Neurological Rehabilitation - Spasticity and Contractures in Clinical Practice and Research

Neurological
Rehabilitation
Spasticity and Contractures in
Clinical Practice and Research
Rehabilitation Science in Practice Series
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Neurological Rehabilitation: Spasticity and Contractures in Clinical Practice and
Research, edited by Anand D. Pandyan, Hermie J. Hermens, Bernard A. Conway
Neurological
Rehabilitation
Spasticity and Contractures in
Clinical Practice and Research
Edited by
Anand D. Pandyan
Hermie J. Hermens
Bernard A. Conway
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Library of Congress Cataloging‑in‑Publication Data
Names: Pandyan, Anand, editor. | Hermens, Hermie J., editor. | Conway,

Bernard A., editor.
Title: Neurological rehabilitation : spasticity and contractures in clinical
practice and research / [edited by] Anand Pandyan, Hermie J. Hermens, and
Bernard A. Conway.
Other titles: Neurological rehabilitation (Pandyan) | Rehabilitation science
in practice series.
Description: Boca Raton, FL : CRC Press/Taylor & Francis Group, 2018. |
Series: Rehabilitation science in practice series | Includes
bibliographical references and index.
Identifiers: LCCN 2017058710| ISBN 9781466565449 (hardback : alk. paper) |
ISBN 9781315374369 (ebook)
Subjects: | MESH: Muscle Spasticity--therapy | Contracture--therapy |
Neurological Rehabilitation
Classification: LCC RC935.S64 | NLM WE 550 | DDC 616.85/6--dc23
LC record available at https://lccn.loc.gov/2017058710
Visit the Taylor & Francis Web site at

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and the CRC Press Web site at

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Contents
Editors..................................................................................................................... vii
Contributors.............................................................................................................ix
1. Definition and Measurement of Spasticity and Contracture.................1

Anand D. Pandyan, Bernard A. Conway, Hermie J. Hermens
and Garth R. Johnson
2. Pathophysiology of Spasticity..................................................................... 25
Jens Bo Nielsen, Maria Willerslev-Olsen and Jakob Lorentzen
3. Functional Problems in Spastic Patients Are Not Caused

by Spasticity but by Disordered Motor Control..................................... 59
Jakob Lorentzen, Maria Willerslev-Olsen, Thomas Sinkjær
and Jens Bo Nielsen
4. The Clinical Management of Spasticity and Contractures

in Cerebral Palsy............................................................................................ 79
Andrew Roberts
5. Clinical Management of Spasticity and Contractures in Stroke....... 101

Judith F. M. Fleuren, Jaap H. Buurke and Alexander C. H. Geurts
6. Clinical Management of Spasticity and Contractures in Spinal

Cord Injury................................................................................................... 135
Martin Schubert and Volker Dietz
7. Clinical Management of Spasticity and Contractures

in Multiple Sclerosis................................................................................... 175
Lorna Paul and Paul Mattison
8. Clinical Assessment and Management of Spasticity

and Contractures in Traumatic Brain Injury......................................... 203
Gerard E. Francisco and Sheng Li
9. Hereditary Spastic Paraparesis and Other Hereditary

Myelopathies................................................................................................ 235
Jon Marsden, Lisa Bunn, Amanda Denton
and Krishnan Padmakumari Sivaraman Nair
Index...................................................................................................................... 289
v
http://taylorandfrancis.com
Editors
Anand D. Pandyan, PhD, is Professor for Rehabilitation Technology and

Head of the School of Health & Rehabilitation at Keele University. He origi-
nally trained as a bioengineer and has a special interest in neurological
rehabilitation, clinically usable measurement and applied clinical research.
His interest in spasticity started during his PhD study (Bioengineering Unit,
University of Strathclyde, Glasgow) and he completed a five-year postdoc-
toral training period at the Centre for Rehabilitation and Engineering Studies
(CREST), Newcastle upon Tyne (with Professors Garth Johnson and Michael
[Mike] Barnes) exploring the phenomenon of spasticity in stroke. His cur-
rent portfolio of research projects, carried out in partnership with therapists
and local clinicians, is aimed at: developing a better understanding of the
pathophysiological basis of spasticity and its impact on people with upper
motor neurone lesions; identifying the therapeutic benefits (and mecha-
nisms of action) associated with treatment involving electrical stimulation;
and exploring the effects of early antispasticity treatment and studying their
long-term impacts. Much of his current research is focussed on neurological
patients with severe levels of disability.
Hermie J. Hermens, PhD, earned his master’s in Biomedical Engineering at

the University of Twente. His PhD, on surface EMG modelling, processing
and clinical applications, was also undertaken at the University of Twente,
and he subsequently became Professor of Neuromuscular Control at the
same institution. He was the initiator and coordinator of the SENIAM project,
which resulted in a broadly accepted worldwide standard on surface EMG
electrode properties and their placement on the muscles. He was, together
with Anand D. Pandyan, actively involved in the European SPASM project,
which resulted in important new insights into the definition of spasticity and
procedures and methods for assessing spasticity in a quantitative way.
Dr. Hermens was co-founder of Roessingh Research and Development
(RRD), originating from the Roessingh Rehabilitation Centre, which has
now grown into the largest institute in the area of rehabilitation tech-
nology and telemedicine in the Netherlands. He gradually switched his
research area from rehabilitation technology towards combining biomedi-
cal engineering with ICT to enable remote monitoring and telemedicine. In
2008, he became Professor of Telemedicine and Head of the Telemedicine
Research Group, at UTwente; in 2010 Director of Telemedicine at RRD and,
in 2012, Director of Technology at the Centre for Care Technology Research
(CCTR) and Visiting Professor at the Caledonian University in Glasgow.
vii
viii Editors
Bernard A. Conway, PhD, is Professor in Biomedical Engineering at the

University of Strathclyde, where he co-directs the Centre for Excellence in
Rehabilitation Research. He earned his PhD in Neurophysiology from the
University of Glasgow and since then has focussed his research interests
on problems related to the loss of control of movement in patients with neu-
rological conditions including spinal cord injury, movement disorders, and
limb loss. Over his career he has enjoyed close collaboration with clinical
colleagues, giving his research a translational perspective. The multidisci-
plinary nature of his research has led to its publication in a diversified group
of journals. He has also been actively involved in supporting funding agen-
cies in various advisory capacities linked to bioengineering, rehabilitation,
health technologies, and ageing. He currently is a trustee of the Institute of
Physics and Engineering in Medicine and Medical Research Scotland.
Contributors
Lisa Bunn Gerard E. Francisco

School of Health Professions Department of Physical Medicine
Faculty of Health and Human and Rehabilitation
Sciences University of Texas Health Science
University of Plymouth Center
Plymouth, United Kingdom and
NeuroRecovery Research Center
Jaap H. Buurke TIRR Memorial Hermann Hospital
Roessingh Research and Houston, Texas
Development
University of Twente Alexander C. H. Geurts
Enschede, Netherlands Radboud University Medical Centre
Department of Rehabilitation
Bernard A. Conway Nijmegen, Netherlands
Department of Biomedical
Engineering Hermie J. Hermens
University of Strathclyde Roessingh Research and
Scotland, United Kingdom Development
University of Twente
Volker Dietz Enschede, Netherlands
Spinal Cord Injury Center
University Hospital Balgrist Garth Johnson
Zürich, Switzerland ADL Smartcare Ltd
Newcastle University
Amanda Denton Newcastle, United Kingdom
School of Health Professions
Faculty of Health and Human Sheng Li
Sciences Department of Physical Medicine
University of Plymouth and Rehabilitation
Plymouth, United Kingdom University of Texas Health Science
Center
Judith F. M. Fleuren and
Roessingh Rehabilitation Centre NeuroRecovery Research Center
Roessingh Research and TIRR Memorial Hermann Hospital
Development Houston, Texas
Enschede, Netherlands
ix
x Contributors
Jakob Lorentzen Anand D. Pandyan

Institute of Neuroscience School of Health and Rehabilitation
University of Copenhagen Keele University
and Keele, United Kingdom
Elsass Institute
Charlottenlund, Denmark Lorna Paul
School of Health and Life Sciences
Jon Marsden Glasgow Caledonian University
School of Health Professions Glasgow, United Kingdom
Faculty of Health and Human
Sciences Andrew Roberts
University of Plymouth Orthotic Research and Locomotor
Plymouth, United Kingdom Assessment Unit
Robert Jones and Agnes Hunt
Paul Mattison Hospital Oswestry
Ayrshire Multiple Sclerosis Service United Kingdom
Douglas Grant Rehabilitation Centre
Ayrshire Central Hospital Martin Schubert
Irvine, United Kingdom Spinal Cord Injury Center
University Hospital Balgrist
Krishnan Padmakumari Zürich, Switzerland
Sivaraman Nair
Department of Neurology Thomas Sinkjær
Royal Hallamshire Hospital Department of Health Science and
Sheffield Teaching Hospitals NHS Technology
Foundation Trust Aalborg University
Sheffield, United Kingdom Aalborg, Denmark
Jens Bo Nielsen Maria Willerslev-Olsen

Institute of Neuroscience Elsass Institute
University of Copenhagen Charlottenlund, Denmark
and
Elsass Institute
Charlottenlund, Denmark
1
Definition and Measurement
of Spasticity and Contracture
Anand D. Pandyan, Bernard A. Conway,

Hermie J. Hermens and Garth R. Johnson
CONTENTS
1.1 Introduction.....................................................................................................1
1.2 Definition of Spasticity...................................................................................2
1.2.1 Can the Words Increased Tone/Hypertonia and Spasticity
Be Used Interchangeably?.................................................................3
1.2.2 Developing the Framework for Defining Spasticity.......................6
1.2.2.1 Increased (Hyper-Excitable/Exaggerated) Reflexes........8
1.2.2.2 Spasms and Clonus..............................................................8
1.2.2.3 Altered Tone or the Response of a Relaxed Muscle
to an Externally Imposed Stretch......................................9
1.2.2.4 Abnormal Movement Patterns and Co-Contraction..... 12
1.2.3 The Classification and Definition of Spasticity in Upper
Motoneuron Syndrome.................................................................... 13
1.2.4 Contractures in Patients with Upper Motoneuron Syndrome......14
1.2.5 The Measurement of Spasticity and Contracture........................ 17
1.2.6 Concluding Thoughts....................................................................... 19
References................................................................................................................ 21
1.1 Introduction
Spasticity is a clinical condition that is expected to develop following a lesion
in the descending tracts of the central nervous system (CNS), at any level (i.e.,
cortex, internal capsule, brain stem, or spinal cord) (Burke [1988]). It is a com-
mon neurological impairment with a reported prevalence of between 20%
and 80% (this will depend on the population under study and the method
of measurement), which is considered clinically important (see subsequent
chapters for disease-specific data). Not all spasticity is considered trouble-
some to patients; however, a significant number of patients with spasticity
will require treatment. Treatment of spasticity is often driven by goals aimed
1
2 Neurological Rehabilitation
at improving function or preventing significant secondary complication such

as pain, pressure sores, limb deformities, etc.
At a pathophysiological level this condition has been studied in reasonable
detail since the 1880s and our current understanding of the pathophysiologi-
cal basis of this condition and its impact on function has been summarised in
Chapters 2 and 3. Unfortunately, the literature related to treatment is scanty
and the quality is predominantly poor (and the team found this to be a sig-
nificant challenge in the compilation of this book). The two main barriers to
good science have been the lack of a proper definition of the term spasticity
and the use of invalid methods of measurement.
Attempting to provide a universally acceptable definition that is both sci-
entifically valid and clinically usable is probably too much of a challenge
for now; however, an attempt will be made to present a framework that may
help in this process. It may help for readers to have an understanding of
this framework before reading the individual disease-specific chapters. The
measurement of spasticity is a much easier problem to deal with as there
are a range of valid measures that are available. This chapter will, therefore,
summarise the state-of-the-art approaches to the measurement of spasticity,
both directly or indirectly.
1.2 Definition of Spasticity
The observations of Landau (1974) that the term spasticity has become such
a habitual part of neurological jargon that no one is expected to define it remains
true today in practice (Landau [1974]). What is more challenging is that this
behaviour appears also to have permeated the published research! In his
editorial, Landau (1974) provides six variations to the definition of spasticity
found in the literature. Unfortunately, since then, many more have appeared
(e.g. Lance [1980a,b,c]; Sanger et al. [2003]; Pandyan et al. [2005]; Malhotra et
al. [2009]).
Currently, there is agreement that spasticity is a condition that can develop
following an upper motoneuron lesion. Most texts would suggest that the
sensory motor problems following an upper motoneuron lesion, of any
origin, can be classified as having positive features and negative features
(Pandyan et al. [2009]). This particular approach to classification can be traced
back to the work of Hughlings Jackson (York and Steinberg [2007]), who con-
sidered that the positive features were associated the exposure of activity
that was previously inhibited by the nervous system and the negative fea-
tures result from the loss of higher-level excitatory control. This classification
was based on Jackson’s thinking of the nervous system as being hierarchical,
with the higher levels having modulatory control over the lower levels. Table
1.1 summarises the features of the upper motor syndrome as commonly
Definition and Measurement of Spasticity and Contracture 3
TABLE 1.1
A Summary of the Positive and Negative Features Associated with the Upper
Motoneuron Syndrome, as Commonly Reported in the Literature
Positive Features Negative Features
Increased reflexes Weakness
Spasticity Fatigueability
Altered tone Loss of dexterity (motor control)
Spasm & clonus
Abnormal movement patterns & co-contraction
reported in the literature and the text, and it is important to note that spastic-
ity was only considered as one feature of the upper motoneuron syndrome.
Spasticity is derived from the Greek root word spastikos, which means draw-
ing or tugging. If one reads the literature from the time of 1830 (see Chapter 4),
it appears that the term spasticity is often associated with a ‘resistance one feels
when passively moving/mobilising a limb segment’ and was also associated
with the terms tone and rigidity (Siegel [1988]). Although a variety of descrip-
tions exist in the literature, the first formal definition appears in the works of
Denny Brown, where he defines spasticity in capsular hemiplegia as the pres-
ence of a soft yielding resistance that appears only towards the end of a passive stretch,
and is associated with increased amplitude stretch reflex (Denny-Brown [1966]). Two
decades later, in a series of post-conference discussions and a presentation,
Lance (1980a,b,c) put forward a series of definitions for the term spasticity. Of
the three definitions, the one that is most commonly cited defines spasticity as
a motor disorder characterised by a velocity dependent increase in tonic stretch reflexes
(muscle tone) and increased tendon jerks resulting from disinhibition of the stretch
reflex, as one component of an upper motoneuron lesion (Lance [1980b]).
However, the literature still appears not to have any form of consensus
with respect to a definition (Pandyan et al. [2005]; Malhotra et al. [2009]).
When the literature was last reviewed, approximately a third of the litera-
ture equated spasticity with increased or altered muscle tone or hypertonia
(and this will be discussed in Section 1.2.1). A third of the literature defined
spasticity according to the Lance (1980b) definition (as cited above) or some
minor variation. A third of the literature did not define the term spasticity at
all, suggesting that not much has been learnt since Landau (1974) or the more
recent article from Thilmann (1993). Accordingly, and before we progress to
discussing a framework for defining spasticity, it is important to first deal
with use of the term (high) tone as a synonym for spasticity.
1.2.1 Can the Words Increased Tone/Hypertonia

and Spasticity Be Used Interchangeably?
The term tonus was originally introduced in 1838 to describe the slight con-
tractile tension in the muscles when at rest (Rushworth [1960] citing Mueller
[1838]). It is fascinating to read the summary of Cobb and Wolf (1932) follow-
ing the First International Congress of Neurology:
Confusion of thought has occurred throughout the diverse use of the

term tonus. However carefully defined it now carries with an incubus
of vague connotation which seems to cloud the issue. Its place as term
applied to striated muscle can be more accurately taken over by such
specific terms as ‘standing reflex’, ‘postural reflex’, and ‘righting reflex’.
The state of the striated muscle at any moment can be described by
adjectives such as slack or taut. Better still the amount of tension can
be measured and stated in quantitative terms. We make a plea that the
term tone be either discarded or returned to its former home in smooth
muscle and kept there.
It is frustrating that we appear not to have learnt very much from the preci-
sion in the literature of the past. There is now clear evidence that in a state
of rest skeletal muscles are electrically silent and that there is good reason to
believe that the advice of Cobb and Wolf (1932) is just as appropriate today
as it was then. However, asking for people to change entrenched behaviour
is unlikely.
There are currently two separate definitions of the term tone that are
acknowledged:
• The first equates tone with the resistance one feels when passively
moving a limb segment about a joint.
• The second equates tone with the readiness to act.
The term hypertonia (or high tone) is related to the first definition of tone (i.e.,
an increased resistance that one encounters during passive limb displacement).
The assumption being made is that any resistance encountered to an exter-
nally imposed passive movement is due to an increased activation of muscles
(e.g. Sanger et al. [2003]). There is now ample evidence that such an assumption
cannot be made (Malhotra et al. [2008]). The resistance that one encounters is
often associated with changes in the biomechanical properties of soft tissues
and joint structures (Figure 1.1). In certain circumstances, increased muscle
activity can contribute to this increased resistance in the absence of any form
of soft tissue and joint changes, but this is rare (Figure 1.1).
The term hypotonia is often related to both definitions of tone. If one
considers the argument in support of a condition of hypotonia against the
first definition of tone then the hypothesis one has to consider is that the
resistance to passive movement in people with hypotonia is lower than nor-
mal. This does make the assumption there is ‘normal tone’. The evidence is
clear: in a relaxed state there is no electrical activity in muscles. The stiffness
measured in patients with a dense flaccid paralysis is also not very different
to people who have no neurological deficits (Barnaby et al. [2002]); Kumar
100 100
70 70
Force (N)
Force (N)
40 40
10 10
20 38 56 74 92 110 128 146 164 182 200 20 38 56 74 92 110 128 146 164 182 200
–20 –20
–50 –50
Angle (degrees) Angle (degrees)
Pre Pre
Lin. reg pre Lin. reg pre
Post Post
Linear reg post Linear reg post
(a) (b)
FIGURE 1.1
Recording of stiffness at the elbow (the slope of the force angle curve) measured before and
after injection of Botulinum Toxin – A (BoNT-A). The trace in gray is before injections and
the trace in black is four weeks after injections. Both patients are responders to treatment of
botulinum toxin, i.e., the injections suppressed the stretch-induced activation of muscles. In
the patient with no contractures (left-hand pane [a]; discussed in Section 2.3) the stiffness was
influenced by the abnormal muscle activity associated with spasticity (stiffness pre-injection
was 0.4 N/deg and post-injection was 0.2 N/deg). Note also that in this patient a catch fol-
lowed by a release can be seen. However, in the patient with the established contractures
(b) there was no change in stiffness, suggesting that the spasticity had no contribution to the
resistance to passive movement (stiffness pre-injection was 1.1 N/deg and post-injection was
1.0 N/deg). (With permission from Pandyan AD et al. [2009] Spasticity, The New Encyclopedia
of Neuroscience. Squire LR, ed. Vol 9. Oxford: Academic Press, pp. 153–163.)
et al. [2006]). In the circumstances, the argument that people with low tone
have lower-than-normal resistance to an externally imposed movement is
untenable. The other argument links the definition of hypotonia to the sec-
ond definition of tone (i.e., the muscles can be activated with a smaller-than-
normal stimulus or the muscle is not in a state of readiness to act). This is a
more complex problem to deal with. In some patients with an upper moto-
neuron lesion there is evidence that a smaller-than-normal stimulus (proprio-
ceptive, cutaneous, etc.) can trigger the activation of an involuntary response
of either an isolated muscle or a group of muscles (see Chapter 2). However,
such patients are often treated, contradictorily, as hypertonic not hypotonic.
One then has to consider whether patients with hypotonia have a lower-than-
normal ‘readiness to act’ and the only interpretation left is that such a person
does not have an ability to act, i.e., they are paralyzed. It is important to high-
light that the original articles on rigidity and spasticity use two specific terms:
hypertonic paralysis and hypertonicity in paralysis. The former term is used to
describe patients who were unable to voluntarily activate muscles (paralysis)
and whose muscles are in a state of contraction. The latter term is used to
describe patients who are unable to activate muscles voluntarily (paralysis) but
an examiner is able to elicit or observe reflex muscle activation (Bennett [1887]).
In summary, the words hypertonia and spasticity cannot be used inter-

changeably. From a first-principles argument, if there was a choice the authors
would probably want to support the position taken by Cobb and Wolf (1932)
and Rushworth (1960), i.e., not to use these terms within the context of neu-
rological rehabilitation. These terms, however, have been extensively used
already and such a recommendation would not be adopted. However, it is
important that readers reflect on this discussion when they interpret the
term tone, both within this book and in the general literature. Furthermore,
for the future, if people choose to use the word tone then it is important that
the term is explicitly defined whenever it is used. The challenges of not pro-
viding such definitions can be seen with the chapters of this book, in particu-
lar the chapters on cerebral palsy and multiple sclerosis (Chapters 4 and 7,
respectively), where the authors have struggled to interpret the term tone as
the literature has not defined this for them.
1.2.2 Developing the Framework for Defining Spasticity

Having accepted that the term spasticity is likely to remain in common use,
one then needs to consider a framework that will help with articulating a
clinically meaningful definition of this term for routine clinical and research
use. More importantly, a valid definition and description is an essential first
step in measurement. The remainder of this section will therefore focus on
developing a framework for the definition and description of the term spas-
ticity. Two teams, in the early part of 2000, explored ways to develop a uni-
versally acceptable definition for spasticity. The first of these teams, the Task
Force on Childhood Motor Disorders, took the approach of splitting existing def-
initions to provide a series of sub-definitions. The second of these teams, A
European Thematic Network to Develop Standardised Measures of Spasticity, took
a diametrically opposite approach of lumping existing definitions into a uni-
versal definition. The two approaches are chronologically described below.
Sanger et al. (2003) provide a series of definition linked to both spasticity
and hypertonia. Their definition for hypertonia will not be discussed further
in this section as the arguments as to why such a definition will not work
have already been presented in Section 2.1. Sanger et al. (2003) defined hyper-
tonia as a case in which one or both of the following signs are present: (1) resistance
to externally imposed movement increase with increasing speed of stretch and varies
with the direction of joint movement and/or (2) resistance to externally imposed move-
ment rises rapidly above a threshold speed or joint angle. Such a definition does not
add much clarity to the definition originally proposed by Lance (1980b); in
fact, one could argue that it confuses the measurement a lot more. At a fun-
damental level, there are two major problems with the above definition: (i) a
velocity-dependent increase in resistance to passive movement is an inherent
viscoelastic behaviour of muscles and tendons (Figure 1.2); and (ii) the thresh-
old speed or joint angle are not defined per se. Under these circumstances one
would argue that the approach to splitting lacks adequate precision.
20 –10º 10º
PF DF
16
25º.s–1
Torque (N.m)
Affected
12 limb
8
5º.s–1
4
FIGURE 1.2
Stiffness measured at the knee joint using two different velocities. The authors Singer et al.
(2003) have clearly demonstrated that changes in velocity-dependent stiffness can be inde-
pendent of spasticity. (With permission from Singer B et al. [2003] Velocity dependent passive
flexor resistive torque in patients with acquired brain injury. Clinical Biomechanics 18:157–165.)
The SPASM Consortium (Pandyan et al. [2005]), after reviewing the litera-
ture came to the conclusion that the term spasticity was being used to refer
to a range of signs and symptoms associated with the upper motoneuron
lesion. This is probably true of clinical practice too, and anecdotal evidence
from discussions with students, researchers and clinical practitioners con-
firms that this is the case. If one were to ensure that all of the relevant lit-
erature associated with the term spasticity was to be reviewed, then there
was a need to develop a definition that was sufficiently broad so as to be
inclusive of all of the clinical manifestation but adequately specific to focus
on the neurological basis of the phenomenon. The consensus definition that
was agreed defined spasticity as disordered sensori-motor control, resulting from
an upper motoneuron lesion, presenting as intermittent or sustained involuntary
activation of muscles. This definition then meant that spasticity was no longer
a term used to denote one component of the upper motoneuron syndrome
(as described in Table 1.1) but all of the positive features upper motoneuron
syndrome (Table 1.2).
TABLE 1.2
The Redefining of Spasticity by the Spasm Consortium Resulted in a Definition
That Was a Reflection of Both the Literature and Clinical Practice
Spasticity as Defined by SPASM
Positive Features Consortium
Increased reflexes Increased reflexes
Spasticity Spasm and clonus
Spasm and clonus Altered tone
Altered tone Abnormal movement patterns
Abnormal movement patterns & co-contraction and co-contraction
Whilst such an all-encompassing definition has some benefit, it is of lim-

ited clinical and research value as this does not provide an unambiguous
framework to inform the measurement process. In order to develop this defi-
nition further it is important the lumped definition can be split or stratified
in a way that could inform the measurement process. This would require the
examination of the individual components and explore if the components
could be classified as spasticity. This process is described below. It is impor-
tant to note that pathophysiology is discussed comprehensively in Chapter 2,
so this chapter will not review pathophysiology.
1.2.2.1 Increased (Hyper-Excitable/Exaggerated) Reflexes

The term increased reflexes will very specifically be equated to the response
observed following a clinical testing of reflexes, i.e., where an examiner taps a
tendon to produce a transient stretch of the muscle that then leads to a subsequent
contraction. Although not formally studied, the literature seems to suggest that
the sensitivity* and specificity† of the stretch reflex response as currently mea-
sured is a poor indicator of spasticity in both acute and chronic populations. The
literature also remains unclear on what constitutes the signature of an increased
reflex: do these terms mean the reflex has a lower threshold, greater magnitude,
longer duration or a combination of all. The reflex response, when tested clini-
cally using a tendon tap, normally will involve mono- andpolysynaptic path-
ways, meaning that the observation of a change in reflex cannot in itself be a
sub-classification of spasticity but rather is a reflection of changed excitability.
Furthermore, as this discussion develops (Sections 1.2.2.2 and 1.2.2.3) it will
become more apparent that many of the other signs and symptoms that can be
classified under the umbrella definition of spasticity is predominantly associ-
ated with changes in excitability within a variety of motor pathways.
1.2.2.2 Spasms and Clonus

A spasm can be defined as a transient but continuous muscular contraction which
can be triggered by a combination of cutaneous and/or visceral triggers and a clo-
nus is defined as a transient but intermittent rhythmic muscle contraction with
proprioceptive and/or cutaneous triggers. Both of these signs are commonly
reported in patients with spasticity. Both of these phenomena are common
in patients with upper motoneuron lesions. Exact prevalence and incidence
cannot be reported as these are not systematically documented. Spasms
can affect both the flexor and extensor muscle groups of patients and can
be influenced by changes in ambient temperature. Anecdotal reports sug-
gest that an increase in spasms is normally associated with a decrease in
temperature. Cutaneous stimuli that are noxious can trigger spasms. There
* Sensitivity: the ability to accurately identify those with spasticity.

† Specificity: the ability to accurately identify those without spasticity.
is some anecdotal evidence that spasms can be influenced by changes in

activity within the autonomic nervous system. However, this association has
not been systematically studied in any depth. It is important to note that
spasms can occur due to reasons other than spasticity, i.e., there is a lack
of specificity. Despite this, if a person has spasms subsequent to the upper
motoneuron lesion one could conclude that this is an indicator of spasticity.
Clonus is also documented to occur, predominantly at the ankle joint, in the
later stages following an upper motoneuron lesion. In studies conducted on
stroke patients, upper limb clonus is very rarely observed at the elbow joint
(<1%) and its prevalence in the lower limb is most likely a consequence of
excitability changes facilitating interactions between neurogenic networks,
reflex loops, and the biomechanics of the muscle/joint system. At this stage,
there is adequate theoretical evidence to consider both spasms and clonus as
sub-classifications under the umbrella term of spasticity.
1.2.2.3 Altered Tone or the Response of a Relaxed Muscle

to an Externally Imposed Stretch
The research underpinning the response of a relaxed muscle to an externally
imposed stretch has probably been studied the most extensively in the litera-
ture. Some of the earliest clinicians and researchers measured spasticity by
studying the muscle response to an externally imposed stretch using either
fine wire or surface electromyography (EMG). It is a pity that somewhere
along the way this approach to studying spasticity has for all practical pur-
poses disappeared in clinical practice.
In neurologically healthy subjects, when a relaxed muscle is passively
stretched no EMG responses are normally observed below velocities of 200
deg/s. However, in patients with an upper motoneuron syndrome a range
of EMG responses can be seen (Figure 1.3). These can be classified as (a) a
velocity-dependent response, (b) a position-dependent response, a combina-
tion of (a) and (b), and (c) a clasp-knife-type response.
Whilst the muscles of most patients will be in a state of rest prior to the start
of the test, there are some patients in whom residual EMG activity at rest is
observed. The literature describes these patients as having ‘spastic dystonia’‡
(Figure 1.4). However, what is important to also note in such patients is the
phenomenon of position dependency, and possibly a combination of velocity
and position dependency can be observed.
Recordings such as those above have been widely observed (by, e.g.,
Tardieu et al. [1954]; Lance [1980a,b,c] and Rymer and Katz [1994]). Readers
are encouraged (after reading Chapter 2 of this publication) to explore the
literature produced by notable authors such as Sherrington, Matthews,
Denny-Brown, Tardieu, Pierrot-Deseilligny, Hultborn, Burke, Lance, etc.,
‡ Although we are not comfortable with this term it will be used until a suitable alternative can
be found (this is unlikely to happen!).
Slow vs fast (Vel & EMG)

500
402.48 0.1
Velocity during
400 fast movement EMG during 0.08
fast movement
300
0.06
Velocity (deg/s)
EMG (mV)
S_Vel S_FEMG
200
F_Vel F_FEMG
Velocity during 0.04
100 slow movement
0.02
0 EMG during slow movement
–1.818 4.406 × 10–3
–100 0
–80 –60 –40 –20 0 20 40
–64.139 S_Angle, F_Angle, S_Angle, F_Angle, 36.153
Angle (deg)
Slow velocity
Fast velocity
Slow_flexor EMG
(a) Fast_flexor EMG

100
99.189 0.29
Velocity during
60 fast movement 0.2
Velocity (deg/s)
EMG (mV)
S_Vel EMG during S_FEMG
40 Velocity during fast movement
F_Vel slow movement F_FEMG
20 0.1
0
EMG during
–5.31 slow movement 4.309 × 10–3
–20 0
–100 –80 –60 –40 –20 0
–97.38 S_Angle, F_Angle, S_Angle, F_Angle, –10.003
Angle (deg)
Slow velocity
Fast velocity
Slow_flexor EMG
(b) Fast_flexor EMG
FIGURE 1.3
Images recorded from the Biceps Brachii muscle of stroke patients. The elbow joint was fully flexed
and then extended using a ‘ramp and hold’ method (Rymer and Katz [1994]). The hold was <5 sec-
onds in duration. Two velocities were used to stretch the joint (an uncontrolled slow velocity and
an uncontrolled fast velocity as annotated on the respective graphs). The EMG during movement
was also collected and the corresponding EMG traces are annotated on the respective graphs. The
EMG activity was notch-filtered (50 Hz) and then smoothed using an RMS procedure as described
in the source article. (a) This graph shows a velocity-dependent response to an externally imposed
movement. There is very little EMG activity during the slow movement; however, there is a large
burst of activity during the fast movement. The EMG activity starts to drop off towards zero at the
end of the stretching movement. (b) This graph shows a position-dependent response to an exter-
nally imposed movement. The EMG activity increase as the muscle is stretched and the activity
remains elevated during the hold phase. It is also important to note the EMG activity during the
quick stretch starts earlier in the range of movement. (Continued)

300
EMG during
294.345 0.269
fast movement
0.25
Velocity during
200 fast movement
0.2
Velocity (deg/s)
EMG (mV)
S_Vel S_FEMG
100 Velocity during 0.15
0.1
0
0.05
EMG during
–5.04 slow movement 9.557 × 10–3
–100 0
–60 –40 –20 0 20 40 60
–48.161 S_Angle, F_Angle, S_Angle, F_Angle, 40.704
Angle (deg)
Slow velocity
Fast velocity
Slow_flexor EMG
(c) Fast_flexor EMG

200 0.1
158.085 EMG during fast 0.084
movement
150 0.08
Velocity during
Velocity (deg/s)
100 0.06
S_Vel fast movement S_FEMG EMG (mV)
Velocity during
50 0.04
0 0.02
EMG during fast
–7.425 movement 0.012
–50 0
–140 –120 –100 –80 –60 –40 –20
–122.589 S_Angle, F_Angle, S_Angle, F_Angle, –27.948
Angle (deg)
Slow velocity
Fast velocity
Slow_flexor EMG
(d) Fast_flexor EMG
FIGURE 1.3 (CONTINUED)

Images recorded from the Biceps Brachii muscle of stroke patients. The elbow joint was fully flexed
and then extended using a ‘ramp and hold’ method (Rymer and Katz [1994]). The hold was <5 sec
onds in duration. Two velocities were used to stretch the joint (a uncontrolled slow velocity and an
uncontrolled fast velocity as annotated on the respective graphs). The EMG during the movement
was also collected and the corresponding EMG traces are annotated on the respective graphs. The
EMG activity was notch-filtered (50 Hz) and then smoothed using an RMS procedure as described
in the source article. (c) This graph shows a combination of velocity- and position-dependent
responses to an externally imposed movement. The EMG activity increase as the muscle is
stretched and the activity remains elevated during the hold phase. It is also important to note the
EMG activity during the quick stretch starts earlier in the range of movement and is of a greater
magnitude. (d) This graph shows the clasp-knife response to an externally imposed movement.
The EMG activity increases rapidly as the muscle is stretched and this slows the movement down.
If the examiner continues with the stretch the EMG activity then reduces. This response occurs
during both the slow and fast stretch and is triggered at relatively slow velocities.
150
100 Angle
50 EMG triceps brachii
EMG biceps brachii Force

–50
0 2000 4000 6000 8000 1 · 104 1.2 · 104 1.4 · 104
Angle
Force
EMG(Flexors)
EMG(Extensors)
FIGURE 1.4
A figure illustrating the phenomenon of spastic dystonia. A patient demonstrating EMG of the
Biceps Brachii at rest. When the muscle is stretched the EMG activity increases as the stretch on
the muscle is increased and as the stretch is carried out using a quicker speed the magnitude
of the activity increases. It is important to note that in this patient stretching of the extensors
lead to activation of the Triceps Brachii. When the Triceps were active the activity in the Biceps
reduced.
all of whom employed direct measures of muscle electrical activity to gain

an understanding of spasticity.
What is obvious is that the stretch-induced response (i.e., velocity-dependent
response, position-dependent response, the velocity- and position-dependent
response and the ‘clasp-knife’ phenomenon) results from an afferent input
to the central nervous system. However, the abnormal muscle activity at
rest (i.e., spastic dystonia) appears to be independent of an afferent input to
the CNS (e.g., loss of cortical inhibition to the brainstem pathways/nuclei).
Within the context of a SPASM definition all of these conditions can be con-
sidered a sub-classification of spasticity.
1.2.2.4 Abnormal Movement Patterns and Co-Contraction

The abnormal movement patterns and co-contractions that are commonly
seen after an upper motoneuron lesion are currently classified under the
term spasticity. However, it is possible that the abnormal patterns of move-
ment and co-contraction one observes during voluntary movement may
result from the compensation to the weakness that co-exists (Chapters 2
and 3 discuss this possibility in greater detail). Furthermore, if one were to
test individuals with no known impairments, enhanced tremor-like oscilla-
tions and co-contractions can be provoked in cases of fatigue or peripheral
loading, the latter being the interia-sensitive mechanical-reflex oscillation

component of tremor (Elble and Koller [1990]). In normal movement, patterns
of co-contraction and the synergetic activation and de-activation of muscles
are the norm and are an essential feature of successful movement execu-
tion in both simple and complex actions. For example, the ability to grip and
transport an object will be severely compromised if one is unable to stabilise
the wrist and simultaneously coordinate the co-contraction of muscles of the
shoulder and elbow joint during this action. Under these conditions classify-
ing abnormal movement patterns and co-contraction as a sub-classification
of spasticity is not appropriate and, collectively, more appropriately reflects
a deficit of control.
1.2.3 The Classification and Definition of Spasticity

in Upper Motoneuron Syndrome
Based on our current understanding, and extending the work of the SPASM
consortium, it is possible to first define spasticity as an emergent feature of
disordered sensori-motor control, resulting from an upper motoneuron lesion, pre-
senting as intermittent or sustained involuntary activation of muscles. Spasticity
can present as:
• Spasms (A transient but continuous muscular contraction which can be

triggered by a combination of cutaneous and/or visceral triggers).
• Clonus (A transient but intermittent rhythmic muscle contraction with
proprioceptive and/or cutaneous triggers).
• Abnormal activation of muscles to an externally imposed stretch,
which can present as a combination of:
• velocity-dependent response;
• position-dependent response;
• ‘clasp-knife’ response.
• A continuous activation of muscles even in a state of rest (spastic
dystonia).
The clinical presentations of spasticity can be modulated by ambient affer-

ent inputs (e.g., touch, temperature, etc.); however, at this stage it is not pos-
sible to expand. Further, the time course of the development of spasticity
has not been well documented. What is clear is that immediately following
a lesion the central nervous system goes into a period of shock and recovery
during which time the system will start to present with varying responses
and time delays. The time course of development of spasticity is likely to be
disease-specific. In stroke, traumatic/hypoxic brain injury, and spinal cord
injury the evidence is that spasticity onset can be rapid (i.e., within 48 hours
or earlier) but often the onset time course is highly variable. The natural
history and time course of onset in many disease populations needs to be

established.
A significant limitation to the proposed definition is the narrow focus on
patients with an acquired upper motoneuron lesion. There are large popula-
tion of patients with acquired/degenerative disease of the nervous system
who present with signs that are similar to those described under spasticity
or spastic dystonia. In particular, patients with Parkinsonism who present
with rigidity and/or cog-wheel rigidity, patients with movement disorders
such as Huntington’s disease, Blepharospasm, and Cervical Dystonia, all of
whom can present with spasms (often termed dystonia) affecting different
parts of the body, and patients with motoneuron disease. Maybe discussion
of this is for a second edition; however, there is much work that needs to be
done to produce such a unifying framework for definition and measurement.
1.2.4 Contractures in Patients with Upper Motoneuron Syndrome

A contracture has been defined as a pathological condition of soft tissues
characterised by stiffness and is usually associated with loss of elasticity and
fixed shortening of the involved tissues (muscle, tendon, ligament, subcuta-
neous tissue, skin, blood vessels, and nerves) and results in loss of movement
around a joint (Botte et al. [1988]; Lehmann et al. [1989]; Harburn and Potter
[1993]; Teasell and Gillen [1993]). Contractures normally occur as a result of
a joint being fixed in a shortened position with a lack of loading to the soft
tissue structures. In the following paragraphs, we will briefly discuss factors
that can contribute to contractures following an upper motoneuron lesion.
Following an upper motoneuron lesion a patient will present with
paralysis or paresis and as a result the muscle and joint structures of the
affected periphery become unloaded. In particular, if a patient does not
regain functionally useful movement then the patient will present with
muscle atrophy, i.e., a decrease in the size of the muscle fibres and there-
fore the muscle itself, a decrease in the force generation capacity within
the muscle, and an increase in the fatiguability of muscles. The increase
in fatiguability probably arises from decreasing glycogen stores and ATP
levels within a muscle (Lieber [2009]). The loss of muscle mass could in
part be explained by an increase in the catabolic enzyme levels within
these muscles that have been paralyzed (Lieber [2009]). The loss of load-
ing, on the soft tissues, may also contribute to an increase in the collagen
crosslinks that occur within the tendon and soft tissue structures and this
can contribute to an increase in stiffness. However, it is important to note
that a patient presenting with no symptoms other than paralysis rarely
presents with contractures in the acute and subacute stages following the
neurological injury (Figure 1.5).
If a patient were to develop contractures, as defined above, in addition to
the lack of loading and motion, the joints should also be held in a shortened
position. Based on the evidence collected by Pandyan and co-workers there
5 3
4
EMG (mV)
EMG (mV)
EMG (mV)
EMG (mV)
Force (N)
Force (N)
Force (N)
Force (N)
2 0.02 0.02 2 0.02 2 0.02
3
2 0.01
1 0.01 0.01 1 0.01 1
1
0 0 0 0 0 0 0 0
– 50 0 50 – 50 0 50 – 50 0 50 – 50 0 50
Angle (deg) Angle (deg) Angle (deg) Angle (deg)
Angle vs Force (slow) Angle vs Force (slow) Angle vs Force (slow) Angle vs Force (slow)
Angle vs Flex or EMG Angle vs Flex or EMG Angle vs Flex or EMG Angle vs Flex or EMG
(ai) (aii) (aiii) (aiv)
4 0.04 4 0.04 4 0.04 4 0.04

EMG (mV)
EMG (mV)
EMG (mV)
EMG (mV)
Force (N)
Force (N)
Force (N)
Force (N)
3 0.03 3 0.03 3 0.03 3 0.03
2 0.02 2 0.02 2 0.02 2 0.02
1 0.01 1 0.01 1 0.01 1 0.01
0 0 0 0 0 0 0 0
–50 0 50 –50 0 50 –50 0 50 –100 –50 0 50
(bi) (bii) (biii) (biv)
5
4 0.04 4 0.04 4 0.04 4 0.04
EMG (mV)
EMG (mV)
EMG (mV)
EMG (mV)
Force (N)
Force (N)
Force (N)
Force (N)
3 0.03 3 3 0.03 3
2 0.02 2 0.02 2 0.02 2 0.02

1 0.01 1 1 0.01 1
0 0 0 0 0 0 0 0
–100 –50 0 50 –100 –50 0 50 100 –100 –50 0 50 –100 –50 0 50
Angle vs Force (slow) Angle vs Force (slow) Angle vs Force (slow) Angle vs Force (slow)
Angle vs Flex or EMG Angle vs Flex or EMG Angle vs Flex or EMG Angle vs Flex or EMG
(ci) (cii) (ciii) (civ)
FIGURE 1.5
The relationship between spasticity, contractures, and function. Graphs illustrating the observation
that the person most prone to developing a contracture is a patient who has not regained functional
movement and who also has concomitant spasticity (graphs ci to civ). Patients who (a) have spastic-
ity and yet recover function (graphs ai to aiv) and (b) have no function and no spasticity (graphs bi
to biv) appear not to develop contractures. In all the graphs above, stiffness (a plot of angle vs. force)
is indicated in gray and stretch-induced muscle activity from the forearm flexors (a plot of angle vs.
EMG activity) is indicated in black. The graphs were plotted for slow movement (ai, aiii, bi, biii, ci, ciii)
and the fast movement (aii, aiv, bii, biv, cii, civ) (unpublished observations from Cameron et al. [2014]).
Measurements were taken at the forearm flexors of the wrist less than two weeks after the stroke
(subscript of I and ii) and repeated six months after stroke (subscripts iii and iv). A patient present-
ing with velocity-dependent spasticity (ai, aiii, aiii, aiv). This person on admission after stroke, had a
NIHSS score of 18 and an action research arm test (ARAT) score of 1. At six months after stroke the
patient had a Barthel index of 15 and an ARAT score of 57. Contractures were assessed during slow
movement (i.e., the range of movement at the wrist had not changed and the stiffness at baseline
and at six months was 0.014 N/deg and at six months was 0.011 N/deg) and there was no evidence
that contractures had occurred. A patient presenting with no spasticity (bi, biii, biii, biv). This person,
on admission after stroke, had an NIHSS score of 17 and an ARAT score of 0. At six months after
stroke the patient had a Barthel index of 18 and an ARAT score of 0. Contractures were assessed
during slow movement (i.e., the range of movement at the wrist had not changed and the stiffness
at baseline and six months were both 0.009 N/deg) and there was no evidence that contractures had
occurred. A patient presenting with a combination of velocity and position-dependent spasticity
at the initial measurement (ci, ciii) and position-dependent spasticity, with potential signs of clonus
at the second measurement (ciii, civ). This person on admission after stroke had an NIHSS score of
13 and an ARAT score of 0. At six months after stroke the patient had a Barthel index of 3 and an
ARAT score of 1. Contractures were assessed during slow movement (i.e., the range of movement
at the wrist had reduced by about 50% at the six-month measurement; the stiffness had increased
from 0.007 N/deg at baseline to 0.047 N/deg at six-months) and there was unambiguous evidence
that contractures were established.
are three possible factors that can contribute to a person holding a limb in a
shortened position: (a) spasticity, (b) pain and (c) reduced cognitive ability.
• Does spasticity contribute to contractures?

Of the various forms of spasticity presented in Figure 1.3, it can be
hypothesised, in patients who have no return of useful function, that
any form of position-dependent spasticity, the ‘clasp-knife’ response,
and ‘spastic dystonia’ can all contribute to a limb being held in a short-
ened positon. If one were to extrapolate from the animal models then it
is possible that the rate of contracture formation is likely to be quicker
in patients with ‘spastic dystonia’ than in patients with a form of
position-dependent spasticity or the ‘clasp-knife’ response (Lieber
[2009]). A general rule appears to be that joints that are held in a short-
ened position through muscle activity develop contractures more rap-
idly than in active muscles held in shortened position. The evidence
from clinical studies reinforce these observations, i.e., people who have
no function and develop spasticity develop contractures more rapidly
than those who do not (Figure 1.4) (Pandyan et al. [2003]; Malhotra et
al. [2011]). People who regain limb function and present with signs
of spasticity do not develop contractures. A general confounder in
the literature is that most people who have studied the relationship
between spasticity and contractures have often used invalid clinical
scales, making interpretation of the results difficult.
• Does pain and cognitive dysfunction contribute to contractures?
Anecdotal evidence from data generated form a recently completed
study (unpublished observations from Cameron et al. [2014]) suggests
that patients with a combination of pain and/or congnitive dysfunc-
tion tend to be more prone to contractures. Many of these patients
were capable of functional movement but were often unable to use
their limbs due the nature of the pain and/or cognitive dysfunction.
The most plausible explanation for this is likely to be the individual
protecting the limb in a shortened positon in an attempt to alleviate
pain. However, these anecdotal associations need to studied more sys-
tematically before any firm conclusion can be made.
The literature seems to suggest that contractures, when they occur, are
more common at the ankle and the wrist when than at other proximal joints
(Sackley et al. [2008]).
If one were to explore the data from animal models and the few longitu-
dinal data in adult patients with acquired brain injuries, including stroke,
it can be found that contractures can develop quiet rapidly, i.e., within 4 to
6 weeks after a stroke (Malhotra et al. [2011]). This is also the time window
within which spasticity is expected to develop. This is an important consid-
eration when one has to start measuring or treating patients.
1.2.5 The Measurement of Spasticity and Contracture
When you can measure ... you know something about it – but when you cannot
measure ... your knowledge is of a meagre and unsatisfactory kind: it may be the
beginning of knowledge but you have scarcely, in your thought, advanced to the
stage of science whatever the matter may be (Lord Kelvin, 1889).
Both spasticity and contractures would come under the classification of

impairments under the ICF classification. From a first-principle basis one
needs to consider spasticity an impairment of the central nervous system
and contractures as an impairment of the musculoskeletal system. Both of
these impairments are likely to have an impact on activity, societal partic-
ipation, and possibly carer burden. From a clinical perspective, it may be
advantageous to measure spasticity indirectly, i.e., measuring the effects of
treatment on activity, societal participation, or carer burden as appropriate
to the needs of an individual patient. The disease-specific chapters have dis-
cussed approaches to measurement as appropriate. Within the context of this
chapter, however, the primary focus will remain on the measurement of the
primary impairments of spasticity and contractures.
The current methods of measurement or assessment can be classified as
clinical scales, biomechanical methods, and neurophysiological methods.
The most direct approach to measuring spasticity and the associated patho-
physiology is by using neurophysiological methods. The biomechanical
methods have the greatest potential to measure contractures. These three
approaches are briefly examined in this section and the relative merits are
discussed.
• Clinical scales to measure spasticity and contractures.

There are two scales that can be used to measure spasms: the
Penn Spasm Frequency Scale and the Spasm Frequency Score (Penn
et al. [1989]; Snow et al. [1990]; Biering-Sørensen et al. [2005]). Both
these scales are patient reported scales and quantify the severity of
spasms at an ordinal level of measurement. The reliability is limited
as this does depend on patient memory of events (Biering-Sørensen
et al. [2005]).
There are a variety of scales that measure the resistance to an
externally imposed passive movement and use these to indirectly
quantify spasticity (e.g., the Ashworth Score and its variations –
the Tardieu Score, the Composite Spasticity Index, etc.) (Platz et al.
[2005]). These scales are the most commonly used measures of
spasticity, and are also the measures that are endorsed by many of
the regulatory authorities (e.g., FDA). Unfortunately, none of these
measures are useful measures of spasticity as these are all signifi-
cantly confounded. The research evidence proving that these scales,
and the general principle of measuring resistance to an externally

imposed movement, are not fit for purpose have originated from
multiple research groups carrying out work on different conti-
nents and will not be rehashed here. If readers are interested, please
see the relevant papers (Pandyan et al. [1999]; Haugh et al. [2006];
Fleuren et al. [2010]). It is a source of regret that many of the more
direct neurophysiological and relatively simple measures that have
underpinned our understanding of spasticity (Rymer and Katz
[1994]) have been replaced by inadequate clinical scales for purposes
of clinical expediency.
• Biomechanical methods to measure spasticity and contractures.
A range of biomechanical methods have been described to mea-
sure spasticity. These can be classified as manual methods (e.g.,
Pandyan et al. [2001]); controlled displacement methods using ramp-
and-hold perturbations (Rymer and Katz [1994]), sinusoidal pertur
bations (Zhang and Rymer [1997]), or random perturbations
(Andersen and Sinkjaer [1996]); controlled torque methods (Walshe
[1992]); or the gravitational method (Bajd and Bowman [1982]). All
of the above methods attempt to measure spasticity by measuring
the resistance to an externally imposed perturbation. The evidence
would suggest that these biomechanical measures are more often
measuring concomitant biomechanical changes in the soft tissue
structures as opposed to measuring spasticity. Furthermore, whilst
attempting to measure spasticity, most methods measure stiffness
eccentrically; under these conditions it is not possible to delineate
the components of stiffness (i.e., that arising from muscle activity,
the intrinsic stiffness within the muscle due the residual actin and
myosin cross bridges, and the contribution from the mechanical
properties of the associated soft tissue structures). The biomechani-
cal methods of measurement have been reviewed previously (Wood
et al. [2005]; Pandyan et al. [2009]). All of the biomechanical methods
have limited clinical applicability when used as measures of spastic-
ity; however, they have a significant role to play in the measurement
of contractures.
Although not commonly used, accelerometers have the potential
to contribute to the measurement of spasms and clonus in a relevant
way (Granat and Edmonds [1999]). While in the past such technology
was expensive, the size and costs of these sensors have significantly
reduced and there is the potential for such technologies to play an
important role in the measurement and management of spasms (e.g.,
24-hour monitoring systems for patients). In addition, it is also now
possible to additionally measure muscle activity data concomitantly.
Whilst such technology is available, there is a need for additional
research to make it accessible to clinicians.
• Neurophysiological methods to measure spasticity.

A range of neurophysiological methods have been described
to measure spasticity or the pathophysiological basis of spasticity.
These methods have previously been comprehensively reviewed
(Voerman et al. [2005]; Pandyan et al. [2009]). The methods of rel-
evance are as follows: the efferent response to an electrical stimulus
(The H-reflex and F-wave); and the efferent response to a mechani-
cal perturbation (tendon tap, manual perturbation, or controlled dis-
placement perturbation – normally a ramp-and-hold stretch). While
most of these methods of measurement are relatively easy to per-
form, in particular the efferent response to a mechanical perturba-
tion, the reliability of these methods of measurement needs to be
better understood. Current experimental evidence would suggest
that H-reflex and F-wave measurements show a large degree of vari-
ability. Furthermore, in patients with an upper motoneuron lesion,
developing a method of standardisation in measuring the muscle
response to a mechanical perturbation is not possible.
Despite the poor levels of reliability, many of these methods of mea
surement provide far more useful information to inform the manage-
ment of spasticity than any of the clinical scales or the biomechanical
measures used in isolation. For example, when selecting patients for
implantation of an intrathecal baclofen pump, an effective way to
identify a suitable patient will be to study the H-reflex response to
a bolus injection of intrathecal baclofen (Macdonell et al. [1989]). In
order to either select patients for treatment with botulinum toxin (or
phenol or a motor nerve dissection) or study the response to treatment
it would make sense to ensure that the muscle/nerve being treated
has an overactive efferent response associated with spasticity (Figures
1.3 and 1.5) as measured using manual neurophysiological methods.
1.2.6 Concluding Thoughts
Spasticity appears to be an inevitable sequela following a lesion in the upper
motoneuron pathways. Within this chapter we provide a framework to clas-
sify spasticity in a way that makes measurement possible. We have also pro-
vided an argument to suggest that patients who have spasticity and who do
not recover useful functional movement are at risk of contractures. The con-
tractures can develop rapidly and often co-exist with spasticity. The options
to treat spasticity are limited:
• Reduce the afferent input to the nervous system (selective dorsal

rhyzotomy).
• Reduce the gain/threshold within the nervous system (pharmaco-
logical treatments that tend to depress the nervous system).
• Reduce the efferent drive to the muscle (botulinum toxin, phenol,

and neurectomies).
• Use muscle relaxants.
The options to treat contractures are even more limited:
• Cyclical Passive Movement (using ergometers or electrical stimulation).

• Stretching using splints, serial casts, or progressive stretching devices.
• Loading the tendons using electrical stimulation.
In order to identify the most useful treatment combination it is essential that

not only the right treatment is selected but that the response to the treatment
is effectively monitored. This chapter will hopefully give some pointers in
ensuring that the right definitions and measurements can inform the meth-
ods of treatment.
Then there is the issue of linking our understanding of spasticity to the
recovery potential of patients. Many of the current first-line treatments for
spasticity have the potential to inhibit the learning that is essential for recov-
ering functionally useful movement (e.g., pharmacological agents routinely
used in clinical practice) (Cameron et al. [2016]). Current practice will need
to be carefully re-examined; however, doing this in the absence of a precise
framework is not appropriate. This chapter hopefully provides such a frame-
work to both clinicians and researchers.
Finally, one must also consider the possibility that spasticity is an epiphe-
nomenon, although this may not be the case in all patients. The literature and
our own work provides evidence that patients who have recovered useful
arm function continue to demonstrate signs of spasticity. Identifying such
patients is important as it is possible that spasticity may be an inevitable first
step in the recovery pathway. The framework may have a role to play in this
classification process.
This book is the first attempt at bringing together a volume of work from a
range of professionals with an interest in spasticity. The framework for the defi-
nition was developed in part by the authors reading the chapters that make up
this volume. There are likely to be some anomalies between the framework and
the summaries within respective chapters. This was expected as the literature
that the respective authors have had to draw upon is imprecise. One would hope
that the framework within this chapter will help guide the research that follows
so that future reviews will be able to coherently summarise the literature with
no ambiguity. As pointed out in Section 2.3, this framework has currently been
developed for patients with upper motoneuron lesions, as identified within this
book. There is a significant volume of work that now needs to be done to provide
a framework that will include a range of other disease conditions where patients
present with signs and symptoms similar to those described in this chapter (e.g.,
Parkinsonism, the various forms of dystonia, and other motoneuron diseases).
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2
Pathophysiology of Spasticity
Jens Bo Nielsen, Maria Willerslev-Olsen and Jakob Lorentzen
CONTENTS
2.1 How to Measure Spasticity – From Clinical Evaluation
to Biomechanical Techniques...................................................................... 26
2.2 The Nature of the Muscle Response to Stretch........................................ 28
2.3 Is Spasticity Caused by Lesion of the Pyramidal Tract?......................... 29
2.4 Spasticity Does Not Appear Immediately after Lesion but
Is Caused by Adaptive Changes in Spinal Networks.............................30
2.5 Pathophysiology of Exaggerated Stretch Reflex Activity:
Adaptive Changes in Spinal Neural Networks........................................ 31
2.5.1 Pathophysiological Role of Motoneuronal Changes.................... 32
2.5.2 Sprouting, New Synapses................................................................ 35
2.5.3 Regulation at Presynaptic Sites: Increasing the Input
from Surviving Fibres...................................................................... 35
2.5.3.1 Presynaptic Inhibition....................................................... 36
2.5.3.2 Post-Activation Depression............................................... 37
2.5.4 Transmission in Group II Pathways............................................... 39
2.5.5 Pathophysiological Role of Changes in Postsynaptic
Inhibition of Motoneurons.............................................................. 40
2.5.5.1 Disynaptic Reciprocal Ia Inhibition................................ 40
2.5.5.2 Recurrent Inhibition.......................................................... 41
2.5.5.3 Autogenetic Ib Inhibition..................................................43
2.5.5.4 Fusimotor Drive, Gamma-Spasticity...............................43
2.6 How Is Clonus Related to Spasticity?........................................................44
2.7 What Causes a Spasm?................................................................................. 45
2.8 Spastic Dystonia Is Not Caused by Increased Stretch Reflex Activity.... 45
2.9 Concluding Remarks.................................................................................... 46
References................................................................................................................ 47
25
2.1 How to Measure Spasticity – From Clinical

Evaluation to Biomechanical Techniques
The clinical evaluation of spasticity currently rests on the eyes and hands of
the clinician. Clinically, spasticity is often inappropriately equated to muscle
tone and is essentially determined by sensing the resistance to passive move-
ment around a joint with the patient in a position that is as relaxed as possible.
By making movements at different velocities the clinician may get a feeling
of whether the resistance is present at all velocities or only during fastest
stretching of the muscles. Sometimes a distinct brief resistance – a catch –
may be determined with quick stretches at specific positions of the joint.
Backed up by other signs such as large – and especially non-symmetrical –
tendon tap reflexes and the presence of clonus, the clinician may perceive that
the resistance is velocity-dependent and may possibly be related to hyperex-
citable stretch reflexes; i.e., that the muscle resistance is caused by spastic-
ity according to Lance’s definition. In many cases the determination of the
presence of spasticity is relatively straightforward and unproblematic (this
may especially be the case when the clinician has knowledge of the underly-
ing disorder, e.g., stroke or spinal cord, but may not necessarily be the case
without this prior knowledge). However, if the patient is not fully relaxed, if
the changes in reflex excitability are not very large, or if other mechanisms
also contribute to increased muscle resistance, it may be very difficult to
accurately determine the nature of the muscle resistance. The presence of
alterations in the elastic properties of the muscle, connective tissue, and/or
tendons especially makes it difficult to perform the evaluation sufficiently fast
and powerfully and it therefore becomes a challenge to determine the pres-
ence of spasticity. The presence of involuntary static muscle activity (spastic
dystonia) and an associated inability of the patient to fully relax the muscle
also make the evaluation difficult. Clinical evaluation of spasticity has con-
sequently been shown to have variable reproducibility within and between
raters (Bhimani et al. 2011, Biering-Sorensen et al. 2006, Haugh et al. 2006,
Mutlu et al. 2008) and to be unrelated to objective biomechanical measures of
spasticity (Lorentzen et al. 2010, Willerslev-Olsen et al. 2013). The Ashworth
scale was introduced in 1964 (Ashworth 1964) as a simple 5-point scale rang-
ing from normal muscle tone (0) to rigidity (4) in order to quantify spasticity
in multiple sclerosis before and after treatment. An additional grade (1+) was
introduced in 1987 to designate slight resistance with a clear catch (Bohannon
and Smith 1987). This modified Ashworth Scale (MAS) is now the most com-
monly used clinical scale, although it is confounded by the same limitations
as the original scale, except for the additional grade. Furthermore, the intro-
duction of this additional grade seems not to have improved the reliability of
the scoring (Bhimani et al. 2011, Biering-Sorensen et al. 2006, Burridge et al.
2005) and a conspicuous over-representation of scores 1 and 2 (Fleuren et al.
2010) suggests that what is scored in most patients is ‘some resistance but not
Pathophysiology of Spasticity 27
too much’ (Biering-Sorensen et al. 2006). The scale has consequently shown
low validity and sensitivity in studies in which it has been related to biome-
chanical measures of stiffness (Biering-Sorensen et al. 2006, Burridge et al.
2005, Lorentzen et al. 2010, Malhotra et al. 2008, Sehgal and McGuire 1998).
It is surprising given these drawbacks that the scale has become the scale of
choice in the clinic, rather than the older Tardieu scale. The Tardieu method
was originally introduced in 1954 (Tardieu et al. 1954) and has been modi-
fied significantly to become the Tardieu scale that is in use today (Haugh
et al. 2006, Held 1969). The essence of the scale is that the examiner has to
move the examined limb at three different velocities (slow, moderate, and as
fast as possible) in order to estimate range of movement, presence of passive
resistance, and presence of spasticity. The scoring of spasticity is based on
the presence of a catch and clonus. Although the Tardieu scale theoretically
should more adequately distinguish passive and active components of mus-
cle resistance than the Ashworth scale, it has not gained as wide a use in the
clinic as the Ashworth scale. Part of the reason for this is that the technique
is more demanding for the examiner and is therefore less easy to perform in
a similar way for two raters. The scale also lacks sufficient dimensionality to
cover patients with very severe spasticity that prevents elicitation of stretch
reflexes and clonus. The focus on the presence of clonus is also problematic
given the uncertainty regarding the mechanisms of clonus and its relation to
spasticity (Mukherjee and Chakravarty 2010).
Biomechanical evaluation of spasticity was introduced in the 1950s by
Tardieu (Tardieu et al. 1954) and later developed by Knutsson (Knutsson
and Martensson 1976). Since then, various devices and techniques have
been developed and tested (Mirbagheri et al. 2005, Mirbagheri et al. 2009,
Mirbagheri et al. 2004, Sinkjaer 1997, Sinkjaer et al. 1992, Sinkjaer and
Magnussen 1994, Sinkjaer et al. 1995, Sinkjaer et al. 1988, Toft et al. 1989b,
Toft et al. 1989c, Wood et al. 2005). The main advantage of these techniques
is that they provide an objective and quantitative assessment of resistance
about a joint. With the addition of EMG measurements from the stretched
muscles, they may provide an objective and precise way of distinguish-
ing reflex-mediated from passive muscle resistance (Lorentzen et al. 2010,
Sinkjaer et al. 1993, Toft et al. 1989b, Willerslev-Olsen et al. 2013). From this
point of view, biomechanical evaluation combined with electrophysiological
measures might be considered a ‘gold standard’ for a combined evaluation
of spasticity and contractures with which other measures may be compared.
However, the expertise and technology involved is too demanding for rou-
tine clinical use. Handheld dynamometers and other simplified biomechani-
cal devices may provide sufficiently reliable and consistent measures, but
none of the commercially available devices have so far shown sufficiently
promising results to be used more widely in the clinic for spasticity evalua-
tion (Barden et al. 2012, Benard et al. 2010, Calota et al. 2008, Kim et al. 2011,
Lee et al. 2004, Lorentzen et al. 2012, Waldman et al. 2013). Only few of the
existing devices claim to provide a distinction between reflex-mediated and
passive muscle stiffness and there is therefore a clear need to develop more
optimal easy-to-use devices that can help the clinician in the routine clinical
diagnosis.
2.2 The Nature of the Muscle Response to Stretch

In order to understand the pathophysiology of spasticity it is useful initially
to consider the responses of a muscle to stretch (1). At velocities below the
threshold of the stretch reflex the resistance against the movement is caused
solely by the passive elastic properties of the muscle, connective tissue, ten-
don, and joint (Lorentzen et al. 2010, Mirbagheri et al. 2005, Mirbagheri et al.
2004, Toft et al. 1989a, Toft et al. 1989b). This resistance is usually called pas-
sive stiffness (Toft et al. 1989a, Toft et al. 1989b) and is far less sensitive to the
velocity of the stretch than the stretch reflex-mediated resistance (Lorentzen
et al. 2010). However, the resistance varies with the position of the joint and
thus the degree of stretch of the muscle (Mirbagheri et al. 2005, Mirbagheri
et al. 2009, Mirbagheri et al. 2004). If the subject is not fully relaxed, neural
activation of the muscle will result in formation of cross-bridges between
myosin and actin filaments that will impede the stretch and add very sig-
nificantly to the stiffness (Figure 2.1). This stiffness is usually called intrin-
sic stiffness, to distinguish it from passive and reflex-mediated stiffness
Adaptation
Normal Lesion (spasticity)
Descending Descending Descending

drive drive drive
Sensory
Sensory Sensory
input
input input
Motoneurone Motoneurone Motoneurone
Output from
Output from
Output from spinal cord
spinal cord
spinal cord
FIGURE 2.1
Theoretical changes in sensory and descending input to spinal motoneurons in the acute and
chronic phase following central motor lesion. The figure illustrates sensory and descending
input to spinal motor neurons in the intact state (Normal), and following a central motor lesion
in both the acute state (Lesion), and in the chronic phase (Adaptation, spasticity). The numbers
and thickness of the arrows represent the power and intensity of the input and outputs.
(Sinkjaer et al. 1993), but it should be emphasised that it is caused by an

(extrinsic) neural signal and may be very difficult to distinguish in practice
from reflex-mediated stiffness given the integration between descending
motor commands and reflexes (Nielsen 2004). When stretches above a cer-
tain threshold (which is determined individually by the sensitivity of muscle
spindles, transmitter release from central synapses, and the excitability of
motoneurons) are applied, a stretch reflex response will be evoked and add
to the resistance against the movement (Figure 2.1). This reflex-mediated
stiffness is, at least in theory, equivalent to the catch that is assessed as part
of the clinical evaluation of spasticity. The mechanical response evoked by
the stretch conceals that there are at least two separate reflex responses in
most muscles (Christensen et al. 2000). These responses may be demon-
strated by EMG measurement from the muscle (Toft et al. 1989b, Toft et al.
1991). The initial (short-latency or M1) response is mediated by the spinal
monosynaptic Ia pathway and is equivalent to the reflex response elicited by
a tendon tap (Morita et al. 1998). The response is generally strongly exagger-
ated in spastic patients (Ibrahim et al. 1993, Sinkjaer and Magnussen 1994,
Sinkjaer et al. 1993). In lower limb muscles the initial response is followed
by a second (medium-latency or M2) and sometimes a third (long-latency
or M3) response (Christensen et al. 2000). The M2 response has been shown
in all likelihood to be mediated by gr. II afferents from the muscle spindles
(Christensen et al. 2000, Grey et al. 2001). Similar to the M1 response, it is gen-
erally exaggerated in spastic patients (Sinkjaer and Magnussen 1994, Sinkjaer
et al. 1993, Willerslev-Olsen et al. 2014). The third response, on the other
hand, is generally reduced or abolished in spastic patients consistent with
the idea that it is mediated by a transcortical pathway that is involved in the
lesion (Christensen et al. 2000). Similar mechanisms probably also contrib-
ute to the stretch response observed at longer latency than the M1 response
(generally called long-latency or M2 response) in upper limb muscles, but
due to the short difference in conduction time for spinal and transcortical
responses, the responses appear to be difficult to separate (Christensen et al.
2000). These later responses in upper limb muscles may therefore be reduced,
unchanged, or exaggerated in the individual patient.
Since the mechanical resistance sensed either by a clinical examiner or a
biomechanical device is the sum of these different reflex responses, trans-
mission in all the involved pathways should be taken into account when con-
sidering the cause of an exaggeration of the muscle resistance.
2.3 Is Spasticity Caused by Lesion of the Pyramidal Tract?

Spasticity is observed following both spinal and cortical lesions and is in the
clinic commonly associated to lesion of the corticospinal tract, but studies in
animals suggest that this is wrong. Tower (1940) was the first to observe in
monkeys that selective lesion of the pyramidal tract produced flaccid pare-
sis without any signs of spasticity (Tower 1940). This was investigated in
more detail in the seminal studies by Lawrence and Kuypers (1968a, 1968b).
They reported that complete unilateral or bilateral pyramidal tract lesion in
monkeys produced severe paresis, whereas lesion of brainstem tracts left the
monkeys with increased reflex excitability and little paresis (1968a, 1968b).
These observations have been confirmed in several subsequent studies in
both monkeys and other animals (Aoki et al. 1976, Metz et al. 1998). The evi-
dence that the pyramidal tract is not involved in the development of spastic-
ity in animals is thus convincing.
The most convincing evidence from human subjects is that of Nathan (1994),
who reported the effect of surgical incision in the spinal cord to relieve chronic
pain. His findings are well in line with the studies in monkeys. In subjects in
whom lateral incisions severing the corticospinal tract were made, no spastic-
ity was observed, whereas this was the case for more ventral lesions, which
severed descending tracts from the brain stem (Nathan 1994). Other studies
on the topic have only involved observations from single subjects. Sherman et
al. (2000), somewhat confusingly, reported increased biceps brachii tendon jerk
without clinical signs of spasticity in a single patient with selective unilateral
lesion of the pyramidal tract (Sherman et al. 2000). In all likelihood, this finding
says more about the clinical examination than anything else. The same may
be the case for the study of Paulson et al. (1986), who reported development of
spasticity in a single patient with selective lesion of the medullary pyramids.
On balance, the human studies thus point in the same direction as the animal
studies in suggesting that spasticity is caused by lesion of brain stem pathways
or their cortical control rather than lesion of the corticospinal tract. The low
occurrence of spasticity in stroke survivors with severe paresis or paralysis as
sign of corticospinal lesion is well in line with this (Wissel et al. 2013).
These findings suggest that lesion of the corticospinal tract alone is
insufficient to start the range of spinal adaptations that result in spasticity.
Apparently, additional affection of the vast innervation of spinal motoneu-
rons and interneurons by reticulospinal pathways and other descending
tracts from the brain stem is required in order to set the adaptive changes in
motion, but we have little understanding of why this is, or of the physiology
or pharmacology of these systems.
2.4 Spasticity Does Not Appear Immediately after Lesion but

Is Caused by Adaptive Changes in Spinal Networks
The excitability of spinal circuitries is depressed during a variable period
in both animals and humans following a spinal lesion, due to what is called
‘spinal shock’ (Ditunno et al. 2004). The mechanisms responsible for spinal
shock are not fully clarified but seem to involve loss of descending excitation,
increased spinal inhibition, reduction of persistent inward currents in the
spinal motoneurons due to loss of serotonergic innervation, reduced neu-
ronal metabolism, and retraction of dendrites and synapses (Ditunno et al.
2004). The time course of development of spasticity following spinal lesion is
likely related both to the gradual relief of spinal shock and the gradual devel-
opment of an hyperexcitable state leading to spasticity. In the clinic, spastic-
ity usually becomes manifest in spinal cord-injured subjects 1–12 months
after the lesion, whereas reflex hyperexcitability is observed in animals
within 1–2 months (Aoki et al. 1976, Ditunno et al. 2004). Spinal shock is not
observed following stroke or supraspinal lesions and it is therefore possible
to follow the development of spasticity without the interference from spinal
shock in such cases. In both animals and humans, it takes several weeks for
spasticity to develop following stroke (Wissel et al. 2013). The importance of
this is that spasticity is not caused by simple release of the spinal circuitries
from a tonic supraspinal inhibition, as believed some years ago (Burke 1988).
This idea ties into another old belief, which has also been proven wrong:
That spinal reflexes are primitive reflexes which in humans are only seen in
the first year of life, but are then suppressed as the corticospinal tract devel-
ops and achieves functional connections with the spinal circuitries. With this
mindset, it follows that, in adults, reflexes, and exaggerated reflexes in par-
ticular, are seen as abnormal and require treatment because they are thought
of as being caused by the release of a normal inhibitory descending influ-
ence. However, what really happens during development is that the cortico-
spinal tract and spinal circuitries become functionally integrated and learn
to collaborate to ensure motor reactions are appropriate for the conditions
that exist at any particular moment in time and the task being undertaken
(Clowry 2007, Nielsen 2004).
Moreover, the gradual development of spasticity puts emphasis on plas-
tic changes in the spinal circuitries as adaptations to the loss of descending
supraspinal drive (Burke 1988).
2.5 Pathophysiology of Exaggerated Stretch Reflex Activity:

Adaptive Changes in Spinal Neural Networks
It may seem self-evident to point out that the task of a spinal motoneuron is
to activate the muscle fibres that it innervates and thereby contribute to pos-
ture and movement. However, this simple notion provides an intuitive way
of understanding the adaptive changes that occur in the spinal networks
in response to lesion of descending pathways. When descending excitation
of the motoneuron is lost, regulatory mechanisms that aim to restore an
efficient output to the muscle set in. A simplified version of this point is illus-
trated in Figure 2.1. In the normal situation, sensory input and descending
drive both contribute to the activation of the motoneurons. Following lesion
of central motor fibres, the descending drive is reduced and the sensory
input is insufficient to maintain a normal output from the spinal cord to the
muscles. As spasticity develops plastic mechanisms that could be considered
compensatory set in. These involve increased descending drive in surviving
motor tract fibres and alteration of intrinsic properties in spinal motoneu-
rons. These changes help to increase the output from the spinal cord to the
muscles, albeit not necessarily to the level before lesion, and they do not nec-
essarily normalise motor control.
In the motoneuron these plastic changes involve up-regulation of mem-
brane channels and receptors that increase the excitability of the membrane
and reduction of the threshold for action potential generation (Figure 2.2). It
also involves the sprouting of nearby fibres (descending fibres as well as sen-
sory afferents and fibres from local interneurons), growth of motoneuronal
dendrites, and establishment of new synaptic sites. Mechanisms that regu-
late transmitter release from sensory afferents (and in all likelihood also cen-
tral motor fibres), such as presynaptic inhibition, ensure that the efficiency of
the synapses that contribute to the motoneuronal drive is increased (Figure
2.2). A general up-regulation of excitation and down-regulation of inhibitory
influences from various interneuronal populations on the motoneurons is
seen. All these mechanisms work in concert with the common aim to main-
tain a functional output from the spinal cord to the muscles. Spasticity thus
reflects an adaptive change in the spinal cord aimed at maintaining a func-
tional output when a significant part of the normal descending excitatory
drive to the motoneurons is lost. It is difficult to see this as a maladaptation.
It is essentially a very sensible adaptation.
2.5.1 Pathophysiological Role of Motoneuronal Changes

The neuronal membrane is packed with receptors and channels that contrib-
ute to the regulation of the excitability of the cell. The number, density, type,
and state of these receptors and channels is regulated by a large number
of intracellular messenger systems. These mediate changes in the receptors
and channels themselves and regulate gene transcription and production of
the proteins necessary for new receptors. The excitability of the cell is thus,
in essence, a dynamic property, which is continuously regulated according
to the immediate and more distant experience of the cell. Dramatic changes
such as loss of a major part of the excitatory drive to the cell therefore have
significant immediate and long-term impact on the trafficking of molecules
and molecular signaling within and between the individual cells.
Voltage-dependent Ca2+ and Na+ persistent inward currents (PICs) play a
central role in this regulation of motoneuronal (as well as interneuronal) excit-
ability (Heckman et al. 2003, Hultborn et al. 2004, Powers and Binder 2001,
(d) Postsynaptic inhibition
(Reciprocal, autogenic lb, recurrent)
(c) Regulation of transmitter release
(Post-activation depression, presynaptic inhibition)
(b) Sprouting, new synapses
(a) Motoneuronal properties (PICs)

la afferents
Pathophysiology of Spasticity
Motoneurons mn mn mn
m. Quadriceps
m. Tibialis anterior
m. Soleus
FIGURE 2.2
The stretch reflex circuitry and spinal pathophysiological mechanisms in spasticity. The figure illustrates the stretch reflex circuitry. Red neurons indi-
cate motor neurons and green neurons indicate 1a afferents. The circuitry is superimposed on the right side of the figure. The motorneurons, located in
the ventral horn, are regulated by different properties: (a) changes of intricic properties of the motor neuron; (b) sprouting; (c) neurotransmitter release
(post-activation depression, presynaptic inhibition); and (d) postsynaptic inhibition (reciprocal, autogenic Ib, recurrent).
33
Rekling et al. 2000). Inward currents produce prolonged depolarisations (pla-

teau potentials) when opposing outward currents are reduced or the Ca2+
channels are facilitated by, e.g., serotonergic and noradrenergic innervation
of the motoneurons (Heckman et al. 2003, Hultborn et al. 2004, Powers and
Binder 2001, Rekling et al. 2000). Under normal circumstances the function of
PICs is, however, much more dynamic and subtle. Although not fully clari-
fied, one important functional role of PICs seems to be to enhance the syn-
aptic effect of excitatory inputs to the motoneurons. EPSPs in motoneurons
produced by pyramidal tract activation are thus boosted by PICs to an extent
that it has been argued that physiological descending drive to the moto-
neurons would be insufficient to drive the motoneurons at the firing fre-
quencies observed during movement without them (Binder 2002, Hultborn
et al. 2004, Hultborn et al. 2003). It has also been argued that EPSPs gener-
ated at dendritic sites distant from the cell soma would be unable to reach
the spike initiation zone without the existence of PICs in the membrane to
increase the gain of the EPSPs (Binder 2002). As already mentioned, PICs
cannot be evoked during the period of spinal shock following spinal cord
lesions unless specifically increased by monoaminergic agonists (Ditunno et
al. 2004, Hultborn et al. 2004). However, plateau potentials may be induced
again at least in some cases in the chronic spinal state without adding any
neurotransmitter precursors or agonists (Hultborn et al. 2004). Bennett et
al. (1999, 2001) developed a rat preparation in which a very low chronic spi-
nal lesion causes pronounced hyperreflexia of the tail without interfering
with normal hind limb or bladder function. PICs were regularly seen in the
chronic test state, but never in the acute post-lesion situation (Bennett et al.
1999, Bennett et al. 2001). This appears to be linked to upregulation of mono-
aminergic receptors, in particular 5-HT(2B) and 5-HT(2C) receptors in the
motoneuronal membrane (Murray et al. 2010, Murray et al. 2011a, Rank et
al. 2011, Ren et al. 2013, Wienecke et al. 2010). It is likely that similar plastic
changes occur also at interneuronal level, although this has not been shown.
Little is known about a possible contribution of PICs to the development
of spasticity in human subjects because of the difficulty in demonstrating
the existence of such intrinsic membrane properties in the intact organ-
ism. However, Nickolls et al. (2004) found that muscle stimulation, which
provided an excitatory sensory drive to the spinal motoneurons, did not
induce plateau-like behavior of motor unit activity in patients with spinal
cord injury as easily as in healthy subjects, but nevertheless argued that pla-
teau potentials might contribute to the clinical manifestations of the patients,
such as spasticity (Nickolls et al. 2004).
From observations of motor unit behavior during spasms in spinal cord-
injured patients, Gorassini et al. (2004) inferred that motor units required sig-
nificantly less synaptic drive in order to be de-recruited at the end of spasms
as compared to the synaptic drive required to recruit them in the beginning
of the spasm. From this they argued that persistent inward currents were
activated during the spasm and appeared to contribute to the occurrence
of the spasms (Gorassini et al. 2004). In line with animal experiments this
appears to depend on upregulation of serotonergic receptors (D’Amico et al.
2013a, D’Amico et al. 2013b). These findings from both animals and humans
are certainly of relevance for the pathophysiology of spasms, but given the
mechanisms involved, upregulation of PICs is unlikely to be a universal
explanation of spasticity. Loss of serotonergic innervation and subsequent
upregulation of 5-HT receptors likely only occurs to any significant extent
following spinal cord injury, but not following supraspinal lesions. This
likely also explains why spasms are rare in spastic patients following stroke.
This in turn undermines the idea that PICs should be causally involved in
the pathophysiology of spasticity. Further work in this area is warranted, but
will require some innovative experimental design.
2.5.2 Sprouting, New Synapses

Following lesions in the central nervous system, several m orphological
changes are usually seen, including outgrowth of dendrites, ‘collateral
sprouting’ from remaining/surviving neurons as a result of partial dener-
vation, and establishment of new synapses (Bareyre et al. 2004, Fouad et al.
2001, Raineteau and Schwab 2001, Raisman 1969, Weidner et al. 2001). Such
adaptations are well documented for terminations of descending fibres on
the spinal motoneurons, especially in spinal cord injury (Fouad et al. 2001,
Raineteau and Schwab 2001). They probably contribute to ‘overactivity’ phe-
nomena such as spastic dystonia (see later) and lack of specificity of volun-
tary motor control following central lesions. They may thus contribute to
the inability of patients in performing precise movement, the tendency to
perform involuntary associated movements, and the development of ‘spastic’
postures involving involuntary excessive activation of postural muscles dur-
ing movement. However, to what extent these mechanisms also contribute to
stretch reflex exaggeration is unclear. Muscle afferents likely also sprout and
innervate vacant synaptic sites from descending fibres on spinal motoneu-
rons, but there is little direct evidence of this.
2.5.3 Regulation at Presynaptic Sites: Increasing

the Input from Surviving Fibres
Although the majority of interest has naturally been devoted to alterations
in transmitter release from sensory afferents in relation to the development
of spasticity, it should be emphasised that it is likely that synapses of sur-
viving descending fibres and spinal interneurons are also upregulated in
order to facilitate activation of the motoneurons following the lesion, as
already mentioned above. However, such changes have, to the best of our
knowledge, not been thoroughly investigated. Presynaptic inhibition elicited
by sensory afferents (see below) has been shown not to be distributed to
descending motor fibres (Nielsen and Petersen 1994, Rudomin et al. 1991).
Post-activation depression (see below) also does not seem to affect transmis-
sion from descending pathways (Hultborn et al. 1996). However, synapses
of descending fibres are, in all likelihood, subjected to some other kind of
regulation and are therefore also likely to be amenable to plastic adaptive
changes following lesion.
2.5.3.1 Presynaptic Inhibition
Presynaptic inhibition of sensory afferent terminals was described origi-
nally in the cat spinal cord by Frank and Fuortes in 1957 (Frank 1957) and
subsequently investigated in more detail by John Eccles and his co-workers
(Eccles et al. 1962a, Eccles et al. 1962b, Eccles et al. 1963; and see reviews
by Rudomin and Schmidt 1999, Willis 2006). The interneurons responsible
for presynaptic inhibition receive considerable input from a range of sen-
sory afferents of different modality throughout the leg, as well as descend-
ing control from the corticospinal tract and brainstem nuclei (Burke 2012,
Jankowska 1992, Rudomin and Schmidt 1999, Willis 2006). The interneurons
in turn project widely in the spinal cord to suppress transmitter release from
sensory afferent terminals on motoneurons by releasing GABA which binds
to receptors located on the presynaptic terminals of the sensory afferents
(Burke 2012, Rudomin and Schmidt 1999). Activation of GABA-A receptors
result in opening of Cl channels, which causes an outward Cl current and
thereby a depolarisation of the terminals (primary afferent depolarisation;
PAD – although other mechanisms may also contribute to this phenomenon
[Hochman et al. 2010]). PAD inactivates some of the voltage-sensitive sodium
channels and thereby reduces the amplitude of any subsequent action poten-
tials. As a consequence, fewer voltage-sensitive Ca channels are opened and
transmitter release from the terminals is reduced (Burke 2012, Rudomin and
Schmidt 1999).
In both human and animal experiments, presynaptic inhibition has been
found to be strongly regulated by supraspinal control centres (Burke 2012,
Meunier 1999, Rudomin et al. 2004). During voluntary movement including
locomotion presynaptic inhibition is turned into a highly focused modula-
tory mechanism that shapes the sensory inflow to spinal motoneurons and
interneurons according to the needs of the given task and the central com-
mand (Dietz et al. 1990, Faist et al. 1996). Activation of some muscles may
thereby be facilitated by removing presynaptic inhibition of the sensory
afferents, while ensuring that unwanted activation of other muscles (such
as antagonists) does not take place (Crone and Nielsen 1989b, Hultborn et al.
1987, Nielsen and Kagamihara 1993). This regulation of presynaptic inhibi-
tion in relation to voluntary movement is of significance for the functional
relevance of spasticity and will be further described in Chapter 3.
Following spinal cord lesion in cats, presynaptic inhibition of sensory
afferents is reduced and this reduction seems to follow the development of
spasticity (Naftchi et al. 1979).
In humans, presynaptic inhibition of Ia afferents on spinal motoneurons

supplying leg muscles has been found to be reduced in multiple sclerosis
and spinal cord-injured subjects with spasticity as compared to a popula-
tion of able-bodied individuals (Faist et al. 1994, Nielsen et al. 1995b). This
is also the case in cerebral palsy individuals with clinical signs of spastic-
ity (Achache et al. 2010). Presynaptic inhibition of Ia afferents from upper
limb muscles is also reduced in spastic stroke survivors (Aymard et al. 2000,
Lamy et al. 2009), but this is not the case for presynaptic inhibition of Ia
afferents from leg muscles (Aymard et al. 2000, Faist et al. 1994, Lamy et
al. 2009). It has therefore been argued that reduced presynaptic inhibition
is unlikely to be involved in the pathophysiology of spasticity, but is more
likely an epiphenomenon (Lamy et al. 2009), possibly in relation to the disuse
of the limb (Lundbye-Jensen and Nielsen 2008). The observation that there
is no correlation between reduced presynaptic inhibition and the degree of
spasticity evaluated by the Ashworth scale is in line with this (Aymard et al.
2000, Lamy et al. 2009, Nielsen et al. 1995b). However, as mentioned above the
Ashworth scale has been shown to be a poor measure of the extent of spastic-
ity and this finding may therefore rather be related to shortcomings of the
clinical evaluation of spasticity.
The success of GABAergic drugs, such as diazepam and baclofen, in
reducing reflexes and diminishing spasticity (Abbruzzese 2002, Macdonell
et al. 1989, Verrier et al. 1975) should not be taken as support that presyn-
aptic inhibition plays an important role for the development of spasticity.
Any drug that reduces transmitter release from sensory afferent terminals
on spinal motoneurons or suppress motoneuronal excitability would have a
similar effect and, contrary to what is sometimes claimed, a specific effect on
an important pathophysiological mechanism would make little difference
(Murray et al. 2011b).
2.5.3.2 Post-Activation Depression
It was originally described by Curtis and Eccles (1960) that Ia EPSPs are
frequency-dependent, with a relative facilitation at short intervals, and a
depression with longer intervals (Curtis and Eccles 1960). Naturally, this also
influences the size of stretch reflexes and it is therefore not surprising that
a similar pattern of facilitation and suppression of the Soleus H-reflex and
stretch reflex may be demonstrated in humans (Crone and Nielsen 1989a,
Grey et al. 2008, Hultborn et al. 1996, Taborikova and Sax 1968). Following
a single elicitation of a stretch reflex or an H-reflex, subsequent reflexes are
strongly depressed for up to 10–15 seconds (Figure 2.3). This depression has
been called post-activation depression since it is seen following a previous
activation of homonymous Ia afferents and is not (or only to a limited extent)
seen for afferents that have not been activated (Hultborn et al. 1996). It is
therefore assumed that the depression results primarily from mechanisms
operating within the presynaptic terminals (Lev-Tov and Pinco 1992, Li and
Healthy subjects (n = 30)

Multiple sclerosis patients (n = 17)
Patients with spinal cord injury (n = 16)
120
Size of H-reflex (% of control reflex)
100
80
60
40
20
0 2 4 6 8 10 12 14 16
120
Angle of Interval after stretch (s)
ankle joint
110
FIGURE 2.3
Post-activation depression and spasticity. The graph illustrates the size of the H-reflex as a per-
centage of the control reflex (y-axes) at different intervals after the stretch (x-axes). Black dots
indicate healthy subjects (n = 30), orange dots indicate multiple scleroses patients (n = 17), and
yellow triangles indicate patients with a spinal cord injury (n = 16).
Burke 2001, Pinco and Lev-Tov 1993). It is unclear whether similar mecha-
nisms are involved but post-activation depression shares many features with
the short-term homosynaptic plasticity described for synapses in the hippo-
campus (Andersson and Hanse 2011).
Post-activation depression is reduced in spastic patients with spinal cord
injury (Nielsen et al. 1993, Nielsen et al. 1995b), multiple sclerosis (Nielsen et
al. 1995; Grey et al. 2008), stroke (Aymard et al. 2000, Grey et al. 2008, Lamy
et al. 2009, Schindler-Ivens and Shields 2000), and cerebral palsy (Achache et
al. 2010), thus ensuring that transmitter release is not significantly reduced
with discharges of Ia afferents at rates above 0.1 Hz (Figure 2.3). This is well
within the physiological range of the firing rate of Ia afferents and normal
activity of Ia afferents must therefore be expected to be influenced by this. It
is also within the range of frequencies used during the neurological examina-
tion of spasticity and the reduction in post-activation depression thus directly
contributes to the exaggeration of the stretch reflex and the increased reflex-
mediated muscle stiffness determined during the examination (Grey et al.
2008). In fact, the data from Grey et al. (2008) indicates that if the neurologi-
cal examiner made sure to test reflexes and muscle stiffness at intervals of
longer than 10 s, no significant reflex alteration as compared to healthy sub-
jects would be detected. In other words, it is only because the neurological
examination usually involves multiple attempts at moving the limb or evok-

ing the reflex, which then causes post-activation depression to be elicited, that
reflex exaggeration is determined in spastic patients. This may also explain
the close correlation between reduced post-activation depression and the
clinical assessment of spasticity (Grey et al. 2008; Lamy et al. 2009; Achache et
al. 2010), although the limitations in this assessment should be kept in mind.
Post-activation depression is also the only mechanism that has been shown
to be affected in both the lower and upper limb in spastic subjects regard-
less of the etiology of spasticity (Achache et al. 2010, Lamy et al. 2009). This
may indicate a key role of reduced post-activation depression in the string
of events leading to spasticity. The simple regulation of the contribution of
sensory inputs to the activation of the motoneurons that it provides is an
attractively simple means of upgrading sensory input when descending
drive is lost. However, it should be pointed out that we still have no clear
understanding of the functional significance of post-activation depression,
as will be further discussed in Chapter 3.
It is not known how a spinal lesion could affect Ia terminals, but an impressive
array of mechanisms have been identified that contribute to short-term synap-
tic plasticity in general (both the initial facilitation and the following depres-
sion; recently reviewed by Zucker and Regehr 2002). Although post-activation
depression appears to be a mechanism intrinsic to the synapses, several studies
have provided evidence that it may be regulated by descending motor com-
mands and is thus a highly regulated mechanism (Nielsen et al. 2007, Raoul
et al. 2012). It is certainly a possibility that loss of this descending regulation
leads to alterations in the mechanisms responsible for the depression, possibly
secondary to alterations in monoaminergic neurotransmitters and their recep-
tors, similar to what has been described for motoneurons (D’Amico et al. 2013b,
Murray et al. 2011b, Rank et al. 2011). It has also been suggested that reduced
post-activation depression may be related to lack of sensory activity secondary
to disuse of the limb (Lundbye-Jensen and Nielsen 2008).
2.5.4 Transmission in Group II Pathways

As already mentioned, muscle stretch and passive manipulation of a limb
as part of clinical and biomechanical evaluation of spasticity also generates
activity in group II pathways that probably contribute to the muscle resis-
tance sensed during the clinical examination. The interneurons mediating
these effects appear to be primarily located in Rexeds laminae IV and VIII,
whereas another group of interneurons located in Rexeds laminae V–VII inte-
grate input from group II afferents and group Ib afferents from Golgi tendon
organs (Jankowska and Edgley 2010). Some of these interneurons are inhib-
itory, whereas others are excitatory and the effect on a given set of spinal
motoneurons by activation of the afferents thus depends heavily on central
regulation of the interneurons (Jankowska 1989, Jankowska and Edgley 2010).
Notably, monoaminergic neurotransmitters effectively suppress transmission
in group II pathways and may thereby produce a selective suppression of the

medium-latency (M2) reflex responses in lower limb muscles (Corna et al. 1995,
Grey et al. 2001). The antispastic effect of Tizanidine (Kamen et al. 2008) may
be related to this selective depression. Most studies have reported exagger-
ated group II reflexes in spastic subjects and there is evidence to suggest that
transmission in excitatory group II pathways are released from descending
monoaminergic suppression in patients with central motor lesions (Nardone
and Schieppati 2005). However, it is not clarified to what extent group II inter-
neurons play a pathophysiological role in spasticity.
2.5.5 Pathophysiological Role of Changes in

Postsynaptic Inhibition of Motoneurons
Motoneurons are under close inhibitory control from a number of spinal
interneuronal populations. The most well-studied are the interneurons
mediating reciprocal Ia inhibition, recurrent inhibition, Ib autogenetic inhi-
bition, and non-reciprocal Group I inhibition (Figure 2.2).
2.5.5.1 Disynaptic Reciprocal Ia Inhibition

It was Charles Sherrington who provided the first evidence of a spinal path-
way that could elicit suppression of antagonist muscles (his reciprocal inner-
vation [Sherrington 1906]), but it was work by John Eccles that demonstrated
the disynaptic nature of the reciprocal Ia inhibitory pathway (Hultborn 2006).
Work by Hans Hultborn in the late 1960s and 1970s clarified the organisation
of the interneurons interposed in the pathway and especially the parallel
activation of descending fibres and sensory afferents on common motoneu-
rons and Ia inhibitory interneurons (Hultborn 1976, Hultborn et al. 1976a,
Hultborn et al. 1976b, Hultborn et al. 1976c, Hultborn et al. 1971, Hultborn
and Udo 1972). This laid the basis for an understanding of the central control
of reciprocal inhibition in relation to voluntary movements in the 1980s and
1990s (Crone et al. 1985, Crone et al. 1987, Iles 1986, Kagamihara and Tanaka
1985, Nielsen and Kagamihara 1992, Nielsen et al. 1992, Shindo et al. 1984,
Tanaka 1976). This control is generally impaired in patients with spasticity,
as will be further discussed in Chapter 3.
For reciprocal inhibition to be of any pathophysiological relevance for spas-
ticity, it is essential that there is evidence that the interneurones interposed
at least in the pathway from ankle dorsiflexors to plantarflexors are tonically
active in healthy subjects at rest (Nielsen et al. 1995a). The pathway thus con-
tributes to maintaining the excitability of soleus motoneurons low in resting
subjects. The reduction of reciprocal inhibition between ankle dorsiflexors
and plantarflexors that has been observed in spastic patients with multiple
sclerosis (Crone et al. 1994), stroke (Bhagchandani and Schindler-Ivens 2012,
Crone et al. 2003, Crone et al. 2000, Okuma and Lee 1996, Okuma et al. 2002,
Okuma et al. 1999), spinal cord injury (Crone et al. 2003), and hereditary
spastic paraparesis (Crone et al. 2004) may therefore potentially contribute
to hyperreflexia and increased reflex-mediated muscle stiffness in the ankle
plantarflexors. Achache et al. (2010) reported that reciprocal inhibition was
similar in healthy subjects and adults with CP, but since there was hardly any
inhibition in healthy subjects, a possible reduction of reciprocal inhibition
in CP subjects may have gone unnoticed. Reciprocal inhibition from ankle
plantarflexors to dorsiflexors is, in contrast, usually found to be increased
in spastic patients (Mailis and Ashby 1990, Yanagisawa et al. 1976). As dor-
siflexor muscles seldom show any spasticity, this may not be too surprising.
Reciprocal inhibition has also been found to be deficient in wrist muscles
(Artieda et al. 1991), but since newer studies have put doubt on the origin and
nature of the inhibition observed between wrist muscles, the significance of
this finding is unclear (Wargon et al. 2006).
It has generally not been possible to find any correlation between reduced
reciprocal inhibition and the degree of spasticity evaluated by the Ashworth
scale, but, given the lack of reliability of the Ashworth scale and the small
size of reciprocal inhibition in many subjects, this is not surprising. On the
other hand, a positive correlation has been found between reduced recipro-
cal inhibition and functional deficits in stroke patients and, regardless of
its pathophysiological role in spasticity, reciprocal inhibition thus appears
to be of clinical importance for at least gait function in spastic patients
(Bhagchandani and Schindler-Ivens 2012, Okuma and Lee 1996).
2.5.5.2 Recurrent Inhibition
Recurrent inhibition is mediated by Renshaw cells, which are located in the
ventral horn of the spinal cord, where they receive excitatory collaterals from
the motor axons and project back to the motoneurons as well as Ia inhibi-
tory interneurones (Figure 2.4). Recurrent inhibition is not easy to study in
human subjects, but Pierrot-Deseilligny and Bussel (1975) have developed
a complex H-reflex technique by which this is possible (Pierrot-Deseilligny
and Bussel 1975). The basis of the technique is to use a previous reflex dis-
charge to activate the Renshaw cells and study the effect of this activation
on a subsequently evoked test reflex. With this technique it has been demon-
strated that recurrent inhibition at rest appears to be normal in most patients
with spasticity (Katz and Pierrot-Deseilligny 1999, Katz et al. 1982). Only in
patients with progressive paraparesis or ALS is a reduction found at rest
and it is doubtful that this reduction contributes to the spasticity observed
in these patients (Mazzocchio and Rossi 1989, Raynor and Shefner 1994).
Changes in recurrent inhibition thus probably play no major role in the
pathophysiology of spasticity.
42
descenderende drive
Healthy subjects (n = 25)
fra bla corticospinale
Hemiplegic patients (n = 11)
nervebane
Paraplegic patients (n = 11)
MS patients (n = 30)
130
la afferenter
120
110
la
motoneuroner mn mn mn 100
90
(% of control reflex)
80
Size of conditioned reflex

m. Quadriceps
70
0 2 4 6 8 10 12
Conditioning-test interval (ms)
m. Tibialis
anterior
m. Soleus
FIGURE 2.4
Disynaptic reciprocal inhibition and spasticity. The figure on the left illustrates the circuitry of disynaptic reciprocal inhibition. Red neurons indicate
motorneurons and greenneurons indicate 1a afferents. Descending drive is represented by the purple line. The graph on the right shows the size of
the conditioned reflex (% of control reflex) at different conditioning-test intervals (0–10 ms). Healthy subjects are indicated as black dots, hemiplegic
(stroke) patients as red dots, paraplegic (SCI) patients as green triangles, and MS patients as yellow triangles. The horizontal dotted line illustrates the
size of the control reflex.
2.5.5.3 Autogenetic Ib Inhibition
Autogenetic Ib inhibition was described originally in the cat spinal cord in
the 1950s (Laporte and Lloyd 1952). The inhibition is caused by activation of
Ib afferents coming from Golgi tendon organs and is mediated by segmental
inhibitory interneurons projecting to the motoneurons of the same muscle.
Ib inhibition may also be demonstrated in human subjects by stimulating
the branch from the tibial nerve that innervates the medial gastrocnemius
muscle and measuring the subsequent depression of the soleus H-reflex
(Pierrot-Deseilligny et al. 1979). Whereas this inhibition is easily demon-
strated in healthy subjects, Delwaide and Olivier (1988) failed to produce any
inhibition on the paretic side in 6 out of 6 hemiplegic patients, but instead
observed a facilitatory effect in many subjects (Delwaide and Oliver 1988).
This may relate to the pronounced facilitatory effect on the soleus H-reflex
following stimulation of the peroneal nerve, which was observed by Crone et
al. (2003) in their study of patients with stroke and spinal cord injury (Crone
et al. 2003). One possible explanation of the occurrence of this facilitation,
which paralleled the development of hyperreflexia, is increased excitability
of excitatory Ib afferent pathways, similar to those described in the cat spi-
nal cord (Gossard et al. 1994, McCrea et al. 1995). Furthermore, it has been
argued that reciprocal inhibition at wrist level is mediated by Ib inhibitory
pathways (Wargon et al. 2006). If so, the observation that reciprocal inhibi-
tion at the wrist level is reduced in hemiplegic patients (Nakashima et al.
1989) may provide further evidence that alteration of Ib inhibition/excitation
plays a role in the pathophysiology of spasticity. It thus seems likely that
changes in the balance between inhibitory and excitatory Ib pathways play
an important role in the development of spasticity and further studies in this
area are certainly needed.
2.5.5.4 Fusimotor Drive, Gamma-Spasticity

Increased fusimotor drive leading to increased sensitivity of the muscle
spindles to muscle stretch was a popular explanation of spasticity some 20
to 30 years ago (so-called gamma-spasticity). It was found during the 1960s
and 1970s that stretch reflexes, which are influenced by the sensitivity of the
muscle spindles, tended to be increased more in spastic patients than the
H-reflex, which is evoked by electrical stimulation of the peripheral nerve
and is therefore not influenced by the sensitivity of the muscle spindles
(Ashby and Verrier 1976). However, subsequent studies have demonstrated
that H-reflexes and stretch reflexes differ in many other ways than their sen-
sitivity to changes in fusimotor drive and a comparison of the two reflexes
therefore cannot be used to make any conclusions regarding changes in
muscle spindle sensitivity (Burke et al. 1983, Burke et al. 1984, Morita et al.
1998). Importantly, microneurography studies have also failed to demon-
strate any changes in the discharge of muscle spindle afferents in spastic
patients, making it unlikely that any significant changes in fusimotor drive

exists (Hagbarth et al. 1973, Wilson et al. 1999a, Wilson et al. 1999b).
2.6 How Is Clonus Related to Spasticity?

Clonus is characterised by rhythmic alternating oscillation at relatively low
frequency (3–8 Hz) at distal joints, in particular the ankle joint, following
muscle stretch that is sufficiently fast to elicit a stretch reflex (or catch). Clonus
is primarily seen in spastic patients and exaggerated stretch reflexes are usu-
ally present when clonus is observed (Mukherjee and Chakravarty 2010).
Clonus is therefore also often considered to be an integrated part of spastic-
ity, as also witnessed by the focus on clonus in the Tardieu scale (Haugh et al.
2006). However, many patients with severe spasticity fail to show clonus and
especially when muscle stiffness is very pronounced clonus is seldom seen
(Mukherjee and Chakravarty 2010). One possible explanation of this is that at
least partly different pathophysiological mechanisms may be involved in the
development of spasticity and clonus. Clonus has traditionally been thought
to be caused by alternating elicitation of stretch reflexes in antagonist mus-
cles (Hidler and Rymer 1999). The observation that the frequency of clonus
depends on the length of the limb segment in which clonus is observed is
consistent with this idea (Hidler and Rymer 1999). Furthermore, clonus has
been observed to be reset by stimulation of peripheral nerves and to dis-
appear when sensory afferent activity is blocked by ischemia (Rossi et al.
1990). Modeling studies also show that increased stretch reflex excitability
with appropriate conduction delays may adequately explain the occurrence
of clonus (Hidler and Rymer 1999). If this is correct, inclusion of clonus in
the definition of spasticity and its use in the Tardieu scale would be justified.
However, several studies have suggested that other mechanisms may at least
contribute to the occurrence of clonus (Beres-Jones et al. 2003, Dimitrijevic et
al. 1980, Walsh and Wright 1987). Dimitrijevic et al. (1980), contrary to Rossi
et al. (1990), failed to interfere with clonus by sensory inputs and demon-
strated examples where clonus was elicited by cutaneous input rather than
muscle stretch. Walsh and Wright (1987) also failed to interfere with clonus
by mechanical loading of the limb. Beres-Jones et al. (2003) observed that
EMG patterns in antagonistic ankle joint muscles during clonus in spinal
cord-injured subjects were often synchronised and unrelated to mechanical
stretch of the muscles (Beres-Jones et al. 2003). These studies, thus, suggest
that central oscillator networks may at least contribute to the occurrence of
clonus. Their central idea is that sensory input to the spinal cord may activate
the rhythmic locomotor network in the cord. This network has been shown
to be capable of oscillating for prolonged periods of time following sensory
input in animals and to some extent also in humans (Calancie et al. 1994,
Dietz et al. 1997, Pinter and Dimitrijevic 1999). Due to the contradictory find-
ings in the various studies it seems at least possible that both mechanisms
may be involved, possibly to varying extents in different patients and may
manifest differently at joints with different loading/stretch conditions.
Regardless of this, caution should be made when relating clonus too closely
to spasticity.
2.7 What Causes a Spasm?

Spasms are involuntary muscle contractions, which last from seconds to
minutes and are usually provoked by a sensory stimulus, although in some
cases no clear sensory stimulus can be determined. Spasms are differenti-
ated from spasticity by the longer duration and strength of the contraction,
which can sometimes be so severe that it becomes painful. Spasms are also
differentiated from spasticity by being elicited preferentially by cutaneous
rather than muscle afferent inputs. Spasms are mainly seen following spi-
nal cord injury, whereas they are rarely seen in stroke patients, even with
very significant exaggeration of stretch reflexes and severe muscle stiffness
(Malik et al. 2014). Spasms are thus clearly pathophysiologically distinct from
exaggerated stretch reflexes. The occurrence of spasms is closely related to
increased withdrawal reflexes following injury and it is generally accepted
that spasms are caused by pathologically increased transmission in flexor
reflex afferent (FRA) circuitries in the spinal cord (Barolat and Maiman 1987).
As already discussed, studies in both animal and human have suggested a
significant role of upregulation of 5-HT receptors, secondary to loss of sero-
tonergic innervation and resulting in increased persistent inward currents
(PICs) in motoneurons and possibly also in interneurons in the FRA circuit-
ries (Bennett et al. 1999, Bennett et al. 2001, D’Amico et al. 2013b, Gorassini
et al. 2004, Murray et al. 2011a). This would explain why spasms are mainly
seen in spinal cord-injured subjects and rarely following stroke or in cerebral
palsy.
2.8 Spastic Dystonia Is Not Caused by

Increased Stretch Reflex Activity
Spastic dystonia is a term that was introduced by Denny-Brown to designate
tonic muscle activity in arm muscles in monkeys following central motor
lesion (Denny-Brown 1966). He observed that the activity persisted when dor-
sal roots were cut and concluded that stretch reflex activity was not involved.
In humans it is seen in the upper limb, where it contributes to the hemi-

plegic posture primarily in subjects with stroke or cerebral palsy (Gracies
2005, Sheean 2002, Sheean and McGuire 2009). In humans a dynamic form
of spastic dystonia is also seen during standing and gait where the subject
may adopt a posture with plantarflexion at the ankle, pronounced extension
at the knee, and associated flexion at the elbow (Gracies 2005, Sheean 2002,
Sheean and McGuire 2009). These features resemble the overflow phenom-
ena observed in patients with extrapyramidal (basal ganglia) lesions, hence
the term dystonia. We have at present no clear indication of what causes spas-
tic dystonia except for the findings in monkeys by Denny-Brown (and which
need to be confirmed in humans). Plastic changes at a spinal level involving
upregulation and sprouting of surviving descending fibres may explain both
the tonic and dynamic form, whereas upregulation of PICs in motoneurons
may possibly explain the tonic form (Gorassini et al. 2004). However, changes
at a cortical level may also play a role and it should also be kept in mind
that stroke often involves other structures than the descending pathways
and that basal ganglia affection is not uncommon in stroke patients. Spastic
dystonia may thus be the end-result of reduced voluntary control of muscles
due to (partial) corticospinal lesion and increased involuntary activation due
to basal ganglia lesion.
2.9 Concluding Remarks
This chapter has emphasised that there is a range of adaptations in spinal
circuitries following lesion of central motor fibres. These adaptations should
be seen as an attempt to ensure a functional output from the spinal cord
following loss of some of the normal supraspinal drive to the spinal moto-
neurons. We have the possibility of testing part of the circuitries that show
adaptation following lesion by imposing muscle stretch and eliciting a sen-
sory input to the spinal cord. The increased muscle resistance that we may
sense in this way thus provides information of only some of the adaptations
that occur, and it is therefore not surprising that spasticity; i.e., hyperactive
stretch reflexes, only provide a partial insight into the full range of clini-
cal manifestations of the adaptations to central lesions. In a broader sense,
these adaptations are also responsible for such manifestations as spasms,
clonus, and spastic dystonia, as well as the movement disabilities encoun-
tered by patients following central motor lesions. These may, to some extent,
be related to spasticity but may also be seen separately. Treatment of patients
with central motor lesions should take the different underlying pathophysio-
logical mechanisms responsible for the various manifestations of spinal cord
adaptations into account. The realisation that sensory feedback is closely
integrated with descending motor commands as a basis of all movements
and that spasticity is a reflection of an upgrading of sensory feedback as a

compensation for loss of descending drive should also warrant caution when
prescribing antispastic medication to patients with some functional ability.
Given the integrated nature of sensory feedback and descending motor com-
mands involved in all voluntary movements, the practice of dorsal rhizot-
omy must also cause some worry (Tedroff et al. 2011).
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3
Functional Problems in Spastic
Patients Are Not Caused by Spasticity
but by Disordered Motor Control
Jakob Lorentzen, Maria Willerslev-Olsen,

Thomas Sinkjær and Jens Bo Nielsen
CONTENTS
3.1 Reflexes Are an Integrated Part of Voluntary Movement....................... 59
3.2 Stretch Reflex Modulation in Spastic Subjects.......................................... 60
3.2.1 Reflex Modulation during Simple Contraction of Agonist
Muscle................................................................................................. 60
3.2.2 Hyperexcitable Stretch Reflexes in the Stance Phase of Gait...... 62
3.2.3 Control of Reflexes in the Antagonist............................................63
3.2.4 Suppression of Reflexes in Swing Phase.......................................63
3.3 Sensory Feedback Contribution to Movement.........................................64
3.4 Long-Latency Stretch Reflexes and Coordination of Movement........... 66
3.5 Interjoint Coordination................................................................................ 67
3.6 Interlimb Coordination................................................................................ 68
3.7 Co-Contraction as a Strategy to Maintain Joint Stiffness....................... 69
3.8 Over-Activity as a General Adaptation to Central Lesion Causing
Disordered Motor Control........................................................................... 70
3.9 Training to Learn New Strategies and Thereby Make Use
of Spasticity.................................................................................................... 70
References................................................................................................................ 71
3.1 Reflexes Are an Integrated Part of Voluntary Movement

The name of Charles Scott Sherrington is, more than anything, linked to the
concept of simple reflexes, although he himself warned against putting too
much emphasis on simple reflex mechanisms without realising the much
more complex integrative function of the nervous system. In 1906 he wrote:
A simple reflex is probably a purely abstract conception, because all parts of the
nervous system are connected together and no part of it is probably ever capable
of reaction without affecting and being affected by various other parts, and it is a
59
system certainly never absolutely at rest. But the simple reflex is a convenient, if
not a probable, fiction. Reflexes are of various degrees of complexity, and it is help-
ful in analyzing complex reflexes to separate from them reflex components which
we may consider apart and therefore treat as though they were simple reflexes.
Sherrington’s student John Eccles (1903–1997), and his student in turn,

Anders Lundberg (1920–2009), investigated many of these complexities of the
spinal reflex networks, emphasising the vast convergence on common inter-
neurons and motoneurons from sensory afferents and descending motor
fibres (Alstermark et al. 2010, Hultborn 2006). Their findings effectively con-
firmed Sherrington’s view of the integrated nature of reflexes. However, it
was not until the 1980s and onwards that human experiments demonstrated
unequivocally that reflexes are modulated during movement and integrated
into the central motor programmes underlying voluntary movement (Burke
2012, Nielsen 2004).
Given the knowledge of the integrative nature of reflexes going back to
Sherrington’s work, it is not surprising that hyperexcitable reflex excitabil-
ity in patients at rest during neurological examination has been shown to
have little relevance for the functional capabilities of those patients. William
Landau expressed this with characteristic bluntness in 1980:
However useful to clinical diagnosis may be the increase of excitability at ante-

rior horn cells and, to some extent muscle spindles, these phenomena have little
more relation to the patients disability than does insertion of the rectal thermom-
eter in pneumonia (Landau [1980]; p. 20).
3.2 Stretch Reflex Modulation in Spastic Subjects

3.2.1 Reflex Modulation during Simple Contraction of Agonist Muscle
Direct demonstration that evaluation of spasticity at rest has little relevance
for the situation during movement was originally provided by Ibrahim et al.
(1993). They measured stretch reflexes in elbow flexors of healthy subjects and
on the lesioned and non-lesioned sides in hemiplegic stroke patients at rest
and during voluntary elbow flexion. Whereas stretch reflexes were strongly
exaggerated on the lesioned side when measurements were made at rest, no
significant difference on the two sides or with respect to healthy subjects
was found during the elbow flexion. Sinkjaer et al. (1993) and Sinkjaer and
Magnussen (1994) at the same time demonstrated that the reflex-mediated
stiffness of the ankle plantarflexor muscles was similar during ankle plan-
tarflexion in spastic patients suffering from stroke or multiple sclerosis as
compared to healthy subjects (Ibrahim et al. 1993, Sinkjaer and Magnussen
1994, Sinkjaer et al. 1993).
Functional Problems in Spastic Patients Are Caused by Disordered Motor Control 61
The lack of difference in reflex excitability during contraction is not sur-

prising given the well-established understanding of the convergence of
descending motor commands and sensory feedback signals on common
spinal neurons (Burke 2012, Nielsen 2004). In healthy subjects stretch reflex
excitability is increased during contraction of the muscle in which the
reflex is evoked through regulation of a number of different mechanisms
that have been investigated during the past 20 to 30 years (Figure 3.1). First,
the depolarisation necessary to activate the motoneurons during a contrac-
tion naturally also makes them more excitable to the input from stretch
reflex afferents. There is no reason why this should be different in spastic
patients. Indeed, making measurements at matched contraction levels, as in
the studies by Ibrahim et al. (1993) and Sinkjaer et al. (1993), ensures that
the motoneuronal excitability will be matched also and that any difference
between healthy and spastic motoneurons will be taken out of the equation.
Healthy subject, at rest Healthy subject, during contraction

Presynaptic
inhibition
Postactivation Reciprocal
depression inhibition
Gr I/II
Gr I/II excitation
inhibition
m. Soleus
m. Soleus
Spastic subject, at rest Spastic subject, during contraction
Gr I/II Gr I/II
excitation excitation
m. Tibialis anterior m. Tibialis anterior
m. Soleus m. Soleus
FIGURE 3.1
Modulation of reflex pathways at rest and during contraction in healthy and spastic subjects.
The figure illustrates the spinal reflex circuitry in healthy subjects at rest and during contrac-
tion (top left and right, respectively) and in spastic subjects at rest and during contraction
(bottom left and right, respectively). Presynaptic inhibition and postactivation depression is
illustrated by a yellow neuron, reciprocal inhibition is illustrated by a blue neuron, and group
Ib/II inhibition (healthy at rest) and excitation (healthy during contraction, spastic at rest and
during contraction) is illustrated with a green neuron. The two muscles represent the soleus
muscle and tibialis anterior.
Another way of saying this is that the neural adaptations that cause the
motoneurons to be more excitable in the resting state cannot be demon-
strated during contraction because it is ensured by the very design of the
measurement that the excitability levels are matched. Since neural adapta-
tions have lowered the threshold of the motorneurons, the spastic subject
with a hyper-excitable motoneuron will have to use relatively less descend-
ing activity during rest to reach a given contraction level as compared to a
healthy subject (note, however, that this may be perceived as a far bigger
effort given the primary lesion of the descending command); i.e., without the
hyper-excitability in the resting state the ability of spastic patients to volun-
tarily activate the muscle would likely have required a much larger effort. A
contributing factor to the depolarisation of the motoneurons is the removal
of inhibitory inputs to the motoneurons. Inhibition of motoneurons from
reciprocal inhibitory interneurons and other classes of interneurons is thus
reduced when a muscle is voluntarily activated (Crone et al. 1987, Nielsen
and Kagamihara 1992). In spastic patients, these inhibitory influences are
already scaled down in the resting state and there is thus no need for the
patient to remove them as part of the central command during movement.
Second, the gain of the stretch reflexes is also increased in healthy human
subjects by increased release of transmitter substances from the sensory
afferent synapses on the motoneurons. At least two mechanisms contribute
to this: post-activation depression, which effectively depresses the reflex in
the resting state, is switched off during contraction (Hultborn and Nielsen
1998) and presynaptic inhibition is greatly reduced for Ia afferents project-
ing to the active motoneurons (Hultborn et al. 1987, Nielsen and Kagamihara
1993). Since both mechanisms are already reduced when at rest in spastic
subjects, little additional change is seen during contraction.
Finally, group Ib/II inhibition is prominent at rest in healthy subjects,
but replaced by excitation during movement (Faist et al. 2006, Stephens and
Yang 1996). This is, in all likelihood, related to gating of transmission in the
pathways, replacing inhibition, which would hinder the activation of the
muscle, by excitation, which will instead help the supraspinal structures in
maintaining muscle activation (Gossard et al. 1994, Jankowska et al. 1993). In
spastic subjects, group Ib/II inhibition is reduced and replaced even in the
resting state by excitation (Achache et al. 2010b, Crone et al. 2003, Delwaide
and Oliver 1988), which persists during voluntary contraction, analogous
with observations made in voluntary movements made by healthy subjects.
3.2.2 Hyperexcitable Stretch Reflexes in the Stance Phase of Gait

In contrast to what is observed in relation to simple static contractions of
a muscle, soleus H-reflexes and stretch reflexes are generally found to be
exaggerated when elicited during the stance phase of gait in spastic patients
suffering from stroke (Cho and Lee 2013, Mazzaro et al. 2006, Mazzaro et al.
2007, Sinkjaer et al. 1996b) or cerebral palsy (Hodapp et al. 2007a, Hodapp
et al. 2007b, Willerslev-Olsen et al. 2014). In healthy subjects, presynaptic

inhibition helps to diminish the size of the H-reflex in the stance phase of
walking as compared to matched levels of EMG activity during standing
(Capaday and Stein 1986, Capaday and Stein 1987, Ethier et al. 2003, Faist et
al. 1996, Ferris et al. 2001, Simonsen and Dyhre-Poulsen 1999, Simonsen et
al. 1995). There is good reason to assume that the spastic patients are unable
to adequately increase presynaptic inhibition and depress the reflex in the
same way as in healthy subjects. In healthy children, this depression appears
to depend on development of the corticospinal tract and is not seen to the
same extent as in adults until the age of 12 to 14 years (Hodapp et al. 2007a,
Hodapp et al. 2007b, Willerslev-Olsen et al. 2014). In children with hemiplegic
CP, the depression of the reflex does not appear on the affected side at least
before the age of 15 (Hodapp et al. 2007a, Hodapp et al. 2007b, Willerslev-
Olsen et al. 2014).
3.2.3 Control of Reflexes in the Antagonist

At the onset of certain contractions, reciprocal inhibition is greatly increased
in order to prevent unwanted activation of the antagonists (Crone et al. 1987,
Crone and Nielsen 1989, Kagamihara and Tanaka 1985, Morita et al. 2001,
Nielsen and Kagamihara 1992). At the same time, presynaptic inhibition of Ia
afferents projecting to antagonist motoneurones is also increased to further
reduce the risk of eliciting stretch reflexes in the antagonist muscles when
they are stretched at the onset of movement (Morita et al. 2001, Nielsen and
Kagamihara 1992, Nielsen and Kagamihara 1993). This regulation of antago-
nist muscles is impaired in patients with spasticity and they therefore fail to
prevent the elicitation of stretch reflexes at the onset of movement (Morita et
al. 2001). It is likely that one strategy adapted by patients in this situation is
to move slower in order to prevent elicitation of reflexes with too-fast move-
ments (Morita et al. 2001, Okuma and Lee 1996).
3.2.4 Suppression of Reflexes in Swing Phase

In healthy subjects, a very profound suppression of soleus H-reflexes and
stretch reflexes is seen in the swing phase of walking (Capaday and Stein
1986, Ethier et al. 2003, Simonsen and Dyhre-Poulsen 1999, Sinkjaer et al.
1996a, Willerslev-Olsen et al. 2014). This likely relates to increased reciprocal
inhibition from ankle dorsiflexors to plantarflexors when the dorsiflexors are
activated to lift the foot above the ground (Petersen et al. 1999). A similar
modulation of the H-reflex has been described during bicycling with a very
profound suppression (likely due to increased reciprocal inhibition from
dorsiflexors to plantarflexors) during upstroke (Pyndt et al. 2003, Pyndt and
Nielsen 2003). In patients with stroke, multiple sclerosis, and cerebral palsy,
a much-less-pronounced suppression of reflexes in swing during gait is
observed (Mazzaro et al. 2007, Sinkjaer et al. 1996b, Willerslev-Olsen et al. 2014).
A similar tendency has also been observed for stroke patients during bicy-
cling, although a significant effect was not observed except for patients with
the most reduced function (Schindler-Ivens et al. 2008). Although it has not
been specifically tested, it seems likely that the inability to adequately sup-
press reflexes in the swing phase relates to impaired control of reciprocal
inhibition as demonstrated for dynamic movements in sitting subjects by
Morita et al. (2001). It may be argued that the relative hyperexcitability of the
reflex in the swing phase prevents the patients from performing fast move-
ments and thereby from walking as quickly as would otherwise have been
possible. To what extent this is really a functional problem is not fully clari-
fied. At some point it has also been assumed that inappropriate control of
the reflex in the swing phase could contribute to premature activation of the
plantarflexors prior to heel strike and cause co-activation of the antagonistic
muscles. A large part of the rationale for using botulinum neurotoxin as a
treatment of toe-walking in children with CP has thus been to prevent pre-
mature activation of plantarflexors. However, premature activation of plan-
tarflexors is often seen in healthy children and there is no clear evidence that
co-activation around the ankle joint prior to ground contact should be more
common in children with CP than in healthy children (Willerslev-Olsen et
al. 2014). Also, the larger stretch reflexes in children with CP in the swing
phase than in healthy children do not seem to contribute to any inadvertent
EMG activity. Similar to what has been found in the stance phase of walk-
ing, sudden shortening of the co-activated plantarflexors in the swing phase
does not result in a drop in EMG activity at the latency of the stretch reflex
(Willerslev-Olsen et al. 2014). Since this muscle shortening will result in ces-
sation of activity in force- and length-sensitive afferents from the plantarflex-
ors, the lack of drop in EMG activity at stretch reflex latency suggests that
there is no contribution of muscle spindle afferent activity to plantarflexor
muscle activity in children with CP during the swing phase of walking. It is
therefore a likely possibility that spasticity does not lead to co-activation and
premature activation of plantarflexors in children with CP and that it does
not contribute to toe-walking in these children.
3.3 Sensory Feedback Contribution to Movement

In healthy subjects, presynaptic inhibition appears to prevent the monosyn-
aptic Ia input to the motoneuornes from contributing substantially to the
activation of the muscles during gait (Capaday and Stein 1986, Donelan et
al. 2009, Grey et al. 2007, Pearson 2004, Pearson 2008, Sinkjaer et al. 2000).
During locomotion in the cat, stimulation of extensor muscle afferents does
not produce any substantial monosynaptic EPSPs in triceps surae motoneu-
rones (Brownstone et al. 1994, Gossard et al. 1994, McCrea et al. 1995), but
rather EPSPs with an at-least-disynaptic latency (McCrea et al. 1995). There

is good evidence to suggest that these EPSPs involve multimodal afferent
convergence (group Ia, Ib, and II) to interneurons that are components of
a locomotor rhythm generator in the cat lumbar spinal cord (Gossard et al.
1994, McCrea et al. 1995). In intact cats it has also been shown that transmis-
sion in load-sensitive rather than length-sensitive afferents are of dominant
importance for the maintenance of extensor muscle activity in the stance
phase of real and fictive gait (Conway et al. 1987, Donelan et al. 2009, Pearson
2004, Pearson 2008). Sudden unloading of the limb thus initiates the flexor
phase, whereas maintenance of load on the muscles during stance – and thus
activity in Ia afferents – provides a continuous excitatory drive to the moto-
neurons. This suggests that interneurons mediating load-sensitive inputs to
the motoneurones rather than the Ia monosynaptic pathway are of major
importance for the muscle activation during gait. This is likely also the
case in human subjects (Sinkjaer et al. 2000). Unloading of the ankle plan-
tarflexor muscles thus produces a depression of soleus EMG activity with a
latency compatible with transmission in a similar pathway as what has been
described in the cat (Donelan et al. 2009, Pearson 2004, Pearson 2008, Sinkjaer
et al. 2000). Furthermore, this depression is not sensitive to a block of Ia affer-
ents (Sinkjaer et al. 2000).
In healthy human subjects, the monosynaptic Ia afferent pathway thus
seems to make only a minor or no contribution to the triceps surae muscle
activity in the stance phase of walking. However, with the exaggeration of
stretch reflexes in spastic patients it could be expected that they would show
some contribution of the pathway to the maintenance of EMG activity, but
this does not seem to be the case. In both adults with stroke and children
with CP, unloading of the ankle plantarflexors in the stance phase of gait
thus produces a depression of soleus EMG activity with a latency similar
to that observed in healthy subjects. If anything, this depression is smaller
in spastic patients than in healthy subjects (Mazzaro et al. 2007, Willerslev-
Olsen et al. 2014), indicating a reduced transmission in the pathway and
a reduced contribution of sensory afferent feedback to the activity of the
soleus muscle. The clinical significance of this finding is that it is not pos-
sible to conclude that sensory input to the spinal cord is exaggerated under
functional conditions based on observations of exaggerated reflex responses
either at rest or under those functional conditions. It should again be remem-
bered, as pointed out by Sherrington, that reflexes are (fictive) simplified con-
cepts (something that we evoke under very unnatural conditions to serve
our diagnostic purposes) that have little relevance to normal physiological
integration of sensory feedback.
If sensory feedback from the active plantar flexor muscles in the stance
phase is of importance in maintaining the muscle activity, as the data from
cat and human laboratory experiments suggest (Donelan et al. 2009, Pearson
2004, Pearson 2008), suppression of this feedback by antispastic medication
may be disadvantageous. This is also supported from over-ground human
experiments. Subjects who are asked to walk without visual feedback across
a platform that is tilted slightly to emulate irregularities in the ground thus
adjust the EMG activity in the plantarflexor muscles according to the plat-
form within a short time after making contact with the platform (af Klint et
al. 2008). It could be shown that this is likely to be caused by load-sensitive
afferents from the plantarflexors and this illustrates that one important func-
tion of this feedback is to provide automatic adjustments to irregularities
in the ground (af Klint et al. 2010, af Klint et al. 2008, Af Klint et al. 2009). If
this feedback is suppressed by antispastic medication or surgical interven-
tion, the ability of the subjects to adjust their gait according to the ground
conditions and limb loading would be assumed to be lost and they would
be forced to pay much more conscious attention to their gait. This is exactly
what is observed when subjects are given antispastic medication such as
baclofen and diazepam (Orsnes et al. 2000, Laurent Bouyer, Jakob Lorentzen,
Maria Willerslev-Olsen, Jens Bo Nielsen, personal observation).
3.4 Long-Latency Stretch Reflexes

and Coordination of Movement
As also described in Chapter 2, several additional reflex components are
observed at latencies longer than the monosynaptic stretch reflex, especially
during contraction. The M2 reflex response in leg muscles is caused by the
activation of spinal interneurons through activation of group II afferents
(Corna et al. 1995, Grey et al. 2001, Nardone and Schieppati 2005) and is gen-
erally found to be exaggerated in spastic subjects similar to the monosyn-
aptic reflex components (Ibrahim et al. 1993, Sinkjaer and Magnussen 1994,
Willerslev-Olsen et al. 2014). The significance of these responses for the func-
tional ability of spastic subjects is unclear, but since the responses mostly
behave similarly to the monosynaptic M1 component, it seems likely that the
above discussion of the M1 component also applies to the M2 component.
The later-occurring M3 responses have a latency that is sufficiently long
for them to be mediated through a transcortical reflex pathway (Christensen
et al. 2000). Animal experiments have unequivocally demonstrated the exis-
tence of such transcortical pathways and indirect evidence from human
experiments support that a transcortical pathway also contributes at least to
the long-latency reflex responses in some muscles in humans (Christensen
et al. 2001, Christensen et al. 2000, Petersen et al. 1998). Most convincingly,
TMS over the primary motor cortex at an intensity sufficiently low to activate
only local inhibitory interneurons efficiently suppresses the long-latency
stretch reflex components in finger muscles (Taylor et al. 1995) and the tibi-
alis anterior muscle (Zuur et al. 2009). For the TA, this is also the case during
gait (Zuur et al. 2009). For other muscles such as the soleus muscle and the
proximal arm muscles the evidence is less convincing and it appears likely
that other pathways, possibly involving brain stem nuclei, also contribute to
the long-latency reflex responses. Similar long-latency responses may also
be observed following cutaneous stimulation of both the fingers and the foot
and, similar to what has been observed for muscle afferents, transcortical
reflex pathways appear to contribute to these responses (Christensen et al.
2000). Given the transcortical nature of long-latency reflexes, it is not surpris-
ing that they are generally found to be absent or greatly reduced in patients
with central motor lesions, including cortical stroke (Christensen et al. 2000,
Trumbower et al. 2013, Zehr et al. 1998).
The functional significance of these long-latency responses and thus the
functional significance of their absence in patients with central motor lesions
is not fully clarified, although suggestions for their possible importance has
been put forward (Dietz and Sinkjaer 2007). The responses are generally
rather stereotyped and appear in a predictable fashion, but at the same time
their latency makes them almost indistinguishable from a voluntary reaction
to a sensory stimulus that occurs only a few milliseconds later. To an even
greater extent than the monosynaptic spinal stretch reflex, these responses
should, therefore, be seen as an integrated part of voluntary movements
rather than as simple stereotypic reflex responses. The sensory feedback
from both muscles and skin provides the cortex with important information
about the supporting ground as well as obstacles encountered during gait,
which permits that functionally relevant adaptations of gait may be executed
(Christensen et al. 2001, Christensen et al. 2000, Zuur et al. 2009). Such adap-
tations will depend on the time in the gait cycle, the particular context, and
the intentions of the subject, to name only a few factors. Integration at a cor-
tical level may help to ensure that these different constraints are taken into
account before the particular reaction to the sensory input is executed. The
reduction and even absence of the responses in patients with central lesions
in all likelihood provides an important contribution to their functional
inability. Without sufficient adjustment and updating of the central com-
mands according to the sensory information, the central control of move-
ment will be deficient. This will involve, in particular, the reactions that are
necessary to maintain balance and adjust gait according to external chal-
lenges. It should again be pointed out that antispastic medication is likely to
diminish further the information carried by the sensory feedback important
for these reactions.
3.5 Interjoint Coordination
Sensory afferents from skin, muscles, tendons, and joints project to spinal
interneurons that influence the activity not only of motoneuroes innervating
muscles acting at the joint from where the afferents originate, but also of
motoneurons innervating muscles acting at other joints in the same limb
(Burke 2012, Jankowska 1992). Relatively little is known about the modula-
tion of transmission in these reflex pathways during movement in healthy
subjects and patients with spasticity. Ia afferents from muscle spindles thus
project monosynaptically to synergistic motoneurons throughout the same
limb (Burke 2012). Failure of presynaptic inhibition of these projections likely
also contributes to some of the gait disturbances in spastic patients. O’Dyer et
al. (2009, 2011) described that exaggerated excitation of soleus muscles from
femoral nerve afferents was directly correlated to increased co-activation of
ankle extensors and knee extensors in stroke survivors (O’Dyer et al. 2009,
O’Dyer et al. 2011). This co-activation was also shown to be well correlated to
functional impairment in the patients (O’Dyer et al. 2011).
Group I and group II afferents from ankle plantarflexors and dorsiflexors
also project to knee extensors and flexors (Burke 2012). The reflex pathway
from ankle dorsiflexors to the knee muscles is relatively suppressed dur-
ing static conditions in sitting or standing subjects, but transmission in the
pathway is greatly facilitated just prior to and just after heel strike during
gait (Iglesias et al. 2008, Marchand-Pauvert and Nielsen 2002a, Marchand-
Pauvert and Nielsen 2002b). The functional importance of this gating of
transmission in the pathway is probably to ensure the stability of the knee
joint when the load of the body is moved onto the supporting limb early in
stance (Iglesias et al. 2008, Marchand-Pauvert and Nielsen 2002b). A similar
modulation is also seen in stroke patients, but with pronounced exaggeration
of the later components of the reflex excitation (Achache et al. 2010a). This
may be a compensation to ensure the stability of the knee joint in light of
muscle weakness (paresis) and may possibly also contribute to the stiffness
of gait in spastic patients.
3.6 Interlimb Coordination
In animals, commissural interneurons that project from one side of the spi-
nal cord to interneurons and motoneurons on the other side are involved in
coordinating activation of the muscles to ensure the occurrence of appropri-
ately timed activity in flexors and extensors (Bannatyne et al. 2009, Butt et
al. 2002, Dietz and Michel 2009, Jankowska et al. 2009). These interneurons
receive in animal models significant input from both sensory afferents (in
particular, group II afferents) and descending fibres (in particular, vestibulo-
spinal fibres) (Bannatyne et al. 2009, Jankowska et al. 2009).
It is unclear to what an extent these spinal pathways influence gait in
human subjects and potentially contribute to the gait deficit in spastic sub-
jects. Following nerve stimulation or muscle stretch, short-latency inhibitory
responses are observed contralaterally, whereas excitatory responses are

generally of such long latency that it cannot be excluded that supraspinal
pathways are involved (Berger et al. 1984, Dietz et al. 1984, Stubbs et al. 2011a,
Stubbs et al. 2011b, Stubbs et al. 2012). In complete spinal cord-injured sub-
jects, sensory input also does not influence the activity of the opposite leg
during treadmill-generated locomotion, suggesting that interlimb coordina-
tion requires supraspinal control (Dietz et al. 2002). Lesion of descending
pathways either in the spinal cord or at cortical level is therefore likely to
interrupt the connections that are essential for coordination of the two legs
(Sousa et al. 2013). Treadmill training where the two legs may be trained
individually or together may thus also depend on re-establishment of supra-
spinal control of the spinal networks rather than training of the spinal net-
works themselves, although evidence to support this possibility has also
been presented (Barbeau et al. 2006, Colombo et al. 2000, Reisman et al. 2010a,
Reisman et al. 2010b).
3.7 Co-Contraction as a Strategy to Maintain Joint Stiffness

For decades it has been assumed that the co-activation of antagonistic mus-
cles is undesirable and the observation of increased co-activation around
a number of joints during functional movements in patients has therefore
been seen as disadvantageous (el-Abd et al. 1993, Poon and Hui-Chan 2009).
The logic in this is that co-activation costs more energy as it requires the ago-
nist to overcome the force of the antagonists. Activation of muscles becomes
more fractionated with fewer groups contributing to successful movement as
motor learning and rehabilitation progress (Nielsen 1998, Smith 1981). This
is also the case in relation to rehabilitation of function in patients following
central lesions (Miyoshi et al. 2010, Ohn et al. 2013, Okuma and Lee 1996).
Activation of muscles becomes gradually more focused and involves increas-
ingly fewer muscles, which are activated less as motor learning and rehabili-
tation progress (Miyoshi et al. 2010, Ohn et al. 2013, Okuma and Lee 1996).
This does not signify, however, that co-activation is necessarily disadvan-
tageous for the patient. On the contrary, co-activation may be the only viable
strategy for the patient to maintain stability around a joint when muscles
are weak due to paresis and paralysis. As demonstrated by Nielsen et al.
(1994), co-activation of muscles around the ankle joint is the most efficient
way of increasing joint stiffness and ensuring stability of the joint (Nielsen
et al. 1994). A co-contraction strategy is adapted also in healthy human sub-
jects whenever steady control of the joint position and maintenance of bal-
ance is a requirement (Nielsen and Kagamihara 1992, Nielsen 1998). That
co-activation may be an efficient functional strategy is witnessed by the fact
that ballet dancers use co-activation around the ankle joint to ensure balance
during various postures and jumps (Nielsen et al. 1993). The co-activation of
knee extensors and ankle plantar- and dorsiflexors may also be examples of
a similar compensatory strategy aimed at ensuring the stability of especially
the knee joint, due to partly paretic and weak muscles (Achache et al. 2010a,
Dyer et al. 2009, Dyer et al. 2011).
3.8 Over-Activity as a General Adaptation to Central

Lesion Causing Disordered Motor Control
As pointed out in several review papers (Gracies 2005a, Gracies 2005b,
Sheean 2002, Sheean and McGuire 2009, Yelnik et al. 2010), as well as in
Chapter 2, spasticity may be seen as part of a more general spinal adapta-
tion to the loss of descending drive resulting not only in exaggerated stretch
responses (at least at rest), but also an upregulation of the synaptic efficacy
of surviving descending fibres. In addition, supraspinal adaptations may
result in an exaggerated and insufficiently focused descending drive to spi-
nal motoneurones that are not normally activated as part of the generated
movement. This inadvertent ‘over-flow’ or ‘over-activity’ is likely the cause
of the ‘spastic dystonia’ seen in many patients with stroke and other cen-
tral lesions. The associated postural disturbances, affection of joint position,
and compromised movement control are clearly of great functional signifi-
cance for patients. It is therefore unfortunate that we have little knowledge
of the underlying causes, except for the original observations in monkeys
that stretch reflex activity is not responsible and that these disturbances
therefore should be seen as separate from spasticity (Denny-Brown 1966).
There is clearly a need for more research to determine the pathophysiologi-
cal changes leading to spastic dystonia and how these changes contribute to
the movement disorder in patients with central lesions in order to optimise
future treatment.
3.9 Training to Learn New Strategies

and Thereby Make Use of Spasticity
It is often reported as a clinical observation that patients with spasticity may
use the muscle activity provided by the exaggerated stretch reflex activity
to stand and maybe even walk (Dietz 2003, Dietz 2008, Dietz and Sinkjaer
2007, Dietz and Sinkjaer 2012). Although this idea is attractive, there is little
direct evidence to support that it is correct. There is, however, convincing
evidence that spasticity does not become more pronounced with training
(Damiano 2014, Dodd et al. 2002, Kirk et al. 2016, Lorentzen et al. 2017, Schram
Christensen et al. 2017) and it is also likely a possibility that a large part of
the beneficial effect of functional training in subjects with spastic movement
disorder may be related to a more optimal integration and interpretation of
sensory feedback signals (Frisk et al. 2017, Willerslev-Olsen et al. 2015). With
our current understanding of the role of sensory feedback in generation of
voluntary muscle activity and as error signals for the updating of central
motor commands (Nielsen 2016), it would make sense to design future inter-
ventions to make use of spasticity to facilitate functional recovery rather than
to diminish it at all cost. If spasticity is seen as a plastic response to reduced
descending input to the spinal cord with the overall aim of maintaining a
functional drive to the muscles, a treatment goal might be to train patients to
adapt new movement strategies where they can more easily make use of the
possibilities provided by the altered sensory feedback.
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4
The Clinical Management of Spasticity
and Contractures in Cerebral Palsy
Andrew Roberts
CONTENTS
4.1 Introduction................................................................................................... 79
4.2 Cerebral Palsy................................................................................................80
4.3 Treatment Objectives.................................................................................... 82
4.4 Medical Treatment........................................................................................85
4.4.1 Oral Medication................................................................................85
4.4.1.1 Benzodiazepines................................................................85
4.4.1.2 Oral Baclofen....................................................................... 86
4.4.1.3 Gabapentin and Pregabalin.............................................. 86
4.4.2 Injection Therapies........................................................................... 86
4.4.2.1 Botulinum Toxin................................................................ 86
4.4.2.2 Phenol.................................................................................. 87
4.5 Therapy........................................................................................................... 88
4.5.1 Stretching........................................................................................... 88
4.5.2 Strengthening.................................................................................... 88
4.6 Surgical Treatment........................................................................................ 89
4.6.1 Neurotomy......................................................................................... 89
4.6.2 Intrathecal Baclofen.......................................................................... 89
4.6.3 Selective Dorsal Rhizotomy............................................................ 91
4.6.3.1 Case Study........................................................................... 94
4.7 Conclusion..................................................................................................... 96
References................................................................................................................ 96
4.1 Introduction
For the past century, clinicians have had to treat the consequences of injury
to the developing nervous system in the absence of a sound understand-
ing of the underlying pathology. Louis Stromeyer was the first to under-
take surgical treatment of a contracture secondary to an upper motoneuron
injury in 1831. Little in England, who suffered from poliomyelitis, had his
heel cord contracture released by Stromeyer and subsequently practised
79
the orthopaedic management of neurological conditions, including cerebral

palsy, which came to be known as Little’s disease [1]. A lack of non-invasive
investigational techniques meant that an understanding of the motor con-
sequences of injury to the developing nervous system was restricted to ani-
mals. The cat and rat are not ideal models for the human and our knowledge
of spasticity, as it affects man, has been deficient until the last two decades.
Experiments in man have not always had encouraging clinical results, as
demonstrated by Foerster’s use of total dorsal rhizotomy for spasticity lead-
ing to deafferentation [2]. Not surprisingly given the complexity of the condi-
tion, progress in the clinical management of spasticity has been slow.
4.2 Cerebral Palsy
Cerebral palsy is a common disabling condition in childhood that encompasses
a large spectrum of conditions. A key characteristic of the cerebral palsies is
that they occur around the time of birth or soon after, injuring the nervous
system at a time when rapid change is occurring during typical development.
At birth, the cortical spinal tracts have not formed. Projections from the motor
cortex develop to infiltrate the ipsilateral and contralateral spinal cord. In the
absence of injury, the ipsilateral projections are selectively removed and the
contralateral projections gradually mature over the first two years of life [3].
Whilst the understanding and characterisation of an individual’s condition
has been aided greatly by the advent of cross-sectional imaging, specifically
magnetic resonance imaging, the correlation between changes seen by the neuro-
radiologist and the problems encountered by the patient is often rather tenuous
[4]. Increasingly, it is appreciated that the precise time of the injury and the envi-
ronment shortly after injury have a significant influence on the effect of a discrete
lesion [5]. The gap between neuro-imaging and reality has been bridged by the
treating clinician often with a degree of imprecision. Fundamental differences
between patients, for example, the presence or absence of ipsilateral corticospinal
drive, are not appreciable without sophisticated diagnostic techniques [6].
As obstetric practice has improved over the last 30 years, the spectrum of
motor disorders resulting from injury has changed. Difficult delivery result-
ing in oxygen deprivation and consequent hypoxic ischaemic encephalopathy
is now an uncommon event, producing fewer children with total-body cere-
bral palsy. The management of neonatal jaundice has also led to a reduction
in kernicterus that was associated with athetoid* cerebral palsy and dystonia.†
* Athetosis is a slow, continuous, involuntary writhing movement that prevents maintenance

of a stable posture [7].
† Dystonia is a movement disorder in which involuntary sustained or intermittent muscle con-
tractions cause twisting and repetitive movements, abnormal postures, or both [8].
The Clinical Management of Spasticity and Contractures in Cerebral Palsy 81
Premature birth leads to a haemorrhagic injury adjacent to the internal capsule

as the foetal brain undergoes a rapid reduction in pressure on emerging from
the intrauterine environment. Immature cerebral blood vessels are weaker than
those at full term and rupture leads to haemorrhage to varying degrees. Severe
haemorrhage may be sufficiently extensive to cause bleeding into the ventricles
and subsequent clot organisation with obstruction of the cerebral aqueduct,
leading to hydrocephalus. Characteristically, the cortico-reticular tracts adjacent
to the pyramidal tracts are involved, reducing the inhibitory drive delivered by
the reticular system to the cord. Whilst cerebral palsy following premature birth
is characterised by spasticity and kernicterus leads to basal ganglia involvement
producing athetosis or dystonia, more generalised hypoxic insults produce a
mixture of motor disorders as a result of multiple lesions distributed through
the hemispheres. Often, hypoxic brain injury will lead to a significant degree of
cognitive impairment with learning difficulties during childhood.
The surgical treatment of contractures and bony deformity in spastic
cerebral palsy is well-established in the treatment of mobility and postural
impairment, but consensus has formed that dystonia is both hard to treat
and unpredictable with regards to outcome. First, dystonia is an abnormality
of pattern rather than a resetting of the length-tension relationship of muscle
seen in spasticity. It is possible through surgery to change a patient from
one dystonic pattern to a completely different pattern, leading to a new but
equally disabling posture. Because dystonia often results in an end-of-range
posture at a joint, uncontrolled muscle force in the post-operative period
has the potential for interfering with tendon transfers and bony procedures
with suboptimal results. No reliable preventative strategy has been agreed
on with respect to surgery in dystonia but good prolonged pain control
and local neuromuscular blockade with botulinum toxin to cover the post-
operative period seemed to help. Unfortunately, dystonia is all too often a
post-operative diagnosis, following a presumed procedure for the conse-
quences of spasticity. The commonest form of cerebral palsy encountered
in Western clinical practice is that associated with premature birth with
unilateral or bilateral internal capsule bleeding leading to periventricular
leucomalacia. Some children with unilateral involvement have a neronal
migration disorder that is often accompanied by spastic dystonia as a result
of a more diffuse problem. Where periventricular leucomalacia is encoun-
tered, the cortex is initially intact. Depending on the lesion distally the motor
area for the lower limb may migrate laterally out of the inter-hemispheric
sulcus towards the motor area for the upper limb. The resulting reduction in
available pyramidal cells and thus eventual potential motor units, as well as
a blurring of the distinction between upper and lower limb motor maps, will
lead to weakness and imperfect control in addition to distal effects of cord
reorganisation in response to reduced reticulo spinal drive. Current clini-
cal practice remains focused on intervention to modify the reflex arc. The
conceptual model in the author’s mind is that spasticity is: ‘the pathological
effect of a failure of hierarchical control of the threshold of the tonic stretch
reflex in support of posture and movement’ [9]. This gross simplification

of the positive and negative effects of the upper motoneuron lesion on the
developing brain is reflected in the simplistic nature of our current treat-
ment strategies. Clinical experience with adults affected by cerebral palsy
confirms that spasticity is usually a long-term phenomenon. One study sug-
gesting that spasticity wanes during childhood based its assessment on the
calf; however, it is likely that contracture of gastrocnemius later in childhood
masks persistent spasticity in soleus, giving the impression of a reduction
in spasticity [10]. Clonus can commonly be elicited in a spastic calf with the
knee flexed, where it is not evident when the same rate and range of motion
are used with the knee in extension.
4.3 Treatment Objectives
Spasticity and contracture are not necessarily problems that require treat-
ment. The establishment of achievable objectives aligned to the wishes
of the child and family is essential. Often, unrealistic expectations need
to be explored and rationalised before an agreed way forward can be
found. A hierarchy of objectives can be generally agreed, with distress-
ing symptoms taking priority over function and cosmesis. In the mul-
ticentre SPARCLE study of children between the age of 8 and 12 years
living with cerebral palsy across the European Union, pain was found to
be the dominant factor that impinged upon quality of life [11]. Previously,
pain was not sought as a symptom when managing children with cere-
bral palsy because children often considered the pain to be ‘normal’ and
did not mention it to their parents or their clinical carers. The majority
of children in the SPARCLE study had sufficient cognitive function that
they were able to use the Child Health Questionnaire and Paediatric Pain
Questionnaire [12,13]. In children with very significant cerebral palsy, their
ability to vocalise their discomfort is often restricted; as a result, there
are pain scores that have been developed for total-body-involved children
[14]. An enquiry about pain should be the first step in identifying possible
objectives for treatment in cerebral palsy. Spasticity may lead to pain by
producing abnormal forces on a particular structure, such as capsule and
synovium, as a result of prolonged posture at the end of the joint’s range.
Prolonged function with abnormal posture may lead to a failure of the
integrity of the foot as a lever of progression, with high pressures over the
navicular or base of the fifth metatarsal leading to pain. Crouch gait may
lead to unacceptable loads on the extensor mechanism of the knee, with
a failure of the distal pole of the patella or the tibial tuberosity leading to
discomfort. Orthotic management, typically with ankle-foot orthoses, can
often be complicated by discomfort when deformity or spasticity lead to
high interface pressures between the device and the child’s skin. Where
cerebral palsy is associated with muscle weakness and high levels of spas-
ticity, prolonged activation of weak muscles can lead to pain. Whether
pain in spastic muscle is the result of lactic acidosis or mechanical stretch
is uncertain. The inability of the child to suppress muscle activation may
lead to discomfort during therapeutic stretching.
Function is impaired as a result of the complex interaction of spasticity,
weakness, and control impairment. Some typical patterns are seen but the
wide variety of defects leads to variability of functional impairment. In the
child affected by periventricular leucomalacia who has sufficient strength
to establish early walking, spasticity affecting the calf leads to the develop-
ment of an equinus gait pattern. Once the child is in equinus, the origin of
the ground reaction vector is advanced and a persistent extending moment
during stance develops around the knee. A persistent extending moment
around the knee negates the need for learning the control of the knee flexors
and extensors that occurs in the typically developing child. Furthermore,
the advanced ground reaction vector requires the hip to remain in flexion.
The secondary contracture of the hip develops and the absence of end-stance
hip extension removes the effect of the ilio-inguinal ligament on the anterior
femoral neck leading to persistent femoral anteversion (Figure 4.1, left-hand
frame). At the time of the adolescent growth spurt, failure of the foot as a
lever often occurs as a result of rapid gain in weight, and the sudden return
FIGURE 4.1
The effect of calf spasticity on ground reaction vector alignment leads to excessive knee exten-
sion and hip flexion during stance. The application of an ankle-foot orthosis makes this worse
until corrections applied to the shoes normalise the ground reaction vector with respect to the
knee joint centre.
Ankle dorsiflexion Ankle dorsiflexing moment Ankle power

30 3.0 5.0
Dors Dors Gen
Deg Nm/kg W/kg
Plan Plan Abs
–90 –1.0 –2.0
FIGURE 4.2
The effect of calf spasticity on ankle posture produces a pathologically increased moment in
the first half of stance, giving a ‘double bump’ in the moment graph (centre) leading to abnor-
mal generation and absorption of power in the power graph (right). Gray band = normal values.
of the ground reaction vector towards the ankle joint centre causes the child
to walk with trunk upright and the thigh anteriorly inclined, producing a
crouch gait pattern with progressive deterioration in walking ability.
Spasticity impedes gait at several points in a gait cycle. In the calf, soleus is
typically more hyper-reflexic than gastrocnemius and frequently causes the
child to vault in mid-stance, expending energy without producing propul-
sion (Figure 4.2).
On examination, gastrocnemius is often less obviously involved with
the features of the upper motoneuron syndrome than soleus, but appears
to have a very ready propensity to become contracted in response to the
posture imposed by its near neighbour. The hamstrings are often signifi-
cantly spastic and may limit knee extension in terminal swing, produc-
ing an excessively flexed posture at initial contact. Rectus femoris requires
precise control because of its rôle at the knee and hip. A burst of activity
is normally seen in the rectus femoris at pre-swing, terminating quickly
once the foot is off the ground to allow inertial forces to flex the knee and
shorten the limb. A lack of useful activity in the calf during stance makes
forward propulsion of the leg difficult in pre-swing and excessive activity
in rectus femoris is required in swing phase as a compensation leading to
a stiff knee gait pattern with a significant increase in energy expenditure
as a result of the higher moment of angular momentum associated with the
extended limb (Figure 4.3).
Bone growth in the presence of spasticity and abnormal posture may
result in torsional deformity in the tibia, uncoupling the ankle plantar
flexion-knee extension couple, or in the proximal femur leading to a defunc-
tioning of the hip abductor mechanism necessary to stabilise the trunk
during stance. Femoral anteversion in the newborn is much higher than
in the adult, with the reduction resulting from hip extension in terminal
stance producing pressure between the anterior femoral neck and the ilio-
femoral ligament. The orientation of the femoral neck alters in response to
1.2 Rectus femoris
0.0
0 20 40 60 80 100
FIGURE 4.3
Rectus femoris surface EMG normal values (gray bars = 1 standard deviation) with a compari-
son trace from a patient exhibiting swing phase spasticity (black trace).
the posteriorly directed pressure by means of Wolff’s law.* Where function

is near-normal, improving the appearance of gait may be of benefit to the
child necessitating de-rotation procedures to align the knee and foot in the
direction of progression.
4.4 Medical Treatment
4.4.1 Oral Medication
4.4.1.1 Benzodiazepines
Benzodiazepines, most notably diazepam, have been investigated for spas-
ticity management in cerebral palsy. In general, benzodiazepines act by
binding to the GABAα receptor found extensively throughout the central
nervous system [15]. Whether the anti-spasticity action of benzodiazepines
is predominantly at cord level, or also at a higher level, is uncertain. A recent
American Academy of Neurology review suggested that the role of diaz-
epam is as a short-term spasticity treatment. Owing to the sedative and
dependency effects of benzodiazepines, medium- or long-term treatment
* Wolff’s law relates to the absorption of bone in areas of low strain and deposition of bone
in areas of high strain. Inhibition of bone resorption by osteoclasts underpins this adaptive
mechanism to load exhibited by the vertebrate skeleton.
should be avoided. Current practice is frequently to use diazepam as a res-

cue medicine for painful spasms, particularly after surgical procedures, but
not to use it on a long-term basis [16].
4.4.1.2 Oral Baclofen
Oral baclofen acts as an agonist on the metabotropic GABAβ receptor, which,
in turn, activates the G-protein K+ channel. In spite of its relatively modest
molecular weight, baclofen penetrates the blood–brain barrier rather poorly.
As a long-term oral medication, progressive increases in dosage are required
until the therapeutic effect is obtained. Nausea, drowsiness, or hypotonia
limit the oral dose of baclofen and often the therapeutic benefit is not seen
before unwanted effects are encountered. Sudden cessation of oral baclofen
may be associated with hallucinations [17]. However, withdrawal of the oral
form is a less severe problem than that encountered during intrathecal use
of the same agent. One clinical trial of oral baclofen showed a favourable
response in 70% of patients in terms of spasticity reduction and passive and
active limb movement, with a 25% incidence of adverse effects, all of which
resolved on withdrawal of medication [18]. The treatment effect is sufficiently
modest that oral baclofen is not widely used in children with spastic cerebral
palsy [16].
4.4.1.3 Gabapentin and Pregabalin

Gabapentin and pregabalin, whilst pharmacologically different, have a similar
spectrum of action against neuropathic pain. Both agents have been evaluated
for the management of spasticity in general, but neither agent has been specifi-
cally used in cerebral palsy or spasticity management [19,20]. Where neuro-
pathic pain complicates cerebral palsy, there may be a role for the use of these
agents, but a wide variety of side-effects often limit their usefulness [19,21].
4.4.2 Injection Therapies
4.4.2.1 Botulinum Toxin
Botulinum toxin type A has been widely used in the management of spas-
ticity in cerebral palsy. Early experiments in spastic mice suggested that
the effect of toxin was temporary [22]. The concept of botulinum toxin as
‘bridging treatment’ whilst the patient grew, allowing definitive treatments
towards the end of growth, became established. It remains common practice
for children to have regular cycles of botulinum toxin injections to main-
tain range of movement. Boyd has identified a consensus that after three
injections, the effect of botulinum toxin in any particular muscle diminishes
[23]. While this lessening of efficacy was originally considered to be due to
antibody formation, it is probably related to dystrophic change with muscle.
Anecdotal reports of muscles becoming inelastic and unresponsive to phys-

iotherapy stretching come from physiotherapists treating children who
have had repeated botulinum toxin injections. Two studies have examined
placebo-controlled botulinum toxin injections to be calf muscle combined
with serial casting. Both studies showed better length either by measuring
muscle length or joint angle at 6 weeks after administration, but marginally
shorter muscles after botulinum toxin, compared with saline, at 12 months
[24,25]. Muscle fibrosis following toxin injection may be the mechanism
underlying this long-term effect of botulinum on muscle length.
The dose of botulinum toxin used depends upon the commercial product,
with the leading suppliers having assays that give different units for prep-
arations delivering similar effects. Initially, cautious dosing regimes were
employed. Higher doses of toxin were gradually introduced until very high
doses per kilogram of body weight were used in a multilevel fashion [26]. The
role of botulinum toxin in managing spasticity in cerebral palsy is licensed in
the calf, but other uses are ‘off-licence’. This is not an impediment to the wide-
spread use of toxin therapy in the upper and lower limbs, as well as in the
management of the spastic bladder. As a trial therapy to evaluate the effect of
muscle lengthening or as a rebalancing treatment, botulinum toxin remains
an extremely useful therapeutic agent in spite of concerns about dystrophic
change after multiple uses. The use of botulinum toxin should be restricted
to muscle where shortening is dynamic rather than structural. The distinc-
tion between structural and dynamic shortening is that slow stretching or
anaesthesia leads to a lengthening of muscle that exhibits dynamic shorten-
ing, but structural shortening is unaffected by anaesthesia. Differentiating
between contracture and spasticity is usually straightforward in cerebral
palsy because spastic dystonia and other velocity-independent motor dis-
orders are relatively uncommon. A slow stretching of muscle and joint will
usually allow the distinction between structural and dynamic contracture.
Where muscle is inappropriately short during activity, either kinematics or
dynamic EMG can be used to identify that activity in a specific muscle or
muscle group is inappropriate when compared with normal.
4.4.2.2 Phenol
Phenol as a 7% aqueous preparation may be used for local nerve blockade.
The corrosive nature of phenol is such that small quantities have to be used,
requiring the careful location of nerves with a nerve stimulator. Typically,
in a child, 0.25 mL of 7% aqueous phenol is injected directly onto the nerve.
The most frequent target for these blocks is the obturator nerve by medial
approach behind the origin of the tendon of adductor longus. Because the
injection has to be precisely targeted on the surface of the nerve, a general
anaesthetic is necessary. The nerve stimulator is gradually turned down
until a response occurs as a very low current and also disappears with only
a slight movement of the needle. The clonic twitching of the adductors in
response to the nerve stimulator can be seen to fade over a period of 1 to

2 minutes after the injection. It then takes between 6 and 9 months for the
nerve to regrow through the lesion following the Wallerian degeneration
induced by the chemical insult.
4.5 Therapy
4.5.1 Stretching
Stretching forms an essential component of maintenance therapy for chil-
dren with spastic cerebral palsy [27]. During sleep, postures of flexion are
often adopted in the trunk and limbs. Whether this flexion is behavioural or
neural in origin, the flexed posture allows the development of contractures
with a progressive deterioration of function both of the hip and at the knee.
Stretching emulates the physiological response of muscle as mechanically
sensitive tissue challenged by a combination of physical play and skeletal
growth. Evidence for this assertion is available in cats, but not in developing
humans [28]. Where control and weakness limit the ability to play and be
active, therapeutic input from therapists, family members, and the patient
to stretch up muscles is important. The duration and intensity of stretch
are important determinants of efficacy. Various animal models have been
used to evaluate effective stretching, suggesting that a 60-minute stretch is
likely to produce a maximum effect and will not be bettered by more pro-
longed stretching. Orthotic devices such as standing frames or contracture-
correction devices can be used to deliver therapeutic stretching in a consistent
fashion, provided compliance is maintained [29].
4.5.2 Strengthening
Strengthening spastic muscles was traditionally viewed as a hazardous
practice, but evidence in the last decade suggests that improvements in
strength can be obtained through resistive strength training, although
there are limits to the extent to which this can be achieved [30]. A concern
that strengthening spastic muscles can lead to an increase in spasticity has
been refuted by clinical studies [31]. Because of the injury to the central ner-
vous system, the number of alpha motoneurons (which have a one-to-one
mapping with pyramidal cells) will be restricted and therefore there will
be a limit imposed on maximal strength. Furthermore, spastic muscle is
stiffer as a result of increased connective tissue and longer, less-compliant
sarcomeres [32]. Finally, children with cerebral palsy have a very limited
ability to recruit motor units, further reducing the force they are able to
produce [33].
4.6 Surgical Treatment
4.6.1 Neurotomy
It is possible to reduce muscle action by partial or total division of the motor
nerve. Unfortunately, this has only a limited application because of either
mixed motor and sensory components within the nerve or lack of a suitable
target. One instance where a single muscle might beneficially be degraded in
its action is soleus, which is often particularly spastic in cerebral palsy. The
motor nerve can be found in the popliteal fossa and its identity confirmed
with electrical testing. An approximately 50% division of the motor nerve
leads to a reduction in strength and, consequently, a reduction in equinus. It
is less commonly practised in the English-speaking community than in con-
tinental Europe [34,35]. The motor branch to soleus is, in an adult, approxi-
mately 1 mm in diameter, making accurate division difficult. The decrement
in action is permanent. Multiple neurotomies in the lower limb may be
useful in removing the unwanted effects of spastic dystonia in stroke [36].
Neurotomy may also be useful in the upper limb, where function is not the
prime objective.
4.6.2 Intrathecal Baclofen
Baclofen, when given by mouth, has a weak effect as a result of poor penetra-
tion of the blood-brain barrier. To overcome this in patients with extensive
spasticity, implantable pumps of increasing levels of sophistication have been
developed.* Daily doses of intrathecal baclofen are typically three orders of
magnitude smaller than that those required to achieve a modest effect when
given orally.
In heavily involved individuals, postural problems secondary to spasticity,
structural problems such as scoliosis, and lack of control and weakness par-
ticularly in the trunk and neck muscles can make seating and care difficult.
Intrathecal baclofen treatment has the advantage of being adjustable so that
unwanted excessive reduction of spasticity unmasking weakness and lack of
control can be reversed. In addition, the ability to vary the pattern of baclofen
infusion throughout the day allows further refinement.
Clearly, invasive and expensive treatments such as intrathecal baclofen
require multidisciplinary assessment and a test dose given by lumbar-
puncture injection into the thecal space.
Because of the profound agonistic effect of baclofen on GABA receptors,
withdrawal and overdose are significant potential hazards. Combined with
the cost of the pump and a programme for refilling the device on a regular
basis, the side-effects and complications necessitate careful patient selection.
* Medtronic, 20 Lower Hatch Street, Dublin 2, Ireland Flowonix Medical, 500 International
Drive, Suite 200, Mt. Olive, New Jersey 07828, USA.
In general, patients who are non-ambulant or patients with very precarious

postural control with total-body involvement are potentially suitable for
intrathecal baclofen treatment. Because of the ability to vary the profile of
drug delivery and the overall dose by means of an external programmer held
over the pump, fine adjustments can be made to optimise spasticity reduc-
tion, while avoiding excessive loss of trunk muscle activation. Furthermore,
if spasticity results from a progressive condition, the overall dose of baclofen
can be increased to account for the increasing levels of spasticity. The pumps
vary in size, with miniature drives, control systems, and a reservoir for the
baclofen. Pumps now tend to be placed in an intermuscular plane beneath
the external oblique muscle in the right iliac fossa. Movement of the pump
within its pocket can lead to discomfort and the need for revision. In smaller
children, even the smallest pumps can lead to discomfort from impingement
on the costal margin, particularly where there is a scoliosis or truncal insta-
bility secondary to impaired control. The catheter connection with the pump
represents one of the potential weaknesses of the system, with the occasional
occurrence of kinks and disconnections. Pump disconnection or failures can
lead to a life-threatening neuroleptic malignant syndrome requiring prompt
identification, intensive-care support, and revision of the catheter or device
[37]. The full syndrome includes rhabdomyolysis, headache, autonomic dys-
function, fever, coma, and death. A strategy for diagnosing problems with
pumps includes plain radiography, contrast injection via a diagnostic port,
and the use of rapid infusion rates of saline to enable fluoroscopic visuali-
sation of the rotor moving within the device. Specific supportive measures
and guidelines to manage acute withdrawal have not been established, with
case reports providing some evidence of effective strategies [38]. Whilst the
catheter has a very fine bore, the dead space (volume of baclofen solution)
contained within the length of the catheter is sufficient, where concentrated
solutions of baclofen are used, to present an overdose hazard if the line is
flushed through in an antegrade direction [39,40]. The catheter is tunneled
subcutaneously from the pump and passes into the thecal sac through a low
lumbar entry point. The height of the intrathecal catheter tip has a bearing
on the distribution of drug within the thecal sac, with relatively high cath-
eters having more effect on trunk tone and lower catheters less of an effect.
Although not primarily intended to affect the upper limbs, patients and fam-
ilies often report an improvement in upper limb function and some aspects
of speech and swallowing after the establishment of intrathecal baclofen [41].
In addition to spasticity, intrathecal baclofen infused through a trial cath-
eter over five days can have a significant effect on dystonia [42]. In patients
with a mixture of motor disorder types, the anti-dystonic effects of baclofen
can be a very valuable feature, particularly when compared with selective
dorsal rhizotomy, which may reveal unwanted dystonic postures uninhib-
ited by the restraint of spasticity. Intrathecal baclofen treatment is expensive
because of the cost of the pump and the refill programme. Savings in total
care costs for children treated with intrathecal baclofen have been reported
as a result of the reduction in whole-body spasticity secondary to the pump

[43]. Compared with intrathecal baclofen, selective dorsal rhizotomy has a
one-off cost but is permanent, is much more confined to the lower limb, and
is unsuitable for motor disorders other than pure spasticity.
4.6.3 Selective Dorsal Rhizotomy

For more than 100 years, disruption of the reflex arc in an attempt to reduce
spasticity has been attempted. Initially, the German neurosurgeon Otfrid
Foroester performed complete rhizotomy with rather poor outcomes, lead-
ing to him abandoning the technique. In the 1960s, the Italian neurosurgeon
Vincenzo Fasano used neurophysiology monitoring to guide partial division
of the dorsal roots, selecting those components of the root that were most
provocative of spasticity when stimulated [44].
Dr Warwick Peacock in South Africa used Fasano’s technique to manage
patients with spastic cerebral palsy diplegia. After moving to the West Coast
of America, Peacock’s technique spread widely among North American neu-
rosurgeons. The selection criteria employed by Dr Peacock required high lev-
els of spasticity; a diagnosis of spastic diplegia and adequate muscle strength.
An emphasis was placed on the careful selection of patients. As with any
technique, a wave of enthusiasm was followed by a period of retrenchment,
with many North American clinicians associated with the management of
cerebral palsy regarding the technique as unhelpful. A wave of enthusiasm
for selective dorsal rhizotomy in Scandinavia has been documented by the
CPUP National Surveillance Program, with an interesting decline in the
number of patients operated on in recent years. Dr Peacock’s technique con-
sisted of an extensive laminectomy from L1 down to L5, enabling visualisa-
tion of the whole of the cauda equine [45] (Figure 4.4).
The ability to confirm the level of exit of a particular root and the lack of
tension on the root at the time of sectioning is set against the extensive inci-
sion required by the original procedure practiced by Peacock. More recently,
a limited approach to the conus where the dorsal roots are sequentially
arranged (until disturbed by the surgeon) has been popularised in North
America [46]. The majority of centres now undertake the conus procedure,
with only a few persisting with Dr Peacock’s original cauda equina proce-
dure. Sectioning of L1 is deemed as important because of the effect of spas-
ticity on the psoas muscle. A degree of debate exists regarding sectioning of
the second sacral nerve. It is claimed that a more durable result arises from
sectioning S2, but concerns over alteration in sphincter function as well as
sexual function in the long term caused some centres to avoid intervening
at S2 [47,48]. Our programme of selective dorsal rhizotomy strictly avoided
S2 and we have noted normal sexual function and sphincter function in
our patients at skeletal maturity. The proportion of root sectioned varies
among series. Dr Peacock advised no more than 50% of the root be sectioned
but the trend has emerged for 75% section. In terms of sensory function,
FIGURE 4.4
Traditional exposure of the cauda equina during selective dorsal rhizotomy.
loss of afferent fibres is often not remarked upon by the patient, but clearly
the difference between a 50% and 75% root section is leaving 50% or 25%
of the sensory fibres. It is not possible to identify which portions of the root
contain cutaneous sensation and which contain joint, fusimotor, and tendon
afferent returns. Neurophysiological monitoring during sectioning is stan-
dard practice, both to confirm the sensory nature of the root and to triage
portions of the root that produce most aberrant spread of motor response
after rootlet stimulation.
It is generally possible to split roots into 4 or 5 sections, which can sub-
sequently be tested. Identifying the sensory root anatomically is relatively
straightforward as it is slightly more mobile than the motor root. The first
sacral root is often somewhat homogeneous and a formal motor test is invalu-
able when sectioning this root, certainly with the cauda equina method.
Some debate has centred around whether neurophysiological monitoring is
of benefit. It is certainly important to handle rootlets gently, avoiding trac-
tion, as this very often leads to erroneous responses. Likewise, repeated test-
ing of rootlets can often result in fatigue and rather variable findings.
A degree of proprioceptive loss results from rhizotomy even with 50% root
section. Some patients demonstrate features of de-afferentation (Figure 4.5).
A particular marker of this is excessive knee flexion in swing phase, as seen
on sagittal plane knee kinematic recordings.
Knee flexion
90
80
Flex
70
60
Angle (degrees)
50
40
30
20
Ext
10
–10
0 10 20 30 40 50 60 70 80 90 100
Normalized (percent)
Ankle dorsiflexion
30
20
Dors
10
0
–10
Angle (degrees)
–20
–30
–40
–50
–60
Plan
–70
–80
–90
0 10 20 30 40 50 60 70 80 90 100
FIGURE 4.5
Deafferentation following SDR is manifested by exaggerated movement particularly at the
knee where excessive flexion occurs in swing phase as a primary abnormality rather than as a
coping mechanism for poor clearance (gray band = normal range).
Selective dorsal rhizotomy, when applied to patients with minimal weak-

ness and significant spasticity (a rather exclusive group), will produce a last-
ing improvement in function, as shown by three-dimensional gait analysis
[49]. Antigravity strength equivalent to MRC grade 4 in the hip and knee
extensors is needed for sustained successful walking function after SDR.
The magnitude of the benefit delivered by rhizotomy is in proportion to the

extent of the spasticity present, as shown on manual testing using the modi-
fied Ashworth scale and the effect on knee kinematics and ankle kinematics
and kinetics. Dynamic surface EMG showing prolonged activation through-
out the gait cycle provides qualitative support for the presence of spasticity
that may benefit from surgical management. Typically, contractures at the
hip and ankle improve over 6 months following the surgery, with knee flex-
ion contractures proving more resistant, probably because of the presence
of extensor weakness either at the hip or the knee. Where contractures have
resolved in children who had been walking in crouch, improvement in inner
range strength often takes 12 months of focused strengthening with the hip
and knee positioned in extension coupled with accurate orthotic management.
The use of ankle-foot orthoses in footwear that is mechanically designed to
encourage knee and hip extension in stance facilitates the process of trans-
lating an improvement in range of movement into one that can be used as
a result of strength developing in that new range. Our experience has been
that children with a slow walking speed prior to rhizotomy have a strong ten-
dency to increase in weight, crossing centiles as weight increases more rap-
idly than growth would require [50]. Presumably, children who walk slowly
have a reduced ability to capitalise on their spasticity reduction because of
their underlying weakness and, with a reduction in the presumed calorie-
burning effect of spasticity, convert their excess calories into weight [50]. The
reduction in spasticity appears to be permanent and the long-term results of
the procedure, again in a carefully selected series, are encouraging [51,52]).
4.6.3.1 Case Study
An 8.5-year-old boy with GMFCS 2 bilateral cerebral palsy following a pre-
mature birth was noted to have crouch gait with a lack of end stance hip
extension. He had bilateral 10° hip flexion contractures with marginally tight
hamstrings and knees that extended fully. At the ankle, he could be brought
to plantigrade with the knee in extension but during gait was on his toes
throughout the gait cycle. He was noted to have good strength, with grade 5
power of hip extension and knee extension. His hips demonstrated high lev-
els of femoral neck anteversion. He underwent a selective dorsal rhizotomy
From L1 to S1 at the age of 9 with maximal root section of 40% at S1 and
between 20 and 30% root section elsewhere. Post-operatively he had intensive
inpatient physiotherapy with ankle-foot orthoses tuned to control the ground
reaction vector. During the remainder of childhood, he continued in orthoses
and had no orthopaedic surgery. At most recent follow-up 10 years afterwards
he was noted to be active, taking part in badminton and other sports. He
mentioned that he had lower back pain after sitting for long periods of time
but otherwise he was free of any symptoms. Cadence and step length had
increased in line with growth, as shown in Table 4.1. Sagittal kinematics at the
knee and ankle showed a significant improvement, as shown in Figure 4.6.
TABLE 4.1
Parameter Changes Pre- and 10 Years Post-SDR
Normalised Stride Normalised Stride
Cadence Speed Speed Length Length
Units Steps/min M/sec Leg Length/sec M Leg Length
Pre-SDR 67.2 1.18 1.84 1.06 1.66
Post-SDR 99.8 1.21 1.27 1.47 1.55
10 Years 124 1.26 1.2
Post-SDR
Pelvic tilt Knee flexion/extension

50 90
Ant Flex
deg deg
Post Ext
–10 –10
Hip flexion/extension Ankle dorsi/plantar

80 30
Flex Dors
deg deg
Ext Plan
–20 –90
FIGURE 4.6
Sagittal kinematics before and 10 years after SDR (green = right and red = left, dark colors are
pre op with gray band indicating normal range).
By reducing spasticity in the hamstrings and quadriceps the position of the

knee and the rate of knee flexion in pre-swing are improved respectively.
In keeping with other reports of the effect of SDR on gait, pelvic alignment
became more sacrum-up. Interestingly, his right ankle kinetics deteriorated
in adolescence after his 6-year post-op gait assessment as he abandoned his
AFOs and developed some tightness of the right ankle (Figure 4.7).
Ankle dors/plan moment Ankle power

2.0 4.7
Dors Gen
Nm/kg W/kg
Plan Abs
–1.0 –3.8
FIGURE 4.7
Ankle kinetics before and 6 years after SDR (green = right and red = left, dark colors are pre op
with gray band indicating normal range).
4.7 Conclusion
Cerebral palsy produces a complex pattern of histological, physiological, and
structural changes in muscles with weakness, shortening, and spasticity.
The wide variety of treatments available for contractures and spasticity in
cerebral palsy partly relates to the lack of a single target as well as the evolv-
ing nature of the condition during growth.
Future opportunities for managing the effects of spasticity on the grow-
ing child include the use of biological agents to improve muscle strength
and increasing understanding of the heterogeneity of receptors within the
central nervous system.
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5
Clinical Management of Spasticity
and Contractures in Stroke
Judith F. M. Fleuren, Jaap H. Buurke and Alexander C. H. Geurts
CONTENTS
5.1 Introduction................................................................................................. 101
5.2 Pathophysiology of Spasticity after Stroke.............................................. 102
5.3 Motor Recovery and Motor Control after Stroke................................... 105
5.4 The Role of Spasticity in the Control of Posture and Gait.................... 108
5.4.1 Muscle Overactivity during the Stance Phase............................ 111
5.4.2 Muscle Overactivity during the Swing Phase............................ 113
5.5 The Role of Spasticity in Arm and Hand Function............................... 115
5.5.1 Spasticity in Patients with a Severely Affected Upper
Limb (UAT 0–1)............................................................................... 117
5.5.2 Spasticity in Patients with a Moderately Affected Upper
Limb (UAT 2–3)............................................................................... 117
5.5.3 Spasticity in Patients with a Mildly Affected Upper Limb
(UAT 4–7)......................................................................................... 118
5.6 Assessment of Spasticity in Stroke Patients............................................ 118
5.6.1 Assessment of Spasticity: Body Function and Structure.......... 119
5.6.2 Assessment of Spasticity: Activity and Participation................ 121
5.7 Management of Spasticity after Stroke.................................................... 122
5.7.1 Noninvasive Methods.................................................................... 123
5.7.2 Invasive, Reversible Methods........................................................ 124
5.7.3 Invasive, Permanent Methods....................................................... 126
5.7.4 Management Strategy for Stroke Patients with Spasticity........ 128
References.............................................................................................................. 128
5.1 Introduction
Stroke, or cerebrovascular accident, is an acquired brain injury due to
an acute disturbance of blood supply to the brain, leading to ischemia.
Blood flow interruption can be caused by thrombotic or embolic occlusion
(ischemic stroke) or by rupture of a cerebral artery (hemorrhagic stroke).
Approximately 110,000 strokes occur in England every year and 800,000 in
101
the United States of America (National Audit Office, 2010; Mozzafarian et al.,
2015). It is one of the top five causes of death and the largest cause of adult
disability in Western countries. The World Health Organization has pre-
dicted that disability-adjusted life years (DALYs) lost to stroke will rise from
38 million in 1990 to 61 million in 2020 (WHO, 2004).
Spasticity after stroke is relatively common. A number of clinical stud-
ies have been performed in the last decade, presenting prevalence figures
between 4 and 46% (Watkins et al., 2002; Sommerfeld et al., 2012; Wissel et al.,
2013; Opheim et al., 2014). The outcomes depend on the used definition of
spasticity, the measurement methods, the time after stroke, and the popu-
lation studied. Most studies included patients with a first-time stroke and
spasticity was defined as 1 point or higher on the Modified Ashworth Scale
(MAS). Watkins et al. (2002) also included patients with recurrent stroke
and used two measurement scales for spasticity, the MAS and the Tone
Assessment Scale. The Tone Assessment Scale is a broader scale assessing
resistance in response to passive movement at more joints and including the
constructs “posturing at rest” and “associated reactions” as well. The preva-
lence of spasticity found in this study, 38% measured 12 months after the
onset in a general stroke population, may still be an underestimate, given the
methods of measurement and definition used.
In the field of Rehabilitation Medicine spasticity is an important topic.
Not the presence of spasticity per se, but the impact of spasticity on daily
life, requires attention in affected individuals. Although some beneficial
effects of spasticity have been reported in the literature (Mahoney et al.,
2007), the presence of post-stroke spasticity is generally associated with
negative consequences. Patients report sensations of stiffness, heaviness,
or pain in the affected limb. Spasms or cramp-like sensations are common,
e.g., during the night. Limb deformities or skin lesions might develop and
spasticity can increase carer burden, due to problems in moving, han-
dling, and positioning in routine daily care. In addition, spasticity can
decrease the functional ability of the affected limb. From the literature, it
can be estimated that in the group of chronic stroke patients with spastic-
ity, 20–30% will have disabling spasticity, for which treatment is needed
(Lundström et al., 2008).
5.2 Pathophysiology of Spasticity after Stroke

The pathophysiology of spasticity is discussed in Chapter 2 and its potential
impact on function in Chapter 3. In cerebral lesions, pathological increase in
muscle activity is explained by the loss of supraspinal control on spinal reflex
activity, which is mainly controlled in the brain stem. For the maintenance
of normal muscle activity, muscle spindles have a key role, transmitting
Clinical Management of Spasticity and Contractures in Stroke 103
signals regarding muscle length and rate of change in muscle length via
group Ia and group II sensory fibres. Sensitivity of the muscle spindles’
dynamic and static responsiveness is under central control, exerted through
alpha and gamma motoneuron coactivation. Together with the Golgi tendon
organs, which supply feedback to the central nervous system on changes
in muscle-generated and applied tension via type Ib afferents, muscle pro-
prioceptive afferent feedback participates in shaping muscle activity pat-
terns. Interneurons integrate multi-sensory afferent information through
excitatory Ia and inhibitory Ib pathways from a variety of muscles. They
receive a wide range of inputs from several different sources, both peripheral
and central (supraspinal), and each interneuron forms widespread synapses
with both homonymous and heteronymous alpha motoneurons. As a con-
sequence, spinal cord reflex responses are highly adaptable and shaped by
the convergence of inputs that inform on proprioceptive and exteroceptive
conditions.
Spasticity is probably the result of an imbalance of inputs from central
motor pathways, such as the (cortico-)reticulospinal and other descending
pathways, to the interneuronal circuits of the spinal cord. Via corticobulbar
tracts, motor areas of the cortex project on the ventromedial reticular for-
mation, the brain stem area where sensory information is being processed
(Sheean, 2002). The main supraspinal inhibitory tract arising from the ven-
tromedial reticular formation is the lateral reticulospinal tract, which runs
very close to the lateral corticospinal (pyramidal) tract with overlap of their
spinal targets (Lemon, 2008). The lateral reticulospinal tract is under facilita-
tory control of corticobulbar tracts, thereby augmenting the inhibitory drive
to the upper and lower limbs in healthy subjects. The main excitatory path-
way, also arising in the brainstem, is the medial reticulospinal tract, which
facilitates the maintenance of anti-gravity tone in muscles situated around
the longitudinal axis of the body. The medial reticulospinal system is, how-
ever, not under cortical control. Damage to the corticobulbar fibres – in the
cortex or lower down the tract – will thus primarily lead to decreased facili-
tation of inhibition of limb reflexes at brain stem level. Consequently, (sub)
cortical lesions involving the corticobulbar tracts give rise to a net loss of
inhibitory control at brain stem level, leading to increased alpha motoneuron
excitability at the cervical and lumbar spinal cord levels and, subsequently,
increase in limb muscle tone.
The overall clinical picture of motor symptoms after stroke depends on
the location and extent of the lesion. Whether spasticity will appear and
to what extent is hard to predict, although generally it is more often pres-
ent in patients with severe paresis. Probably associated, spasticity is found
to be more common and more severe in the upper than in the lower limbs
(Sommerfeld et al., 2012). If present, spasticity usually appears in the first few
days to weeks after the cerebral damage, possibly related to the dissolving
diaschisis at cerebral level and a process of plastic rearrangement of inter-
neurons at brainstem and spinal levels.
After stroke, common patterns of motor dysfunction can be recognised

(Mayer et al., 1997), given the fact that the middle cerebral artery territory
is the most frequently affected site. In the upper limb, the typical distribu-
tion of potentially affected muscle groups includes the shoulder adductors,
shoulder internal rotators, elbow flexors, forearm pronators, wrist flexors,
finger flexors, thumb flexors, and thumb adductor. In the lower limb the hip
flexors, thigh adductors, knee flexors and extensors, ankle plantar flexors,
ankle invertors, and toe flexors are often involved.
Affected muscles, both paretic and/or spastic, often follow a so-called
anti-gravity distribution, a term used for muscle groups that help to main-
tain trunk and head posture by counteracting gravity. There is an increased
appearance of stereotyped multi-joint movement patterns (“pathological
limb synergies”) and decreased ability to uncouple these. It is sometimes
considered a regression to phylogenetically older movement patterns, based
on limb synergies and primitive reflexes, arising from more basic systems in
the brainstem, basal ganglia, and cerebellum. Stereotyped movement pat-
terns can be observed in abnormal posture at rest (Kline et al., 2007), but
also as “rigid patterns” during active movement. There are indications that
the lower motor networks originating from the brainstem have more dif-
fuse projections onto alpha motoneurons at the spinal level, explaining the
less-selective activation and abnormal co-contractions of muscle groups
(Dewald et al., 1995). It is very likely that the above-mentioned lateral retic-
ulospinal tracts play an important role in subserving these stereotyped
movement patterns in an attempt to compensate for the loss of direct cor-
ticospinal connections to the cervical and lumbar motor neuron pools. For
example, strengthening of the normally weak activation of hand muscles by
the reticulospinal tract could lead to a certain degree of functional recovery
(Baker, 2011). As such, “spastic” muscular overactivity may be a useful func-
tional compensation rather than a phenomenon that must be eliminated (van
Kordelaar et al., 2012).
Both positive motor symptoms, i.e., the increased (stretch) reflex activity
in the antigravity muscles (afferent-mediated) and the more pronounced
presence of rigid synergy patterns (efferent-driven) co-exist post stroke and
therefore are hard to disentangle in clinical practice. Strictly following the
umbrella definition for spasticity used in this book, the efferent-driven rigid
synergy patterns are not included, which complicates the assessment of
whether “true” spasticity is present. However, in clinical practice the exact
pathophysiology and semantics with regard to the definition seem to be less
relevant, because the clinical focus is primarily on whether treatment for
“muscle overactivity” is required and – if yes – on its goal. In both cases,
careful reflection on the negative impact versus the positive contribution of
“muscle overactivity” is needed. In case treatment is indicated, therapeutic
options do not basically differ between the two.
Other clinical phenomena such as clonus, flexor and extensor spasms can
also be included in the used definition (see Chapter 1). Clonus, which may
be the presentation of intrinsic oscillating spinal neuronal networks (after

chronic loss of supraspinal input and diminution of load-related sensory
input [Beres-Jones et al., 2003]), is frequently observed in stroke patients,
mainly in the ankle plantar flexors, but sometimes in other muscle groups
as well (wrist flexors, finger flexors). Typical flexor and extensor spasms, as
observed, for example, in spinal cord-injured patients, are less common after
stroke. The multi-joint flexor or extensor reactions seen after stroke are prob-
ably related to manifestations of pathological limb synergies and primitive
reflexes. However, overlap in pathophysiology is unclear.
Early after a cerebral lesion, changes in mechanical, visco-elastic proper-
ties of muscle fibres and other soft tissues occur as a result of paresis and
immobility. Histological transformations in the muscles, such as muscle
fibre atrophy and loss of sarcomeres, have been shown to contribute to mus-
cle stiffness, leading to increased tension development upon passive muscle
lengthening and enhanced reflex sensitivity (Dietz, 2000; O’Dwyer et al.,
1996; Gracies, 2005 [I]). Accumulation of intramuscular connective tissue,
increased fat content, and degenerative changes at the musculotendinous
junction also cause reduced muscle compliance. Structural alterations in
other soft tissues, including joints, ligaments, vessels, and skin, also contrib-
ute to reduced range of motion (see Chapter 1).
5.3 Motor Recovery and Motor Control after Stroke

In the first weeks after stroke, neurological recovery shows a nonlinear pat-
tern. Early improvements in functioning are assumed to reflect intrinsic
recovery processes such as restitution of penumbral tissue, dissolving dias-
chisis, and reorganisation of cortical and cortico-spinal neurons (Kwakkel
et al., 2004; van Kordelaar et al., 2014). The degree of recovery after stroke is
largely defined within the first days after stroke onset. The extent of improve-
ment observed in the first days or weeks post-stroke and the initial severity
of disability are important indicators of the outcome at 6 months after stroke.
In patients with first-ever ischemic anterior or middle cerebral artery strokes,
motor recovery is almost completed within 4 to 10 weeks (Kwakkel et al.,
2006; van Kordelaar et al., 2014), independent of the severity of the initial
stroke. Theoretically, enhanced neuroplasticity could also allow for faster
learning of compensatory strategies while performing tasks during this time
window. In terms of functional recovery, most patients reach a plateau 3 to 6
months after onset (Kwakkel and Kollen, 2013).
Restoration of motor function tends to follow a stepwise sequence up
to the degree of recovery that an individual patient can reach (Twitchell,
1951; Brunnstrom, 1970). Areflexic flaccid paresis or paralysis is followed by
return of reflexes, increase in muscle activity, and development of spasticity.
Stages Description
Stage 1 Flaccidity is present and no movements of the limbs

can be initiated.
Stage 2 The basic limb synergies or some of their components
may appear as associated reactions or minimal
voluntary movement responses may be present.
Spasticity begins to develop.
Stage 3 The patient gains voluntary control of the movement
synergies, although full range of all synergy components
doest not necessarily develop. Spasticity is severe.
Stage 4 Some movement combinations that do not follow the
synergies are mastered and spasticity begins to
decline.
Stage 5 More difficult movement combinations are possible as
the basic limb synergies lose their dominance over
motor acts.
Stage 6 Spasticity disappears and individual joint movements
become possible.
FIGURE 5.1
Brunnstrom stages. (With permission from Brunnstrom, S [1970]. Movement Therapy in
Hemiplegia: A Neurophysiological Approach. New York: Harper & Row.)
Subsequently, voluntary movements can appear as part of rigid flexion and/

or extension synergies, followed by movements outside such synergies, to
the final stage, in which muscle activation is normalised and occurrence of
normal movement is possible (Figure 5.1).
For many stroke patients, regaining independent gait is an important goal
in the rehabilitation process. In general, the prognosis for regaining some
lower limb function after middle cerebral artery stroke is fairly good. At
6 months post-stroke, 60 to 80% of all surviving patients are able to walk
independently, yet with very different levels of ambulation (Perry et al.,
1995) and, in association, notable weight-bearing asymmetry (Buurke et al.,
2005; Kamphuis et al., 2012). A number of studies have shown that not only
the muscle strength of the hemiparetic leg, but particularly the compensa-
tory ability of the unaffected leg, is significantly associated with achieving
independent gait. Although it used to be common practice to pursue return-
ing to “normal” motor behavior in rehabilitation training after stroke, it
has become clear in the last decade that movement patterns on the affected
side are characterised by more or less fixed synergies observable early after
stroke, especially in relatively severely affected patients. Balance and gait
recovery in these patients is closely related to learning compensatory move-
ment strategies (de Haart et al., 2004; Buurke et al., 2005; Den Otter et al.,
2006; Buurke et al., 2008).
For the upper limb, the prognosis after middle cerebral artery stroke is
much less favorable. Prospective cohort studies suggest that 33 to 66%
of stroke patients with an initially paralytic upper limb do not show any
recovery in upper limb function 6 months after stroke. Depending on which
outcome measure was used, 5 to 20% of these patients achieve full recov-
ery of the upper limb at 6 months (Kwakkel and Kollen, 2013). It was found
that only patients with some movement in the upper limb within 4 weeks
post-stroke had a 94% chance to improve their Action Research Arm Test
(ARAT) scores at 6 months post-stroke (Kwakkel et al., 2003). The presence of
shoulder abduction and voluntary finger extension within 3 days after stroke
appeared to be essential for regaining some dexterity: patients with some
finger extension and shoulder abduction at day 2 after stroke onset had a
98% probability of achieving an ARAT-score ≥ 10 at 6 months. Patients with-
out this voluntary motor control had a probability of only 25%. Sixty percent
of the patients with some finger extension within the first three days reached
maximum scores on the ARAT at 6 months (Nijland et al., 2010).
Spasticity is just one component in disordered motor function after stroke.
Careful assessment of all signs and symptoms that might contribute to
impaired motor function in the individual patient with stroke is essential to
understand the full clinical picture and selecting the appropriate interven-
tion. Movement dysfunction after stroke arises from a complex interaction
between “negative” motor features (such as paresis, fatigability, and slow-
ness), “positive” motor features (reflex hyperexcitability, emergence of primi-
tive reflexes, and spasticity), and changes in the mechanical properties of
muscles and other soft tissues. The decreased voluntary motor unit recruit-
ment to generate muscle force on the one hand and the increased involuntary
motor unit recruitment on the other hand, in varying combinations and to
differing extents, lead to less fluent and less effective motor output (Gracies,
2005 [II]). Impairment of selective muscle control might be misinterpreted as
simple weakness, but it is primarily characterised by inadequate timing and
selective activation of individual muscles. This loss of control is usually more
severe distally than proximally, related to the high dependency of the dis-
tal limbs on direct corticospinal tracts. More “primitive” locomotor patterns
commonly become a substitute source of control. As a result, smooth move-
ment patterns are limited due to the inability to modulate direction, speed,
and intensity of movements. As pointed out earlier, changes in mechanical
properties of the muscles and other soft tissues lead to reduced tissue com-
pliance and secondarily increased reflex sensitivity, thereby contributing to
inadequate motor control.
Besides motor symptoms, sensory and cognitive functions play an
important role in normal motor control as well. Purposeful action is pos-
sible because movement control is continuously supported by an ongoing
stream of sensory information. Proprioceptive feedback is needed for fast
adjustments of ongoing movements (feedback control), but also for long-term
maintenance of internal body representation, on which anticipatory move-
ments can be programmed (feedforward control). Thus, somatosensory
impairments may underlie disturbances in both feedback-mediated and
feedforward-mediated motor processes. Cognitive dysfunctions, such as dis-
turbed visuospatial perception or apraxia, can also hinder performance of a
motor task. Other psychological factors associated with confidence, such as

fear of falling, may also have a negative impact on motor performance.
5.4 The Role of Spasticity in the Control of Posture and Gait

Postural control, i.e., maintaining posture under different circumstances,
is achieved by different strategies. It is influenced by motor, sensory, and
cognitive processes, which can be disturbed after stroke. Posture must be
controlled in both static and dynamic situations. While sitting or standing
still, adequate trunk control is demanded when support or assistance is
absent. Adequate trunk control is required to perform activities of daily liv-
ing. Numerous studies have shown that trunk control, or sitting balance, at
an early stage after stroke, can predict outcomes for activities of daily living
at a later stage (e.g., Hsieh et al., 2002). Decreased trunk control can lead to
problems with positioning in a chair or in bed. Paresis, sensation loss, dis-
turbed body orientation in space, and/or visuospatial neglect are primarily
responsible.
During voluntary movement, the postural balance is continuously adapt-
ing to perturbations. Knowledge of these perturbations is integrated into
motor programmes and used in anticipatory motor planning (feed-forward).
These responses are refined or learned throughout life and eventually oper-
ate automatically. Postural readjustment on unexpected perturbations is
based on stereotyped response patterns. Some of these are innate, but others
have to be acquired by motor learning, dependent on feedback of visual,
vestibular, and somatosensory information (Kandel et al., 2000).
In healthy adults, routine walking is considered an automatic and rhyth-
mic motor act that does not require a high level of conscious effort or atten-
tion. There is evidence from many vertebrate species and humans that the
basic locomotor patterns are generated in the spinal cord. These networks,
called central pattern generators (CPGs), are considered to play a key role
in regulating both the pattern, magnitude, and timing of muscle activa-
tions that make up the gait cycle (Duysens et al., 1998; Kandel et al., 2000;
Kiehn et al., 2010). In addition, these networks utilise proprioceptive feed-
back related to limb posture, loading, and foot contact in order to refine and
tune the step cycle to prevailing conditions and preserve postural integrity.
Close interaction with the reflex networks and supraspinal descending con-
trol mechanisms (cortical and sub-cortical) further refine walking patterns
and assist in the initiation and cessation of stepping, obstacle avoidance, and
changes in direction and speed.
A large part of the stroke population regains walking capacity (Functional
Ambulation Categories ≥ 3). However, postural control often remains com-
promised, resulting in a higher incidence of falls and a great impact on
independence in activities of daily living and gait (Kamphuis et al., 2013).

Unsupported standing requires more motor skill of the hemiparetic patient.
Weight-bearing asymmetry, in favor of the non-paretic leg, and increased
postural sway are characteristic in these patients (Geurts et al., 2005). Training
of weight-bearing symmetry used to be main focus in balance rehabilitation.
As pointed out earlier, evidence for the assumption that restoration of more
symmetrical weight distribution leads to improved postural stability after
stroke is lacking. In fact, weight-bearing asymmetry has recently been sug-
gested to be a compensatory strategy, for instance, to enhance the kinetic
contribution of the non-paretic leg to balance in quiet standing (Kamphuis
et al., 2013), rather than being the cause of postural instability. Another the-
ory suggests that weight-bearing asymmetry compensates for the contra
lesional tilt of the postural and visual vertical by adjustment of body posture
via increased loading of the ipsilesional side (Barra et al., 2009).
The decreased ability to stabilise the distal segments of the paretic lower
limb is the main contributing factor to the postural instability in stance.
Although the role of spasticity in maintaining standing posture might not
be principal, spasticity can threaten stability biomechanically, as a result of
dysfunctional joint posture due to the muscular imbalance, particularly at
the level of the affected ankle and foot.
The walking pattern after stroke shows typical abnormalities, both clini-
cally and electromyographically, which is directly reflected in a decrease in
walking velocity. Clinically, hemiplegic gait is typically characterised by the
affected leg in extension, sometimes with circumduction in swing phase,
and equinovarus deformity of the foot. Muscle activation patterns in the leg
during gait, measured with surface electromyography, show large differ-
ences in timing compared with healthy persons, but appear not to change
significantly in time after stroke (Den Otter et al., 2006; Buurke et al., 2008).
Although large inter-individual differences are found, some common char-
acteristics can be observed in the timing of muscle activity associated with
hemiparetic gait. Increased muscle activity is observed in several muscle
groups, but is not necessarily problematic. Conversely, increased co-activation
might be a valuable compensation strategy to enhance stability of the
affected, but also of the unaffected, limb. This theory is illustrated by two
studies, in which increased co-activation was found in the upper and lower
leg muscles during stance phase (Den Otter et al., 2007; Buurke et al., 2008).
Den Otter et al. (2007) found increased co-activation of biceps femoris and
rectus femoris in the affected leg during single support phase and the first
double support phase. In the lower leg, longer total durations of gastroc-
nemius activity were found during the first double support phase. In the
tibialis anterior, longer durations of activity were observed during swing
phase, whereas smaller total durations of activity were found during single
support. Remarkably, similar patterns were found for the non-affected leg,
except for the mean total duration of tibialis anterior activity during the first
double stance phase of the paretic leg (Figure 5.2).
Biceps femoris Rectus femoris
* *
Proportion of time active

* *
1 1
0 0
DS1 SS DS2 SW DS1 SS DS2 SW
Tibialis anterior Gastroenemius medialis

Control
*
Unaffected log
1 * * 1 Affected log
*
0 0
DS1 SS DS2 SW DS1 SS DS2 SW
FIGURE 5.2
Mean (+SD) duration of muscle activity of Biceps femoris (top-left panel), Rectus femoris (top-
right panel), Tibialis anterior (bottom-left panel), and Gastrocnemius medialis (bottom-right
panel), for each of the four subphases of the gait cycle (DS1, first double support phase; SS, sin-
gle support phase; DS2, second double support phase; SW, swing phase). (With permission
from Den Otter AR, Geurts AC, Mulder T, Duysens J. Abnormalities in the temporal patterning
of lower extremity muscle activity in hemiparetic gait. Gait Posture. 2007 Mar;25[3]:342–52.)
Compensation strategies for decreased stability in the trunk and affected

upper leg were also suggested in the study of Buurke et al. (2008), in which
delayed “off”-times in erector spinae, gluteal muscles, rectus femoris, vas-
tus lateralis, and semitendinosus were found on the affected side. In this
study, the unaffected leg showed abnormalities as well, of which the extra
burst in semitendinosus during stance was most prominent (Figure 5.3). This
was explained as compensation strategy for the diminished push-off of the
affected leg, causing extension of the unaffected hip, thereby facilitating the
swing of the affected leg. Compensation strategies for decreased stability in
the trunk were also suggested, as delayed “off”-times in erector spinae and
gluteal muscles were found on the affected side.
Both studies illustrate that increased muscle activity does not necessarily indi-
cate “problematic spasticity”. Only when muscle activity timing errors interfere
with one of the prerequisites of gait (in particular stability in stance phase, foot
clearance in swing phase, and/or prepositioning of the foot for initial contact)
(Gage, 1993), risk of falling increases and treatment must be considered.
Semitendinosus
(unaffected side)
Week 3
50
0
50 Week 6
0
Week 9
50
0
Week 12
50
0
Week 24
50
0
0 100
% of gait cycle
FIGURE 5.3
The extra and consistent burst of the semitendinosus muscle of the unaffected leg during
stance, measured at 3, 6, 9, 12 and 24 weeks post-stroke. Along the y-axis the amplitude of the
normalised smooth rectified EMG (SRE) in microvolts is presented. The x-axis shows the nor-
malised time of the stride. The horizontal black bars represent the windows from median on
to median off times. The smaller gray bars indicate the 25 and 75 percentiles of the median on
and off times. (From Buurke et al., 2008.)
5.4.1 Muscle Overactivity during the Stance Phase

Stability is the main prerequisite of gait during the stance phase. Decreased
stability in stance usually leads to reduction of step length and reduced
walking velocity. A frequently observed clinical characteristic is equin-
ovarus of the ankle and foot, a functional deformity leading to inadequate
ankle control. In the sagittal plane, excessive plantar flexion is a result of
paresis of dorsal flexors in combination with involuntary muscle activity
of the plantar flexors. During stance phase, soleus and/or gastrocnemius
(a)
(b)
FIGURE 5.4
Stroke patient with clonus of gastrocnemius (a) and soleus (b) in stance phase of the left leg.
overactivity can lead to persistent ankle plantar flexion and to disabling

anterior-posterior instability (Figure 5.4). The ankle rocker is decreased
and the torque to reach the forefoot rocker is increased, usually leading to
a higher knee extension torque (the so-called “ankle plantar flexion knee
extension couple”).
In the coronal plane, muscular imbalance between evertors and inver-
tors is often seen. When activity of the lateral foot elevators, i.e., the long
toe extensors and peroneus tertius, is decreased during swing phase,
excessive varus of the hindfoot will occur (Perry and Burnfield, 2010). In
mild cases, a slight (lateral) foot clearance deficit occurs during swing and
initial contact is made at the lateral side of the foot, but a fast return to
plantigrade support is seen during the loading response. In these cases,

the anterior tibialis muscle is activated based on selective control or as
part of a flexor synergy. Extensor muscle synergy takes over as soon as
weight is loaded onto the affected foot, leading to tibialis anterior relax-
ation. In more severe cases, varus may persist throughout the stance phase
as a result of prolonged anterior tibialis activity, which is often accom-
panied by (excessive) posterior tibialis muscle activity. When the dys-
functional equinovarus posture persists during the stance phase, the
supporting surface of the foot will decrease, by increased loading of the
forefoot and/or lateral foot, thereby decreasing stability in stance. When
more proximal control (knee extension, hip extension) is reduced as well,
stance stability, step length, and walking velocity are compromised even
more. As a result, these patients experience an increased risk of falling
and are frequently unable to walk either unassisted or without orthotic
devices (Weerdensteyn et al., 2008).
Other types of muscle overactivity that might emerge during stance phase
include extensor hallucis longus muscle overactivity, leading to hyper
extension of the hallux (“striatal toe”), which may interfere with comfort of
footwear. Inappropriate activity of intrinsic foot muscles and long toe flexors
may result in painful forefoot and toe flexion and difficulty with the forefoot
rocker.
5.4.2 Muscle Overactivity during the Swing Phase

In the swing phase, equinovarus of the ankle interferes with foot clearance
and with appropriate prepositioning of the foot for initial contact and load-
ing (Renzenbrink et al., 2012). In the sagittal plane, paresis of ankle dorsiflex-
ors is the most prominent cause. It can be aggravated by pathological activity
of the plantar flexor muscles (Figure 5.5). In the coronal plane, paresis of the
lateral foot elevators and overactivity of the invertors constitute the main
cause of the varus deformity.
Adequate foot clearance can also be at risk due to “stiff knee gait,” the phe-
nomenon of reduced knee flexion in early swing. Normal peak knee flexion
in this phase is 60–65 degrees and is induced by ankle plantar flexion force
during push-off in pre-swing, in combination with hip flexion. Knee exten-
sor muscles are normally relaxed in early swing, although rectus femoris has
a short period of action during stance to swing transition (Nene et al., 2004).
An exact definition of stiff knee gait for stroke patients is not available. For
children with cerebral palsy a cut-off value below 45 degrees of peak knee
flexion or a delayed knee peak flexion is generally used (Sutherland and
Davids, 1993). Whether overactivity of rectus femoris or pathological activity
FIGURE 5.5
Stroke patient with premature soleus activity contributing to disturbed prepositioning of the
left foot in terminal swing.
of vastus muscles is the underlying cause should be assessed with surface

electromyography (Figure 5.6). In almost all cases decreased plantar flexion
power is an important contributing factor.
Sometimes the extensor hallucis longus shows overactivity during the
swing phase as well. This can be a part of the dystonic “striatal toe” phenom-
enon. However, when the overactivity is restricted to the swing phase and
shows a phasic pattern, it is much more likely a compensation for reduced
tibialis anterior muscle strength.
FIGURE 5.6
Stroke patient with stiff knee gait. Rectus femoris muscle (yellow) is (over)active during initial/
mid-swing phase.
5.5 The Role of Spasticity in Arm and Hand Function

After stroke, upper extremity weakness is the most common impairment,
occurring in about 80% of patients (Langhorne et al., 2009). Only 5 to 20%
fully recover (Nakayama et al., 1994; Kwakkel and Kollen, 2013). It was found
that the prevalence of spasticity in the upper limb one year after stroke, in
a group of patients with initially impaired upper limb function, was 46%
(Opheim et al., 2014).The severity of spasticity, measured with the Modified
Ashworth Scale, increased during the first year. Presence of spasticity after
1 year was associated with poorer sensorimotor function, more pain, reduced
range of motion, and reduced sensibility.
In the upper limb spasticity rarely has functional benefit. To describe the
role of spasticity and the degree of additional disability due to spasticity,
post-stroke arm-hand function can be subdivided into three groups, based
on the Utrecht Arm/Hand Test (UAT), an ordinal measurement scale. The
UAT is a bedside 8-point scale for the evaluation of upper extremity impair-
ment after stroke (Kruitwagen-van Reenen et al., 2009), based on the recov-
ery stages according to Twitchell (1951) (Figure 5.7):
1. UAT 0-1: severely affected, no arm-hand function.
2. UAT 2-3: moderately affected, some arm-hand function.
3. UAT 4-7: mildly affected, useful arm-hand function.
Score 0: A-functional arm.

Observation: Shoulder movement only exists
through movement of the torso; retraction/elevation
of the shoulder is not possible.
Score 1: Flexion-synergy of the arm.

Observation: In an attempt to wilful action the arm
always moves in flexion pattern of elbow, wrist and
fingers.
Score 2: First distal selectivity.

Observation: The flexion pattern occurs predominantly,
however when extending the elbow palmair flexion of
the wrist is possible.
Score 3: Dorsal flexion wrist and fist.

Observation: When extending the elbow palmair
flexion and dorsal flexion of the wrist is possible. The
patient can open and close the fist.
Score 4: ‘Carrying a suitcase’.

Observation: MCP2 to 5 extension; IP flexion is
possible. The patient can grasp and let go of a suitcase
handle; can abduct and adduct the fingers. Cylinder
grasp and tweezers grasp are not possible.
Score 5: ‘Cylinder grasp’.

Observation: The patient can grasp a mug and release
willfully.
Score 6: ‘Tweezers grasp’.

Observation: The patient can fixate a pen in tweezers
grasp and release the pen.
Score 7: Clumsy hand.

Observation: The patient can perform all tasks, but
slower and clumsier.
FIGURE 5.7
The Utrecht Arm/Hand Test . (With permission from Kruitwagen-van Reenen ET, Post MW,
Mulder-Bouwens K, Visser-Meily JM. A simple bedside test for upper extremity impairment
after stroke: validation of the Utrecht Arm/Hand Test. Disabil Rehabil. 2009;31[16]:1338–43.)
5.5.1 Spasticity in Patients with a Severely

Affected Upper Limb (UAT 0–1)
A recent study, exploring the relationship between MRI outcomes and
upper limb spasticity after stroke (defined as Modified Ashworth score of
1 or higher), suggests that a higher lesion volume was associated with more
severe spasticity (Cheung et al., 2016). A longitudinal study explored the
time course of development of both spasticity and contractures at the wrist
in 30 stroke patients without arm function within 6 weeks of a first stroke
(Malhotra et al., 2011). Spasticity was measured by quantifying the muscle
activity during passively imposed stretch at two velocities. The authors
found that 28 patients (92%) showed signs of spasticity throughout the study
period of 36 weeks. Participants who recovered arm function (n = 5) showed
signs of spasticity at all assessment points, but did not develop contractures.
Patients who did not regain arm function (n = 25) had signs of spasticity and
changes associated with contracture formation at every time point tested.
Besides the development of contractures, spasticity in arm and hand can
have other adverse consequences, like pain, skin lesions, and interference
with daily care.
5.5.2 Spasticity in Patients with a Moderately

Affected Upper Limb (UAT 2–3)
During motor recovery, basic limb synergies emerge and, when recovery
proceeds, eventually diminish in time. After stroke, particularly strong cou-
pling was found between shoulder abduction and elbow flexion (Dewald
et al., 1995; Beer et al., 1999). This hinders the execution of functional move-
ment, since voluntary lifting the arm for reaching induces simultaneous
involuntary elbow flexion, thereby diminishing the reaching distance. When
elbow extensors are paretic and not strong enough to overcome this antago-
nist force (“reduced output paresis”), functional use of the arm is limited.
A kinematic study into the influence of gravity compensation on arm move-
ment after stroke showed that the active range of elbow extension increases
during 2-dimensional planar reaching movements with arm support when
compared with similar unsupported movements (Beer et al., 2004). Similar
results were found during 3-dimensional reaching tasks, reaching upward to
a target at shoulder height. Reaching distance appeared to be slightly larger
when gravity compensation was applied (Prange et al., 2011), but muscle
activity patterns did not change (Prange et al., 2009). On the other hand, syn-
ergy patterns seem to increase in strength in more complex tasks, an obser-
vation which is well-known by clinicians. This supports the hypothesis that
patients with moderate upper-limb paresis suffer from a lack of automaticity
of motor control, which is challenged in a dual-task situation (Houwink et
al., 2013). It remains a point of discussion whether this phenomenon of inap-
propriate co-contraction should be regarded as decreased reflex inhibition
(“spasticity”) or as resultant of abnormal efferent drive originating from

brainstem areas. An alternative hypothesis is that these different patterns of
joint coupling serve as a compensation strategy, allowing the performance of
functional tasks despite the presence of motor deficits in the paretic upper
limb (Levin et al., 2009). The number of degrees of freedom to be controlled is
reduced by fixating the joints in the arm, while using the trunk to move the
arm and hand to the target (Van Kordelaar et al., 2012).
5.5.3 Spasticity in Patients with a Mildly Affected Upper Limb (UAT 4–7)

In mildly affected stroke patients, daily activities that do not require near-
maximal effort do not elicit abnormal coupling between shoulder and elbow
movements (Prange et al., 2010). However, in this group of patients with
functional capacity of the arm and hand, smooth movement patterns may
still be impaired to a certain degree (Chae et al., 2002). Spasticity or “muscle
overactivity” might play a role in terms of increased co-contraction. Again, it
can be debated whether this activation pattern hinders or enables functional
use. Clinically, movement patterns are characterised by the ability to use
a joint outside a basic synergy pattern, i.e., the capacity to uncouple multi-
joint activation patterns, particularly active wrist extension, finger extension,
and finger spreading. However, this capacity may still be limited, due to the
amount of attention that is needed to perform the task. In the mildest cases
only subtle deficits in the ability to perform rapidly alternating movements
(dysdiadochokinesis) is seen.
5.6 Assessment of Spasticity in Stroke Patients

Assessment of spasticity post-stroke is mainly relevant when problematic
spasticity is present, i.e., when it leads to secondary complaints or com-
plications, or when it hinders functional ability. In that case, treatment
must be considered. In the literature, consensus on which measurement
tool should be used is lacking, partly due to the unsatisfactory validity
and reliability of the available instruments. In addition, practical limita-
tions play a role, as many clinicians prefer quick, easy-to-use, and cheap
methods (Burridge et al., 2005). Several characteristics of spasticity itself
make meaningful measurement difficult as well: spasticity tends to vary
during the day and behaves differently in dynamic versus static situations
(Dietz and Sinkjaer, 2007; Fleuren et al., 2008). This implies that the degree
of spasticity measured at rest, e.g., with a passive stretch test, does not nec-
essarily correlate with the degree of spasticity during active movement,
such as walking or reaching. In addition, a discrepancy between the clini-
cians’ and patients’ perception can exist (Voerman et al., 2009). In patients
with spinal cord injury, their perception of spasticity appeared to be influ-

enced by personal factors such as pain, coping strategy, and by environ-
mental factors (Voerman et al., 2011). It seems reasonable to assume that
in the early phase after stroke, the manifestation of spasticity will be an
unknown phenomenon for most patients, requiring education to put it in
the right perspective.
5.6.1 Assessment of Spasticity: Body Function and Structure

The available instruments for spasticity can be categorised into three groups:
clinical, biomechanical, and neurophysiological methods (Johnson, 2005).
They mainly address spasticity at the level of “Body function and structure”,
the first domain in the ICF classification (WHO, 2001). The biomechanical
and neurophysiological measurement methods are mostly used in labora-
tory settings, although neurophysiological methods are increasingly applied
in advanced clinical diagnostics as well, mostly during gait analysis.
Clinical methods include several instruments with different measurement
characteristics and assessing different constructs (see Table 5.1).
TABLE 5.1
Illustrations of Clinical Methods to Assess Spasticity
Group Measurement Tool Construct Performed By
A. Measurement of Muscle Tone
Ashworth Scale Resistance to passive Clinician
movement
Modified Ashworth Scale Resistance to passive Clinician
movement
Tardieu Scale Resistance to passive Clinician
movement; angle of catch
Visual Analogue Scale E.g., resistance to passive Clinician
movement Patient
E.g., perceived muscle tone
during certain activity
B. Measurement of Joint Posture/Range of Motion (ROM)

ROM by visual estimation ROM Clinician
ROM with goniometer ROM Clinician
Maximum interknee distance ROM Clinician
Ankle posture at rest Angle Clinician
C. Measurement of Other Clinical Phenomena

Spasm Frequency Scale Frequency of spasms Patient
Clonus Score Number of cycles during Clinician
clonus
Source: Derived with permission from Platz T, Eickhof C, Nuyens G, Vuadens P. Clinical scales
for the assessment of spasticity, associated phenomena, and function: a systematic
review of the literature. Disabil Rehabil. 2005;27(1–2):7–18.
The Ashworth Scale and its modified version are still common practice in
the clinical setting and are widely used in scientific research as well. They
are both ordinal scales that aim to score spasticity. However, to be a mea-
sure of spasticity, a scale can only be valid when the increase in resistance to
passive movement is caused by an increase in neural, stretch-related reflex
activity (Vattanasilp and Ada, 1999; Pandyan et al., 2003). This is probably
not the case, as the resistance to passive movement is a sum total of reflex
muscle activity and non-neural mechanical characteristics (Pandyan et al.,
1999; Fleuren et al., 2010). Therefore, adjusting the measured construct into
the resistance to passive movement of a limb, as perceived by the clini-
cian, would be more consistent with what is actually being rated (Table 5.2).
Although the methodological value of the adapted scale might be ques-
tioned, it completes the clinical examination without the misconception of
measuring true spasticity.
Biomechanical measurement methods assess muscle activation indirectly,
by calculation of the applied force (or moment) needed for passive rotation
of a joint over a certain range. This rotation can be performed manually, by
instrumented displacement, or by gravity, like in the pendulum test for the
knee (Vodovnik et al., 1984). Obviously, the complexity to discriminate the
contributions of neural and non-neural components to the resistance to pas-
sive movement is one of the main limitations of these methods. Although
new techniques with application of haptic robots and advanced modelling
techniques are in progress to discriminate more accurately between neural
and mechanical components of velocity-dependent stiffness (De Gooijer et
al., 2013, Sloot et al., 2015), these are not yet accessible for clinical use. Second,
agreed protocols for the tests and normative data of age-matched controls
are lacking in the current literature (Wood et al., 2005).
TABLE 5.2
Perceived Resistance to Passive Movement (PRPM) Test
Perceived Resistance to Passive Movement
0 No increased resistance
1 Slightly increased resistance (a catch) when the limb is moved in flexion or extension
2 More marked increase in resistance, but limb easily moved
3 Considerable increase in resistance, passive movement is difficult
4 Limb is rigid in flexion or extension
Technique: Patient in relaxed position (document position of the patient). Instruct the patient
not to assist or oppose the movement. First, test the passive range of motion of the joint by
slow flexion or extension. Subsequently, perceived resistance is assessed within the entire
range with a faster movement, covering the whole range within 1 second. The movement
can be repeated maximally 2 times (note the lowest score).
Source: With permission from Fleuren J, Voerman G, Nene A, Snoek G, Hermens H. Protocol
for spasticity assessment in patients with complex spasticity. Roessingh Rehabilitation
Centre and Roessingh Research and Development, Enschede, 2012 (not published).
With neurophysiological measurement methods, electrical activity of

involved muscles is measured. The use of the Hoffmann reflex, the electri-
cal equivalent of the mechanical tendon reflex, has been studied extensively
(Voerman et al., 2005). The same accounts for some other electrically elic-
ited reflexes. However, their clinical relevance is limited. The use of surface
electromyography (sEMG) for the recording of (reflex) muscle activity dur-
ing functional tasks or during passive movement can be a valuable addition,
when applied in a standardised way. The construct validity is potentially
good, as it comes close to the definition of spasticity. However, due to large
inter- and intra-subject variability, parameters related to intensity of mus-
cle activity cannot be used reliably. Interpretation of data is mainly depen-
dent on timing parameters, which can be compared to available datasets of
healthy subjects during a standardised task, such as walking. Timing errors
represent any inappropriate phasing of muscle activity. The activity of any
muscle may be prolonged or shortened, continuous or absent. Its onset and
cessation may be premature or delayed. Each of these phasing errors may
alter the pattern of sequential movements during gait (Perry and Burnsfield,
2010). In the case of “overactivity,” the inappropriate timing may be related to
altered reflex threshold values, but it can also be related to abnormal efferent
drive (De Niet et al., 2011).
5.6.2 Assessment of Spasticity: Activity and Participation

When the goal of treatment is to improve daily functioning, other methods
should be considered to assess (the functional consequences of) spasticity.
In general, the association between a decrease in spasticity and an improve-
ment of functioning is rather weak (Ada et al., 1998). However, an individual
patient may benefit from spasticity treatment when it allows less effort for
the performance of a specific activity. For example, a decrease in spasticity
of the elbow flexor muscles can increase the reaching distance and, conse-
quently, improve the utility of the hand. In general, detailed history-taking
of the patients’ perception and needs is an essential first step. Self-report
instruments, such as the Canadian Occupational Performance Measure, the
Goal Attainment Scale, or Visual Analogue Scaling (using a well-defined
construct), may be helpful in this process. When treatment aims to improve
arm or hand capacity in a stroke patient, the Action Research Arm Test (Lyle,
1981) or the Stroke Upper Limb Capacity Scale (Houwink et al., 2011) can be
chosen to evaluate the effects of treatment. For the improvement of gait, timed
walking tests, e.g., the 10-meter Walking Test (Collen et al., 1990), 6-minute
Walking Test (Eng et al., 2002), and Timed Up and Go Test (Podsiadlo et al.,
1991) are easily applicable. For more accurate diagnostics of spasticity during
gait, for example, when neuromuscular blocks or ankle-foot surgery is con-
sidered, instrumented gait analysis with kinematic recording and dynamic
EMG is required.
Example: Patient W
Mrs W is a 57-year-old patient who suffered a left-sided stroke 4 years
ago, which led to right-sided hemiplegia and mild cognitive impair-
ments. She can walk approximately 100 meters outside with a wheeled
walker, but starts toe-dragging when walking longer distances. Because
of hyperextension of the right knee during stance phase she underwent
phenol blocks of the right tibial nerve several times, with fairly good
results. However, during swing phase stiff knee gait is observed. Mrs W
hopes to be able to walk longer distances without tripping. Her physiat-
rist suggests instrumented gait analysis. The clinical question is whether
the reduced foot clearance is related to decreased knee flexion in swing
phase and – if so – to assess the cause. Is the stiff knee a result of a lack
of propulsion force from the calf muscles, is it caused by overactivity
of the rectus femoris muscle during swing, or both? For this analysis
measurement of joint angles, ground reaction force and dynamic elec-
tromyography of gastrocnemius and/or soleus muscle, rectus femoris,
and vastii is needed.
5.7 Management of Spasticity after Stroke

As emphasised in earlier paragraphs, spasticity treatment is indicated only
when its presence is considered problematic. Decision-making is based on
the patients’ needs and characteristics, such as the distribution of spastic-
ity, the perceived degree of discomfort, and the secondary risks of spastic-
ity. On the other hand, clinical decisions depend on the available treatment
options, their invasiveness and reversibility (Table 5.3).
It can be helpful to distinguish between focal, regional, multifocal, or
generalised spasticity. Focal spasticity is limited to one or a few muscles
TABLE 5.3
Overview of Treatment Methods in Terms
of Invasiveness and Reversibility
I Noninvasive methods
• Elimination of provocative factors
• Physical therapy
• Oral medication
II Invasive, reversible methods
• Nerve blocks
• Neuromuscular blocks
• Intrathecal medication
III Invasive, permanent methods
• Neurosurgical procedures
• Orthopedic procedures
acting at the same joint, e.g., elbow flexors. Regional spasticity includes a
group of muscles innervated by the same (e.g., the tibial) nerve. Generalised
spasticity is seen when spasticity is not limited to a muscle group of muscle
synergy.
5.7.1 Noninvasive Methods
Noninvasive treatment options with temporary effect are usually a first step
in spasticity treatment. A decrease in spasticity provides new information
about the actual impact of spasticity and its contribution to the clinical prob-
lem. First, spasticity-provoking factors need to be identified and eliminated.
Suddenly increasing spasticity can be a response to a certain internal or
external stimulus. A variety of factors can provoke this increase (Phadke et
al., 2013). Any physical stimulus is a possible provoking factor, such as pres-
sure sores, infection, constipation, or pain. Clinicians should routinely exam-
ine for spasticity-triggering factors, e.g., by evaluation of proper positioning,
by regular skin inspection, and adequate management of bladder and bowel
function. In addition, psychological factors may affect the degree of spastic-
ity. Emotional stress, anxiety, and being rushed to perform an activity are
described to increase self-reported spasticity (Phadke et al., 2013). Education
of the patient and their carers is highly relevant in this respect.
Physical therapy is not primarily aimed at spasticity reduction. In stroke
patients, physical therapy is commonly applied to facilitate active muscle
control and to maintain the joints’ range of motion and muscle length. There
are some techniques that can reduce spasticity, but only for a short time
period, such as application of heat, stretching of the muscles, and hippo-
therapy. Surface neuromuscular electrical stimulation is used, but spasticity
treatment is usually not the main goal. Although the intervention may have
a short-term inhibiting effect on spasticity, possibly via reciprocal inhibition
by stimulation of the (non-spastic) antagonist or by exhausting the stimu-
lated spastic muscle, a long-term effect on upper limb spasticity in stroke
patients without functional arm movement has not been shown (Malhotra
et al., 2013). Post-stroke, orthotic devices are often applied to the wrist and
hand. Although it is controversial as to whether orthotic treatment is effec-
tive in the reduction of muscular contracture (Tyson and Kent, 2011), it is
suggested that in combination with botulinum toxin treatment, prescription
of an orthotic device may aid in the preservation of muscle length.
Oral spasmolytic drugs are usually considered in more generalised spas-
ticity. Baclofen, a gamma-aminobutyric acid (GABA) agonist, is often used
as the first-choice drug in patients with spasticity. It reduces the motor out-
put of spastic muscles, as GABA is one of the main inhibiting neurotrans-
mitters in the central nervous system, leading to hyperpolarisation of the
post-synaptic membrane of the 1a afferent. The optimal dosage must be
individually evaluated. Sedation is a common side effect in stroke patients,
potentially leading to (increase in) attention and memory deficits, ataxia,
and confusion. Benzodiazepines enhance the inhibiting effect of GABA, but

obviously a sedative effect may be present. Tizanidine, an alpha-2-adrenerge
agonist, has an indirectly inhibiting effect on polysynaptic reflexes, probably
via facilitation of glycine, another important inhibitory neurotransmitter
in the central nervous system. Dantrolene sodium is a postsynaptic muscle
relaxant that lessens excitation-contraction coupling in muscle cells, prob-
ably by interfering with the calcium release from the sarcoplasmic reticu-
lum. An advantage of this peripherally acting drug is a lower risk of central
side effects. However, both dantrolene sodium and tizanidine have a poten-
tial for hepatotoxicity, so liver function examination should be performed at
regular intervals.
Despite the widespread use, the evidence for the efficacy of orally admin-
istered antispastic agents is scarse and weak (Montane et al., 2004). In placebo-
controlled trials with dantrolene, tizanidine, baclofen, or diazepam, the
experimental drug was significantly better than placebo in patients with
stroke, but the therapeutic effect was modest. Adverse effects were generally
more frequent in the active treatment groups than in the placebo groups,
up to 64% in a dantrolene group (Ketel and Kolb, 1984; Katrak et al., 1992).
Drowsiness, weakness, and fatigue were most often reported. Therefore,
generally speaking, these drugs should be applied cautiously for spastic-
ity treatment after stroke. Particularly when the aim is to improve function,
their effect is often disappointing. Nonetheless, specific indications such as
symptom reduction, especially during the night, or presence of otherwise-
intractable spasticity may justify their use.
5.7.2 Invasive, Reversible Methods

For the treatment of focal or regional spasticity, different types of neuromod-
ulation can be useful options. Neurolysis of well-accessible motor branches
of peripheral nerves impairs the conduction along that nerve. The most fre-
quently used agents for this procedure are phenol and alcohol. The effect
is not permanent and the duration is highly variable, on average about 6
months. In stroke patients, a nerve block of the tibial nerve, a mixed motor
and sensory nerve to the calf muscles, tibialis posterior, and toe flexors, with
phenol 5–7% solution is the most commonly applied. The proper indication
is the presence of hindering clonus of the ankle plantar flexors, interfering
with stance stability. Other well-accessible nerves are the musculocutane-
ous nerve (which innervates a.o. elbow flexors) and obturator nerve (for
disabling hip adductor spasticity). However, blocks of mixed nerves with
phenol, such as the tibial nerve, carry the risk of neuropathic pain in the
sensory region of the nerve. Since botulinum toxin has appeared on the mar-
ket and was licensed for spasticity treatment, the use of nerve blocks has
decreased. In particular the more difficult procedures have become less pop-
ular. Nevertheless, some clinicians claim greater clinical efficacy of phenol
for specific indications (Manca et al., 2010).
Nowadays, intramuscular injection of botulinum toxin is an estab-

lished, well-tolerated, but relatively expensive treatment for focal spasticity.
Botulinum toxin prevents the release of acetylcholine from the pre-synaptic
nerve terminals, thus blocking the peripheral cholinergic transmission at
the neuromuscular junction. This results in reduced muscle contraction. The
clinical effects are dose-dependent and temporary. Usually, the effects taper
off after 3 to 4 months. Botulinum toxin is injected in the muscle belly of
specifically selected muscles. As it diffuses within the muscles, the injec-
tions do not have to be placed precisely in the region of motor endplate (of
which the exact location is usually unknown), which makes the procedure
fairly easy. Nevertheless, ultrasound guided injections are recommended for
proper muscle targeting. Adequate dosages and concentrations for spasticity
treatment with intramuscular injections of botulinum toxin are extensively
described in different guidelines.
There is a substantial body of evidence for the effectiveness of botuli-
num toxin in the management of upper and lower limb spasticity in stroke
patients. However, its contribution to the improvement of upper limb func-
tion has not been clearly established (Shaw et al., 2011). In general, the focus
of botulinum toxin treatment in the upper limb is on improving posture
and passive function of the non-functional arm and hand, with the aim to
support hygiene and the independent performance of various activities of
daily life, such as grooming, dressing, etc. The effects of botulinum toxin
injections on active function of the upper limb are less strongly supported
by the literature. As for the lower limb, focal spasticity interfering with the
prerequisites of gait, as described in paragraphs 5.4.1 and 5.4.2, can effec-
tively be treated with botulinum toxin. Particularly the triceps surae, poste-
rior tibial, rectus femoris, extensor hallucis and toe flexor muscles are fairly
easily accessible with ultrasound guidance or electrical stimulation.
If spasticity causes multifocal problems, e.g., both in the affected upper and
lower limb, botulinum toxin can be helpful as well, but dose limitations may
reduce its applicability. Therefore, additional strategies must be considered.
Due to its reversibility, repeated treatment may be required over several
years. Botulinum toxin has shown sustained activity with repeated use.
However, a lack of response can occur, possibly due to inaccurate selection
of the correct muscle, inadequate injection technique, increasing non-neural
contribution to the muscle stiffness, or – rarely – the presence of neutral-
ising antibodies (Wissel et al., 2009). For some patients, repeated injections
may be undesirable. Therefore, an alternative approach is to use botulinum
toxin treatment as a diagnostic procedure prior to surgical techniques (see
next paragraph). The reversibility gives the opportunity to evaluate the effect
without permanent consequences.
Intrathecal baclofen (ITB) might be an attractive option in case of more
generalised spasticity. Unlike oral baclofen, the intrathecal route bypasses
the blood-brain barrier, thereby dramatically reducing the required dose and
minimising the occurrence of side effects. In the literature on ITB in stroke,
significant reduction of spastic hypertonia in upper and lower limbs has been
described (Meythaler et al., 2001; Ivanhoe et al., 2006) without affecting the
strength of the unaffected side. In addition, improvement of hemiplegic gait
was reported. Catheter tip placement and dose adjustments after ITB pump
implantation have a significant influence on clinical outcomes. ITB distribu-
tion can be influenced by the location of the catheter tip and by changing
the infusion mode. When only spasticity in the leg is aimed to treat, catheter
tip location in the lower thoracic region will suffice. It is subject of discus-
sion whether, in case spasticity in the upper limb must be reduced as well,
the catheter tip should be located more cranially in the high thoracic region
or at the cervical level (Heetla et al., 2014). In ambulatory stroke patients, a
test phase with an external pump, prior to definitive pump implantation, is
highly recommended, to make sure that walking ability is preserved during
treatment (Bleyenheuft et al., 2007).
5.7.3 Invasive, Permanent Methods

Nonsurgical management of spasticity provides temporary relief of symp-
toms and does not interfere with spontaneous recovery after stroke. Surgical
intervention should be avoided during this time. In the chronic phase of
stroke, roughly starting after 6 months when the clinical condition has sta-
bilised, surgical management can be valuable. In the nonfunctional upper
limb, problems with cosmetics and hygiene are addressed mostly. Persistent
stiffness in the arm or a clenched fist may be difficult and painful to han-
dle during washing and dressing. In addition, patients may have objections
against repeated botulinum toxin injections. In a functional hand, surgeons
tend to hold back due to the risk of loss of active function. In the lower limb,
functional goals are easier to pursue. When the aim is to improve gait, surgi-
cal intervention should be based on instrumented gait analysis.
Neurosurgical procedures are uncommon in stroke patients. Selective neu-
rotomy of the tibial nerve is described in a Belgian study (Bollens et al., 2013)
as an alternative treatment for overactivity of the calf muscles. In this study,
triceps surae, tibialis posterior, and flexor hallucis longus muscles were dener-
vated selectively and permanently, which resulted in a long-lasting effect. On
gait parameters, such as ankle kinematics during stance and swing phase,
tibial nerve neurotomy and botulinum toxin treatment showed similar effect.
Orthopedic or plastic surgery (tendon lengthening and/or transfer) is indi-
cated in the case of fixed muscle contracture or to adjust imbalanced muscle
activity. Treatment of spasticity is usually not the primary goal, although
reduction of spasticity may be a desired secondary effect, considered a result
of an altered threshold for stretch reflex activity due to the increased length.
In the spastic lower limb, several surgical techniques can be performed for
correction of deformities (Kamath et al., 2009). Some procedures do address the
negative consequences of spasticity on gait. In general, these options should be
preserved for patients with at least a fair prognosis with respect to regaining
walking ability. For example, a commonly performed procedure is the per-

cutaneous Achilles tendon lengthening, during which three small incisions
are made at the back of the ankle along the Achilles tendon, one laterally and
two medially. The tendon stretches as the fibres are cut and the ankle is dorsi-
flexed to the desired angle (Canale and Beaty, 2008). In the case of a structural
pes equinovarus, lengthening of spastic soleus and/or gastrocnemius can be
performed in combination with release of posterior tibial muscle to improve
ankle-foot stability during the stance phase as well as to provide proper prep-
ositioning of the foot for loading. Prior to surgery, the effect of weakening
of the muscles can be evaluated by performing a neuromuscular block. If a
dynamic pes varus deformity is present during swing phase, a split anterior
tibial tendon transfer can be performed, provided that the tibialis anterior
shows sufficient muscle strength. The lateral half of the anterior tibial tendon
is released from its insertion and transferred to the cuboid bone (Canale and
Beaty, 2008). If the tibialis anterior is too weak, an alternative may be to trans-
fer the tendon of an overactive posterior tibial muscle to the cuboid bone to
support a balanced dorsiflexion of the foot. An arthrodesis of the talonavicu-
lar joint may also support a balanced ankle dorsiflexion when the lateral foot
elevators (long toe extensors and peroneus tertius) are paretic. Extensor hal-
lucis longus transfer to the mid-dorsum of the foot can be performed to treat
a troubling striatal toe, but may also provide additional dorsiflexion force for
the ankle. Spasticity of the long toe flexor muscles often leads to clawing of
the toes and contributes to equinus deformity of the foot. Particularly after
Achilles tendon lengthening, as the foot is brought into a more plantigrade
position, shortening of the long toe flexors might be revealed. In that case,
concomitant correction of claw toes is advised, e.g. by tenotomy of the long toe
flexors. In the case of forefoot equinus, release of the short toe flexors (intrin-
sics) should be considered as well (Canale and Beaty, 2008).
In the thigh, tendon transfer of rectus femoris can be considered in a patient
with stiff knee gait. When dynamic EMG analysis reveals a rectus femoris
muscle that is abnormally active during swing phase, a diagnostic neuro-
muscular block of the rectus femoris can be performed, to assess whether
it leads to improvement on peak knee flexion during swing (Tenniglo et al.,
2014). For a medial transfer, the rectus femoris is separated from the vastii.
The rectus tendon is then dissected and transferred through the medial
intermuscular septum to the semimembranosus (Canale and Beaty, 2008).
In the upper extremity, spasticity reduction is observed after release of
elbow flexors (brachioradialis, biceps brachii, and/or brachialis muscles), pro-
nator teres, and wrist flexors (flexor carpi ulnaris and radialis, and the pal-
maris longus). Muscles that contribute to finger flexion deformities are flexor
digitorum superficialis and profundus, which can be fractionally lengthened
by incising the tendon fibres obliquely at the musculotendinous junction.
However, superficialis to profundus transfer will provide more lengthening
and opening of the hand. After release of the extrinsic finger flexors, persist-
ing intrinsic muscle spasticity may be revealed, leading to an intrinsic-plus
deformity. In that case, surgical tendon release of the intrinsic muscles must
be performed as well. Tendon transfers, for example, transfer of the flexor
carpi ulnaris tendon to the extensor carpi radialis brevis tendon to provide
for stronger wrist extension, are uncommon in stroke patients. Generally,
patients lack active wrist extension, and – if present – wrist flexor lengthen-
ing is believed to provide sufficient wrist extension (Tafti et al., 2008).
5.7.4 Management Strategy for Stroke Patients with Spasticity

When an indication for treatment of problematic spasticity is assessed, a
stepwise approach is recommended. Potential provoking factors of spastic-
ity must always be identified and eliminated if present. In the early phase
after stroke reversible treatment options are preferred. Depending on the
distribution of spasticity, focal spasmolysis is often the first choice, because
of its effectiveness and reversibility. Focal injections have the drawback of
being invasive, but debilitating side effects, as observed frequently after
oral medication, are much less common. Oral medication can be prescribed
when more generalised spasticity is present, but its use is mostly restricted
to symptom reduction, especially during the night.
More permanent treatment options become relevant in the chronic phase,
roughly from 6 months post-stroke onwards, as an alternative to repeated
focal injections. Selective neurotomy of the tibial nerve may be an effective
substitute, but it is rarely performed to treat spastic pes equinovarus up till
now. Otherwise, tendon lengthening and release procedures, possibly in
combination with tendon transfer to enhance active function, are available
treatment options for both upper and lower limb spasticity. However, much
more adequately conducted research is necessary to build on sufficient evi-
dence and to support treatment algorithms.
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6
and Contractures in Spinal Cord Injury
Martin Schubert and Volker Dietz
CONTENTS
6.1 Introduction................................................................................................. 136
6.1.1 Epidemiology and Specific Aspects of Spasticity in SCI.......... 137
6.1.2 Spinal Shock, Recovery of Spinal Excitability,
and Development of Spastic Movement Disorder..................... 139
6.1.3 Pattern of Spastic Movement Disorder Depends
on Patho-Anatomy.......................................................................... 141
6.2 Pathophysiology-Based Treatment of Spasticity.................................... 143
6.2.1 Clinical Signs of Spasticity............................................................ 144
6.2.2 Spastic Movement Disorder.......................................................... 144
6.2.3 Therapeutic Consequences............................................................ 145
6.3 Patient Selection and Therapeutic Approach......................................... 147
6.3.1 Indication for Treatment of Spasticity in SCI.............................. 147
6.3.2 Clinical Assessment of Spasticity in SCI..................................... 148
6.3.3 Clinical Presentation and Anatomical Distribution
of Spasticity...................................................................................... 149
6.3.4 Physiological Effects of Training.................................................. 150
6.3.5 The Mainstay of Spasticity Treatment in SCI Is Physical
Therapy............................................................................................. 150
6.3.6 Oral Systemic Anti-Spastic Pharmacotherapy........................... 152
6.3.7 Intrathecal Anti-Spastic Pharmacotherapy................................. 155
6.3.8 Focal Anti-Spastic Pharmacotherapy: Chemodenervation....... 157
6.3.9 Surgical Correction of Contractures............................................ 160
6.3.10 Focal Anti-Spastic Surgical Treatment: Selective Dorsal
Rhizotomy........................................................................................ 161
6.4 The Complex Spastic SCI Patient: Selection of Therapeutic
Approach...................................................................................................... 162
6.4.1 Case 1: Combination Therapies: Oral Systemic and Focal........ 163
6.4.2 Case 2: Combination Therapies: Intrathecal Systemic
and Focal.......................................................................................... 164
References.............................................................................................................. 164
135
6.1 Introduction
As in other pathologies involving lesions of the central motor system, spastic-
ity in SCI can be defined as disordered sensorimotor control, resulting from
an upper motor neuron lesion and presenting as intermittent or sustained
involuntary activation of muscles by sensory input. Activation is indepen-
dent of the type and location of triggering sensory input. It can be touch, pain,
temperature, or proprioceptive stimuli, or it can be mediated by vegetative
stimuli. As in other types of central nervous system (CNS) lesion, spasticity
per se is a pathological condition that is part of a motor syndrome related to
loss of voluntary motor control and related changes in sensory-motor inte-
gration and adaptation within the motor system. These changes and adapta-
tions may include adverse as much as beneficial effects for patients’ level of
function and subjective well-being. For instance, it can contribute to muscle
strength and thus function where voluntary strength is lost, thereby sup-
porting stance or gait in incomplete SCI. Hence, spasticity in SCI as much as
in other CNS pathologies may be seen as a compensatory state of a deficit of
sensory-motor control that is usually associated with a lower level of func-
tional CNS organisation. This potentially leads to more disability if negative
effects prevail and balance between voluntary and involuntary activation is
lost. Only in this case is treatment needed. In any case, treatment should be
focused only on these negative effects and should be done with a specific
aim. Such aims can be function, pain control, reducing of care burden, or
prevention of complication such as impending contractures. It must always
involve an interdisciplinary consideration of the patient’s special situation of
impairment. Thus, treatment will usually require that medical staff, patient,
and his/her relatives discuss the treatment aim and agree upon a treatment
concept. This chapter will first deal with the manifestation of spasticity
in SCI and how it can be beneficial or detrimental to function. It will then
describe particular features of SCI spasticity based on spinal syndromes and
their pathophysiology. While there is good understanding of changing excit-
ability of spinal motoneurons below the level of lesion as derived from ani-
mal models [1–3], these are not deemed representative of the spastic motor
disorder in human SCI and thus have little meaning in the context of clini-
cal practice. Although there is some experimental work in the human that
supports the notion of changing excitability of infra-lesional spinal moto-
neurons as a basis for the generation of muscle spasms [4], models derived
from this work rely on several assumptions of analogy with animal models
and have no significance for practical treatment of spasticity in human SCI.
This is mainly due to the fact that the anatomy of the spinal lesion is more
relevant for clinical presentation than modeled excitability changes at the
cellular level. The anatomy of a human spinal lesion results in phenotypes
with implications for functional deficits that have more effect on spasticity
treatment than underlying pathophysiology of presumed neural interaction
Clinical Management of Spasticity and Contractures in Spinal Cord Injury 137
at the spinal segmental level. Therefore, the effects of spasticity in SCI will
be discussed in terms of phenotypes and their implications for function and
need for treatment.
6.1.1 Epidemiology and Specific Aspects of Spasticity in SCI

Spasticity is seen as a major health problem by many patients with SCI [5,6].
Although spasticity can be seen as a compensatory adaptation to the loss of
voluntary motor control, it may also severely limit patients’ mobility when
overshooting and thus can negatively affect independence in activities of
daily living (ADL) and work. Prevalence of spasticity in SCI is reportedly as
frequent as 40–74%, depending on the type of survey and whether external
or self-reported outcomes were drawn upon [1,5–9]. In most surveys, spas-
ticity is rated as the most disabling complication, followed by pain, sexual,
bowel, and bladder dysfunction and pressure ulcers. There is an interrelation
of spasticity, pain, reduced mobility, contractures, and pressure sores [5,6,10].
Many patients report pain as a consequence of spasticity. In fact, spastic and
neuropathic pain can be inseparable in the clinical condition. Independent
of geographic region, the prevalence of secondary health conditions such
as spasticity is known to vary across demographic and SCI characteristics.
Spasticity was more often reported in SCI with incomplete lesions or tet-
raplegia [5,7,8,10].
SCI as a unique form of CNS damage comes with certain features that are
characteristic to its patho-anatomy. As the lesion is a focused one, severing
the infra-lesional part of the cord from the supralesional CNS, characteris-
tics of SCI will influence the manifestation and the distribution of spasticity.
Neural mechanisms are discussed to be the primary contributors to spas-
ticity following SCI by some authors [9], whereas others emphasise the rel-
evance of mechanisms underlying muscle hypertonia that are unrelated to
increased stretch reflex activity. Intrinsic changes in the muscle tissue itself,
e.g. loss of sarcomeres, histochemical changes, and composition of muscle
fibres, ultrastructure and proportion of extracellular matrix, have been sug-
gested to have a significant impact on spastic hypertonia [11–16]. From a
clinical viewpoint, the original definition by Lance [17] is not sufficient to
understand resulting functional impairment. It is also not helpful in delin-
eating indication for treatment as it does not explain the syndrome of spastic
motor disorder. Clinical signs of spasticity are not related to spastic move-
ment disorder. The functional impairment that follows a central motor lesion
will be influenced and modified by spasticity. However, it is not a direct con-
sequence of the clinical syndrome that was clinically defined by Lance as ‘a
velocity-dependent increase in tonic stretch reflex with exaggerated tendon
jerks, clonus, and spasms, resulting from hyper-excitability of the stretch
reflex’ [2,18]. This is due to several aspects. On the one hand, the definition by
Lance does not capture the signs and symptoms of what is usually referred
to as spastic motor disorder. It does not include the impending secondary
changes within muscle and connective tissue leading to contractures as an

unwanted final point of missed treatment.
On the other hand, it overemphasises the significance of the hyper-
excitability of the stretch reflex while negating the functional significance of
loss of polysynaptic reflex activity [19]. Spasticity in SCI evolves with time
after lesion. It varies with location of lesion level and other SCI characteristics
such as central cord damage and completeness of the lesion. Clinical aspects
of spasticity are diverse, including muscle hypertonia, flexor or adductor
spasms, clonus, and dyssynergic patterns of contraction. Muscle hypertonia,
an abnormal increase in muscle stiffness, can be regarded as a defining fea-
ture of spasticity. Other than exaggerated reflexes, it has both diagnostic and
therapeutic significance [16]. This heterogeneity in clinical presentation can-
not be explained by exaggeration of the stretch reflex alone. There is abun-
dance of clinical and experimental neurophysiological work extending on the
suspected mechanisms of spasticity in SCI and the reader is referred to the
respective chapter. However, it should be mentioned that there is controversy
about the putative role of hyper-excitability of spinal motoneurons as a major
cause in the emergence of spinal spasticity. This was put forward based on
the observation of low-frequency invariant spontaneous self-sustained firing
in motor units from 5 out of 15 SCI patients [4]. It was explained as a con-
sequence of altered intrinsic voltage-dependent persistent inward currents
(PICs; e.g., persistent inward calcium currents) [1]. The hypothesis was pri-
marily derived from animal work and then indirectly tested in human SCI
[4]. Under normal circumstances, PICs are assumed to have physiological
roles at the MN level in amplifying synaptic inputs to provide a sustained
excitatory drive that allows motoneurons to fire repetitively following a brief
synaptic excitation. In SCI patients in whom involuntary muscle spasms
could be elicited by various types of afferent stimulation, a self-sustained fir-
ing of motoneurons was observed which would last for seconds at unusually
low and regular discharge frequency. Based on several assumptions derived
from animal experiments it was suggested, that this slow spontaneous firing
likely occurs without appreciable synaptic noise and is driven to a substantial
degree by PICs intrinsic to the motoneuron [4]. This would not necessarily
be in contradiction with observations of reduced motor unit action poten-
tials [20] and reduced overall activity of the motor units during functional
movement [12,21–23] as well as a reduction of functional long-latency reflexes
on the one, and enhanced short latency reflex excitability and spontaneous
muscle spasms on the other side [19,24]. However, self-sustained firing of
motoneurons was only observed and described following induced muscle
spasms and not during functional movement. It is unclear whether it could
commonly be observed in chronic spinal injury or if it is only present during
induced spasms. Long-term intramuscular single-motor unit recordings in
the human, which could substantiate the finding, are lacking. It remains to
be determined if there is a relation with functional impairment or if there is a
significant role of the phenomenon in the development of contractures.
There is more human experimental data supporting the idea that spasticity
involves synaptic mechanisms such as recurrent inhibition [25], reduction in
Ia-reciprocal inhibition [26,27], and reciprocal inhibition of flexor reflex affer-
ents [28]. In summary, changes of motoneuron and interneuron plasticity
are assumed to play a significant role in spinal spasticity, which early after
an SCI are thought related to postsynaptic mechanisms such as receptor up-
regulation, and later during the recovery phase would be associated primar-
ily with pre-synaptic mechanisms [1,9,29]. However, these changes are not
observed immediately after spinal trauma. They evolve with time, suggest-
ing gradual changes of neural adaptation following SCI.
6.1.2 Spinal Shock, Recovery of Spinal Excitability,

and Development of Spastic Movement Disorder
When describing the natural course of disease following SCI it must be dis-
tinguished between pathologies with acute onset and those that result in
slow alteration of the cord, e.g., due to tumor or other etiology with increas-
ing compression. Following an acute onset there will be a phenomenon of
a sudden loss of reflexes and muscle tone, commonly referred to as ‘spinal
shock’. The term was introduced by Hall in 1841, who, in describing the sud-
den loss and recovery of reflexes, for the first time linked it with the term
‘reflex arc’ [30].
Our present idea is that a flaccid motor paresis is observed immediately
after acute onset of a complete SCI when there are no motor responses to
external stimuli below the level of lesion. During the subsequent days and
weeks, motor reactions to external stimuli and reflex activity gradually reap-
pear in a more or less systematic manner [24]. The phenomenon of spinal
shock remains an issue of debate and controversy. Due to involvement of the
autonomous system in acute SCI, there is some overlap with cardiovascu-
lar symptoms, i.e., arterial hypotension and cardiac compensatory response.
The question of duration of spinal shock can be seen as a matter of definition
of the delimiting type of motor reaction or reflex [31]. Depending on what
is chosen as the distinguishing motor criterion, cessation of spinal shock
may be assumed with the appearance of a ‘delayed plantar response’ (DPR),
which occurs within hours after SCI and persists for hours to a few days
[32,33]. If deep tendon reflexes (DTR) are chosen as the criterion, then dura-
tion of spinal shock is longer and will comprise several weeks. DTR return
in the majority of patients but the Babinski sign may or may not be present,
which seems to be related to the presence of spasticity [34]. Appearance of
interlimb reflexes indicates late changes reflecting increased polysegmen-
tal spinal reflex excitability 6–12 months after SCI [35]. Competitive synapse
growth originating from preserved long descending motor input [36] and
segmental reflex inputs [29] are postulated as underlying the individual out-
come and clinical presentation of recovery of voluntary motor control and
spastic motor disorder [35].
Complete and incomplete SCI were claimed to be distinguishable by the

extent and duration of spinal shock in several studies lasting only minutes
to hours in ‘slight’ injuries [32,37]. Furthermore, response amplitude to ten-
don tap and reflex spread to adjacent segments are sensitive indicators of
preserved supraspinal control over lower limb musculature in subjects with
acute SCI and may thus be helpful for prediction of recovery [32]. Conversely,
this would be well in line with the clinical observation of long-lasting flaccid-
ity as an indicator of complete SCI. Within this spectrum of motor responses
and gradually increasing motor activity following spinal shock it is difficult
to distinguish spasticity as a single and clearly defined motor phenomenon.
Spreading reflex activity and clonus is regarded a clinical sign of evolving
spasticity. Muscle hypertonia and polysegmental reflexes may appear as
involuntary contractions and spasms, thus adding to the picture of spastic
motor syndrome of SCI [35]. In the clinical view, the transition from spinal
shock to spasticity is a continuum of an initially gradual increase in motor
excitability [24] with characteristic changes in muscle stiffness, spasms, and
subsequent reduction of short- and increase in long-latency reflex excitabil-
ity. In contrast to tetraplegic patients, paraplegia resulted in M-wave and
flexor reflex amplitudes that were found to decrease, indicating that spas-
tic motor disorder eventually is not associated with increased excitability of
motoneurons and premotoneuronal network [12,24].
Neurophysiological methods have deepened our understanding of under-
lying excitability changes in spinal circuits and peripheral nerves during
this transition [20,24,29,38,39]. During spinal shock, the loss of tendon tap
reflexes and flaccid muscle tone is associated with low excitability of spi-
nal motor neurons, as tested by neurographic methods (F-waves) and with
a loss of flexor reflexes, whereas only H-reflexes can be elicited because the
unexcitable intrafusal gamma fibre system is bypassed by direct electrical
stimulation of 1a afferents. Reduced excitability of peripheral mixed nerves
was shown to be based on high threshold stimulus–response relationships
that were apparent from the early phase of spinal shock. This coincided
with depolarisation-like features reaching a peak after 12 and 17 days for
the median and common peroneal nerves, respectively [20,38,40]. Between
Days 68 and 215 after SCI at the end of rehabilitation Boland and cowork-
ers (2011) found that excitability for upper and lower limbs had returned
towards normative values, but not for all parameters. These reductions of
excitability of the peripheral motor axon were described to be paralleled
by the development of spasticity despite reduced excitability of the motor
axon. This supports the notion that spasticity occurs without overactivity
of the motoneurons and their axons. During the transition to spasticity, the
reappearance of tendon tap reflexes and muscle tone can parallel the occur-
rence of spasms and is associated with the recovery of excitability of spi-
nal motoneurons as indicated by increasing F-wave persistence and flexor
reflex excitability [24] but there is no excess activity of the motor system
causing spasticity. Little change in spinal excitability can be shown after
this transition phase as the decrease in compound muscle action potentials

(CMAP/M-wave) and reduced flexor reflex amplitude suggest a secondary
degeneration of spinal circuits and motoneurons subsequent to severe spinal
trauma [20,24,41]. Furthermore, flexor reflex excitability depends on the level
of lesion, indicating that spinal interneurons and pre-motoneuronal circuits
may depend on the extent of infra-lesional intact spinal network [24,32]. As
an overall conclusion of these neurophysiological observations during tran-
sition from spinal shock to spasticity, it must be emphasised that spasticity in
SCI develops without a net increase in spinal excitability.
6.1.3 Pattern of Spastic Movement Disorder Depends on Patho-Anatomy

Traumatic SCI usually results in a diffuse damage zone of the spinal cord
extending for 2–3 segments, clinically reflected by a ‘zone of partial preser-
vation’. In incomplete SCI, the distribution and extent of segmental damage
is of great relevance for recovery. Contusion injuries inherently represent
the combined damage of both segmental central and peripheral neural
structures [42]. Preserved function of neuronal circuits below the level of
the lesion is the target of rehabilitation training. Spasticity develops only
in this zone. Next to severity and completeness of the injury, clinical spinal
syndromes are relevant as they can show distinct patterns of recovery and
spastic motor disturbance due to specific epidemiology and anatomical dis-
tribution of lesion in the spinal cord [43].
The anterior cord syndrome (ACS), due to a flexion injury of the spine,
results in predominant damage of the ventral cord, the segmental ventral
horn cells, and spinothalamic and long motor tracts. This is also possible
when a minor mechanical impact triggers a disturbance of the blood supply
from the anterior spinal artery [44]. In patients with diffuse non-penetrating
spinal injuries, the clinical syndrome is characterised by segmental flaccid
paresis and spastic paresis with disturbance of pain and temperature sensa-
tion caudal to the lesion level but sparing of light touch and proprioception,
which are mediated in the dorsal tracts of the cord. Incidence is low, account-
ing for only 2.7% of all traumatic spinal injuries [45] and less than 1% of all
spinal syndromes [43]. Traumatic ACS as defined by Schneider [46] affects
the anterior two-thirds of the cord and hence involves damage of the lat-
eral corticospinal tracts. This is associated with a poor prognosis and minor
recovery rates of muscle force and poor coordination.
Traumatic central cord syndrome (CCS) is the most common acute incom-
plete cervical spinal cord injury, accounting for 44% of all spinal syndromes
and for 9% of all SCI in a recent study of 839 spinal cord injuries [43,47].
About 20% of patients with cervical spinal cord injuries present a clinical
CCS [47]. The syndrome is characterised by predominant upper extremity
weakness and clumsy hands, and less severe lower extremity dysfunction
and sensory and bladder dysfunction. Spasticity will be generalised with a
focus on the hands as paresis and loss of motor function is most pronounced
here unless lesion level is within the range of the motoneurons supplying the
hand muscles, as this will result in peripheral-type lesion with atrophy and
flaccid paresis. However, most cervical lesions occur at cervical levels C4 to
C6, maximum at C5, while very few affect C7 or C8 segmental levels [43,48],
thus mostly sparing motoneurons of the hand muscles, which are localised
below. CSS represents the oldest age group, with the lowest admission func-
tional level of all SCI clinical syndromes, which is a cofactor in determining
relatively poor recovery of hand function in this group, despite its favor-
able outcome compared to traumatic incomplete cervical SCI in general [43],
which is in the range of the group of Brown-Sequard [49]. Hand spasticity
in these patients can add to their functional impairment in activities of daily
life due to loss of manual dexterity. However, walking ability can also be
severely impaired by spasticity of the trunk and legs. CCS was originally
thought to result from post-traumatic centro-medullary hemorrhage and
edema [50], or from a Wallerian degeneration, as a consequence of spinal
cord compression in a narrowed canal [47].
The central focus of spinal damage in combination with the special
somatotopic organisation of the corticospinal tract, where motor tracts for
the upper are localised more centrally than those for the lower extremities,
were assumed to be responsible for the predominance of motor deficits in
the hands in CSS. However, more recent anatomical analysis and primate
animal studies suggest that the syndrome is due to the specific effects of a
cervical spinal lesion on direct corticomotor (pyramidal) tracts given their
significant role in manual motor control [51]. This would be in line with
the seminal findings of these direct cortico-motoneuronal projections by
Bernhard and Bohm [52] and with these authors’ appreciation and consid-
eration of this anatomical feature, which is unique in primates and humans.
A loss of the capacity for ‘fractionation’ of movements and control of small
groups of muscles in a highly selective manner [53] is as much character-
istic of CCS as an impairment of the acquisition of new motor skills [54].
Therefore, when considering the significance of direct cortico-motoneuronal
control in human manual dexterity [51], CSS may be considered a prototypi-
cal condition where spinal cervical lesion inflicts damage predominantly on
pyramidal tract axons affecting fine motor control and coordination of the
hand. Loss of fine motor control in general and, hence, particularly in the
condition of CSS is associated with spastic motor disorder, which can lead
to contracture and pain, predominantly in the upper extremity. This mostly
concerns the flexor muscles of the hands.
A hemisection of the cord leads to Brown-Séquard Syndrome (BSS),
which was first described in 1851 by the neurologist Charles Edouard
Brown-Séquard [55] as ipsilateral ataxia and spastic paresis due to pro-
prioceptive and motor loss in association with contralateral loss of pain
and temperature sensation below the level of lesion. A surgical unilateral
lesion dividing most of the ipsilateral tracts of the spinal cord resulted in
complete flaccid paresis of the ipsilateral limbs only for a few hours, after
which voluntary movements began to reappear [56]. Within days after such
a sharp lesion, patients were able to exert slow digital movements, and
walking ability was attained within 2 weeks. Slow and feeble manual func-
tion recovered within less than 3 weeks of the operation. This indicates
that recovery and redundancy in corticospinal control is strong in human
SCI. However, this syndrome is rare in traumatic SCI and its recovery is
generally less favorable than in the cases with a sharp penetrating spinal
lesion, as described by Nathan, indicating that there must be more exten-
sive and diffuse lesion of spinal tracts in lateralised traumatic SCI [57].
Although BSS-like syndromes with more or less lateralisation of lesion are
relatively rare in Europe and account for less than 4% of all traumatic SCI
[43], they are nevertheless relevant as prognosis is known to be most favor-
able among incomplete traumatic SCI [43,57,58], particularly with regard
to ambulation. Physiologically, recovery occurs in a rather characteristic
order, with proximal extensors prior to distal flexors on the more affected
side and vice versa on the less affected side [58]). This is attributed to the
unilateral (distal flexors) and bilateral (proximal extensors) distribution of
preserved fibres and their recovery due to sprouting and formation of col-
laterals. The recovery is most likely owed to lumbar midline crossing fibres
[59,60]. Spasticity usually is present, but does not pose a problem in these
patients.
Conus medullaris syndromes amount to 1.7% and posterior cord syn-
drome to less than 1% in the analysis of McKinley and coworkers [43]. Data
on these groups are sparse. In general, spinal syndromes tend to need shorter
rehabilitation length of stay, indicating that sufficient functional outcome is
reached after shorter duration of rehabilitation, which is likely secondary
to an in-complete pattern of lesion and high proportion of preserved spinal
nerve fibres [43]. Spasticity usually only occurs in the plantar-flexors and
digital muscles where there is an epi-conus lesion leaving intact ventral horn
motoneuron cells that are disconnected from supraspinal input.
6.2 Pathophysiology-Based Treatment of Spasticity

Spasticity even today is frequently thought to be reflected in an ‘extra-
activity’ in limb muscles mediated by exaggerated reflexes leading to muscle
overactivity. Also, most articles in this volume are focused on these phenom-
ena. The consequence of this thinking is that spasticity should be treated
by attenuating reflex and muscle activity by antispastic drugs or botulinum
toxin injections. However, for over 40 years convincing evidence has been
available indicating that these assumptions hold only partially for ‘clinical
spasticity’ but not for spastic movement disorder, which hampers the patient
(for review [61]).
In contrast to clinical signs of spasticity, it is characterised by a reduced

limb muscle activation. According to the studies on spastic movement
disorder, secondary to a CNS lesion, alterations of mechanical muscle
fibre properties occur in association with low tonic muscle activity, which
allows the development of spastic muscle activity to compensate the
reduced dynamic muscle activation during functional movements after,
e.g., a stroke. This enables the patient, for example, to support the body
during stepping. The consequence of this compensatory mechanism in
mobile patients is that anti-spastic drugs can accentuate paresis. In the
following paragraphs, we will discuss the multiple aspects of evidence in
more detail.
6.2.1 Clinical Signs of Spasticity

The diagnosis of a spastic paresis is based on the examination of tendon
tap reflexes and muscle stiffness in the passive subject. Early after an acute
damage of the CNS, tendon tap reflexes are exaggerated, but muscle stiffness
develops only after some weeks. When stretching a limb muscle of a spas-
tic patient (Ashworth Test) during the clinical examination a tonic muscle,
activation occurs in this muscle, leading to an increased resistance [62]. This
observation has led to the assumption that exaggerated reflexes result in an
increased muscle activity and, consequently, are responsible for the move-
ment disorder. However, electrophysiological investigations on the neuronal
adaptations after a complete spinal cord injury indicate a divergent course of
increasing clinical signs of spasticity but decreasing or stable values of their
potential neuronal correlates (M-wave, F-wave, H-reflex, and flexor reflex)
[24]. Consequently, non-neuronal mechanisms were assumed to contribute
to spastic muscle stiffness. In addition, according to all investigations of
natural, complex movements in patients with spasticity, the assumption of a
relevant ‘extra-activity’ contributing to spastic muscle stiffness could not be
confirmed [19].
6.2.2 Spastic Movement Disorder

For a patient with spasticity, the impaired performance of hand or leg/
stepping movements and their treatment are of importance, not the clini-
cal signs found during examination. During active movements such as gait
a low amplitude, tonic activation of upper and lower limb muscles can be
observed, i.e., a normal modulation of EMG activity is lacking while a nor-
mal timing of muscle activity is largely preserved [12,63]. The reduction of
limb muscle activity is suggested to be due to a diminished excitatory drive
from supraspinal centers and an attenuated activity of certain polysynaptic
(or long-latency) reflexes [64,65]. Polysynaptic reflexes are known to modu-
late limb muscle activity [64] and thereby adapt the movement pattern to the
environmental requirements.
In contrast, short latency reflexes neither in healthy subjects nor in

patients with spasticity contribute significantly to muscle activity during
natural movements [19]. These observations indicate that the muscle activ-
ity required during movement performance (e.g., to support the body dur-
ing the stance phase of stepping) develops on a lower level of organisation
after a CNS damage [19,61,66]. Consequently, the muscle tone required is not
achieved by a modulated muscle activation as it is the case in healthy sub-
jects. Instead, muscle hypertonus develops with the stretching of the toni-
cally activated muscle. This represents a more simple mode of muscle tone
generation, which is also based on structural alterations of a muscle second-
ary to a CNS lesion, i.e., a loss of sarcomeres [66], muscle fibre changes and
increase of structurally deteriorated extracellular matrix [14–16]. Increased
passive tension in the muscle is unrelated to stretch reflex activation. At the
single-fibre level, elevated passive tension was found in muscle cells express-
ing fast myosin heavy chain isoforms, especially MyHC-IIx, but not in those
expressing slow MyHC. Type IIx fibres were present in higher-than-normal
proportions in spastic muscles, whereas type I fibres were proportionately
reduced [16]. This is equivalent to an alteration of the contractile properties
toward tonic muscle characteristics. According to these authors, ultrastruc-
tural changes of the extracellular matrix such as expanded connective tis-
sue, but also decreased mitochondrial volume fraction and appearance of
intracellular amorphous material, suggest that the global passive muscle
stiffening in SCI spasticity is caused by structural and functional adapta-
tions outside and inside the muscle cells, which alter their passive mechani-
cal properties. This change compensates in part for the loss of neurogenic
muscle activation and allows, for example, for support of the body during
the stance phase of stepping. However, the performance of quick/fast move-
ments becomes impossible by this mode of regulation of muscle stiffness.
Muscle spasms do not play a role in this. Patients with spasticity do not only
suffer from an impaired motor output but a defective control and processing
of afferent signals contribute to the movement performance [65].
Thus, in patients with spasticity, in comparison with healthy subjects,
muscle activity is enhanced in the passive state, i.e., during the clinical exam-
ination, but is reduced during active natural movements. The spastic signs
observed during the clinical examination can therefore hardly be translated
to the movement disorder. Clinically, spastic signs are more pronounced in
damage of the spinal cord compared to a cerebral lesion. However, from a
pathophysiological point of view there exist only quantitative but no qualita-
tive differences.
6.2.3 Therapeutic Consequences
Exaggerated reflexes do little to contribute to the movement disorder that
impairs the patient. Nevertheless, most anti-spastic drugs are directed to
reduce the activity of short-latency reflexes mediated by group Ia fibres in
order to reduce muscle stiffness. However, mobile patients require spastic

muscle stiffness to support their body during stepping to compensate for
paresis [61]. Therefore, anti-spastic drugs can accentuate paresis and conse-
quently can lead to a worsening of function. Similarly, some authors argue
that botulinum toxin type A is assumed to result in a largely cosmetic effect
on spastic signs without functional improvement [67,68], although this toxin
might reduce the activity of the intrafusal fibres [69,70]. Intrathecal baclofen
might also reduce hyperactive reflexes without producing significant weak-
ness [71–73]. In conclusion, therapeutic interventions in patients with spastic
paresis due to an incomplete SCI should be focused on the training, relearn-
ing, and activation of residual motor function [74,75], and the prevention
of secondary complications, such as muscle contractures [76]. Anti-spastic
drug therapy might predominantly benefit immobilised patients by reduc-
ing muscle stiffness and relieving muscle spasms [77], which might in turn
improve nursing care for these patients. In cases where function is ham-
pered by a focal imbalance of specific muscle groups resulting in movement
impairment or contracture, focal botulinum toxin is known to be effective
in improving pain, helping to avoid or to reduce contractures, and facilitat-
ing function. Its action is by a weakening and relaxation of muscle activity
resulting in a biomechanical change in the muscle’s function. It makes the
muscle amenable to stretching and lengthening in order to restore to some
extent the interaction of antagonists. Thus, in addition, the weakening of the
agonist allows to some extent a strengthening of the antagonist muscles and
thereby it is possible to restore some of the disturbed antagonistic balance
[78]. This is independent of mobility of the patient but will require at least
some mobility of the affected limb when targeting functional improvement.
In contrast, mobile patients can benefit from a functional arm and leg
(locomotor-) training, which is associated with a recovery of function [19,61].
In animal experiments it could be shown that afferent signals induced by the
functional training to spinal cord neurons below the lesion lead to a directed
neuroplasticity [79] that is associated with a physiological mode of limb mus-
cle activation. In contrast, according to this study, a lack of training of natural
movements leads to a chaotic sprouting associated with a neuronal dysfunc-
tion, which might hamper a successful regeneration in the future in chronic
SCI subjects [80]. The clinical consequence of a functional training in mobile
patients is that with the improvement of function during the course of train-
ing less spastic muscle stiffness is required for movement performance, i.e.,
a new equilibrium between improved mobility and less pronounced signs of
spasticity becomes established [61].
As a consequence it follows that, in mobile patients, anti-spastic medi-
cation can impede recovery of natural movements, as the performance of
natural movements requires some spastic muscle stiffness for compensation
of the paresis, i.e., lack of sufficient muscle activation [81]. Robotic devices
can support this repetitive training. They allow longer training times and
can provide useful feedback information to the patient about the course of
functional recovery [82]. In immobilised patients a neuronal dysfunction

develops about 1 year after injury [21,83] likely as a consequence of the loss
of afferent feedback signals due to the immobility. This is reflected in rodent
experiments by an undirected sprouting of tract fibres below the level of
lesion [79].
6.3 Patient Selection and Therapeutic Approach

A consideration of treatment of spasticity is made when the patient or the
attending medical team observes persistent or pending signs of impairment
or harm associated with spasticity. As spasticity evolves with time after SCI
(due to spinal shock in severely affected patients), this is more likely to occur
some weeks after the injury during rehabilitation. It is important to follow
a strategy ruling out possible external triggers and after analyzing the exact
circumstance of the phenomenon before initiating a treatment. Thus, it is
important to obtain the view of the other members in the medical team and
inquire about the observations of the patient and their relatives prior to the
decision to treat. Management of these patients is teamwork, as is the entire
rehabilitation of SCI. Initial questions will pertain to the level of indepen-
dence and mobility of the patient. While there are exceptions, ambulatory
function mostly may preclude or limit treatment approaches with intrathecal
application of baclofen, which is mostly reserved for immobilised patients
with severe incapacitating spasticity leading to contractures.
6.3.1 Indication for Treatment of Spasticity in SCI

Despite the complex theoretical and pathophysiological knowledge of under-
lying mechanisms associated with alteration of stiffness and reflex function,
the management of spasticity in SCI is to a large extent empirical. An indi-
cation for treatment of spasticity in SCI exists when it may cause harm and
interference with function, nursing, or subjective well-being [78]. This may
be expressed by the patient or by the nursing staff and treating therapist
and physician [84]. A consensus should be reached as to the reason to treat
and treatment aim [78,84]. The most common treatment goals in spastic SCI
are enhancement of mobility and speed, increase of endurance and speed of
ambulation or wheelchair propulsion, improvement of transfers, improve-
ment of reaching, grasping, grooming and dressing, relief from pain, and
painful muscle spasms, improvement of tolerance to wear splints and ortho-
sis, which in turn will be needed to improve mobilisation of limbs and secure
therapy effects aimed at prevention of contractures, prevention of contrac-
tures, promotion of hygiene, improve positioning, and facilitate mobilisation
and other therapies [78].
Depending on distribution of spastic symptoms and their interference

with function, mobility for nursing aims, or subjective well-being of the
patient, a treatment regimen can be chosen [78,84]. Management of spastic-
ity is always a multidisciplinary and polymodal process, which includes
physical and pharmacological measures. It has to be considered that the
effects of spasticity might not always be negative. Spasticity can stabilise
weakened legs, allowing a patient to stand or transfer and have improved
mobility. Spasticity can also be a functionally helpful factor by being pro-
tective against skeletal muscle atrophy, decreasing the incidence of fracture.
Moreover, spasticity has been reported to increase glucose uptake and will
improve metabolism, thereby reducing the risk for diabetes in SCI [85] as
well as augmenting cardiovascular function and energy consumption. The
goal of treatment of spasticity must therefore consider the balance of func-
tional benefits from spasticity and its adverse effects in allowing and facili-
tating motor function and nursing in immobilised patients.
6.3.2 Clinical Assessment of Spasticity in SCI

Prior to any initiation of treatment, it is essential to have a thorough descrip-
tion of the extent and degree of the spasticity. Furthermore, the patient’s
day-to-day functioning should be known. Spasticity can prevent simple
maneuvers essential in daily life, such as transfer and the placing of hands
and arms to control an electric wheelchair, rendering manual hygiene or cath-
eterisation difficult. Personal accounts of the patient as well as information
from those who know the patient should be obtained. This is particularly rel-
evant when planning treatment of focal spasticity with chemo-denervation,
as it must be determined after first injection of botulinum b toxin whether
the dosage and pattern of application is optimal. When evaluating and dis-
cussing treatment options, a clear goal should be determined for what is
to be achieved by the treatment. In the clinical examination, it is impor-
tant to assess the range of active and passive movements as well as painful
limitations of movement or abnormal limb positions. While not function-
ally relevant, as it is not strongly related to loss of function, the most widely
used assessment scales are the Ashworth Scale and the Modified Ashworth
Scale [86,87]. It is therefore not recommendable to assess treatment effects,
except in testing response to intrathecal baclofen (see below). Other scales
come with the same limitations [88–90] and are therefore of limited clinical
value. Assessment can be done with the aid of video clips from before and
after treatment [84]. Electromyography (EMG) can be useful to identify and
inject spastic muscles in focal treatment by chemo-denervation. However,
EMG cannot be used to assess degree of spasticity. Individual patient his-
tory, with an emphasis on functional limitations of specific activities in daily
life, are more helpful to determine, if treatment is effective and satisfactory.
There are established and validated scales and scores in SCI to assess and
quantify activities of daily life (ADL), e.g., the Spinal Cord Independence
Measure [91–93]. SCIM and other scores cover the main ADL domains rel-
evant to SCI, such as mobility (6 minute walking test, 10 m walking test,
walking index in SCI: WISCI) [94,95], self-care (SCIM), unilateral hand func-
tion (Graded Redefined Assessment of Strength, Sensibility, and Prehension:
GRASSP) [96,97], and bladder and bowel management (SCIM) [98]. Most of
these scores have been validated and shown to be responsive to change and
can serve as a tool to evaluate effects of anti-spastic treatment if function is
a treatment aim [93,99]. In any case, it is recommendable to include patient-
reported outcomes relating to quality of life and participation when defining
treatment outcomes in any individual case and in clinical trials. Assessment
prior to and after treatment should then include both patient-reported and
externally rated functions in the activity of daily life. These are functionally
relevant and can contribute to a patient’s well-being, while scores for the
rating of clinical spasticity are not suited, and will likely not contribute to, a
patient’s benefit from treatment.
6.3.3 Clinical Presentation and Anatomical Distribution of Spasticity

Patho-anatomical distribution and severity of spinal lesion, among other fac-
tors, determine localisation of spasticity. Spastic symptoms may be more or
less focal or regional, e.g., most prominent in the upper extremity in a cen-
tral cord syndrome or pronounced in the legs in a thoracic complete spinal
lesion. Generalised spasticity may affect the trunk and abdominal muscles,
leading to pain or respiratory constraints. Spasticitiy of the upper extrem-
ity after SCI typically presents with shoulder adduction and inward rota-
tion, elbow, wrist, and finger and thumb flexion, and pronation. Typically,
patients’ hands tend to be fixed with closed fists, resulting in an impairment
of reaching, grasping, and releasing. Spastic hypertonus of the pelvic striate
muscles can impede micturition and defecation. Distribution and localisa-
tion of symptoms will guide the choice and form of application of anti-spastic
treatment. A sudden increase in spasticity should prompt the attending phy-
sician to screen for underlying pathology that can be completely indepen-
dent of the spastic motor disorder. The first step in the management of all
problematic spasticity is to identify, address, and treat any remediable causes
and factors [100] such as an over-filled bladder, obstipation, acute infections,
syringomyelia, or bone fractures may substantially influence the degree of,
or suddenly initiate, spasticity and must be determined [84]. An assessment
of the clinical and functional consequences for the patient is decisive before
management. If such measures are ineffective then it is appropriate to pur-
sue or increase medical treatment until a therapeutic response is obtained. It
is important to notice and attribute sudden changes in spasticity especially
in SCI because infection of the urinary tract, fever, constipation, skin lesions,
and local bone or joint injuries may not present in the usual way and go
unnoticed below the level of lesion. In fact, increase of spasticity may be the
leading and only symptom. Consequently, worsening of spastic symptoms
should prompt search for the most common and likely ailments of SCI
and spastic symptoms may immediately be alleviated by appropriate (and
causal) treatment of bladder infection or skin sores. Therefore, a thorough
check of patient history (e.g., for recent falls or injuries) as well as a thorough
examination should be initiated in cases of sudden change of spasticity. If
triggers are found their causal treatment may be prior and effective to also
treat harmful spasticity.
6.3.4 Physiological Effects of Training

A slowing of peak velocity of plantar-flexor muscles was shown to be related
to loss of strength and spasticity in SCI patients [101]. Spasticity and injury
level determine the pattern of abnormality in gait after spinal cord injury
[102]. Spasticity and paresis may thus be seen as directly related to the extent
of functional motor impairment. There are few systematic studies on this
issue [103–105] and recent work shows that functional improvement can be
induced by different types of functional motor training while simultane-
ously affecting volitional control and spasticity [106]. Endurance and pre-
cision training were shown to facilitate descending excitatory as well as
spinal inhibitory networks in patients with incomplete SCI in parallel with
improvement of walking function and reduction of the cutaneo-muscular
reflex excitability. The latter involves excitatory and spinal inhibitory com-
ponents. Training-induced parallel increase of volitional control and spinal
inhibitory components of the cutaneo-motor reflex suggests that spared
descending pathways originating from the motor cortex can be strength-
ened by the intervention, hence increase of motor control will parallel a
decreased susceptibility for involuntary muscle spasms [106,107]. Thus, vari-
ous types of functional motor training and physiotherapy may, in addition
to strengthening the descending excitation of the spinal cord, also increase
the strength of inhibitory spinal networks activated by both descending and
peripheral afferent pathways. These neurophysiological changes may then
lead to improvement of volitional control of movement as well as reductions
in involuntary muscle spasticity, such as reflected in the reduced spasm-like
cutaneo-muscular reflex.
6.3.5 The Mainstay of Spasticity Treatment in SCI Is Physical Therapy

As was argued earlier, all patients with spasticity should be urged to exer-
cise. If this is not sufficiently effective, the patient should have physiotherapy
with guidelines for exercises that counteract the spasticity. Physical ther-
apy does not have to be costly and can be performed by any caregiver who
supports and guides a patient in his activity. For an immobile patient who
is able to move with help, regular transfers and mobilisation twice a day
may be critical to prevent contractures. For someone who can barely stand
or walk, such a help for active mobilisation twice a day may be crucial for
him in order not to lose his remaining capacities. We have often seen spas-
tic patients who, once bed-ridden, never regained their former ambulatory
capacity without any other cause than transient immobilisation. The most
important factor is regular activation in short bouts that do not exhaust the
patient. Systematically increasing training intensity in order to keep stress
levels low is likely recommendable as a basic principle of physical therapy
and may improve any outcome [108].
If no treatable causes triggering spasticity can be found, the team should
decide whether focal or general signs of spasticity prevail and require treat-
ment. In focusing on functional deficits, the first level of treatment and the
basis for any further escalation should be physical therapy. This recommen-
dation is based on the notion of the ambivalent role of spasticity in central
paresis and impaired motor control. In a systematic analysis of the disturbed
motor control following SCI [19,109] it was suggested that replacing lost pat-
terned activation of the spinal cord by activating synaptic inputs via assisted
movements and/or electrical stimulation may help to recover lost spinal
inhibition, thus leading to a reduction of uncontrolled activation of the spi-
nal cord to improve its function [109]. Increasing the excitation of the spinal
cord with spared descending and/or peripheral inputs by facilitating move-
ment, instead of suppressing it pharmacologically is therefore the primarily
suggested approach to improve residual motor function and manage spastic-
ity after SCI. Any treatment of spasticity will then be a combination of phys-
iotherapy passively mobilising the spastic limb or body part and increasing
active movement within the limits of residual motor function. Physiotherapy
can be administered whether the patient is mobile or immobilised. Therapy
can be tailored to the patient’s needs and capabilities. It is associated with
the welcome effect of personal attention. Water therapy in itself can help to
reduce muscle stiffness and will, as a side effect, reduce tension-inducing
load as it eliminates gravity and thereby reduces defensive hypertonus and
alleviates mobilisation.
Recently, treatment concepts such as those described by Bobath and Vojta
(for review see [110]) have not been pursued very rigorously. While primarily
used in pediatric facilities in the past for treatment of spastic cerebral palsy,
they are not common concepts in SCI treatment. They are worth mention-
ing as systematic approach with the scheme to activate complex stereotyped
movement patterns that are believed to reside in the network of the spinal
cord (Vojta) or to inhibit spastic symptoms in flexor muscles of the upper and
extensors in the lower extremities (Bobath). However, there are no validated
studies to support this notion.
Locomotor training (LT) has become a standard of treatment of leg mus-
cle function for ambulation and stance balance control in SCI [110–112]. The
observation that LT can ameliorate spasticity is based on observations made
in cats with complete spinal lesions [113]. LT on a treadmill is combined with
bodyweight support, reducing gravitational forces by 20–50% by means
of mechanical support by an overhead harness. As subjects walk on the
treadmill with a reduced load on their lower extremities, coordinated step-

ping movements and patterned muscle activation can be facilitated by the
moving treadmill. In a recent review evaluating the current LT approaches
for gait rehabilitation in a total of 384 individuals with incomplete SCI, it was
shown that evidence on the effectiveness of locomotor therapy is still limited
[114]. While all approaches showed some potential for improvement of ambu-
latory capacity there is no superior method and effects were limited. Main
effects in the included studies were shown for gait velocity and distance,
hence a functional improvement which may be assumed to be associated
with an indirect improvement of muscle tone and its regulation. However,
only a subgroup of studies included measures of spasticity and this outcome
was neither systematically analyzed nor reported in the review.
6.3.6 Oral Systemic Anti-Spastic Pharmacotherapy

If necessary, generalised spasticity can be treated with oral medication.
Several drugs with antispastic effect are available with various mechanisms
of action. Baclofen, tizanidine, benzodiazepines, gabapentin, clonidine, and
cannabinoids are centrally acting drugs. Gabapentin, clonidine, and can-
nabinoids are not officially approved for the treatment of spasticity in SCI.
They are well-established drugs with known risk profiles and some low-
level evidence for antispastic activity and may therefore be considered as
second- or third-line treatment options in SCI spasticity on an individual
basis. Dantrolene and botulinum toxin type A have peripheral action. The
latter will be discussed in a separate paragraph. A synopsis of available oral
pharmaceutics, their main effect of action and metabolism, and side effects
is given in Table 6.1. Some of these drugs were especially developed to treat
spasticity after SCI. For instance, baclofen was first introduced in 1964 for
this use. Baclofen is structurally similar to g-aminobutyric acid (GABA). It
binds to GABA-B receptors in the brainstem and dorsal horn of the spinal
cord. By suppressing the release of excitatory neurotransmitters involved
in monosynaptic and polysynaptic reflexes, it is assumed to reduce muscle
stiffness and spasms [115].
Treatment effects of oral anti-spastic drugs are not well-documented. Most
of the studies upon which anti-spastic pharmacological treatment has so far
been based date from the 1970s, 1980s, and 1990s of the last century. While
still being cited in modern work, these early studies lack modern standards
of good scientific and clinical practice and the paucity of newer work may, at
best, indicate that there is little interest to build a better base of evidence in
pharmacological treatment of spasticity in SCI. New literature often appears
in the form of reviews of the same poorly controlled original studies. Such
systematic reviews repeatedly show that there is insufficient evidence to
assist clinicians in a rational approach to anti-spastic treatment for SCI
[85,116]. These reviews, as well as several others, showed that study quality is
low. Thus, therapy is mostly empirically guided, and randomised controlled
TABLE 6.1
Common Oral Antispastic Medicationa
Drug (Trade Name) Dosage (mg) Mechanism Metabolism Side Effects Specials
Baclofen (Lioresal) 3 × 5–3 × 30 GABA-A (spinal) Hepatic Sleepiness, nausea, Caution: withdrawal;
weakness, hypotonus, intrathecal dose 1/100 to
respiratory depression (IT) 1/1000 of oral dose
Clonazepam (Rivotril) 0.5–3 × 2 GABA-A (spinal Hepatic Sleepiness, nausea, Caution: withdrawal
and cerebral) weakness, hypotonus
Tizanidine (Sirdalud) 3 × 2–4 × 6 Alpha 2 Hepatic Sleepiness, nausea, Slow dose increase!
weakness, hypotonus,
dry mouth
Tolperisone (Mydocalm) 3 × 150 Formatio reticularis, Hepatic (Rare) gastro-intestinal Acts primarily on trunk
polysynaptic symptoms, hypotonus muscles
reflexes
THC and CBD* (Sativex) 24–48 ECS (CB1, CB2 Hepatic Dizziness, sleepiness, Aerosol
receptors) nausea, mood disorder
Dantrolene (Dantamacrin) 2 × 25–5 × 50 Striated muscle Hepatic Hepatopathia, sleepiness, Second line due to side
nausea, weakness, effects
Clonidine (Catapresan) 2 × 0.075–3 × 0.15 Alpha 2 Hepatic Hypotonus, bradycardia Second line
Gabapentine (Neurontin) 3 × 100–3 × 800 GABA (indirect) Renal Dizziness, sleepiness Second line, for spastic
pain
a Baclofen, clonazepam, tizanidine, and tolperisone are first-choice drugs; THC and CBD, dantrolene, clonidine, and gabapentine are second-choice
drugs.
* Oral spray, mix of: THC = Delta-9-Tetrahydrocannabinol; CBD = Cannabidiol, maximum dosage 12 × 100 ul.
trials (RCT) are rare and done only in very limited numbers of patients. A
large systematic review with specific focus on SCI [116] returned a yield of
262 references, of which only eight met the inclusion criteria of cross-over
RCT, with 100 patients (80 males) enrolled in these 8 cross-over studies, 14 of
which were spinal forms of multiple sclerosis. Three of these studies tested
efficacy of intrathecal application of baclofen (ITB; see paragraph below). One
parallel multi-center trial compared tizanidine with placebo [117] among
118 patients (104 males), all of whom had an SCI (traumatic etiology in 108
patients) at cervical and thoracic level, proving efficacy without additional
loss of strength. However, there was no improvement of ADL [117,118].
Outcomes in most studies were measured in terms of spasticity scales
(MAS or other), while only one study assessed the performance of activities
of daily life, showing no improvement [117,118]. The poor quality of included
studies, and the marked differences in study designs, outcome assessments,
and methods of reporting, did not allow for the performance of a quantita-
tive combination (meta-analysis) of the results. The same applies to other
similar reviews [85,116].
While efficacy is low, adverse drug reactions were reported to be common.
Within the scope of these reviews, only a couple of studies were of direct
comparisons of antispastic drugs (e.g., tizanidine vs diazepam or baclofen),
where no significant differences were found clinically [85,116], whereas dif-
ferential effects on flexor and extensor leg muscles were observed in a direct
comparison of baclofen and tizanidine, while neither drug caused weakness
at low dosage [119]. However, in the latter study on 10 chronic SCI patients, no
clinical or functional data were presented. The general methodological qual-
ity of most studies was poor according to the systematic review by Taricco
et al. [116] was poor, impeding meta-analysis or firm conclusions regarding
the clinical management of spasticity. Poor efficacy of anti-spastic drugs on
muscle hypertonus was attributed to the fact that most anti-spastic drugs
reduce reflex activity. In contrast, as pointed out earlier, recent pathophysi-
ologic evidence has suggested that exaggerated reflexes contribute little to
spastic muscle hypertonia [61]. In the majority of mobile patients, impair-
ment of functional movements is clinically more relevant than impairment
of muscle tone. Functional movements were only assessed in half of the tri-
als. Daily living activities and the overall patients’ status were also rarely
assessed, which contrasts with the therapeutic objective of routine clinical
practice. In conclusion, for various reasons, there was not enough evidence
from available clinical trials to assess, and compare, the effects of drugs com-
monly used to relieve spasticity after spinal cord injury. Hence, the overall
perception on oral anti-spastic treatment in SCI is today one of obfuscation,
best expressed by the following quote from one recent review: ‘published
reports depict a […] gloomy panorama on the treatment of chronic spasticity
by oral route’ [85].
Based on empirical recommendations, a combination of pharmaco-
logical agents at low dosage is assumed to help reduce side effects while
increasing efficiency. The choice of the drug or combination thereof will

be made based upon the individual response of the patient, age group,
prior experience, price, and profile of side effects and potential interaction
with other medication (e.g., tizanidine must not be combined with gyrase
inhibitors such as ciprofloxazine, as this would cause relevant interac-
tion with the toxic effects of the anti-spastic drug). Any of these systemic
treatments should be amended with focal physiotherapy, but can also be
combined with focal chemodenervation (botulinum toxin or phenol, see
below). This is more relevant, as adherence to anti-spastic medication is
problematic, hence dosage should be kept minimal when combined with
non-pharmacological treatment. In a large study of 2840 subjects with vari-
ous types of central motor syndrome (including stroke, spinal cord injury,
traumatic brain injury, cerebral palsy, and multiple sclerosis), adherence
to anti-spastic medication was at best 50% of treatment periods [120]. This
may indicate an unmet need for better anti-spastic medication and better
guidance with treatment.
In a recent systematic pharmacological approach, efficacy of spasticity
treatment with tetrahydrocannabinol (THC) was assessed in a placebo-
controlled trial in 25 SCI patients [121]. A major reason for drop-out was the
increase of pain and psychological side effects. The latter should be reduced
when using a combination of THC and cannabidiol, a partial antagonist that
is now commercially available as an aerosol for the treatment of spasticity in
multiple sclerosis [122,123]. However, when compared to established drugs,
the cost of this preparation is high.
6.3.7 Intrathecal Anti-Spastic Pharmacotherapy

The effective treatment of generalised spasticity is achieved by intrathecal
application of baclofen (ITB), first introduced by Penn and Kroin in 1984 [89].
Studies on outcome measures such as the Ashworth Scale and spasm score
as well as studies assessing quality of life have suggested the superiority of
ITB over oral baclofen [124,125]. Despite a lack of trials directly comparing
oral administration of baclofen and ITB, it is commonly agreed that ITB is
indicated when spasticity continues to produce a clinical disability, despite
trials of high dosages of oral treatments in patients who have functional
goals and/or significant pain and disability. ITB allows for flexible dosing
patterns to suit an individual patient’s lifestyle [100]. Thus, whenever gen-
eralised spasticity cannot be adequately controlled with oral medication,
i.e., due to insufficient effects on muscle hypertonus despite maximum dos-
age or due to intolerable side effects at sufficient dosage with a combina-
tion of oral drugs, reversion to ITB should be considered. Severe sequelae of
spasticity, such as contractures or progressive neurogenic scoliosis, may be
among the conditions that should prompt consideration of ITB where appli-
cable. Despite the considerable cost of the device and the effort required to
test efficacy for each patient prior to implantation, this route of application
has clear advantages over oral administration. Efficacy is empirically supe-

rior to that of oral therapy and can be achieved with little or no side effects.
The effect of ITB is estimated to be 100 times greater than with oral admin-
istration. Due to the much-enhanced pharmacological effect, patients do
not experience drowsiness or dizziness, while muscle hypertonus can be
effectively reduced in the lower extremities and in the trunk. Patients with
high degree of functional impairment due to immobilisation are most likely
to benefit from this therapy. There is some limitation of efficacy in the arms
and shoulders because with ITB the concentration of baclofen diminishes
in the cranial direction [126]. Furthermore, effects in the upper extremity
will be weaker due to the recommended position of the intrathecal catheter
no more cranially than the level of Th1, to avoid central effects of the drug,
such as depression of respiratory function and vigilance. It is assumed that
a more cranial position of the catheter may lead to toxic concentrations of
the drug at the brain stem level and thereby significantly increase the risk
of critical side effects associated with depression of respiratory and rhythm-
regulating midbrain centers. Furthermore, positioning of the catheter tip
should be optimised with respect to the main focus of spasticity. If it is in
both the upper and lower extremities then one should attempt to place the
catheter tip as high as T1; if the spasticity only affects the lower extremities,
it can be placed between T6 and T10 [100].
It is recommended to evaluate the patients and their caretakers to deter-
mine whether they and caregiving teams meet the demands required to
ascertain pump management and maintenance. It must be explained to the
patient and their caregivers that it is crucial to make follow-up appointments
to keep track of effects and adverse events. Relative contraindications are
anticoagulant therapy with coagulation disorders, anatomic abnormality
of the spine, and localised or systemic infection. It is generally agreed to
only implant ITB pumps in non-ambulatory patients. This is due to the fact
that the effect of baclofen on muscle hypertonus is non-specific and will also
pertain to volitional muscle activation. In fact, in spastic patients it may be
impossible to distinguish spastic tone from volitional strength directed to
main posture. Therefore, postural control and endurance of ambulation can
be deteriorated with ITB due to impaired gait and balance control. There
may be few cases where spastic muscle hypertonus or muscle spasms inter-
fere with volitional control, thus impeding or reducing gait performance.
Under these conditions it may be worth considering ITB in ambulatory
patients. However, it is strongly recommended to implant the subdermal
pump only after an extended test period with ITB administered by external
pump via temporary lumbar catheter. This is necessary in order to familia-
rise the patient with the effects that are to be expected and in order to test if
ambulation can be maintained despite ITB doses that are sufficient to control
spasticity. At the same time this may be a first step towards finding of the
individual optimal dose and patient’s expectations can be adjusted prior to
more invasive steps and costly implantation.
Irrespective of the issue of ambulation, intrathecal test doses should be

applied in all cases where ITB is considered in order to ensure treatment
efficacy prior to implantation. Usually a test dose of 50 ug is applied as an
intrathecal bolus via spinal tap and the patient must be monitored for respi-
ratory depression or arrythmia during the following 6 hours. If no effect is
seen the procedure will be repeated on the following days, increasing the
dose in 25-ug steps up to 75 ug (second day) and if necessary to 100 ug (third
day). This scheme relies on experience from a large multi-center study when
ITB was first introduced [115]. If there is no clear or beneficial effect at a dose
of 100 ug it is unlikely that the treatment with ITB will be successful.
While highly effective, ITB bears a risk of various complications.
Implantation and management of ITB should therefore be confined to dedi-
cated centers with experienced teams. There should be an emergency ser-
vice available or accessible round the clock, as malfunction of ITB can be
associated with sudden baclofen withdrawal, putting patients at vital risk
if untreated. There are early as well as recent reports indicating a consider-
able complication rate of 0.011 per month, or 12–13% per year. Of these com-
plications, the majority (78%) were related to catheter malfunction [115,127].
Another more recent and prospective study presented an even higher fre-
quency of adverse events, distinguishing surgical (53%), device-related (29%,
predominantly catheter dysfunctions), and drug-related events (18%) [128].
Drug-related side effects and complications usually comprise drowsiness,
nausea, hypotension, and respiratory depression. They occur mostly dur-
ing testing of ITB when bolus is applied or when adjustments are made to
the pump settings. There are reports about development of tolerance [129].
Another severe complication may arise in malfunction of the pump or, more
frequently, in dislocation or disconnection of the catheter. In these cases,
withdrawal reactions can lead to malignant muscle hypertonia with hyper-
thermia, hyperreflexia, potential autonomic instability, seizures, and hallu-
cinations. Patients should be taken under surveillance and treated by oral
administration of the drug.
There is slow development of drug tolerance even with ITB, as was shown
in an early prospective long-term studies [115] and in more recent studies
[115,127] where the authors of this retrospective analysis found an initial
development of tolerance during 5 years but that the mean applied dosage of
baclofen stabilised after 5 years at a dosage of ca. 500 ug/day. No significant
increase in dosage was found thereafter.
For a good overview of ITB management, technical details and complica-
tions, side effects, and special considerations the reader is referred to the
recent publication by Khurana [100].
6.3.8 Focal Anti-Spastic Pharmacotherapy: Chemodenervation

An indication for chemodenervation exists in focal spasticity causing harm
or showing progression. Physical management as part of good nursing care,
physiotherapy, occupational therapy, exercise, stretching and strengthening

of limbs, splinting, and pain relief are the basis of spasticity management
[78]. Therefore, this should be provided as a basis of any additional treatment
with more invasive techniques, such as chemodenervation. Local spastic-
ity may benefit from oral anti-spastic medication but should preferrably be
treated with focal therapy of the spastic muscle(s), thereby avoiding systemic
side effects. The most common measures are botulinum toxin A (botulinum
neuro toxin, BoNT) and motor point and nerve block by phenol/alcohol as a
cheaper alternative, though potentially at the cost of more local side effects
and pain. Early RCT have proven efficacy of BoNT in the treatment of spastic-
ity in etiologies other than SCI [130,131]. In a RCT comparing BoNT to phe-
nol blockade of the tibial nerve to treat spastic foot after stroke, BoNT was
superior to phenol [132]. This and the other controlled trials together with
the potential local damage that can be inflicted by the injection of alcohol or
phenol has nowadays also led to primary use of BoNT in the treatment of
focal spasticity in SCI. Despite its recognition and acceptance in the manage-
ment of local spasticity in SCI [78], there is a lack of high-quality evidence
for its efficiency in SCI spasticity, as is revealed by recent systematic review
[133]. Although this literature search, looking at management of spasticity in
a sample population with a majority of SCI patients, identified 9 studies on
BoNT and 10 on phenol/ethanol, none of them were RCT and none of them
were adequately powered. This is true for many studies on the treatment of
spasticity, often due to poor study design, low numbers, a variable manage-
ment approach, and diverse, non-standardised treatment schemes. As in
other etiologies, improvement of function is difficult to show or achieve [134],
which is, among other reasons, due to the fact that reduction of spastic muscle
hypertonus, as often used as a primary outcome, does not directly translate to
an improvement in function. Furthermore, motor dysfunction in spastic pare-
sis is usually mainly caused by weakness and the other ‘negative’ features of
upper motoneuron syndrome, and not by muscle overactivity [19].
The effect of local treatment with BoNT injected into spastic muscles
causes local weakness via blockade of the neuromuscular junction. The toxin
is internalised by the presynaptic motoneuron, where it inhibits the release
of acetylcholine [135]. The effect of injections is time-limited due to collat-
eral sprouting and regrowth of nerve endings and formation of synapses,
thus the treatment must usually be repeated after 2–6 months. International
guidelines recommend a combination of botulinum toxin injections and
physiotherapy. Phenol and ethanol produce neurolysis when injected close
to the nerve endings that supply spastic muscles. Injection of these agents
causes denaturation, which disrupts neural transmission and subsequently
diminishes muscle activity resulting from central disinhibition. Adverse
events are directly related to the mechanism of action, i.e., muscle weakness
reducing or disturbing functional abilities with both drugs and, addition-
ally, dysesthesia or denervation pain in treatment with ethanol/phenol.
Specific indications and aims for anti-spastic treatment with focal che-
modenervation include: functional improvement (enhanced speed and
mobility, quality, or endurance of gait or wheelchair propulsion, transfers,
dexterity and reaching, and sexual functioning), symptom relief (pain and
muscle spasms, allow wearing of splints, improved hygiene, prevention of
contractures), postural improvement (enhanced body image), decreased care
burden (alleviation of dressing and hygiene processes, positioning for feed-
ing, etc.), enhanced service responses (prevention of need for unnecessary
medication and other treatments, facilitation of therapy, delay or preven-
tion of surgery) [78]. It must be remembered that the treatment of spasticity
is physical primarily in order to influence and control consecutive biome-
chanical changes. A programme of physical treatment should be established
before and continued during and after pharmacological intervention. Muscle
stretching improves the therapeutic effect of BoNT and vice versa [136], but,
as in other areas of the field, RCT to produce high-level evidence are lacking.
Selection of injection points, dosage, and injection of BoNT should be done
by trained and experienced physicians. Gaining the skills requires time and
commitment. The placing of the injection should be guided by ultrasound or
EMG, which is recorded from the injection needle or by electrical stimulation
of the muscle at the intended target position. The aim of EMG guidance is to
record muscle action potentials at the intended injection site and assess their
interference pattern on muscular activation [78]. Activation can be difficult to
interpret in view of mass synergies in spasticity. Nevertheless, this will help
to detect and distinguish spastic activity from contracture as has mainly
been shown in the upper extremity in children with cerebral palsy [137–139]
but is commonly used in SCI [133]. It can thereby also serve to focus injec-
tions to the endplate [140,141]. Local muscle stimulation by electric pulses
that run through the injection needle can be used to localise the motor point
and thereby likely improve efficacy of BoNT treatment, as is indicated by
the growing body of studies elaborating on improved injection techniques
[140,142–144]. In order to get good results, careful thought and planning is
required. BoNT has a good propensity to seek neuromuscular junctions but
placing the toxin as close as possible may best be achieved by electric stimuli
at the lowest intensities to achieve better results. A high-volume dilution and
an endplate-targeted injection are apparently superior to a low volume and
endplate non-targeted injection, when injecting biceps brachii with BoNT in
patients with spastic hemiparesis [140]. It may be assumed that these results
can be extended to SCI but experimental or clinical data are missing. A num-
ber of articles are available to guide the treatment of spasticity with BoNT-A
in particular [145,146]. These highlight the principles of treatment and the
need for patients with spasticity to be managed by a multi-disciplinary team.
They present checklists and extend on the right conditions to obtain optimal
outcomes and, importantly, they assist in patient selection and the organisa-
tion of services [78].
Contractures cannot be treated with BoNT as they indicate an inactive

muscle. However, in our experience contract muscle fibres in a spastic mus-
cle may be localised next to muscle fibres that are still active. Therefore, it
may be reasonable to attempt injection even when a muscle is significantly
shortened in contracture due to spasticity. The criterion for focal treatment
should then be electrical activity in the EMG and intensive stretching and
possibly splinting should follow the injection. Next to the surgical lengthen-
ing of muscles and tendons these measures are to our knowledge the only
ones to treat states where contractures have already occurred. In conclusion,
BoNT and ethanol/phenol are used in the SCI population to manage limb
spasticity. BoNT is nowadays the prevailing drug in use, with good results,
good therapeutic safety, and empirical as well as some scientific evidence of
success. However, these interventions have not been rigorously studied in
individuals with SCI.
6.3.9 Surgical Correction of Contractures

A significant association between spasticity and contractures, i.e., reduced
range of motion (ROM), is known in relation to spasticity in traumatic SCI
[10]. In spastic paraplegia, this can typically affect the ankle plantarflex-
ion, flexion of the knee, or flexion-adduction of the hip, where it will lead
to impairment of positioning, gait, and transfers. If not sufficiently treat-
able pharmacologically, peripheral surgeries to release joints, muscles, and
tendons can be satisfactory in selected cases, some of which may regain
ambulatory capacity [147–149]. In tetraplegia, spasticity in the upper limb is
generally more incapacitating because it has potentially negative effects on
hand function as well as on transfers and mobility [150]. It typically involves
shoulder adduction/internal rotators, together with elbow, wrist, finger and
thumb flexors, and forearm pronators, and long-standing spasticity can
cause soft-tissue structures to adapt to the shortened flexed and pronated
position, subsequently leading to contractures. Hand spasticity typically
results in difficulties related to reaching, grasping, and releasing items [150].
Surgery aims to improve the ability to grasp, release, and open the hand by
lengthening or releasing tendons. These procedures have been developed
for the past 20 years and nowadays provide a reliable decrease in tension in
the spastic agonists. They may allow for an improvement of remaining func-
tioning of antagonists when overpowering agonists are released, thereby
reestablishing a better balance and synergy [150–152]. Furthermore, surgi-
cal transposition of the muscle-tendon unit can improve or reestablish joint
stability in the spastic hand and it can help to reduce pain and the risk of
developing contractures [150,153]. Surgical lengthening of tendons or release
of contractures may be part of a concept of reconstruction of arm and hand
function in tetraplegia; however, tendon transfers are not performed at the
same time as lengthenings and releases to avoid poor balance of the hand.
Restoration of elbow and wrist extension or handgrip has high potential to
improve autonomy and mobility, and abilities such as eating, personal care,
and self-catheterisation and productive work in at least 70% of tetraplegic
patients [154].
An indication for surgical treatment can be seen if pharmacological treat-
ment is insufficient or causes intolerable side effects. Another reason for focal
surgery may be proof of antibodies against BoNT, rendering this drug inef-
fective as a treatment alternative in dynamic focal spasticity. Hypertonus
should be stable over time and must have a limiting effect on daily activi-
ties. The patient should be well-informed and motivated to sustain and sup-
port post-operative treatment. Surgical treatment of contractures should be
part of an entire treatment concept in first defining targeted improvements,
allowing early mobilisation within 24 h by use of special suture techniques
providing sufficient stability, splinting, and maintenance of activities of daily
living, and subsequent systematic coordination and endurance training
[150]. Given these prerequisites, post-operative improvement of hand func-
tion and patient reported benefit can be substantial and may be expected
during a time period up to one year [155].
6.3.10 Focal Anti-Spastic Surgical Treatment:

Selective Dorsal Rhizotomy
Selective dorsal rhizotomy (SDR) is an invasive therapeutic approach taken
in selected children with spastic diplegia from cerebral palsy (CP), which
is well-established for its positive effects on muscle tone and strength [156],
range of motion, and ambulatory function [157–159]. In the CP population
improvement in motor function after SPR was shown to be more than could
be explained by the associated with intensive physiotherapy [158]. However,
standardised assessment of gross motor function after one year led to con-
troversial findings indicating that effects of SDR on function are modest and
hard to extrapolate [160,161]. Long-term follow-up of CP patients for 5–15 years
indicates that spasticity is effectively treated by SDR, while functional ben-
efit is minor and depends on severity of the lesion [162–164]. However, other
long-term follow-up studies, including patient-reported outcomes, show that
the spasticity-reducing effect of SDR, although pronounced, did not seem to
improve long-term functioning and contractures reoccurred in a significant
number, indicating that contracture development in CP is not mediated by
spasticity alone [165,166]. Spinal side effects, increase of pain, and hip luxa-
tion were seen, which, together with a gradual loss of the initial improvement
[165,167,168], suggests caution for the indication of this invasive procedure.
The role of this operation in the treatment of other spasticity causes is less
well defined. A recent literature review to survey outcomes from SDRs per-
formed outside the CP population showed that SDR have also been reported
in patients with SCI and myelopathy with severe spasticity [169]. In this
series, a total of 35 SCI patients, including patients with transverse myeli-
tis and myelomeningocele, were reported. In a subgroup of traumatic SCI,
spasticity and pain could be improved in the majority of cases and ambula-
tory performance was unchanged or also improved after the surgery in a
case of spasticity following transverse myelitis [170]. Another early report
on a small number of MS patients suffering from myelitis or myelopathy
as well as one case of traumatic SCI claimed similarly favorable outcomes
with respect to spasticity and ambulation [171]. The presumed mechanism
by which SDR reduces spasticity and improves remaining motor function is
by modulation (reduction) of afferent inputs to lower motor neurons to com-
pensate for a loss of upper motor neuron regulation (inhibition), although
the details of this mechanism are poorly understood [169]. The fact that the
surgical intervention of SDR is effective independent of the level of lesion of
the descending first-order motoneurons (i.e., CP or SCI) would support this
notion. This is also supported by the observation of largely reduced spastic-
ity following other surgical interventions involving SDR in SCI, e.g., with
anterior sacral root stimulation for treatment of neurogenic bladder dysfunc-
tion following SCI [172].
Although these outcomes from SDR surgery are described as favorable
and the use of SDR is suggested to be expanded to include pathologies
such as spinal lesion [170], post-operative assessments and follow-up times
are not standardised across reports and there are no systematic long-term
observations in SCI. The example in CP children demonstrates that rigor-
ous assessment standards must be applied to validate long-term outcomes
given the fact that the intervention induces permanent changes within the
nervous system. In conclusion, although the few reports on SDR in SCI may
be promising, there is insufficient evidence to consider SCI diagnosis to be
an indication for SDR. SDR may have a role in otherwise treatment-resistant
spasticity in SCI, as could be shown in three pediatric patients with SCI
[173]. However, it must be kept in mind that SDR, as an irreversible neuroab-
lative procedure, should be performed with great caution and in selected
cases only [169].
6.4 The Complex Spastic SCI Patient:

Selection of Therapeutic Approach
In this concluding section, two case reports will be presented illustrating
difficulties that may specifically arise in the treatment of spasticity in SCI.
They show how single pharmacological treatment may not be satisfactory
due to systemic side effects or insufficient improvement of hypertonus and
spasms. While a systematic approach and planning of treatment should
include informed consenting and active cooperation of the medical team
with the patient and their caregiver, it is important to also acknowledge
patient history and observations on treatment effects, since the clinical exam
can only test conditions during a very short time period, which is often not
representative of the majority of daily life. In this description, subtle details
may be relevant.
6.4.1 Case 1: Combination Therapies: Oral Systemic and Focal

A 60-year-old female suffered spinal ischemia with incomplete Brown
Sequard Syndrome at the Th8 level ASIA impairment scale C. She recov-
ered walking ability using 2 canes within 5 months of rehabilitation and
was released, returning to work as a part-time teacher. Within the follow-
ing 6 months she developed increasing spasticity of the legs, which was
treated orally with 5 mg of baclofen twice a day. Spasticity was not liming
ambulatory capacity or other leg motor function and therefore this dose was
not increased in order to allow the patient to continue to drive. However,
repeated falls were noted, starting during rehabilitation and continuing dur-
ing the following months. A first fall-related intra-articular fracture of the
first phalanx of the left foot was documented by the orthopedic surgeons
2.5 years after the spinal injury, which was treated by casting. Within 5 years
of SCI sudden unexpected falls resulted in 3 other fractures, e.g., a left malle-
olar fracture treated surgically after 3.5 years, a right metatarsale III/IV frac-
ture after 4.5 years, and a right tri-malleolar fracture with dislocation after
5 years. A more detailed history-taking revealed that she had had unexpected
flexing spasms of the hip and knee in every of these instances. Usually these
spasms were triggered by episodes of back pain or bowel movements. As in
other falls the flexion spasms resulted in sudden instability of stance and
repeated uncontrollable movements of the legs. On several occasions, these
movements had resulted in fractures when the uncontrollably moving leg
had hit the floor or another object. Treatment of the instable intra-articular
tri-malleolar fracture was initiated with external fixation. This resulted in
exacerbation of hip flexion spasms and massive increase of hypertonus in
triceps surae, posterior and anterior tibial muscles of the affected side, which
could not be sufficiently treated orally or by BoNT injections. As exacerba-
tion of spasticity lead to further dislocation of the fracture including the
fixateur externe, the external fixation had to be removed and was replaced
with an internal fixation. Oral medication was intensified, combining a daily
dose of tizanidine 12 mg and baclofen 55 mg. The patient was discharged
with this medication after consolidation of the fracture and rehabilitation
of walking function during 3 months after the fracture. During subsequent
controls, she reported side-effects in the form of dizziness and sleepiness,
impeding her driving. This lead to a dose reduction to 40 mg baclofen but,
subsequently, flexion spasms increased again. Focal treatment of hip flexors
with BoNT was initiated, resulting in a satisfying control of frequency and
intensity of the spasms.
6.4.2 Case 2: Combination Therapies: Intrathecal Systemic and Focal

A 21-year-old male suffered traumatic SCI with incomplete tetraplegia at the
C3 level ASIA impairment scale C in a severe farming vehicle accident. After
decompression surgery, the spine was internally stabilised from cervical 3
to thoracic 2 in several operations. During rehabilitation, he required early
repeated BoNT injections in his overactive elbow flexors to allow continued
arm training with sufficient elbow extension. Additional oral antispastic
medication amounting to 75 mg of baclofen and 6 mg of tizanidine did not
sufficiently reduce abdominal spasms and leg spasticity. A further increase
of medication was followed by central side effects such as sleepiness and
reduced alertness. Intrathecal testing with baclofen resulted in excellent
response regarding lower body spasticity. Therefore, intrathecal baclofen
was initiated following implantation of a permanent intrathecal catheter
connected to a subcutaneous programmable pump 4 months after SCI. This
improved lower body spasticity significantly at a final intrathecal dose of
130 ug baclofen at a concentration of 500 ug/ml. Oral anti-spastic medica-
tion could subsequently be tapered and alertness and participation in reha-
bilitation training improved substantially. Rehabilitation over a period of
6 months resulted in partial independence for activities of daily life and the
patient achieved mobility in an electric wheelchair, which he operates with
his better right hand. Intermittent BoNT injections continued to help control
his overactive elbow flexors to allow maintenance of sufficient elbow exten-
sion, which is also a prerequisite for correct positioning of the arm used to
control the electric wheelchair. Recently, focal chemodenervation had to be
extended because increasing wrist flexion spasticity had led to significant
deterioration of the hand position, almost rendering his proper control of the
wheelchair impossible. Additional injections in his right flexor carpi ulnaris
resulted in efficient reduction of hypertonus in this muscle, reestablishing
proper manual control. Further opportunity for improved hand control was
evaluated recently by planning reconstructive hand surgery, as the neuro-
logical level had lowered to functionally C5 following chemodenervation
of hyperactive wrist flexors, improving poor balance of wrist control and
allowing active training of the antagonists for better wrist extension.
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7
and Contractures in Multiple Sclerosis
Lorna Paul and Paul Mattison
CONTENTS
7.1 Multiple Sclerosis; Incidence, Epidemiology, and Disease Course..... 176
7.2 Pathophysiology of MS and Spasticity.................................................... 178
7.3 Disease-Modifying Therapy in MS.......................................................... 179
7.4 Spasticity in MS........................................................................................... 179
7.5 Management of Spasticity in MS.............................................................. 181
7.5.1 Pharmacological Treatments......................................................... 181
7.5.1.1 Treatments for Generalised Spasticity: Oral
Medications....................................................................... 181
7.5.1.2 Baclofen............................................................................. 182
7.5.1.3 Tizanidine......................................................................... 182
7.5.1.4 Dantrolene......................................................................... 183
7.5.1.5 Gabapentin........................................................................ 183
7.5.1.6 Cannabinoids.................................................................... 184
7.5.1.7 Benzodiazepines.............................................................. 186
7.5.1.8 Evidence-Based Guidelines for Oral
Antispasticity Medications: Spanish and German
Consensus Document...................................................... 186
7.5.1.9 Treatments for Focal Spasticity...................................... 187
7.5.1.10 Phenol Chemodenervation............................................. 187
7.5.1.11 Botulinum Toxin.............................................................. 188
7.5.1.12 Intrathecal (IT) Baclofen.................................................. 189
7.5.2 Non-Pharmacological Treatments................................................ 190
7.5.2.1 Physical Activity/Exercise for the Management
of Spasticity in MS........................................................... 191
7.5.2.2 Transcutaneous Electrical Nerve Stimulation
(TENS) for the Management of Spasticity in MS......... 191
7.5.2.3 Transcranial Magnetic Stimulation for the
Treatment of Spasticity in MS........................................ 193
175
7.5.3 Other Non-Pharmacological Interventions

for the Management of Spasticity in MS..................................... 194
7.5.3.1 Surgery.............................................................................. 195
7.5.4 Strategy for the Management of Spasticity in MS...................... 195
References.............................................................................................................. 197
7.1 Multiple Sclerosis; Incidence, Epidemiology,

and Disease Course
Multiple sclerosis (MS) is a common neurological disorder causing disability
in young people in the developed world, with approximately 2 million peo-
ple affected by the condition worldwide and 100,000 people affected in the
UK (McAlpine and Compston 2005). MS is a progressive illness with neuro
inflammatory and neurodegenerative components generally accepted to
have an underlying auto-immune aetiology.
While an epidemiological gradient of prevalence has long been recognised,
with cases more commonly seen the farther away from the equator, there are
exceptions to this trend, with rates in Sardinian people approaching those of
Northern Europeans and prevalence being low in the Inuit people of Canada
(Koch-Henriksen and Sorensen 2010).
Present thinking suggests that MS occurs as a result of genetic predisposi-
tion allied to environmental factors. Circumstantial evidence implicating a
lack of vitamin D as a significant environmental factor in the aetiology comes
from studies which have demonstrated that season of birth may be impor-
tant, with those born in the summer months in the Northern Hemisphere
being more likely to develop the illness than those born during the winter
(Torkildsen et al. 2012). This hypothesis was strengthened by the discovery
of an association between the genetic locus HLA DRw1*15 on chromosome
6 and risk of MS, this particular gene being important in the regulation of
immune responses and also critically being dependent on vitamin D for
proper function (Ramagopalan et al. 2009). There have however been more
than 50 genes linked to increased risk of MS, suggesting that the genetic
predisposition is complex.
Viral triggers have also been implicated with the strongest evidence link-
ing Epstein Barr Virus (EBV) infection in childhood or early teenage years as
a potential significant factor in producing the “abnormal” immune response
(Ascherio and Munger 2010).
Since the condition can affect any part of the central nervous system (brain
and spinal cord) people with MS can experience a wide variety of sensory,
motor, visual, brainstem, and autonomic dysfunction, d epending upon which
areas of the brain and spinal cord are involved.
Different clinical courses and phases of the illness are recognised based
primarily on symptom presentation and clinical findings. These have been
Clinical Management of Spasticity and Contractures in Multiple Sclerosis 177
used to categorise the illness and, since the introduction of disease-modifying

treatments in the mid-1990s, to inform treatment decisions (Figure 7.1).
Relapsing-remitting MS (RRMS) describes a clinical course characterised
by acute onset of new, or significant worsening of existing, symptoms last-
ing for more than 24 hours and not associated with infection. Recovery from
such episodes may occur spontaneously or following treatment with corti-
costeroids. This pattern of disease is seen in approximately 80% of patients
early in the course of the condition. The majority of these acute exacerbations
either resolve completely or substantially at this stage.
Progressive-relapsing disease describes a course where acute exacerba-
tions are experienced similar to RRMS but with incomplete recovery from
Progressive-relapsing multiple sclerosis
Steady decline since onset with super-

imposed attacks.
Secondary progressive multiple sclerosis
Initial relapsing-remitting multiple sclerosis

that suddenly begins to have decline without
periods of remission.
Primary progressive multiple sclerosis
Steady increase in disability without attacks.

Increasing disability
Relapsing-remitting multiple sclerosis
Unpredictable attacks which may or may not

leave permanent deficits followed by periods
of remission.
Time
FIGURE 7.1
Four clinical patterns of MS.
each episode so that early disability accumulation becomes a marked fea-

ture of this presentation. The majority of patients who initially present with
RRMS will eventually develop a more progressive phase of disability accu-
mulation with an absence of the typical relapses that were a feature of the
earlier presentation. This clinical situation is called secondary progressive
MS and develops typically between 15 and 20 years after diagnosis.
Primary progressive MS is a clinical entity in which relapses are not a fea-
ture but the patient experiences increasing levels of disability from diagnosis.
It occurs in approximately 10% of those diagnosed with MS and the course of
this type of clinical presentation is very variable, ranging from rapidly deterio-
rating levels of function to very little discernible change over a 20-year period.
7.2 Pathophysiology of MS and Spasticity

Unlike the majority of neurological conditions causing spasticity, MS is not a
monophasic illness. In conditions such as stroke, spinal cord injury, cerebral palsy,
and traumatic brain injury there is a single insult to the central nervous system
(CNS) resulting in an imbalance of efferent or afferent control of the normal spi-
nal and cortical mechanisms of homeostasis that maintain normal muscle tone
(this term and the anomalies associated with its use are d iscussed in Chapter 1).
Multiple sclerosis, however, is a dynamic condition with repeated injury to
the CNS at different sites and affecting different pathways within the brain
and spinal cord at different times over a long time interval. Acute exacerba-
tions (relapses) occur in the majority of patients, particularly in the first 10–
15 years following diagnosis and these may sometimes manifest as changes
in tone either because of inflammatory change within myelin causing inter-
ruption of normal nerve conduction or because of sensory symptoms brought
on by the relapse causing adverse nociceptive afferent input. Such changes in
tone may resolve spontaneously or with treatment of the relapse with steroids.
MS is characterised by neuroinflammatory components which principally
affect the myelin sheath and often give rise to acute neurological distur-
bances, which the patient may recognise as a relapse, although it is clear from
the use of enhanced MRI imaging that many such inflammatory episodes are
sub-clinical, i.e., do not give rise to symptoms. Such episodes may completely
resolve or over time lead to scarring (sclerosis) and loss of metabolic support
for the underlying nerve axon, which may degenerate as a consequence.
However, it is also apparent, particularly in the primary progressive vari-
ant of MS, that axonal degeneration may occur independently of inflamma-
tion as a separate immunologically mediated process. There is also some
evidence to suggest that axonal degeneration can occur as a separate process
in the early stages of relapsing/remitting MS (Su et al. 2009).
In either case, the overall effect is a progressive loss of nerve axons within
the brain and spinal cord. Given the widespread distribution of lesions within
the brain and spinal cord, clearly interruption to normal excitatory and inhib-
itory pathways may occur at any level, although loss of supraspinal inhibitory
control of reflex activity is the dominant mechanism leading to progressive
spasticity in MS. Axonal degeneration and spinal cord atrophy are cardinal
features found in patients with MS affected by significant spasticity.
7.3 Disease-Modifying Therapy in MS
Disease-modifying treatments for MS have so far been disappointing in rela-
tion to prevention of accumulation of disability, with clinical trial outcomes
having been centred around relapse reduction. This has meant that regula-
tory bodies such as the National Institute for Care and Clinical Excellence
(NICE) in the United Kingdom have defined the indications for use of disease-
modifying treatments around this parameter.
More recently introduced treatments, such as natalizumab, fingolimod,
dimethyl fumarate, and alemtuzumab have a greater effect upon short-term
accumulation of disability (as measured by EDSS) but are reserved at least in
the case of nalaizumab and fingolimod for second-line treatment where first-
line agents have been unsuccessful (Kappos et al. 2010, Polman et al. 2006).
A range of newer disease-modifying drugs is imminent. Ocrelizumab, a
monoclonal antibody treatment targeting B cells, has recently been reported
to reduce disability progression in patients with primary progressive MS, by
approximately 20% over a 24-week period compared to placebo, as well as hav-
ing favourable effects upon both the number of T2 weighted lesions on MRI and
total brain volume (Montalban et al. 2017). Further long-term studies are required
to confirm this effect. Such developments and others in current clinical trials
may well alter treatment strategies in the future, but for many people affected
by MS the main therapeutic goal is to effectively manage symptoms rather than
disease modification, although clearly the two aims are not mutually exclusive.
7.4 Spasticity in MS
Spasticity is one of the commonest symptoms experienced by people affected
by MS, occurring in up to 80% of patients at some stage of the disease, with
approximately 50% of those affected having troublesome symptoms of pain
and discomfort or impaired mobility as a consequence (Rizzo et al. 2004).
Overall figures of between 40 and 80% are reported (Flachenecker et al. 2014).
The different prevalence rates are explained in part to the various definitions
of spasticity or the method used to assess spasticity, e.g., Rizzio et al. used
self-report methods where spasticity was described as “unusual tighten-
ing of muscles,” whereas a number of other studies have used the Modified
Ashworth Scale (Flachenecker et al. 2014).
The classic clinical features of spasticity are increased muscle tone, stiffness,
pain, and reduced mobility. This is also true in MS; however, other “symptoms”
of spasticity in MS include muscle weakness, fatigue, bladder dysfunction, sleep
disturbances, anxiety, and depression (Flachenecker et al. 2014, Rizzo et al.
2004). Specifically in MS, spasticity more commonly affects the lower limbs com-
pared to the upper limbs or trunk (Flachenecker et al. 2014). Spasticity is not, how-
ever, an isolated symptom and there is a complex interrelationship with other
symptoms, which may be factors in contributing to the burden of symptomatol-
ogy. Pain and bladder dysfunction, symptoms experienced by more than 50% of
people with MS, are important contributors producing or exacerbating spasticity.
There are a number of factors that are known to be associated with increased
levels of spasticity. In particular, there is a linear relationship between increas-
ing severity of spasticity and both increasing disease duration and disability
level (Flachenecker et al. 2014, Rizzo et al. 2004). There is also a clear relation-
ship between spasticity and reduced walking ability, urinary dysfunction
and sleep disturbance (Zettl et al. 2014). Other factors reported to be associ-
ated with the presence of spasticity in MS are increasing age, male gender,
and progressive forms of the disease (Flachenecker et al. 2014, Rizzo et al.
2004). Furthermore, requiring a walking aid/wheelchair, being unemployed,
and increased use of health care resources have also been stated as associated
with spasticity in people with MS (Flachenecker et al. 2014, Rizzo et al. 2004).
The few studies in this area have been cross-sectional, thus can only derive
associations between spasticity in MS and demographic and clinical charac-
teristics. In addition, the factors associated with spasticity are not indepen-
dent, e.g., increasing age is associated with increasing levels of disability and
both are associated with the presence of spasticity. Some relationships are
direct and some and indirect; e.g., the association between unemployment
and spasticity is unlikely to be a direct relationship, other associated factors
such as fatigue may play a significant and more direct role. The situation is
therefore complex, with many possible mediating factors involved.
Ultimately, spasticity, as currently understood, has a negative impact on
function, activities of daily living (ADL), and quality of life for people with
MS (Flachenecker et al. 2014, Rizzo et al. 2004). This, in turn, has other con-
sequences, with increased carer burden and reduced employability of the
person affected. In addition, there are higher socio-economic costs for indi-
viduals and their families, as well as increased statutory social care and
health service-related costs. A recent study of resource use related to spastic-
ity in MS undertaken in Sweden estimated the costs per patient per year to
exceed €114,000, with costs increasing proportionately to increasing levels of
spasticity as indicated on a NRS (Svensson et al. 2014). Similarly quality of
life scores on the EQ-5D were also related to increasing levels of spasticity
in a study carried out on 419 patients with MS in Germany (Flachenecker
et al. 2014). Interestingly, the health care costs only account for around 7%
of all costs associated with spasticity; the main costs are attributable to non-
medical and indirect costs such as personal assistance, informal care, and
patient and caregiver loss in productivity.
7.5 Management of Spasticity in MS
The management of spasticity in MS requires a good understanding of
the nature and natural history of the disease within an experienced multi-
disciplinary team setting. An understanding of the evidence base under-
pinning therapeutic interventions and an awareness of tolerability of the
adverse effect/benefit relationship to treatment is essential. Spasticity itself
can in some circumstances be of benefit with the bracing effect of a degree
of increased lower limb spasticity compensating for muscle weakness and
facilitating walking and transfer abilities.
A review of the available management options follows, with examination
of the evidence for efficacy of these interventions, followed by a suggested
practical clinical approach to integrating the different treatment strategies
into typical clinical scenarios.
7.5.1 Pharmacological Treatments
Pharmacological management can be divided into systemic treatments, in
situations where the patient has more generalised spasticity symptoms, or
focal treatments that aim to target specific localised affected muscle groups.
The evidence base for the most commonly used medications in treating
spasticity related to MS is generally poor, reflected in both the Cochrane
review (Shakespeare et al. 2000) and the NICE guidelines for MS; however,
there have been more recent attempts to produce evidence-based guide-
lines by Spanish and German authorities using the Scottish Intercollegiate
Guidelines Network (SIGN) guidance framework of weighting of evidence
and strength of recommendations.
7.5.1.1 Treatments for Generalised Spasticity: Oral Medications

Oral medication taken for spasticity is often poorly tolerated because of sig-
nificant side effects, with adherence rates of less than 50% reported in a large-
scale retrospective study in the USA (Halpern et al. 2013). This is reflected
in German data showing that 41% of physicians and 36% of patients were
dissatisfied with their current management of spasticity (Flachenecker 2013).
7.5.1.2 Baclofen
Baclofen has been in use since the mid-1970s and is the most commonly pre-
scribed oral anti-spasticity agent. It is structurally similar to GABA and acts
agonistically on GABAB receptors, restricting the influx of calcium at pre-
synaptic terminals, suppressing the release of excitatory neurotransmitters. It
acts on both monosynaptic and polysynaptic reflex pathways leading to inhi-
bition of γ efferent motor responses (Bormann 1988, Feldman et al. 1980),
but more possibly on the presynaptic inhibitory pathways in the spinal cord.
While its principal site of action is at spinal cord level, baclofen also has cen-
tral actions at brainstem and cortical levels, which result in its major side effects
of fatigue, somnolence, and nausea (Addolorato et al. 2006). Muscle weakness
and liver function abnormalities also occur but are less frequent. Halpern et
al. (2013) recently reported that adherence to baclofen therapy was only 20.4%
in a large retrospective study of a population of patients commenced on anti-
spasticity medication over a 5-year period in the USA (Halpern et al. 2013).
A relatively small number of randomised controlled trials (RCTs) have
compared baclofen with placebo in MS-related spasticity and have reported
reducing spasticity and frequency and severity of spasms. However, none
would be considered to be of sufficient quality to allow firm recommenda-
tions for treatment; suffering from a lack of consistency in outcome measure-
ment, selection bias, or insufficient power (Shakespeare et al. 2000).
A limited number of small-scale head-to-head studies comparing baclofen
with tizanidine and baclofen with diazepam have not demonstrated the
superiority of either drug in terms of clinical efficacy or patient tolerability
(Bass et al. 1988).
Pragmatically however, baclofen is commonly used and is recommended
as first-line treatment for spasticity associated with MS in the most recent
NICE guidelines for MS in the UK. Dosage ranges from 5 mg to 100 mg daily,
with dose titration commencing with 5 mg at night increasing progressively
until the desired clinical response is obtained or the patient experiences
unacceptable side effects. In practice doses, above 60 mg daily in divided
doses tend to produce only modest clinical benefits but significantly increase
unwanted side effects.
7.5.1.3 Tizanidine
Introduced in the early 1980s as a novel treatment for spasticity, tizanidine
acts as an α-2 agonist modulating the release of excitatory neurotransmitters at
pre-synaptic level. Animal studies have demonstrated effective suppression of
polysynaptic reflexes in the spinal-transected cat. Its mode of action produces
a reduction in facilitation of spinal motor neurones (Newman et al. 1982).
The UK tizanidine study group reported a 20% mean reduction in overall
muscle tone assessed by a composite Ashworth score at multiple sites com-
pared with placebo in an RCT involving 182 subjects with MS (Group 1994),
although a similar study from the USA published simultaneously involving

similar numbers and primary outcome measure was unable to confirm this
(Smith et al. 1994). Both studies, however, suffered from high drop-out rates;
in the UK study, only 70 of the original 182 complied fully with the study pro-
tocol (29 tizanidine, 41 placebo). No functional gains were found in relation to
improved ambulation or activities of daily living (ADL) capabilities.
Dosage scheduling typically starts at 2 mg daily, increasing every third
day in 2-mg increments. Effective adult daily dosages are usually within the
range of 16–28 mg, with a maximum recommended daily dose of 36 mg in
divided dosages.
Side effects commonly include dry mouth, drowsiness and light-headedness;
rarer adverse effects are hallucinations, asthenia, and liver function test
abnormalities the latter being reversible on withdrawal of the drug.
Tizanidine has similar rates of compliance to baclofen (Halpern et al. 2013)
but is significantly more expensive than baclofen and for this reason is often
listed as a second-line agent in hospital formularies.
7.5.1.4 Dantrolene
Dantrolene differs from the centrally acting drugs baclofen and tizanidine
in that its principal site of action is within skeletal muscle itself. It blocks
calcium release from the sarcoplasmic reticulum in skeletal muscle, inter-
fering with the excitation-contraction coupling necessary to produce muscle
contraction (Pinder et al. 1977).
Although several RCTs in people with MS have reported favourable reduc-
tions in muscle tone with dantrolene compared to placebo (Gelenberg and
Poskanzer 1973) and one double-blind crossover comparative study show-
ing equivalence of effect with diazepam (Schmidt et al. 1975), these studies
were undertaken over 30 years ago, with no validated outcome measures
(physician-assessed spasticity being the primary outcome measure).
The principal limiting factor in the use of dantrolene is its propensity to
produce significant muscle weakness very often within a narrow therapeutic
range. Initial dosing is 25 mg daily, increasing in 25-mg increments every
3–4 days to a maximum of 200 mg daily if tolerated.
Because of its muscle weakness-inducing properties, dantrolene may be
more suitable for patients who are not mobile. Other commonly reported side
effects include drowsiness and gastrointestinal upset, nausea, and diarrhoea.
Severe and irreversible liver damage can occur with dantrolene therapy and
routine monitoring of liver function tests is mandatory (Durham et al. 1984).
7.5.1.5 Gabapentin
Gabapentin was originally developed as a novel anti-convulsant for the
treatment of partial seizures in the early 1990s, and was subsequently dem-
onstrated to have significant beneficial effects on neuropathic pain.
Structurally, it is similar to the γ-aminobutyric acid (GABA) neurotrans-

mitter, and it was postulated that it exerted its actions by GABA-mimetic
properties acting on GABA receptors. However, this is not the case since it
does not bind to GABAa, GABAb, or glutamate receptors (Shimizu et al. 2004).
Experimental animal work has indicated a possible antagonistic effect on
NMDA receptors producing calcium channel blockade and this may explain
both the effects on pain modulation via dorsal root ganglia and ascending
spinal cord afferent pathways as well as spinal motor output. It may also be
that the amelioration of neuropathic pain as an external trigger is significant
in reducing noxious afferent input and may explain its effects on reducing
spasm and spasticity (Kukkar et al. 2013).
Mueller et al. undertook a small study (n = 15) with a randomised crossover
design of the short-term effects of gabapentin on spasticity in MS patients,
and reported favorable outcomes in terms of Ashworth scores and spasm
frequency compared to placebo (Mueller et al. 1997).
A subsequent well-controlled crossover design RCT in 21 patients with MS
confirmed the findings of the Mueller study (Mueller et al. 1997), with gaba-
pentin producing significant benefits in relation to reduced Ashworth scores
and spasm frequency with patient-reported improvement in functional abil-
ity (Cutter et al. 2000).
Optimal dosage is within the range of 1200–1600 mg daily, but doses up to
a maximum of 3600 mg daily are well tolerated. Current NICE guidelines for
MS suggest that gabapentin should be considered as a first-line therapy for
spasticity in patients with MS (National Clinical Guideline 2014).
7.5.1.6 Cannabinoids
Cannabis has been used medicinally for over 4000 years, being mentioned in
a pharmacopeia written by the Chinese Emperor Shen Nung in 2700 BC as a
treatment for gout, rheumatism, malaria, and dysmenorrhoea.
Historically, cannabis has been used by large numbers of patients affected
by MS; Chong et al. reported a survey of UK MS patients in which over 80%
of those surveyed had tried cannabis, with more than 70% claiming benefi-
cial effects in terms of symptomatic relief (Chong et al. 2006).
Two types of endogenous cannabinoid receptors have been identified
in humans. The CB1 receptor is widely distributed throughout the central
nervous system, most densely expressed within the substantia nigra and
globus pallidus (Herkenham et al. 1990). Stimulation of the CB1 receptor
produces suppression of neurotransmitter release presynaptically, in turn
leading to suppression of excessive motor output, which provides a putative
explanation for its potential to influence both muscle spasm and stiffness
(Pan et al. 2008).
CB2 receptors are expressed within the immune system, being found on
lymphocytes and raising the possibility of an immune-modulatory effect
on autoimmune disorders including MS; however, the recently completed
CUPID study found no beneficial effects of cannador (2.5 mg δ9THC plus

1.25 mg of cannabidiol) on slowing progression of the disease compared to
placebo (Zajicek et al. 2013).
Two large RCTs have reported on the effects of oral cannador on spastic-
ity in MS. The CAMS study involving 657 subjects demonstrated no differ-
ence in effect between the interventional and placebo treated groups over a
15-week period (Zajicek et al. 2003). However, the 1-year extension phase of
the study showed that the active intervention group did have a significant
reduction in Ashworth scores, suggesting that longer-term treatment may be
required to produce an effect (Zajicek et al. 2005).
The MUSEC study used a patient self-reported category rating scale (CRS)
encompassing subjective muscle stiffness, body pain, muscle spasms, and
quality of sleep as the primary outcome measures. Over a 10-week treat-
ment phase, 279 patients were randomised to either cannador or placebo fol-
lowing dose titration. Although most participants reported improvement on
the parameters of the CRS, the improvements reported were significantly
greater for the cannador-treated group (Zajicek et al. 2012).
Sativex is an oromucosal spray containing 27 mg of δ 9THC and 25 mg of
cannabidiol (per ml, with each metred dose giving 2.7 mg and 2.5 mg, respec-
tively, of each constituent per spray). The oromucosal route leads to quicker
absorption and higher peak plasma concentrations than the oral route, while
avoiding the much higher and unpredictable plasma concentrations that are
a feature of inhaled (smoking) cannabis. This may to some extent explain the
relatively low incidence of psychoactive side effects reported with sativex
and oral cannador.
Two RCTs (Collin et al. 2007, Wade et al. 2004) used an 11-point neurologi-
cal rating scale to assess subjects symptomatic response to sativex on muscle
stiffness. One study reported a 0.5 mean reduction in NRS compared with
placebo for a 6-week treatment phase (Collin et al. 2007); the second showed
no difference in NRS over a 14-week treatment phase (Wade et al. 2004).
Post hoc analysis of subgroups, however, indicated that for some patients
the magnitude of effect was much greater, which introduced the concept of
responders versus non-responders. It is postulated that genetic variation in
CB1 receptors affects ability for long-term potentiation of synaptic transmis-
sion (Mori et al. 2014), which may explain this finding. Two further studies
have since been conducted with a 4-week sativex treatment phase to identify
treatment responders before randomisation to a 12-week RCT for treatment
responders only. These studies showed that for treatment responders sativex
was effective compared with placebo with a least a 30% improvement in
NRS.
A meta-analysis published by Wade et al. calculated that the odds ratio
for improvement in spasticity by sativex in treatment responders is 1.67 (CI)
1.05–2.65, p = 0.030 (Wade et al. 2010).
Clinical trial experience showed that sativex was well tolerated; the most
common adverse effects reported were drowsiness, dizziness, and ataxia.
Sativex is now licensed in the UK for use in patients with moderate to severe
spasticity due to MS who have not responded adequately to other anti-
spasticity medication. However, it is not currently recommended by NICE
for use within the National Health Service in the UK.
7.5.1.7 Benzodiazepines
Benzodiazepines have GABAa-agonistic properties, resulting in pre-synaptic
inhibition of post synaptic poly- and monosynaptic reflexes (Pedersen 1974).
Evidence of efficacy of benzodiazepines is limited to small, poorly con-
trolled clinical trials, the majority of which were comparative studies of
diazepam with baclofen and dantrolene and showed comparable effects
of diazepam in terms of reducing spasticity and muscle spasm (From and
Heltberg 1975, Schmidt et al. 1975). Diazepam was, however, less well toler-
ated and its side effect profile means that it has limited usefulness in prac-
tice, as the dosage required for any effective spasticity reduction produces
unacceptable levels of sedation for the majority of patients.
Problems of dependency and concerns about safety exist, since overdosage
can lead to significant respiratory depression, coma, and death, while abrupt
withdrawal can produce severe anxiety and epileptic seizures.
In practice, the most useful role of benzodiazepines is the control of pain-
ful nocturnal muscle spasm with clonazepam 1–3 mg at night being an effec-
tive regime, which, because of its shorter half-life, is less likely to produce
unwelcome sedation the following day.
7.5.1.8 Evidence-Based Guidelines for Oral Antispasticity Medications:

Spanish and German Consensus Document
Grading the evidence base for the most commonly used anti-spasticity drugs
utilising SIGN guidelines methodology was first reported by Gold and Oreja-
Cuevara following a consensus meeting involving 250 Spanish neurologists
and published in 2013 (Table 7.1) (Gold and Oreja-Guevara 2013). A similar
process was undertaken in Germany using a PubMed literature review to
derive evidence levels and to grade recommendations. The Spanish and
TABLE 7.1
German/Spanish Guidelines for Anti-Spasticity Drugs in MS
Medication Evidence Class Recommendation Grade
Baclofen Ib-II A
Tizanidine 1b A
Gabapentin 1b A
Sativex 1a A
Dantrolene/benzodiazepines Insufficient None
Source: Adapted from Gold, R. and Oreja-Guevara, C., Expert Rev Neurother, 13(12 Suppl),
55–9, 2013.
German guidelines are very similar and contrast with the conclusions of the
draft NICE guidelines for spasticity management, which comment upon the
paucity of good quality evidence to support recommendations in this area.
7.5.1.9 Treatments for Focal Spasticity

Focal spasticity refers to a situation in which increased tone is particularly
problematic and confined to isolated muscle groups where systemic treat-
ment would be inappropriate because of unwanted side effects or a negative
effect of producing muscle weakness in unaffected muscles.
Treatment options are regional nerve blockade with neuroablative agents
such as phenol or direct injection into the affected muscles with botulinum
toxin.
Clinical applications in MS would typically include alleviation of hip
adductor tone “with scissoring” interfering with comfortable seating posi-
tioning or making toileting and perineal hygiene difficult, increased calf
muscle tone producing equino varus-type deformation at the ankle joint,
impairing gait and compromising the fitting of suitable orthoses. Less
commonly in MS finger or wrist flexion tone, compromising function, will
respond to local treatment.
Phenol is significantly cheaper than botulinum and has the advantage that
onset of action is instantaneous.
7.5.1.10 Phenol Chemodenervation
Phenol in a concentration of between 5–7% mixed with glycerine has a neu-
rolytic effect, causing chemolysis of myelin and nerve axons but preserving
the endoneurial tubes, which form a framework for subsequent nerve regen-
eration (Felsenthal 1974). The onset of the anaesthetic effect is instantaneous,
with reduction in spasticity of muscle groups supplied by the chemolyzed
peripheral nerve being observed within 24 hours.
The technique requires an experienced operator and is time-consuming.
Closed-nerve blockade involves identification of individual nerve motor
branches using a needle nerve stimulator in order to avoid injection into sen-
sory nerve fibres, with consequent painful dysaesthesiae for the patient.
Published evidence of the effectiveness of phenol chemodenervation in
MS is sparse, with no RCTs being undertaken and most evidence coming
from case reports or individual physicians’ experiences. Such reports, how-
ever, suggest gains in relation to relief from painful spasm, improved seating
positioning, improved hygiene and personal care, and a reduction in skin
breakdown.
In MS, the technique is most usually reserved for severe lower limb spas-
ticity and involves unilateral or bilateral lysis of the obturator nerve. The
beneficial effects last for between 6–9 months on average and the technique
can be repeated as often as required.
In situations where it is difficult clinically to decide whether severe spas-

ticity or fixed contractures are producing flexion deformities, a similar
motor nerve injection of short-acting local anesthetic can be used to predict
response to chemolysis prior to phenol ablation (Elovic et al. 2009).
7.5.1.11 Botulinum Toxin
Botulinum toxin is derived from the bacterium clostridium botulinum, the
organism responsible for botulism, a severe form of food poisoning charac-
terised by widespread muscular paralysis. However, when injected directly
into individual muscle groups, systemic absorption does not occur and
effects are confined to local limited spread within 30–40 mm of the region
injected.
Botulinum blocks the neuromuscular junction, preventing presynaptic
release of acetylcholine. Seven distinct toxins have been identified but botu-
linum toxin types A and B are the only types manufactured commercially.
Type A is the most effective and most widely used (Hambleton 1992).
There is limited adequately controlled clinical trial evidence of the use of
botulinum toxin in MS related spasticity. Three RCTs have, however, reported
positive effects on hip adductor tone, resulting in reduced spasticity scores,
reduction in painful spasm, and improved hygiene (Snow et al. 1990). A
dose-ranging study reported similar positive outcomes with response rates
being better to higher doses (1500 units total dosage of Dysport) (Hyman
et al. 2000). The positive effects on hip adductor spasticity were confirmed by
a more recent study (Ochudlo 2012). There is evidence that intensive phys-
iotherapy following botulinum injection improves the response, and one
study reported improved outcomes with vibration therapy combined with
botulinum (Paoloni et al. 2013).
Specific muscles to be injected are identified using electromyography,
neurostimulation, or ultrasound guidance. Dosing schedules are dependent
upon the size of the muscle to be injected. Of particular note, the two most
commonly used brands of botulinum, dysport (manufactured by Ipsen)
and botox (manufactured by Allergan), are not interchangeable in terms
of equivalent dosage scheduling and it is important to ensure that the cor-
rect dose for each of these products is used. The onset of action is within
3–5 days post-injection and beneficial effects last for between 3 and 6 months
on average.
Lessening effect with repeat injections may indicate the development
of neutralising antibodies, the incidence of such development has been
reported from as low as 2% of patients treated, up to 44% in different series.
Development of antibodies is proportional to the frequency and number of
total treatment sessions and to the dosage used (Jankovic and Brin 1991).
Treatment is usually well tolerated, the most commonly reported side
effects being transient discomfort at the injection site.
7.5.1.12 Intrathecal (IT) Baclofen

Patients with severe lower limb spasticity not responding to adequate doses
of oral or local anti-spasticity treatment or who are intolerant of side effects
of such treatments may be considered for intrathecal baclofen.
This involves the surgical implantation of a subcutaneous battery-powered
pump with a reservoir containing baclofen in liquid form into the tissues of
the abdominal wall, from which a catheter is fed into the subarachnoid space
allowing microdoses of baclofen to be delivered directly and continuously
into the cerebrospinal fluid (CSF) bathing the lumbar and sacral spine. The
net effect is to deliver concentrations of the drug at the site of action approxi-
mately four times higher than those achieved by oral dosing but with only
1% of the equivalent oral dose (Penn et al. 1989). The most troublesome sys-
temic adverse effects of the drug are thus avoided, with reduced fatigue and
improved cognition being reported by patients.
Prior to surgical implantation patients are usually admitted for a test
dose given via lumbar puncture. The initial dosage of 25 mcg is admin-
istered and the response monitored over a 6-hour period, where a 2-point
drop in the composite Ashworth score summed at hip, knee, and ankle
joints is considered a positive response. If no response is obtained to the
starting dose, increasing dosages of 50 mcg, 75 mcg, and 100 mcg are given
on successive days. If no response is obtained to a dose of 100 mcg then
the definitive procedure to implant the system should not go ahead (Parke
et al. 1989). However, most patients will respond and the dose at which
a response is obtained determines the initial daily starting dose for the
implanted system.
Although few clinical trials have been undertaken specifically in MS
patients there is consistency of reported outcomes in studies with mixed
populations, including those with MS. Penn et al. reported reduced spastic-
ity as measured with the Modified Ashworth scores, improved spasm scores,
improvement in ADL skills, and also improved bladder function in a double-
blind placebo-controlled study with 20 subjects (10 MS and 10 spinal cord-
injury subjects) (Penn et al. 1989).
Although the majority of patients treated with IT baclofen are not ambu-
latory, the use of newer programmable pumps has extended treatment to
patients who retain mobility with successful symptom improvement with-
out mobility impairment (Lee et al. 2017).
Long-term efficacy of intrathecal baclofen in MS patients was reported by
Yardley et al., who undertook a retrospective review of patients treated with
IT baclofen pump at the National Hospital for Neurology and Neurosurgery
in London between 1997 and 2013 (Yardley et al. 2013). Data was obtained for
71 subjects, with a mean follow-up period of 3.54 years. Objective improve-
ments in spasticity, as measured by the Ashworth scale, and patient-reported
outcomes of reduced spasm, stiffness, pain, and discomfort were recorded
and 56 of the subjects had been able to completely discontinue previous oral
anti-spasticity medication. Adverse events were low but 10 subjects experi-

enced intrathecal catheter dysfunction requiring replacement.
Generally, adverse events including drowsiness, headache, and hypoten-
sion occur in less than 5% of patients undergoing the procedure once the
dose titration phase is completed.
Baclofen pump implantation is expensive, both in terms of neurosurgi-
cal expertise and time and the cost of the pump, and is therefore generally
reserved for people who have had a full exposure to alternatives, oral, and/
or local treatments for spasticity.
7.5.2 Non-Pharmacological Treatments
Almost one-third of those with MS take no medications for their spasticity
(Flachenecker 2013) and rely on non-pharmacological methods of manage-
ment. Between 50% (Rizzo et al. 2004) and 78% (Flachenecker 2013) of people
with MS are referred to physiotherapy for spasticity management.
A Cochrane review in 2013 evaluated the evidence for non-pharmacological
interventions for spasticity in MS (Amatya et al. 2013). The review identi-
fied only 9 randomised controlled trials, of which 3 studied treatments in
combination, e.g., botulinum toxin injection with or without physiotherapy.
The studies focussed on a range of interventions; physical activity (exercise,
yoga, sports climbing), whole-body vibration (WBV), transcutaneous electri-
cal nerve stimulation (TENS), transcranial magnetic stimulation (TMS), and
electromagnetic therapy.
The review reported that the studies were generally of low methodological
quality and used a range of therapies, outcome measures, and heterogeneous
patient populations such that a meta-analysis of the results of studies on
non-pharmacological management of spasticity in MS was not possible. The
overall conclusion of the Cochrane review was that there was “low-level”
evidence that physiotherapy provides some added benefit to injection with
botulinum, up to 12 weeks after injection; 2 weeks of intermittent theta burst
stimulation (iTBS) reduces spasticity (either in isolation or combined with
physiotherapy); transcranial magnetic stimulation (TMS), and pulsing mag-
netic field reduce spasticity in the short term.
There was no evidence that TENS, WBV, or sports climbing reduced spas-
ticity. Due to the small number of studies and the relatively poor overall
quality of the studies, the review concluded that the effectiveness of most
non-pharmacological interventions for spasticity in MS is unproven and that
larger, more methodologically robust studies are required.
It is clear, then, that, like many pharmacological treatments, further robust
research is required before non-pharmacological interventions can with con-
fidence be recommended for the management of spasticity in people with
MS. In determining the future direction and the research priorities within
this field it is important to look in more detail at studies that have previously
been undertaken, and that may or may not have been included within the
Cochrane review or that have been published more recently.
7.5.2.1 Physical Activity/Exercise for the Management of Spasticity in MS

Tarakci et al. (2013), in a paper published since the Cochrane review, dem-
onstrated that a 12-week, thrice-weekly group exercise programme consist-
ing of balance, strengthening, stretching, and functional activities led to
statistically significant reduction in lower limb spasticity as assessed by the
Modified Ashworth Scale (MAS) (Tarakci et al. 2013). As well as improving
the spasticity of the lower limb muscle groups (hip flexors, hamstrings, and
soleus) there was also an improvement in walking speed and stair climb-
ing, which may or may not have been related to the reduction in lower limb
spasticity.
Velikonja et al. (2010) evaluated the effectiveness of sports climbing and
yoga, once a week for 10 weeks, on a range of outcome measures in 20 people
with MS. Neither intervention reduced spasticity as measured by the MAS,
but the pyramidal function component of the EDSS reduced in the climb-
ing group (Velikonja et al. 2010). The authors proposed that when climbing
downwards the lower limbs would be weightbearing and stretched, thus
potentially reducing spasticity. They also suggested that sports climbing
generally improves strength, balance, and co-ordination and may facilitate
neuroplasticity.
In terms of combined interventions, Giovanelli et al. (2007) demonstrated
that botulinum toxin injections were effective in reducing spasticity, as mea-
sured by the Modified Ashworth Scale and a visual analogue scale; however,
the addition of physiotherapy for 15 days after the injection augmented the
effect. Physiotherapy was described as active and passive exercise, stretch-
ing, and strengthening (Giovannelli et al. 2007).
One of the challenges in interpreting the results of physical interventions
to reduce spasticity in people with MS, and indeed in other neurological
conditions, is that interventions that are described as single interventions,
for example, exercise or physiotherapy, are actually interventions that have
a number of components, such as stretching, active muscle contraction,
balance activity, etc. Future studies are required to examine the effects of
physical interventions for the management of spasticity by systematically
manipulating the frequency, intensity type, and time (FITT) of activity and
evaluating the resultant effect of spasticity in people with MS.
7.5.2.2 Transcutaneous Electrical Nerve Stimulation (TENS)

for the Management of Spasticity in MS
Transcutaneous electrical nerve stimulation (TENS) is a non-invasive ther-
apy where electrical stimulation is applied to pads on the skin that stimulate
low-threshold mechanoreceptors. Although the focus of its clinical use is

in the management of pain, there is some evidence to suggest that TENS
is effective in reducing spasticity in neurological conditions such as stroke
(Karakoyun et al. 2015, Laddha et al. 2016) and cerebral palsy (Alabdulwahab
and Al-Gabbani 2010). There are few studies investigating the effects of TENS
on spasticity in MS.
The first study of the effects of TENS in MS that considered spasticity as
an outcome measure, in this case the primary outcome measure, was a small
pilot study of 10 people with MS (Armutlu et al. 2003). This study used mus-
cle electromyography to assess spasticity along with the MAS. The study
reported that 20 minutes of TENS per day for 4 weeks significantly reduced
lower limb spasticity in people with MS, although there was no control
group in this study.
Miller et al. compared a 1-hour and 8-hour daily application of TENS for
2 weeks in terms of spasticity, pain, and spasm (Miller et al. 2007). The Global
Spasticity Score was used, which encompasses the MAS, the clonus score,
and the patellar tendon reflex. Spasm was assessed with the Penn Spasm
Scale and pain using a simple visual analogue scale. Neither TENS applica-
tion time resulted in a statistically significant reduction in lower limb spas-
ticity, although there was more improvement with the 8-hour application
as compared to the 1-hour application. However, pain and spasm reduced
significantly when using TENS for 8 hours per day. The small but non-
significant effect on spasticity, as measured by the Global Spasticity Scale,
was encouraging, but longer-term studies are required. No adverse events
were reported.
In a more recent study, Shaygennejad et al. (2013) compared 4 weeks
of oral baclofen (10 mg twice daily for 1 week, then 25 mg twice daily for
3 weeks) with 4 weeks of TENS in people with MS and lower limb spasticity
(Shaygannejad et al. 2013). The results demonstrated that spasticity, as mea-
sured by the MAS, reduced in both groups but more so in the TENS group.
Of note, four of the participants in the baclofen group had to withdraw to
adverse side effects.
In all three studies the TENS settings were similar (a pulse frequency of
100 Hz and a pulse width of 0.25–0.3 ms). Taken together, there is some evi-
dence of the benefits of TENS for the management of spasticity in MS. One
of the advantages of TENS, like many other non-pharmacological interven-
tions, is that it is non-invasive and therefore there are few side effects beyond
skin irritation from the application of electrodes. Against that, TENS requires
some set-up by the person with MS (or assistance of someone else) and it
is more useful for focal, as opposed to general, spasticity. So perhaps the
limited evidence would support that clinicians consider TENS for patients
with good upper limb function and focal spasticity, whereas for those with
more generalised spasticity, pharmacological management may be more
efficacious and appropriate. The optimum management strategy may be a
combination of pharmacological and non-pharmacological interventions,

but this requires further investigation.
7.5.2.3 Transcranial Magnetic Stimulation

for the Treatment of Spasticity in MS
Transcranial magnetic stimulation (TMS) is a commonly used non-invasive
investigative method of activating the brain. Traditionally used as a tool in
human neurophysiological studies, recent developments in stimulator design
have created interest in its therapeutic use through an ability to produce
localised repetitive or high-frequency burst stimulation of cortical areas.
In MS, the number of studies investigating the effects of TMS on spastic-
ity is currently limited, but there is evidence emerging that repetitive TMS
(rTMS) or intermittent theta burst TMS (iTBS) protocols can evoke sustained
reductions in markers of spasticity and that these effects can be potentiated
and impact on function when combined with exercise therapy (Centonze et
al. 2007, Mori et al. 2010, Mori et al. 2011).
Centonze et al. (2007) initially demonstrated that repeated daily sessions
of 5-Hz rTMS over a 2-week period when directed to cortical areas project-
ing to the spastic leg of MS patients resulted in a reduction of the H-reflex/
M-wave ratio and a reduction in spasticity as measured using the Modified
Ashworth scale (MAS). These changes persisted for at least 7 days follow-
ing the termination of rTMS treatment. Single or sham rTMS sessions had
no effect. This work was further expanded to investigate the action of iTBS
on spasticity in MS patients (Mori et al. 2010) and later used in combina-
tion with exercise therapy in a double-blind, sham controlled trial (Mori et
al. 2011). When studied alone, iTBS (Mori et al. 2010), like rTMS (Centonze
et al. 2007), reduced spasticity as measured by MAS and also decreased
H-reflex excitability. The effects observed with iTBS were achieved at lower
stimulation intensities when compared with rTMS, making this a more
practical therapeutic approach. In these studies, the authors suggest that
the observed effects on spasticity from rTMS and iTBS could result from
induced neuroplasticity changes brought about by repetitive corticospinal
conditioning of spinal circuits mediating presynaptic inhibition. While the
mechanism of action of rTMS and iTBS require further research, the iTBS
protocol, when used in combination with exercise therapy, showed signifi-
cant reduction in spasticity when measured with the MSSS-88 (Mori et al.
2011). In addition, fatigue, ADL, and quality of life improved for people
with MS treated with exercise and iTBS in combination. The results of this
initial trial suggest that exercise therapy and iTBS, when combined, signifi-
cantly improve spasticity and the functional consequences associated with
spasticity. The mechanism by which this combined effect is seen is not fully
understood, it may be that iTBS “primes” the motor cortex to anticipate the
neuroplastic adaptations that may occur with repetitive exercise therapy.
The changes in endogenous neurotransmitters and genetic expression may

also explain these results.
7.5.3 Other Non-Pharmacological Interventions

for the Management of Spasticity in MS
Hippotherapy is an alternative or complementary therapy where the move-
ment of the horse affects the movement of the patient’s trunk and pelvis in
such a way as to elicit righting and balance reactions. A few studies, involving
relatively small numbers of participants, have shown hippotherapy to have a
positive effect on balance in people with MS (Bronson et al. 2010, Silkwood-
Sherer and Warmbier 2007). The mechanism by which this occurs has not
been investigated. Although a reduction in spasticity may partly explain the
results observed, no studies have included an evaluation of spasticity within
their outcome measures, thus the effect of hippotherapy on spasticity in MS
has yet to be elucidated.
Although there is anecdotal evidence that Lycra garments may be effec-
tive in reducing spasticity in people with neurological conditions, equivocal
results have emerged from the few studies undertaken (Elliott et al. 2011,
Watson et al. 2007) and no studies have specifically investigated the effec-
tiveness of Lycra garments in MS.
Neuromuscular electrical stimulation cycling (NMES) has mainly been
investigated following spinal cord injury. In NMES, the patient is seated
on a recumbent exercise bicycle and electrical stimulation is applied to the
affected, large muscle groups of the leg in a manner that allows the indi-
vidual to cycle. One study has examined the effectiveness of NMES in MS
where increases in the volume of the thigh were reported and anecdotally 2
of the 8 participants recounted a reduction in spasticity, although this was
not formally determined (Fornusek and Hoang 2014).
Whole-body vibration (WBV), where users stand on a vibrating platform,
has been shown to have some positive effects on increasing muscle strength
in MS (Schyns et al. 2009) and in improving mobility in those less severely
disabled (Kantele et al. 2015). In terms of its effect on spasticity in MS, one
study demonstrated that 4 weeks of thrice-weekly exercise with WBV
reduced the spasm score of the MSSS-88 compared to 4 weeks of exercise
alone (Schyns et al. 2009). There was no effect on the MAS or other functional
outcome measures such as the timed up and go (TUG). As with other studies
this was a small pilot study with only 16 participants, 4 of whom failed to
complete the crossover study due to the WBV exacerbating an existing knee
problem (n = 1) and being unable to commit to attending the therapy centre
3 times per week (n = 3). A recent systematic review suggested there was
insufficient evidence to support the use of WBV in MS (Huang et al. 2017).
In summary, and in agreement with the results of the Cochrane review,
there is limited and early evidence that some non-pharmacological interven-
tions (e.g., iTBS, exercise, TENS) might have a positive effect on spasticity for
people with MS. There is an urgent need to move beyond small-scale pilot
studies to undertake larger-scale multi-centre trials of these interventions to
improve the evidence base to support or refute the use of these interventions
in clinical practice.
7.5.3.1 Surgery
Orthopaedic surgical procedures are generally undertaken for the conse-
quences of spasticity, i.e., fixed contractures causing pain or interfering with
function; either ambulation or positioning for sitting.
Tenotomy or tendon-lengthening procedures are undertaken to allow posi-
tioning of joints into more natural angles, for example, achilles tenotomy will
allow an inverted and flexed ankle joint to be placed into a more neutral and
functional position to improve the gait pattern and ambulation or to facilitate
fitting of an appropriate orthosis (Waters et al. 1982). Similar procedures can
be undertaken on the hamstrings to allow a greater range of knee flexion or on
the hip adductors to facilitate positioning for improved toileting and hygiene.
Selective dorsal rhizotomy, first described over 100 years ago by Foerster
as a potential treatment for spastic diplegia associated with cerebral palsy,
involves selectively sectioning afferent nerve roots in the dorsal horn of the
spinal cord, eliminating over-excitatory sensory stimulation of the reflex arc.
The technique has been refined to limit the invasiveness of the surgical lami-
nectomy required to expose the nerve roots and to allow much more selectiv-
ity of the individual nerve roots to be electrically ablated. Modern approaches
now ensure preservation of proprioceptive afferent input using intra-operative
electrophysiological identification of individual nerve fibres to be sectioned.
Dorsal rhizotomy is now widely used with generally good functional out-
comes in children and adults affected by cerebral palsy; however, experi-
ence is limited in adults with other neurological disorders. A recent review
of the use of the procedure in adults with conditions other than cerebral
palsy identified 74 MS patients who had undergone the procedure in North
America (Gump et al. 2013). One study had specifically focused on MS with
15 subjects included where pre-operatively 11 subjects were completely bed-
ridden and 4 were wheelchair-dependent. Post-operatively, 8 were ambulant
with crutches, 4 used wheelchairs, and only 2 remained bedridden.
Further prospective studies, specifically in MS patients, are required before
the technique can be considered as an established treatment.
7.5.4 Strategy for the Management of Spasticity in MS

Management of spasticity in MS is a multidisciplinary process and a recent
consensus framework confirms treatment should be firmly based upon
assessment, negotiation, and goal-setting (Turner-Stokes et al. 2017).
Assessment consists of identifying functional difficulties or troublesome
symptoms from the perspective of the patient and their carers, as appropriate.
The presence of increased tone is of itself not a reason to intervene. Indeed,

increased tone may have some benefits for the patient compensating for
muscle weakness and allowing improved mobility or transferring ability.
Once functional impairment/troublesome symptoms (e.g., pain, spasm)
have been identified a full clinical assessment should be undertaken to iden-
tify affected muscle groups and the extent to which problems are focal, i.e.,
localised to a particular muscle group or region, or more generalised affect-
ing muscles in different anatomical regions.
The severity of the spasticity should be recorded, with the Modified
Ashworth Scale being the most frequently used assessment in MS. Any exac-
erbating factors should be clearly identified and recorded.
Differentiating between severe spasticity and fixed contractures may
sometimes be difficult and regional anaesthetic blocks can be helpful in dif-
ferential diagnosis and may prevent inappropriate treatment.
Goal-setting follows on from assessment and involves a partnership
approach with the patient identifying outcomes that are important to them,
and may include relief of pain, improved mobility, functional capability, and
improved seating position.
Outcomes have to be realistic and achievable, taking into account the degree
of spasticity, muscle groups affected, and natural history of the condition.
Knowledge of disease-modifying treatments is essential. With the introduc-
tion of more effective drugs to control disability progression assumptions
that disability levels (and degree of spasticity) will inevitably continue to
increase may no longer be valid. There is some evidence that such an effect
can be seen in terms of treatment with glatiramer acetate, a current first-line
drug for treatment of RRMS. The ESCALA study showing improvement in
terms of spasm frequency, muscle tone, and pain in patients who switched
DMT from β-interferon to glatiramer (Meca-Lallana et al. 2012).
Initial phases of management involve elimination, where possible, of nox-
ious stimuli that affect afferent input, pain (neuropathic or nociceptive),
pressure ulcers, bladder symptoms including recurrent infections, bladder
instability/dysynergy, acute relapse/inflammatory activity of the underlying
illness. This may involve obtaining up-to-date MRI imaging of brain and spi-
nal cord with gadolinium enhancement. Optimising management of these
factors should always be the first step in management of spasticity and spasm.
With both generalised and focal spasticity where the degree of spasticity
is moderate (MAS < 2) the patient should first be referred for physiotherapy
(see above).
Where spasticity is more extensive or not adequately responding to physi-
cal therapy the next level of intervention will depend upon whether the
spasticity is generalised or focal. For generalised spasticity, initial treatment
should be with one of the first-line agents baclofen, tizanidine, or gabapen-
tin. Dosage should start at a low total daily dose titrating upwards at 3-day
intervals until the desired effect is obtained or the patient experiences intol-
erable adverse effects.
If sufficient control of spasticity is not obtained, combining first-line ther-

apies, e.g., baclofen plus gabapentin, should be the next step. Second-line
treatments, such as dantrolene or sativex, should be introduced where com-
binations of first-line drugs are ineffective or not tolerated.
Treatment failure should trigger assessment for intrathecal baclofen ther-
apy or surgery especially where lower limb spasticity is causing difficulties
in seating position or toileting.
With focal spasticity not responding to physical therapy, botulinum
toxin is the first-line approach to management; such treatment needs to be
combined with vigorous physiotherapy stretching to produce an optimal
response (Giovanelli et al. 2007). Longer-term control of focal spasticity may
be obtained by regional nerve ablation with phenol.
Multidisciplinary reassessment of the effectiveness of treatment to ensure
continued response and to determine whether additional measures are
required is essential, particularly in an often-progressive condition such as
MS.
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8
Clinical Assessment and Management
of Spasticity and Contractures
in Traumatic Brain Injury
Gerard E. Francisco and Sheng Li
CONTENTS
8.1 Introduction................................................................................................. 204
8.2 Impact of Contractures and Spasticity on Recovery............................. 206
8.3 Clinical Presentations................................................................................ 207
8.4 Brain Injury Complications That May Worsen Spasticity.................... 209
8.5 Treatment Goals.......................................................................................... 209
8.5.1 Case 1................................................................................................ 210
8.6 Assessment.................................................................................................. 212
8.6.1 Clinical Assessment....................................................................... 212
8.6.2 Biomechanical Assessment........................................................... 214
8.7 Management................................................................................................ 216
8.7.1 Physical Modalities......................................................................... 216
8.7.2 Stretching and Casting for Contracture vs. Spasticity
Management.................................................................................... 217
8.7.3 Electrical Stimulation..................................................................... 218
8.7.4 Oral Medications............................................................................. 219
8.7.5 Focal Therapies................................................................................ 220
8.7.5.1 Botulinum Toxins............................................................ 220
8.7.5.2 Case 2.................................................................................222
8.7.5.3 Phenol and Alcohol Neurolysis.....................................223
8.7.6 Intrathecal Therapies......................................................................223
8.7.7 Surgical Interventions.................................................................... 226
8.7.8 Controversial and Promising Treatments................................... 227
References.............................................................................................................. 227
203
8.1 Introduction
Disruption of upper motor neuron (UMN) pathways following a traumatic
brain injury (TBI) results in a multitude of clinically meaningful sensori-
motor limitations, among which is spasticity. Almost always, spasticity,
along with muscle-shortening due to paralysis and immobilisation, leads to
soft tissue and joint contractures, which further aggravate the loss of range
of motion and limb movement. Muscle contracture, or shortening of muscle
length, often develops when paralyzed muscles are immobilised as early as
2 weeks (Verplancke et al. 2005). In addition, immobilisation in a shortened
position often facilitates muscle fibre loss and atrophy, accumulation of intra-
muscular connective tissue, increased fat infiltration, degenerative changes
at myotendinous junctions, and may further result in an increase in mechan-
ical spindle response by stretch (Gracies 2005). Therefore, muscle shortening
is also often accompanied by a similar phenomenon in other soft tissues,
including fascia, nerve, blood vessels, ligament, and skin. Contracture and
spasticity often co-exist and, taken together, they constitute significant com-
ponents of a vicious, mutually augmenting cycle (Botte et al. 1988; O’Dwyer
et al. 1996; Gracies 2005) (Figure 8.1). As a result, a patient with TBI and spas-
ticity not only has limited functional abilities but also has challenges in par-
ticipating in a rehabilitation programme to promote recovery.
Unlike in stroke, very little has been published regarding the incidence
of spasticity following TBI. Potential reasons for this include the fact that
majority of TBI are mild and without sensorimotor complications; the lack
of universal criteria for diagnosing spasticity and distinguishing it from
related conditions, such as dystonia; and that most studies report spasticity
incidence in those with acquired brain injuries, which include non-traumatic
aetiologies. Another major reason is that the distinction between spasticity
and contractures is often unclear. Estimates of the incidence of contracture
in TBI are limited by the potential co-existence of spasticity. In an inves-
tigation of 75 persons with ‘craniocerebral trauma’ consecutively admit-
ted to inpatient rehabilitation, contractures were found in as many as 84%
within a 12-month period, but it is unclear how many of these had co-morbid
spasticity (Yarkony and Sahgal 1987). In a more recent study (Singer et al.
2004) of 105 persons with moderate-to-severe non-traumatic and traumatic
brain injuries admitted to a rehabilitation unit, contracture was observed
less frequently. Only 17 (16.2%) had ankle contracture, which was found to
correlate closely with spastic hypertonia. Using the Ashworth Scale, spastic-
ity was detected in only 13.3%. An additional 21.9% were classified as hav-
ing dystonic muscle overactivity at rest and during volitional movement or
change in body position. At our facility, spastic hypertonia as measured by
the Modified Ashworth Scale was detected among 25.8% of 120 consecutive
persons with TBI admitted to inpatient rehabilitation directly from acute
trauma or neurosurgical care (Le et al. 2000).
Spasticity and Contractures in TBI 205
Interruption/damage
of corticospinal Loss of supraspinal
pathways inhibition
Negative UMN Positive UMN

findings findings
Weakness Muscle overactivity,

incoordination spasticity
Immobilization due Immobilization due

to paralysis to tightness
Contracture Hypertonia
FIGURE 8.1
Development of contracture due to spasticity and immobilisation.
Contracture can occur as early as 14 days in the ankle joint after a severe
TBI (Verplancke et al. 2005). However, the incidence of contracture after TBI
varies across major joints. In a prospective study of 105 patients with a new
diagnosis of moderate-to-severe brain injury over a 12-month period, there
was a 16.2% contracture rate (Singer et al. 2004). Pohl and Mehrholz (2005)
reported that 56% of 50 patients with severe cerebral damage had a contrac-
ture in at least one shoulder. Yarkony and Sahgal (1987) documented con-
tractures in the hip (81%), shoulder (76%), ankle (76%), and elbow (44%) joints
within a 1-year period among 75 patients with TBI. Risk factors for develop-
ment of contracture include spasticity (Singer et al. 2004), severity of injury
(Singer et al. 2004; Pohl and Mehrholz 2005), and duration of coma (Yarkony
and Sahgal 1987; Pohl and Mehrholz 2005). Pohl et al. (2007) also suggested
that contractures may be associated with reduced non-spastic positive fea-

tures of the upper motor neuron syndrome, such as reduced involuntary
muscle activity in a stretched position in patients with severe brain damage.
8.2 Impact of Contractures and Spasticity on Recovery

Spasticity and contracture usually co-exist in muscles that are shortened
in patients with TBI, such as the shoulder adductors and internal rotators,
elbow flexors, forearm pronators, and wrist and finger flexors in the upper
extremity. Often, the presence of contracture influences assessment of spas-
ticity in patients with severe brain injury, particularly in the shoulder and
hand (Mehrholz et al. 2005).
Contractures are more likely to develop in patients who do not recover
motor function. Malhotra et al. (2011) examined the time course of develop-
ment of spasticity and contractures at the wrist after stroke in a longitudinal
observational study. Spasticity was measured by quantifying muscle activ-
ity during passively imposed stretches at two velocities. Contractures were
measured by quantifying passive range of movement and stiffness. Upper
limb functional movement was assessed using the action research time test.
Thirty patients who had no arm function within the first 6 weeks of stroke
were followed for 36 weeks. Twenty-eight (92%) patients developed spastic-
ity throughout the study period. Patients who recovered arm function (n =
5) showed signs of spasticity at all assessment points but did not develop
contractures. Patients who did not recover useful arm function (n = 25) had
signs of spasticity and abnormalities associated with contracture formation
at all time points tested. The findings from this study highlight the impor-
tance of early interventions to prevent development of contracture. Physical
modalities such as stretching, casting, and splinting are beneficial for this
purpose. Electrical stimulation has shown some evidence in reducing the
rate of contracture formation (Malhotra et al. 2013).
Presence of lower extremity spasticity may be used as a clinical marker
to predict recovery of ambulation after TBI. Lower extremity spasticity is a
sensitive (71.4%) and specific (81.5%) predictor of the inability to ambulate
at discharge. The absence of lower extremity spasticity, however, was a bet-
ter predictor of ambulation recovery than the presence of spasticity was a
predictor of non-ambulatory status at hospital discharge (Dumas et al. 2003).
In some situations, however, spastic hypertonia that results in extension of
lower limb muscles may be beneficial in situations where weakness pre-
cludes the ability to maintain the upright posture during standing activities
and walking. Although spasticity does not consistently hinder functional
recovery, early management has shown to be beneficial for recovery (see
Section 8.7).
8.3 Clinical Presentations
While the underlying aetiologies and anatomic lesions vary, the clinical pre-
sentations of spasticity, along with contractures, are not dissimilar from
other conditions involving any insult to the brain. While the primary lesion
in stroke is typically unifocal, in TBI multiple areas in both cerebral hemi-
spheres may be involved in the development of spasticity and hence a mixed
pattern of clinical presentation may be observed. Thus, the ‘classic hemiple-
gic’ posture often seen in stroke, characterised by shoulder internal rota-
tion and adduction, forearm pronation, elbow, wrist, and finger flexion, knee
extension, ankle plantarflexion, and toe flexion, may not be observed in per-
sons with TBI. Instead, both sides of the body may be involved with varying
degrees of spasticity of muscles within a limb. In some persons with TBI,
spasticity is limited to only one or two muscle groups and is not significant
enough to warrant treatment. Table 8.1 lists muscles that may be involved in
commonly observed postural abnormalities due to spasticity.
In evaluating spasticity in persons with TBI, a clinician should astutely
assess not only the severity of spasticity and extent of muscle involvement,
but also discern how much of the presenting problem is due to weakness
versus spasticity. For instance, when a person with TBI walks with hip cir-
cumduction, knee hyperextension, and a foot drop, two possible underlying
problems include weakness of the hip flexors, knee flexors, and ankle dor-
siflexors, or spasticity of the hip extensors, knee extensors, and ankle plan-
tarflexors. Different permutations of these possibilities may account for the
presenting abnormality in gait and influence a clinician’s choice of interven-
tions (e.g., oral medication, botulinum toxin injection, or intrathecal baclofen,
with or without a concurrent strengthening programme).
An interesting and clinically challenging sequela of traumatic brain injury
that is often observed in those in vegetative or minimally conscious states
is paroxysmal sympathetic hyperactivity, a prominent feature of which is
posturing either in the decorticate or decerebrate pattern. An international,
multidisciplinary consensus group (Baguley et al. 2014) described this syn-
drome as:
recognised in a subgroup of survivors of severe acquired brain injury, of simul-

taneous, paroxysmal transient increases in sympathetic [elevated heart rate,
blood pressure, respiratory rate, temperature, sweating] and motor [posturing]
activity.
In the past, different terms have been used to describe this syndrome, includ-
ing ‘autonomic storming’, ‘dysautonomia’, and ‘paroxysmal autonomic instabil-
ity with dystonia’. The motor posturing part is often viewed as a severe form of
spasm or spasticity and is frequently managed as such, in addition to treatment
efforts to control the underlying sympathetic hyperactivity. Francois et al. (2001)
TABLE 8.1
Muscles Potentially Involved in Common Postural Abnormalities Due to Spasticity
Postural Abnormality Muscles Potentially Involved
Shoulder adduction Pectoralis major
Latissimus dorsi
Coracobrachialis (especially when shoulder is
flexed forward)
Shoulder internal rotation Subscapularis
Teres major
Pectoralis major
Elbow flexion Brachialis
Biceps
Brachioradialis
Pronator teres
Elbow extension Triceps
Forearm pronation Pronator teres
Pronator quadratus
Wrist flexion Flexor carpi radialis
Flexor carpi ulnaris
Wrist extension Extensor carpi radialis
Extensor carpi ulnaris
Metacarpophalangeal (knuckle) flexion Lumbricals
Finger flexion Flexor digitorum superficialis (proximal phalanx)
Flexor digitorum profundus (distal phalanx)
Thumb flexion Flexor pollicis brevis (proximal)
Flexor pollicis longus (distal phalanx)
Trunk flexion Quadratus lumborum
Lattisimus dorsi
Hip flexion Psoas
Iliacus
Rectus femoris
Hip extension Gluteus maximus
Hip adduction Adductor complex
Knee extension Quadriceps complex
Knee flexion Hamstrings
Gastrocnemius
Ankle plantarflexion Gastrocnemius
Soleus
Tibialis posterior
Flexor digitorum longus
Flexor hallucis longus
Ankle inversion Tibialis posterior
Tibialis anterior
Extensor hallucis longus
Great toe hyperextension Extensor hallucis longus
Small toe flexion Flexor digitorum brevis (proximal)
Flexor digitorum longus (distal)
reported successful treatment of this condition recalcitrant to conventional

treatment with intrathecal baclofen. The successful outcome may have not
been solely due to the well-known spasmolytic effect of baclofen, but to a sym-
patholytic effect of this GABA (gamma amino butyric acid) agonist.
8.4 Brain Injury Complications That May Worsen Spasticity

Traumatic brain injury results in a wide spectrum of medical complications.
In a retrospective study that reviewed medical complications of 116 patients
in 2000–2006, the authors reported urinary incontinence in 32.7%, heterotopic
ossification (HO) in 18.1%, and post-traumatic seizure in 13.8% on admission to
rehabilitation (Safaz et al. 2008). These medical complications and their treat-
ment may interact with spasticity. For example, HO is reported to be signifi-
cantly associated with spasticity after a TBI. In a total of 107 TBI patients with
spasticity, HO was present in 40 patients (Dizdar et al. 2013). In the experience
of many clinicians, a sudden change in spasticity may result from progression
intracranial complications, such as hydrocephalus, or co-morbidities, among
which urinary tract infections are commonly observed. Medications used to
treat TBI-related complications, such as psychostimulants used to treat inat-
tention, benzodiazepines to manage agitation, and anti-epileptics, have also
been observed to affect spasticity. Zafonte et al. (2004) suggest assessment of
spasticity several times per day, since muscle tone may be affected by medica-
tions, procedures, and other medical conditions, such as pain.
8.5 Treatment Goals
When planning interventions for spasticity, setting goals is of prime impor-
tance to help focus the type and course of therapies, and manage outcome
expectations. It is not uncommon for a patient to desire recovery to ‘normal’,
or close to normal, anatomy and function following treatment, but often this is
not possible. Other typical goals include reduction in pain, easy use of ortho-
sis, and decrease in caregiver burden. Many clinicians, on the other hand,
focus on technical outcomes, such as reduction in spasticity as measured by
the Ashworth or Tardieu scales, and improvement in range of motion, despite
these scales having limited validity. Thus, a common challenge encountered
in the clinical setting is how to accommodate the seemingly diametric goals
identified by the patients, their caregivers, and clinicians.
Esquenazi et al. (2013) categorised goals, identified by the patient, as either
‘active’ or ‘passive’. The former refers to tasks that are performed by the
TABLE 8.2
Examples of Passive and Active Spasticity Treatment Goals
Passive Active
Prevention of contractures and Increased active movement
deformities Improved ability to transfer from one surface to another
Spasm and pain relief Improved ankle dorsiflexion (‘heel strike’) during gait
Improved splint wear Increased ability to pick up and release objects with the
Facilitated hygiene hand
patient, while the latter, for the patient. Examples are illustrated in Table
8.2. This is a systematic way to define treatment objectives, in that it helps
define further higher-order goals and therapy needs. Achievement of so-
called active goals should not be seen as an end, but rather signals the need
for re-assessment of other interventions, as illustrated by the following case
(Figure 8.2).
8.5.1 Case 1
Mr AS is a 49-year-old male who suffered a non-penetrating brain injury
from a motorcycle crash 2 years ago. He was discharged from therapies due
to ‘lack of progress’ in recovering left arm function. He identified ‘difficulty
extending elbow to reach’. He is able to grasp small objects, but is unable
to open his hand volitionally to release objects. He is also unable to wear a
hand splint and is concerned that he is unable to clean his hand well. He has
been taking baclofen 10 mg twice daily, until a few weeks before review.
On examination while seated, the left elbow was held in 75 degrees of flex-
ion. The forearm was fully pronated, the wrist was flexed about 30 degrees
and the fist clenched (thumb fully flexed underneath the fingers, which are
FIGURE 8.2
Case 1: 49-year-old male with TBI and spastic left upper limb.
also fully flexed at both proximal and distal interphalangeal joints). He was
able to actively extend the elbow through about 30 degrees from the resting
position. He was able to actively extend the fingers, but not enough to open the
fist. In the supine position, the following were the Ashworth and Tardieu find-
ings (Tables 8.3 and 8.4).
Mutual treatment goals were as follows: passive (1) relax finger and thumb
flexors to allow hand hygiene; and passive (2) wear hand splint to prevent
worsening of finger contractures; active (1) decrease elbow flexor tightness to
increase reaching ability; and active (2) release objects from hand grasp. He
received botulinum toxin injection to the biceps, brachialis, brachioradialis,
flexor carpi ulnaris and radialis, pronator teres and quadratus, flexor digitorum
superficialis and profundus, lumbricals, and flexor pollicis longus. Four weeks
post-injection, there was dramatic improvement in Ashworth and Tardieu
scores, and he recovered more active elbow extension, forearm supination, and
hand opening. Based on these changes, new therapy goals were identified:
1. Serial casting to provide sustained stretch to the finger flexors, fol-

lowed by re-fitting for a static hand splint;
2. Functional electrical stimulation of wrist and finger extensors to
facilitate hand opening during functional activities;
3. Functional re-training for object reaching, grasping, and release.
The above scenario is desirable to many, as the patient was able to recover
more active movement, which has made it possible for further functional
re-training, even after 2 years post-TBI. The appropriate intensity and
task-specificity of the exercise programme, in turn, can facilitate cortical
re-organisation and plasticity that translates to functional improvement.
The evidence of efficacy of constraint-induced movement therapy in TBI is
limited, but should not be discounted in light of the robust literature in the
stroke population (Hakkennes and Keating 2005).
Given the complexity of spasticity’s impact on function and wellness, both
passive and active goals usually co-exist in one individual. Teasing out the
individual goals may help identify specific treatments to address each goal
TABLE 8.3
Case 1: Ashworth Scale Scores
Muscle Group Ashworth Score
Elbow flexors 3
Elbow extensors 1
Wrist flexors 1
Wrist extensors 1
Finger flexors 3
Finger extensors Unable to test
Thumb flexors 4
TABLE 8.4
Case 1: Tardieu Scores
Tardieu Spasticity
Joint Tardieu Spasticity Angle Grade
Elbow flexion 15 degrees 2
Elbow extension 25 degrees 1
Wrist flexion 0 degrees 2
Wrist extension 5 degrees 0
Finger flexion Unable to test 2
Finger extension (PIP) Approx. 10 degrees 0
Thumb flexion Unable to test 1
Thumb extension (distal) Approx. 10 degrees 0
and prioritise the timing of interventions. While achievement of passive

goals is largely meant to correct anatomic deformities and posture or as a
means to prevent further complications, successful control of spasticity of the
finger flexors may allow subsequent splinting efforts that will help prevent
recurrence, or worsening of the clenched fist deformity. It is also important
to remember that as a person recovers form a brain injury, the characteristic
and impact of spasticity changes over time, perhaps as a reflection of recov-
ery of upper limb movement (Katz et al. 1998). Thus, a regular re-assessment
of functional status and re-identification of goals, and thus further treatment
plan, should be carried out, as illustrated in the case above.
Most goal-setting is done ‘informally’, in that the patient and clinician ver-
bally agree on goals of treatment and assess outcome globally. There exist
more formal goal-setting measures, among which the most popular is Goal
Attainment Scaling (GAS). This tool was initially developed in the mental
health field, but was later adapted to rehabilitation, specifically spasticity
management (Turner-Stokes et al. 2010). GAS allows the patient (or caregiver)
to identify meaningful goals, rather than relying upon a standardised list.
Goals are identified and mutually agreed upon by the patient and clinician,
and are weighted based on importance. The likelihood of achieving goals is
identified a priori, and against which the degree to which goals are actually
achieved during the course of treatment are compared.
8.6 Assessment
8.6.1 Clinical Assessment
As with any other condition, a comprehensive assessment begins with a
thorough history. Peculiar to spasticity assessment is obtaining information
regarding the impact of spasticity on a person’s well-being and functional
activities. Some important historical points included in Table 8.5 are exam-
ples of how to obtain information about spasticity and its functional impacts.
These questions may influence further evaluation and treatment decisions.
In certain situations, it is helpful to seek input from the patient’s caregivers
if TBI-related cognitive and language problems preclude a person’s ability to
provide accurate information.
With regard to examination, a systematic approach to assessing impairments
and functional capabilities is recommended (Figure 8.3). After obtaining a his-
tory with emphasis on the functional impact of spasticity, the examiner should
observe the person move the limb in question. It is preferable to start with hav-
ing the person perform active movements, as passive stretching of the limbs
may affect active performance. This will also give the examiner an estima-
tion of a person’s ability to overcome spasticity and the limitation in range of
motion either due to strength deficit, co-contraction, or discomfort.
TABLE 8.5
Some Important Historical Points in Spasticity Assessment
Is the limb tight all the time or only at certain times?
Does a particular position or movement trigger tightness?
Is the tightness related to spasms?
Does the tightness cause pain?
Have there been episodes of skin compromise due to tightness or spasm?
Does the tightness result in difficulty with cleaning?
Does the tightness result in difficulty donning splints?
Does the tightness limit ability to move limbs, reach for objects, and use the hands?
Does the tightness of the lower limbs result in problems with transferring form one surface
to another or with walking?
What treatments for muscle tightness have been tried previously and their outcome?
What are the current medications?
Was there a recent increase in tightness (that may warrant further diagnostic testing to rule
out a new neurologic problem)?
Any recent medical problems?
History Active Passive Functional

assessment assessment assessment
• See Table 8.5 • Ask the • Goniometric • Functional
patient to assessment scales (e.g.,
actively of range of Frenchay
move limbs motion test; Timed
• Asworth up-and-go)
scale (or • Assess gait
modification) • Patient-
• Tardieu specific
method functional
task
assessment
FIGURE 8.3
Proposed sequence of clinical assessment of spasticity.
Following this, passive examination should be carried out. While it is

known that the Ashworth Scale (and its modified version) (Ashworth 1964)
is replete with limitations, chiefly because it measures hypertonia and con-
tracture, rather than the velocity-dependent nature of spasticity, it remains
the most widely used clinical measure of spasticity. This could be due to its
historical popularity and simplicity, especially when compared the Tardieu
method (Gracies 2009), which involves more detailed goniometric measure-
ment. Various clinical assessment measures have been described, none of
which are specific to TBI. These include the Penn Spasm Frequency Scale
(Penn et al. 1989), Tone Assessment Scale (Gregson et al. 1999), and King’s
Hypertonicity Scale (King 1987).
As previously mentioned, most goals identified by patients are functional
in nature, and their assessment requires active engagement of the patient in
the upright position. Yet, it is not uncommon for clinicians to judge treatment
outcomes based on changes in the Ashworth scores, which are assessed
passively, while the patient is either supine or upright. Functional assess-
ment can be performed systematically using a pre-designed scale, such as
the Frenchay Scale (or its modification), which is not TBI-specific. Using this
scale requires that an individual perform specific, pre-determined func-
tional activities, such as putting toothpaste on a toothbrush and brushing
teeth. Functional assessment can also be carried out using patient-specific,
or individualised, tasks that the patient has identified as personal and mean-
ingful treatment goals. Outcome of therapy in the latter method is usually a
global impression both by the patient (or caregiver) and clinician.
8.6.2 Biomechanical Assessment
Resistance to passive stretch is composed of three components: passive mus-
cle stiffness, active muscle stiffness, and neurally mediated reflex stiffness.
Experimentally, total joint stiffness is first measured in response to a con-
trolled angular perturbation. The measured total stiffness is then decom-
posed into reflex and non-reflex components. Changes in non-reflex muscle
stiffness could presumably be due to changes in peripheral muscle tissue,
such as fibrosis, fat infiltration, and muscle atrophy. Change in reflex stiff-
ness could be due to a change in the descending influences on the monosyn-
aptic reflex between the muscle spindle afferents and the α-motor neurons.
Therefore, the mechanical changes may provide insights into the underlying
neural pathway or muscle tissue changes or both.
Biomechanical quantification of joint stiffness is usually performed in
the research laboratory. For example, for ankle joint stiffness quantification
(Sinkjaer and Magnussen 1994), a patient is placed in a customised instru-
mented dynamometer in which joint movement is accurately measured dur-
ing joint angular perturbation. Muscle EMG activity and limb dynamics
are measured. The patient is instructed to voluntarily activate his muscle
to generate a plantarflexion moment of ~5 Nm as background torque. Then
the ankle is rapidly dorsiflexed (perturbation), resulting in abrupt torque

increase. The initial portion of this torque increase is resulted from the non-
reflex components of the system – passive and active muscle properties – as
well as the inertial properties of the device. However, after significant reflex
activity was present as indicated by the EMG activity, total torque increases
further, reflecting the intrinsic muscle plus the reflex-mediated stiffness. In
a separate experiment, the same patient receives electrical stimulation of the
tibial nerve to cause the plantarflexors to generate the same amount of back-
ground torque (5 Nm). The ankle is plantarflexed and torque measured. This
provides an estimate of the non-reflex stiffness component, which includes
active muscle stiffness as well. Finally, subtraction of muscle stiffness from
total stiffness yields both reflex and non-reflex components of the joint stiff-
ness. There are numerous variations on this approach (Mirbagheri et al. 2000;
Mirbagheri et al. 2001; Zhang et al. 2002; Li et al. 2006; Chung et al. 2008).
When applied to spastic muscles, the common findings are velocity-
dependent increase in reflex component during controlled passive stretch
(Kamper and Rymer 2000; Zhang et al. 2000; Zhang et al. 2002; Kamper et al.
2003; Li et al. 2006; Chung et al. 2008). The findings are consistent with the com-
monly used definition of ‘velocity-dependent increase in tonic stretch reflex’
(Lance 1980). It has also been reported that there is increased non-reflex intrin-
sic muscle stiffness (Sinkjaer and Magnussen 1994). This finding suggests that
there was a change in the muscle itself rather than just a change in the nervous
system that accounted for the clinical presentation of the spastic limb.
These laboratory-based biomechanical quantifications can provide insights
into changes in mechanical properties of spastic muscles and neutrally medi-
ated reflex properties as well. These quantification devices are cumbersome
or analysis is time-consuming, making it difficult to be directly utilised in
the clinical settings. Findings from these biomechanical approaches, how-
ever, could help better assess spasticity clinically. For example, findings from
the following laboratory research study could be translated into clinical prac-
tice. From animal studies, we have learned that primary muscle spindles (Ia)
are velocity-sensitive and secondary spindle afferents are length-dependent
and there are interactions between the two in animal models (Lennerstrand
and Thoden 1968; Houk et al. 1981). In patients with spastic finger flexors
after stroke, Li et al. (2006) reported that reflex responses (EMG and torque)
of finger flexors were significantly greater at high stretching speeds than at
lower speeds when the wrist joint was held in the same position. However,
the reflex responses to a fixed stretching speed were significantly greater at
longer muscle length (when the wrist was held in the neutral position) than
a shorter muscle length (when the wrist was in 45 degrees of flexion). These
results confirmed that velocity dependence was greater at longer lengths
and length dependence was greater with faster stretches. Overall, stretch
responses are both velocity- and length-dependent. Essentially, this study
provides evidence that spasticity is also position-dependent, in addition to
being velocity-dependent. Therefore, it is very important to pay attention to
joint position (equivalent to muscle length) when examining spastic muscles

at bedside. For instance, the severity of finger flexor spasticity varies when
the wrist position changes.
A few other instrumented methods have been developed to objectively
quantify spasticity. But no measurement of passive stiffness is involved.
Based on the tonic stretch reflex threshold measured from EMGs in response
to manually stretching spastic muscles, Calota et al. (2008) developed a por-
table device and demonstrated velocity-dependent dynamic stretch reflex
threshold for spasticity measurement. This method provides electrophysi-
ological measures of spasticity. It is not able to measure mechanical proper-
ties of spastic muscles that is associated with contracture. Another device,
such as the myotonometer, measures muscle stiffness at rest and/or during
voluntary contraction by recording displacement of the probe perpendicular
on the target muscle and the amount of force applied to the probe by the
examiner. The myotonometer measurement is found to have good intra- and
inter-rater reliability, and is correlated well with clinical measurement of
spasticity by MAS (Leonard et al. 2001; Leonard et al. 2003). This measure-
ment, however, does not differentiate active vs. passive stiffness, nor provide
reflex component of the stretch response.
8.7 Management
Management options include physical modalities and physiotherapy, oral
medications, botulinum toxin injections, nerve blocks with alcohol and phenol,
intrathecal baclofen pump, and surgery. When to initiate treatment of spastic-
ity after a TBI is unclear but an astute clinical approach is to consider any of
these options once spasticity becomes problematic, and especially if it appears
to adversely affect recovery and progress in rehabilitation. In the acute care set-
ting early intervention promotes prevention and management of the secondary
effects of spasticity before they become severe. While, in the chronic setting, an
additional treatment goal is to facilitate recovery of movement and function.
8.7.1 Physical Modalities
Physical modalities are a mainstay in the first line of treatment, since they
are widely available and not associated with systemic side effects such as
those associated with drugs. Passive stretching with flexion and extension of
the knee has been shown to be effective in reducing spasticity and increas-
ing ROM in patients with brain injury (Starring et al. 1988). Splinting and
serial casting can also be used in the acute setting for sustained stretching
(Booth et al. 1983; Preissner 2002; Mortenson and Eng 2003; Pohl et al. 2003;
Bovend’Eerdt et al. 2008).
Casting has been extensively used in the clinical settings as an effective tool
to reduce contracture and spasticity and to increase ROM in patients with neu-
rological impairments, including TBI. A systematic review on the use of upper
extremity casting to achieve reductions in spasticity, contracture, or pain in the
elbow, wrist, or hand has revealed lack of high-quality evidence to support or
abandon such practice (Lannin et al. 2007). The authors founded high variabil-
ity in casting protocols, which indicates no consensus for casting.
Casting alone seems sufficient to prevent contracture and reduce spastic-
ity if the intervention is initiated early after severe brain injury. In a double-
blind placebo-controlled study (Verplancke et al. 2005), of the 235 subjects
with severe brain injury who were screened, only 35 patients were enrolled
and randomised into three groups within 10 days of initial brain injury: stan-
dard physical therapy treatment without casting (group I), lower leg casting
plus injections with either saline (group II), or with Onabotulinum toxin A
(group III, 200 units) into gastrocnemius and soleus muscles. All subjects
received 12 weeks of treatment. The mean range of improvement in the angle
of passive ankle dorsiflexion was 4.59 degrees in group I, 11.69 degrees in
group II and 13.59 degrees in group III. Concomitantly, spasticity of plan-
tarflexors was significantly reduced only in groups II and III, but not in
group I. Group III patients also demonstrated a significant improvement
in the Glasgow Outcome Scale. In other words, this study demonstrates
that casting alone is sufficient in preventing ankle deformity and spasticity
reduction in patients after severe brain injury. The role of additional botuli-
num toxin for this purpose needs further investigation.
Casting may enhance the effect of botulinum toxins (Farina et al. 2008). In
this study, 13 patients with stroke and equinovarus foot were randomised to
receive either onabotulinumtoxin toxin injection or ankle-foot casting treat-
ment (n = 6) or onabotulinumtoxin alone (n = 7). The time since onset of stroke
ranged from 6 months to 2 years at enrollment. The tibialis posterior and calf
muscles were injected in each patient. Castings were worn at night for 4 months.
At 2 months, therapeutic effects were observed in both groups according to
static and dynamic baropodometric tests, MAS and the 10-meter walking
test. At four months, the injection and casting group showed further clinical
improvement, while the injection alone control group returned to baseline per-
formance. Therefore, prolonged stretching of spastic muscles after the injection
affords long-lasting therapeutic benefit, enhancing the effects of the toxin alone.
Although this study was in persons with stroke, the results may be applicable
in persons with TBI who present with similar lower limb deformities.
8.7.2 Stretching and Casting for Contracture vs. Spasticity Management

A recent study reported promising clinical outcomes using individualised
stretching to reduce wrist and finger muscle stiffness and passive ROM
(Copley et al. 2013). In this study, 10 patients with moderate (MAS 1+ or 2)
wrist and finger flexor muscle stiffness after acquired brain injury, including
traumatic brain injury, were randomised to the individualised splint and

non-splint groups. The splint group received an individualised, thermoplas-
tic resting mitt splint. The goal was to place each participant’s muscles on
low-load, prolonged stretch. If the standard resting position (20-degree wrist
extension) resulted in observable excessive stretch on the wrist, finger, or
thumb flexor muscles (e.g., wrist flexing out of splint, fingers clawing into
splint, fingernails blanching, or hyperextension of metacarpophalangeal or
interphalangeal joints), the degree of wrist extension was decreased. The
splint group patients received 2–4 hours of splinting each day for 3 months.
A follow-up measure was taken 1 month later. As compared to baseline,
splint-wear resulted in significantly increased wrist and finger passive ROM,
and decreased finger spasticity and stiffness, while non-splint-wear had neg-
ative clinical effects on these parameters, ranging from zero effect to a large
negative treatment effect. This study suggests that, in the selected group of
patients, individualised stretching should be considered for reduction in
muscle stiffness and spasticity and maintenance of passive ROM.
Casting and physical therapy interventions could reduce the burden of
care in patients with a vegetative or minimally conscious state. In a recent
retrospective study, the authors examined the dependency levels and phys-
iotherapy interventions in 10 patients in a vegetative or minimally conscious
state (Wheatley-Smith et al. 2013). All patients presented with hypertonic-
ity including contractures and all initially received a manual stretching/
passive movement programme. Casting/splinting was employed in 8 cases
and 7 received botulinum toxin injections. Standing regimes were initiated
for 8 patients. All patients were able to sustain a seating regimen, and care
burden was reduced, although no patient emerged out of either vegetative
or minimally conscious state, and remained fully dependent for care needs.
8.7.3 Electrical Stimulation
Electrical stimulation may be utilised to temporarily reduce spasticity (Seib
et al. 1994). In 5 patients with TBI and 5 with spinal cord injury (SCI) result-
ing in spasticity, surface electrical stimulation was applied over the tibialis
anterior muscle. The authors found that ipsilateral ankle viscoelastic stiff-
ness immediately decreased in 9 of 10 subjects and remained significantly
depressed for up to 24 hours after electrical stimulation. Contralateral ankle
spasticity did not significantly change, however. Using the same subjects
under sham conditions, no significant decrease in spasticity occurred. In
another report, a long-lasting effect on spasticity reduction was reported if
electrical stimulation was triggered by voluntary breathing, i.e., BreEStim
(Li and Rymer 2011). A group of chronic stroke and TBI patients with mod-
erate to severe finger flexors spasticity received one session of 30 minutes
of BreEStim to finger extensors; finger flexor spasticity was immediately
significantly reduced, and the reduction lasted for 4 weeks in the follow-up
period.
The efficacy of electrical stimulation on spasticity reduction was not observed

in another study (Leung et al. 2012). In this multi-centre, randomised, examiner-
blinded trial, 36 patients with first stroke or TBI and mild-to-moderate wrist
flexion contractures were randomised into 2 groups. The experimental group
received electrical stimulation to the wrist and finger extensor muscles for
1 hour a day over 4 weeks while the control group received no electrical stimu-
lation. Both groups wore a splint for 12 hours a day during this 4-week period.
Outcomes were measured at baseline, at the end of the intervention period
(4 weeks), and after a 2-week follow-up period (6 weeks). There was no statisti-
cally significant difference between 2 groups in passive wrist extension, wrist
and finger extensor strength, wrist flexor spasticity, and motor control of the
hand at 4 and 6 weeks. This study shows that splinting alone is as effective as
the electrical stimulation and splinting treatment for the management of wrist
contracture after acquired brain injury. A recent study confirmed that electrical
stimulation treatment help reduce contractures in stroke patients with a non-
functional arm, but had no effect on spasticity or stiffness (Malhotra et al. 2013).
Overall, passive stretch via different methods including splinting, casting,
sustained stretching, and positioning has been the mainstream of physical
and occupational therapy management for contracture and spasticity pre-
vention and treatment. There are various reports of effectiveness of this
modality as described above. A Cochrance systematic review on the effects
of passive stretch on contractures concludes that if stretch is performed over
fewer than 7 months, it does not have clinically important effects on joint
mobility for those with or at risk of contractures (Katalinic et al. 2010). When
combined with other interventions, passive stretch may augment the effect
of botulinum toxin treatment, and electrical stimulation effect.
8.7.4 Oral Medications
Pharmacological agents are commonly used to reduce spasticity but their com-
mon adverse effects limit their use in this population. Commonly prescribed
medications include baclofen, tizanidine, dantrolene, and benzodiazepine.
Applications of these medications for spasticity management after TBI have
recently undergone thorough reviewed by Zafonte et al. (2011) and in the other
chapters of this book. While effective in decreasing spasticity, these medica-
tions’ side effects, such as sedation and drowsiness, can magnify arousal or
cognitive dysfunction often experienced by persons with TBI. Perhaps this
explains why adherence to oral anti-spasticity medications is poor. In a recent
study (Halpern et al. 2013), retrospective administrative claims of 2840 per-
sons in a large national US health system were analysed. These persons were
treated with oral baclofen, tizanidine, and dantrolene for spasticity resulting
from various aetiologies, including TBI, over a period of 5.5 years. Adherence
was measured as continuous medication possession ration (MPR). MPR > 0.80
indicates a good adherent. MPR was 20.4% for baclofen and 9.1% for tizanidine.
TBI patients had 77.5% lower odds of adherence than stroke patients.
8.7.5 Focal Therapies
8.7.5.1 Botulinum Toxins
Intramuscular botulinum toxin injection is an attractive therapeutic option for
the management of spasticity in TBI patients because of its focal action with-
out significant side effects (Esquenazi et al. 2013). The primary mechanism
of action in spasticity is the pre-synaptic inhibition of acetylcholine release,
at the neuromuscular junction, that leads to reduction in muscle contraction
and consequently decreased spasticity (Jahn 2006). Due to functional repair
of the neuromuscular junctions affected by the toxin (de Paiva et al. 1996),
clinical effects last only about 3 months. In the USA, there are four commer-
cially available toxins: abobotulinumtoxinA (Dysport™), incobotulinumtox-
inA (Xeomin™), onabotulinumtoxinA (Botox™), and rimabotulinumtoxinB
(Myobloc™). They are distinctly different in formulation, purification, and
dosing. In the USA, doses of up to 600 units of onabotulinumtoxinA are com-
monly used. Although not supported by systematic dose-ranging studies,
the safety of higher doses (800–1200 units) has been reported in the treat-
ment of spasticity in adults (Goldstein 2006).
Accumulated evidence from clinical research has supported a Level A rec-
ommendation (the AAN classification) for treatment of upper and lower limb
spasticity (Esquenazi et al. 2013). One of the challenges, as mentioned earlier,
is deciding how early botulinum toxin can be administered in persons with
TBI. Findings from a recent randomised double-blind placebo-controlled
study demonstrated effectiveness of early intervention on spasticity reduc-
tion (Fietzek et al. 2014). In this study, 52 patients within 3 months after
stroke, traumatic brain injury, or hypoxic encephalopathy were randomised
to receive either botulinum toxin or placebo treatment for unilateral or bilat-
eral spastic pes equinovarus with MAS of at least 1+. Patients received uni-
lateral or bilateral injections with 230 or 460 units of onabotulinumtoxinA,
respectively, in the treatment group in the first cycle. A second, open injec-
tion was optional at week 12. Both groups of patients had a similar baseline.
Patients who had received injection initially had lower MAS compared with
placebo at week 12. During the open-label phase, patients from the placebo
group showed further deterioration of muscle tone despite starting from a
similar baseline and receiving injection. Spastic feet that had received injec-
tion in the first cycle had comparatively lower MAS scores over all follow-up
data and at week 24. Overall, this study demonstrates benefits of botulinum
toxin injection in the subacute phase for spasticity management.
Early management of severe spasticity is unfortunately often neglected
in the acute phase. Severe contractures may develop within a few weeks,
particularly in patients with severe brain injury. This prolongs the recovery
process and increases risks of developing contracture (Pohl et al. 2007). Early
intervention with botulinum toxin with intensive therapies, e.g., injected
on the sixteenth day after brain injury in a case report (Lippert-Gruner
and Svestkova 2011), reported to increase the chance of a more favourable
functional outcome. Similar to effectiveness of focal spasticity management

with botulinum toxin injection, continuous administration of intrathecal
baclofen is indicated to reduce generalised spasticity and autonomic dis-
orders as well in the early phase of severe brain injury (Cuny et al. 2001;
Francois et al. 2001). However, early treatment with focal injection needs to
be judged carefully. Injection to calf muscles will reduce spasticity to allow
casting and prevent predictable plantarflexion contracture, and thus better
outcome.
On the other end of the temporal spectrum, the use of botulinum toxin
years after acquired brain injuries has been shown to be beneficial. Clemenzi
et al. (2012) examined the efficacy of repeated botulinum toxin A injection in
21 patients with spasticity due to severe acquired brain injury and no further
improving with rehabilitation treatment and oral anti-spastic medications
with a 1-year follow-up. Half of the patients enrolled were treated for the
first time with injection after a median length of 5 years since severe ABI.
All patients received 2 to 4 repeated injections in the 12-month period. The
authors found that a shorter interval between the onset of severe acquired
brain injury and the first botulinum toxin injection correlated to a better
spasticity reduction and Barthel index improvement. This study also dem-
onstrated effective spasticity reduction and functional improvement even
botulinum toxin injection was given later. However, this study did not find
correlation between the number of injections and clinical outcome. The
authors suggested secondary plastic changes in the motor cortex, in addition
to peripheral mechanisms of botulinum toxin at the neuromuscular junction.
The effect of dilution of botulinum toxin, i.e., the same dose of botulinum
toxin mixed with a high volume of saline, has been studied (Francisco et
al. 2002; Francisco 2004; Lee et al. 2004; Gracies et al. 2009; Lee et al. 2009).
Gracies et al. (2009) reported enhanced neuromuscular block and spastic-
ity reduction with dilutions. In a double-blinded randomised controlled
trial, 21 patients were randomised into 3 groups: group 1: 100 mouse units
(MU)/mL dilution, 0.4 cc/site, 4-quadrant injection; group 2: 100 MU/mL
dilution, 0.4 cc/site, 4 sites along endplate band; group 3: 20 MU/mL dilution,
2 cc/site, 4-quadrant injection (n = 7 per group). Each patient received a total
of 160 units of different dilutions and locations into biceps brachii. The injec-
tion reduced elbow flexor spasticity angle on the Tardieu scale, decreased
co-contraction between biceps and triceps during voluntary elbow flexion,
but increased maximal voluntary extension power and active range of elbow
extension. Agonist and antagonist flexor EMG activity reduction in group 3
was greater than in groups 1 and 2, whereas increase in active range of elbow
extension was greater in group 2 (10%) than in groups 1 and 3. Elbow flexor
spasticity was significantly reduced in groups 2 and 3 only. These findings
suggested that high-volume or endplate-targeted injections achieve better
clinical outcomes, including greater neuromuscular blockade and spastic-
ity reduction, and active range of elbow extension improvement, than low-
volume, non-targeted injection in spastic elbow flexors. High volumes of the
same dose of botulinum toxin did not result in better clinical outcomes in
two other studies (Francisco et al. 2002; Lee et al. 2009). Francisco et al. (2002)
found no difference in Ashworth score reduction between high- and low-
volume injections of a 60-unit dose of botulinum toxin into spastic wrist and
finger flexors of adult patients caused by acquired brain injury.
As stated specifically in the commonly quoted definition by Lance (1980),
spasticity is only 1 component of the UMNS. Thus, the management of spas-
ticity should take into account the other UMNS components. Management
should be interdisciplinary and centred on meaningful and practical goals,
rather than the severity of spasticity in individual muscles. Since the sever-
ity and significance of spasticity vary amongst individuals, their impact on
well-being and function are not the same. Severity is usually gauged by
clinical measures, such as the Ashworth Scale or Tardieu method, whereas
significance is characterised by the impact of spasticity on a particular task.
Hence, a spastic elbow flexor with Ashworth score of 3 that does not cause
discomfort or problem with hygiene may be left untreated, whereas finger
flexors with an Ashworth score of 1 but limiting the ability to functionally
use the hand may warrant treatment. That said, spasticity requires treat-
ment only when muscle overactivity is disfiguring, disabling, predisposing
to more complications, or intervening with functional activities.
8.7.5.2 Case 2
Mr AO is a 50-year-old male who suffered a TBI from a motor vehicle crash
12 years earlier. He complained of persistent tightness of the left index finger
(digit II) that precludes the ability to bimanually type on the computer key-
board (Figure 8.4).
He had previously received oral tizanidine, but had to discontinue due
to drowsiness. He has been receiving botulinum toxin injections to his fin-
ger flexors over the last several years (dose range 50–100 units of onabotu-
linumtoxinA). While spasticity of digits III–V has improved to the point that
he is able to once again type on a keyboard, tightness of the digit II flexor
FIGURE 8.4
Case 2: 50-year-old male with TBI and spastic left index finger.
has made it impossible to use all fingers for this particular activity. He sub-
sequently received 100 units of onabotulinumtoxinA chiefly to the part of
the flexor digitorum superficialis muscle that appeared to represent fibres
to digit II (as visualised on ultrasound). This resulted in relaxation of this
digit, allowing him to re-train bimanual keyboard use. His Ashworth score
improved from 2 to 1. When the spasticity recurred about 3 months later, i.e.,
the Ashworth score increased to 2 and he became unable to actively extend
digit II, he received 125 units of onabotulinumtoxinA. The injection was
once again limited to the part of the flexor digitorum superficialis muscle to
digit II, confirmed by ultrasound. About 3 weeks later, the Ashworth score
improved to 0, and although the patient felt some weakness in finger flexion,
he was able to resume training on bimanual keyboard use.
This case illustrates the importance of recognising the significance, rather
than severity, of spasticity on the functional abilities of a person with TBI. It
also illustrated individualisation of treatment, as the dose of onabotulinum-
toxinA used was higher than what most clinicians would consider using.
8.7.5.3 Phenol and Alcohol Neurolysis

A focal treatment that antedates botulinum toxin therapy is neurolysis using
either phenol or alcohol (Gracies et al. 1997). Unlike botulinum toxins, the
efficacy and safety of this technique in various patient populations with
spasticity is not well-studied. Phenol (5–6%) and alcohol (35–60%) initially
exert their spasmolytic effect through protein denaturation of the nerve
membrane, and in some cases the axons, leading to chemical neurolysis.
Further, phenol decreases muscle hypertonia probably as a result of dener-
vation and degeneration of muscle spindles (Bodine-Fowler et al. 1996; Wolf
and English 2000). Immediately after injection of phenol, muscle hypertonia
decreases likely due to the agent’s anaesthetic properties. True neurolytic
effect does not set in until a few hours after injection and depending on the
dose and concentration used, may last for a few months. Muscle reinnerva-
tion is the likely mechanism for recurrence of hypertonia. Unlike botulinum
toxins, phenol and alcohol appear to be associated with more side effects.
Most commonly observed are injection site pain, swelling, weakness, and
post-injection dysesthesia (Gracies 1997). The risk of pain and dysesthesia is
high, particularly when mixed nerves are injected (Stevenson, Jarrett 2006).
Accidental spread into the vascular system may result in systemic effects,
such as such as tremors, convulsions, and CNS depression.
8.7.6 Intrathecal Therapies
Various medications have been used for intrathecal delivery, but the most
commonly used for spasticity is baclofen. Unlike the oral form, intrathe-
cal baclofen involves infusion of small doses of the drug. Since intrathecal
baclofen (ITB) is delivered close to its site of action in lamina III of the spinal
cord, the need for a higher concentration (and thus, dose) to bypass the blood-
brain barrier is obviated. Consequently, the smaller dose that is therapeuti-
cally effective does not result in adverse events observed with the relatively
higher effective doses of oral baclofen. To wit, many patients with TBI expe-
rience sedation or drowsiness with 80 mg/day of oral baclofen, but tolerate
intrathecal doses of as much as 1000 mg/day, which is roughly one-eighth of
the oral dose. Although baclofen introduced intraspinally primarily affects
GABA receptors in the spinal cord, a certain amount of the medication is
carried by the cerebrospinal fluid as it bathes the brain, where GABAB-ergic
interneurons are also affected (Siebner et al. 1998).
An implanted programmable pump that contains a refillable drug reser-
voir and a computer chip that regulates a battery delivers baclofen into the
intrathecal space through a silicone catheter. Following clinical assessment
for suitability for ITB therapy (see Table 8.5), a screening trial that involves
a single intrathecal bolus of 50–150 mg of baclofen through a spinal needle
is typically performed. An alternative technique, which involves continuous
intrathecal infusion through an external catheter, is performed more com-
monly in children with dystonia or in those with dysautonomia (or paroxys-
mal sympathetic hyperactivity) due to anoxia or severe TBI.
The literature supporting the efficacy of ITB in managing TBI-related
spasticity is limited, largely because most studies enrolled persons with
‘acquired brain injuries’, which are typically dominated by stroke survivors.
Meythaler et al. (1999) reported significant improvement in 17 patients with
TBI after 1 year of continuous ITB treatment. The average lower extremity
Ashworth score decreased from 3.5 ± 1.3 (SD) to 1.7 ± 0.9 (p < 0.0001), spasm
score from 1.8 ± 1.3 to 0.2 ± 0.5 (p < 0.0001), and reflex score from 2.5 ± 1.1 to
0.1 ± 0.3 (p < 0.0001). The average upper extremity Ashworth score decreased
from 2.9 ± 1.5 to 1.6 ± 1.0 (p < 0.0001), spasm score from 1.2 ± 1.5 to 0.2 ± 0.6
(p < 0.0001), and reflex score from 2.2 ± 0.5 to 1.0 ± 0.8 (p < 0.0001). Mean ITB
dose was 302 mcg/day. In addition to improvement in these metrics, some
patients obtained significant functional benefits: one who was wheelchair-
dependent became independent in ambulation, and another who was able
to walk with assistive devices prior to ITB implantation became an indepen-
dent ambulatory up to 2 miles per day with ITB therapy.
ITB is usually indicated 1 year after onset of TBI, but it has also been used
earlier. Concerns regarding early ITB use are largely extrapolated from ani-
mal studies, which suggested that baclofen, a GABA-ergic compound, slowed
neurologic recovery (Brailowsky et al. 1986). However, it is widely acknowl-
edged that delayed or inadequate treatment of spastic hypertonia may result
in costly complications such as contractures, persistent pain, and failure to
benefit from rehabilitation efforts. Francois et al. (2001) described four patients
with severe TBI (Glasgow Coma Scale score 3 or 4) and ‘autonomic disorders
and spasticity who failed to respond to conventional treatment’, who received
ITB at a mean of 25 days (range 21–31) post-TBI. Through a subcutaneously
tunneled intrathecal catheter, 25 mcg of baclofen was continuously infused.
At a mean dose of 385 +/−185 mcg/day, Ashworth scores were significantly

reduced on the upper and lower limbs. Concurrently, there was a significant
improvement in the frequency and intensity of autonomic symptoms (tachy-
cardia, episodic systolic hypertension, and profuse sweating). In a retrospec-
tive study (Francisco et al. 2005), 14 individuals with spastic hypertonia due
to trauma (5), anoxia (6), and stroke (3) received ITB therapy within the first
year of disease onset. On follow-up 14 months post-ITB implant (mean daily
dose 591.5 mg/day) modified Ashworth scores significantly improved from
baseline. Disability Rating Scale scores did not change significantly, suggest-
ing that there was no deterioration in functional status. Other noted gains
were decreased pain and improved gait speed and motor skills. The only
complication reported was spinal leak in one subject. This appears to be sup-
ported by animal studies. Using a rat model of closed TBI, Bose et al. (Bose et
al. 2013), demonstrated that 1 month of ITB treatment initiated 1 week post-
experimentally induced TBI prevented early onset of spasticity (measured by
using velocity-dependent ankle torque and ankle extensor muscle electro-
myography recordings) and significantly reduced occurrence of late-onset
spasticity with no significant adverse effects on cognitive and balance per-
formance. The positive spasticity outcome was observed to be accompa-
nied by a remarkable up-regulation of gamma-aminobutyric acid (GABA)/
GABAB, norepinephrine, and brain-derived neurotrophic factor expression
in spinal cord tissue.
On the other end of the spectrum are patients benefitting from ITB many
years after TBI onset. Three adult males who sustained a TBI 14, 17.1, and
19.9 years prior to receiving ITB pump experienced significant improve-
ment in lower limb spasticity as measured by the Modified Ashworth
Scale (Francisco et al. 2007). Although FIM-mobility scores did not change
from baseline, some functional domains such as gait, transfers, and sit-
ting, assistance for activities of daily living (ADL) and nursing care, com-
munity mobility, and participation in recreational activities improved. In
another case series (Sara et al. 2009), sporadic cases of recovery from persis-
tent vegetative state (PVS) after administration of ITB have been reported.
Five patients with PVS treated with ITB showed signs of recovery of con-
sciousness as early as 2 weeks after pump implantation, measured by the
Coma Recovery Scale (Revised) (CRS-R). Although the exact mechanism is
unknown, the authors hypothesised that the improvement in conscious-
ness could have been due to modulation of spinal cord segmental activi-
ties and neuronal centripetal outputs reaching the cortex, or modulation of
sleep-wake cycles.
In general, ITB therapy is safe, although challenges, usually due to catheter
malfunction, can occur. Abrupt reduction in infusion of ITB due to cath-
eter or pump malfunction may result in a withdrawal syndrome that may
appear similar to but pathophysiologically distinct from autonomic dysre-
flexia, malignant hyperthermia, and neuroleptic-malignant syndrome. It is
best managed by early re-institution of baclofen administration. Delay in
TABLE 8.6
Some Possible Causes of ITB System Malfunction
Catheter
Fracture
Kink
Disconnection of catheter from pump
Occlusion (e.g., catheter tip granuloma)
Pump
Mechanical failure
Battery failure
Human error
Refill error
Programming error
addressing withdrawal symptoms may lead to a life-threatening syndrome

characterised by high fever, altered mental status, severe rigidity, and, in
more advanced cases, seizures and withdrawal. Coffey et al. (2002) and
Francisco et al. (2009) reviewed the topic more extensively. In addition to
immediate restoration of ITB infusion, other drugs, including dantrolene
sodium and cyproheptadine (Meythaler et al. 2003), have been described as
helpful in mitigating some of the symptoms of ITB withdrawal syndrome.
After re-instituting baclofen infusion, the underlying cause of the with-
drawal syndrome must be sought and addressed definitively. Table 8.6 lists
some potential causes of ITB system malfunction. Special attention must be
paid to persons with TBI, who have a ventricular shunt. Malfunction of the
shunt may alter the relative concentration of baclofen in the cerebrospinal
fluid and thus may cause symptoms of either over- or under-infusion.
8.7.7 Surgical Interventions
The surgical management of spasticity is a well-accepted treatment option
for children with cerebral palsy, as also indicated in patients with severe
spasticity and/or contracture by other neurological impairments, includ-
ing TBI. Surgical interventions include neuroablative procedures, such as
peripheral neurotomies and dorsal rhizotomies, and orthopaedic reconstruc-
tive procedures, such as tendon lengthening and tendon transfer (Sindu et
al. 2014). When excessive spasticity and/or contracture are not sufficiently
controlled by therapy and pharmacological treatment, tendon lengthening
is often considered in persons after TBI. By lengthening the tendon, cor-
recting abnormal joint posture, and relieving the associated pain, surgical
treatment allows therapy to resume, and sometimes results in meaningful
functional gain. Surgical intervention is a permanent treatment, however.
Optimal management of spasticity by non-surgical means should be reached
before surgical treatment is recommended. As in Case 1, patients regain
functional movement in the hand and fingers after aggressive botulinum

injections for spasticity management. The functional gain in Case 1 may not
have been achieved if the patient had had tendon lengthening of finger and
thumb flexors. On the other hand, it is prudent to differentiate contributions
of spasticity and contracture to abnormal joint postures before considering
surgical treatment. A diagnostic nerve block can help characterise how much
of the loss of range of motion and resistance to passive movement is due to
contracture or spasticity, since an anaesthetic agent is likely to affect only the
latter. Results of a diagnostic nerve block can help guide the plan of care. For
example, in a patient with flexed knee deformity, if a temporary diagnostic
sciatic nerve motor branch block results in increased knee extension, spastic-
ity is likely the primary cause of the deformity. Botulinum toxin injection
or motor branch block with phenol should be considered. Stretching of the
knee flexors and strengthening of the knee extensors should be employed.
If there is no significant change in the knee range of motion after a sciatic
nerve block, a static deformity, i.e., knee contracture, is determined. In the
early period of recovery, orthotic management to control knee flexion is con-
sidered, while surgery in the form of distal hamstring lengthening is consid-
ered for a static deformity in late recovery.
8.7.8 Controversial and Promising Treatments

Various treatment modalities have been described in the literature as poten-
tial treatments for spasticity. Most of these are single case reports or case
series and are not specific to TBI. These include acupuncture (Fink et al.
2004), aromatherapy (Ashworth et al. 2012), peripheral nerve (Bakhtiary and
Fatemy 2008), spinal (Pinter et al. 2000), and non-invasive brain stimulation
(Gunduz et al. 2014).
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9
Hereditary Spastic Paraparesis
and Other Hereditary Myelopathies
Jon Marsden, Lisa Bunn, Amanda Denton

and Krishnan Padmakumari Sivaraman Nair
CONTENTS
9.1 Introduction................................................................................................. 236
9.2 Distal Axonopathies: Hereditary Spastic Paraparesis........................... 237
9.2.1 Prevalence and Genetics................................................................ 237
9.2.2 Clinical Presentation...................................................................... 237
9.2.3 Pathology......................................................................................... 238
9.2.3.1 Cellular Changes.............................................................. 238
9.2.3.2 Changes in Descending and Ascending Tract
Function............................................................................. 240
9.2.3.3 Changes in Cortical Activation with Movement......... 241
9.2.4 Symptoms Associated with HSP.................................................. 243
9.2.4.1 Limb Stiffness................................................................... 243
9.2.4.2 Paresis................................................................................ 246
9.2.4.3 Sensory Loss..................................................................... 247
9.2.4.4 Bladder............................................................................... 247
9.2.4.5 Bony Changes................................................................... 247
9.2.4.6 Fatigue............................................................................... 248
9.2.4.7 Mood and Quality of Life............................................... 248
9.2.5 Impact of Spasticity and Associated Symptoms
on Functional Ability................................................................248
9.2.6 Balance.............................................................................................. 248
9.2.7 Walking............................................................................................ 249
9.2.8 Outcome Measurement.................................................................. 252
9.2.9 Interventions.................................................................................... 253
9.2.9.1 Pharmacological and Surgical Treatment
of Spasticity....................................................................... 253
9.2.9.2 Physical Interventions..................................................... 257
9.2.9.3 Service Delivery............................................................... 258
9.3 Spinocerebellar Degenerations................................................................. 258
9.3.1 Autosomal Dominant..................................................................... 258
235
9.3.2 SCA3 or Machado-Joseph Disease............................................... 259

9.3.2.1 Symptomatic Management............................................. 262
9.3.3 Autosomal Recessive...................................................................... 266
9.3.4 Friedreich’s Ataxia and Late-Onset Friedreich’s Ataxia........... 266
9.3.4.1 Management of FDRA..................................................... 267
9.4 Motor Neuron Disorders and Familial Amyotrophic Lateral
Sclerosis........................................................................................................ 268
9.4.1 Amyotrophic Lateral Sclerosis...................................................... 268
9.4.1.1 Prevalence and Genetics................................................. 268
9.4.1.2 Pathology........................................................................... 269
9.4.1.3 Clinical Presentation....................................................... 269
9.4.2 Interventions.................................................................................... 271
9.4.2.1 Disease-Modifying Therapy........................................... 271
9.4.2.2 Symptomatic Management............................................. 271
9.5 Leukodystrophies....................................................................................... 273
9.5.1 Demyelinating and Dysmyelinating Disorders......................... 273
9.5.2 Hypomyelinating Disorders......................................................... 273
9.5.3 Spongiform Disorders.................................................................... 273
9.5.4 Cystic Disorders.............................................................................. 274
9.6 Adrenoleukodystrophy.............................................................................. 274
9.6.1 Prevalence and Genetics................................................................ 274
9.6.2 Clinical Presentation...................................................................... 274
9.6.3 Interventions.................................................................................... 275
9.7 Summary...................................................................................................... 275
References.............................................................................................................. 276
9.1 Introduction
This chapter will explore the impact of spasticity and associated symptoms
in hereditary myelopathies with a particular focus on hereditary spas-
tic paraparesis (HSP). Hereditary myelopathies include syndromes with a
genetic cause that involves spinal cord structures. To a variable extent they
will have upper motor neuron (UMN) symptoms of spastic paraparesis.
Importantly, in the majority of cases, structures outside the spinal cord are
affected, resulting in a diversity of symptom presentation. Four main clinical
groups can be distinguished.1
1. Distal axonopathies of the spinal cord, e.g., HSP.

2. Spinocerebellar degenerations, e.g., spinocerebellar ataxia3 (SCA3),
late-onset Freidreich’s ataxia.
3. Motor neuron disorders, e.g., familial amyotrophic lateral sclerosis.
Hereditary Spastic Paraparesis and Other Hereditary Myelopathies 237
4. Inborn errors of metabolism, e.g., adrenomyeloneuropathy, biotini-

dase deficiency, cerbrotendinous xanthomatosis, glycogenosis type
IV, Krabbe’s disease metachromatic leucodystrophy, and phenyl
ketoneuria.
Based on clinical presentation alone it can be often quite difficult to dis-

tinguish between conditions. People with the complex forms of HSP, for
example, can have cerebellar signs and mimic the presentation seen in
spinocerebellar ataxias. Similarly, spinocerebellar ataxias such as SCA3
(Machado-Joseph disease) can present with significant spasticity and mimic
HSP.2 Adrenomyeloneuropathy can sometimes mimic HSP.3–6
An example of the clinical presentation and management from each clinical
group of hereditary myelopathies will be described. The level of understand-
ing of the underlying genetics can vary between the different hereditary
myelopathies and this will be briefly described. Further, the hereditary
myelopathies can have quite diverse additional symptoms and pharmacolog-
ical and rehabilitation management. This will be described with particular
emphasis placed on the management of spasticity and the upper motor neu-
ron syndrome and its impact on functional ability.
9.2 Distal Axonopathies: Hereditary Spastic Paraparesis

9.2.1 Prevalence and Genetics
Hereditary spastic paraparesis (Strumpell-Lorrain syndrome) has a preva-
lence of 4–6 per 100,000, although this can rise up to ~20 per 100,000 in isolated
populations.7 It is a heterogeneous genetic condition. More than 50 gene loci
have been identified that can cause HSP.8 All types of inheritance have been
described: autosomal dominant (70% of cases), autosomal recessive, X-linked,
and maternal mitochrondrial. The age of onset can vary from childhood to
late adult life (70 years of age).8
There is also a high incidence of spontaneous mutations and asymptomatic
carriers.9 In SPAST(SPG4), the most common type of autosomal dominant
HSP (40–45% of cases), spontaneous mutations to the spastin gene, can occur
in 13% of cases where symptoms are restricted to the legs.10 Epidemiological
studies suggest that 45–67% of autosomal dominant and 71–82% of autoso-
mal recessive cases diagnosed with spastic paraparesis have no genetic diag-
nosis after systematic testing.11
9.2.2 Clinical Presentation
Anita Harding originally described two broad classifications for HSP.12
The type 1, uncomplicated presentation is characterised by the symptoms
of lower limb spasticity, hyperreflexia, paresis, and a positive (up-going)

Babinski response. Additional symptoms of urinary urgency and impaired
vibration thresholds may also be present. Most cases of autosomal dominant
HSP are the type 1, pure presentation.
In the type 2 presentation people have the same spastic paraparesis pre-
sentation as seen in type I but with other additional symptoms. Autosomal
recessive presentations tend to have a complicated presentation and addi-
tional symptoms include:
• Cerebellar ataxia and signs.

• Dementia and cognitive deficits. These are associated with thinning
of the corpus callosum.
• Amyotrophy.
• Peripheral neuropathy.
• Cataracts or pigmentary retinopathy.
• Dry, itchy skin (ichthyosis).
• Epilepsy.
The most common types of HSP for each mode of inheritance and perti-
nent clinical features are presented in Table 9.1, with more rare presentations
described in detail elsewhere.8,13
9.2.3 Pathology
9.2.3.1 Cellular Changes
In the last decade, there has been an increase in the understanding of the
changes in neuronal cell function that lead to HSP. This section will briefly
review these changes and more detail can be gained from recent reviews of
this area.8,13
Neurons within ascending and descending tracts that connect the brain
and the lower segments of the spinal cord are over 1 m long. Protein and
lipid synthesis and detoxification of harmful substances mainly occur within
the cell body and the endoplasmic reticulum (ER)-golgi apparatus system.
A system of axonal transport is therefore required that actively transports
newly synthesised materials from the cell body to the axon and neurotrophic
factors and damaged organelles from the axon terminal to the cell body.14
Axonal transport relies on a cytoskeletal network within the axon made of
microtubules and actin filaments. Specialised motor proteins bind to and
move substances in an anterograde or retrograde direction through this net-
work, a process that is ATP-dependent, i.e., requires energy. Genes causing
HSP encode proteins that are involved in the ER-golgi system (e.g., ATL-1
(SPG3A); REEP(SPG31); RTN2 (SPG12)); or axonal transport. SPAST (SPG4),
for example, plays a role in microtubule turnover, whilst KIF5A (SPG10) is a
member of the kinesin family of motor proteins.8
TABLE 9.1
Genetic Location; Protein and Broad Cellular Function; Prevalence and Key Clinical Features
Cellular Estimated
Gene Name & Locus Protein Function Prevalence Pertinent Features
Autosomal Dominant (AD-HSP)
SPAST (SPG4) 2p22 Spastin protein Microtubule severing, ER 40–45% of AD Childhood–late adult
morphogenesis, Endosomal trafficking, cases Mainly pure HSP
inhibition of bone morphogenic
protein signalling
SPG3A 14q12-q21 Atlastin Intracellular trafficking, ER 10% of cases Early onset
morphogenesis, and BMP signalling Pure HSP
Autosomal Recessive (AR-HAP)

SPG11 15q Spatascin Endosomal trafficking 50% of AR–HSP Thin corpus callosum, cognitive
impairment, and severe axonal
neuropathy
SPG7 16q Paraplegin Mitochondrial m-AAA ATPase ~30 families Variable onset, cerebellar signs, optic
atrophy, neuropathy
X-linked
SPG1 Xq28 L1CAM Cell adhesion and signalling, neurite Over 100 cases Cognitive impairment hypoplasia of the
outgrowth, neuronal cell migration corpus callosum, adducted thumbs and
and survival hydrocephalus
SPG2 PLP1 Major myelin protein in oligodendroglia <100 cases Quadriplegia, nystagmus, cognitive
impairment, seizures
Hereditary Spastic Paraparesis and Other Hereditary Myelopathies
Mitochondrial
No SPG designation ATP synthase 6 Mitochondrial localisation, ATP 1 family Late onset disorder
synthesis
Source: Adapted from Salinas, S. et al., Lancet Neurol 7, 1127–1138, 2008; and Noreau, A. et al., Exp Cell Res, 18–26, 2014
239
Molecules can be internalised (endocytosis) or externalised (exocystosis)

into the cells or degraded by lysosomes. Endosomes are central to the move-
ment of vesicles that contain these molecules. The endosomes are linked with
the plasma membrane, golgi apparatus, and lysosomes. There are several
genes linked with HSP that encode proteins that are involved in endosomal
trafficking (e.g., in SPG47 & SPG50-52 components of protein complexes that
play a role in secretory/endocytic pathway are affected).
All cells require the mitochondria to produce ATP via oxidative phosphor-
ylation. Longer axons with their large volume and reliance on axonal trans-
port seem particularly susceptible to disorders of mitochondrial function
and several genes have been identified that impair mitochondrial regulation
and cause HSP (e.g., SPG7 encodes paraplegin and SPG13 encodes chapero-
nin 6).
More recently, genes involved in lipid metabolism have been associated
with HSP. Lipids are involved in energy storage, signaling, and in the forma-
tion of the plasma and intracellular membranes, which cover a large area in
longer neurons. Proteins have been described, for example, that are involved
in lipid metabolism, hydrolyzing phospholipids into fatty acids (DDHD2,
SPG54), or in the processing of gangliosides that are signal transducers
within the plasma membrane (e.g., B4GALNT-1, SPG26). The production of
the myelin sheath by oligodendrocytes can also be affected and genes caus-
ing HSP can be expressed in oligodendroglia, but not in motor neurons (e.g.,
SPG2).8,13
Overall, the pattern suggests that abnormal cellular trafficking/axonal
transport results in degeneration of the nerves. The distal-most parts of the
long axons are first affected as molecules need to be transported across a
long distance and this requires more energy to function (i.e., those axons
projecting to/from the spinal cord segments supplying the lower limb). The
recent finding of genes being involved in lipid metabolism and in oligoden-
drocyte function, however, highlights that a common mechanism for all
causes of HSP may not be present. Given the heterogeneous presentation
of HSP, more work is required to understand the genotype-phenotype rela-
tionship in terms of symptom presentation, longitudinal progression, and
prognosis with intervention.
9.2.3.2 Changes in Descending and Ascending Tract Function

The pathology in HSP is one of a dying back axonal degeneration predom-
inately affecting the corticospinal tracts. The longer tracts that supply the
lower limbs are affected first, with shorter tracts supplying the trunk and
arms being affected later with disease progression.15 In keeping with this,
the lower limb motor-evoked potentials (MEPs) following stimulation of
the motor cortex using transcranial magnetic stimulation (TMS) are either
absent or have a higher threshold. Further, when a response is present the
central conduction time is prolonged. In contrast, hand muscle responses to

motor cortex stimulation are usually normal.16–20
The most common MRI change is thinning of the cervical and thoracic spi-
nal cord. Although MRI and volume-based morphometry of the brain may
be normal, in SPAST (SPG4), changes are seen with diffusor tensor imag-
ing (DTI).21 The DTI reveals white matter changes in the posterior limb of
the internal capsule and peritrigonal white matter. Frontal lobe white matter
changes are more marked, with longer disease duration.21 In complicated
presentations, such as SPG11, white matter changes are more marked and
also involve the striatum and brainstem.22–24
Degeneration of the ascending tracts lying in the fasiculus gracilis of the
dorsal columns carrying somatosensory information from the lower limbs
have also been described.17 Lower limb somatosensory-evoked potentials
can be reduced in size. A reduction in vibration threshold is seen in ~40–60%
of patients, although, interestingly, other sensory signs are not commonly
seen on clinical testing.25 Similarly, although people with HSP do not usually
present with brainstem signs, white matter loss in the brainstem and abnor-
mal brain stem auditory-evoked responses may be seen.26 Degeneration of
the spinocerebellar tracts and an associated with loss of volume in the poste-
rior fossa have also been described in SPG427 and in complicated forms overt
cerebellar signs can be seen. Cerebellar signs are particularly prominent in
SPG7 and 15.
9.2.3.3 Changes in Cortical Activation with Movement

On fMRI, comparisons have been made between activation patterns asso-
ciated with movement of the relatively unaffected hand and ankle move-
ments. Ankle movements in autosomal dominant (AD)-HSP and SPG4 show
variable changes with reduced contralateral sensorimotor cortical activa-
tion28 and increased activation of bilateral motor cortex and supplemen-
tary and premotor cortex29 and the ipsilateral cerebellum.28 In two studies
normal activation was seen with hand movements,28,29 whilst Koritnik et al.
(2009) found increased contralateral sensorimotor cortex and bilateral pos-
terior parietal cortex activation with hand movements.30 The finding that
changes in activation may be seen when moving an unaffected body part
(the hand) is suggestive of functional reorganisation. Therefore, changes in
cortical activation when moving an affected body part (the ankle) may not
be solely related to performance differences between people with HSP and
healthy controls.30 As described after stroke, the different patterns of corti-
cal activation may reflect differences in the degree of pathology affecting
the sensorimotor system with more widespread, bilateral changes reflect-
ing more severe pathology.31 Patterns of functional re-organisation will also
reflect additional factors such as the impact of environmental factors and
task-related activity.
BOX 9.1 PATIENTS’ EXPERIENCE OF HSP: POTENTIAL

BENEFITS OF ACTIVITIES AND EXERCISE CLASSES
Bob was a keen runner; he had experienced symptoms of pain around
the pelvis for 7–8 years before he was diagnosed with HSP-type SPG4
in 1999. With hindsight, his pain may have been related to strategies
he adopted while running to compensate for his increasing stiffness
in the legs.
Following diagnosis, Bob trialled baclofen at a low dose. He described
‘minor, if any’ improvement in his walking, and unfortunately he expe-
rienced significant and intolerable side effects of fatigue, drowsiness,
and ‘brain fog’. Bob stopped taking the baclofen and has not tried any
other type of anti-spasticity medication. In part, this is because he feels
that his spasticity still has a low-to-medium impact on his walking but
also because he has taken up flying on a regular basis and, under civil
aviation authority rules, cannot take baclofen.
Bob’s walking difficulties have progressed over time; he currently
has difficulty walking in the house and tends to cling onto furniture
and walls. Outside, he uses two crutches; he finds that ball-point fer-
rules provide the most effective grip when he places his crutches at
more acute angles. He drives an automatic car with hand controls.
In Bob’s description: ‘my legs—they refuse to do what my Brain is
telling them to do. When walking my knees hyperextend, and I get
this swelling, pain, and tenderness at the back of my knees. I often
drag my toes and then my foot turns in [inverts] and can roll over’.
Bob describes his legs as stiff when he walks; he does get ankle clonus
but very rarely gets spasms. To compensate for the stiffness in his legs
Bob moves his trunk a lot while walking; unsurprisingly, he has gradu-
ally, over the years, developed lower back pain and reduced standing
balance. He falls occasionally and this tends to be immediately after
getting up from sitting for a prolonged period (>1 hr). Bob can experi-
ence significant fatigue, particularly toward the end of the day. At these
times he may choose to use a wheelchair or rollator. Bob is clear that his
fatigue is not only related to how much he physically does but also the
degree of concentration required to safely move and function plus the
emotional stress and impact this can have.
For the first 10–15 years, Bob found functional electrical stimulation
(FES) useful. He worked with the clinicians at the National FES cen-
tre in the UK, where he developed a stimulation pattern of the trunk
and hip abductors that helped to minimise the excessive trunk sway
he experienced while walking (described in 2). Bilateral stimulation
for foot drop was also useful for a time. Recently, Bob decided to stop
using FES as it was no longer significantly helping his walking. He feels
that FES may be more beneficial in the early stages of the condition.
Instead he uses rigid ankle-foot orthoses; these keep his toes up and
stop the inversion of his foot.
Throughout the years of managing his symptoms Bob has remained
active and incorporates daily stretches for up to 5–10 minutes targeting
his plantarflexors, hamstrings, and quadriceps. Once a week he attends
a 30-minute exercise class that is run by a trainer who is an ex-Olympic
athlete with multiple sclerosis. In addition, Bob has recently discovered
Riding 4 the Disabled’; he describes this as ‘fantastic’; as well as being
enjoyable it helps his balance and core trunk strength.
9.2.4 Symptoms Associated with HSP

9.2.4.1 Limb Stiffness
Increased limb stiffness is a defining feature of HSP. The stiffness is due to a
combination of increased passive stiffness and enhanced excitability of the
stretch reflexes.32 People with HSP do not seem to have continuous muscle
activity whilst trying to rest, i.e., ‘spastic dystonia’. Cramps, particularly of
the ankle plantarflexors, and lower limb flexor/extensor spasms, elicited by
stimulation of the plantar aspect of the foot, have been reported.
Increases in passive stiffness can be seen when the joints of relaxed partici-
pants (as confirmed using surface EMG) are slowly stretched at speeds that do
not elicit a stretch reflex (e.g., at 5o/s). Faster stretches elicit a short-latency stretch
reflex that is higher in amplitude compared to healthy controls and results in
a further increase in stiffness. The difference between the stiffness measured
at fast and slow speeds is an estimate of the stretch-reflex mediated stiffness
and is proportional to the evoked EMG response.32 Measuring stiffness in this
way, however, does not take into account the impact of passive changes and
stretch reflex activity on the viscous response.33 We have recorded stretch reflex
thresholds as low as 10o/s in people with HSP. This has implications for clini-
cal assessments using scales such as the Tardieu scale, where the slow stretch
that measures the passive component should be purposefully below the stretch
reflex threshold (e.g., a 90° movement should take >9 s to perform).
The mechanisms underlying hypertonia in HSP have not been as fully
explored as they have been in other conditions. Whether increased passive
stiffness is associated with an increase or change in the amount or quality
of the connective tissue as seen in cerebral palsy and spinal cord injury or
is associated with shortened muscle fascicles as measured using ultrasound
has, to date, not been reported.34,35
A limited exploration of the role of altered spinal cord inhibitory circuits
in the genesis of spasticity has been performed. Mazzocchio and Rossi (1989)
found in people with progressive spastic paraparesis and HSP that the
Renshaw-mediated recurrent inhibition was less than in healthy controls.

Further, there was a smaller reduction in recurrent inhibition with volitional
movement compared to controls.36 This may in part explain why stretch
reflex-mediated stiffness is not significantly different from healthy controls
when a muscle is preactivated to ~10% of the maximum voluntary contraction
and then stretched.32 A theoretical explanation based on current evidence
from people with HSP and other conditions is as follows: at rest, reductions
in spinal cord inhibitory circuits (e.g., recurrent and reciprocal inhibition) in
people with spasticity contribute to a heightened stretch reflex size.37 In con-
trast, with preactivation of the muscle, inhibitory activity reduces in healthy
participants but does not reduce as much in people with HSP.38 This could
result in similar values of spinal cord inhibition when the muscle is preac-
tivated and thus a similar response to muscle stretch. Further, the overall
stiffness is, in part, mediated by active cross bridge formation resulting in
similar stiffness values between the two groups. From a practical basis, as
other groups have highlighted, this has implications for the role of spasticity
in causing difficulties with functional movements.39,40 The high resistance
to movement when a resting muscle is passively stretched during a clinical
examination on a treatment couch may therefore not correspond to the resis-
tance occurring when the same muscle is stretched during a functional task
when it is pre-activated (see also impact on functional ability, below).
Changes in other spinal cord inhibitory circuits, such as reciprocal and
presynaptic inhibition, the development of motor neuronal plateau poten-
tials and changes in 1a afferent neurotransmitter release that occurs with
repetitive stimulation (reduction in post-activation depression) reported in
other UMN syndromes have not been assessed in people with HSP. Recent
work has found that there are differences in the patterns of inhibitory spi-
nal cord circuit alterations in adults where spasticity developed over the
developmental period (people with cerebral palsy) compared to adults with
acquired spasticity (people with adult-onset stroke).41 In adult cerebral palsy
a reduction in presynaptic inhibition is observed but there are no reduc-
tions in reciprocal inhibition in contrast to the person with adult-acquired
spasticity.41 Given that many types of HSP have an onset in early childhood
(1 year and above42), it would be interesting to compare spinal cord inhibi-
tory circuitry in early- and late-onset HSP and whether this leads to any
quantifiable impact on the response to muscle stretch and function.
Cortical modulation of stretch reflexes is also abnormal in HSP. Usually in
healthy control participants the soleus H-reflex is facilitated by prior stimula-
tion of the motor cortex leg area at interstimulus intervals of 10 and 20 ms and
70–90 ms. This early facilitation is lost in people with HSP and a new form of
facilitation at an interstimulus interval of 40 ms is seen. This was felt to reflect
the longer desynchronised central conduction times in HSP 43 (Figure 9.1). These
changes were not related to motor function. Whether soleus H-reflex modula-
tion during the stance and swing phases of walking is disrupted in HSP as
described in other conditions with spasticity is currently unknown. However,
TMS TMS
10 ms
(a) Electrical stimuli (b) Electrical stimuli
450
400
350
300
250
%
200
150
100
50
0
0 10 20 30 40 50 60 70 80 90
(c) ISI [ms] Controls Patients
FIGURE 9.1
Cortical modulation of the H-reflex was assessed by stimulating the cortex using TMS at different
inter-stimulus intervals (ISI) in the range 0–100 ms prior to stimulating the H-reflex. The H-reflex
responses for a healthy participant (a) and person with HSP (b) are shown with ISI 0–90 ms super-
imposed. A comparison of the control (n = 10) and HSP (n = 10) groups show that early facilitation
of the H-reflex at ISI = 10 and 20 ms is less in HSP, possibly reflecting longer desynchronised central
conduction times. Panel (c) shows the mean amplitude of the soleus muscle H reflex for each inter-
stimulus interval. This is expressed as a percentage of the baseline H reflex which was about 10%
of the supramaximal M response. (Adapted from Serranova, T. et al., Neurosci Lett, 437, 15–19, 2008.)
phase-dependent modulation of cutaneous reflexes elicited in tibialis anterior

and biceps femoris by stimulation of the sural nerve are smaller in HSP.44
As with other conditions, the central changes resulting in spasticity in HSP
are unclear. The degree of spasticity (as measured by the Modified Ashworth
Scale) is negatively correlated to activity in Brodman’s area 4 and 1-2-3, mea-
sured using fMRI during ankle movements.28 However, here spasticity may
simply be a marker of disease severity and not reflect a causative relationship.
The cortical silent period is an interruption of a voluntary muscle contraction
following stimulation of the contralateral motor cortex using TMS. Earlier inhibi-
tion is in part spinally mediated, whilst later suppression reflects the activation
of GABAB (gamma-aminobutyric acid) receptor-mediated cortical inhibitory cir-
cuits.45 In HSP (SPG4), the cortical silent period is shortened, indicating reduced
activity of motor cortical inhibitory interneurons. The reduction in the cortical
silent period in turn was associated with the degree of spasticity as measured
by the Ashworth Scale.17 This has correlates in stroke and amyotrophic lateral
sclerosis (see below), where a shortened cortical silent period is associated with
the development of spasticity.46–48 Using paired-pulse TMS, other groups have
found an increase in intracortical facilitation in AD-HSP.49 The increase in
intracortical facilitation may reflect a reduction in GABA-interneuronal activ-
ity (in keeping with the shortened cortical silent period) but may also reflect
an increase in glutamateric transmission or a compensatory mechanism to
increase corticospinal transmission. Interestingly, the changes in intracortical
facilitation were found in areas controlling hand muscles. Thus, the association
between changes in cortical silent period and spasticity may either be causative
or reflect the co-occurrence of paresis and spasticity and compensatory mecha-
nisms to maintain or increase corticospinal output.49
9.2.4.2 Paresis
Lower limb weakness co-occurs with spasticity in HSP. Muscle strength is
commonly described as being clinically less affected than that seen in other
acquired UMN syndromes.13 Objectively isometric maximal voluntary con-
traction of lower limb muscles in HSP has been measured using dynamom-
etry.32 The isometric contraction aimed to avoid reductions in applied torque
by stretch reflex activation in antagonist muscle groups that may occur dur-
ing isokinetic testing. Isometric muscle strength was lower in all lower mus-
cle groups tested (Figure 9.2). When combined flexor and extensor muscle
strength at the ankles, knees, and hips was compared to healthy controls
there was a proximal to distal gradient of weakness.
2.5
2 HSP CONT
Torque (Nm/kg)
1.5
0.5
0
Hip add
Hip abd
Hip flex
Hip ext
Knee ext(sitting)
Knee flex(sitting)
Ank PF
Ank DF
Muscle group
FIGURE 9.2
Differences in isometric strength between people with HSP (n = 20) and healthy controls (n = 18).
The two muscles most affected were the ankle dorsiflexors and the
hip abductors, which were on average ~50% the strength of that seen in
age and gender matched controls.32,50 Significant differences in the ratio
between agonist-antagonist muscle strength are also seen. The ratio of
hip abductor/hip adductor strength, for example, is significantly lower in
people with HSP. This muscle imbalance with relative sparing of some
muscle groups such as the hip adductors may account for ‘spastic gait pat-
terns’ such as scissoring while walking rather than being attributable to
spasticity per se.
9.2.4.3 Sensory Loss
Vibration threshold is increased in ~40% of people with HSP and is greater
distally at the hallux.25 This may reflect degeneration of the fasiculus gracilis
but also spinocerebellar degeneration as conscious perception of vibratory
signals may be mediated by both pathways.51,52
9.2.4.4 Bladder
Bladder dysfunction is seen in ~75% of people with HSP,53,54 but is often
not reported. A retrospective review revealed symptoms of urgency (51.0–
72.4%), frequency (55.1–65%), urinary incontinence (55.2–69.4%), hesitancy
(51.7%), and incomplete bladder emptying (36.75%).53,54 Urodynamic analysis
revealed detrusor overactivity in 82.7% of cases and detrusor sphincter dys-
synergia in 65.5% of cases. Detrusor overactivity was associated with higher
post-void residuals and symptoms of urinary frequency and nocturia.53
9.2.4.5 Bony Changes
As HSP is a condition that can have an onset during development there is the
potential for bony change similar to that seen in CP or Freidriech’s ataxia/
Charcot-Marie Tooth disease. These may contribute to motor dysfunction.
In children with HSP, hip joint motion in the transverse plane while walk-
ing is similar to typically developing children, in contrast to children with
cerebral palsy and spastic diplegia (CP-SD) who demonstrate high internal
rotation. Although not confirmed by X-rays, this suggests that in early-onset
HSP there is a physiological correction of femoral anteversion compared to
children with CP-SD, in whom symptoms are present from birth. Pes cavus
is commonly seen in HSP. The high arched foot and altered heel alignment
could affect the line of pull of the plantarflexors, reducing the effective plan-
tarflexor torque during the push-off phase of walking. People with HSP com-
monly have an increased lumbar lordosis and, as highlighted below, trunk
motion is often increased while walking; this is associated with a high inci-
dence (>75%) of lower back pain.
9.2.4.6 Fatigue
As with other long-term neurological conditions, fatigue is common and
shows similar complexities. The degree of fatigue, for example, is not always
related to the amount of physical activity performed and cognitive tasks,
stress, and anxiety may also impact on fatigue and walking performance.
9.2.4.7 Mood and Quality of Life

Reduced mobility is also associated with the presence of depression, as mea-
sured by the Beck depression inventory, with 28/48 (58%) of cases showing
depression, which in 75% of these cases was mild.55 Quality of life is reduced
in people with HSP and is lower in people with more severe disease (as mea-
sured by the Spastic Paraplegia Rating Scale56), reduced walking ability, and
the presence of a type 2 complicated presentation.57,58
9.2.5 Impact of Spasticity and Associated Symptoms on Functional Ability

People with HSP in particular have difficulties with walking, balance, and
falls. Discussion and focus groups with people with HSP in the UK (n =
30; unpublished, observations59) have highlighted the difficulties with func-
tional tasks. Understanding these perceptions are important when elucidat-
ing the relative impact of symptoms such as spasticity and limb stiffness.
People with HSP find that walking backwards (such as stepping back to
open a door), walking on uneven terrain, and walking on cambers or slopes
can be particularly difficult. Falls can be precipitated by a loss of balance
but also by tripping caused by foot drop as the foot either contacts external
objects or catches the other foot or leg in swing phase. Walking is reported
to require increased attention as people have to concentrate on their foot
placement and performing concurrent tasks (i.e., walking and talking) can
be difficult. Walking and lower limb stiffness was often (>50% of respon-
dents) modulated by the environmental temperature, with stiffness higher
and walking more difficult in cold weather compared to warm weather –
although very hot, humid climates were reported to cause excessive fatigue
and limit walking ability.
9.2.6 Balance
Causes of poor balance in HSP could be due to multiple factors, such as
impaired central afferent and/or efferent signal processing, poor central inte-
gration of multi-sensory afferent signals, spasticity, and secondary changes
in muscle strength and musculo-tendinous stiffness.
People with HSP show delayed lower limb muscle responses to forward
and backward postural perturbations.60 This is presumably in part due to
dorsal column-medial leminiscal and spinocerebellar degeneration leading
to impaired processing of afferent signals that detect the onset, size, and
direction of the perturbation. An important role in afferent as opposed to
efferent pathway pathology in causing balance dysfunction is supported by
the fact that the onset of the lower limb muscle response following a pertur-
bation is normalised when the perturbation is paired with an acoustic signal
eliciting a startle response.60,61 This suggests that the efferent pathways medi-
ating the startle response (presumed to be the reticulospinal tract) are intact.
An improvement in muscle onset times with a startle response is also seen
in healthy controls but it is more marked in people with HSP.60,61 Enhanced
startle responses have been reported following pontine stroke, where they
are felt to arise due to a disruption of the cortical control of lower brain stem
centres.62 As many cortical projections to the brainstem arise from collaterals
of the corticospinal tract a similar cause of enhanced responses to a startle
could occur in people with HSP. The relative importance of abnormal pro-
cessing of afferent information is supported by other groups that have found
that higher degrees of standing postural sway are associated with increased
vibratory thresholds.50
Muscle weakness also contributes to poor balance. Greater postural sway
in the mediolateral plane is associated with greater weakness in the hip
abductors. Greater antero-posterior sway during quiet standing and follow-
ing a forward perturbation is correlated with greater weakness in the ankle
plantarflexors.50,63
The role of spasticity in mediating imbalance remains unclear. De Niet et al.
(2012) found that greater stffness (as measured by the Modified Ashworth
Scale) resulted in greater imbalance following a toe-up perturbation in HSP.63
This perturbation stretches the ankle plantarflexors and requires a stabilis-
ing response in the tibialis anterior. Interestingly, the strength of the tibi-
lais anterior (as measured using manual testing) did not affect the response
size. In contrast, Marsden and Stevenson (2012) measured ankle passive and
stretch reflex mediated stiffness in people with HSP using motor-driven
perturbations. They found that greater total ankle stiffness and stretch-
mediated stiffness were associated with less antero-poterior sway.50 They
suggested that higher ankle stiffness may serve to aid stability.
9.2.7 Walking
Walking difficulties is a characteristic feature in HSP. A study of 194 people
with HSP in Norway highlighted that 31% were classified as having mild
symptoms; 32% as walkers that were unable to run; 25% as walkers depen-
dent on walking aids; and 11% as wheelchair-dependent.42
People with HSP walk with a slower velocity, have a smaller step length,
an increased stride and step time, and a larger base of support.64–66 The walk-
ing pattern in HSP has been characterised in several studies. Using cluster
analysis, Wolf et al. (2011)66 identified 5 clusters similar to that described pre-
viously for children with cerebral palsy67–69 (Figure 9.3).
Crouch Recurvatum Stiff knee Jump knee Norm like

40 40 40 40 40
PelvicTilt
20 20 20 20 20
0 0 0 0 0
0 50 100 0 50 100 0 50 100 0 50 100 0 50 100
60 60 60 60 60
HipFlexExt
40 40 40 40 40
20 20 20 20 20
0 0 0 0 0
–20 –20 –20 –20 –20
0 50 100 0 50 100 0 50 100 0 50 100 0 50 100
80 80 80 80 80
KneeFlexExt
60 60 60 60 60
40 40 40 40 40
20 20 20 20 20
0 0 0 0 0
0 50 100 0 50 100 0 50 100 0 50 100 0 50 100
DorsiPlanFlex
20 20 20 20 20
0 0 0 0 0
–20 –20 –20 –20 –20
–40 –40 –40 –40 –40
–60 –60 –60 –60 –60
–80 –80 –80 –80 –80
0 50 100 0 50 100 0 50 100 0 50 100 0 50 100
Gait cycle [%] Gait cycle [%] Gait cycle [%] Gait cycle [%] Gait cycle [%]
FIGURE 9.3
Walking patterns in people with HSP and CP, highlighting different types of gait presentation.
Crouch gait: characterised by increased hip and knee flexion during stance phase. Recurvatum:
characterised by increased knee hyperextension in mid-stance. Stiff knee: characterised by
reduced knee motion in swing phase. Jump knee: characterised by increased knee ﬂexion at
loading response and almost-normal knee function later in the gait cycle. Normative: a gait
cycle similar to normative data obtained from healthy control participants.
Comparisons have been made between people with HSP and spastic
diplegia due to cerebral palsy (CP-SD). In part, this is driven by the desire to
identify characteristics that may aid in the differential diagnosis of CP-SD.
The proportion of people with prolonged knee and hip extension character-
istic of a recurvatum pattern and prolonged ankle plantarflexion in stance
phase was higher in people with HSP.64,66 Increased amplitude and speed of
trunk movement in the sagittal plane was also greater in people with HSP
compared to people with CP-SD who tend to show higher shoulder motion
(flexion/extension and elevation) akin to the ‘guarding’ seen by infants in the
early stages of walking.65
There are several impairments that correlate with the characteristic walk-
ing patterns seen in people with HSP. For example, greater stiffness in the
hip flexors, as assessed using the Ashworth Scale, is associated with reduced
active range of movement and slower walking speeds. Other studies have
focused on specific aspects of the gait cycle, such as ankle equinus and stiff
knee gait, as outlined below.
Early studies modeling walking have highlighted that movement of the

leg in swing phase from knee flexion through to knee extension in terminal
swing is in part passive in nature, reflecting the motion of a multi-linked pen-
dulum moving as a result of torques generated at the end of stance phase.70
More recent modeling studies have highlighted the importance of muscle
activity during swing phase in regulating the motion of the leg.71,72 Eccentric
lengthening of the rectus femoris muscle, for example, controls the initial
rapid knee flexion at the start of the swing phase while hamstring muscle
activity acts to control the subsequent extension of the knee at the end of the
swing phase. Modeling studies have also highlighted the importance of the
ankle plantarflexors and hip flexors in generating torques that initiate swing
phase.73,74
Using dynamometry to produce motor-driven perturbations and test
strength, Marsden et al. (2012) explored impairments that were associated
with reduced knee flexion; the stiff knee gait. Of the variables prospectively
assessed (knee extensor passive and stretch-mediated stiffness, ankle plan-
tarflexion and hip flexion strength) they found that increased knee extensor
passive stiffness and weakness in the ankle plantarflexors were associated
with reduced ankle power and an increased knee extensor moment in pre-
swing, and in turn reduced knee flexion velocity and amplitude.32 Lower
knee flexion velocity at the start of swing phase was also associated with
less knee extension at the end of stance phase, reflecting the impact on the
pendular motion of the leg (unpublished observations).
This study highlights the relative importance of passive stiffness and
weakness in producing stiff knee gait. It also brings into question the rela-
tive role of knee extensor spasticity in limiting knee motion. Although knee
extensor spasticity was significantly higher in people with HSP compared
to controls, this was not correlated with a limitation in knee flexion.32 This
could reflect the fact that with activation of the muscle at the end of stance
phase the stretch-reflex mediated stiffness is normalised, as described above.
However, the lack of correlation could also reflect the methods used. Knee
extensor stiffness was measured with the participant in supine while they
rested or preactivated the muscle. Although this reflects the assessment of
limb stiffness in clinical practice, stretch reflex activation during walking
was not assessed. In other UMN conditions it has been reported that the
stretch reflex activity in the knee extensors normally modulates while walk-
ing, being higher in amplitude during stance as opposed to swing phase.
This is felt to reflect changes in the degree of muscle activation (and so the
excitability of the motor neuron pool) but also modulation in pre- and post-
synaptic inhibitory circuits within the spinal cord.75 In other conditions with
spasticity, this degree of modulation is reduced.76 Therefore, stretch reflex
behavior at rest may not reflect that seen during functional movements.
However, in support of the finding of a lack of relationship between knee
extensor spasticity and stiff knee gait, Piccini et al. (2011) recorded less rec-
tus femoris activity while walking in children with HSP in contrast to those
with CP-SD where excessive activity was noted.65 Other studies measuring
spasticity using motor-driven stretches have highlighted a potential role of
spasticity in limiting joint motion while walking. Higher plantarflexor stiff-
ness (due to a combination of passive and stretch-mediated stiffness) was
associated with reduced ankle dorsiflexion during walking.77 This effec-
tively lengthens the limb during swing phase and contributes to the trips
and falls seen in people with HSP.
Central motor conduction time to leg muscles as assessed using TMS does
not correlate with gait parameters in HSP.78 This is in keeping with studies
in stroke suggesting that corticospinal tract damage (as determined via DTI,
MRI, and TMS) may not be a key determinant in limiting walking ability,79,80
unlike its fundamental role in fine fractionated finger motion and hand
function. This may be because walking is more dependent on subcortical
circuitry81 and/or because people are able to compensate for weakness by
using other body segments to aid progression and by altering lower limb
alignment relative to the ground reaction force to aid stability in stance.
There are several compensatory strategies that people with HSP seem to
adopt to aid walking. Increased hip flexion during swing phase is associated
with greater toe clearance.65,77 The excessive trunk and pelvic motion seen
in many people with HSP may also aid leg swing.65 Higher trunk and pelvic
horizontal and coronal motion is seen in people with less flexion of the knee
during swing phase (unpublished observations) and may aid leg swing. Knee
recurvatum brings the ground reaction force in front of the knee and could
be a compensatory strategy to compensate for weakness in antigravity mus-
cles such as the knee extensors, which are more frequently MRC grade 1–2
and weaker compared to people with CP-SD.64,65 Alternatively, knee hyper-
extension may be related to an increase in the plantarflexion/knee extension
couple associated with increased plantarflexion stiffness as is often reported
in CP-SD.65 Determining the exact reasons for knee hyperextension in HSP is
important in guiding treatments as reducing the ability to hyperextend the
knee (e.g., with splinting) may result in instability in the presence of knee
extensor weakness.65
These potential compensatory strategies may not be wholly beneficial.
Increased trunk motion associated with an increased lumbar lordosis, ante-
rior tilt of the pelvis,65,66 and tight hip flexors may contribute to the high
incidence of lower back pain. Further, knee recurvatum can be associated
with stretching of the soft tissue on the posterior aspect of the knee and
subsequent knee pain.
9.2.8 Outcome measurement
There is a relative paucity of disease-specific rating scales for HSP. The spas-
tic paraplegia rating Ssale (SPRS) described by Schule et al. (2006) is a stan-
dardised, 13-item tool that combines measures of walking performance, stair
climbing, rising from a chair, lower limb spasticity, muscle power, range of
BOX 9.2 PEOPLE’S EXPERIENCES OF HSP: THE

BENEFITS OF ITB AND KEEPING ACTIVE
Pam describes symptoms of HSP occurring throughout all of her life;
she was finally diagnosed 18 years ago, after 2 years of investiga-
tions, when she was 33. Within her family, her grandmother, mother,
and brother all experience walking difficulties. She does not have a
genetic diagnosis and does not feel that having one would make much
difference.
Pam walks with one stick and describes poor balance and the need to
rest every 5 minutes as her legs become tired. She has difficulty climb-
ing and descending stairs. Pam has lost confidence in her walking and
falls about once a week. She tends to catch her toes as she lifts her feet:
‘I go straight down and am unable to use my arms to save myself’. Pam
explains that her legs can feel both stiff and weak and is particularly
marked after any activity. She used to do stretches but did not find
them helpful; instead, she explains: ‘I find a couple of hours out in the
afternoon wandering around the shops is more beneficial than being
sat in the house doing exercises’.
Pam has an intrathecal baclofen pump that was implanted 1.5 years
ago. She found that oral baclofen made her very sleepy but this is no
longer a problem with the ITB pump. Since having the pump, Pam feels
she stoops less and has a more upright posture when walking.
Before the operation, she had symptoms of urgency (‘wanting to go
quickly’). In the last year Pam feels her bladder function has deterio-
rated. She now feels she wants to go but the urinary flow has stopped,
leading to her having an accident afterwards (symptoms akin to blad-
der sphincter dyssynergia). She has her pump filled locally and finds
this very convenient and sees a rehabilitation consultant once a year.
movement, pain, and bladder and bowel function. An inventory of compli-

cating signs and symptoms differentiates between pure and complex forms
of HSP. The SPRS takes 15 minutes to complete and higher scores indicate
worsening disease severity. The SPRS has high levels of inter-rater agreement
(intraclass correlation coefficient = 0.99), internal consistency (Cronbach, α =
0.91), criterion (r = 0.83, p < 0.001), and construct validity.56
9.2.9 Interventions
9.2.9.1 Pharmacological and Surgical Treatment of Spasticity
The role of anti-spasticity medications in the management of spasticity
and function have been explored in several studies. However, they show
considerable bias with studies showing low sample sizes, a lack of control
groups, and blinding. A retrospective review of botulinum toxin injec-
tions into the hamstrings, hip adductors, and gastrocnemius of 12 children
(6.9 years +/− 4.9 years) with HSP reported a decrease in stiffness (as mea-
sured by the Ashworth Scale) and improvement in motor function (as mea-
sured by a 2.4 +/− 3.2 change in the gross motor function measure [GMFM])
over an average 13.2-month (11.0) period.82 The GMFM is an ordinal measure
assessing movement ability in lying, sitting, standing, and walking. Given
the lack of a control group, the results on function should be interpreted with
caution. Comparing the results to children with CP of the same age and sever-
ity (as measured by the gross motor classification scale), the GMFM changes
by ~5 points over a 1-year period83 as the child develops new skills. Therefore,
these results could simply result from changes in motor function with devel-
opment. Subjectively, 11 out of 12 parents felt that there was an improvement
in motor function with 2 out of 12 reporting an improvement in activities of
daily living.82 A series of 19 case reports in adolescents and adults with HSP
described the use of botulinum toxin injections into multiple muscle groups
(hip adductors, Iliopsoas, plantarflexors, rectus femoris, and posterior tibial).
Reductions in stiffness were widely reported and this could be associated
with changes in posture (e.g., the ability to cross the legs) and function (e.g.,
walking) although 7 out of 19 reported no or minimal global subjective effect.
The functional effects were more marked in people with mild or moderate
spasticity. Increased weakness was reported in 3 out of 19 people, which was
felt to be an unmasking of underlying weakness following spasticity reduc-
tion.84 Similar effects have been reported in 15 people with HSP who had
injections into the hip adductors, plantarflexors, or posterior tibial muscles.
Reductions in adductor and plantarflexor spasticity were reported and 6 out
of 15 showed an improvement in walking velocity. The functional ambulation
category (FAC) and Rivermead motor assessment did not change.85
Oral anti-spasticity medications are frequently used in HSP, including
baclofen and tizanidine. To date, there have been no trials of these medica-
tions in HSP. Clinical opinion suggests that they can be associated with wide-
spread fatigue and improve function in only a limited number of people.84,85
Gabapentin is a GABA agonist originally used to treat epilepsy and neuro-
pathic pain. Its effects were assessed in a cross-over trial of 10 people with
HSP (SPG4).86 Blood samples confirmed that a therapeutic dose (4000 mg/
day) was present during the intervention periods. There were no differences
between gabapentin and placebo in terms of subjective report of disability,
clinical assessment of lower limb reflexes, strength or limb stiffness, walking
scales or motor intracortical excitability as measured using TMS. In an open-
label trial of methylphenidate in people with sporadic and hereditary spastic
paraparesis no effect was found on walking speed or walking parameters
after a 6-month period of use.87
Intrathecal baclofen has the advantage of reducing side effects asso-
ciated with oral baclofen such as weakness and fatigue. Double-blind
administration of a bolus of baclofen into the intrathecal space is associated

with a clear reduction in stiffness and deep tendon reflexes that is main-
tained with long-term administration.88 However, the impact on walking has
only been assessed using case studies. Without the use of control groups
or single case study designs with multiple baseline measures these studies
clearly present with a risk of bias, although they do highlight some potential
benefits and limitations. Improvements have been seen in walking speed,
walking kinematics/kinetics, and angle-angle plots with either a single bolus
or continuous infusion over time.89–91 Other movements such as squatting
also show a normalisation with a change from co-contraction to a recipro-
cal pattern of lower limb activation with a bolus of baclofen.92 The timing of
administration and the titration of the ITB dose is important. Satisfaction is
higher in people in whom the implant occurs while they are still ambulant.
Initially, people can report weakness.93 The reported therapeutic dose has
varied from 60–264 mg/day and may vary depending on the underlying pat-
tern of symptoms.89 As well as potentially impacting on walking ability, ITB
may improve sleep time and efficiency and reduce periodic leg movements.
These improvements were reported in a study of 20 people with spasticity, of
whom 1 had HSP; they were not accompanied by any change in lung func-
tion tests or sleep-related respiratory patterns.94 Bladder function has also
been reported to have improved with ITB.95
In 4 adults with pure (type 1) hereditary spastic paraparesis (genetic diag-
nosis not given) the effects of selective dorsal root rhizotomy from L2–S2
nerve roots have been described. Following the procedure, reductions in
tone and spasm frequency accompanied a subjective improvement in stand-
ing posture, stability, and walking with a decrease in scissoring of gait.96
BOX 9.3 PATIENTS’ EXPERIENCES OF HSP:

HSP ACROSS THE LIFESPAN
BIll is 54 years old, he has experienced symptoms since birth. Up to
the age of 27 his diagnosis was described as a ‘best estimate’ of cere-
bral palsy. There was no known family history in previous generations.
When his elder brother became affected in his early thirties, this acted
as a trigger for Bill to get ‘re-diagnosed’. At the time there was no spe-
cific gene testing but they were both given the diagnosis of HSP. Gene
testing followed later with a positive diagnosis of SG4. Since that time,
Bill’s mother (aged 80) has tested positive for SPG4. She had experi-
enced difficulty with mobility since her mid-sixties but not to the same
extent as her son’s; she has recently had a fairly severe stroke and now
is unable to bear weight. Another brother has also recently tested posi-
tive for SPG4 but so far is not showing any symptoms.
Bill walked without aids for several years. People would often com-
ment: ‘we don’t know how he walks, but he does’. Bill describes: ‘typi-
cally I used to aim at where I needed to be, and grabbed hold of walls/
furniture/shoulders to get there’. He started to use a wheelchair at the
age of 38. It had been suggested a number of years previously, but he
had resisted. It turned out to be of great benefit, enabling outdoor mobil-
ity, which he had previously lost. Bill now uses a wheelchair for most of
his community mobility; at home he uses elbow crutches, but is limited
to very short distances and describes his walking as ‘both uncomfort-
able and very slow’. He tends to swing on his crutches, rather than take
steps. Bill can just manage the stairs, so long as there are hand rails on
both sides, but this too is very effortful and slow.
A significant problem continues to be spasticity and painful spasms;
these are problematic in the day, but also at night, causing sleep dis-
turbance. This exacerbates his fatigue, which is an ongoing symp-
tom requiring management. He also experiences a constant ‘ache’
and the feeling that ‘my muscles never properly relax’. Bill did expe-
rience bladder frequency and urgency – this is now managed with
self-catheterisation.
Bill had an intrathecal baclofen pump implanted in 2011. He describes
this as very beneficial; he has noticed a big improvement in his spas-
ticity, with the drug now delivered over 24 hours without any of the
unwelcome side effects of the oral medications. He had tried most
of the anti-spasticity medications and had found them problematic
mostly for 2 main reasons. ‘The dose required to positively affect my
legs caused too much weakness in my upper body – which was a key
part in enabling me to get around. So overall the drugs tended to make
me less mobile, and, second, they caused fatigue and I needed to sleep
most afternoons’.
Bill has tried various other treatments over the years. Plaster casts to
stretch his calf muscles were a regular feature in his younger years. He
remembers ‘hating those casts’. He would wear casts for 6–8 weeks a
year, with them being changed weekly to increase the stretch. At other
times in his childhood he had removable plaster casts for regular but
intermittent use.
Bill has tried functional electrical stimulation but did not find any
benefit from it, unlike other HSP support group members. He has
found physiotherapy, exercises, and stretching to be ‘very beneficial’,
but finds physiotherapy difficult to get to. He regularly stretches and
feels it is important for stretching at home to become ‘routine’. Bill has
invested in a ‘Theratrainer’ bike and an ‘EasyStand’ hydraulic chair; he
aims to use each of them for 30 mins, once a week.
9.2.9.2 Physical Interventions
Physical therapy is commonly prescribed for people with HSP. Techniques
include progressive resisted exercises, stretches, task-related training of
walking, and interventions targeting cardiovascular fitness.97,98 Although
focus groups highlight that people feel they benefit from physical therapy,
there have been no studies exploring their benefits. Given the paucity of
evidence following systematic reviews for techniques such as stretching on
spasticity and passive stiffness in other upper motor neuron syndromes, it is
important that this is evaluated.99
Orthoses have been prescribed to aid foot drop caused by combined anterior
tibial weakness. If plantarflexor spasticity or stiffness is marked, the orthosis
often needs to be quite rigid; hinging the ankle joint in these cases can aid
stair descent, which requires a degree of ankle dorsiflexion. The aim of an
orthosis has to be clearly defined. Some people with HSP may hyperextend
their knee to compensate for knee extensor weakness; in these cases reducing
ankle plantarflexion may actually enhance instability by bringing the ground
reaction force behind the knee joint requiring knee extensor activation.65
Marsden et al. investigated the immediate effects of functional electrical
stimulation (FES) of the common peroneal nerves bilaterally to aid foot drop
during swing phase.77 Participants were long-term (>1 year) users of FES with
either sporadic or hereditary spastic paraparesis. Walking speed increased
with FES by 10% compared to no stimulation; there was no effect on walking
efficiency as measured using the physiological cost index. Some participants
had novel patterns of stimulation including stimulating the contralateral hip
abductors and ipsilateral trunk extensors at the start of swing phase that also
aided the clearance of the toe during swing phase.77 Chronic electrical simu-
lation to improve muscle strength has also been reported in one case with
familial spastic paraparesis. Here the quadriceps and tibialis anterior muscles
were stimulated bilaterally 2–3 times/week over 3 months. A 27% improve-
ment in walking speed was observed with an improvement in the degree of
crouch in stance phase.100 Further work is required to ascertain whether there
are long-term carry-over effects of FES and whether isolated electrical stimula-
tion produces objective changes in muscle strength and function.
Hydrotherapy offers people with HSP the opportunity to use the buoyancy
and drag of water to perform range of motion, strengthening, and endur-
ance exercises and to take advantage of the effects of warming (see below).
A 10-week hydrotherapy (5 weeks group, 5 weeks individual, with sessions
twice/week) programme was assessed in 10 people with HSP. Following the
programme, the participants showed reduced total range of movement at the
ankle, knee, and hip in the transverse plane, enhanced hip internal rotation,
and an increase in hip extension moment in initial stance phase while walk-
ing. This was interpreted as being due to an increased use of compensatory
strategies (see above) to aid foot clearance rather than a change in underlying
impairment.101
The effects of localised changes in temperature of neuromuscular func

tion, foot tap speed, and walking ability have been explored in HSP by Denton
et al. (2016). On separate days, the temperature of 1 shank was raised (~10°C)
or lowered (~13°C) using a temperature-controlled water bath. Increases in
lower limb peripheral nerve conduction velocity, the rate and amplitude of
ankle muscle force output, and a reduction in plantarflexor stretch-reflex-
mediated stiffness was observed with warming, with opposite effects being
seen with cooling. Further, despite only one leg being targeted there was an
increase in maximal walking speed with warming (~10%) and a similarly
sized decrease with cooling. Many of the effects on temperature were similar
in magnitude in people with HSP compared to matched controls. However,
the decrease in walking speed with cooling was more marked in people
with HSP. This was interpreted as resulting from the fact that due to bilateral
lower limb involvement a slight reduction in neuromuscular function in one
leg has a marked effect on functional ability. In contrast, healthy participants
were able to compensate for this by using other body parts (e.g., trunk and
opposite leg). These findings support the subjective view of people with HSP
that their symptoms are worse in cold weather and suggests that strategies
such as the use of insulating garments in colder weather, external warming
(e.g., with heat packs, hydrotherapy) or exercise to increase internal tempera-
ture may aid stiffness and mobility.
9.2.9.3 Service Delivery
Due to the rarity of HSP knowledge of the condition and service delivery for
this condition can be variable. Poor local knowledge about the condition and
its management by health care professionals, difficulty in accessing specialist
services (in terms of availability and time), poor service co-ordination (e.g.,
between neurologists, genetic counsellors, and allied health professionals)
and access to evidence-based treatments were issues raised in focus groups of
people with HSP in a rural setting within the UK. Further, focus groups with
carers highlighted the often large and continual burden placed upon them
and the need to establish supportive networks.59 One particular source of net-
work support is the national support groups present in many countries that
provide educational and emotional support throughout the disease process.
9.3 Spinocerebellar Degenerations
9.3.1 Autosomal Dominant
Anita Harding originally described three classifications of autosomal dom-
inant cerebellar ataxias (ADCAs).12 Type 1 is characterised by a cerebellar
syndrome with ophthalmoplegia, pyramidal or extra pyramidal signs, cog-

nitive impairment, or peripheral neuropathy. This presentation is caused
by variable degenerations of the cerebellum, basal ganglia, cerebral cortex,
optic nerve, pontomedullary systems, spinal tracts, or peripheral nerves.
Pigmentary retinopathy accompanies a variable presentation of cerebellar
and extra-cerebellar signs in ADCA II, otherwise similar to ADCA I. A third
group, ADCA type III, includes relatively pure cerebellar ataxias where the
degenerative process is limited to the cerebellum. Clinically characterised
ADCAs are now increasingly also referred to as the spinocerebellar atax-
ias (SCA) denoting the genetic classification system. There are numerous
SCAs identified and some labels reserved, as outlined in Table 9.2.106 The
SCAs are clinically heterogeneous but they often present with progressive
cerebellar ataxia. This usually starts with symptoms of ataxia while walk-
ing and poor balance followed by symptoms of limb ataxia, dysarthria,
and visual problems. Visual problems, although often not the first signs/
symptoms detected by the patient have been proposed as an early sign, since
the advent of pre-symptomatic genetic testing.102 Visual problems can be
caused by either oculomotor abnormalities secondary to cerebellar degen-
eration (e.g., saccadic dysmetria, impaired smooth pursuit and nystagmus)
or non-cerebellar causes (e.g., maculopathy, gaze palsies, slowed saccades).
Maculopathy can precede the appearance of the cerebellar ataxia in SCA7 by
up to 20 years.103,104 Cerebellar degeneration often is accompanied by involve-
ment of the brainstem and spinal cord, although relatively isolated cerebel-
lar degeneration can occur (e.g., in SCA6).105 A description of the pathology,
clinical presentation, and intervention of SCA3 the most common SCA pre-
senting with additional UMN signs will be described.
9.3.2 SCA3 or Machado-Joseph Disease

Depending on ethnicity, SCA3 accounts for between 21 and 56% of SCA
cases.107 Prevalence varies according to founder effects. It is a polyglutamate
(polyQ) disease caused by a CAG repeated expansion of the ATXN3 gene
on chromosome 14q. The protein encoded by ATXN3, ataxin-3, is a deubiq-
uitinating enzyme that cleaves ubiquitin off substrates. It is felt that this
enzyme’s function, and thus biochemical pathways dependent upon ubiq-
uitin, are affected in SCA3.108 The age of onset varies from childhood to late
adult life and there is an inverse correlation between the number of CAG
repeats and the age of onset and disease severity.109
The pathology includes atrophy of the middle cerebellar peduncles, dentate
nucleus of the cerebellum, and pontine nucei, i.e., cerebello-thalamo-cortical
motor loops. The pathology also affects the substantia nigra, subthalamic
nuclei (basal ganglia thalamocortical loops), red nuclei, anterior horn cells,
and motor cranial nerves. Additional pathology has been described in the
somatosensory, auditory, and occulomotor systems. Brainstem involve-
ment affecting the dopaminergic and cholinergic system is also present.
TABLE 9.2
Spinocerebellar Types, Genetics, and Clinical Features
Gene Name
(Chromosome Location
and Locus) Protein and Mutation Pertinent Features
ADCA I Cerebellar syndrome plus
ophthalmoplegia, pyramidal or extra
pyramidal signs, cognitive
impairment or peripheral neuropathy
SCA1 6p22.3 ATXN1 Ataxin 1 CAG repeat Ataxia, pyramidal signs, neuropathy,
ophtalmoplegia
SCA2 12q24.13 ATXN2 Ataxin 2 CAG repeat Ataxia, slow saccades, neuropathy
SCA3 14q32.12 ATXN3 Ataxin 3 CAG repeat Ataxia, pyramidal signs,
ophthalmoplegia, neuropathy,
dystonia
SCA4 16q24-qter SCA4 Unknown Ataxia, sensory neuropathy
SCA8 13q21 KLHL1AS Kelch-like 1 CTG repeat Ataxia, sensory neuropathy
SCA9 Reserved Unknown
SCA10 22q13.31 ATXN10 Ataxin 10 ATTCT repeat Ataxia and epilepsy
SCA12 5q32 PPP2R2B PPP2R2B CAG repeat Ataxia, tremor
SCA13 19q13.33 KCNC3 KCNC3 MM Ataxia, mental retardation
SCA14 19q13.42 PRKCG PRKCG MM Ataxia, myoclonus dystonia
SCA17 6q27 TBP TBP CAG repeat Ataxia, chorea, psychiatric
manifestations, dementia, epilepsy
SCA18 7q31-q32 Unknown Ataxia, sensory neuropathy
SCA19* 1p21-q21 Unknown Ataxia, myoclonus, cognitive
impairment
SCA20 11 Unknown Ataxia, disphonia
SCA21 7p21.3-p15.1 Unknown Ataxia, parkinsonism
SCA22* 1p21-q23 Unknown Ataxia
SCA23 20p13-p12.2 Unknown Ataxia, sensory neuropathy
SCA25 2p21-p15 Unknown Ataxia, sensory neuropathy
SCA27 13q33.1 FGF14 FGF14 MM Ataxia tremor mental retardation
SCA28 18p11.22-q11.2 Unknown Ataxia, opthalmoplegia
DRPLA 12p13.31 ATN1 Atrophin 1 CAG repeat Ataxia, myoclonus, seizures,
psychiatric manifestation, dementia
Undefined** 16q22.1 PLEKHG4 Puratrophin Ataxia, sensory neuropathy
1 5’ SNS
ADCA II Variable similar presentation to
ADCA plus the presence of
pigmentary retinopathy
SCA7 3p14.1 ATXN7 Ataxin 7 CAG repeat Cerebellar ataxia, pyramidal signs,
pigmentary maculopathy
ADCA III Relatively pure cerebellar ataxias
where the degenerative process is
limited to the cerebellum
(Continued)
TABLE 9.2 (CONTINUED)

Spinocerebellar Types, Genetics, and Clinical Features
Gene Name
(Chromosome Location
and Locus) Protein and Mutation Pertinent Features
SCA6 19p13.13 CACNAIA CAG repeat Almost pure cerebellar ataxia
CACNAIA (occasional dystonia or
Parkinsonism described)
SCA5 11q13.2 SPTBN2 Beta-III spectrin D, MM Almost pure cerebellar ataxia
SCA11 15q14-q21.3 SCA11 Unknown Almost pure cerebellar ataxia
SCA15 3p24.2-pter ITRP1 ITRP1 D Almost pure cerebellar ataxia
SCA16 8q23-q24.1 Unknown Almost pure cerebellar ataxia
SCA24 1p36 Unknown Almost pure cerebellar ataxia
SCA26 19p13.3 Unknown Almost pure cerebellar ataxia
Source: Adapted from Giunti, P. and Wood, N. Adv Clin Neurosci Rehabil 75, 18–21, 2007.
The corticospinal tract, however, is not severely affected and central motor
conduction times have been found to be normal.107,110–112
Symptoms include progressive ataxic gait and balance and dysarthria.
Associated with this are symptoms of spasticity, hyperreflexia, and nystag-
mus. In some cases, cerebellar-cognitive changes are also observed, namely
deficits in memory, executive dysfunction, naming, and attention; visuo-
spatial processing and calculation, however, appear spared.113 In later stages,
there is opthalmoplegia and slowing of saccades, amyotrophy, and dystonic
posturing. There can also be peripheral nerve involvement leading to a loss
of distal sensation and areflexia that is more prominent in older people.
Difficulty falling asleep and increased nocturnal wakening are more com-
mon in older people with brainstem involvement and can be associated with
central apnoea and restless legs syndrome.107
The presenting symptoms vary with the age of onset, and different types of
presentation have been described (Table 9.3), type 2 being the most common,
TABLE 9.3
Clinical and Subtype Clinical Characteristics
Mean Age of Onset
SCA3 Type (Range) Symptoms
1 25 years Spasticity, rigidity, bradykinesia
with minimal ataxia
2 38 years (20–50) Progressive ataxia and upper motor
neuron signs (spasticity, paresis)
3 48 years (40–75) Ataxia and peripheral nerve
involvement with amyotrophy and
generalised areflexia
4 Variable age of onset Parkinsonian phenotype
5 25 years (12–48)114 ‘Pure’ progressive spastic paraplegia
seen in ~57–75% of cases. Earlier-onset cases and those with large CAG
repeat expansions tend to have signs of spasticity.110 The presence of early
UMN signs with minimal cerebellar signs can make SCA3 difficult to distin-
guish from HSP and this has been described as the type 5 presentation.2,110,114
9.3.2.1 Symptomatic Management
SCAs are progressively degenerative in nature and ultimately lead to death
over a typical period of 15 to 30 years. SCA6 is, however, an exception due to
the late onset and slower progressive nature of the disease and is often not
life-limiting. No therapeutic strategies are as yet available to target primary
disease pathways in those with SCA and therefore current management
approaches involve designing treatments to alleviate symptoms.
Recommendations for the symptomatic treatments of spasticity,
Parkinsonism, dystonia, and cramps have been outlined and include benzo-
diazepines, baclofen, and carbamazepine.115,116 A case study has described the
use of botulinum toxin injections for lower limb spasticity and cramps that
produced no side effects although the clinical benefits were not described.117
In contrast botulinum toxin injections for associated cervical dystonia have
been associated with dysphagia.118 A double-bind randomised controlled
trial119 of the antibiotics sulfamethoxazole and trimethoprim (co-trimoxazole)
have not supported the improvements in spasticity and rigidity described
by earlier smaller trials.120,121 Some people with SCA3 can show levadopa-
responsive dystonia and therefore patients should undergo a levadopa trial
if dystonia is present. SCAs involving Parkinsonian features, such as SCA2
and 3 (MJD), often respond to dopaminergic therapy, such as levodopa122–125
and dopaminergic drugs can also be helpful in ameliorating restless legs
to aid uninterrupted sleep.125–127 Amantadine is sometimes used to treat
BOX 9.4 SYMPTOM PRESENTATION AND

BALANCE DYSFUNCTION IN SCA3 AND SCA6
Despite balance being an early and well-described symptom, the mech-
anistic underpinnings of balance impairment remain poorly under-
stood. Tables 1–3 of Box 9.4 compare the differences between a relatively
pure group of 16 people with cerebellar ataxia (SCA6) to 4 individual
subjects with SCA3. These presentations outline the variability of SCA3
presentations and the multi-factorial potential for signs and symptoms
to contribute to balance impairment, in contrast to SCA6, where the
balance impairment involved is likely to solely be due to cerebellar dis-
ease. Table 1 highlights differences in clinical scores.
As can be seen in Table 2, people with SCA3 more frequently have
abnormalities in upper motor neuron signs, sensory loss, and spasticity/
spasms.
TABLE 1
Functional Overview of Individual SCA3C Cases Contrasted with Typical SCA6 Group
Loss of Functional
SARA Highest- Berg Score Independence
(/40, Most Scoring (/56, Best (FIM Score /126, Abnormal
SCA Age at Severe Elements Balance Falls in Last Best Indepen- Mobility Aid MMSE
Type Age Sex Onset Ataxia) of SARA Function) 6 Months dence) Use (Score)
SCA3a 40 m 28 17 Gait 31 Y (n = 3, lost Y (117) Y (rollator) N (24)
balance)
SCA3b 53 f 45 2 Gait 56 N N (126) N N (30)
SCA3c 49 M 35 14 Gait 20 Y (n = 3, legs Y (120) Y (sticks) N (24)
gave way/
lost balance)
SCA3d 54 f 40 27.5 Gait 5 Y (n = 7, lost Y (117) Y (WCH) Y (12)
balance)
SCA6: 62.3 7m, 52.2 12 (6.1) Gait 35.0 (17.4) 1.9 (2.1) Y 122.3 (4.7) None (n = 8) Abnormal
mean (10.2) 9f (16.4) Stick (n = 5) MMSE
(SD) Crutch (n = 3) (score)
Rollator (n = 2)
WCH (n = 2,
outdoor only)
263
264
TABLE 2
Individual SCA3 Sensorimotor Assessment Contrasted to Typical SCA6 Group
Proprioceptive Muscle Weakness
Loss (Hallux Abnormal (Triceps Surae), Increase in Tone
Longus Position Abnormal Monofilament (/5, Best Muscle (Ashworth Scale, Spams (Penn
SCA type in Space Test) Babinski (< 9/10) Strength) Ankle PF) ROM Restrictions Spasm Scale)
SCA3a N N N (av 10) N (5/5 bilateral) N (1/5 bilateral) N N
SCA3b N Y (absent) Y (av 8.5) N (5/5 bilateral) N (1/5 bilateral) Y (-5 DF bilateral) N
SCA3c Y (bilateral) N Y (av 1) Y (4/5 bilateral) Y (3/4 bilateral) Y (-5 DF bilateral) Y (4)
SCA3d Y (bilateral) Y (absent) Y (av 4) N (5/5 bilateral) N (1/5 bilateral) N Y (2)
SCA6: mean No No No (mean: 9.9 Mean: 4.6 SD: 0.6 No No None
(SD) SD: 0.3)
TABLE 3
Individual SCA3 SARA Scores Contrasted to Typical SCA6 Group
Hand
Nose to Movements
Sitting Finger Chase Finger (Dysdiado- Heel Shin
SCA Type Gait Stance Balance Speech (Dysmetria) (Tremor) chokinesia) (Co- ordination) Total BalSARA
SCA3a 5 2 2 0 3 1 2 2 17 9
SCA3b 1 0 0 0 0.5 0 0 0.5 2 1
SCA3c 3 3 0 2 1 1 1 3 14 6
SCA3d 6 5 2 3 3 3 2.5 3 27.5 13
SCA6: 3 (1.7) 1.5 (1.0) 0.3 (0.7) 2.1 (1.1) 1.3 (1.0) 0.5 (0.5) 1.6 (1.0) 1.7 (1.2) 12.0 (6.1) 4.8 (3.1)
mean (SD)
265
dystonia and bradykinesia.125,128 Those experiencing muscle cramps, most

commonly encountered in SCA3, can trial magnesium, chinine, quinine, or
mexiletine drug therapies.129 As with other SCAs and cerebellar disorders
the pharmacological management of ataxia is limited.115,130 Tandospirone
may improve symptoms of ataxia, depression, and insomnia.116
Rehabilitation is recommended, including physical therapy to address
strength, balance, and gait and offer advice on falls management as well as
speech therapy and dietetics to address issues of dysphagia and dysarthria, to
prevent aspiration pneumonia, weight loss, and dehydration.131 Maintenance
of mobility and fatigue management with appropriate use of walking aids and
wheelchairs is also required as the disease progresses and it is recommended
that these should be prescribed before falls cause fractures and long-lasting
immobilisation.125 Splints and orthoses may prevent trauma from over-
supination or pain from over-extension of the knee.125 No evidence exists, how-
ever, for the efficacy of these interventions leading to uncertainty and variability
in approaches. Management recommendations for SCA3 are currently mainly
based on the evidence base for treating people with Parkinson’s disease.108,132
9.3.3 Autosomal Recessive
Most autosomal recessive ataxias have symptoms of limb ataxia and impaired
balance and walking. Additional signs include vertigo, dysphagia, and dip-
lopia.133 Unlike the autososomal dominant ataxia that present with associ-
ated extrapyramidal and pyramidal signs, the autosomal recessive ataxias
often have additional signs of sensorimotor neuropathy, resulting in loss of
proprioception and vibration sense.133
9.3.4 Friedreich’s Ataxia and Late-Onset Friedreich’s Ataxia

Friedreich’s ataxia (FRDA) is the most common autosomal recessive ataxia,
affecting 2 per 100,000. In ~98% of cases it is caused by a GAA repeat expan-
sion on the Frataxin gene on chromosome 9q13. The age of onset is inversely
related to the size of the repeat. Frataxin is localised to the mitochondrial
matrix and associated with iron metabolism and homeostasis. It is deficient
in FRDA and increased mitochondrial iron accumulation, increased oxida-
tive stress, impaired ATP production, and cell death are seen.133,134
Degeneration of the dorsal columns, spinocerebellar tracts, and dentate
nucleus occurs in FRDA. It is characterised by progressive ataxia (affect-
ing balance, walking limbs, and speech) and sensory signs. Axonal sensory
neuropathy results in areflexia and a loss of proprioception and vibration
sense. Corticospinal tract involvement leads to paresis and extensor plan-
tar responses.135 Non-neurological involvement includes cardiomyopathy in
~50% and diabetes mellitus in ~10%. With disease progression, symptoms
of kyphoscoliosis and pes cavus/equinovarus become prominent and these
can affect respiratory function and walking.136
Variations of the typical Friedreich’s ataxia presentation exist in ~10% of

cases having a positive molecular test for Friedreich’s ataxia. People can
show Friedreich’s ataxia with retained reflexes (FARR) and also late-onset
Friedreich’s ataxia (LOFA) or very late-onset Friedreich’s ataxia (VLOFA)
where symptom onset occurs after 25 and 40 years, respectively.137 Unlike
typical Friedreich’s ataxia, people with LOFA show signs of spasticity (40% of
cases) and have retained reflexes (46% of cases).138,139 Non-neurological symp-
toms such as cardiomyopathy, sphincter disturbances, scoliosis, and pes
cavus are less frequent in atypical FRDA.139 In VLOFA, a spastic tetrapare-
sis without marked ataxia or neuropathy has been described.140 Oculomotor
abnormalities may be absent in atypical FA. People with LOFA have a slower
progression and smaller GAA expansions. Another atypical FRDA is found
in Acadian families from New Brunswick, Canada. These individuals can
have the same onset and symptoms as FRDA but without the involvement
of cardiomyopathy and diabetes and may also show retained reflexes and
spasticity.
9.3.4.1 Management of FDRA
There is currently no specific information on the management of LOFA and
VLOFA. Therefore, a brief overview of the management of FRDA will be
provided.
9.3.4.1.1 Co-enzyme Q10 and Idebenone

Co-enzyme Q10 is a mitochondrial molecule that is part of the electron trans-
fer chain. It is a potent antioxidant and can maintain other antioxidants such
as vitamin E. Idebenone is a structural analogue of co-enzyme Q10 but it is
more water-soluble and has a lower molecular weight and may thus show
greater bioavailability.134 There is some evidence from randomised con-
trolled trials in the USA and Europe to suggest improved cardiac function
and maintenance or improvements in fine motor skills following ideben-
one.134 However, as reviewed by Parkinson et al., this seems to be dependent
on the prescribed dose and baseline disease severity (improvements may be
more marked in ambulant, less severe children). The impact on neurological
signs and in particular functional ability and quality of life is unclear.134
9.3.4.1.2 Symptomatic Management
Rehabilitation for FRDA involves a multi-disciplinary team, including speech
therapists and dieticians (to address communication issues, dysphagia, diabetes-
management), occupational therapists, orthotists, and physiotherapists.141 A
retrospective review of in-patient rehabilitation in people with FRDA found
improvements in function (as measured by the functional independent mea-
sure) that continued to improve on discharge.142 Physiotherapy commonly
consists of progressive resisted exercises and stretching.143 In addition, mobil-
ity can be improved by aids (e.g., walking aids/wheelchairs) and orthoses
or shoes for pes cavus.144 Orthopaedic management of scoliosis may also be

required and early management of the pes cavus foot has been suggested.145
Uptake of home rehabilitation programmes by people with FRDA can
be sparse (~10%).143 This could be related to perceptions of a lack of exper-
tise by prescribing therapists about the condition as well as a lack of access
to appropriate therapists. Issues around a lack of time and energy and the
association of treatment with the presence of disability are further barriers
highlighted.143 The compliance with therapy may be increased by the use of
interactive whole-body controlled video game technology. Intensive train-
ing over an 8-week period of balance and co-ordination skills resulted in
improvements in ataxic symptoms, balance, and walking.146,147 Endurance
training is feasible in people with FRDA and can lead to improvements in
markers of cardiovascular fitness. A static exercise bike was used for train-
ing, which has the advantage of reducing balance requirements, and cardiac
function was monitored during training.148
Intrathecal baclofen has been used to reduce painful spasms in a case with
FRDA,149 whilst oral baclofen and botulinum toxin have been recommended
for spasticity management.141 There are no clinical trials or reports on the
management of spasticity in late onset FRDA.
9.4 Motor Neuron Disorders and Familial

Amyotrophic Lateral Sclerosis
Motor neuron disease: amyotrophic lateral sclerosis (ALS) accounts for
70–90% of cases of motor neuron disease and is characterised by predomi-
nant lower motor neuron (LMN) signs of weakness in combination with mild
UMN signs of spasticity and brisk reflexes. A minority of people with ALS,
termed UMN-Dominant, have pyramidal signs and severe spino-bulbar
spasticity with slight LMN signs. In 2–5% of people with motor neuron dis-
ease there is exclusive involvement of UMNs, termed primary lateral scle-
rosis. In contrast, people without any clinical or electrophysiological UMN
signs and only LMN signs are labeled as progressive muscular atrophy. The
remaining subtypes of MND are characterised by LMN signs affecting the
bulbar muscles (progressive bulbar palsy) or UMN involvement affecting
the bulbar muscles (pseudobulbar palsy).150
9.4.1 Amyotrophic Lateral Sclerosis

9.4.1.1 Prevalence and Genetics
ALS has a prevalence of 3.4–5.4 per 100,000. The age of onset is usually in
late adult hood (65 years), and survival time is 2–3 year for bulbar onset and
3–5 years for limb presentation onset. People with an UMN-dominant pre-

sentation have a longer survival time.150
Familial ALS (FALS) is diagnosed where there is a first- or second-degree
relative of the index case. FALS accounts for 4.6% of cases of ALS.151 Familial
ALS is usually inherited in an autosomal dominant manner but autosomal
and recessive patterns of inheritance have been described. Mutations in the
SOD1 gene, the first gene on chromosome 21 found to cause FALS, accounts
for 20% of familial ALS cases. The gene C9ORF72 is linked to chromosome
9p21 and makes up ~43% of FALS and 7% of sporadic cases. This form of
FALS is associated with frontotemporal dementia. The genes TARDBP, FUS,
VCP, UBQLN2 and OPTN comprise the majority of the remaining genes
causing FALS.152,153
9.4.1.2 Pathology
ALS is associated with degeneration of the corticospinal tract and alpha and
gamma motor neurons and interneurons in the spinal cord and Betz cells
within the primary motor cortex. There is additional degeneration in the
deep frontal and temporal white matter, corpus callosum, brainstem (includ-
ing serotonergic neurons), and motor nuclei of the basal ganglia.154 People
with ALS and an expansion in the gene C9ORF72 have additional pathology
in the frontal cortex and hippocampus (CA4 area) in keeping with the asso-
ciation of frontotemporal dementia.153
Hyperexcitability in the motor cortex is seen early on in the disease course;
there is a reduction in GABAA-mediated short-interval intracortcal inhibition
(SICI), a reduced motor threshold, and a decrease in the cortical silent period,
which is mediated in part by GABAB interneurons. Cortical hyperexcitability
is felt to reflect degeneration of inhibitory interneurons in the motor cortex
and may contribute to the presence of positive symptoms such as cramps,
fasciculations, fibrillations, sharp waves, and spasticity. With disease pro-
gression there is a reduction in cortical excitability reflecting degeneration of
corticomotorneuronal pathways.155
Signs of hyperexcitability in the motor system such as the UMN positive
signs are poor prognostic indicators. In SOD1 carriers cortical hyperexcitabil-
ity can be seen prior to symptom onset and is associated with early weak-
ness.156,157 The reduction in SICI correlates with disease duration and motor
deficit. It is hypothesised that cortical hyperexcitability can alter glutamate
metabolism and lead to a dying forward of connected anterior motor neurons.
An alternate hypothesis is that the hyperexcitability reflects a compensatory
process that aims to increase central drive to the degenerating LMNs.155
9.4.1.3 Clinical Presentation
In ALS, the onset of symptoms is usually focal weakness in the proximal or
distal upper or lower limbs. Weakness develops in the other segments and
limbs and this may be accompanied by bulbar and respiratory weakness.

On examination, muscle fasciculations are visible. Upper limb symptoms
are associated with bulbar signs (dysphagia and dysarthria).158 The degree
of lower limb weakness predicts the level of walking ability (e.g., inability,
independence in the community, home ambulation).159–161 Loss of ambula-
tion occurs when the lower limb strength was on average 13.7% (±7.4) of the
predicted normal level.159 In one cohort, loss of ambulation occurs on average
after 46.7 months, about 11–15 months after provision of gastrostomy and
non-invasive ventilation.162 In people with genetic linkage to chromosomes
9p21 and an expansion in the gene C9ORF72 there are associated signs of
frontotemporal dementia in 35% of cases including personality change, irri-
tability, obsessions, poor insight, and deficits in frontal executive tests.2,163
In many people, painful cramps and flexor spasms can occur in the latter
stages. Bulbar symptoms may be UMN and LMN in nature. Tongue move-
ments may be slow due to spasticity and fasciculations and wasting of the
tongue may be present. The jaw jerk may be brisk, especially with bulbar
onset disease. Respiratory muscle weakness can lead to dyspnoea on exer-
tion, orthopnoea, disturbed sleep, morning headaches, daytime somnolence,
weak cough, and paradoxical abdomen movements.153 Death is usually due
to respiratory failure and pulmonary complications.
Spasticity is present in ALS as determined using clinical and electrophysi-
ological measures (i.e., the H-reflex).164,165 However, upper motor neuron signs
can be difficult to elicit in ALS, with only 50% of cases showing an exten-
sor plantar response.154 Spasticity is often hard to detect in weak muscles in
ALS.154 This may reflect the co-occurrence of lower motor neuron signs that
mask patterns of cortico-spinal tract-induced paresis and enhanced tendon
reflexes. LMN signs are not seen in progressive lateral sclerosis and here
spasticity is more marked.154 In addition, interneuronal degeneration within
the spinal cord in ALS could also limit the emergence of hyperexcitable ten-
don reflexes.154 Direct pathology affecting the Renshaw cells within the spi-
nal cord, for example, may explain why the Renshaw-mediated recurrent
inhibition is reduced to a greater extent than seen after spinal cord injury.165
Rigidity, felt as an increased resistance of a limb to movement in both direc-
tions, can also be present in ALS. Extrapyramidal signs as indicated by rigidity
and a shortening reaction were assessed in a selected cohort of people with
ALS (n = 39) who had stiffness (> 2 Ashworth in both legs) but minimal weak-
ness (at least 4/5 MRC manual testing). People who met this inclusion criterion
made up 17% of the total sample assessed. In this subsample extrapyramidal
signs in combination with spasticity were seen in 69%, with the remainder
presenting with spasticity alone.166 People with mixed rigid-spasticity presen-
tation had worse balance, more retropulsion, and more severe neck stiffness.166
The presence of extrapyramidal signs is reflected in the reduced dopaminer-
gic activity assessed using PET and reduced D2-receptor binding as assessed
using SPECT.167–169 As there are large corticostriatal connections, striatal
involvement may be caused by glutamate excitotoxicity.
In ALS degeneration of serotonergic (5-HT) neurons that project to the spi-

nal cord is observed post-mortem and in the SOD1 animal model.170 In spinal
cord injury loss of serotonergic projections from the brainstem dorsal raphe
nuclei leads to secondary up-regulation of 5HT receptors on lower motor
neurons that results in hyperexcitability, plateau potential generation, and
spasticity.171,172 Therefore, the loss of serotonergic neurons in ALS may under-
lie the development of spasticity.
The involvement of tracts other than corticospinal tract in the genesis of
spasticity in ALS is underlined by the fact that corticospinal tract degeneration
can be seen in 50% of people with a clinical diagnosis of progressive muscle
atrophy who had no UMN signs when alive.173 Therefore, findings such as a
correlation between precentral gyrus degeneration, as measured by DTI, and
spasticity174 may simply reflect the co-occurrence of motor cortex pathology
and spasticity in more severe cases of ALS and not reflect a causative link.
9.4.2 Interventions
9.4.2.1 Disease-Modifying Therapy
Riluzole prolongs median survival by 2–3 months if taken for 18 months
(100 mg) in people with clinically definite ALS and symptoms of less than
5 years who are under 75 years and have a forced vital capacity of >60%.175
Riluzole partly resolves the reduction in SICI and may act by inhibiting glu-
tamate release and reducing cortical hyperexcitability.176 In addition, effects
on peripheral nerve function (a reduction in superexcitability and refractori-
ness) have been reported.176
9.4.2.2 Symptomatic management
Respiratory management: monitoring of respiratory function using force vital
capacity (FVC), sniff nasal inspiratory pressures, and nocturnal oximetry is
important as respiratory insufficiency is the major cause of death. Criteria for
starting non-invasive ventilation (NIV) are outlined in Table 9.4. NIV increases
survival and quality of life. NIV is usually initially used for nocturnal hypoven-
tilation with support during the day provided with increasing symptoms.150
Nutritional management: dysphagia and upper limb weakness can lead to
aspiration, malnutrition, weight loss, and dehydration.150 Early management of
dysphagia includes dietary advice, alteration of food consistency, and teaching
swallowing techniques. Due to a ~10% increase in the metabolic rate, people
with ALS require higher calorie intake.177 Supplementary enteral feeding is
recommended if the body weight falls below 10% of a person’s pre-diagnostic
weight. A PEG (percutaneous endoscopic gastrostomy) is the usual option for
enteric feeding. However, insertion does require sedation and so may compro-
mise respiratory function and should be performed before the FVC is < 50%.
Insertion of PEG under NIV assistance or percutaneous radiologic gastrostomy
or radiologically inserted gastrotomy may be required under these conditions.150
TABLE 9.4
Suggested Criteria for Non-invasive Ventilation (NIV)
Symptoms related to respiratory muscle weakness. At least one of:
• Dyspnoea
• Orthopnoea
• Disturbed sleep (not caused by pain)
• Morning headache
• Poor concentration
• Anorexia
• Excessive daytime sleepiness (Epsworth Sleep Score > 9)
and evidence of respiratory muscle weakness (FVC ≤ 80% or SNP ≤ 40 cmH2O)
and evidence of either:
significant nocturnal desaturation on overnight oximetry
or
morning ear lobe blood gas pCO2 ≥ 6.5 kPa
Note: Provisional European consensus criteria for NIV (European ALS/MND Con
sortium and European Neuromuscular Centre workshop on non-invasive ven-
tilation in MND, May 2002).
Source: With permission from Leigh PN, Abrahams S, Al-Chalabi A, Ampong MA,
Goldstein LH, Johnson J, Lyall R, Moxham J, Mustfa N, Rio A, Shaw C,
Willey E. King’s MND Care and Research Team. The management of motor
neurone disease. J Neurol Neurosurg Psychiatry. 2003 Dec;74[4]:iv32–iv47.
Spasticity and rigidity in ALS: oral medications such as baclofen and gaba-
pentin are not always effective in relieving spasticity and pain associated
with spasms.178,179 Side effects such as weakness, sleepiness, and fatigue have
also been described with higher doses of oral baclofen.180 In these cases, the
effects of intrathecal baclofen has been explored. In a retrospective assess-
ment of 6 cases who had ALS for a mean of 47.4 months, ITB reduced pain in
75% of people with the degree of pain relief being predicted by the response
to a preoperative bolus test dose.181 In two other cases ITB was also associ-
ated with reduction in painful spasms.180,182
Exercise in ALS: exercise trials in early-stage ALS have been systematically
reviewed by Lui et al. (2009).183 Exercise regimes consisted of treadmill training
and moderate progressive resisted exercises and stretches. Although small-to-
moderate effect sizes were found favoring the intervention (e.g., for FVC, fatigue,
strength, and function), the variability of the effect was very large and overall the
results are inconclusive to date. Reductions in spasticity have been described fol-
lowing exercise but only after the first 3 months, with no effect being seen after
6 months between the no-exercise control group and the intervention group.164
More recently the feasibility of supported treadmill training has been investi-
gated in ALS (n = 9). Patients undertook an 8-week programme consisting of train-
ing 3 times/week for 30 minutes where 5 minutes of exercise were interspersed
with 5 minutes of rest. There was a 33% dropout but improvements were seen in
walking over 6 minutes and fatigue rating with no deterioration in perceived func-
tion, FVC, or muscle strength, which showed non-significant improvements.185
Cortical stimulation: cortical hyperexcitability is felt to cause a dying forward

of connected anterior motor neurons in ALS and is thus a potential target for
therapy.155 Repetitive cortical stimulation using TMS has been used to reduce
cortical hyperexcitability. Other groups have used high-frequency transcranial
excitatory stimulation, as there is evidence from animal studies that this may
have a neuroprotective effect by increasing brain-derived neurotrophic factor
(BDNF) expression. Synapse-specific activity has been shown to regulate BDNF
transcription, transport, secretion, and trafficking of its receptor. BDNF in turn
is felt to regulate synaptic efficacy and growth of dendrites and axons; processes
that underpin synaptic plasticity.186 There is evidence that a single nucleotide
polymorphism in the BDNF gene can affect the response to r TMS in healthy
participants and post-stroke.187,188 These differences in people’s responsiveness to
stimulation may underlie the variability in the results seen; a Cochrane review
of randomised controlled trials of cortical stimulation studies in ALS up to 2010
found no evidence of effect in the trials thus far performed.189
9.5 Leukodystrophies
The leukodystrophies are inherited myelin disorders affecting myelin devel-
opment and maintenance in the central nervous system. A classification of
the leukodystrophies is given below, with examples of the more common
types.190 Up to half of people with leukodystrophies do not get a specific diag-
nosis. The age of onset varies with the type. The involvement of white matter
tracts commonly leads to spasticity and UMN signs, although reduced limb
stiffness (hypotonia) can be seen, e.g., in childhood onset. Extrapyramidal
signs and ataxia may also be present. Impaired swallowing, respiration, and
cognition, and epilepsy, may also be seen.190,191
9.5.1 Demyelinating and Dysmyelinating Disorders

• X-linked adrenoleukodystrophy
• Krabbe disease
9.5.2 Hypomyelinating Disorders
• Pelizaeus-Merzbacher disease
• Alexander disease
9.5.3 Spongiform Disorders
• Canavan disease
9.5.4 Cystic Disorders
• Vanishing white matter disease
9.6 Adrenoleukodystrophy
9.6.1 Prevalence and Genetics
Adrenoleukodystrophy (ADL) is an X-linked recessive disorder character-
ised by adrenal insufficiency and demyelination in the central and periph-
eral nervous system. They are caused by a defect in a peroximal membrane
transporting protein, leading to the accumulation of very-long-chain fatty
acids in tissues and plasma. De novo mutations occur in 19% of cases.192
Clinical severity is not related to the length of the very-long-chain fatty acids.
It occurs in 0.5–3.3 per 100,000 males and there are several forms.
9.6.2 Clinical Presentation
Cerebral inflammatory presentation can start during childhood (3–10 years),
adolescence (11–21 years), or adult life (>21 years). It accounts for ~50% of
cases and is characterised by perivascular lymphocyte infiltration in the
parieto-occipital region (85% of cases) or frontal lobe region (15% of cases).193
Child ADL has symptoms of ataxia, spasticity, dysphagia, deafness, visual
deficits, personality changes, and, in ~30%, seizures.194 Neurological deterio-
ration occurs over 2–3 years until there is complete disability, a vegetative
state, and death.
Adrenomyeloneuropathy (AMN) is seen in ~45% of cases.193 Here, onset
is 28 (+/−9) years. It is characterised by non-inflammatory distal axonal loss
and secondary demyelination affecting the dorsal columns and corticospinal
tracts and a peripheral neuropathy.195 It is characterised primarily by lower
extremity spasticity, paresis, and loss of vibration sensibility that affects
walking and balance.195 Bladder and bowel function can also be affected.
Sensory loss can appear in isolation or with symptoms of paresis and spastic-
ity.195 In ~20% of cases there is additional cerebral pathology. Somatosensory
and brainstem EPs and MEPs, transcortical, long-latency stretch reflexes
from the hand, are prolonged and/or reduced in amplitude, in keeping with
the pathology affecting the dorsal columns and corticospinal tract.196–199
In AMN, postural sway is increased in amplitude and correlates with the
degree of lower limb weakness and sensory loss.195,200 Walking is slower
than normal but the pattern is relatively unimpaired in patients with
isolated sensory loss. Strength loss and spasticity result in a crouch and
stiff knee gait with reduced ankle motion. A cross-sectional study of 142
people with AMN found that lower limb strength is the main predictor of
functional ability. Vibration thresholds also predicted functional ability,

while ankle spasticity was correlated with walking velocity and a timed
up-and-go test.200,201
AMN symptoms can mimic hereditary or familial SP 3,4,202 and symp-
toms of ataxia mimicking a spinocerebellar degeneration have also been
described.5,6 Differential diagnosis is important in cases of sporadic SP and
where male-to-male transmission is absent as the more severe cerebral child-
hood form arises from the same gene mutation as AMN.3
Primary adrenal insufficiency (‘Addison-only presentation’) comprises
the remaining 20% of cases. Here, people do not have neurological symptoms.
Symptom-free males with the gene deficit have been described. Females are
carriers and can exhibit symptoms of adrenal failure. In 55–63% of cases,
neurological symptoms akin to AMN are seen with/without peripheral neu-
ropathy (~57%) and a high incidence of fecal incontinence (28%).204 The age
of symptom onset in females is a decade later than males (~38 years), the
symptoms milder, and the progression slower. Cerebral involvement can be
seen in female carriers.
9.6.3 Interventions
Management of AMN consists of the following193,205:
1. Adrenal hormone replacement therapy for those with adrenal

insufficiency.
2. Dietary therapy: Lorezo’s oil (a 4:1 mixture of glyceryl trioleate and
glyceral trierucate) and moderate reduction of fat intake can lower
VLCFA in the plasma.193 The therapy does not slow progression rate
of those who are already symptomatic, especially if they have the
cerebral inflammatory presentation. Open-label trials suggest that
Lorezo’s oil can slow the progression of pure AMN and can be pre-
ventative in asymptomatic boys.
3. Hematopoietic stem cell transplantation has been reported to be effec-
tive in presymptomatic or early symptomatic childhood cerebral ADL.
Treatments of symptoms such as spasticity have only been reported in case

reports, for example, for the use of dantrolene effect in AMN206 and ITB in
cerebral child ADL.194
9.7 Summary
The hereditary myelopathies represent a relatively rare and diverse group
of conditions. As such, research into the pathophysiology of a condition is
often sparse and requires multi-centre and multi-national approaches. An

understanding of the underlying genetics of each condition over time could
lead to disease-modifying therapies and improvements in the information
provided during genetic counselling.
In many cases spasticity and paresis are seen in combination with a
variety of other signs such as ataxia, extrapyramidal signs (rigidity, bra-
dykinesia, tremor) and sensory loss. Symptom onset can occur at various
times throughout life and this may result in differences in the presence and
relative impact of secondary complications such as contracture, increased
passive stiffness, and bony deformity. Spasticity is therefore just one of a
multitude of impairments that may impact on functional ability. Although
spasticity and hypertonia can limit mobility it may have a positive impact on
stability and therefore should not be considered an obligate target for treat-
ment. Future work will help to elucidate the relative importance of different
impairments in limiting function and quality of life and the effectiveness of
symptomatic interventions.
With the hereditary myelopathies there is symptom progression over time.
Differences in the rate of disease progression and the severity and extent of
CNS damage will presumably affect the ability of the neuromusculoskel-
etal system to adapt to environmental demands (e.g., training and rehabili-
tation) and therefore the effectiveness of interventions that aim to restore
functional ability. In cases where the adaptability and plasticity of the sys-
tem is limited compensatory techniques that aim to maintain or improve
functional ability through the use of altered strategies and aids and adapta-
tions may be more appropriate. Which approach is adopted and the overall
goals of treatment may vary over the disease trajectory in an individual and
with the aims of the patient, their family, and carers. A greater understand-
ing of these issues will lead to improved symptomatic management.
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Index
Page numbers followed by f, t, and n represent figures, tables, and notes, respectively.
A tizanidine dosage scheduling in, 183

traumatic brain injury in, 225
AbobotulinumtoxinA, 220
Alcohol neurolysis, 223
Accelerometers, 18
Altered tone, 9–12; see also Spasticity
Achilles tendon, 127
Ambulatory stroke patients, 126
Action research arm test (ARAT) score,
Amyotrophic lateral sclerosis (ALS),
15f, 107, 121
268–269
Activation of muscles, 69
Ankle dorsiflexion, 127
Activities of daily life (ADL), 137, 148,
Ankle dorsiflexors, 68, 113
154, 180, 225
Ankle-foot orthosis, 83f, 94
Activity and participation, 121
Ankle kinetics, 96f
Addison-only presentation, 275
Antagonist muscles, regulation of, 63
Adolescents, 83, 254
Anterior cord syndrome (ACS), 141
Adrenal hormone replacement therapy,
Anti-gravity distribution, 104
275
Antigravity strength, 93
Adrenoleukodystrophy (ADL); see also
Anti-spastic drug therapy, 146, 152
Hereditary spastic paraparesis
Areflexic flaccid paresis, 105
(HSP)
Arm and hand function, role of
clinical presentation, 274–275
spasticity in
interventions, 275
about, 115–116
prevalence and genetics, 274
spasticity in patients
Adrenomyeloneuropathy (AMN)
with mildly affected upper limb
about, 237, 274–275
(UAT 4-7), 118
management of, 275
with moderately affected upper
Adults
limb (UAT 2-3), 117–118
acquired brain injury, 222
with severely affected upper limb
adult-onset stroke, 244
(UAT 0-1), 117
affected by cerebral palsy, 82
Ashworth scale, 94, 120, 148, 211t
cerebral palsy in, 244
Ashworth score, 17
dorsal rhizotomy in, 195
ASIA impairment scale C, 163, 164
femoral anteversion in, 84
Athetosis, 80n
with hereditary spastic paraparesis,
Autogenetic Ib inhibition, 43; see also
254, 255
Postsynaptic inhibition of
hyperexcitable stretch reflexes in,
motoneurons
63
Autosomal dominant cerebellar ataxias
inhibitory spinal cord circuit
(ADCA), 258–259, 260t–261t;
alterations in, 244
see also Spinocerebellar
motor branch to soleus in, 102
degenerations
routine walking, 108
Autosomal recessive ataxias, 266; see also
spasticity in, 220
Spinocerebellar degenerations
with stroke, 65
289
290 Index
Axonal degeneration, 179 Cerebral palsy and spastic diplegia

Axonal sensory neuropathy, 266 (CP-SD), 247, 250
Cerebral palsy/clinical management of
spasticity
B
cerebral palsy, characteristics of, 80–82
Baclofen, 37, 123, 152, 163, 182 injection therapies
pump implantation, 190 botulinum toxin type A, 86–87
Balance dysfunction, 262 phenol, 87–88
Basal ganglia lesion, 46 oral medication
Beck depression inventory, 248 benzodiazepines, 85–86
Benzodiazepines, 85–86, 124, 152, 186 gabapentin and pregabalin, 86
Biomechanical evaluation of spasticity, oral baclofen, 86
27; see also Spasticity overview, 70–80
Biomechanical measurement methods, surgical treatment
120 intrathecal baclofen, 89–91
Bladder dysfunction, 247 neurotomy, 89
Body function/structure, 119–121, selective dorsal rhizotomy, 91–96,
119t, 120t 95t
Bone growth, 84 therapy
Bony changes, 247 strengthening spastic muscles, 88
Botulinum neurotoxin (BoNT), 158–160 stretching, 88
treatment of toe-walking in treatment objectives, 82–85
children, 64 Chemodenervation, 148, 157–160
Botulinum toxin, 124–125 Children
focal therapies for TBI, 220–222 botulinum toxin injections, 87
management of spasticity in MS, 188 with cerebral palsy, 64
type A, 86–87 contractures in, 94
Brain-derived neurotrophic factor dorsal rhizotomy for, 195
(BDNF), 273 with dystonia, 224
Brain injury complications on spasticity, with HSP, 247, 251
209; see also Spasticity hyperexcitable stretch reflexes in, 63
Brown-Séquard Syndrome (BSS), 142 neronal migration disorder in, 81
Brunnstrom stages, 106f oral baclofen for, 86
Bulbar symptoms, 270 selective dorsal rhizotomy (SDR) for,
161
SPARCLE study of in, 82
C
with spastic cerebral palsy, 88, 254
Calf spasticity, 83f, 84f; see also Spasticity surgical management of spasticity, 226
Canadian Occupational Performance upper extremity in, with cerebral
Measure, 121 palsy, 159
Cannabinoids, 152, 184–186 Clasp-knife response, 11f, 16
Casting, 217 Clonidine, 152
for contracture vs. spasticity Clonus, 8–9, 13, 44–45
management, 217–218 Closed-nerve blockade, 187
Central cord syndrome (CCS), 141, 142 Clostridium botulinum, 188
Central pattern generators (CPG), 108 Co-contraction; see also Spasticity
Cerebral inflammatory presentation, abnormal movement patterns and,
274 12–13
Cerebral palsy, characteristics of, 80–82 for joint stiffness, 69–70
Index 291
Cognitive dysfunctions, 107 Delayed plantar response (DPR), 139

Collateral sprouting, 35 Demyelinating/dysmyelinating
Coma, 90, 186, 205, 224, 225 disorders, 273; see also
Coma Recovery Scale (Revised) (CRS-R), Leukodystrophies
225 De novo mutations, 274
Commissural interneurons, 68 Depression, 40, 43, 62, 63, 65, 156, 266
Complex spastic SCI patient CNS, 223
combination therapies post-activation, 36, 37–39, 244
intrathecal systemic/focal (case respiratory, 157, 186
study), 164 Diazepam, 37, 85, 186
oral systemic/focal (case study), Dietary therapy, 275
163 Diffusor tensor imaging (DTI), 241
Composite Spasticity Index, 17 Disability-adjusted life years (DALY),
Compound muscle action potentials 102
(CMAP), 141 Disability Rating Scale, 225
Contractures Disease-modifying therapy, 271
biomechanical methods to measure, Disordered motor control, 70
18 over-activity and, 70
in cerebral palsy, see Cerebral palsy/ Disordered sensori-motor control, 7
clinical management of Distal axonopathies; see also Hereditary
spasticity spastic paraparesis (HSP)
defined, 14 balance in HSP, 248–249
measurement of, 17–19 cellular changes, 238–240, 239t
in patients with upper motoneuron clinical presentation, 237–238
syndrome, 14–16 cortical activation with movement,
by spasticity/immobilisation, 241
204, 205f descending/ascending tract
surgical correction of, 160–161 function, changes in, 240–241
surgical treatment of, 81 outcome measurement, 252
Contralateral ankle spasticity, 218; physical interventions, 257–258
see also Spasticity prevalence and genetics, 237
Conus medullaris syndromes, 143 service delivery, 258
Coordination, 141, 142, 161, 205f, 265t spasticity, pharmacological/surgical
interjoint, 67–68 treatment of, 253–255
interlimb, 68–69 spasticity/associated symptoms
Cortical activation with movement, on functional ability, 248
241 walking difficulties, 249–252
Cortical hyperexcitability, 269 Disynaptic reciprocal Ia inhibition,
Cortical stimulation, 273 40–41; see also Postsynaptic
Corticospinal tract, 266 inhibition of motoneurons
Cramps, 243 Dorsal rhizotomy, 195
Cystic disorders, 274; see also Dorsiflexors, 40, 41
Leukodystrophies Dynamometry, 251
Dysdiadochokinesis, 118
Dysfunctional equinovarus posture,
D
113
Dantrolene, 152, 183 Dystonia, 80n
Dantrolene sodium, 124 about, 46
Deep tendon reflexes (DTR), 139 clinical management, 81
292 Index
E Focal chemodenervation, 159, 164

Focal spasticity, 125; see also Spasticity
Education of patient, 123
treatments for, 187
Electrical stimulation, 206, 218–219
Focal therapies
Electromyography (EMG), 10, 64, 148
botulinum toxin injection, 220–222
Endocytosis, 240
case study, 222–223
Endosomes, 240
phenol/alcohol neurolysis, 223
Endurance training, 268
Force vital capacity (FVC), 271
EPSP, 34, 64–65
Frataxin, 266
Epstein Barr Virus (EBV) infection, 176
Frenchay Scale, 214
Exaggerated reflexes, 8
Frequency, intensity type, and time
Exaggerated stretch reflex activity;
(FITT), 191
see also Spasticity,
Friedreich’s ataxia (FRDA)
pathophysiology of
about, 266–267; see also
about, 31–32
Spinocerebellar degenerations
motoneuronal changes,
management of
pathophysiological role of,
Co-enzyme Q10 and idebenone,
32–35
267
postsynaptic inhibition
symptomatic management,
of motoneurons,
267–268
pathophysiological role of
Frontal lobe white matter, 241
changes in, 40–44
Functional ambulation category (FAC),
presynaptic sites, regulation at, 35–39
254
sprouting, 35
Functional electrical stimulation (FES),
transmission in group II pathways,
257
39–40
Fusimotor drive, gamma-spasticity,
Exercise
43–45; see also Postsynaptic
in ALS, 272
inhibition of motoneurons
in MS, 191
F-wave measurements, 19
Exocystosis, 240
Extensor hallucis longus, 114
Extrapyramidal signs, 270 G
GABAergic drugs, 37
F Gabapentin, 86, 152, 183–184, 254
GABA receptor, 36, 86, 89, 184
Familial ALS (FALS), 269; see also Gait control, role of spasticity in, see
Motor neuron disorders/ Postural control/gait control,
familial ALS role of spasticity in
Fatigue, 248 Gamma-aminobutyric acid (GABA), 123,
Femoral anteversion, 84 152, 245
Flexor reflex afferent (FRA) circuitries, Gamma-spasticity, 43–45; see also
45 Spasticity
FMRI, 241, 245 Glasgow Outcome Scale, 217
Focal anti-spastic pharmacotherapy, Global Spasticity Score, 192
157–160 Goal Attainment Scale, 121
Focal anti-spastic surgical treatment, Goal Attainment Scaling (GAS), 212
161–162 Golgi tendon organs, 39, 43
Index 293
Graded Redefined Assessment of clinical presentation, 269–271

Strength, Sensibility, and disease-modifying therapy, 271
Prehension (GRASSP), 149 pathology, 269
Gross motor function measure (GMFM), symptomatic management,
254 271–273, 272t
overview, 236–237
spinocerebellar degenerations
H
autosomal dominant cerebellar
Handheld dynamometers, 27 ataxias (ADCA), 258–259,
Hand spasticity, 142, 160 260t–261t
Hematopoietic stem cell autosomal recessive ataxias, 266
transplantation, 275 Friedreich’s ataxia (FRDA)/
Hemiplegic gait, 109 late-onset Friedreich’s ataxia
Hereditary myelopathies, 236 (LOFA), 266–268
Hereditary spastic paraparesis (HSP) SCA3 or Machado-Joseph disease,
adrenoleukodystrophy (ADL) 259–262, 261t, 266
clinical presentation, 274–275 symptoms associated with
interventions, 275 bladder dysfunction, 247
prevalence and genetics, 274 bony changes, 247
case study, 242, 253b, 255b–256b fatigue, 248
distal axonopathies limb stiffness, 243–246
balance in HSP, 248–249 mood/quality of life, 248
cellular changes, 238–240, 239t paresis, 246–247
clinical presentation, 237–238 sensory loss, 247
cortical activation with Heterotopic ossification (HO), 209
movement, 241 High tone, 4
descending/ascending tract Hippotherapy, 194
function, changes in, 240–241 Hoffmann reflex, 121
outcome measurement, 252 H-reflex
physical interventions, 257–258 about, 43, 140
prevalence and genetics, 237 measurements, 19
service delivery, 258 technique, 41
spasticity, pharmacological/ 5-HT receptors, 34, 35, 45
surgical treatment of, 253–255 Hydrotherapy, 257
spasticity/associated symptoms Hyper-excitable reflexes, 8
on functional ability, 248 Hyperexcitable stretch reflexes, 62–63
walking difficulties, 249–252 Hypertonia, 4
leukodystrophies Hypertonicity in paralysis, 5
cystic disorders, 274 Hypomyelinating disorders, 273; see also
demyelinating/dysmyelinating Leukodystrophies
disorders, 273 Hypotonia, 4–6
hypomyelinating disorders, 273
spongiform disorders, 273
I
motor neuron disorders/familial
amyotrophic lateral sclerosis Idebenone, 267
amyotrophic lateral sclerosis Impairments, classification of, 17
(ALS), 268–269 IncobotulinumtoxinA, 220
294 Index
Increased reflexes, 8 hypomyelinating disorders, 273

Injection therapies; see also Cerebral spongiform disorders, 273
palsy/clinical management Limb stiffness, 243–246
of spasticity Lipids, 240
botulinum toxin type A, 86–87 Locomotor training (LT), 151, 152
phenol, 87–88 Long-latency, defined, 29
Interjoint coordination, 67–68 Long-latency stretch reflexes/
Interlimb coordination, 68–69 coordination of movement,
Interlimb reflexes, 139 66–67
Intermittent theta burst stimulation Lower extremity spasticity, 206
(iTBS), 190 Lower limb weakness, 246
Intermittent theta burst TMS (iTBS), 193 Lower motor neuron (LMN), 268
Intramuscular botulinum toxin
injection, 220
M
Intrathecal anti-spastic
pharmacotherapy, 155–157 Machado-Joseph disease, 259–262, 261t,
Intrathecal application of baclofen (ITB), 266; see also Spinocerebellar
155, 255 degenerations
Intrathecal baclofen (ITB), 89–91, Maculopathy, 259
125–126, 146, 189–190, 254 Mechanical resistance, 29
Intrathecal therapies, for TBI, 223–226, Medication possession ration (MPR), 219
226t Microneurography, 43
Intrinsic stiffness, 28 Mildly affected upper limb (UAT 4-7),
Invasive/permanent methods, for stroke spasticity in patients with, 118
patients, 126–128 Moderately affected upper limb (UAT
Invasive/reversible methods, for stroke 2-3), spasticity in patients with,
patients, 124–126 117–118
Isometric muscle strength, 246 Modified Ashworth Scale (MAS), 26,
102, 115, 148, 191, 193
Monoaminergic neurotransmitters, 39
J
Monosynaptic Ia afferent pathway, 65
Joint posture, measurement of, 119 Mood/quality of life, 248
Joint stiffness, 214 Motoneuronal changes,
pathophysiological role of,
32–35
K
Motoneurons, 32
Kernicterus, 80 postsynaptic inhibition of, see
King’s Hypertonicity Scale, 214 Postsynaptic inhibition of
motoneurons
Motor-evoked potentials (MEP), 240
L
Motor nerve, 89
Late-onset Friedreich’s ataxia Motor neuron disorders/familial ALS
(LOFA), 266–268; see also amyotrophic lateral sclerosis (ALS),
Spinocerebellar degenerations 268–269
Leukodystrophies; see also Hereditary clinical presentation, 269–271
spastic paraparesis (HSP) disease-modifying therapy, 271
cystic disorders, 274 pathology, 269
demyelinating/dysmyelinating symptomatic management, 271–273,
disorders, 273 272t
Index 295
Motor recovery/motor control after Nocturnal oximetry, 271

stroke, 105–108 Noninvasive treatment, for stroke
Movement patterns, abnormal, 12–13; patients with spasticity,
see also Spasticity 123–124
MS, see Multiple sclerosis (MS) Non-invasive ventilation (NIV), 271, 272t
Multiple sclerosis (MS) Non-pharmacological treatments, in MS
disease-modifying treatments for, 179 about, 190–191
incidence/epidemiology/disease physical activity/exercise for spasticity
course, 176–178 management in MS, 191
pathophysiology of/spasticity, transcranial magnetic stimulation
178–179 (TMS) for, 193–194
spasticity in, 179–181 transcutaneous electrical nerve
spasticity management in MS stimulation (TENS) for, 191–193
hippotherapy, 194 Non-reflex stiffness, 214, 215
neuromuscular electrical Nonsurgical management of spasticity,
stimulation cycling (NMES), 126
194 Normal tone, 4
non-pharmacological treatments, Nutritional management, 271
190–194
pharmacological treatments,
O
181–190, 186t
strategy for, 195–197 Obturator nerve, 124
surgery, 195 Ocrelizumab, 179
whole-body vibration (WBV), 194 Onabotulinum toxin A, 217, 220
Muscle afferents, 35 Oral anti-spasticity medications, 254
Muscle fibre atrophy, 105 evidence-based guidelines for,
Muscle hypertonia, 138, 140 186–187, 186t
Muscle overactivity, 104 Oral baclofen, 86
and increased co-contraction, 118 Oral medication; see also Cerebral
during stance phase, 111–113 palsy/clinical management of
during swing phase, 113–115 spasticity
Muscle reinnervation, 223 about, 181, 219
Muscle resistance, 26 benzodiazepines, 85–86
Muscle stiffness, 38 gabapentin and pregabalin, 86
Muscle weakness, 249 oral baclofen, 86
Myotonometer, 216 Oral spasmolytic drugs, 123
Oral systemic anti-spastic
pharmacotherapy, 152–155, 153t
N
Orthopaedic surgical procedures, 195
National Institute for Care and Clinical Orthoses, 257
Excellence (NICE), 179, 181 Orthotic devices, 88, 123
Neuroleptic malignant syndrome, 89 Orthotic management, 82
Neurolysis, 124 Over activity phenomena, 35, 70
Neuromuscular electrical stimulation
cycling (NMES), 194
P
Neurons within ascending/descending
tracts, 238 Paralysis, hypertonic, 5
Neurotomy, 89 Paresis, 246–247
NIHSS score, 15 Participation, activity and, 121
296 Index
Passive stretching, 216 Primary adrenal insufficiency, 275

Penn Spasm Frequency Scale, 17, 214 Primary afferent depolarisation (PAD),
Perceived resistance to passive 36
movement (PRPM) test, 120t Problematic spasticity, 110
Percutaneous endoscopic gastrostomy Progressive-relapsing disease, 177
(PEG), 271 Proprioceptive feedback, 107
Persistent inward currents (PIC), 32, 34, Proteins, 240
45, 138 Pyramidal tract, lesion of, 29–30
Persistent vegetative state (PVS), 225
Phenol
Q
and alcohol neurolysis, 223
chemodenervation, 187–188 Quality of life, 248
in injection therapies, 87–88, 158, 223
Physical activity for spasticity
R
management in MS, 191
Physical modalities, 216–217 Ramp and hold method, 10f
Physical therapy, 123, 150, 257 Randomised controlled trials (RCT),
Physiotherapy, 151, 191 154, 182, 185
Pigmentary retinopathy, 259 Range of Motion (ROM), measurement
Plantarflexor, 40, 41, 64 of, 119
spasticity, 257 Recurrent inhibition, 41; see also
Plastic surgery, 126 Postsynaptic inhibition of
Polyglutamate (polyQ) disease, 259 motoneurons
Polysegmental reflexes, 140 Reduced range of motion (ROM), 160
Polysynaptic reflexes, 144 Reflexes
Position-dependent spasticity, 10f–11f, 16 in antagonist, control of, 63
Post-activation depression, 36, 38 excitability, 61
Postsynaptic inhibition of motoneurons increased, 8
autogenetic Ib inhibition, 43 integrated part of voluntary
disynaptic reciprocal Ia inhibition, movement, 59–60
40–41 modulation in simple contraction of
fusimotor drive, gamma-spasticity, agonist muscle, 60–62
43–44 in swing phase, suppression of,
recurrent inhibition, 41 63–64
Postural control/gait control, role of Reflex hyperexcitability, 31
spasticity in Reflex-mediated stiffness, 28–29
about, 108–111 Reflex response, 8
muscle overactivity during stance Rehabilitation
phase, 111–113 about, 266
muscle overactivity during swing after stroke, 106
phase, 113–115 Rehabilitation Medicine spasticity, 102;
Pregabalin, 86 see also Spasticity
Premature birth, 81 Relapsing-remitting MS (RRMS), 177
Presynaptic inhibition, 36–37 Relaxed muscle, response of, 9–12
Presynaptic sites, regulation at; see also Renshaw cells, 41
Spasticity, pathophysiology of Renshaw-mediated recurrent inhibition,
about, 35–36 270
post-activation depression, 37–39 Repetitive cortical stimulation, 273
presynaptic inhibition, 36–37 Repetitive TMS (rTMS), 193
Index 297
Respiratory muscle weakness, 270 contractures in patients with

Rigidity, 3 upper motoneuron syndrome,
Rimabotulinumtoxin B, 220 14–16
Routine walking, 108 framework development for,
6–12, 7t
altered tone or response of
S
relaxed muscle, 9–12
Sativex, 185 increased (hyper-excitable/
SCI, see Spinal cord injury (SCI) exaggerated) reflexes, 8
Scottish Intercollegiate Guidelines spasms and clonus, 8–9
Network (SIGN) guidance, 181 hypertonia (or high tone), 4
Sedation, 123 hypotonia, 4–6
Selective dorsal rhizotomy (SDR), 91–96, measurement of spasticity/
95t, 161–162 contracture, 17–19
Self-report instruments, 121 by SPASM Consortium, 7, 7t
Sensitivity, 8n in upper motoneuron syndrome,
Sensory feedback contribution to 13–14
movement, 64–66 in multiple sclerosis (MS), 179–181
Sensory loss, 247 neurophysiological methods to
Severely affected upper limb (UAT 0-1), measure, 19
spasticity in patients with, 117 overview, 1–2
Short-interval intracortcal inhibition pathophysiology-based treatment of
(SICI), 269 about, 143–144
Smooth rectified EMG (SRE), 111f clinical signs of spasticity, 144
Sniff nasal inspiratory pressures, 271 spastic movement disorder,
Soleus H-reflex, 37, 62, 244 144–145
SPARCLE study, 82 therapeutic consequences, 145–147
Spasm pharmacological/surgical treatment
about, 8–9, 13 of, 253–255
causes of, 45 in SCI, clinical assessment of, 148–149
defined, 8 treatment in SCI, 150–152
SPASM Consortium Spasticity, pathophysiology of
defining spasticity, 7, 7t by adaptive changes in spinal
Spasm Frequency Score, 17 networks, 30–31
Spastic dystonia, 16, 45–46, 70 clonus, relation to spasticity, 44–45
Spasticity exaggerated stretch reflex activity
and associated symptoms on about, 31–32
functional ability, 248 motoneuronal changes, 32–35
biomechanical evaluation of, 27–28 postsynaptic inhibition of
biomechanical methods to measure, motoneurons, 40–44
18 presynaptic sites, regulation at,
clinical evaluation of, 26–27 35–39
clinical presentation/anatomical sprouting, 35
distribution of, 149–150 transmission in group II
clinical signs of, 144 pathways, 39–40
definition by lesion of pyramidal tract, 29–30
abnormal movement patterns/ muscle response to stretch, nature
co-contractions, 12–13 of, 28–29
about, 2–3, 3t spasms, causes of, 45
298 Index
spastic dystonia, 45–46 over-activity as general adaptation to

spasticity measurement (from clinical central lesion, 70
evaluation to biomechanical reflexes, integrated part of voluntary
techniques), 26–28 movement, 59–60
Spasticity management in MS; see also sensory feedback contribution to
Multiple sclerosis (MS) movement, 64–66
hippotherapy, 194 stretch reflex modulation in spastic
neuromuscular electrical stimulation subjects
cycling (NMES), 194 control of reflexes in antagonist, 63
non-pharmacological treatments hyperexcitable stretch reflexes in
about, 190–191 stance phase of gait, 62–63
physical activity/exercise for, 191 reflex modulation during simple
transcranial magnetic stimulation contraction of agonist muscle,
(TMS) for, 193–194 60–62
transcutaneous electrical nerve suppression of reflexes in swing
stimulation (TENS) for, 191–193 phase, 63–64
pharmacological treatments training for learning, 70–71
baclofen, 182 Specificity, 8n
benzodiazepines, 186 Spinal cord atrophy, 179
botulinum toxin, 188 Spinal Cord Independence Measure
cannabinoids, 184–186 (SCIM), 149
dantrolene, 183 Spinal cord injury (SCI)
focal spasticity, treatments for, 187 complex spastic SCI patient
gabapentin, 183–184 combination therapies, intrathecal
intrathecal (IT) baclofen, 189–190 systemic/focal (case study), 164
oral antispasticity medications, combination therapies, oral
evidence-based guidelines for, systemic/focal (case study), 163
186–187, 186t epidemiology/specific aspects of
oral medications, 181 spasticity in, 137–139
phenol chemodenervation, 187–188 overview, 136–137
tizanidine, 182–183 patient selection/therapeutic approach
strategy for, 195–197 clinical assessment of spasticity
surgery, 195 in, 148–149
whole-body vibration (WBV), 194 clinical presentation/anatomical
Spastic movement disorder distribution of spasticity, 149–150
development of, 139–141 contractures, surgical correction
on patho-anatomy, 141–143 of, 160–161
pathophysiology-based treatment of, focal anti-spastic
144–145 pharmacotherapy,
Spastic paraplegia rating Scale (SPRS), chemodenervation, 157–160
252 focal anti-spastic surgical
Spastic patients, functional problems in treatment, selective dorsal
co-contraction for joint stiffness, rhizotomy (SDR), 161–162
69–70 indication for treatment, spasticity
interjoint coordination, 67–68 in SCI, 147–148
interlimb coordination, 68–69 intrathecal anti-spastic
long-latency stretch reflexes/ pharmacotherapy, 155–157
coordination of movement, mainstay of spasticity treatment in
66–67 SCI, physical therapy, 150–152
Index 299
oral systemic anti-spastic Stretch reflex-mediated resistance, 28

pharmacotherapy, 152–155, 153t Stretch reflex modulation in spastic
physiological effects of training, 150 subjects
spasticity, pathophysiology-based control of reflexes in antagonist, 63
treatment of hyperexcitable stretch reflexes in
about, 143–144 stance phase of gait, 62–63
clinical signs of spasticity, 144 reflex modulation during simple
spastic movement disorder, contraction of agonist muscle,
144–145 60–62
therapeutic consequences, 145–147 suppression of reflexes in swing
spastic movement disorder and phase, 63–64
patho-anatomy, 141–143 Striatal toe, 113, 114
spinal shock/recovery of spinal Stroke
excitability/development of about, 101–102
spastic movement disorder, motor recovery/motor control after,
139–141 105–108
Spinal excitability, recovery of, 139–141 pathophysiology of spasticity after,
Spinal networks, adaptive changes in, 102–105
30–31 spasticity management after
Spinal shock, 31, 139–141 about, 122–123, 122t
Spinocerebellar ataxias (SCA), 259–262, invasive, permanent methods,
261t, 266 126–128
Spinocerebellar degenerations invasive, reversible methods,
autosomal dominant cerebellar 124–126
ataxias (ADCA), 258–259, management strategy for, 128
260t–261t noninvasive treatment, 123–124
autosomal recessive ataxias, 266 Stroke, contractures in/clinical
Friedreich’s ataxia (FRDA)/late-onset management of spasticity
Friedreich’s ataxia (LOFA), about stroke, 101–102
266–268 in arm and hand function
spinocerebellar ataxia3 (SCA3)/ about, 115–116
Machado-Joseph disease, with mildly affected upper limb
259–262, 261t, 266 (UAT 4–7), 118
Splinting, 218 with moderately affected upper
Splints and orthoses, 266 limb (UAT 2–3), 117–118
Spongiform disorders, 273; see also with severely affected upper limb
Leukodystrophies (UAT 0–1), 117
Sprouting, 35 motor recovery/motor control after
Standing posture, 109 stroke, 105–108
Stiff knee gait, 113, 251 in postural control/gait control
Stiffness about, 108–111
at elbow, 5f muscle overactivity during stance
measured at knee joint, 7f phase, 111–113
Strengthening spastic muscles, 88 muscle overactivity during swing
Stretching, 88 phase, 113–115
for contracture vs. spasticity stroke, pathophysiology of spasticity
management, 217–218 after, 102–105
Stretch reflex activation, 251 stroke, spasticity management after
Stretch reflexes, 38, 43, 62 about, 122–123, 122t
300 Index
invasive, permanent methods, Tonic supraspinal inhibition, 31

126–128 Tonus, 3, 4
invasive, reversible methods, Training
124–126 for learning, 70–71
management strategy for stroke physiological effects of, 150
patients with spasticity, 128 Transcranial magnetic stimulation
noninvasive treatment, 123–124 (TMS), 193–194, 240
stroke patients, spasticity assessment in Transcutaneous electrical nerve
about, 118–119 stimulation (TENS), 191–193
activity and participation, 121 Transmission in group II pathways,
body function and structure, 39–40
119–121, 119t, 120t Traumatic brain injury (TBI)
Stroke patients, spasticity assessment in biomechanical assessment, 214–216
about, 118–119 brain injury complications on
activity and participation, 121 spasticity, 209
body function/structure, 119–121, clinical assessment, 212–214, 213t
119t, 120t clinical presentations, 207–209, 208t
Stroke Upper Limb Capacity Scale, 121 contractures/spasticity on recovery,
Strumpell-Lorrain syndrome, 237 206
Supraspinal control of spinal networks, 69 management options
Surface electromyography (sEMG), 121 electrical stimulation, 218–219
Surface neuromuscular electrical focal therapies, 220–223
stimulation, 123 intrathecal therapies, 223–226, 226t
Surgical treatment oral medications, 219
intrathecal baclofen, 89–91 physical modalities, 216–217
in MS, 195 stretching/casting for contracture
neurotomy, 89 vs. spasticity management,
selective dorsal rhizotomy, 91–96, 95t 217–218
for TBI, 226–227 surgical interventions, 226–227
Symptomatic management, SCA, 262 treatment modalities, 227
overview, 204–206
treatment goals, 209–212, 210t–212t
T
Treadmill training, 69
Tardieu scale, 27, 243 Trunk control, 108
Tardieu Score, 17, 212t
TBI, see Traumatic brain injury (TBI)
U
Tendon-lengthening procedures, 195
Tendon transfers, 128 Upper limb symptoms, 270
Tenotomy, 195 Upper motoneuron syndrome
Tetrahydrocannabinol (THC), 155 spasticity in, 13–14
Tetraplegia, 160 Upper motor neuron (UMN), 204, 236,
Tibial nerve, 124, 126 268
Timed Up and Go Test, 121 Utrecht Arm/Hand Test (UAT), 116, 116f
Tizanidine, 40, 124, 152, 163, 182–183
Tone
V
about, 3, 4
altered, 9–12 Velocity-dependent response, 10f–11f
Tone Assessment Scale, 102, 214 Very late-onset Friedreich’s ataxia
Tongue movements, 270 (VLOFA), 267
Index 301
Visual Analogue Scaling, 121 Wallerian degeneration, 88, 142

Visual problems, 259 Water therapy, 151
Whole-body vibration (WBV), 194
Wolff’s law, 85n
W
Walking difficulties, 249–252
Z
Walking index in SCI (WISCI), 149
Walking Test, 121 Zone of partial preservation, 141

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Neurological Rehabilitation - Spasticity and Contractures in Clinical Practice and Research

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Neurological

Marcia J. Scherer, PhD

Dave Muller, PhD

Paediatric Rehabilitation Engineering: From Disability to Possibility, edited by

© 2018 by Taylor & Francis Group, LLC

No claim to original U.S. Government works

Printed on acid-free paper

International Standard Book Number-13: 978-1-4665-6544-9 (Hardback)

Library of Congress Cataloging‑in‑Publication Data

Names: Pandyan, Anand, editor. | Hermens, Hermie J., editor. | Conway,

Visit the Taylor & Francis Web site at

and the CRC Press Web site at

1. Definition and Measurement of Spasticity and Contracture.................1

3. Functional Problems in Spastic Patients Are Not Caused

4. The Clinical Management of Spasticity and Contractures

5. Clinical Management of Spasticity and Contractures in Stroke....... 101

6. Clinical Management of Spasticity and Contractures in Spinal

7. Clinical Management of Spasticity and Contractures

8. Clinical Assessment and Management of Spasticity

9. Hereditary Spastic Paraparesis and Other Hereditary

Anand D. Pandyan, PhD, is Professor for Rehabilitation Technology and

Hermie J. Hermens, PhD, earned his master’s in Biomedical Engineering at

Bernard A. Conway, PhD, is Professor in Biomedical Engineering at the

Lisa Bunn Gerard E. Francisco

Jakob Lorentzen Anand D. Pandyan

Jens Bo Nielsen Maria Willerslev-Olsen

Anand D. Pandyan, Bernard A. Conway,

at improving function or preventing significant secondary complication such

1.2.1 Can the Words Increased Tone/Hypertonia

Confusion of thought has occurred throughout the diverse use of the

In summary, the words hypertonia and spasticity cannot be used inter-

1.2.2 Developing the Framework for Defining Spasticity

Whilst such an all-encompassing definition has some benefit, it is of lim-

1.2.2.1 Increased (Hyper-Excitable/Exaggerated) Reflexes

1.2.2.2 Spasms and Clonus

* Sensitivity: the ability to accurately identify those with spasticity.

is some anecdotal evidence that spasms can be influenced by changes in

1.2.2.3 Altered Tone or the Response of a Relaxed Muscle

Slow vs fast (Vel & EMG)

Slow vs fast (Vel & EMG)

Slow vs fast (Vel & EMG)

Slow vs fast (Vel & EMG)

FIGURE 1.3 (CONTINUED)

50 EMG triceps brachii

EMG biceps brachii Force

all of whom employed direct measures of muscle electrical activity to gain

1.2.2.4 Abnormal Movement Patterns and Co-Contraction

loading, the latter being the interia-sensitive mechanical-reflex oscillation

1.2.3 The Classification and Definition of Spasticity

• Spasms (A transient but continuous muscular contraction which can be

The clinical presentations of spasticity can be modulated by ambient affer-

history and time course of onset in many disease populations needs to be

1.2.4 Contractures in Patients with Upper Motoneuron Syndrome

4 0.04 4 0.04 4 0.04 4 0.04

2 0.02 2 0.02 2 0.02 2 0.02

• Does spasticity contribute to contractures?

1.2.5 The Measurement of Spasticity and Contracture

Both spasticity and contractures would come under the classification of

1.2.1 Can the Words Increased Tone/Hypertonia

1.2.2 Developing the Framework for Defining Spasticity

1.2.2.1 Increased (Hyper-Excitable/Exaggerated) Reflexes

1.2.2.2 Spasms and Clonus

1.2.2.3 Altered Tone or the Response of a Relaxed Muscle

1.2.2.4 Abnormal Movement Patterns and Co-Contraction

1.2.3 The Classification and Definition of Spasticity

1.2.4 Contractures in Patients with Upper Motoneuron Syndrome

1.2.5 The Measurement of Spasticity and Contracture

2.1 How to Measure Spasticity – From Clinical

2.2 The Nature of the Muscle Response to Stretch

2.3 Is Spasticity Caused by Lesion of the Pyramidal Tract?

2.4 Spasticity Does Not Appear Immediately after Lesion but

2.5 Pathophysiology of Exaggerated Stretch Reflex Activity:

2.5.1 Pathophysiological Role of Motoneuronal Changes

2.5.2 Sprouting, New Synapses

2.5.3 Regulation at Presynaptic Sites: Increasing

2.5.4 Transmission in Group II Pathways

2.5.5 Pathophysiological Role of Changes in

2.5.5.1 Disynaptic Reciprocal Ia Inhibition

2.5.5.4 Fusimotor Drive, Gamma-Spasticity

2.6 How Is Clonus Related to Spasticity?

2.7 What Causes a Spasm?

2.8 Spastic Dystonia Is Not Caused by

3.1 Reflexes Are an Integrated Part of Voluntary Movement

3.2 Stretch Reflex Modulation in Spastic Subjects

3.2.2 Hyperexcitable Stretch Reflexes in the Stance Phase of Gait

3.2.3 Control of Reflexes in the Antagonist

3.2.4 Suppression of Reflexes in Swing Phase

3.3 Sensory Feedback Contribution to Movement

3.4 Long-Latency Stretch Reflexes

3.7 Co-Contraction as a Strategy to Maintain Joint Stiffness

3.8 Over-Activity as a General Adaptation to Central

3.9 Training to Learn New Strategies