudal site is typically the mainstay of therapy for
In patients that have an indwelling epidural patients who undergo bony lower extremity pro-
catheter, there are additional considerations. In cedures such as femoral or pelvic osteotomies.
addition to the standard vital signs and pain Typically the agents used are ropivacaine com-
assessments, it is important to assess sedation bined with an opioid either fentanyl or more
(sedation scoring) and the catheter entry site. recently hydromorphone. Additional opioids are
Sedation assessment can be difficult in patients avoided, while the catheter is infusing opioid.
with compromised mental status, but following a Ketorolac and diazepam are administered on a
baseline with subsequent assessments can indi- scheduled basis for 24 h. Ondansetron and Nubain
cate if the patient is becoming obtunded from the are administered as needed for nausea and pruritis.
Patients with CP undergoing posterior spinal ▶ Medical Management of Spasticity in Children

fusion have pain management which may be deter- with Cerebral Palsy
mined by the amount of trauma sustained ▶ Postoperative Pain and Spasticity Management
intraoperatively. In our institution, some of these in the Child with Cerebral Palsy
patients remain intubated in the postoperative
period and will have continuous infusions of opioid
and/or sedation medication administered. In those
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Regional Anesthesia in Patients
Kesavan Sadacharam, Robert P. Brislin, and R. Scott Lang
Contents
Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1160
Caudal Anatomy and Analgesia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1161
Epidural Anatomy/Analgesia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1165
Epidural Placement in Patients with a Baclofen Catheter . . . . . . . . . . . . . . . . . . . . . . . . 1166
Neuraxial Blockade in Patients after Spinal Instrumentation . . . . . . . . . . . . . . . . . . . . 1167
Peripheral Nerve Blocks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1168
Surgical Site and Type of Regional Blocks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1169
Hip and Thigh Surgeries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1169
Lumbar Plexus Block . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1169
Fascia Iliaca Compartment Block . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1171
Thigh Surgery and Femur Fracture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1172
Knee Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1174
Sciatic Nerve Block . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1174
Adductor Canal Block . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1175
Foot and Ankle Surgeries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1176
Regional Blocks for the Upper Extremity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1177
Shoulder Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1177
Upper Arm, Elbow, Forearm, Wrist, and Hand Surgery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1178
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1182
Abstract
Pain management in patients with cerebral
palsy is often complex due to coexisting med-
ical conditions, which make them vulnerable
K. Sadacharam (*) · R. P. Brislin · R. S. Lang
Division of Surgical Anesthesiology, Department of to the side effects of the opioid-based pain
Anesthesiology and Perioperative Medicine, Nemours/ management. In this instance, regional anes-
Alfred I. duPont Hospital for Children, Wilmington, thesia can be used to improve the quality of
DE, USA
analgesia and help to minimize the need
e-mail: kesavan.sadacharam@nemours.org;
robert.brislin@nemours.org; Robert.Lang@nemours.org for administration of opioids. Traditionally,

https://doi.org/10.1007/978-3-319-74558-9_85
1160 K. Sadacharam et al.
epidural and caudal anesthesia are the most procedures and techniques to improve pain manage-
common regional anesthesia techniques used ment for patients during the perioperative period.
in patients with cerebral palsy. However, Traditionally, central neuraxial blockade,
peripheral nerve blocks have become popular which includes caudal and epidural analgesia, is
in the last decade due to favorable evidence to the most popular technique to provide analgesia in
improve the quality of analgesia in children patients with cerebral palsy. Advantages of central
undergoing orthopedic procedures. The com- neuraxial blockade include familiarity with tech-
pelling evidence in favor of the use of periph- nique among most anesthesiologists, ability to
eral regional nerve blocks in the general prolong analgesia with placement of catheter,
pediatric population argues strongly for its and ample evidence of its benefits (Hopkins
inclusion in the pain management of children 2015) in improving outcomes both during the
with cerebral palsy. This chapter discusses the surgery and after the surgery. During surgery,
various options of regional procedure for central neuraxial blockade is known to minimize
common orthopedic procedures in patients blood loss. After surgery, it is reported to mini-
with cerebral palsy and illustrates each nerve mize the incidence of deep venous thrombosis
block in detail. Further, we describe the feasi- (Hopkins 2015).
bility of performing regional nerve blocks in Peripheral nerve blocks have also become pop-
challenging situations such as in patients with ular within the past decade in children undergoing
spinal instrumentation and baclofen catheter orthopedic procedures. This popularity is due to
in situ. favorable evidence from adult studies, increased
familiarity with ultrasound among practitioners,
improved training during anesthesiology resi-
Keywords
dency, and rarity of adverse events related to
Caudal epidural · Lumbar epidural · Peripheral
peripheral nerve blocks in the literature. Children
nerve block · Brachial plexus block · Femoral
with cerebral palsy more frequently have lower
nerve block
extremity procedures to improve functional out-
comes (e.g., ambulation) and to facilitate comfort-
able posture. Postoperative pain management is
Introduction challenging due to inconsistency in the assess-
ment of pain; increased risk of opioid-based pain
Regional anesthesia plays an integral part in pain management due to adverse events; and the need
management during the perioperative period for for additional medications, such as benzodiaze-
patients with cerebral palsy (▶ Chap. 80, “Postop- pines, to control muscle spasms, which can
erative Pain and Spasticity Management in the worsen the opioid-related side effects.
Child with Cerebral Palsy”). Adequate pain con- The evidence for the use of peripheral nerve
trol is essential to both provide comfort as well as blockade in children with cerebral palsy, however,
to attend to the general wellbeing of patients. In is limited. Cerebral palsy is primarily a motor
addition, good pain control facilitates early recov- disorder resulting from injury to the developing
ery from surgery and can help prevent some of fetal or infant brain, and there are multiple etiolo-
the potential side effects of immobility, such as gies. The primary neurological manifestation in
embolism and pneumonia. In general, intravenous cerebral palsy is the upper motor neuron disorder.
(IV) pain medication is used widely. However, IV The lack of inhibitory impulses from upper motor
pain medications must be chosen and administered neurons to the anterior horn of the spinal cord
carefully to provide adequate pain control and pre- results in spasticity and motor disorder. The
vent some of the side effects of the medications. For upper motor neuron disorder is not generally asso-
these reasons, regional anesthesia is used to help ciated with peripheral sensory neuron disorders.
minimize the need for IV administration and has As a result, peripheral nerve blocks in patients
continued to evolve as a subspecialty with new with cerebral palsy theoretically do not affect the
81 Regional Anesthesia in Patients with Cerebral Palsy 1161
anatomy or physiologic function beyond the dura- a projection, the sacral cornua. The cornu serves
tion of the action of local anesthetics. as an important landmark in the identification of
the sacral hiatus for caudal epidural block. Alter-
natively, the sacral hiatus can be located with an
Caudal Anatomy and Analgesia imaginary equilateral triangle, with the base
connecting the posterior superior iliac spines and
Caudal epidural anesthesia is one of the most the apex at the sacral hiatus (Fig. 2). The sacral
common regional anesthesia techniques hiatus is an inverted “U” shape; it is bound super-
performed in children. The caudal procedure has ficially by skin, subcutaneous tissue, and the
been in practice for a long time, and it is one of the sacrococcygeal membrane. At its sides, it is bor-
safest regional anesthesia procedures performed dered by the sacral cornua. Moreover, the apex of
in children (Suresh et al. 2015) (Fig. 1). The the sacral hiatus is the inferior portion of the fused
caudal canal is the epidural space found between articulating process of third sacral vertebra.
the termination of the dural sac and sacral canal. The contents of the sacral canal include the
The distal portion of the sacral canal is defective distal portion of the dural sac, cauda equina, epi-
in the dorsal side due to non-fused lamina of the dural fat, and epidural venous plexus. The caudal
fourth and fifth sacral vertebrae. The defective canal contents are the same for both children and
portion of the canal is referred to as the sacral adults. However, the width of the sacral hiatus and
hiatus. The incomplete articular remnants of the epidural fat vary with age. In general, epidural fat
non-fused sacral vertebra elongate distally to form content increases with age. The width of the sacral
Fig. 1 Safety of caudal

block. (Used with
permission: Suresh S,
Long J, Birmingham P, et al.
Are caudal blocks for pain
control safe in children? An
analysis of 18,650 caudal
blocks from the Pediatric
Regional Anesthesia
Network Database.
Anesthesia and Analgesia
2015;120:151–156)
Fig. 2 Anatomy landmark

for sacral hiatus. (Used with
permission: Lees D,
Frawley J, Taghavi K, Ali
Mirjalili S. A review of the
surface and internal
anatomy of the caudal canal
in children. Paediatric
Anesthesia 2014;
24:799–805)
hiatus is about 9 3 mm in neonates and the sacral hiatus and the dural sac varies in the
increases to about 17 3 mm in adults (Lees different populations studied (Kim et al. 2014).
et al. 2014). The anteroposterior diameter of the The length of the sacral canal between the apex of
sacral hiatus varies in the population between the sacral hiatus and the dural sac determines the
4.6 2 mm to 6.1 2.1 mm (Kao and Lin likelihood of accidental dural puncture and subse-
2017). The success of the caudal block using the quent intrathecal injection of local anesthetics. In
landmark technique using the triangle noted a study done by Adewale et al. (2000) in older
above can be affected by the anteroposterior diam- children, the mean distance between the upper
eter of the sacral hiatus. In one study, an ante- margin of the sacrococcygeal membrane and
roposterior diameter less than 3.7 mm was dural sac was 31 mm. The length of the
associated with difficulty in accessing the caudal sacrococcygeal membrane and depth of caudal
epidural space (Kim et al. 2014). The dural sac space at the sacrococcygeal membrane was
usually terminates between S1 and S2. Further, found to be 24 mm and 5 mm, respectively
the length of the sacral canal between the apex of (Adewale et al. 2000) (Figs. 3 and 4).
The landmark technique is the most commonly
used technique to access the caudal space. This
technique is dependent on anatomic landmarks
and the presence of normal anatomy. However,
the sacral canal is closed in 3% of the patients,
which makes access to the caudal epidural space
impossible. The sacral cornu is an important land-
mark to locate the sacral hiatus for the insertion of
the needle. In most patients, the cornu is palpated
at S4; however there are a 15% probability that the
apex is located at S3 or S5 and 5% probability that
it is located at S1 to S2 level (Sekiguchi et al.
2004). In addition, the cornu is absent in 54% of
cases. This variation in the location of the apex
can have an impact on the frequency of accidental
dural puncture during the performance of caudal
epidural anesthesia. In addition, there are also
variations of the sacral hiatus in 7% of the patients
Fig. 3 Distance between various anatomical landmarks
for caudal block – figure. (Used with permission: for various reasons, such as the absence of the
Adewale L, Dearlove O, Wilson B, Hindle K, Robinson sacral hiatus, a bony septum, and complete agen-
DN. Paediatric Anesthesia 2008;10:137–141) esis (Sekiguchi et al. 2004). Absence of the sacral
Fig. 4 Distance between various anatomical landmarks for caudal block – table. (Used with permission: Adewale L,
Dearlove O, Wilson B, Hindle K, Robinson DN. Paediatric Anesthesia 2008;10:137–141)
hiatus makes the caudal epidural space and the availability of a pain service team to
inaccessible. manage the catheter postoperatively. A caudal
During the performance of caudal epidural catheter can be placed before the surgery; there-
anesthesia, the child is positioned in the lateral fore, analgesia can be extended by continuous
decubitus position or prone. The choice of posi- infusion or multiple boluses of local anesthetic
tion depends on the comfort level of the practi- during the perioperative and postoperative
tioner, with the lateral decubitus being the most periods. The caudal space is accessed with a
commonly used. Low-level disinfection tech- Tuohy or Crawford needle. Once the entry of the
nique has been shown to be sufficient for single- needle into the caudal epidural space is confirmed,
shot caudal injection due to lack of evidence of the catheter is inserted up to the desired level. A
infection in the literature (Alakkad et al. 2015). catheter with a stylet is commonly used to place
The caudal space can be accessed with the use of a the epidural catheter via the caudal route. In gen-
short, beveled needle. In practice, there is a great eral, for orthopedic procedures, it is sufficient to
deal of variation in the type of needle used. How- have the tip of the catheter either at the upper
ever, the 22G 2-inch short beveled Tuohy needle lumbar or lower thoracic level. The placement of
is the most widely used. The short length and the catheter is confirmed through epidurogram by
beveled tip decrease the risk of accidental dural injection of contrast. The correct placement of the
or vascular puncture. In addition, the presence of a catheter is indicated by spread of contrast in the
stylet prevents the clogging of the needle with a epidural space (Brislin and Rose 2005). The
skin plug. After normal anatomy is confirmed epidurogram is still considered the “gold stan-
with palpation, the needle is inserted at an angle dard” for verification of catheter placement. How-
of approximately 30 degrees to 45 degrees to ever, drawbacks of the epidurogram include side
“pop” through the sacrococcygeal membrane. effects associated with use of contrast, exposure to
Once the membrane is pierced, the angle of the radiation, and additional required operating room
needle is dropped to almost parallel to the sacrum time. Recently, ultrasound is becoming popular to
to advance further a few millimeters into the epi- guide and confirm the placement of the caudal
dural space. Hitting the anterior table of sacrum catheter with equal success (Park et al. 2013).
with the tip of needle before entering the epidural The placement of the needle and the catheter in
space is a problem encountered frequently with the epidural space can be visualized in real time
this procedure and can be corrected by withdraw- with ultrasound followed by Doppler confirma-
ing and dropping the angle of the needle to less tion of injectate (Fig. 5).
than 45 degrees before further advancement. A The most common local anesthetics used to
second difficulty with this procedure is placement bolus caudal epidural anesthesia are 0.2%
of the needle tip in the subcutaneous tissue. This ropivacaine or 0.25% bupivacaine. Epinephrine
occurs when the angle of the needle is less than in the dose of 1:200000 is usually mixed with
30 degrees before the sacrococcygeal membrane the local anesthetic to detect intravascular injec-
is pierced. Once the needle is within the epidural tion of the drug. Administration of a test dose is
space, it is important not to advance further than a recommended before injection of the entire dose
few millimeters to avoid dural puncture. Further, of local anesthetic. The test dose identifies intra-
correct placement can be confirmed by negative vascular injection by an increase in heart rate and
aspiration of cerebrospinal fluid or blood before a change in the morphology of the “T” wave in the
injection of local anesthetic. ECG due to both the epinephrine and local anes-
The caudal epidural can be performed as a thetic (Fisher et al. 1997). The local anesthetic
single injection, or a catheter can be placed to should be injected slowly, allowing time to iden-
prolong the analgesia during the postoperative tify intravascular injection. The injection into the
period. The decision to perform a single injection caudal epidural space should be easy, with mini-
or to place a catheter depends on the complexity mal resistance. Excessive resistance to injection
of surgery, disposition of the patient after surgery, could be due to placement of tip of the needle in
Fig. 5 Sonoanatomy of
caudal space with needle
in situ
Table 1 Armitage formula of opioid administered can be minimized or, in

Dose of local anesthetic many instances, its use can be avoided. The child
Type of surgery (ropivacaine or bupivacaine) can be awakened after the surgery pain-free,
Lumbosacral 0.5 ml/kg which leads to improved patient and parental sat-
Thoracolumbar 1 ml/kg isfaction. These benefits also facilitate quicker
Midthoracic 1.25 ml/kg recovery after surgery and minimize other com-
plications such as respiratory depression and
vomiting.
In general, the duration of the single-shot cau-
the periosteum of the sacral bone. In addition, skin dal block is around 4 to 6 hours (Pullerits and
over the sacrum should be visualized to identify Holzman 1993). But, addition of epinephrine,
possible injection of drug in the subcutaneous clonidine, neostigmine, or tramadol is found to
tissue due to malposition of needle. In general, prolong the block anywhere from 3 to 10 hours
the dose of the local anesthetic should not exceed (Engelman and Marsala 2012) (Fig. 6). The wide
the maximum dose according to body weight. variation in the duration of analgesia from a
Alternatively, the dose can be modified depending single-shot caudal block is due to numerous fac-
on the site of surgery as per the Armitage formula tors that could impact quality of analgesia. Patient
(Armitage 1986). Armitage recommended a dose age, weight, dose of local anesthetic, addition of
of local anesthetic for caudal block based on the additives to local anesthetic, and site of surgery
body weight and site of surgery (Table 1). can all impact the quality and duration of analge-
The successful single-shot caudal epidural sia. The placement of a caudal epidural catheter
block offers significant benefits both during the will help extend the analgesia for several days
surgery and the early postoperative period. During after the surgery. However, removal of the cathe-
surgery, successful block helps maintain general ter after 3 days is preferred to reduce risk of
anesthesia with a lower concentration of inhala- infection. Analgesia can be maintained by contin-
tional anesthetics and decreases intraoperative uous infusion or multiple bolus doses of local
blood loss (Kim et al. 2011). Further, the amount anesthetic with or without opioids.
Table 2 Variation of position of spinal cord and dural sac

with age
Age group Spinal cord Dural sac
Neonates and infants L3 S3 or S4
Older children and adults L1 S1 or S2
the spinal cord ends at L3 and does not reach the

adult level of L1 until at least age 1 year (Table 2).
Thus, it is recommended that the site of needle
entry be at the L3-L4 or L4-L5 level to avoid
Fig. 6 Additives and duration of action of caudal anes- accidental spinal cord injury. In general, the
thesia. (Used with permission: Engelman E, Marsala intervertebral space is identified by the landmark
C. Bayesian enhanced meta-analysis of postoperative anal- technique. Tuffer’s line is an imaginary line
gesic efficacy of additives for caudal anesthesia in children.
Acta Anaesthesiologica Scandinavica 2012;56:817–822) connecting the top of the iliac crests and corre-
sponds to the L4 spinous process or L4-L5
intervertebral space (Ellis 1988). The line is the
landmark to identify safe level of intervertebral
Epidural Anatomy/Analgesia space. Alternatively, the desired lower lumbar
intervertebral space is palpated by moving the
Caudal epidural analgesia is the most commonly finger cephalad from the coccyx and sacrum.
used form of regional anesthesia in children. Patients with cerebral palsy frequently have sco-
However, in some instances, lumbar epidural liosis, and this can make the identification of
analgesia can be advantageous. In contrast to cau- lumbar spine intervertebral spaces difficult in
dal analgesia, lumbar epidural is usually this population. In such instances, it may be nec-
performed to place a catheter for continuous infu- essary to perform radiography in the operating
sion rather than as a single injection. The catheter room for the identification of the correct vertebral
in the caudal space is prone to soiling with feces level and intervertebral space.
due to proximity to the anal passage and, thus, In children younger than 5 years, a lumbar
potential risk of contamination (McNeely et al. epidural catheter can be placed with the shorter
1997). On the other hand, a catheter placed in 2-in Tuohy needle. Specially designed pediatric
the lumbar epidural space is relatively easier to epidural kits are available. In older children, the
maintain, and, thus, extending analgesia for sev- adult epidural kit with a 4-inch 18 G epidural
eral days is more likely possible. Specially needle may be used. Although the spinal anatomy
designed epidural catheter kits for use in children of small children is the same as in adults, there are
are available and have made it easier to perform subtle variations. In small children, the
lumbar epidural analgesia in children. ligamentum flavum is not well developed. As a
For insertion of a lumbar epidural catheter, the result, the anchoring of the Tuohy needle in the
patient is usually placed in the lateral position. ligamentum flavum is less easily appreciated than
Unlike in adults, epidural placement in children in adults. Thus, it is necessary to make small
is generally performed with general anesthesia. movements, with slow advancement of the needle
The low lumbar approach is sufficient to cover to prevent dural puncture. With experience, navi-
the dermatomes for all orthopedic procedures. gation through these tissues and ligaments
The advantage of the lumbar epidural catheter is becomes easier. In children, it is recommended
that the dose of local anesthetic infusion can be to use loss of resistance with saline to locate the
lowered as the tip of the catheter is expected to be epidural space. In small children, use of air for
close to the dermatome of the surgery. In infants, loss of resistance is discouraged due to risk of air
embolism and patchy epidural block because of epidural catheter is not radiopaque. However,
impaired spread of local anesthetics. There are catheters with a stylet are radiopaque and, thus,
multiple case reports of embolism due to use of easy to view radiographically. Another advantage
air for identification of the epidural space (Coté of a stylet catheter is that it navigates inside the
et al. 2009). epidural space better due to its stiffness. In our
In general, the entry of the needle in the practice, we routinely use a catheter without a
intervertebral space in children is perpendicular stylet, although if there is any anticipated diffi-
to the skin and parallel to the table in the lateral culty or if we encounter a problem during the
position. However, in patients with cerebral palsy, insertion, we then switch to catheter with a stylet
the needle entry may have to be modified due to (Gunter and Eng 1992). Further, the stylet cathe-
the high incidence of scoliosis. Once the epidural ters are preferable if the location of the tip is
space is located, the catheter is inserted to the anticipated to be within the thoracic region, due
desired level. It is not recommended to insert to ease of insertion with this type of catheter and
more than 6 centimeters of catheter in the epidural feasible radiographic confirmation of its tip.
space due to risk of intravascular placement or
one-sided epidural analgesia (Sadacharam and
Bandi 2010) (Table 3). Correct catheter placement Epidural Placement in Patients
is confirmed by negative aspiration of cerebrospi- with a Baclofen Catheter
nal fluid and blood. Correct placement is further
confirmed by injection of local anesthetic mixed Patients with cerebral palsy who undergo lower
with 1:200000 epinephrine to rule out intravascu- extremity surgeries may have indwelling intrathe-
lar injection. Since most epidurals in children are cal baclofen catheters. Due to the medical com-
placed after induction of general anesthesia, it is plexity of these patients, especially in children
preferred to not administer muscle relaxant to with quadriplegic cerebral palsy, opioid-based
maintain spontaneous respiration until correct pain management after the surgery may lead to
placement of the epidural catheter is confirmed. complications like respiratory depression, nausea,
In this way, accidental intrathecal injection of vomiting, and aspiration. As a result, placement of
local anesthetic can be identified by a sudden an epidural or caudal catheter may be beneficial in
cessation of spontaneous respiration. Overall, minimizing complications and improving out-
radiographic confirmation with contrast of cathe- comes. Potential drawbacks of an epidural cathe-
ter placement is not necessary. However, if place- ter in a patient with a baclofen pump could be
ment is difficult, then it is advisable to confirm accidental damage to the baclofen pump or cath-
placement radiographically before using the epi- eter, introduction of infection, and risk of intra-
dural catheter. Radiographic confirmation will thecal entry of local anesthetics. However, with
indicate the correct placement of the catheter in careful planning and execution of the procedure,
the epidural space and identify precise anatomic the abovementioned risks can be mitigated to
location, therefore predicting successful postoper- provide good postoperative analgesia and reduce
ative analgesia (Taenzer et al. 2010). The standard opioid-related complications.
A case report published by Piper et al. details
Table 3 Strategies to prevent intravenous placement of the methods used to prevent complications of
epidural catheter epidural placement in patients with a baclofen
Strategies to prevent accidental intravascular catheter (Piper et al. 2006). Prior to placement,
placement of epidural catheters the functionality and history of the baclofen pump
Fluid injection before insertion of catheter should be discussed with the orthopedic surgeon,
Lateral position for epidural placement and the patient and family should be aware of this
Use of single-orifice, wire-embedded catheters discussion. The potential risks and benefits should
Limit insertion of catheter to equal or less than 6 cm in be explained in detail to the patient or caregiver.
the epidural space
Placement of an epidural catheter should be in a
Fig. 7 Epidural needle in situ in a patient with baclofen Fig. 8 Epidural needle in situ in patient with baclofen
pump, lateral view pump, anteroposterior view
patient with a newly placed baclofen pump, as it

increases the risk of infection and the entry of surgery and use of the epidural (Figs.7 and 8). In
local anesthetic injected through the epidural cath- general, the risk of epidural abscess with the epi-
eter into the intrathecal space. The ideal time to dural catheter is rare; however, there is paucity of
perform an epidural in these patients has not been evidence in patients with concomitant baclofen
determined, but in general, it is about 2 months catheters. Therefore, duration of epidural analgesia
after intrathecal catheter placement (Piper et al. postoperatively should be limited to less than
2006). The next step is to identify the exact loca- 3 days or as soon as the patient can be transitioned
tion of the baclofen catheter tip and entry point of to oral analgesics, whichever is earlier.
catheter in the intrathecal space. The baclofen
pump is usually placed away from the midline in
the anterior abdominal wall, and catheter entry is Neuraxial Blockade in Patients after
most commonly done as a paramedian approach. Spinal Instrumentation
The most common level for the baclofen pump
and catheter is in the lumbar area. Once the entry Children with spine instrumentation for scoliosis
point of the baclofen pump catheter is identified, frequently return for later surgery in the pelvis and
the needle insertion for the epidural catheter is lower extremities (▶ Chap. 118, “Surgical Treat-
about one or two vertebral spaces away. It is best ment of Scoliosis Due to Cerebral Palsy”). Post-
to perform the epidural in the space above the operative pain management in these patients may
insertion of baclofen catheter, but there is no evi- be complicated due to the presence of spine instru-
dence against placing it in one or two vertebral mentation. The decision to perform neuraxial
levels below the insertion site. Number of analgesia in these patients depends upon the med-
attempts to locate the epidural space should be ical complexity and the type of spine instrumen-
limited as each attempt increases the risk of hema- tation used. Spine instrumentation has evolved
toma and subsequent infection. Once the epidural from Harrington rods to the current pedicle
catheter is placed, location of the epidural needle/ screws. Therefore, the first step is to identify
catheter location and of an intact intrathecal bac- type of instrumentation and whether osteotomy
lofen catheter should immediately be confirmed of spinous process was performed during the pro-
radiographically, before proceeding with the cedure. Multiple issues may be encountered
during the performance of neuraxial blockade in successful catheter placement, insertion was
these patients. First, the primary landmark of the attempted multiple times. The authors in this
spinous process is not evident if the instrumenta- case series did not find any difference in the vol-
tion included osteotomy. Second, prior surgery ume or concentration of local anesthetic required
may have led to scar tissue and the subsequent in patients where the epidural catheter placement
loss of definition of anatomy, in particular, the was successful. However, access to the caudal
texture of the ligamentum flavum, which is one space in these patients may be easier than in
of the important anatomical landmarks for those with a lumbar epidural catheter. In our
neuraxial block. Loss of needle resistance to iden- experience, use of fluoroscopy facilitates the
tify epidural space may not be easily felt, leading identification of the caudal space and insertion
to failed epidural or accidental dural puncture. of the needle (Fig. 9). However, insertion of a
Hubbert performed epidural anesthesia in catheter may be challenging due to the presence
17 laboring patients with the history of Harrington of scar tissue cephalad to the lumbosacral junc-
rod placement for scoliosis (Hubbert 1985). Of tion depending on the distal limit of spine
17 patients, only 5 had successful catheter inser- instrumentation.
tion. In one patient, the catheter was in the spinal
space. In the remaining 11 patients without a
Peripheral Nerve Blocks
Peripheral nerve blocks have become popular in

the last decade for children undergoing orthope-
dic procedures. The increased popularity is due
to favorable evidence from adult literature,
increased familiarity with ultrasound, improved
training during residency, and the rarity of
published adverse events. For children with
cerebral palsy, these procedures more frequently
involve the lower extremities to improve func-
tional outcomes in ambulation and posture.
Postoperative pain management is challenging.
In neurologically impaired children, assessment
of pain is inconsistent. There is increased risk
with opioid-based pain management due to the
known opioid-related adverse events (▶ Chap.
80, “Postoperative Pain and Spasticity Manage-
ment in the Child with Cerebral Palsy”). In addi-
tion, need for additional medications such as
benzodiazepines to control muscle spasms can
worsen the opioid-related side effects. Evidence
for the use of peripheral nerve blocks in children
with cerebral palsy is limited; peripheral nerve
blocks have become popular in children only in
the last few years. The compelling evidence in
favor of the use of peripheral regional nerve
blocks in the general pediatric population argues
Fig. 9 Epidural catheter and epidurogram in patient with strongly for its inclusion in the pain management
prior spine instrumentation of children with cerebral palsy.
Surgical Site and Type of Regional Lumbar Plexus Block

Blocks
The upper part of the lower extremity is a chal-
Hip and Thigh Surgeries lenging anatomical area for analgesic coverage
when performing peripheral regional blockade
The most common types of hip and thigh surger- (Table 4). Two common regional anesthesia tech-
ies performed in children with cerebral palsy are niques used for hip procedures are the lumbar
pelvic osteotomy; femoral osteotomy; peri- epidural and multiple individual peripheral nerve
acetabular osteotomy; and multiple soft-tissue blocks. Both of these options have disadvantages.
procedures such as adductor tenotomy, Achilles Epidural analgesia provides bilateral blockade
tendon release, and hamstring release and length- and is often not necessary for unilateral surgeries.
ening (▶ Chap. 131, “Hip Reconstruction in Chil- In addition, patients with a lumbar epidural
dren with Cerebral Palsy”). The hip joint is require a urinary catheter to prevent urinary reten-
innervated by the femoral, sciatic, obturator, and tion. On the other hand, multiple peripheral nerve
lateral femoral cutaneous nerves. Thus, epidural blocks provide unilateral anesthesia or analgesia.
analgesia and lumbar plexus block are the The individual nerves targeted for multiple
regional anesthesia techniques used for pelvic peripheral nerve blocks for hip surgery are the
osteotomy. However, fascia iliaca block may pro- femoral, obturator, lateral femoral cutaneous,
vide adequate postoperative analgesia and reduce and genitofemoral nerves. Successful block of
opioid consumption. In this section of the chapter, all these nerves takes time and is not always
the lumbar plexus and fascia iliaca block are reliable. Lumbar plexus block provides an effec-
discussed. Epidural analgesia is discussed tive alternative. Potentially, the lumbar plexus
elsewhere. block can be performed with an injection of a
single bolus of local anesthetic. The lumbar
plexus is composed of a combination of the ven-
tral rami of the first through fourth lumbar spinal
nerves, with a contribution from T12. It lies deep
Table 4 Lumbar plexus block
within the psoas muscles, and, hence, this proce-
Lumbar plexus block dure is sometimes termed the “psoas compartment
Primary indications block.” The plexus is concentrated around the
Total hip arthroplasty fourth lumbar vertebra and, therefore, provides
Surgical repair of fractured neck and shaft of femur opportunity for blockade with a single injection
Primary nerves blocked with block
of local anesthetic. The lumbar plexus is bordered
Femoral
anteriorly by the psoas muscle and its fascia;
Obturator
medially by the body of the lumbar vertebra; and
Lateral femoral cutaneous nerve
posteriorly by the transverse process of the verte-
Advantages
Provides unilateral block for one-sided surgery in
bra, ligaments, and quadratus lumborum muscle
contrast to bilateral block with epidural (Fig. 10).
Single shot injection Lumbar plexus block in combination with a
Less hypotension in comparison to epidural sciatic nerve block provides analgesia of the entire
Less urinary retention thus urinary catheter not lower limb for lower extremity surgery. However,
indicated the lumbar plexus block is considered challenging
Less pruritis due to the deeper location of the plexus; variation
Complications in the depth of the plexus; and the close proximity
Total spinal of the plexus to vital structures like the spinal
Accidental epidural spread
cord, the retroperitoneum, and the internal
Retroperitoneal hematoma
abdominal organs. The goal of the lumbar plexus
Injury to intra-abdominal organs
block is to inject local anesthetic into the fascial
Fig. 10 Spread of contrast with lumbar plexus block
Fig. 11 Surface landmark

for lumbar plexus block
(Used with permission:
Mannion S. Psoas
compartment block. BJA
Education
2001;7:162–166)
plane on the posterior surface of the psoas muscle. lumbar plexus. The transverse process of the L5
Although most of the literature about the lumbar vertebra is the shortest of the lumbar vertebra and,
plexus block is regarding adults, it has been suc- thus, the needle will miss the L5 transverse pro-
cessfully and safely performed in children cess to reach the lumbar plexus. Subsequently,
(Walker et al. 2011; Dalens et al. 1988). Winnie multiple different approaches have been described
described the most common landmark used to with mixed success. In recent times, ultrasound
perform this block in 1975 (Winnie 1975). The has been increasingly used to perform this block.
authors used the intersection of the intercristal line However, the localization of the lumbar plexus is
and a perpendicular line drawn through the poste- difficult due to acoustic shadows of the transverse
rior superior iliac spine parallel to the spine as the process of the L4 vertebra, especially in older
entry point for the needle (Fig. 11). The needle is children older than 12 years. The lumbar plexus
inserted with a medial inclination to reach the block has been associated with significant
complications due to the technical complexity using a landmark technique. The principal land-
related to its performance. Significant complica- mark used is the line between the pubic tubercle
tions that have been reported in the literature are and anterior superior iliac crest, which is divided
accidental total spinal, epidural spread, local anes- into thirds. The needle entry point is 1 cm caudal
thetic toxicity, puncture of vital organs, and retro- to the intersection of middle third and lateral third
peritoneal hematoma (Aveline and Bonnet 2004; of the line. The local anesthetic is deposited deep
Dogan et al. 2014). Therefore, in summary, lum- to both fascia lata and fascia iliaca. During the
bar plexus block can be performed in patients with performance of the block, the penetration of both
cerebral palsy. However, the practitioner should fascia is felt as a double pop. Dalens et al. reported
be aware of the increased risk in patients with a good spread of contrast media anterior and
cerebral palsy due to the prevalence of scoliosis medial to the iliacus muscle (Dalens et al. 1989).
and the challenges therefore presented. The spread of contrast media provided an indirect
confirmation of spread and coverage of all three
nerves.
Fascia Iliaca Compartment Block One major disadvantage of the technique
described by Dalens et al. is the reliance on the
Winnie first described the 3-in-1 femoral block to tactile sensation of the double pop as the needle
provide unilateral analgesia for hip, thigh, and pierces through the fascia lata and fascia iliaca
knee surgeries (Winnie 1975) (Table 5). However, (Dalens et al. 1989). The failure to identify the
3-in-1 block is not as reliable as lumbar plexus “pop” can lead to incorrect deposition of local
block. The outcomes were equivocal due to anesthetic and failure of the block. To overcome
incomplete analgesia of the obturator and lateral this problem, ultrasound is used to deposit the
femoral cutaneous nerve distributions. As a result, local anesthetic in the correct place, underneath
Dalens et al. (Dalens et al. 1989) studied the the fascia, by direct visualization of the needle
anatomy of the fascia iliaca and the distribution path. There are two approaches for the ultra-
of local anesthetic underneath the fascia to sound-guided fascial iliaca block. In the first
develop a new technique called the fascia iliaca approach, the local anesthetic is deposited below
block. The goal of the block is the same as the the inguinal ligament. The high-frequency ultra-
3-in-1 technique, namely, to anesthetize three sound probe is placed in the transverse plane
nerves, the femoral, lateral femoral cutaneous, below the inguinal ligament in the anterior thigh
and obturator nerves anteriorly. This is in contrast to visualize the femoral artery, iliacus muscle, and
to the posterior approach done with the lumbar fascia iliaca. Then, an in-plane approach is used to
plexus block. Both are used to provide analgesia place the needle underneath the fascia iliaca, and
before, during, and after surgery with reasonable local anesthetic is injected in the plane between
success. the fascia iliaca and the iliacus muscle lateral to
In contrast to the 3-in-1 block, the fascia iliaca the femoral nerve. It is a high-volume block and
block is performed away from the femoral artery usually necessitates 30 ml to 40 ml of local anes-
thetic to ensure good spread to cover all three
nerves. In children, the maximum dose of the
Table 5 Fascia iliaca block local anesthetic is not exceeded (e.g., the maxi-
Advantages mum dose of ropivacaine is 2 mg/kg). The second
Easy technique approach is a high-dose longitudinal supra-
Easy to teach inguinal fascia iliaca block (Desmet et al. 2017).
Less risk of severe complications The ultrasound is placed in the sagittal plane to
Ultrasound-guided block is feasible visualize the anterior superior iliac spine. The
Disadvantages
ultrasound probe is then moved medially to visu-
Large volume of local anesthetic necessary
alize the fascia iliaca, sartorius muscle, iliacus
High chance of missing obturator nerve coverage
muscle, and internal oblique muscle. Local
anesthetic is injected under the fascia iliaca to lumbar vertebrae. First, it runs through the psoas
facilitate cephalad spread to increase the success muscle and then between the psoas and iliacus
of block. With this approach, Desmet et al. dem- before entering the thigh posterior to inguinal
onstrated decreased postoperative morphine con- ligament. At the inguinal ligament, the femoral
sumption and better pain scores in patients who nerve is lateral and posterior to the femoral artery
had total hip arthroplasty (Desmet et al. 2017). and is sandwiched between the iliacus muscle and
fascial iliaca. Although the nerve lies in close
proximity to the artery, it is not in the same vas-
Thigh Surgery and Femur Fracture cular fascia of the artery and vein. Immediately
distal to the inguinal ligament, the nerve divides
The femoral, obturator, and lateral femoral cuta- into anterior and posterior divisions. The anterior
neous nerves innervate the thigh and femur. The division supplies the skin of the medial and ante-
anterior division of the femoral nerve innervates rior surface of the thigh. The posterior division
the anterior thigh, and the posterior division inner- supplies the anterior thigh and branches further
vates the anterior medial skin of the thigh. The into the saphenous nerve, muscular branches to
sensory innervation to anterior lateral and poste- the quadriceps muscle, and the articular branch to
rior aspects of the thigh terminating in prepatellar the knee joint.
plexus is by the lateral femoral cutaneous nerve. The femoral nerve is generally blocked at the
In addition, the obturator nerve provides innerva- level of the inguinal ligament. This can be done by
tion to the posterior medial thigh. As a result, landmark technique with the use of a nerve stim-
depending upon the actual site of surgery, all the ulator, or with ultrasound. The use of ultrasound
three nerves have to be anesthetized together or in helps identify the femoral nerve in real time and
isolation. inject local anesthetic in close proximity to the
nerve with precision. Hence, the landmark tech-
Femoral Nerve Block nique has become obsolete. A high-frequency
The femoral nerve is the largest branch of lumbar linear ultrasound probe is used to perform the
plexus and is formed by the dorsal divisions of the block. The probe is placed in the transverse direc-
anterior rami of the second, third, and fourth tion at th

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Freeman Miller

With 1503 Figures and 175 Tables

Nancy Lennon Margaret E. O’Neil

ISBN 978-3-319-74557-2 ISBN 978-3-319-74558-9 (eBook)

In 2005, Springer published a landmark textbook with the title “Cerebral

Director, Hugh Williamson Kerr Graham, M.D., FRCS(Ed), FRACS

Acknowledgments from the First Edition

The support of the administration of the Nemours Foundation, especially the

understanding the complex material in which Erin Browne excelled. This

Section 1: Diagnosis and Pathology

Part I Diagnosis and Pathology ............................ 1

1 The Child, the Parent, and the Goal in Treating

Part II Etiology of Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

2 Cerebral Palsy and the Relationship to Prematurity ...... 23

10 Risk Factors for Developing Cerebral Palsy . . . . . . . . . . . . . 111

Part III Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 129

11 Epidemiology of Cerebral Palsy . . . . . . . . . . . . . . . . . . . . . . . 131

12 Health and Healthcare Disparities in Children with

Part IV Pathology ......................................... 175

13 Neuroimaging Pathology in Cerebral Palsy . . . . . . . . . . . . . . 177

14 Current Imaging: PET Scan Use in Cerebral Palsy . . . . . . . 217

15 Neuromuscular Junction Changes in Spastic

16 Muscle Changes at the Cellular-Fiber Level in

17 Muscle Size, Composition, and Architecture in

18 Bone Size, Architecture, and Strength Deﬁcits in

Part V Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 285

19 When and How to Evaluate the Child with Possible

20 Cerebral Palsy Prognosis Based on the Physical and

21 Classiﬁcation Terminology in Cerebral Palsy . . . . . . . . . . . . 309

22 Measuring Outcomes in Children with Cerebral Palsy . . . . . 325

Section 2: General Medical

Part VI General Medical Concerns . . . . . . . . . . . . . . . . . . . . . . . . . . 347

24 General Nutrition for Children with Cerebral Palsy . . . . . . . 349

Part VII Central Neurologic Problems . . . . . . . . . . . . . . . . . . . . . . . 455

31 Epilepsy in the Child with Cerebral Palsy . . . . . . . . . . . . . . . 457

Part VIII Psychologic and Psychiatric Problems . . . . . . . . . . . . . . 495

34 Psychiatric Disorders in Children with Cerebral Palsy . . . . 497

35 Autism Spectrum Disorder in the Child with Cerebral

Part IX Neuromotor Function .............................. 557

38 Motor Control and Muscle Tone Problems in

Part X Gastrointestinal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 727

49 Overview of Feeding and Growth in the Child with

50 Gastrostomy and Jejunostomy Feedings in Children with

51 Gastroesophageal Reﬂux in the Child with Cerebral

52 Medical and Surgical Therapy for Constipation in

Part XI Ear, Nose, and Throat . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 781

53 Medical Management of Sialorrhea in the Child with

54 Surgical Options for Sialorrhea Management in

55 Auditory Rehabilitation in Children with Cerebral

56 Upper Airway Obstruction in the Child with Cerebral

57 Surgical Management of Tracheostomies

Part XII Genitourinary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 841

58 Toilet Training and Bladder Control in Children

59 Neurogenic Bladder in Cerebral Palsy: Upper Motor

Part XIII Pulmonary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 905

63 Bronchopulmonary Dysplasia and Cerebral Palsy . . . . . . . . 907

Part XIV Endocrine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 957

68 Short Stature in Children with Cerebral Palsy . . . . . . . . . . . 959

Part XV Eyes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1013

72 Testing Visual Function and Visual Evaluation Outcomes

73 Strabismus Management in the Child with

74 Cortical Visual Impairment in the Child with

Part XVI Dental . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1057