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 NEUROMUSCULAR
DISORDERS
TREATMENT AND MANAGEMENT
This page intentionally left blank
     
 Second Edition

NEUROMUSCULAR
DISORDERS
TREATMENT AND
MANAGEMENT
Tulio E. Bertorini, MD
Professor of Neurology and Pathology,
and Director of the Clinical
Neurophysiology Fellowship
University of Tennessee
Center for the Health Sciences
Director of EMG Laboratory Methodist
University Hospital
Director of Wesley Neurology Clinic and
The Muscular Dystrophy and ALS Clinics,
Memphis, Tennessee

iii
Elsevier
3251 Riverport Lane
St. Louis, Missouri 63043

NEUROMUSCULAR DISORDERS, TREATMENT AND MANAGEMENT,

SECOND EDITION ISBN: 9780323713177

Copyright © 2022 by Elsevier, Inc. All rights reserved.

No part of this publication may be reproduced or transmitted in any form or by any means, electronic or
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Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance
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This book and the individual contributions contained in it are protected under copyright by the Publisher
(other than as may be noted herein)

Cover image
Top: IBM - Rimmed vacuoles (left) and a ragged red fiber (right) seen in Inclusion Body Myositis stained with Gomri’s
Modified Trichrome (200x)

Bottom: Inflammatory - Inflammatory cells stained with hematoxylin and eosin (100x)

Notices

Practitioners and researchers must always rely on their own experience and knowledge in evaluating and
using any information, methods, compounds or experiments described herein. Because of rapid advances
in the medical sciences, in particular, independent verification of diagnoses and drug dosages should be
made. To the fullest extent of the law, no responsibility is assumed by Elsevier, authors, editors or contrib-
utors for any injury and/or damage to persons or property as a matter of products liability, negligence or
otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the
material herein.

ISBN: 9780323713177

Content Strategist: Melanie Tucker

Director, Content Development: Ellen Wurm-Cutter
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Publishing Services Manager: Shereen Jameel
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Printed in India

Last digit is the print number: 9 8 7 6 5 4 3 2 1

 To my wife, Emma, for her patience, support, and
encouragement; my children, Tulio J. Paola and F­ rancisco;
my grandchildren, Nicolas, Rafael, and G
­ abriela; and the
memory of my parents, Nico and Queta.

To the Peruvian American Medical Society (PAMS) for

their dedication to the care of the indigent and improving
medical education in Peru.

To the Ernesto Guevara class of the San Fernando

Medical School in Lima on the golden anniversary of
their graduation.

To my patients.

To all that died in the front lines fighting the

COVID-19 pandemic.
Preface
There have been great advances in the diagnosis and eval-
uation of patients with segmental and generalized neuro-
muscular disorders since the first edition of this book. Tests
applied to different types of the disorders are discussed in
the introduction as well as specific chapters.
The management of these diseases have also improved
significantly, particularly in cardiac and pulmonary care,
and in the management of autonomic and peripheral neu-
ropathies, and for this reason these chapters have been ex-
panded. We have also expanded chapters in orthopedic sur-
gery and rehabilitation with the use of robotics to manage
patients with chronic weakness.
Immunotherapy has improved greatly with the use of
new monoclonal antibodies, which increases the armamen-
tarium of clinicians that take care of autoimmune disor-
ders. The basic aspects of immunotherapy are covered in
Chapter 7, but also are detailed chapters dedicated to au-
toimmune neuropathies and myopathies, and disorders of
neuromuscular disorders of neuromuscular junction.
The most important development in neuromuscular dis-
orders has been the discovery of pathogenic genes and im-
proved testing in hereditary conditions, which has allowed
vi
us to diagnose patients even without muscle biopsies, and
this has led to genetic therapies. We have included a new
chapter that introduces the readers to these treatments,
which are also discussed in detail in those chapters dedi-
cated to hereditary myopathies and neuropathies.
Some topics are discussed in various chapters, causing
some repetition, but the intent is that each reader could
consult individual chapters independently.
These have been very difficult times, because of the
COVID-19 pandemic, which affects more severely patients
with weakening neuromuscular disorders. Medical care has
also been complicated by this, and COVID-19 infections are
associated with neuromuscular conditions that are discussed
in different chapters.
The pandemic has also created difficulties in the com-
pletion of this book, and I am most grateful to the Elsevier
personnel and the other collaborators that have helped
overcome these difficulties. I am also very thankful that they
dedicated their time and effort to the completion of this
volume, which I believe will be very useful to those taking
care of patients with neuromuscular disorders.

We wish to acknowledge the great secretarial help of Cindy
Burchfield and Ginger Lindsey, and the excellent artwork of
Jason Peck. We also acknowledge the contribution of Joseph
Null and Mariallen Shadle for excellent histology work and
photography.
We extend our sincere appreciation to Dr. Michael Cart-
wright and Dr. Francis Walker for providing great ultra-
sound figures.
Acknowledgments
Finally, we want to acknowledge the excellent and dedi-
cated collaboration from the authors of the different chap-
ters, and express gratitude to Wesley Neurology and UTHSC
for their support, and to Kathleen Nahm and Nadhiya Sekar
at Elsevier for editorial help.
vii
Contributors

Annas Aljassem, MD, MHSA Vinay Chaudry, MD, MBA, FRCP

Assistant Professor Professor
Physical Medicine & Rehab Neurology
Oakland University William Beaumont, Rochester Hills Johns Hopkins University School of Medicine, Baltimore
Michigan Maryland
United States United States
Chapter 6 Chapter 14

Bassam A. Bassam, MD, FAAN Marinos C. Dalakas, MD, FAAN

Professor Professor of Neurology
Neurology Chief Neuromuscular Division
University of South Alabama, Mobile Neurology
Alabama Thomas Jefferson University, Philadelphia
United States Pennsylvania
Chapter 10, 21 United States
Chapter 22
Tulio E. Bertorini, MD
Professor Marcus Deschauer, MD
Department of Neurology Professor Technical University Munich
University of Tennessee Health Sciences, Memphis Neurology
Tennessee Klinikum rechts der Isar, Munich
United States Germany
Chapter 1, 7, 10, 21 Chapter 23

Aimee K. Boegle, MD, PhD Rima N. El-Abassi, MD, ABPN, ABCN

Instructor Assistant Professor
Neurology Neurology
BIDMC/Harvard Medical School, Boston Louisiana State University, Metairie
Massachusetts Louisiana
United States United States
Chapter 18 Assistant Professor
Neurology
William W. Campbell Jr., MD, MSHA South East Louisianan Veterans Health Care System,
COL, MC, USA (Ret) New Orleans
United States Louisiana
Chapter 17 United States
Chapter 15
Sonia Caraballo-Cartagena, MD
Neuromuscular Fellow John D. England, MD
Neurology Professor and Chair
University of Puerto Rico, San Juan Neurology
Puerto Rico LSUHSC, New Orleans
Chapter 16 Louisiana
United States
Diana Castro, MD Chapter 15
Assistant Professor of Pediatrics, Neurology,
and Neurotherapeutics Diana M. Escolar, MD, FAAN
Pediatrics Chief Medical Officer
University of Texas Southwestern, Dallas miRagen Therapeutics, Inc., Boulder
Texas Colorado
United States United States
Chapter 13 Chapter 20

viii
 CONTRIBUTORS ix

Jonathan Daniel Finder, MD Maxwell Harris Levy, MD

Professor of Pediatrics Clinical Neurophysiology Fellow
Pediatrics Neurology
University of Tennessee Health Science Center, Memphis Louisiana State University Health Science Center,
Tennessee New Orleans
United States Louisiana
Chapters 2, 10 United States
Chapter 15
Christopher H. Gibbons, MD, MMSc
Associate Professor of Neurology Thomas E. Lloyd, MD, PhD
Neurology Associate Professor
Harvard Medical School, Boston Neurology and Neuroscience
Massachusetts Johns Hopkins University School of Medicine, Baltimore
United States Maryland
Chapter 5 United States
Chapter 14
Levi M. Hall, PharmD
Clinical Pharmacy Specialist Catherine Lomen-Hoerth, MD, PhD
Department of Pharmaceutical Services Professor
Beaumont Health, Royal Oak Neurology
Michigan UCSF, San Francisco
United States California
Assistant Professor United States
Foundational Medical Studies Chapter 12
Oakland University William Beaumont School of Medicine,
Rochester Carlos A. Luciano, MD
Michigan Professor
United States Neurology
Chapter 6 University of Puerto Rico School of Medicine, San Juan
Puerto Rico
Alicia Henriquez, MD Puerto Rico
Pediatric Neuromuscular Fellow Chapter 16
Neurology
University of Texas Southwestern, Dallas Daniel L. Menkes, MD
Texas Professor and Chair
United States Neurology
Chapter 13 Oakland University William Beaumony, Royal Oak
Michigan
Mohammed K. Ismail, MD United States
Associate Professor of Medicine Chapter 6
Division of Gastroenterology
University of Tennessee Health Science Center, Memphis Christopher W. Mitchell, MD
Tennessee Neurologist
United States Department of Neurology
Chapter 4 West Tennessee Neuroscience and Spine, Jackson
Tennessee
Mark Landau, MD, FAAN United States
Staff Neurologist Chapter 7
Neurology
Tripler Army Medical Center, Honolulu William Motley, MD, DPhil
Hawaii Director of Translational Medicine
United States Flare Therapeutics, Cambridge
Associate Professor Massachusetts
Neurology United States
Uniformed Services University of the Health Sciences, Chapter 14
Bethesda
Maryland
United States
Chapter 17
x CONTRIBUTORS

Pushpa Narayanaswami, MD Michael Spickler, MD

Associate Professor Resident
Neurology Physical Medicine and Rehabilitation
Beth Israel Deaconess Medical Center/Harvard Medical Beaumont Royal Oak, Royal Oak
School, Boston Michigan
Massachusetts United States
United States Chapter 6
Chapter 11, 18
Christopher F. Spurney, MD
Shin J. Oh, MD Associate Professor
Distinguished Professor Emeritus Cardiology
Neurology Children’s National Health System, Washington
University of Alabama at Birmingham, Birmingham District of Columbia
Alabama United States
United States Chapter 3
Chapter 19
Carolina Tesi Rocha, MD
Laura Rosow, MD Associate Professor of Neurology
Assistant Professor Neurology
Neurology Stanford University, Palo Alto
UCSF, San Francisco California
California United States
United States Chapter 20
Associate Director of ALS Center
Department of Neurology Dorothy Weiss Tolchin, MD, EdM
University of California, San Francisco, California Instructor, part-time
United States Physical Medicine and Rehabilitation
Chapter 12 Harvard Medical School, Boston
Massachusetts
Jennifer E. Schramm, MD United States
Pediatric Cardiology Fellow Director of Medical Student Education
Pediatric Cardiology Physical Medicine and Rehabilitation
Children’s National Hospital, Washington Spaulding Rehabilitation Hospital/Harvard Medical
District of Columbia School, Charlestown
United States Massachusetts
Chapter 3 United States
Chapter 8
Shreesh Shrestha, MD
Chief Resident in Patient Safety and Quality Improvement Matthias Vorgerd, MD
Internal Medicine Adjunct Professor
UTHSC, Memphis Ruhr University, Bochum
Tennessee Germany
United States
Chapter 4 William C. Warner Jr., MD
Professor
Nicholas J. Silvestri, MD Orthopedics
Associate Professor of Neurology University of Tennessee, Memphis
Neurology Tennessee
University at Buffalo Jacobs School of Medicine and United States
Biomedical Sciences, Buffalo Chapter 9
New York
United States Saša Živković, MD, PhD
Chapter 5 Professor
Department of Neurology
Michael Soliman, MD University of Pittsburgh School of Medicine, Pittsburgh
Fellow of Neuromuscular Diseases Pennsylvania
Louisiana State University, New Orleans Louisiana United States
United States Chapter 11
Chapter 15
 Contents

PART   1 GENERAL PRINCIPLES 10 Perioperative Management of Patients With

Neuromuscular Disorders, 206
IN THE TREATMENT Tulio E. Bertorini, MD | Jonathan Daniel Finder, MD |
AND MANAGEMENT Bassam A. Bassam, MD, FAAN
OF NEUROMUSCULAR 11 Molecular and Genetic Therapies, 225
DISORDERS Pushpa Narayanaswami, MD | Saša Živković, MD, PhD

1 Introduction: Evaluation of Patients With

Neuromuscular Disorders, 2 PART   2 TREATMENT AND
Tulio E. Bertorini, MD MANAGEMENT OF
2 Respiratory Complications in Neuromuscular
SPECIFIC NEUROMUSCULAR
Disorders, 40 DISORDERS
Jonathan Daniel Finder, MD
12 Treatment and Management of Adult Motor
3 Cardiac Complications of Neuromuscular
Neuron Diseases, 248
Disorders, 52 Laura Rosow, MD | Catherine Lomen-Hoerth, MD, PhD
Christopher F. Spurney, MD | Jennifer E. Schramm, MD
13 Treatment and Management of Spinal Muscular
4 Gastrointestinal Complications of Neuromuscular
Atrophy and Congenital Myopathies, 261
Disorders, 79 Diana Castro, MD | Alicia Henriquez, MD
Mohammed K. Ismail, MD | Shreesh Shrestha, MD
14 Treatment and Management of Hereditary
5 Autonomic Dysfunction in Neuromuscular
Neuropathies, 278
Disorders, 97 William Motley, MD, DPhil | Vinay Chaudry, MD, MBA, FRCP |
Christopher H. Gibbons, MD, MMSc | Nicholas J. Silvestri, MD Thomas E. Lloyd, MD, PhD

6 A Practical Approach to the Treatment of Painful 15 Treatment and Management of Autoimmune

Polyneuropathies, 118 Neuropathies, 312
Annas Aljassem, MD, MHSA | Levi M. Hall, PharmD | Michael Rima N. El-Abassi, MD, ABPN, ABCN | Michael Soliman, MD |
­Spickler, MD | Daniel L. Menkes, MD Maxwell Harris Levy, MD | John D. England, MD

7 Principles and Guidelines of Immunotherapy in 16 Treatment and Management of Infectious,

Neuromuscular Disorders, 143 Granulomatous, and Toxic Neuromuscular
Christopher W. Mitchell, MD | Tulio E. Bertorini, MD Disorders, 345
Carlos A. Luciano, MD | Sonia Caraballo-Cartagena, MD
8 Rehabilitation in Neuromuscular
Disorders, 160 17 Treatment and Management of Segmental
Dorothy Weiss Tolchin, MD, EdM Neuromuscular Disorders, 380
William W. Campbell Jr., MD, MSHA | Mark Landau, MD, FAAN
9 Orthopedic Surgery in Neuromuscular
Disorders, 186 18 Treatment and Management of Disorders of
William C. Warner Jr., MD Neuromuscular Hyperexcitability and Periodic
Paralysis, 414
Aimee K. Boegle, MD, PhD | Pushpa Narayanaswami, MD

xi
xii CONTENTS

19 Treatment and Management of Disorders of the 22 Treatment and Management of Autoimmune

Neuromuscular Junction, 446 Myopathies, 554
Shin J. Oh, MD Marinos C. Dalakas, MD, FAAN

20 Treatment and Management of Muscular 23 Treatment and Management of Hereditary

Dystrophies, 492 Metabolic Myopathies, 572
Carolina Tesi Rocha, MD | Diana M. Escolar, MD, FAAN Matthias Vorgerd, MD | Marcus Deschauer, MD

21 Neuromuscular Manifestations of Acquired Index, 595

Metabolic, Endocrine, and Nutritional
Disorders, 528
Bassam A. Bassam, MD, FAAN | Tulio E. Bertorini, MD
 PART 1
GENERAL PRINCIPLES
IN THE TREATMENT
AND MANAGEMENT
OF NEUROMUSCULAR
DISORDERS
 1 Introduction: Evaluation of
Patients with Neuromuscular
Disorders
Tulio E. Bertorini, MD
This book is dedicated to the treatment of neuromuscu-
lar disorders (NMDs), which include those that affect the
anterior horn cells, nerve roots, plexi, peripheral nerves,
neuromuscular junction, and muscles (Fig. 1.1) (Dubowitz,
1996); some also affect other areas of the nervous system,
such as amyotrophic lateral sclerosis (ALS). These disorders
may be caused by genetic defects or may be acquired, as the
autoimmune diseases, may be secondary to general medi-
cal conditions or may arise as complications of surgery. To
make therapeutic decisions about these disorders, clinicians
should be able to recognize their clinical presentation and
characteristics. This chapter provides a brief introduction to
the evaluation of patients with NMDs.
MEDICAL HISTORY AND SYMPTOMS
The evaluation should include obtaining detailed medical
and family histories as well as identifying possible complicat-
ing factors. In children, information should be obtained on
the prenatal period and delivery, especially if the patient was a
“floppy baby,” and details of the patient’s developmental mile-
stones should be recorded (Brooke, 1999; Dubowitz, 1996).
Identifying general medical problems is important be-
cause some NMDs are associated with other conditions,
such as endocrine and connective tissue diseases that
might affect other organs. Medications also should be con-
sidered, because many are known to produce neurologic
complications.
Muscle weakness is a common symptom, except in patients
with sensory or autonomic neuropathy or in some radiculop-
athies and entrapment syndromes. The rate of progression
varies, and in some conditions, such as Guillain-Barré syn-
drome (GBS), electrolyte imbalance, toxic neuropathy, and
myopathy associated with rhabdomyolysis, it is rapid (Box
1.1). In disorders of neuromuscular transmission, such as
myasthenia gravis (MG), weakness fluctuates during the day.
In periodic paralysis, weakness is recurrent (Brooke, 1986),
whereas in other disorders, such as muscular dystrophies, or
in hereditary and some autoimmune neuropathies, it is sub-
acute or chronic (Box 1.2) (Bertorini, 2002; Brooke, 1986).
The distribution of weakness also is important in diag-
nosis; for example, it is proximal in spinal muscular atro-
phies and most myopathies, except for some disorders in
which it is more distal, for example, inclusion body myositis
(IBM) and Miyoshi myopathy. In myopathies, weakness usu-
ally is symmetric, although asymmetry can be seen in some
2
diseases like fascioscapulohumeral dystrophy and IBM. In
polyneuropathies, this characteristically begins in the legs
but may initially manifest more prominently in the upper
extremities, as in multifocal neuropathy, and also in brachial
plexopathies, and cervical spinal canal disorders as well as in
ALS. This follows the territory of roots or nerves in radicu-
lopathies, focal neuropathies, (Bertorini, 2002), mononeu-
ritis multiplex, and entrapment neuropathies.
Dysphagia, diplopia, and ptosis also help to identify NMDs
because they occur in some myopathies and also in disor-
ders of neuromuscular transmission, such as MG. Symptoms
of respiratory difficulty should be recognized and treated
promptly because this can be the first manifestation of some
disorders such as MG, GBS, ALS, and some myopathies,
such as acid maltase deficiency, whereas in other disorders,
it appears at later stages (Bertorini, 2002, 2008). During the
evaluation, one should always inquire about sleep difficul-
ties, as sleep apnea can be seen in some of these diseases.
Difficulty combing the hair and placing objects in high
cabinets commonly occurs in patients with shoulder-girdle
weakness, whereas difficulty writing and grasping objects in-
dicates involvement of the forearm and hand muscles, as in
ALS and IBM. Weakness of the hip extensors usually causes
inability to rise from a low chair or a toilet seat, whereas
difficulty ascending stairs indicates dysfunction of the hip
flexors and quadriceps muscles. More severe weakness of
the quadriceps muscles occurs in IBM, causing difficulty
descending stairs (Brooke, 1986; Griggs, Mendell, & Mill-
er, 1995). When the distal muscles are affected, foot drop
may cause a steppage gait and difficulty negotiating curves
or changing courses, as seen in polyneuropathies, distal dys-
trophies, and ALS.
Muscle stiffness, tightness, and spasms occur as a result
of spasticity in disorders affecting the upper motor neuron,
but these also occur in patients with motor unit hyperac-
tivity, such as “stiff-person” and Isaac syndromes and the
myotonias. Those with inflammatory myopathies, polymy-
algia rheumatica, fasciitis, and hypothyroidism also com-
plain of stiff limbs. Cramping at rest or during exercise is
a prominent symptom of the cramp-fasciculation syndrome
(Masland, 1992) and also some neuropathies. In metabolic
myopathies, this usually occurs during or after exercise, or
after fasting in some cases. Fatigue is common in disorders
of neuromuscular transmission, such as Eaton-Lambert syn-
drome (ELS) and MG, but also in myopathies, even though
weakness is the major symptom. In ELS, there may be tem-
porary improvement after a brief exercise.
 CHAPTER 1 — INTRODUCTION: EVALUATION OF PATIENTS WITH NEUROMUSCULAR DISORDERS 3

Root
Radiculopathy

Dorsal root ganglion

Sensory
ganglioneuropathy

Anterior horn cell

SMA
ALS
Root
Radiculopathy

Plexus
Radiation plexitis

Autonomic nerve

Peripheral nerve
Demyelinating neuropathies
Axonal neuropathies

Unmyelinated
fiber

Myelinated fibers
Demyelinating neuropathies
CIDP

Fig. 1.1 Anatomic elements of the pe-

ripheral nervous system and related
Neuromuscular junction neurologic disorders. ALS, Amyotrophic
Lambert-Eaton syndrome lateral sclerosis; CIDP, chronic inflam-
Myasthenia gravis
matory demyelinating polyneuropathy;
SMA, spinal muscular atrophy. (Adapted
from Bertorini, T. E. (2002). Overview and
Muscle classification of neuromuscular disorders.
Myopathies In T. E. Bertorini (Ed.). Clinical evaluation
and diagnostic tests for neuromuscular
disorders (pp. 1–13). Woburn, MA: Butter-
worth-Heinemann.)

Decreased sensation as well as paresthesias and neuropath-
ic pain are symptoms of peripheral neuropathies (Ochoa,
1995). These symptoms are localized in the affected areas in
those with radiculopathies, plexopathies, and entrapment
neuropathies. Autonomic dysfunction can occur in some
neuropathies and also in ELS, and the clinician should ask
the patient for dysautonomic symptoms such as orthostatic
hypotension and urinary and sexual dysfunction.
PHYSICAL EXAMINATION
A careful general physical examination is essential to arrive
at a diagnosis, and the clinician should assess cardiac and
lung function, examine the eyes for cataracts and retinal dis-
ease, and check for hearing loss and lipoma, which are often
seen in mitochondrial disorders. Visceromegaly and skin
changes are present in some patients with neuropathies, for
example, those with POEMS (polyneuropathy, organomega-
ly, endocrinopathy, monoclonal gammopathy, skin changes)
syndrome. Skin abnormalities can also be seen in connective
tissue disorders, whereas patients with dermatomyositis have
a characteristic rash, including the Gottron sign, carpenter
fingers, and dilatation of the periungual capillaries (Fig
1.2) (also see figures of patients in Chapter 22) (Bertorini,
2002). High arches of the feet are seen in hereditary motor
sensory neuropathy.
Clubbing of the fingers is seen in some chronic lung dis-
orders, whereas Mees lines are seen in patients with arsenic
and other poisoning (Fig 1.3).
Intellectual function should be assessed because it could
be impaired, such as in some cases of ALS and in myotonic
dystrophy. Examination of posture and gait is useful to de-
termine if there is hyperextension of the knees, if there is
evidence of a waddling gait in myopathies, and if there is a
spastic or ataxic gait, or the steppage seen in peripheral neu-
ropathy and some distal dystrophies should test tandem gait
which is abnormal in cerebellar disease. Difficulty walking on
tiptoes is seen in people with gastrocnemius and soleus weak-
ness, whereas walking on heels cannot be done in persons
with foot dorsiflexor weakness. Patients should be asked to
get up and down from a stool to determine if there is thigh
muscle weakness. The examiner should also notice difficulty
arising from the chair or going upstairs, and if the patient
has the characteristic Gower maneuver, when arising from
the floor, due to proximal muscle weakness (Fig. 1.4), and
4 PART 1 — GENERAL PRINCIPLES IN THE TREATMENT AND MANAGEMENT OF NEUROMUSCULAR DISORDERS
Box 1.1 Neuromuscular Disorders That
May Present with Acute Generalized
Weakness
Motor Neuron Diseases
Poliomyelitis, West Nile virus infection
Amyotrophic lateral sclerosis (rarely)
Neuropathies
Guillain-Barré syndrome and variants
Porphyria, particularly acute intermittent
Dinoflagellate toxins
Diphtheria
Arsenic poisoning and other acute toxic neuropathies
West Nile virus infection
Disorders of Neuromuscular Transmission
Botulism and other biologic toxins (black widow spider bites,
snake bites)
Organophosphate poisoning
Eaton-Lambert myasthenic syndrome (rarely)
Hypermagnesemia
Myasthenia gravis
Myopathies
Rhabdomyolysis (from various causes, including metabolic,
toxic, and infectious)
Polymyositis/dermatomyositis
Infectious myositis (e.g., trichinosis, toxoplasmosis)
Electrolyte imbalance (e.g., hypohyperkalemia, hypermagne-
semia, hypocalcemia, hypercalcemia, hypophosphatemia)
Hyperthyroidism
Toxins
Intensive care myopathy (after immobilization with paralyzing
agents and steroids in the intensive care unit)
Box 1.2 Examples of Conditions That
 ­Present with Progressive Subacute or
Chronic Proximal Muscle Weakness
Progressive spinal muscular atrophy
Bulbospinal muscular atrophy (Kennedy disease)
Amyotrophic lateral sclerosis (sometimes)
Chronic inflammatory demyelinating neuropathy
Eaton-Lambert myasthenic syndrome
Myasthenia gravis
Endocrine diseases (e.g., hypothyroidism, Cushing disease,
hyperparathyroidism)
Drugs (e.g., steroids, cholesterol-lowering agents, zidovudine,
colchicine, chloroquine)
Toxins (e.g., alcoholic myopathy)
Electrolyte imbalance
Congenital myopathies (usually of earlier onset)
Muscular dystrophies
Polymyositis and dermatomyositis
Inclusion body myositis
Adult “nemaline” or “rod” myopathy
Mitochondrial myopathy
Juvenile and adult forms of acid maltase deficiency
Carnitine deficiency
Other metabolic myopathies
should observe if there is hyperlordosis with proximal atro-
phy in myopathies and distal atrophy in neuropathies and
whether it is symmetric or focal (Figs. 1.5 and 1.6) or wheth-
er it affects the upper or lower extremities more prominent-
ly. The clinician should examine the patient for muscle hy-
pertrophy, which is seen in some dystrophies and disorders
of neuromuscular hyperactivity such as myotonia congenita
(Fig. 1.7). Examination of muscle tone also is important to
determine whether there is hypotonia, particularly in infants
(Fig. 1.8 and Box 1.3), or spasticity and also to determine if
there is limitation of passive joint movement like from mus-
cle fibrosis that occurs in various myopathies (Fig. 1.9).
Examination of the eyelids and eye movements is helpful
to diagnose acute paralysis in diabetic ophthalmoplegia and
Miller-Fisher syndrome or chronic paralysis in mitochondrial
myopathy and oculopharyngeal dystrophy (Fig. 1.10). Fluctu-
ating ophthalmoplegia and ptosis are seen in MG (Fig. 1.11)
(Barton & Fouladvand, 2000). Assessment of the pupils deter-
mines the presence of Horner syndrome (Fig. 1.12), where-
as poorly reactive pupils may be seen in some neuropathies
(Bertorini, 2002, 2008). The examiner should also assess the
presence of eyelid myotonia in the myotonic disorders.
Prominent facial weakness occurs in GBS, but also in MG
and some dystrophies (Fig. 1.13). A decreased or hyperactive
gag reflex, as in ALS, not only might provide help in the diag-
nosis but also might determine the risk of aspiration. Tongue
atrophy and fasciculations are characteristically seen in motor
neuron diseases, whereas a typical forked tongue occurs in MG
(Fig. 1.14). Examination of the neck muscles helps to identify
neck extensor muscle weakness causing head drop (Fig. 1.15
and Box 1.4) (Narayanaswami & Bertorini, 2000). Rarely, pa-
tients with myasthenia can also have a “drop” jaw syndrome.
Manual muscle testing with proper grading helps to de-
termine the distribution and degree of involvement and
assess the progression of the disease, as well as diagnose
and localize segmental neurologic disorders. For example,
focal atrophy in ulnar innervated muscles is seen in ulnar
neuropathy, and there is thenar atrophy in median neurop-
athy or both in C8 radiculopathy and lower plexus lesions.
Moreover, dynamometry using different methods, particu-
larly with handheld dynamometers, is used to monitor the
progression of muscle weakness.
The examination should also include observation for
fasciculations, which are more common in motor neuron
disorders but also are seen in some neuropathies, such as
multifocal motor neuropathy. Increased reflexes with the
presence of the Babinski sign indicate involvement of the
corticospinal tracts, as in ALS, whereas generalized hypo- or
areflexia is seen in peripheral neuropathies, spinal muscular
atrophy, and some neuromuscular transmission disorders,
such as ELS and botulism. Distal reflexes are lost early in
neuropathies and are preserved until the later stages in my-
opathies (Table 1.1). The examiner also should observe the
patient for grip myotonia (Fig. 1.16) and percussion myoto-
nia, myoedema, and slow relaxation of the ankle reflexes, as
seen in hypothyroidism.
The sensory examination helps to assess the type and dis-
tribution of deficits to determine whether they are distal or
symmetric or follow the dermatomes of nerve roots or indi-
vidual nerves and whether they affect more severely the large
myelinated axons (proprioceptive deficits), the unmyelinat-
ed axons (dysautonomia, pain, and temperature deficits),
 CHAPTER 1 — INTRODUCTION: EVALUATION OF PATIENTS WITH NEUROMUSCULAR DISORDERS 5

A B

C
Fig. 1.2 (A) Heliotrope rash in a child with dermatomyositis. (B) Diffuse erythematous facial rash in an adult with dermatomyositis. (Adapted
from Bertorini, T. E. (2002). Overview and classification of neuromuscular disorders. In T. E. Bertorini (Ed.). Clinical evaluation and diagnostic tests for
neuromuscular disorders (pp. 1–13). Woburn, MA: Butterworth-Heinemann.) (C) Also see Gottron sign, erythema of the knuckles on dermatomyositis.
(2D) Periungual capillary dilatation and carpenter finger in dermatomyositis.)
6 PART 1 — GENERAL PRINCIPLES IN THE TREATMENT AND MANAGEMENT OF NEUROMUSCULAR DISORDERS

Fig. 1.3 White lines (Mees lines) noticed in the fingernails of a patient with arsenic poisoning. (Adapted from Bertorini, T. E. (2002). Overview and
classification of neuromuscular disorders. In T. E. Bertorini (Ed.). Clinical evaluation and diagnostic tests for neuromuscular disorders (pp. 1–13). Wo-
burn, MA: Butterworth-Heinemann.)

Fig. 1.4 Patient with juvenile acid maltase deficiency showing the Gower sign. Also notice the hyperextension of the elbow while sitting. (From
Bertorini, T. E. (2002). Clinical evaluation and clinical diagnostic tests. In T. E. Bertorini (Ed.). Clinical evaluation and diagnostic tests for neuromuscular
disorders (p. 31). Woburn, MA: Butterworth-Heinemann.)
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hypochondriasis, intellectual feebleness, and insanity. Two forms of
hereditary alcoholism have been recognized: First, that in which the
disease or defect of the parent is transmitted to the offspring; and
second, that in which the disease or defect is not directly transmitted
to the offspring, but a morbid tendency which manifests itself in
diseases or defects of a different kind.49
49 1. Heredite de similitude, Alcoolisme hereditaire homotype; 2. Heredite de
transformation, Alcoolisme hereditaire heterotype.

1. The appetite for strong drink is frequently transmitted from parents

to the children, just as other traits of the mind or body. Sometimes it
develops early, sometimes late in life; as a rule, however, this
hereditary propensity shows itself at an early age, and is apt to be
intensified at the time of puberty and the menopause. Objections
have been urged against the theory of hereditary alcoholism. Among
these the strongest is perhaps that the taste for drink in the offspring
of alcoholic subjects is the result rather of opportunity and example
than of heredity. The frequency with which alcoholic tendencies
develop themselves in children reared and educated away from their
parents, and the number of cases in which these tendencies show
themselves only at an advanced period of life, long after the
influence of example in childhood has ceased, sufficiently disprove
this assumption. The hereditary influence does not, however,
invariably manifest itself in the desire for drink. On the contrary, not
rarely it consists in feebleness of nervous constitution, characterized
by irritability, want of mental repose, or a restless or vicious
disposition which demands constant excitement. Hence such
individuals, although intellectually well developed, are often scarcely
more than moral imbeciles, in whom the passion for drink may be
replaced by the opium habit, addiction to gaming and to other vices,
and whose career is shaped largely by an inordinate and insatiable
craving for excitement of all kinds. Hereditary alcoholism follows the
laws of heredity in general. The tendency may be transmitted directly
from one generation to another, or may skip one or more
generations, taking in the intermediate periods some different form.
2. The second variety is that in which the symptoms of chronic
alcoholism are manifested in the offspring in the absence of the
direct action of alcohol; that is to say, not the taste for alcohol, but
the results of the gratification of that taste are transmitted, just as
epileptic or hysterical patients may transmit to their offspring epilepsy
or hysteria; thus it is not rare to encounter in the descendants of
alcoholic parents perverted sensation, both general and special,
hyperæsthesia, anæsthesia, flying neuralgias which do not always
follow the course of particular nerves, but frequently affect in a
general way the head or the members or manifest themselves as
visceral neuralgias. These persons are much troubled with headache
from slight causes and with migraine. Nor are disturbances of vision
rare, nor vertigo. Insomnia is also frequent in such individuals, and
augments the other symptoms. Digestive troubles also frequently
occur, notwithstanding a regular and perfectly temperate life. Such
persons are often subject to hallucinations of sight and hearing, and
are liable to have delirium in trifling illnesses.

The second form of hereditary alcoholism manifests itself in a wholly

different manner. The descendants, without a special appetite for
strong drink, and in the absence of the special morbid manifestations
above described, are singularly liable to mental and nervous
diseases of various kinds. Among these convulsions and epilepsy
are especially frequent; hysteria and various forms of insanity also
occur. In this group of cases we find every degree of arrest of
intellectual development, from mere feeble-mindedness to complete
idiocy. As manifestations of the influence of alcoholism upon the
offspring may be cited certain moral peculiarities otherwise
inexplicable, such as are seen in children who at a very tender age
show themselves vindictive, passionate, and cruel, to whom the
sufferings of others afford pleasure, who torment their companions
and torture their pets, and show precocious vicious tendencies of all
kinds. Later in life these persons become lazy, intolerant of
discipline, vagabonds, unstable of character, without the power of
application and without moral sense. Given to drink, defiant of law,
they constitute the great body of tramps, paupers, and criminals. The
children of alcoholic subjects are often feeble and puny, pale, badly
nourished, and curiously subject to morbid influences.

IV. Dipsomania.

Dipsomania, which has also been described under the term

oinomania, is rather a form of insanity than of alcoholic disease. The
characteristic symptoms are, however, in the greater number of
instances, due to indulgence in alcohol. The subjects of this affection
usually belong to families in which insanity, and especially this
particular form of insanity, is hereditary.

There are two forms of dipsomania—the essential and the

symptomatic. Of these, the latter is the more frequent. Its
consideration requires in this connection very few words. It manifests
itself by an irresistible desire on the part of many insane people for
alcohol. It occurs both in the prodromic and in the fully-established
periods of insanity. It is especially common in various forms of mania
and in the prodromic periods of general paralysis. The dominating
influence in essential dipsomania is heredity. Occasional causes
may bring on particular attacks, but their influence is secondary.
Dipsomania cannot be looked upon as a distinct recurrent affection
in an otherwise healthy person. At some period in their lives, and
often long before the occurrence of characteristic paroxysms,
dipsomaniacs show peculiarities indicating defects of mental
organization. Certain symptoms of dipsomania are often mistaken for
its cause. Thus, dyspepsia is more frequently an effect than a cause
of the alcoholic excesses. The despondency, irritability, restlessness,
hysterical manifestations, and insomnia which precede the attack are
not the cause of it: they are its earliest symptoms.

The affection usually begins insidiously and is progressive. As a rule,

although not always, it begins in early adult life. The manifestations
of this disease are essentially intermittent and paroxysmal, but the
impulse to drink must be regarded as a symptom which may be
replaced by other irresistible desires of an impulsive kind, such as
lead to the commission and repetition of various crimes, as the
gratification of other depraved appetites, robbery, or even homicide.
The paroxysms are at first of short duration, and are followed by
return to the previous regular and decent manner of life. They
become, however, by degrees, more violent and more prolonged. At
first lasting for a few days or a week, by and by they extend to
periods of a month or six weeks, the attack wearing itself out, and
recurring with a periodicity sometimes variable and sometimes
constant. In the intervals of these attacks for a considerable time the
patients very often lead sober, chaste, and useful lives. At length,
however, evidences of permanent mental trouble are manifested,
and the case settles into confirmed insanity. The attack is usually
preceded by evidences of mental derangement; the patient becomes
restless and irritable; sleep is irregular and unrefreshing; he
complains of general malaise, and is anxious, troubled by vague
apprehensions. He presently abandons his usual occupations and
gives himself up to disordered impulses, among which alcoholic
excesses are the most frequent and the most easily gratified.
Sometimes the patient passes his time at taverns drinking with all
comers; at others he shuts himself up in a chamber and gratifies his
desire for drink to the most extreme degree alone. Dipsomaniacs not
rarely leave their homes and associates without warning or
explanation, and pass the period of the paroxysm among associates
of the most disreputable character. The desire for drink is gratified at
all costs, and not infrequently they return to their friends without
money and without sufficient clothing, most of it having been sold or
pawned in order to purchase drink. The paroxysm is succeeded by a
period of more or less marked mental depression, during which the
patient not rarely voluntarily seeks admission to some asylum.

The true nature of dipsomania is frequently overlooked. As a

symptom of hereditary insanity it is in striking contrast with the
habitual propensity to drink which occurs in the ordinary alcoholic
subject. The latter seeks occasions to drink. He renews his excesses
not intermittently, but habitually. If in consequence of disgrace or
misfortune or under strong moral suasion he is for a time
abstemious, it is only to renew and to continue his indulgence upon
the first favorable occasion. On the contrary, the true dipsomaniac
recognizes his malady and struggles against it. Even more: for a
time he shows much skill in concealing it. He avoids occasions to
drink, and, reproaching himself for his mad and unreasonable desire,
seeks by every means to overcome his impulse to it. The ordinary
drunkard may become insane because he drinks; the dipsomaniac
drinks because he is insane.50
50 Magnan, Le Progrès médical, 1884.

Dipsomaniacs are apt to manifest precocious or retarded intellectual

development. They are from infancy or childhood especially prone to
convulsive or other paroxysmal nervous phenomena. They are often
choreic, often hysterical. This association with instability of the
nervous system is related to the fact that dipsomania is more
common in women than in men.

DIAGNOSIS.—1. Acute Alcoholism.—The diagnosis of the ordinary

form of acute alcoholism, with the exception of alcoholic coma,
requires no consideration. The diagnosis of alcoholic coma from
profound coma due to other conditions is, in the absence of the
previous history of the case, always attended with difficulty, and is in
certain cases quite impossible. It is therefore of great practical
importance to obtain the history where it is possible to do so. The
odor of alcohol upon the breath is of less positive diagnostic value
than would at first thought appear. In the first place, sympathetic
bystanders may have poured alcoholic drinks down the throat of one
found unconscious, or, in the second place, individuals who have
taken a certain amount of drink may be, and not unfrequently are,
seized with apoplexy in consequence of the excitement thereby
induced. The more common conditions with which alcoholic coma is
confounded are apoplexy from cerebral hemorrhage and narcotic
poisoning, especially opium-poisoning. To these may also be added
uræmic coma and, under exceptional circumstances, sunstroke. In
all these cases the circumstances under which the individual has
been found are of diagnostic importance.

In alcoholic coma the pupils are more commonly dilated than

contracted, the heart's action feeble, the respiration shallow, the
muscular relaxation symmetrical, and the temperature low. There is
a strong odor of alcohol upon the breath.

In apoplexy from cerebral hemorrhage the condition of the pupils will

depend upon the location of the clot. They may be moderately
dilated, firmly contracted, or unequal. The enfeeblement of the
heart's action is, as a rule, less marked than in profound alcoholic
coma. The pulse may be small or full and slow or irregular. It is
usually slow and full. The respiration is often, although not invariably,
slow and stertorous. Not uncommonly, the eyes and also the head
deviate from the paralyzed side. If the coma be not absolute, the
muscular relaxation is unilateral. The temperature is at first slightly
below the normal, but less, as a rule, than in alcoholic coma; after
several hours it rises to or above the normal.

In complete opium narcosis the insensibility is profound; the heart's

action is slow or rapid, but feeble; the respirations slow and shallow
or quiet or stertorous; the face at first flushed, afterward pallid and
cyanosed; the pupils minutely contracted or dilated as death
approaches; and the muscular relaxation complete, with abolition of
reflex movements. In cases of doubt it is important to use the
stomach-pump.

Uræmic coma is apt to be preceded by or alternate with convulsions.

The pupils are more commonly slightly contracted than dilated, but
are without diagnostic significance. The temperature is not elevated;
it may even be low. The face may be pallid, pasty, and puffy, and
there may be general anasarca if the nephritis be parenchymatous.
On the other hand, in interstitial nephritis there is hypertrophy of the
heart, without evidence of valvular disease, and some degree of
puffiness of the lower extremities. In doubtful cases the urine should
be drawn by a catheter and subjected to chemical and microscopical
examination.51 Diabetic coma occurs suddenly without convulsions.
This condition may be suspected when the emaciation is extreme or
upon the recognition of sugar in the urine.
51 The following is the method recommended by Green (Medical Chemistry,
Philadelphia, 1880) for the detection of alcohol in the urine: If its reaction be acid, the
urine is exactly neutralized by potassium acid carbonate. It is then distilled on a water-
bath in a flask or retort connected with a condensing apparatus. When about one-
sixth of the liquid has passed over the distillate will, if alcohol be present, present the
following characteristics: first, the peculiar alcoholic odor; second, a specific gravity
lower than water; third, upon being mixed with dilute sulphuric acid and treated with a
few drops of potassium bichromate solution the liquid becomes green, owing to the
separation of chromic oxide; the odor of aldehyde may at the same time be observed.
This reaction is not characteristic, but may serve to confirm other tests. Fourth, if
dilute alcohol be shaken with an excess of solid and dry potassium carbonate in a
test-tube, the greater part of the water will be appropriated by the potassium
carbonate, and two layers of liquid will be formed. The alcohol constitutes the upper
layer, and if sufficiently concentrated will burn upon the application of a flame. Finally,
a small trace of alcohol may be separated from the urine without difficulty after the
ingestion of alcoholic liquids by means of a good fractionating apparatus. Less than 1
per cent. of alcohol cannot be detected.

Sunstroke is characterized by dyspnœa, gasping respiration,

jactitation, and intense heat of the skin. The pulse varies. It may be
full and labored or feeble and frequent. The face is usually flushed.
The pupils, at first contracted, are afterward dilated. The coma is apt
to be interrupted by transient local or general convulsions.

It is impossible to lay down any rules by which the maniacal form of

acute alcoholism may be at once diagnosticated from acute mania
from other causes. For the characteristics of the convulsive form of
acute alcoholism and those forms which occur in persons of
unsound mind the reader is referred to the descriptions of those
conditions. The diagnosis of acute poisoning by alcohol in lethal
doses can only be established during life by investigation of the
history of the case.

II. Chronic Alcoholism.—The lesions of chronic alcoholism, as has

already been pointed out, are not in themselves peculiar to that
condition. Many of them occur with more or less frequency in morbid
states not induced by alcohol. It is their association and progressive
character which gives to chronic alcoholism its individuality. The
occasional prominence of certain symptoms or groups of symptoms
may thus in particular cases lead to some confusion of diagnosis,
especially where the history is unknown or the habits of the
individual are concealed. In the greater number of cases, however,
the association of symptoms is such as to render the diagnosis, even
in the absence of a direct history, a comparatively easy one.

Chronic alcoholism is a condition rather than a disease—a condition

characterized by varying lesions of the viscera and nervous system,
by profound disturbances of nutrition, and by grave mental and moral
derangements. This fact being recognized, the cardinal error of
diagnosis to be guarded against is that of overlooking the condition
upon which the disease itself with which we have to do depends or is
associated. Congestion, inflammation, sclerosis, and steatosis affect
the various organs of the body and produce their characteristic
symptoms. Profound and lasting disturbances of nutrition demand
our attention. Psychical derangements of all grades, from mere
moodiness to confirmed and hopeless insanity, take place. These
affections must be diagnosticated for themselves here as elsewhere
in clinical medicine. The recognition of the underlying condition can,
however, alone supply the key to their true pathology.

Delirium tremens is occasionally diagnosticated with difficulty from

some forms of insanity not caused by drink. Here transitory and fixed
delusions, not mere terrors and hallucinations, are of importance, not
less than the absence of the varied and complex associations of
symptoms which are characteristic of alcoholism. The delirium of the
acute infectious diseases may be mistaken for delirium tremens.
Pneumonia, typhoid fever, and the exanthemata occasionally begin
with delirium resembling in some respects delirium tremens. Here
the history of the case, the pyrexia, and the general condition of the
patient are sufficient to establish the diagnosis if the danger of error
be borne in mind.
III. Hereditary Alcoholism.—The diagnosis of this condition can only
be established by careful investigation of the family history and
systematic study of the stages of progression by which the morbid
condition presented by the patient has been reached.

IV. Dipsomania.—The diagnostic points are the hereditary

transmission of this or other forms of insanity—the mental instability
of the patient in early life and in the intervals of the paroxysms, the
intermittent or cyclical recurrence of the attack, the morbid impulses
of a different kind associated with the impulse to drink, and the
struggle of the patient against his recurring impulses to
uncontrollable excesses.

PROGNOSIS.—The prognosis in acute alcoholism of the ordinary form

is favorable, so far as the immediate attack is in question. The
prognosis in rapidly-developing, overwhelming coma from enormous
doses of alcohol is in the highest degree unfavorable. Acute coma
from moderate doses usually passes off in the course of some
hours. It occasionally, however, terminates in fatal pneumonia.

The prognosis in delirium tremens of the ordinary form is favorable. It

becomes, however, more and more grave with each recurring attack.
Delirium tremens in patients suffering from advanced disease of the
heart, lungs, liver, or kidneys, or complicated by acute diseases of
these organs, is apt to prove fatal.

The prognosis of chronic alcoholism is gloomy. If the lesions be not

advanced, permanent discontinuance of alcoholic habits may be
followed by restoration of health, but, unfortunately, the
discontinuance is too often merely temporary, the habit being too
strong to be permanently broken off.

The prognosis in hereditary alcoholism is unfavorable, both as

regards the alcoholic habit and as regards the development of
serious diseases of the nervous system under adverse
circumstances, even in the absence of the direct action of alcohol.
The prognosis in dipsomania is unfavorable. The paroxysm may
recur many times without apparent serious result; the patient in the
course of some days or weeks recovers, abandons his evil courses,
and resumes his usual occupations. After a time, however, the
insanity of which the dipsomania is the recurring manifestation
declares itself as a more or less permanent state. The outbreaks
become more frequent and more prolonged, the mental condition in
the intervals progressively more morbid, until the patient lapses by
degrees into confirmed insanity.

The prognosis in all forms of alcoholism, both acute and chronic, is

rendered in a high degree uncertain by the psychical disorders which
characterize so many of its phases. In consequence of some of
these conditions the patient loses at once his appreciation of bodily
dangers and his power to avoid them; by reason of others, to escape
imaginary evils he plunges into real ones; and finally some of them
are of such a nature that they impel him to the blind and unreasoning
commission of the most grievous crimes, including suicide and
homicide.52
52 “I believe that more suicides and combined suicides and homicides result in this
country from alcoholism in its early stages than from any other cause whatsoever” (T.
S. Clouston, Clinical Lectures on Mental Diseases, Am. ed., 1884).

TREATMENT.—The prophylaxis of alcoholism has regard to

communities at large and to individuals. The prevention of the evils
of excess by the control of the sale of drink constitutes one of the
more important objects of state medicine. At the same time, the
traffic in alcohol is curiously evasive of legal enactments. The
difficulties attending the enforcement of sumptuary laws are well
known. Restrictive laws concerning the making and sale of alcoholic
drinks, while partaking of the nature of sumptuary laws are of more
comprehensive character, being obnoxious to powerful commercial
interests and to the sense of personal liberty of large numbers of
persons of all classes. As a result of organized opposition and
individual violation they are to a great extent inoperative as regards
the prevention of alcoholism.
Aside from the question of revenue from taxation, the practical
influence of law is in this matter somewhat limited, being confined
chiefly to the prevention of the sale of liquors to minors and persons
already intoxicated, and to ineffectual attempts in certain countries to
regulate the quality of the drink sold. The penalties for personal
drunkenness which does not lead to overt acts are, as a rule, wholly
inadequate to restrain it. The best results upon anything like an
extended scale have been obtained by the co-operative action of
philanthropic individuals in endeavoring to influence the moral tone,
especially among workingmen, to diminish temptations, and to
provide for leisure hours, in the absence of drink, reasonable
amusements and occupation to occupy the time ordinarily spent in
taverns and similar places.

The decrease in the consumption of alcoholic drinks in the United

States within recent years is doubtless due in part to increasing
popular knowledge concerning the dangers of alcoholic excess and
to the growth of a more wholesome public sentiment. It is, however,
in part also due to poor wages among workingmen.

As regards the individual, prophylaxis against alcoholism consists

either in total abstinence from, or in the most guarded indulgence in,
alcoholic beverages. It is unfortunate that individuals whose moral
and physical organization is such as renders them most liable to
suffer from the consequences of alcohol are by that very fact most
prone to its temptations, and hence contribute largely to the subjects
of alcoholism. These individuals are found among the ignorant, the
very poor, and especially among neurotic subjects of all classes of
society. Due consideration of this fact cannot fail to establish the
responsibility of those fortunately not belonging to these classes, in
two respects: first, that of example; and second, that of personal
restraint from the standpoint of heredity. The influence of heredity
among races addicted to alcohol has not yet attracted the attention it
deserves. It is probable that much of the tolerance for alcohol
exhibited by individuals, families, or even nations, is to be accounted
for by heredity. Still more probable is it that most of the evils and
crimes that befall alcohol-drinking communities and individuals are
due directly or indirectly to the abuse of this agent. No argument
against the indulgence in narcotics can be more potent than that
derived from a consideration of the laws of heredity.

I. The Treatment of Acute Alcoholism.—The medical treatment of

mere drunkenness requires no consideration. The rapid elimination
of alcohol, and the transient nature of its pathological effects in
excesses which are not repeated or prolonged, explain the
spontaneous recovery, which is usually sufficiently prompt and
permanent. The physical suffering and mental distress following
unaccustomed excesses are of salutary influence. Under certain
circumstances a powerful effort of the will is sufficient to control, at all
events for a time, the more moderate effects of alcohol. A similar
result follows the use of cold douches, the Turkish bath, and full
doses of certain preparations of ammonium, particularly the officinal
solution of the acetate of ammonium. In alcoholic stupor of an acute
kind the patient may be left to himself, care being taken that the
clothing is loosened and that the position is such as to prevent local
paralysis from the nerve-pressure. Alcoholic coma, if of moderate
intensity, may be managed in the same way. Profound alcoholic
coma requires, however, more energetic measures. Frictions,
artificial warmth, stimulating enemata, as of turpentine or of hot salt
and water, an ounce to the pint, hypodermic injections of strychnia or
atrophia in minute doses and occasionally repeated, inhalations of
ammonia, and occasional cold affusions, followed by brisk frictions
with warm flannel and faradism of the respiratory muscles, may be
needed to tide over the threatened fatal collapse. The stomach
should be at once washed out with hot coffee.

In the convulsive form of acute alcoholism chloral in twenty-grain

doses, repeated at intervals until sixty grains have been given,
usually serves to arrest, or at all events to moderate, the paroxysm.
It may be administered by the mouth or in double doses by the
rectum. If chloral be inadmissible by reason of weakness of the
circulation, paraldehyde may be substituted in doses of from half a
drachm to one drachm, repeated at intervals of from one to two
hours until quietude is produced. Where the convulsive paroxysms
are of great violence it may be necessary to control them by the
cautious administration of ether by inhalation.

The mania of acute alcoholism calls for energetic management. To

avert injury to the patient himself or to those about him he must be
confined, if practicable, in a suitable apartment in a hospital; if not, in
his own house and carefully watched. Here, as a rule, paraldehyde,
chloral, or large doses of the bromides constitute our most efficient
means of medication.

In all forms of acute alcoholism it is a rule admitting of no exception

to at once withhold alcohol in every form and all doses. If, under
exceptional circumstances, great nervous depression or flagging
circulation seems to call for the use of alcohol in small amounts, it is
far better to substitute other drugs. The frequently repeated
administration of hot beef-tea or rich broths in small doses, with
capsicum and the use of the various preparations of ammonia, or
small doses of opium with or without quinia and digitalis, proves
useful in proportion to the skill and discrimination with which they are
selected and repeated. It is a good plan to commence the treatment
with an active purge.

In the acute collapse following excessive doses—lethal doses—the

stomach is to be immediately emptied by the tube or pump and
washed out with warm coffee. In the absence of the stomach-tube
emesis may be provoked by the use of mustard or sulphate of zinc
or by hypodermic injection of apomorphia. The patient must be
placed in the recumbent posture and surrounded with hot blankets.
The cold douche may be occasionally applied to the head and face,
and the muscles of respiration may be excited to action by faradism.
Artificial respiration and friction of the extremities may also be
required. Inhalations of ammonia may be used. The flagging heart
may be stimulated by occasionally tapping the præcordia with a hot
spoon—Corrgan's hammer. Hypodermic injections of digitalis may
also be employed. Overwhelming doses of alcohol, leading promptly
to collapse, usually prove fatal despite all treatment.
II. The Treatment of Chronic Alcoholism.—Whatever may be the
prominence of particular symptoms or groups of symptoms, whether
they indicate derangement of the viscera, of the nervous system, or
of the mind, whatever their combination, the fundamental therapeutic
indication in chronic alcoholism is the withdrawal of the poison. The
condition is directly due to the continuous action of a single toxic
principle: its relief when practicable, its cure when possible, are only
to be obtained by the discontinuance of that poison. This is a matter
of great, often of insurmountable, difficulty. The obstacles are always
rather moral than physical. Occasional or constant temptation, the
iron force of habit, the malaise, the faintness, the craving of the
nervous system, and, worse than all, the enfeebled intellectual and
moral tone of the confirmed drunkard, stand in the way. Even after
success seems to have been attained, and the patient, rejoicing in
improved physical health and in the regained companionship and
consideration of his family and friends, feels that he is safe, it too
often happens that in an unguarded moment he yields to temptation
and relapses into his old habits. A patient of the writer, after seven
years' abstinence from drink, again became its victim in
consequence of the incautious suggestion of a young medical man,
met at a summer hotel, to take brandy for some transient disorder,
and died after eight months of uncontrollable excesses. It is
necessary to guard the patient against the temptation to drink. To
secure this he may he sent as a voluntary patient for a length of time
to a suitable institution, or, still better, he may place himself under the
care of a conscientious, clear-headed country doctor in a sparsely-
settled region, preferably in the mountains or at the seaside. The
malaise, depression, insomnia, and other nervous symptoms when
of moderate degree are best treated by abundance of nutritious and
easily-assimilable food, taken often and in moderate amounts. To
this end gastro-intestinal disturbances may be practically
disregarded, except in so far as they regulate the selection of a
highly nutritious diet. As a matter of fact, in the early periods of
chronic alcoholism, while visceral lesions of a grave character are
yet absent, appetite and digestion alike improve in the majority of
cases upon the withdrawal of alcohol, provided a sufficiently
abundant and easily assimilable dietary is insisted upon. Grave
visceral lesions characterize a more advanced alcoholic cachexia
and necessarily complicate the treatment. Nevertheless, even here
the indication is the withdrawal of the poison. The nervous symptoms
require special medication. The whole group of tonics, from simple
bitters to quinia and strychnia, is here available. It is impossible to
lay down rules for the treatment of particular cases except in the
most general manner. In the absence of conditions calling for special
treatment, such as gastritis, hepatic or pulmonary congestion, fatty
heart, etc., good results follow the frequent administration of small
doses of quinia and strychnia; thus, the patient may take one grain of
quinia six or eight times a day, or a little gelatin-coated pill containing
1/200–1/100 of a grain of strychnia every hour during the waking day,

amounting in all to one-twentieth, one-tenth, or one-fifth of a grain in

the course of twenty-four hours. This treatment is often followed by
the relief of tremor, the quieting of nervous irritability, and the
production of good general results. The malaise, the general
depression, and especially the sinking feeling at the pit of the
stomach so often complained of by patients, are best relieved by
food. Fluid extract of coca is also useful in these conditions. The
value of cocaine in the management of the nervous symptoms of
chronic alcoholism, and in particular as a temporary substitute for
alcohol, is doubtful. The writer, having used it in a number of cases
by the mouth and hypodermically in doses of ¼–1 grain, has had
variable results. In some cases it temporarily relieved the craving
and concomitant symptoms; in others it failed wholly: in one instance
one-fourth of a grain was followed by great nervous depression. It is
desirable not to inform the patient of the nature of the remedy,
especially if its use be followed by good results, lest the cocaine
itself supplant alcohol as an habitual narcotic. Cold or tepid
sponging, the occasional hot bath at bedtime, and the Turkish bath
are useful adjuvants to the treatment. As a rule, opium is
contraindicated. Sleep often follows the administration of a cupful of
hot broth or milk at bedtime. Lupulin is here useful, and the writer
has come to regard an ethereal extract of lupulin in doses of from
one to three grains as a valuable and harmless hypnotic. If
necessary, hypnotic doses of chloral or paraldehyde may be used,
but care is required in their administration, and their early
discontinuance is advisable. If anæmia be profound, chalybeate
tonics do good, and among the preparations of iron pills of the dried
sulphate with carbonate of potassium (Blaud's pills) are especially
useful.

The obesity of drunkards, as a rule, diminishes on the withdrawal of

alcohol. Under circumstances of partial or complete abstinence from
drink measures to reduce the weight of such patients are wholly
inadmissible.

In conditions characterized by failure of mental power, in beginning

dementia or threatened insanity, the syrup of the hypophosphites,
the compound syrup of the phosphates, or cod-liver oil should be
administered. These remedies are likewise useful in various forms of
alcoholic paralysis, as are also faradism and galvanism employed
secundum artem. The various forms of alcoholic insanity require
special treatment, only to be had in institutions designed for the care
of patients suffering from mental diseases in general.

Whilst it is desirable in the treatment of all forms of chronic

alcoholism to secure the permanent discontinuance of the alcoholic
habit, the skill, judgment, and experience of the physician must
determine the degree of rapidity with which this, when practicable, is
to be done. The number of cases in which alcohol can be
discontinued at once and finally is limited; those in which it can be
wholly given up in the course of a few days constitute the largest
proportion of the cases; finally, in a small number of cases alcohol
can only be withdrawn cautiously and by degrees.53 Whilst it is in
most cases essential to remove the patient from his customary
surroundings and companionships, it is in the highest degree
important to provide for him mental occupation and amusement. To
this end a wholesome open-air life, with sufficient daily exercise to
induce fatigue, is highly desirable, as indeed is the companionship of
interested and judicious friends.
53 It must be borne in mind that in chronic alcoholism acute maladies of all kinds,
including traumatism, both accidental and surgical, act as exciting causes of delirium
tremens. The part played by the abrupt diminution or withdrawal of alcohol under such
 circumstances is often an important one. It is the opinion of the writer that a certain
amount of alcohol should be administered for a time at least in the accidental injuries
and acute sicknesses of alcoholic subjects, and that the reduction should be gradually
made.

The Treatment of Delirium Tremens.—The patient should be

confined in a large, well-aired apartment, without furniture except his
bed, and when practicable he should have a constant attendant. The
favorable influence of a skilful nurse in tranquillizing these patients is
very great. The custom of strapping them to the bed by the wrists
and ankles is to be deprecated. If the case be a mild one, and
especially during convalescence, open-air exercise in the sunshine
with an attendant is of benefit; care must, however, be taken to
guard against the danger of escape.

Under no circumstances should visitors be permitted to see the

patient. In young persons the treatment may be preceded by an
active saline or mercurial purge. In elderly persons, those suffering
from cachectic conditions, or in cases characterized by marked
debility and feeble circulation—conditions frequent in persons who
have had repeated attacks—it is not desirable to purge. Alcohol
should be either wholly withdrawn or more or less rapidly diminished.
It must be replaced by abundant food in the form of concentrated
broths or meat-extracts. In cases of vomiting these must be given
hot and in small doses frequently repeated. Bitter infusions may also
be given, or milk or equal parts of milk and Vichy water. If there be
thirst, the effervescent waters may be given freely. Patients often
drink with satisfaction and apparent benefit hop tea, which may be
made simply with water or with equal parts of water and porter.

The medicinal treatment will depend to a large extent upon the

peculiarities of the case. In mild cases a combination of the watery
extract of opium in small doses, not exceeding a quarter of a grain,
with quinia and digitalis, repeated every four or six hours, is often
useful. Although the view once entertained that the graver symptoms
were the result of prolonged sleeplessness is no longer tenable, the
induction of sleep, or at all events of mental and physical repose, is
among the more important therapeutical indications. For this purpose
hypnotic doses of opium are not only not desirable, but are even, in
the majority of instances, attended with danger. The sleep which
follows repeated and increasing doses of opium in delirium tremens
has too often terminated in coma deepening into death. As
calmatives, extract of cannabis indica, hyoscyamus, or the fluid
extract of piscidia are useful. As hypnotics, the bromides, chloral,
and paraldehyde yield, in the order here given, the best results. The
bromides are better in large single doses than in small doses often
repeated, better in combination than singly. Chloral, either by the
mouth or by the rectum, in doses of from twenty to forty grains, is
often followed by beneficial sleep. It is contraindicated where the
heart's action is much enfeebled. Paraldehyde, in doses of half a
drachm to one drachm, repeated at intervals of two or three hours
until sleep is induced, is still more efficient. This drug may be
administered without the fear of its exerting a depressing influence
upon the heart. The depression characteristic of grave delirium
tremens may be combated by repeated small doses of champagne
or by carbonate of ammonium in five- or ten-grain doses; the
vomiting, by withholding food and medication by the mouth, and
giving them for some hours wholly by the rectum or hypodermically.
Excessive restlessness is sometimes favorably influenced by cold
affusion, followed by brisk friction and warm blankets with continuous
artificial heat. The cold pack has proved useful.

Digitalis may be employed, ex indicatione symptomatica, but the

enormous doses of tincture of digitalis used by the late Jones of
Jersey and others are here mentioned only to be condemned.

To sum up, the chief indications for treatment are complete isolation,
the withdrawal of alcohol, abundant, readily assimilable, nutritious
food, and control of the reflex excitability of the nervous system.

III. Hereditary Alcoholism.—The treatment of the vicious propensities

of the descendants of alcoholic parents does not fall directly within
the province of the physician. It is among the most difficult problems
of education. The recognition of the cause of evil traits manifested in
childhood and youth may do something to avert dangers commonly
unsuspected. All things considered, the outlook is not hopeful. The
recognition, on the part of the physician, of the influence of
hereditary alcoholism in cases of arrested development, feeble
organization, or declared disease of the nervous system will perhaps
do less to aid his treatment in many cases than to reconcile him to its
want of full success. The cry of warning is to those who are eating
sour grapes that the teeth of their children will be set on edge.

IV. Dipsomania.—The general indications for the treatment of

dipsomania are two: first, the management of the paroxysm; second,
the control of the general condition itself.

First, then, during the paroxysm the patient must be saved, in so far
as is possible, from the danger of injuring himself or others and from
squandering his property. If the excesses are of such a degree as to
render it practicable, the same treatment must be carried out as in
cases of acute alcoholic mania and delirium tremens—namely,
confinement in a suitable apartment under the care of an
experienced nurse and the control of the doctor. Unfortunately, this
plan is not always practicable in the early days of the outbreak. Here
tonics, coca, and repeated small doses of quinia and strychnia are of
advantage. Courses of arsenic at the conclusion of, and in the
intervals between, the paroxysms are of use, on account of the
excellent influence they exert on the general nutrition. These may be
advantageously alternated with iron, cod-liver oil, and the compound
syrup of the phosphates or of the hypophosphites. Hydrotherapy
may also be used with advantage, and the influences of a well-
regulated hydropathic establishment are much more favorable than
those of institutions specially devoted to the treatment of alcoholic
subjects. In the latter the moral atmosphere is apt to be bad; the
patients support each other, and too often conspire to obtain in
secret that which is denied them openly, or, if the discipline be too
strict for this, they sympathize with each other in their restraint, react
unfavorably upon each other in the matter of shame and loss of self-
respect, and plot together to secure their liberty.
Few dipsomaniacs in the earlier periods are proper subjects for
treatment in hospitals for the insane. If cerebral excitement or
sleeplessness persist after the paroxysms, chloral, paraldehyde, or
the bromides in large doses may be used to secure sleep. Various
combinations of the bromides are often of use where the single salts
fail. It must not be forgotten that during the paroxysm there is great
danger lest the patient do himself or others harm. When there are
indications of an impending attack, and during the period of
depression following the attacks, benefit is derived from the daily use
of bitter infusions. As a matter of fact, however, the management of
these cases is among the most unsatisfactory of medical
undertakings. The difficulty is increased by the latent character of the
mental disorder in the intervals between the attacks. Even when
such patients voluntarily enter hospitals for the insane, they cannot
be retained there sufficiently long to derive any permanent benefit.
What we want is, in the words of Clouston, “an island where whiskey
is unknown; guardianship, combined with authority, firmness,
attractiveness, and high, bracing moral tone; work in the open air, a
simple natural life, a return to mother Earth and to Nature, a diet of
fruits, vegetables, bread, milk, eggs, and fish, no opportunity for one
case to corrupt another, and suitable punishments and deprivations
for offences against the rules of life laid down. All these continued for
several years in each case, and the legal power to send patients to
this Utopia for as long a period as medical authority determines, with
or without their consent.”

THE OPIUM HABIT AND KINDRED AFFECTIONS.