RM Rehabilitation Quick Reference QR RehabilitationRehabilitation MedicineMedicine QuickQuick ReferenceReference Ralph M. Buschbacher Ralph M. Buschbacher, MD Series Editor Buschbacher Ralph M. Series Editor Series Editor

Neuromuscular Nathan D. Prahlow, MD Neuromuscular John C. Kincaid, MD

Become more efficient in your practice RM Neuromuscular with Rehabilitation Medicine Quick Reference QR

Designed for the busy practitioner, Neuromuscular provides succinct coverage of the assessment and treatment of a wide spectrum of neuromuscular diseases and conditions, ranging from common to extremely rare and from relatively benign to universally fatal. Including more than 90 alphabetically arranged topics presented in a consistent format for maximum clinical utility, this nuts-and-bolts resource delivers point-of-care information for effectively managing peripheral disorders and neuromuscular . The book is organized in seven broad sections covering mononeuropa- thies, , the neuromuscular junction, and plexopathies, motor neu- ron diseases, muscle diseases, and movement disorders. Within these sections the authors address the individual and varied diseases and syndromes that comprise the field of neuromuscular and electrodiagnostic medicine, and offer a clinical roadmap for evaluation and treatment. With the improvement of function as the primary goal, the book focuses on diagnoses usually managed by neurologists and physiatrists and facilitates the relationship between these fields in the treatment of neuromuscular disease. Every entry is standardized for quick look-up in the office or clinic, and features description, etiol- ogy, risk factors, clinical features, natural history, diagnosis, red flags, treatment, prognosis, helpful hints, and suggested readings.

All Rehabilitation Medicine Quick Reference titles provide: n  Consistent Approach and Organization—at-a-glance outline format allows readers to find the facts they need instantly n  Concise Coverage—of must-know information broken down into easy-to-locate topics Prahlow Kincaid n  Fast Answers to Clinical Questions—diagnostic and management criteria for problems commonly encountered in daily practice n  Hands-on Practical Guidance—for all types of interventions and n  Multi-Specialty Perspective—ensures that issues of relevance to all rehabilitation team members are addressed Recommended Shelving Category Physical Medicine & Rehabilitation, Nathan D. Prahlow and John C. Kincaid

11 W. 42nd Street New York, NY 10036 9 781933 864488 www.demosmedpub.com Neuromuscular Rehabilitation Medicine Quick Reference Ralph M. Buschbacher, MD Series Editor Professor, Department of Physical Medicine and Rehabilitation Indiana University School of Medicine Indianapolis, Indiana

n Spine Andre N. Panagos n Spinal Cord Thomas N. Bryce n Traumatic Brain Injury David X. Cifu and Deborah Caruso n Maureen R. Nelson n Musculoskeletal, Sports, and William Micheo n Kevin M. Means and Patrick M. Kortebein n Ki Y. Shin n Neuromuscular Nathan D. Prahlow and John C. Kincaid Neuromuscular

Rehabilitation Medicine Quick Reference

Editors

Nathan D. Prahlow, MD Residency Program Director Assistant Professor of Clinical Physical Medicine and Rehabilitation Department of Physical Medicine and Rehabilitation Indiana University School of Medicine Indianapolis, Indiana John C. Kincaid, MD Kenneth L. and Selma G. Earnest Professor of Neurology Director, Fellowship Program Professor of Physical Medicine and Rehabilitation Indiana University School of Medicine Indianapolis, Indiana

NEW YORK Visit our website at www.demosmedpub.com

ISBN: 978-1-933864-48-8 e-book ISBN: 978-1-61705-006-0

Acquisitions Editor: Beth Barry Compositor: Exeter Premedia Services Private Ltd.

© 2014 Demos Medical Publishing, LLC. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission of the publisher.

Medicine is an ever-changing science. Research and clinical experience are continually expanding our knowledge, in particular our understanding of proper treatment and drug . The authors, editors, and publisher have made every effort to ensure that all information in this book is in accordance with the state of knowledge at the time of production of the book. Nevertheless, the authors, editors, and publisher are not responsible for errors or omissions or for any consequences from application of the information in this book and make no warranty, expressed or implied, with respect to the contents of the publication. Every reader should examine carefully the package inserts accompanying each drug and should carefully check whether the dosage schedules mentioned therein or the contraindications stated by the manufacturer differ from the statements made in this book. Such examination is particularly important with drugs that are either rarely used or have been newly released on the market.

Library of Congress Cataloging-in-Publication Data Neuromuscular /editors, Nathan Prahlow, John Kincaid. p.; cm. — (Rehabilitation medicine quick reference) Includes bibliographical references. ISBN 978-1-933864-48-8—ISBN 978-1-61705-006-0 (eBook) I. Prahlow, Nathan D., editor of compilation. II. Kincaid, John C., editor of compilation. III. Series: Rehabilitation medicine quick reference. [DNLM: 1. Neuromuscular Diseases—rehabilitation—Handbooks. 2. Movement Disorders—rehabilitation— Handbooks. 3. Neurodegenerative Diseases—rehabilitation—Handbooks. WE 39] RC346 616.8—dc23 2013034861

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Printed in the United States of America by Bradford and Bigelow. 13 14 15 16 17 / 5 4 3 2 1 Contents

Series Foreword ������������������������������������������������������������������������������������������������������ ix Preface �������������������������������������������������������������������������������������������������������������������� xi Acknowledgments ��������������������������������������������������������������������������������������������������� xiii Contributors ����������������������������������������������������������������������������������������������������������� xv

I Mononeuropathies 1. Axillary Neuropathy ������������������������������������������������������������������������������������������� 2 2. Facial Neuropathy (Bell’s Palsy) ������������������������������������������������������������������������� 4 3. Femoral Neuropathy ������������������������������������������������������������������������������������������� 6 4. Inguinal Neuropathies (Iliohypogastric, Ilioinguinal, and Genitofemoral ) ��������������������������������������������������������������������������������������� 8 5. Intercostobrachial Neuropathy ��������������������������������������������������������������������������� 9 6. Lateral Femoral Cutaneous Neuropathy (Meralgia Paresthetica) ��������������������10 7. Long Thoracic Neuropathy ��������������������������������������������������������������������������������12 8. Medial Antebrachial Cutaneous Neuropathy ����������������������������������������������������13 9. Median Neuropathy—Anterior Interosseous Neuropathy (Kiloh-Nevin Syndrome) ������������������������������������������������������������������������������������15 10. Median Neuropathy—In the Arm to Mid- ��������������������������������������������17 11. Median Neuropathy—At the Wrist () ������������������������19 12. Musculocutaneous and Lateral Antebrachial Cutaneous Neuropathy ����������� 21 13. Obturator Neuropathy ������������������������������������������������������������������������������������� 23 14. Peroneal (Fibular) Neuropathy: Common, Deep, and Superficial Branch Lesions ����������������������������������������������������������������������������� 24 15. Phrenic Neuropathy ����������������������������������������������������������������������������������������� 26 16. Pudendal Neuropathy ������������������������������������������������������������������������������������� 27 17. —In the Arm ����������������������������������������������������������������������� 28 18. Radial Neuropathy—Posterior Interosseous Neuropathy ������������������������������� 30 19. Radial Neuropathy—Superficial Radial Sensory Neuropathy ������������������������� 32 20. Sciatic Neuropathy ������������������������������������������������������������������������������������������� 33 21. Spinal Accessory Neuropathy ������������������������������������������������������������������������� 35 22. Suprascapular Neuropathy ����������������������������������������������������������������������������� 36 23. Tibial Neuropathy—In the Ankle and Foot ������������������������������������������������������� 38

v vi Contents

24. Tibial Neuropathy—From Knee to Ankle ��������������������������������������������������������� 40 25. Trigeminal and Neuropathy ������������������������������������������������������������� 42 26. —At the ��������������������������������������������������������������������� 44 27. Ulnar Neuropathy—At the Wrist ����������������������������������������������������������������������� 46 28. Vagal (Laryngeal) Neuropathy ������������������������������������������������������������������������� 48

II Polyneuropathies 29. Acute Inflammatory Demyelinating (Guillain-Barré Syndrome) ������������������������������������������������������������������������������� 52 30. Amyloid Neuropathies ������������������������������������������������������������������������������������� 54 31. Cancer-Related Polyneuropathies ������������������������������������������������������������������� 56 32. Chronic Inflammatory Demyelinating Polyradiculoneuropathy ����������������������� 58 33. Critical Illness ������������������������������������������������������������������������� 60 34. Hereditary Motor and Sensory Neuropathy/Charcot-Marie-Tooth Disease ������������������������������������������������������������������������������������������������������������� 62 35. Idiopathic Polyneuropathy ������������������������������������������������������������������������������� 64 36. Medication-Induced Polyneuropathy ��������������������������������������������������������������� 66 37. Multifocal Motor Neuropathy ��������������������������������������������������������������������������� 68 38. Neuropathy Due to Herpes Zoster (Shingles) ������������������������������������������������� 70 39. Neuropathy Due to Leprosy ����������������������������������������������������������������������������� 72 40. Polyneuropathy Due to Chemical Toxins and Metals ��������������������������������������74 41. Polyneuropathy Due to Nutritional Deficiency ������������������������������������������������� 76 42. Polyneuropathy Due to Vasculitis ��������������������������������������������������������������������� 78 43. Polyneuropathy in Mellitus ��������������������������������������������������������������� 80 44. Polyneuropathy in Lyme Disease ��������������������������������������������������������������������� 82 45. Polyneuropathy Related to HIV ��������������������������������������������������������� 84 46. Porphyric Neuropathy ������������������������������������������������������������������������������������� 86

III Neuromuscular Junction 47. Botulism ����������������������������������������������������������������������������������������������������������� 90 48. Congenital Myasthenia Gravis ������������������������������������������������������������������������� 92 49. Lambert-Eaton Myasthenic Syndrome ����������������������������������������������������������� 94 50. Myasthenia Gravis ������������������������������������������������������������������������������������������� 96 51. Organophosphate Poisoning ��������������������������������������������������������������������������� 98

IV Radiculopathies/Plexopathies 52. Brachial ��������������������������������������������������������������������������������������� 102 53. Lumbosacral Plexopathy ������������������������������������������������������������������������������� 104 54. Neuralgic Amyotrophy (Parsonage-Turner Syndrome) ��������������������������������� 106 55. ����������������������������������������������������������������������������������������������� 109 56. —Neurogenic ��������������������������������������������������������112 57. Thoracic Outlet Syndrome—Vascular ������������������������������������������������������������114 Contents vii

V Motor Neuron Diseases 58. Amyotrophic Lateral Sclerosis ������������������������������������������������������������������������118 59. Hereditary Spastic Paraplegia ������������������������������������������������������������������������120 60. Poliomyelitis ����������������������������������������������������������������������������������������������������122 61. Post-Polio Syndrome ��������������������������������������������������������������������������������������124 62. Primary Lateral Sclerosis ��������������������������������������������������������������������������������126 63. Progressive Bulbar Palsy ��������������������������������������������������������������������������������128 64. Progressive Muscular Atrophy ������������������������������������������������������������������������130 65. Spinal and Bulbar Muscular Atrophy (Kennedy’s Disease) ����������������������������132 66. Spinal Muscular Atrophy ��������������������������������������������������������������������������������134 VI Muscle Diseases 67. Becker Muscular Dystrophy ����������������������������������������������������������������������������138 68. Dermatomyositis ��������������������������������������������������������������������������������������������140 69. Duchenne Muscular Dystrophy ����������������������������������������������������������������������142 70. Emery-Dreifuss Muscular Dystrophy ��������������������������������������������������������������144 71. Fascioscapulohumeral Dystrophy ������������������������������������������������������������������146 72. Hyperkalemic Periodic Paralysis ��������������������������������������������������������������������148 73. Hypokalemic Periodic Paralysis ����������������������������������������������������������������������150 74. Limb-Girdle Muscular Dystrophies ����������������������������������������������������������������152 75. McArdle’s Disease (Glycogen Storage Disease Type V) ��������������������������������154 76. Myotonia Congenita ����������������������������������������������������������������������������������������156 77. Myotonic Dystrophy ����������������������������������������������������������������������������������������158 78. Paramyotonia Congenita ��������������������������������������������������������������������������������161 79. Polymyositis ����������������������������������������������������������������������������������������������������162 80. Pompe Disease (Glycogen Storage Disease Type II) ����������������������������������� 164 81. ��������������������������������������������������������������������������������������������� 166 82. Schwartz-Jampel Syndrome ������������������������������������������������������������������������� 168 VII Movement Disorders 83. Blepharospasm ����������������������������������������������������������������������������������������������172 84. Dystonia ����������������������������������������������������������������������������������������������������������174 85. Essential Tremor ����������������������������������������������������������������������������������������������176 86. Friedreich’s Ataxia (Primary Spinocerebellar Degeneration) ��������������������������178 87. Huntington’s Disease ������������������������������������������������������������������������������������� 180 88. Parkinson’s Disease ����������������������������������������������������������������������������������������182 89. Torticollis ������������������������������������������������������������������������������������������������������� 184 90. Tourette’s Syndrome ������������������������������������������������������������������������������������� 186 91. Writer’s Cramp ����������������������������������������������������������������������������������������������� 188

Index ����������������������������������������������������������������������������������������������������������������������191

Series Foreword

The Rehabilitation Medicine Quick Reference (RMQR) harnessed an excellent set of authors. So what we have in series is dedicated to the busy clinician. While we all strive to this series is, I hope and believe, a tremendous reference keep up with the latest medical knowledge, there are many set to be used often in daily clinical practice. As series times when things come up in our daily practices that we editor, I have of course been privy to these books before need to look up. Even more important . . . look up quickly. actual publication. I can tell you that I have already started Those aren’t the times to do a complete literature to rely on them in my clinic—often. They have helped me search, or to read a detailed chapter, or review an article. become more efficient in practice. We just need to get a quick grasp of a topic that we may not Each chapter is organized into succinct facts, presented see routinely or just to refresh our memory. Sometimes a in a bullet point style. The chapters are set up in the same subject comes up that is outside our usual scope of practice, way throughout all of the volumes in the series, so once you but that may still impact our care. It is for such moments get used to the format, it is incredibly easy to look things up. that this series has been created. And while the focus of the RMQR series is, of course, Whether you need to quickly look up what a Tarlov rehabilitation medicine, the clinical applications are much cyst is, or you need to read about a neurorehabilitation broader. complication or treatment, RMQR has you covered. I hope that each reader grows to appreciate the RMQR is designed to include the most common RMQR series as much as I have. I congratulate a fine problems found in a busy practice and also a lot of the less group of editors and authors on creating readable and common ones as well. useful texts. I was extremely lucky to have been able to assemble an absolutely fantastic group of editors. They, in turn, have Ralph M. Buschbacher, MD

ix

Preface

A broad group of diagnoses is encompassed by the term the treating clinician must have the improvement of “Neuromuscular Disease.” The frequency with which function as a primary goal. Although functional improve- clinicians encounter these conditions ranges widely, from ment is an obvious goal when one has a peripheral nerve the common (carpal tunnel syndrome, with an incidence of injury that has undergone corrective , one must 1 in 20) to the extremely rare (congenital myasthenic syn- also focus on functional improvement in the patient drome). The severity of the illnesses similarly varies dra- with a condition that will be lifelong or even fatal: For matically, from generally benign (hereditary neuropathy the patient with amyotrophic lateral sclerosis, functional with liability to pressure palsies), to universally fatal (spinal mobility may be improved when a power wheelchair is muscular atrophy, type 1). The pathophysiology of the dis- utilized. ease processes includes abnormalities in the central nervous Although the RMQR series as a whole focuses on the ­system, neuronal cell bodies, peripheral nerves, neuromus- diagnoses encountered in the field of physical medicine cular junction, and the muscles themselves. Causes may and rehabilitation, this volume explores diagnoses often be environmental, inherited, developmental, age related, managed by our colleagues in the field of neurology. Just overuse, injury, or exposure to poisons. Treatment options as we have the most excellent arrangement where both might include supportive care, medical management of the physiatrist and the neurologist may serve as electro- symptoms, therapeutic modalities, immune modulation, diagnosticians, this volume serves to facilitate the great injections, , or practices. interaction between these two fields in the treatment of Despite all of the variability one encounters when patients with neuromuscular diseases. leafing through this volume in the Rehabilitation Medicine Quick Reference (RMQR) series, one thing is clear: Each Nathan D. Prahlow, MD of these diagnoses affects the patient’s function. Therefore, John C. Kincaid, MD

xi

Acknowledgmentsxiii

This project grew from a seemingly innocent question I thank Dr. Buschbacher for asking me to author this asked by series editor Dr. Ralph Buschbacher: “Would volume of the series, and Beth Barry for her infinite you be interested in helping put together another book on patience during the editorial process. I appreciate the EMG?” For this opportunity and for his assistance in edit- many great things I have learnt from my colleagues in ing and revising, I thank Ralph, and look forward to future physical medicine and rehabilitation. collaborations! I also thank my family—Julie, Joshua, Caleb, and Jonathan—for supporting me and giving me John C. Kincaid, MD the time to work on this project.

Nathan D. Prahlow, MD

xiii

Contributorsxv

Matthew Axtman, DO Nathan D. Prahlow, MD Orthopaedics & Residency Program Director Spectrum Health Assistant Professor of Clinical Physical Medicine and Grand Rapids, Michigan Rehabilitation Department of Physical Medicine and Rehabilitation Cynthia L. Bodkin, MD Indiana University School of Medicine Assistant Professor of Clinical Neurology Indianapolis, Indiana IU School of Medicine Department of Neurology Gabriel Smith, MD Indiana University Health Resident Indianapolis, Indiana Department of Physical Medicine and Rehabilitation Mayo School of Graduate Shashank J. Davé, DO, FAAPMR Rochester, Minnesota Clinical Assistant Professor Department of Physical Medicine and Rehabilitation Susan X. Yu, DO Department of Neurology Department of Occupational Health Services Co-Chief Physical Medicine and Rehabilitation Kaiser Permanente Indiana University School of Medicine Los Angeles, California Indianapolis, Indiana Shangming Zhang, MD, FAAPMR Gentry Dodd, MD Assistant Professor Resident Physician Medical Director, Physical Medicine and Rehabilitation Department of Physical Medicine and Rehabilitation Outpatient Clinic Indiana University School of Medicine Department of Physical Medicine and Rehabilitation Indianapolis, Indiana Penn State Milton S. Hershey Medical Center Penn State College of Medicine John C. Kincaid, MD Hershey, Pennsylvania Kenneth L. and Selma G. Earnest Professor of Neurology Director, Clinical Neurophysiology Fellowship Program Professor of Physical Medicine and Rehabilitation Indiana University School of Medicine Indianapolis, Indiana

xv

I Mononeuropathies Axillary Neuropathy John C. Kincaid MD

Description Diagnosis Syndrome due to a lesion of the Differential diagnosis Etiology nn Arthritis of the shoulder joint nn nn Compression of the nerve in its course posterior and Inflammation or degeneration of the tendons/muscles inferior to the shoulder joint, during traumatic shoulder of the shoulder nn dislocation, occurring in approximately 40% of cases Cervical radiculopathy at the C5 level nn nn Inflammatory as a component of brachial Brachial plexitis with predominant involvement of the plexitis axillary nerve nn nn Compression of the nerve due to positioning in Focal manifestation of a polyneuropathy such as surgery or other instances of prolonged mononeuritis multiplex sedation/nonresponsiveness History nn Entrapment as the nerve exits the axilla through the nn Abrupt onset of shoulder abduction weakness in the quadrilateral space setting of trauma to the shoulder Epidemiology nn Onset during recurrent, vigorous motions of the Most often occurs as a component of trauma to the shoulder, such as ball pitching nn shoulder Onset over a several-week time frame if brachial plexitis is the etiology: spontaneous onset of pain Pathogenesis followed several weeks later by motor and sensory nn Demyelination and axonopathy due to the primary deficits pathogenesis nn Surface numbness over the lateral and posterior nn Inflammatory neuritis aspects of the deltoid Risk Factors Traumatic shoulder dislocation nn Weakness of arm abduction and atrophy of the deltoid; note that the anterior branch of the nerve Clinical Features supplies the anterior and middle portions of the nn Weakness of shoulder abduction muscle, whereas the posterior branch supplies the nn Atrophy of the deltoid: note that the anterior and posterior aspect of the muscle. medial components of the muscle are supplied by the nn Impairment of cutaneous sensation over the lateral anterior branch of the nerve, whereas the posterior and/or posterior aspects of the deltoid aspect of the muscle is supplied by the posterior nn Mild weakness of external rotation of the shoulder branch of the nerve. due to teres minor involvement in which the posterior nn Sensory loss over the surface of the midportion of the branch of the nerve is affected muscle due to the involvement of the anterior branch of the nerve, and over the surface of the posterior Testing aspect of the muscle due to the involvement of the nn Needle EMG of the deltoid and adjacent muscles posterior branch. of the shoulder to assess the scope and severity of nn Weakness and atrophy of the teres minor due to involvement and to help define prognosis during involvement of the posterior branch of the nerve follow-up nn of the axillary nerve if the Natural History practitioner is skilled in the technique Slow improvement over months to 2 years if reinnerva- nn Imaging of the shoulder joint and associated tion is successful muscles/tendons

2 Axillary Neuropathy 3

Treatment Prognosis nn Manage lesions of the shoulder joint and associated Improvement in motor and sensory deficits over months muscles/tendons, including anti-inflammatory and analgesic medications for pain Suggested Readings nn Antineuropathic pain medications usually do not Stewart, John D. Focal Peripheral Neuropathies. 4th ed. significantly improve the symptoms if the lesion is (pp. 173–180). West Vancouver, BC, Canada: JBJ Publishing;

2010. Mononeuropathies I:

neurogenic. nn Anti-inflammatory medications may reduce shoulder Wilbourn AJ, Ferrante MA. Upper limb neuropathies. In: Dyck PJ, Thomas PK, eds. . 4th ed. pain if joint or components are the (pp. 1469–1471). Philadelphia, PA: Elsevier; 2005. predominant etiology. nn to address range of motion and strengthening Facial Neuropathy (Bell’s Palsy) John C. Kincaid MD

Description Diagnosis Syndrome due to a focal lesion of the facial nerve Differential diagnosis Etiology Central nervous system lesion of the facial motor path- ways: lower face is predominantly involved nn Inflammatory neuritis within the facial canal of the temporal bone: idiopathic or as a History manifestation of an immunity altering condition, nn Pain in the ear or retroauricular area for hours to a such as of Lyme disease or sarcoidosis day preceding onset of facial weakness nn Nerve trauma from temporal bone fractures, parotid nn Unilateral facial weakness, which tends to be abrupt surgery, mandibular fractures, or repair thereof, in onset acoustic neuroma surgery nn Vague sensory symptoms in the face: “numbness.” nn Compression by neoplasms: parotid lesions, invasive nn Abnormal taste sensations lesions of the temporal bone nn Alerted hearing

Epidemiology Physical examination Yearly incidence of about 20 cases per 100,000 of population nn Unilateral weakness of forehead, periorbital, and perioral muscles plus the platysma Pathogenesis nn Normal sensation in the trigeminal territory nn Autoimmune inflammation of the nerve nn Herpetic vesicles in the external ear (rare) nn Trauma to neighboring structures such as the mandible, temporal bone Testing nn Compression secondary to infiltration by neoplastic nn Facial nerve conduction studies performed 14 or cells from adjacent structures such as the parotid more days after onset can help define lesions as gland or temporal bone to predominantly demyelinating versus axonal Risk Factors nn Needle EMG done 21 or more days after the onset nn Diabetes can help distinguish demyelinating versus axonal nn Pregnancy predominance: fibrillation potentials indicate nn Melkersson-Rosenthal syndrome: recurring attacks of axonal pathology, whereas the preserved ability to facial edema, facial paralysis, and lingua plicata activate some voluntary potentials indicates at least nn Herpes Zoster outbreak involving the sensory some degree of preserved axonal continuity innervation of the ear: Ramsay Hunt syndrome nn Imaging studies if deficits persist beyond 6 months

Clinical Features Treatment nn A unilateral lesion is more common nn Oral steroids begun in the first 48 to 72 hours in nn Right- or left-side involvement of equal incidence patients with complete paralysis have a higher chance nn Facial weakness in a “peripheral pattern,” that is, upper, of recovery mid, and lower facial innervated muscles equally affected nn The addition of an anti-herpes virus agent-like acyclovir does not improve the outcome Natural History nn Surgical decompression of the facial canal within the Improvement in the majority of patients over a 3-week first 14 days of onset does not seem to improve the period after onset. long-term outcome

4 Facial Neuropathy (Bell’s Palsy) 5

Prognosis Suggested Readings nn 70+ % have a full recovery Klein C. Diseases of the seventh cranial nerve. In Dyck PJ, nn Up to 10% may have residual weakness and may Thomas PK, eds. Peripheral Neuropathy. 4th ed. (pp. 1219-1252). Philadelphia, PA: Elsevier; 2005. experience reinnervation phenomena, such as synkinetic Sullivan F, Swam I, et al. Early treatment with prednisolone or movements, abnormal tearing, or hemifacial spasm acyclovir in Bell’s Palsy. N Engl J Med 2007;357:1598–1607. I: Mononeuropathies I:

Femoral Neuropathy John C. Kincaid MD

Description Diagnosis Syndrome due to a lesion of the femoral nerve along its Differential diagnosis course from the level of the psoas muscle into the thigh nn Arthritis involving the hip joint nn Lumbar radiculopathy involving the 2nd, 3rd, or 4th Etiology nerve roots nn Compression by hematoma or other masses along nn Lumbar plexopathy with predominant involvement of the nerve from the level of the lateral border of the the femoral nerve psoas caudally through the level of the inguinal ligament History nn Nerve trauma during intra-abdominal surgery, hip nn Acute onset when the lesion occurs intraoperatively or arthroplasty, hip fracture, or vascular access procedures due to penetrating trauma in the groin or thigh nn Onset over hours to a few days when retroperitoneal nn Penetrating injury from gun shots or stab wounds hematoma formation is the etiology nn Diabetic or idiopathic radiculoplexopathy with nn Onset over weeks if plexitis is the cause predominant involvement of the femoral nerve Physical examination nn Weakness of knee extension Epidemiology nn Mild weakness of knee extension (major weakness of Less common than lesions of the hip flexion suggests a proximal lesion at or proximal to the level of the femoral branch to the iliacus) Pathogenesis nn Absence or reduction of the knee muscle stretch reflex nn External compression of the nerve with resulting nn Atrophy of the quadriceps in long-standing cases demyelination and axonopathy nn Loss of sensation in the anterior thigh and medial nn Direct trauma during penetrating injury lower leg nn Inflammatory neuritis or vasculitis affecting the vasa nn Loss of sensation also including the lateral thigh nervorum suggests a proximal lesion at the level of the psoas where femoral and lateral cutaneous are adjacent Risk Factors nn Normal strength in leg adduction and ankle extension nn Intra-abdominal surgery Testing nn Hip arthroplasty nn Needle EMG shows denervation in the quadriceps nn Vascular access procedures through the femoral artery but normal results in the hip adductors and tibialis or vein anterior nn Conduction study of the femoral nerve may show reduced Clinical Features amplitude of the compound muscle action potential nn Weakness of knee extension (CMAP) or absence of the response nn Hip flexion may also be weak if the rectus femoris is nn Imaging of the hip joint and pelvis when fractures are involved suspected nn and sensory loss in anterior thigh nn Imaging of the pelvis to identify hematoma, abscess, and medial lower leg (saphenous nerve distribution) or neoplastic lesions along the course of the nerve nn Pain of variable intensity in the groin and thigh Treatment Natural History nn Consideration of surgical intervention when May improve over many months depending on the nature retroperitoneal or femoral sheath hematoma is the of the lesion etiology

6 Femoral Neuropathy 7

nn Analgesics if neuropathic pain is a major feature Suggested Readings nn Physical therapy to maximize muscle strength Katirji B, Wilbourn A. Mononeuropathies of the lower improvement limb. In: Dyck PJ, Thomas PK, eds. Peripheral Neuropathy. 4th ed. (pp. 1487–1510). Philadelphia, PA: nn Knee bracing to compensate for quadriceps weakness Elsevier; 2005 Stewart, John D. Focal Peripheral Neuropathies. 4th ed. Prognosis (pp. 540–555). West Vancouver, BC, Canada: JBJ

Improvement in sensory and motor symptoms may occur Publishing; 2010. Mononeuropathies I: over months Inguinal Neuropathies (Iliohypogastric, Ilioinguinal, and Genitofemoral Nerves) John C. Kincaid MD

Description Physical examination Syndrome due to a focal lesion of these nerves in their nn Decreased light touch and pin prick sensation course from the psoas to the groin in the: ––Lateral hip and/or lower anterior abdomen Etiology (iliohypogastric) nn Trauma during intrapelvic surgery or compression by ––Inguinal canal and upper part of the scrotum or retroperitoneal masses labia (ilioinguinal) nn Trauma to or entrapment of the nerve during inguinal ––Anterior proximal thigh and upper part of the herniorrhaphy or other surgical procedures on the scrotum or labia (genitofemoral) lower anterior abdominal wall nn Normal strength of hip flexion, leg abduction, and adduction and knee extension Epidemiology nn Normal patellar muscle stretch reflex The ilioinguinal nerve may be traumatized in up to 20% nn Unilateral impairment or absence of the cremasteric of patients undergoing inguinal hernia repair. reflex (genitofemoral)

Pathogenesis Testing Local demyelination and axonopathy due to compression nn Nerve conduction studies of these nerves are not of or trauma to the nerve technically reliable nn Needle EMG of proximal leg and upper lumbar Risk Factors paraspinal muscles should be normal nn nn Inguinal herniorrhaphy Imaging studies of the spine and pelvis to investigate the L1 spinal and retroperitoneal region Clinical Features nn Pain in lower anterior abdomen and groin Treatment nn Numbness and in the groin nn Analgesic, anti-inflammatory, and antineuropathic pain medications may help Natural History nn Re-exploration of the inguinal canal when onset Symptoms tend to be persistent follows inguinal herniorrhaphy

Diagnosis Prognosis Differential diagnosis nn Inguinal pain often persists long term nn Hip arthritis or nn Radiculopathy involving the 1st lumbar level Suggested Readings nn Upper lumbar plexopathy Amid PK, Hiatt JR. New understanding of the causes and History ­surgical treatment of postherniorraphy inguinodynia and orchalgia. J Am Coll Surg. 2007;205:381–385. nn Pain in the groin Stewart, John D. Focal Peripheral Neuropathies. 4th ed. nn Numbness and paresthesia in the lower anterior (pp. 576–591). West Vancouver, BC, Canada: JBJ abdomen, inguinal region, and/or scrotum/labia Publishing; 2010.

8 Intercostobrachial Neuropathy John C. Kincaid MD

Description History I: Syndrome due to a lesion of the intercostobrachial nerve nn Pain in the axilla perceived as surface or deep Mononeuropathies nn Numbness and/or paresthesia in the axilla and Etiology proximal medial arm nn Nerve trauma during surgery in the axilla or nn Swelling of the arm due to disturbance of normal compression by an invading neuroplasm lymph flow

Epidemiology Physical examination nn nn Chronic postmastectomy pain is felt by 20% to 65% of Decreased sensation to light touch or pin prick in those undergoing breast surgery for cancer axilla and proximal medial arm nn nn An estimated 33% of these cases are due to Strength of shoulder and proximal arm muscles intercostobrachial neuropathy should be normal nn The intercostobrachial nerve is damaged in 80% to Testing 100% of breast cancer surgeries nn Nerve conduction studies of median, ulnar, and Pathogenesis medial antebrachial cutaneous nerves to evaluate for lower brachial plexopathy nn Nerve trauma during axillary lymph node dissections nn Needle EMG of C8 and T1 muscles to evaluate in breast cancer surgery for lower brachial plexopathy or lower cervical nn Compression of the nerve by neoplastic infiltration radiculopathy from apical lung tumors

Risk Factors Treatment nn Surgical treatment of breast cancer with axillary nn Analgesic, anti-inflammatory, and antineuropathic lymph node dissection pain medications in an attempt to lessen neuropathic pain Clinical Features nn Nerve block of the intercostobrachial nerve to nn Pain in axilla verify neurogenic causation and to localize the nn Paresthesia and sensory loss in the axilla and lesion proximal medial arm nn Physical therapy to optimize shoulder motions

Natural History Prognosis nn Onset immediately postoperatively or within a few nn Symptoms tend to be persistent months of the surgical procedure nn Symptoms tend to be persistent Suggested Readings Stewart, John D. Focal Peripheral Neuropathies. 4th ed. Diagnosis (pp. 183–185). West Vancouver, BC, Canada: JBJ Publishing; Differential diagnosis 2010. Torresan RZ, Cabello C, et al. Impact of preservation of the nn Lesion of the shoulder joint or associated soft tissue intercostobrachial nerve in axillary lymphadenopathy due to nn Radiculopathy involving the T1 or T2 levels breast cancer. Breast J. 2003; 9:398–392.

9 Lateral Femoral Cutaneous Neuropathy (Meralgia Paresthetica) John C. Kincaid MD

Description nn Lumbar plexopathy Syndrome due to a focal lesion of the lateral cutaneous nn Femoral neuropathy nerve of the thigh History Etiology nn Symptoms are more often unilateral nn Compression within the pelvis by retroperitoneal mass, nn Abrupt onset of lateral thigh pain and numbness hematoma, or surgical retractors following intra-pelvic or inguinal surgery nn Trauma at the level of the inguinal ligament by surgical nn Gradual onset when associated with obesity, wearing procedures or compression of the nerve by lithotomy overly tight pants or in idiopathic cases positioning, tight clothing, obesity, bulky objects in nn Cutaneous hypersensitivity in the lateral thigh front pants pockets, or prolonged/recurrent leaning nn Normal strength in hip and thigh functions against external structures at the height of the groin or upper thigh Physical examination nn Idiopathic (most common) nn Decreased sensation to light touch or pin prick in lateral thigh Epidemiology nn Normal strength in hip flexion, knee extension, and Likely the most common lower extremity mononeuropathy leg adduction nn Normal bulk of quadriceps Pathogenesis nn Normal knee muscle stretch reflex Local demyelination and in more severe lesions axonopa- nn Pressure at the level of the inguinal ligament at thy due to external compression of the nerve or just medial to the anterior superior iliac spine may reproduce or worsen the lateral thigh Risk Factors paresthesia nn Obesity nn No pain with palpation of the greater trochanter nn Intra-pelvic or inguinal surgery nn Wearing overly tight pants Testing nn Nerve conduction studies of the lateral cutaneous Clinical Features nerve are technically reliable only in thin individuals nn Burning and numb-type paresthesias in the lateral and a normal response must be present on the thigh contralateral side for the values of the symptomatic nn Loss of sensation in the lateral thigh side to be interpretable nn Nerve conduction studies in normomorphic or heavy Natural History individuals are not reliable May improve over months with weight reduction nn The expected abnormality in conduction studies is reduction of the nerve action potential amplitude or Diagnosis absence of a measureable response Differential diagnosis nn Needle EMG of the quadriceps and adductor muscles nn Arthritis involving the hip joint should be normal nn Trochanteric bursitis nn Imaging study of the pelvis if a retroperitoneal lesion is nn Lumbar radiculopathy at the L1 or L2 level a possible cause

10 Lateral Femoral Cutaneous Neuropathy (Meralgia Paresthetica) 11

Treatment Prognosis nn Analgesic, anti-inflammatory, and antineuropathic Improvement over months if an identifiable lesion is pain medications usually do not significantly improve present and management such as weight loss, therapeutic the symptoms nerve block, or surgical decompression can be instituted nn Manage intra-pelvic lesions, which may be compressing the nerve Suggested Readings nn Mononeuropathies I:

Weight reduction nn Stewart, John D. Focal Peripheral Neuropathies. 4th ed. Local anesthetic block of the nerve for diagnostic and (pp. 556–567). West Vancouver, BC, Canada; 2010. potentially therapeutic purposes Wiezer M, Franssen H, et al. Meralgia paresthetica: nn Surgical decompression of the nerve at the inguinal Differential diagnosis and follow-up. Muscle Nerve. ligament 1996;19:522–524. Long Thoracic Neuropathy John C. Kincaid MD

Description History Syndrome due to a lesion of the nn Pain in the arm/proximal shoulder area nn Weakness of flexion and abduction motions of the Etiology shoulder (due to poor stabilization of the scapula) nn Trauma to the nerve as a component of injury to the Physical examination shoulder and surrounding soft tissues nn Winging of the medial border of the scapula during nn Inflammatory neuritis as component of brachial flexion and protraction motions of the shoulder plexitis nn Mild diffuse weakness in flexion and protraction nn Idiopathic motions of the shoulder nn The bulk and strength of other parascapular muscles Epidemiology should be normal if the lesion is limited to the long Uncommon but classic lesion thoracic nerve. nn Cutaneous sensation in the shoulder and arm areas Pathogenesis should be normal if the lesion is limited to the long nn Demyelination and axonopathy due to primary thoracic nerve. etiology nn Inflammatory neuritis Testing nn Traction injury to the nerve nn Needle EMG of the serratus anterior as well as parascapular and proximal arm muscles Risk Factors nn Nerve conduction study of the long thoracic nerve if nn Other trauma to the shoulder region the practitioner is experienced with the technique nn Wearing heavy backpack Treatment Clinical Features nn Analgesic and anti-inflammatory medications may nn Weakness of flexion or abduction motions of the improve the shoulder/proximal arm pain shoulder nn Orthopedic or physical medicine evaluation of the nn Acute pain in the shoulder or arm preceding the onset shoulder to rule out a lesion of the joint or rotator cuff of muscular dysfunction nn Imaging of the shoulder to rule out a lesion of the nn Long-term pain in the shoulder and proximal arm shoulder joint or rotator cuff during shoulder motions nn Physical therapy to optimize strength of other parascapular muscles Natural History nn Muscle transfer surgery if severe weakness and associated shoulder motion dysfunction persist nn Pain and muscular dysfunction may improve over beyond about 6 months months to about 1 year Prognosis Diagnosis nn Improvement of shoulder motion and reduction of Differential diagnosis pain may occur over months to about 1 year nn Arthritis of the shoulder nn Rotator cuff syndrome due to inflammation or Suggested Readings degeneration of the tendons of the parascapular Friedenberg SM, Zimprich T. The natural history of long thoracic and spinal accessory neuropathies. Muscle Nerve. 2002;25:535–539. muscles Stewart, John D. Focal Peripheral Neuropathies. 4th ed. nn Acute brachial plexopathy/plexitis (pp. 162–167). West Vancouver, BC, Canada: JBJ Publishing; nn Spinal accessory neuropathy 2010.

12 Medial Antebrachial Cutaneous Neuropathy John C. Kincaid MD I: Mononeuropathies I:

Description nn Lower trunk or medial cord brachial plexopathy Syndrome due to a lesion of the medial cutaneous nerve nn Neurogenic thoracic outlet syndrome of the forearm nn Ulnar neuropathy elbow nn Focal manifestation of polyneuropathy Etiology History nn Penetrating injury in the upper arm nn nn Trauma to the nerve during surgery on the ulnar Onset following penetrating injury of the arm or nerve at the elbow following surgery to treat ulnar neuropathy at the nn Compression in the lower of the elbow nn fascicles, which will give rise to the medial cutaneous Pain in the medial elbow region and along the surgical nerve scar line if the lesion arises postoperatively Physical examination Epidemiology nn Decreased sensation to light touch or pin prick in Rare lesion: encountered most often as a complication of medial forearm surgery for ulnar neuropathy at the elbow nn Normal sensation in the ulnar territories of the hand and digits unless an ulnar lesion preceded the onset of Pathogenesis the medial cutaneous nerve lesion Direct trauma to the nerve during penetrating nn Normal muscle bulk and strength in ulnar and or surgery on the at the elbow with resulting median hand intrinsic muscles unless deficits are demyelination and axonal damage attributable to a prior ulnar neuropathy nn Risk Factors Absence of exam features of Horner’s syndrome nn Tinel’s sign and pain provocable by palpation may be Surgery for ulnar neuropathy at the elbow present at the site of nerve entrapment/injury Clinical Features Testing nn Pain in the medial elbow, which may be provocable nn Local anesthetic block of the nerve confirms the by elbow motion or palpation of or pressure on the origin of the pain and paresthesias entrapment site nn Ulnar and median conduction studies should be nn Tingling and/or numb-type paresthesias in the medial normal unless a lesion of either of those nerves forearm extending from the elbow to the wrist preceded onset of the medial cutaneous neuropathy nn Sensory and motor functions of the ulnar nerve nn Needle EMG of C8–T1 supplied ulnar, median, and should be normal distal radial muscles should be normal unless a lesion of those nerves was present prior to the onset of the Natural History medial cutaneous neuropathy nn May improve over several months nn Imaging of the cervical spine and brachial plexus by magnetic resonance imaging (MRI) should be Diagnosis normal as should cervical spine films done to identify Differential diagnosis cervical ribs nn Medial epicondylitis nn Degenerative arthritis of the elbow Treatment nn Cervical radiculopathy involving the C8 or T1 nerve nn Antineuropathic pain medications roots nn Therapeutic nerve block

13 14 Medial Antebrachial Cutaneous Neuropathy nn Occupational therapy for desensitization nn Improvement in pain and allodynia if surgery is nn Exploration of the nerve at the site of injury for release performed for patients not responding to conservative of entrapment or resection of a neuroma if pain and management hypersensitivity persist beyond 6 months Suggested Readings Prognosis Dellon A, Mackinnon S. Injury to the medial antebrachial cutaneous nerve during cubital tunnel surgery. J Hand Surg (Br). nn Improvement over several months with 1985;10:33–36. conservative treatments such as massage and Stewart, John D. Focal Peripheral Neuropathies. 4th ed. (pp. desensitization 183–193).West Vancouver, BC, Canada: JBJ Publishing; 2010. Median Neuropathy—Anterior Interosseous Neuropathy (Kiloh-Nevin Syndrome) John C. Kincaid MD I: Mononeuropathies I:

Description nn Upper or middle trunk brachial plexopathy Syndrome due to a lesion of the anterior interosseous nn Local manifestation of a polyneuropathy such branch of the as mononeuritis multiplex or multifocal motor neuropathy Etiology nn Rupture or laceration of the tendon of the flexor nn Inflammation of the anterior interosseous nerve or the pollicis longus fascicles within the main trunk of the median nerve, History which will give rise to the anterior interosseous nerve nn Weakness of flexion of the tip of the thumb and index nn Entrapment/compression of the anterior interosseous finger producing inability to properly form an “OK” branch of the median nerve by fibrous band gesture components of forearm muscles such as the pronator nn Pain in the forearm, elbow, upper arm, or shoulder teres or flexor digitorum superficialis preceding onset of muscle weakness by days to a few nn Penetrating trauma, which selectively or predominantly weeks in case of autoimmune inflammatory neuritis involves this branch of the median nerve nn No sensory symptoms such as numbness or tingling in Epidemiology the median sensory areas Rare lesion, encounter about once annually in an 1800- Physical examination patient per year EMG laboratory. nn Weakness of flexion of the tip of the thumb, index, and at times middle finger Pathogenesis nn Normal strength in median innervated hand intrinsic nn Demyelination and axonopathy of the fascicles within the muscles: abductor pollicis brevis, opponens pollicis, main trunk of the median nerve or the brachial plexus, and the first two lumbricals which give rise to the anterior interosseous branch nn Normal strength in median innervated forearm muscles such as pronator teres and flexor carpi Risk Factors radialis None nn Normal sensation in the median nerve and C6 or C7 territories Clinical Features Testing nn Weakness in flexion of the tip of the thumb and index nn Standard median motor and sensory nerve conduction finger studies should be normal nn Pain in the forearm or upper arm nn Needle EMG should show denervation in forearm nn No sensory deficits muscles supplied by the anterior interosseous branch Natural History of the median nerve and normal results in hand and forearm muscles supplied by the main trunk of the nn May improve over months if reinnervation is successful nerve nn Diagnosis Conduction studies can be performed in the anterior interosseous branch if the practitioner is skilled/ Differential diagnosis confident in the technique: the expected findings nn Proximal median neuropathy predominantly would be reduction of the compound muscle action involving the anterior interosseous fascicles potential (CMAP) from the flexor pollicis longus and nn Cervical radiculopathy involving the 6th or 7th nerve perhaps prolongation of the latency from the stimulus roots site to the muscle.

15 16 Median Neuropathy—Anterior Interosseous Neuropathy (Kiloh-Nevin Syndrome) nn Imaging studies of the distal to rule out a nn Surgical exploration of the elbow/proximal forearm supracondylar bone spur if no clinical or EMG signs of beginning recovery are nn Magnetic resonance imaging (MRI) of the cervical present by 3 to 6 months after onset spine to rule out radiculopathy at the C6 or C7 level Prognosis nn Improvement over months to about 2 years in Treatment spontaneous onset cases nn Reduce repetitive elbow/forearm activity such as repetitive pronation/supination Suggested Readings nn Conservative observation over 3 to 6 months Stevens JC. Median neuropathy. In: Dyck PJ, Thomas PK, eds. while watching for recovery in spontaneous Peripheral Neuropathy. 4th ed. (pp. 1453–1454). Philadelphia, PA: Elsevier; 2005. onset cases Stewart, John D. Focal Peripheral Neuropathies. 4th ed. nn Repeat needle EMG at 8 to 12 weeks after onset can (pp. 207–214). West Vancouver, BC Canada: JBJ Publishing; reveal whether reinnervation is occurring 2010. Median Neuropathy—In the Arm to Mid-Forearm John C. Kincaid MD I: Mononeuropathies I:

Description nn Persistence in cases due to nerve compression by a Focal lesion of the median nerve at sites proximal to the supracondylar bone spur or entrapment in the region level of the carpal tunnel of the pronator teres unless the nerve is surgically decompressed Etiology nn Penetrating injuries during venous or arterial access Diagnosis procedures in the antecubital fossa Differential diagnosis nn Compression injury due to fractures of the distal nn humerus or proximal radius Carpal tunnel syndrome nn nn Entrapment by aberrant bony spicules arising from Cervical radiculopathy involving the 6th or 7th nerve the distal medial humerus (the supracondylar spur) roots nn or by muscular and fascial structures just distal to the Upper or middle trunk brachial plexopathy nn elbow (pronator syndrome) Lateral or medial epicondylitis nn Focal manifestation of polyneuropathy, such Epidemiology as mononeuritis multiplex or multifocal motor Very rare lesion neuropathy History Pathogenesis nn Abrupt onset of pain and sensory symptoms in the Demyelination and axonopathy due to compression, pen- median territory and weakness of median supplied etration, or vascular compromise forearm and hand muscles during or shortly after venipuncture or arterial access procedures in the Risk Factors antecubital fossa, or in association with fractures in the nn Venipuncture or arterial puncture in the antecubital elbow region fossa nn Insidious onset of symptoms in lesions caused by nn Fractures of the humerus or elbow compression at the supracondylar spur or within the nn Vascular access creation in the forearm for dialysis pronator teres nn Production of or worsening of forearm pain and Clinical Features hand sensory symptoms during repeated or forceful nn Weakness in the median nerve hand functions: forearm pronation when entrapment in the region of thumb abduction and opposition, flexion of the the pronator teres is the etiology metacarpophalangeal (MCP) joint of digits II and III nn Development of symptoms of causalgia (complex nn Weakness of forearm pronation, wrist flexion, and regional pain syndrome type II) after traumatic injuries finger flexion of digits I to IV nn Numb and tingling-type paresthesias in digits I to IV Physical examination and the palm nn Decreased sensation to light touch or pin prick in tips nn Manifestations of complex regional pain syndrome of digits I to IV and the palm may develop in the hand and forearm nn Weakness of thumb abduction and opposition, wrist flexion, forearm pronation, and flexion of digits Natural History I to IV nn Improves over months to about 1 year in cases due to nn Atrophy of thenar and median supplied forearm penetrating trauma of elbow fractures muscles

17 18 Median Neuropathy—In the Arm to Mid-Forearm nn Local tenderness and Tinel’s sign over the median Treatment nerve in the region of the elbow nn Analgesic and antineuropathic pain medications may nn Reproduction of or worsening of forearm pain improve neuropathic pain symptoms and hand sensory symptoms by resisted forearm nn Surgical decompression when a supracondylar bony pronation spur is present or when the diagnosis of pronator nn Allodynia and abnormalities of finger, hand, and syndrome is made distal forearm skin temperature if complex regional nn Appropriate and prompt management of complex pain syndrome has developed regional pain syndrome if present Testing nn Median nerve conduction studies, which show Prognosis nn reduced amplitudes of the motor and sensory Improvement over months to about 1 year in cases due responses, normal motor and sensory distal latencies, to nerve trauma nn and often mild slowing of the forearm conduction Improvement in sensory and motor symptoms over velocities weeks to months in cases due to entrapment nn Conduction studies in the adjacent nerves are normal unless polyneuropathy is present Suggested Readings nn Needle EMG, which shows denervation in median Stevens JC. Median neuropathy. In: Dyck PJ, Thomas PK, eds. supplied hand and forearm muscles Peripheral Neuropathy. 4th ed. (pp. 1452–1454). Philadelphia, PA: Elsevier; 2005; nn Imaging of the elbow region to identify a Stewart, John D. Focal Peripheral Neuropathies 4th ed. supracondylar bony spicule of the distal humerus or (pp. 200–207). West Vancouver, BC, Canada: JBJ Publishing; fractures of the elbow 2010. Median Neuropathy—At the Wrist (Carpal Tunnel Syndrome) John C. Kincaid MD I: Mononeuropathies I:

Description nn Atrophy of thenar muscles in more severe cases Syndrome due to a focal lesion of the median nerve as it nn Lesions due to penetrating trauma to the nerve often enters the hand lack the nocturnal and position-related pain and sensory components Etiology nn Entrapment of the median nerve as it enters the hand Natural History through the carpal tunnel nn May improve over days to weeks with reduction in nn Nerve trauma from penetrating injures or fractures of hand motion activities or after completion of pregnancy the distal forearm or wrist Diagnosis Epidemiology nn Most common focal neuropathy Differential diagnosis nn Prevalence of 3% to 4% in the general population nn Arthritis involving the wrist or thumb nn Three times more common in females nn Tendonitis of finger flexor or thumb extensor muscles nn 40 to 60 year age group more often affected nn Cervical radiculopathy involving the 6th or 7th nerve nn Pregnancy roots nn Upper or middle trunk brachial plexopathy Pathogenesis nn Neurogenic thoracic outlet syndrome nn Idiopathic cases are most common nn Proximal median neuropathy nn Exposure to vibrating hand tools, repetitive flexion/ nn Focal manifestation of polyneuropathy extension of the wrist and repetitive forceful hand grip History nn Reduced tunnel dimensions due to arthritis of the nn Wrist or forearm pain, which worsens at night, while wrist joint, ganglia, or congenital narrowing holding the hand on a steering wheel or during nn Generalized edema in mid-to-late pregnancy repetitive motion of the wrist or hand nn Infiltration of the tunnel by mucinous material in nn Sensory symptoms occurring in or worsening in the hypothyroidism or amyloid accumulation same setting as the pain nn Risk Factors Weakness of pincher motion of thumb-middle fingers nn Obesity Physical examination nn Underlying polyneuropathy nn Decreased sensation to light touch or pin prick in tips nn Vascular access creation for hemodialysis of digits I to IV in moderate-to-severe cases nn Pregnancy nn Two point discrimination threshold greater than 2 to 3 mm on tip of digits I to IV Clinical Features nn Weakness of thumb abduction and opposition in nn Pain in the wrist and forearm moderate-to-severe cases nn Pain described as “deep in the bone” nn Atrophy of thenar muscles in moderate-to-severe nn Tingling and/or numb-type paresthesias in the digits cases I to IV concurrent with the pain nn Tinel’s sign over the median nerve at the wrist nn Improvement in the pain or paresthesias with change nn Reproduction of or worsening of finger sensory in hand position or shaking (flicking) the hand symptoms by 10 to 30 seconds of wrist flexion nn Symptoms usually begin in the dominant hand but (Phalen’s sign) commonly become bilateral nn Flexion of distal thumb and tips of digits II to IV are nn Weakness of “pincher” motions involving digits I to IV normal 19 20 Median Neuropathy—At the Wrist (Carpal Tunnel Syndrome)

Testing nn Improve ergonomics of hand, upper limb, and neck nn Nerve conduction studies show prolongation of nn Wrist orthosis worn at night median distal latencies, sensory axons being affected nn Steroid injection into the carpal tunnel if orthotic does earlier or more severely than motor not eliminate or greatly improve symptoms nn Sensory and then motor response amplitudes become nn Surgical decompression of the carpal tunnel if reduced in more severe cases orthosis or steroid injection does not eliminate or nn Median motor and sensory conduction velocities in greatly improve symptoms the forearm remain normal except in severe cases where mild slowing of motor velocity can be found Prognosis nn Conduction studies in the adjacent nerves are normal nn Improvement after surgery, pain often fully relieved as unless polyneuropathy is present soon as postoperative pain clears nn Needle EMG, which shows denervation in median nn Improvement in sensory and motor symptoms supplied hand muscles in moderate-to-severe cases may be delayed by weeks or months if persisting but median supplied forearm muscles as normal rather than transient deficits were present nn examination of the median nerve at the preoperatively or if any underlying polyneuropathy wrist in an emerging diagnostic tool whose ultimate is present. role remains to be better defined Suggested Readings Treatment Jablecki CK, Andary MT, et al. Practice parameter: nn Analgesic, anti-inflammatory, and antineuropathic Electrodiagnostic studies in carpal tunnel syndrome. Neurology. 2002;58:1589–1952. pain medications usually do not significantly improve Stewart, John D. Focal Peripheral Neuropathies. 4th ed. the symptoms (pp. 214–241). West Vancouver, BC, Canada: JBJ nn Reduce hand activity Publishing; 2010. Musculocutaneous and Lateral Antebrachial Cutaneous Neuropathy I: Mononeuropathies I:

John C. Kincaid MD

Description nn Brachial plexitis involving the upper trunk or lateral Syndrome due to focal lesion of the musculocutaneous cord nerve or its lateral antebrachial cutaneous branch nn Biceps tendon rupture

Etiology History nn nn Compression of the nerve in shoulder dislocation or Weakness of elbow flexion, which is most often of fracture of the proximal humerus abrupt onset and in association with trauma to the nn Penetrating trauma by gun shot or stab wound shoulder or proximal arm nn nn Venipuncture in the lateral antecubital fossa Sensory symptoms of the lateral forearm (occurs nn Acute brachial plexitis without motor dysfunction if only the lateral nn Onset after vigorous elbow motions as in carrying antecubital branch is involved) heavy objects or pitching a ball nn Shoulder and upper arm pain for several weeks and then onset of weakness if brachial plexitis is the Epidemiology etiology nn Rare lesion: occurs most often in association with Physical examination shoulder dislocation or humeral fracture nn Weakness of elbow flexion and supination nn Pathogenesis Atrophy of the biceps and brachialis muscles nn Impaired or absent biceps muscle stretch reflex nn Demyelination and axonopathy due to compressive or nn Impaired cutaneous sensation over the lateral aspect penetrating lesions of the forearm nn Inflammatory neuritis Testing Risk Factors nn Needle EMG of the biceps, brachialis, and other nn Shoulder dislocation and proximal humeral fracture muscles supplied by C5 and C6 nn Venipuncture in the lateral antecubital fossa nn Sensory nerve conduction studies of the lateral antebrachial nerve looking for reduction in the Clinical Features amplitude or absence of the sensory action potential nn Weakness of elbow flexion nn Motor conduction study of the nerve to the biceps nn Sensory disturbance in the lateral aspect of the looking for reduced amplitude of the compound forearm muscle action potential. Comparison to the opposite side may be helpful in defining Natural History abnormality nn Improvement over several months to about 1 year nn Radiographic studies of the shoulder and proximal humerus if the onset scenario suggests trauma Diagnosis nn Magnetic resonance imaging (MRI) of the cervical Differential diagnosis spine to evaluate the C5 and C6 spinal segments nn Cervical radiculopathy involving the 5th or 6th nerve nn MRI of the brachial plexus looking for enhancement roots of the upper trunk or lateral cord

21 22 Musculocutaneous and Lateral Antebrachial Cutaneous Neuropathy

Treatment Suggested Readings nn Manage associated trauma of the shoulder or humerus Stewart, John D. Focal Peripheral Neuropathies. 4th ed. nn Physical medicine and physical therapy evaluations to (pp 177–182). West Vancouver, BC, Canada: JBJ Publishing; 2010. optimize recovery of muscle function Wilbourn AJ, Ferrante MA. Upper limb neuropathies. In: Dyck PJ, Thomas PK, eds. Peripheral Neuropathy. 4th ed. Prognosis (pp. 1471–1474). Philadelphia,PA: Elsevier; 2005. nn Improvement in motor and sensory functions over several months to about 1 year after onset Obturator Neuropathy John C. Kincaid MD

Description nn Lumbar radiculopathy at the L1 or L2 level I: Syndrome due to a focal lesion of the obturator nerve nn Lumbar plexopathy/plexitis Mononeuropathies History Etiology nn Pain in the groin or medial, proximal thigh nn Nerve trauma due to intra-pelvic surgery nn Instability/weakness in walking due to loss of adductor nn Nerve trauma during fractures of the pelvis or hip muscle power nn Compression by intra-pelvic masses: neoplasm or endometriosis Physical examination nn Compression during parturition: fetal head versus nn Weakness of leg adduction maternal positioning nn Sensory loss in the medial thigh nn Entrapment in the obturator canal Testing nn Epidemiology Imaging of the pelvis to investigate the retroperitoneal and pericystic or perirectal area Rare lesion in isolation, much less common than femoral nn Imaging of the hip joint and bony pelvis or sciatic neuropathy nn Needle EMG of the adductor muscles and the Pathogenesis quadriceps nn Local demyelination and in more severe lesions, Treatment axonopathy nn Analgesic, anti-inflammatory and nn Inflammatory neuritis as a component of the lumbar antineuropathic pain medications may partially plexitis syndrome improve symptoms nn Risk Factors Expectant observation over months if the lesion is associated with intra-pelvic surgery or nn Intra-pelvic surgery delivery nn Prolonged obstetric labor nn Manage endometriosis and other intra-pelvic lesions nn Clinical Features Diagnostic block of the obturator nerve nn Surgical decompression of the nerve in the obturator nn Pain in the groin and upper medial thigh canal nn Weakness of hip adduction Prognosis Natural History nn Improvement over weeks to months nn May improve over weeks to months when a single episode of nerve compression is the etiology Suggested Readings Sorenson EJ, Chen JJ, Daube JR. Obturator neuropathy: Diagnosis Causes and outcome. Muscle Nerve. 2002;25:605–607. Stewart, John D. Focal Peripheral Neuropathies. 4th ed. Differential diagnosis (pp. 568–573). West Vancouver, BC, Canada: JBJ nn Arthritis of the hip joint Publishing; 2010.

23 Peroneal (Fibular) Neuropathy: Common, Deep, and Superficial Branch Lesions John C. Kincaid MD

Description Natural History Syndrome due to focal lesion of the peroneal nerve along nn Abrupt onset when associated with trauma its course from the knee to the ankle nn Insidious onset when associated with repetitive leg crossing or a compressive mass lesion such as a Etiology nn Nerve trauma from traction, penetrating or lacerating injuries, or compression during fibular fracture Diagnosis nn Compression during repetitive leg crossing Differential diagnosis nn Entrapment in the region of the fibular head during nn Lumbar radiculopathy involving the 4th or 5th nerve repetitive or prolonged kneeling or squatting root nn Compression by a ganglion cyst or benign nerve tumor nn Lumbosacral plexopathy nn Focal manifestation of a polyneuropathy such nn Sciatic neuropathy as mononeuritis multiplex or multifocal motor neuropathy History nn Weakness of ankle and toe extension producing foot Epidemiology drop or foot slap Commonly encountered lesion, only lateral cutaneous nn Numbness and tingling on the lower lateral leg and neuropathy is a more common lower extremity lesion dorsum of the foot Physical examination Pathogenesis nn Weakness in ankle dorsiflexion, toe extension, and nn Compression, traction, or laceration of the nerve with foot eversion, or a combination of these deficits, resultant demyelination and axonopathy depending on the lesion location nn Risk Factors Atrophy of the muscles of the anterior compartment of the lower leg nn Knee or lower leg trauma nn Sensory loss in the superficial and/or deep peroneal nn Repetitive leg crossing, particularly when associated territories with significant weight loss nn Surgical procedures on the knee Testing nn Peroneal motor nerve conduction studies can show Clinical Features reduction of compound muscle action potential nn Lesions of the common peroneal nerve: weakness in (CMAP) amplitude from knee, fibular head, ankle, or ankle dorsiflexion, toe extension, and foot eversion a combination of these stimulation sites depending on along with tingling and/or numb-type paresthesias on the nature of the lesion. A low amplitude response from the lateral aspect of the leg and dorsum of the foot the knee but normal responses from the fibular head nn Lesions of the deep branch of the nerve: weakness of and ankle suggest a focal demyelinating-type lesion ankle dorsiflexion and toe extension plus tingling and/ at the knee. Low amplitude responses at each of these or numb-type paresthesias of the web space between sites indicate loss as the predominant pathology. toes I and II but without weakness in foot eversion Conduction velocities may be slow in the knee to nn Lesions of the superficial branch of the nerve: ankle or knee to fibular head segments of the nerve. weakness of foot eversion plus tingling and/or The motor distal latency should be normal. Motor numb-type paresthesias on the distal lower leg and conduction study to the tibialis anterior may be helpful dorsum of the foot but without weakness in ankle if the study to the extensor digitorum brevis shows dorsiflexion or toe extension no measurable response. Sensory conduction study

24 Peroneal (Fibular) Neuropathy: Common, Deep, and Superficial Branch Lesions 25

of the superficial peroneal branch will be abnormal nn Ankle foot orthosis to stabilize ankle extensor/everter if the axons of this branch have been damaged but functions will be normal if conduction block at the knee is the nn Surgical exploration of the nerve in the knee region if predominant pathology. a mass lesion is seen on imaging studies nn If axonal damage is present, the needle EMG will nn Tendon transfer to correct persistent weakness of show denervation in peroneal supplied leg and ankle extension

foot muscles but will produce normal results in the Mononeuropathies I:

short head of the biceps femoris and in nonperoneal Prognosis supplied muscles. Needle EMG can also be helpful in nn Improvement over weeks to months after determining the status of reinnervation after the initial elimination of repetitive leg crossing or after surgical lesion. decompression if a mass lesion has been found nn Magnetic resonance imaging (MRI) of the knee region nn Needle EMG can help define the status of to define skeletal and soft tissue anatomy, especially reinnervation when a causative lesion is not apparent nn Ultrasound examination of the nerve in the distal Suggested Readings upper leg to fibular head region Katirji B, Wilbourn A. Mononeuropathies of the lower limb. In: Dyck PJ, Thomas PK, eds. Peripheral Neuropathy. 4th ed. Treatment (pp. 1487–1510). Philadelphia, PA: Elsevier; 2005. Stewart, John D. Focal Peripheral Neuropathies. 4th ed. nn Reduce or eliminate leg crossing at the knee and (pp. 472–509). West Vancouver, BC, Canada: JBJ Publishing; repetitive squatting or kneeling 2010. Phrenic Neuropathy John C. Kincaid MD

Description History Syndrome due to a focal lesion of the phrenic nerve nn Orthopnea or dyspnea on exertion after surgical procedures in the chest or neck Etiology nn Difficulty weaning from ventilation after chest or nn Trauma to the nerve during cervical, cardiac, or other neck surgeries chest surgeries; during regional anesthesia involving the nn Pain in the neck or shoulder if inflammatory neuritis brachial plexus or jugular intravenous line placement is the etiology nn Inflammatory neuritis as a component of brachial plexitis or Herpes Zoster involving the C3 to C5 levels Physical examination nn Motor neuron disease predominantly involving the C3 nn Neurologic examination will usually be normal to C5 segments of the spinal cord nn Signs of accessory respiratory muscle activation nn Infiltration by neoplasms may be present

Epidemiology Testing Rare lesion except in the setting of where nn Chest radiography to evaluate for elevation of the the nerve may develop abnormal function in up to 10% diaphragm on the involved side of cases. nn Fluoroscopic evaluation of the diaphragm during inspiration/expiration Pathogenesis nn Nerve conduction study of the phrenic nerve nn Nerve trauma producing demyelination and axonal nn Needle EMG of shoulder/arm muscles if brachial degeneration plexitis/plexopathy is suspected nn Autoimmune inflammatory neuritis nn Needle EMG of the diaphragm if the physician is competent in this technique Risk Factors Cardiac surgery Treatment Clinical Features nn Expectant observation over months to about 2 years nn Orthopnea and dyspnea on exertion while reinnervation may occur nn Pain in the neck or shoulder if the neuropathy is nn Appropriate management of respiratory deficits: due to inflammatory neuritis upright sleeping position, nocturnal positive airway nn Weakness in other territories of the upper brachial pressure plexus if the phrenic neuropathy is a component of brachial plexitis/plexopathy Prognosis Natural History nn Requires 3 to 6 months of observation to determine if nn May improve over weeks to many months depending reinnervation will occur on the etiology Suggested Readings Diagnosis Stewart, John D. Focal Peripheral Neuropathies. 4th ed. (pp. 88–91). West Vancouver, BC, Canada: JBJ Publishing; Differential diagnosis 2010. nn Intrinsic lung lesion Tsao BE, Ostrovskiy DA. Phrenic neuropathy due to neuralgic nn Trauma to the diaphragm or its tendons amyotrophy. Neurology 2006;66:1582–1584.

26 Pudendal Neuropathy John C. Kincaid MD

Description Diagnosis I: Mononeuropathies Syndrome due to a lesion of the pudendal nerve Differential diagnosis nn Etiology Other pelvic lesions involving the , perivesicular, or perirectal areas nn Compression or irritation of the nerve by intra-pelvic nn Inguinal neuropathy lesions, such as endometriosis or neoplasm nn External compression of the nerve in the perineum by History prolonged, localized weight bearing, such as bicycle nn Abrupt onset following trauma to the nerve riding nn Slow or insidious onset in lesions due to recurring nn Nerve trauma from penetration during therapeutic external compression or intra-pelvic mass lesions injections, by fractures of the pelvis, during Physical examination surgery involving the pelvic floor, or during nn Decreased sensation to light touch or pin prick in the prolonged/recurrent labor perianal area, scrotum or labia, or along the shaft and tip of the penis or clitoris Epidemiology nn Rare lesion Testing nn Pelvic examination by a knowledgeable practitioner to Pathogenesis identify lesions of the perineum nn Local demyelination and axonopathy due to the nn Pelvic imaging to identify mass lesions primary lesion nn Electrodiagnostic evaluation [nerve conduction studies (NCS) and needle EMG] of the pelvic floor by a Risk Factors practitioner experienced in these techniques nn nn Endometriosis Diagnostic pudendal nerve block nn Long-distance bicycling Treatment nn Surgical procedures involving the pelvic floor nn nn Multiparous state Analgesic, anti-inflammatory, and antineuropathic pain medications may improve pain and paresthesias Clinical Features nn Alter seat angle or seat style if compression due to bicycle riding is the etiology nn Symptoms are most often unilateral nn Surgical decompression if an entrapment-type lesion nn Pain in the perineum is suspected nn Numbness and/or paresthesia in the perianal area, perineum, scrotum or labia, and shaft and head of the Prognosis penis or clitoris nn Improvement may occur in weeks to months if a nn Erectile and ejaculatory dysfunction modifiable causation is present Natural History Suggested Readings nn Lesions due to local pressure on the nerve, such as Stav K, Dwyer PL, Roberts L. Pudenal neuralgia. Fact or fiction? by long-distance bicycle riding, may improve over Obstet Gynecol Surv. 2009;64:190–199. weeks to months after changing seating position or Stewart, John D. Focal Peripheral Neuropathies. 4th ed. seat style (pp. 457–460). West Vancouver, BC, Canada: JBJ Publishing; 2010.

27 Radial Neuropathy—In the Arm John C. Kincaid MD

Description History Syndrome due to a focal lesion of the distal nn Abrupt onset of wrist and finger extension weakness to the shoulder up to the elbow segment of the nerve during trauma to the upper arm or upon awakening from a prolonged period of excessive sedation Etiology nn Paresthesias and numbness over the dorsal forearm, nn Humeral fractures at the mid to mid-distal level distal radial forearm, and radial aspect of the hand nn Prolonged external compression of the nerve Physical examination against the humerus during periods of impaired nn Weakness of wrist and finger extension consciousness nn Impaired contraction of the brachioradialis nn Trauma from intramuscular injections nn “Pseudo” weakness of ulnar hand intrinsic muscles if the nn Compression from vigorous contraction of the triceps hand is not supported into a neutral flexion–extension or external objects such as rifle slings position during ulnar hand muscle testing nn Normal triceps strength Epidemiology nn Normal triceps muscle stretch reflex Uncommon but classic peripheral nerve lesion nn Sensory loss over the dorsal forearm, distal radial forearm, and radial aspect of the hand Pathogenesis Testing Local demyelination and axonopathy due to the primary nn Motor nerve conduction study of the radial nerve may lesion show partial conduction block in the region of the spiral groove. Risk Factors nn The finding of a normal to near-normal radial compound action potential amplitude with nn Impaired responsiveness due to alcohol, sedating stimulation distal to the lesion at the level of the medication, excessive fatigue, or coma elbow when performed for more than 5 days after nn Underlying polyneuropathy such as hereditary onset suggests the lesion is predominantly due to local neuropathy with liability to pressure palsy conduction block (neurapraxia/demyelination). nn A normal sensory action potential from the radial Clinical Features sensory branch obtained 5 to 10 days after the onset nn Weakness of wrist and finger extension also supports the lesion being due to local conduction nn Sensory impairment in the superficial radial territory block at the site of the lesion. nn Low or absent motor or sensory response amplitudes Natural History from elbow level stimulation 10 to 14 days after onset nn Tends to improve over days to about 8 weeks when suggests axonal damage as the predominant pathology. the pathogenesis is local demyelination producing nn Needle EMG performed 3 to 4 weeks after onset can conduction block also help reveal the degree of any axonal damage: nn Recovery time frame is much longer when axonal abundant fibrillation potentials and positive sharp damage predominates waves indicate axonopathy. nn Repeat needle EMG at 2-month intervals after onset Diagnosis can help detect reinnervation and define prognosis when deficits have persisted beyond 6 to 8 weeks. Differential diagnosis nn Imaging of the nerve by magnetic resonance imaging nn Stroke producing upper motor neuron-type weakness (MRI) or ultrasound can help define the status of nn C7 radiculopathy nerve continuity if fracture or penetrating injury was nn Middle trunk or posterior cord brachial plexopathy the etiology.

28 Radial Neuropathy—In the Arm 29

Treatment Prognosis nn Physiatric and physical therapy evaluations to nn Good over 6 to 8 weeks if conduction block (neurapraxia) determine the optimal range-of-motion exercises is suggested by nerve conduction studies and orthoses while strength deficits are present nn Guarded if axonal damage (axonotmesis) is suggested nn Antineuropathic pain medication, such as gabapentin by nerve conduction studies or pregabalin, may help if bothersome paresthesias are

Suggested Readings Mononeuropathies I:

present. nn Consider surgical exploration at 8 to 12 weeks if Stewart, John D. Focal Peripheral Neuropathies. 4th ed. (pp. 315–347). West Vancouver, BC, Canada: JBJ Publishing; 2010. nerve conduction studies continue to show a pattern Wilbourn AJ, Ferrante MA. Upper limb neuropathies. of complete axonotmesis and needle EMG shows no In: Dyck PJ, Thomas PK, eds. Peripheral Neuropathy. 4th ed. signs of beginning reinnervation. (pp. 1474–1478). Philadelphia, PA: Elsevier; 2005. Radial Neuropathy—Posterior Interosseous Neuropathy John C. Kincaid MD

Description nn Cervical radiculopathy involving the 6th or 7th Syndrome due to a lesion of the posterior interosseous nerve roots with predominant involvement of finger branch of the radial nerve extensors (pseudoposterior interosseous syndrome) nn Brachial plexitis with predominant involvement of Etiology axons to the finger extensors nn Entrapment of this branch of the radial nerve as it passes nn Proximal radial neuropathy through the supinator muscle (Arcade of Frohse) nn Multifocal polyneuropathy: multifocal motor nn Compression by lipoma, ganglia, or hypertrophied neuropathy or mononeuritis multiplex synovium History nn Nerve trauma due to fracture of the proximal ulna or nn Spontaneous, insidious onset versus less common radius pattern of abrupt onset following vigorous, repetitive supination/pronation activities Epidemiology nn Variable pain component: proximal forearm or wrist nn Rare lesion, encountered about once every 2 years in an location if present 1800-patient per year tertiary level nn No sensory loss or paresthesia-type symptoms (EMG) laboratory Physical examination Pathogenesis nn Weakness in extension of digits I to V: thumb, index, nn Demyelination and axonopathy due to compression of or middle fingers may be predominantly involved in the nerve some patients nn Atrophy of extensor digitorum communis may occur Risk Factors in longstanding cases nn Proximal fractures of the ulna or radius nn A variable degree of tenderness along the course of the nn Repetitive vigorous pronation and supination nerve in the region of the supinator (5–10 cm distal to the lateral epicondyle) Clinical Features nn Sensory examination in the posterior cutaneous nerve nn Weakness of finger extension, all fingers versus of the forearm and superficial radial nerve territories predominant weakness of the thumb, index, or middle should be normal. fingers Testing nn Radial motor nerve conduction studies may show Natural History reduced amplitude of the compound muscle action nn May improve over days to weeks with reduction of potential recorded from the extensor digitorum forearm overuse communis or extensor indicis proprius as well as nn More commonly the deficits persist until the nerve is prolonged latency to those muscles with elbow-level surgically decompressed nerve stimulation. nn Sensory responses in the superficial radial nerve Diagnosis should be normal. Differential diagnosis nn Conduction studies in the adjacent nerves should be nn Lateral epicondylitis normal unless polyneuropathy is present.

30 Radial Neuropathy—Posterior Interosseous Neuropathy 31

nn Needle EMG shows denervation in radial supplied precipitating event or if no improvement has occurred hand muscles distal to the supinator after a 4 to 6 week period of observation after a nn Imaging studies of the proximal radius and ulna if causative event traumatic event has occurred (current or remote time frames) Prognosis nn Imaging of the region of the supinator by ultrasound nn Improvement spontaneously or after surgical

or magnetic resonance imaging (MRI) in idiopathic Mononeuropathies I: decompression in a time course partly definable based cases to evaluate for lesions such as ganglia or lipoma on the degree of denervation present in the needle Treatment EMG nn Analgesic, anti-inflammatory, and antineuropathic pain medications usually do not significantly improve Suggested Readings the symptoms Stewart, John D. Focal Peripheral Neuropathies. 4th ed. nn (pp. 314–347). West Vancouver, BC, Canada: JBJ Publishing; Reduce forearm and hand use, particularly repetitive 2010. pronation/supination activities Wilbourn AJ, Ferrante MA. Upper limb neuropathies. nn Surgical decompression of nerve through the region In: Dyck PJ, Thomas PK, eds. Peripheral Neuropathy. 4th ed. of the supinator if onset was gradual without a clear (pp. 1474–1478). Philadelphia, PA: Elsevier; 2005. Radial Neuropathy–Superficial Radial Sensory Neuropathy John C. Kincaid MD

Description History Syndrome due to a lesion of the superficial branch of the nn Onset usually follows a definable event radial nerve nn Distal forearm and dorsal hand paresthesias, which may worsen with wrist motions Etiology nn Cutaneous hypersensitivity in the area of the nn Direct compression by overly tight watch bands, paresthesias handcuffs, or casts in the mid-to-distal forearm Physical examination nn Nerve trauma from intravenous catheter insertion, nn during surgery in the distal forearm or wrist region or Sensory deficits in the nerve’s cutaneous area over the direct trauma during a fracture distal radial forearm and dorsum of the thumb, index, and middle digits Epidemiology nn Tinel’s sign at the site of nerve compression nn Annual incidence is 0.003% in the general population nn Normal strength in finger and wrist extensor muscles Pathogenesis Testing Local demyelination and axonopathy depending on the nn severity of the lesion. Radial sensory conduction studies show reduced action potential amplitude or absence of a measurable Risk Factors response nn Intravenous catheter insertion in the distal, radial nn Radial motor conduction studies should be normal forearm nn Conduction studies in adjacent nerves are normal nn Surgical treatment of de Quervain’s syndrome unless polyneuropathy is present nn Needle EMG of the radial forearm and nonradial C5 Clinical Features or C6 muscles should be normal nn Tingling and/or numb-type paresthesias in the distal, radial forearm and dorsum of the thumb, index, and Treatment middle digits nn Conservative observation over 4 to 12 week time nn Normal finger and wrist extensor strength in the course finger and wrist extensor muscles nn Antineuropathic pain medications may lessen the intensity of paresthesias and allodynia Natural History nn Treat concomitant conditions, such as de Quervain’s nn May improve over weeks to months Diagnosis Prognosis Differential diagnosis nn Improvement over weeks to months is expected but nn Extensor tendonitis of the thumb (de Quervain’s bothersome paresthesias and allodynia may persist for syndrome) many months to years nn Carpal tunnel syndrome nn Cervical radiculopathy involving the 5th or 6th nerve Suggested Readings roots Stewart, John D. Focal Peripheral Neuropathies. 4th ed. nn Upper trunk brachial plexopathy (pp. 315–347). West Vancouver, BC, Canada: JBJ Publishing; 2010. nn Proximal radial neuropathy Wilbourn AJ, Ferrante MA. Upper limb neuropathies. nn Focal manifestation of multifocal polyneuropathy, In: Dyck PJ, Thomas PK, eds. Peripheral Neuropathy. 4th ed. such as mononeuritis multiplex (pp. 1474–1478). Philadelphia, PA: Elsevier; 2005. 32 Sciatic Neuropathy John C. Kincaid MD

Description Diagnosis I: Mononeuropathies Syndrome due to a focal lesion of the sciatic nerve between Differential diagnosis the level of the piriformis muscle and the popliteal fossa nn Lumbar radiculopathy at the L5 or S1 level Etiology nn Lumbosacral plexopathy nn nn Nerve trauma due to pelvic or hip fracture, total hip Arthritis of the hip joint nn arthroplasty, penetration by gun shots, stab wounds, Inflammation or instability of the sacroiliac joint or intramuscular injection History nn Compression by hematoma or neoplasm nn Abrupt onset of symptoms shortly following trauma nn Entrapment by the piriformis muscle or at the time of awakening from surgery nn Epidemiology Indolent course in or intraneural neoplasm nn Occurs in about 1% of first time total hip replacement nn Weakness and pain tend to dominate the surgeries and up to about 5% of patients undergoing symptomatology repeat procedures nn Sensory deficits most commonly reported in the nn Rare lesion otherwise peroneal (fibular) territory Pathogenesis Physical examination Compression producing local demyelination and axonal nn Motor deficits in the peroneal (fibular) territory damage tend to be the more prominent: weakness of ankle nn Extraneural lesions are much more common extension and foot eversion nn Intraneural lesions such as peripheral nerve tumors nn Motor deficits in posterior tibial supplied muscle are extremely rare are often present but to a lesser degree: weakness of plantar flexion, foot inversion, toe flexion Risk Factors nn Depending on the location of the lesion knee, flexion nn Total hip arthroplasty, especially revision procedures may also be weak nn Fractures of the pelvis, hip, or femur nn Ankle reflex is reduced or absent on the affected nn Prolonged periods of unconsciousness or immobility side nn Intramuscular injections into the gluteus maximus nn Hip abduction and/or hip extension strength should be normal and the presence of weakness in these Clinical Features motions indicates that the lesion is in the sacral plexus nn Weakness in extensor and flexor motions of the ankle or nerve root rather than the sciatic nerve and toes nn Sensory deficits in the peroneal (fibular), posterior nn Weakness of knee flexion may also be present tibial, and sural nerve territories nn Sensory deficits in the peroneal (fibular), posterior nn Reproduction of or worsening of by tibial, and sural territories flexion-adduction-internal rotation-type maneuvers nn Neuropathic pain in the foot and in some instances the entire leg Testing nn Complex regional pain syndrome can occur in this nn Motor nerve conduction studies should show setting reduced or absent compound muscle action potentials in the peroneal (fibular) and at times Natural History posterior tibial nerves. Conduction velocities tend nn May improve over weeks to about 2 months in lesions to be mildly slow in an “axonal pattern” and distal that are predominantly demyelinating. Deficits can latencies should remain normal. Focal slowing in the persist for many months or be permanent when knee to fibular head segment of the peroneal nerve axonal damage predominates should not be present. 33 34 Sciatic Neuropathy nn Sensory conduction studies will show low Treatment amplitude or absent responses in the superficial nn Analgesic and antineuropathic pain medications may peroneal and sural nerves if axon loss is a significantly improve the symptoms component of the lesion nn Physical therapy to optimize function and facilitate nn Peroneal and F-wave responses will be recovery slowed or absent nn Ankle foot orthosis to stabilize foot drop nn The H reflex may be slowed or absent depending on nn Decompression of the nerve in the piriformis if a the degree of involvement of the posterior tibial nerve lesion at that site is supported by the evaluation component nn Needle EMG will likely show signs of axonal damage Prognosis in peroneal and to a lesser degree posterior tibial nn Improvement over weeks to months in cases due to nerve territories. Gluteal muscles and the lumbar total hip arthroplasty, fractures of the femur, and paraspinals should be normal if the lesion is at the penetrating injury sciatic nerve rather than the lumbosacral plexus or nerve root. Suggested Readings Katirji B, Wilbourn A. Mononeuropathies of the lower limb. nn Depending on the specific scenario, imaging studies In: Dyck PJ, Thomas PK, eds. Peripheral Neuropathy. 4th ed. of the hip joint, lumbar spine, pelvis, lumbosacral (pp. 1487–1510). Philadelphia, PA: Elsevier; 2005. plexus, and proximal leg, including the piriformis Stewart, John D. Focal Peripheral Neuropathies. 4th ed. (pp. 432– muscle may be needed. 471). West Vancouver, BC, Canada: JBJ Publishing; 2010. Spinal Accessory Neuropathy John C. Kincaid MD

Description History I: Syndrome due to a lesion of the spinal accessory nerve nn Weakness of shoulder shrug and abduction Mononeuropathies movements of the arm Etiology nn Pain in the upper shoulder and lateral neck nn Trauma to the nerve during radical nerve surgery or nn Onset may follow a definable event such as surgery or lymph node biopsy may occur spontaneously nn Blunt force and traction on the nerve in the setting of Physical examination shoulder trauma nn Atrophy of trapezius: upper, middle, or lower nn Inflammation of the nerve as part of the brachial components plexitis syndrome nn Muscle bulk and strength of sternomastoid muscle is Epidemiology normal unless the lesion is very proximal nn Scapular winging, more notable in arm abduction A lesion of this nerve occurs most often in the setting rather than protraction movements of surgery on the anterior lateral neck for treatment of nn Normal cutaneous sensation unless adjacent sensory cancer or as a complication of lymph node biopsy in the nerves are also affected: the lesser occipital and greater lower lateral neck. auricular nerves being the more likely to show deficits Pathogenesis Testing nn Demyelination and axonopathy secondary to the nn Nerve conduction studies of the spinal accessory nerve primary etiology show reduction of compound muscle action potential nn Inflammatory neuritis (CMAP) amplitude on the affected side nn Needle EMG shows denervation in the upper, middle, Risk Factors or lower portions of the trapezius nn Cancer surgery on the neck nn Lymph node biopsy in the posterior-lateral neck Treatment nn Expectant observation over 3 to 6 months to Clinical Features determine if reinnervation will occur nn Weakness of shoulder motions nn Cable grafting of the nerve when it must be sacrificed nn Pain in the lower neck and top of the shoulder during radical surgery for cancer nn Physical therapy to improve shoulder motion and Natural History strength nn May improve over months to about 1 year Prognosis Diagnosis nn Improvement over months to about 1 year depending Differential diagnosis on the success of reinnervation nn Cervical radiculopathy Suggested Readings nn Arthritis of the shoulder Stewart, John D. Focal Peripheral Neuropathies. 4th ed. (pp. 91–95). nn Rotator cuff dysfunction West Vancouver, BC, Canada: JBJ Publishing; 2010. nn Brachial plexopathy/plexitis Kim DH, Cho YJ, Tiel Rl. Surgical outcomes of 111 spinal nn Long thoracic neuropathy ­accessory nerve injuries. Neurosurg. 2003;53:1106–1112.

35 Suprascapular Neuropathy John C. Kincaid MD

Description nn Cervical radiculopathy involving the 5th or 6th nerve nn Syndrome due to a focal lesion of the suprascapular roots nerve nn Brachial plexopathy or plexitis with predominant involvement of the Etiology History nn Entrapment in the region of the suprascapular notch on nn Weakness in shoulder abduction and external rotation the superior aspect of the scapula or in the spinoglenoid motions notch as the nerve passes under the spine of the scapula nn Pain in the superior aspect of the shoulder (not nn Damage to the nerve in the setting of trauma to or present in all patients) dislocation of the shoulder nn Traction on the nerve at the level of the suprascapular Physical examination notch in repetitive sports activities, such as baseball nn Weakness in shoulder abduction and external pitching or volleyball playing rotation (only the latter may be present in some nn Focal manifestation of brachial plexitis cases) nn Atrophy of supra- and infraspinatus muscles Epidemiology nn Normal strength and bulk of the deltoid, biceps, and Rare lesion serratus anterior muscles nn Pain in the superior shoulder region during resisted Pathogenesis shoulder abduction or during palpation of the region nn Demyelination and axonopathy of the suprascapular notch nn Inflammatory neuritis Testing nn Compression from a shoulder cyst nn Needle EMG of muscles supplied by the upper trunk Risk Factors of the brachial plexus including the supra- and infraspinatus nn Shoulder trauma nn Nerve conduction study of the suprascapular nerve if nn Competitive baseball pitching or volleyball playing the practitioner is skilled in this technique nn Clinical Features Magnetic resonance imaging (MRI) of the shoulder joint and associated soft tissue structures, including nn Weakness in shoulder abduction and external rotation assessment of the size of the suprascapular notch; may nn Weakness only in external rotation if the lesion is in see a cyst compressing the nerve the spinoglenoid notch nn Local anesthetic block at the suprascapular nn Pain in the upper posterior shoulder area, may be notch if pain is a significant component of the absent in some patients syndrome nn No cutaneous sensory abnormalities Treatment Natural History nn Conservative observation if the lesion is due to nn May improve over months if a specific etiology is shoulder trauma or is an isolated manifestation of identified and is corrected brachial plexitis nn Diagnosis Appropriate management of degenerative lesions of the shoulder joint and associated soft tissue Differential diagnosis structures nn Lesion of the shoulder joint or associated muscular nn Reduction or modification of shoulder motions in and tendon structures lesions related to sports activities

36 Suprascapular Neuropathy 37

nn Surgical decompression of the nerve at the suprascapular Suggested Readings notch if local pain is a prominent manifestation and if Antoniadis G, Richter HP. Suprascapular nerve entrap- local anesthetic block improves the pain ment: Experience with 28 cases. J Neurosurg. 1996; 85:1020–1025. Stewart, John D. Focal Peripheral Neuropathies. 4th ed. Prognosis (pp. 166–172). West Vancouver, BC, Canada: JBJ Publishing; nn Improvement in strength over months 2010. I: Mononeuropathies I:

Tibial Neuropathy—In the Ankle and Foot John C. Kincaid MD

Description nn Tibial neuropathy arising proximal to the ankle Syndrome due to a focal lesion of the distal portion of the nn Polyneuropathy tibial nerve nn Plantar or other soft tissue lesions of the foot Etiology History nn nn Nerve trauma due to fracture Abrupt onset of motor and sensory deficits following nn Entrapment in the tarsal tunnel traumatic lesions nn nn Compression of the interdigital sensory branches at Gradual onset in compressive lesions within the tarsal the metatarsal head (Morton’s neuroma) tunnel or at the metatarsal head Physical examination Epidemiology Rare lesions, much less common than lesions of the sci- Ankle and proximal foot lesions atic or peroneal nerves nn Weakness of toe flexion and abduction if the lesion is at the ankle Pathogenesis nn Atrophy of tibial innervated foot muscles nn External nerve trauma with resulting demyelination nn Normal ankle muscle stretch reflex and axonal pathology nn Sensory loss in the territories of the medial plantar, nn Entrapment in potentially constricting spaces lateral plantar, and calcaneal nerves or any combination of these if the lesion is at the ankle Risk Factors nn Sensory loss in two adjacent toes if the lesion is at the nn Distal tibial fractures metatarsal head nn Arthritis of the ankle joint nn Tinel’s sign from the nerve at the level of the medial nn Wearing “overly fashionable” high heeled shoes malleolus or abductor hallucis nn Normal examination of the peroneal and saphenous Clinical Features nerves nn The lesion is predominantly unilateral Interdigital nerve lesions (Morton’s neuroma) Ankle and proximal foot lesions nn Reproduction of pain and/or paresthesia with deep nn Weakness of toe flexion and abduction palpation of the interdigital space, most often between nn Sensory loss in the medial, lateral, or both plantar the 3rd and 4th metatarsal heads, if the lesion is at the nerve territories on the plantar surface of the foot level of the interdigital nerve nn Sensory loss over the plantar aspect of the heel Testing Interdigital nerve lesions (Morton’s neuroma) nn Pain in region of the metatarsal head during weight Ankle and proximal foot lesions bearing nn Tibial motor nerve conduction studies should show prolongation of the distal latency to the abductor Natural History hallucis and/or abductor digiti minimi pedis if the nn May improve over weeks to many months after lesion is at the ankle. Compound muscle action changes in activities involving the foot or change in potential (CMAP) amplitudes may be reduced if axon shoe style loss is also present. Conduction velocity in the knee to ankle segment should be normal unless significant Diagnosis axon loss is present. Differential diagnosis nn Mixed nerve conduction studies of the medial and lateral nn Sciatic neuropathy plantar nerves, if obtainable, may show prolongation of nn S1 radiculopathy distal latency and loss of sensory nerve action potential nn Sacral plexopathy (SNAP) amplitude.

38 Tibial Neuropathy—In the Ankle and Foot 39

nn Conduction studies in the peroneal and sural nerves nn For Morton’s neuroma excision of the neuroma should be normal (fibroma) of the symptomatic interdigital nerve if nn Needle EMG will likely show denervation in tibial conservative treatments fail supplied foot muscles but muscles proximal to the ankle should be normal Prognosis nn Imaging studies of the ankle and foot to identify nn Improvement in sensory symptoms and motor signs

compressive lesions, such as ganglion cysts over months with modification of foot activities or Mononeuropathies I:

shoe styles, or after surgical decompression Treatment nn Reduce or modify foot activities Suggested Readings nn Change to more supportive, less “overly fashionable” Katirji B, Wilbourn A. Mononeuropathies of the lower limb. In: Dyck PJ, Thomas PK, eds. Peripheral Neuropathy. 4th ed. shoes (pp. 1487–1510). Philadelphia, PA: Elsevier; 2005. nn Steroid injection in the tarsal tunnel or symptomatic Stewart, John D. Focal Peripheral Neuropathies. 4th ed. metatarsal head interspace (pp. 510–539). West Vancouver, BC, Canada: JBJ Publishing; nn Surgical decompression of the tarsal tunnel 2010. Tibial Neuropathy–From Knee to Ankle John C. Kincaid MD

Description nn Focal manifestation of a multifocal polyneuropathy Syndrome due to focal damage to the tibial nerve between such as mononeuritis multiplex the knee and the ankle level nn Rupture of the Achilles tendon nn or other soft tissue lesions of the foot Etiology History nn Nerve trauma due to penetrating injury or fracture nn Abrupt onset of motor and sensory deficits following nn Compression by synovial cysts in the knee region traumatic lesions nn Benign nerve tumor nn Gradual onset in compressive lesions such as synovial Epidemiology cysts or intraneural tumors Rare, much less common than sciatic, peroneal, or femoral Physical examination lesions nn Weakness of ankle plantar flexion and foot inversion nn Weakness of toe flexion and abduction Pathogenesis nn Atrophy of calf and tibial supplied intrinsic foot muscles nn External nerve trauma with resulting demyelination nn Loss of or reduction of the ankle muscle stretch reflex and axonal pathology nn Sensory loss in the sural territory and plantar aspect nn Compromise of the vascular supply to the nerve of the foot nn Signs of autonomic overactivity if causalgia is present Risk Factors Testing nn Trauma to the femur, knee, tibia, or associated soft nn Motor nerve conduction studies should show loss of tissue compound muscle action potential (CMAP) amplitude nn Surgical procedures on the knee at both the knee and ankle stimulation sites and nn Regional anesthesia procedures involving the sciatic mild slowing of conduction velocity (note that the nerve CMAP amplitude may drop by up to 50% between Clinical Features the ankle and the knee stimulus sites in some normal individuals). The distal latency should remain normal. nn Weakness of ankle flexion and foot inversion, weakness nn Sensory nerve conduction studies may show loss of of toe flexion, and toe abduction sensory nerve action potential (SNAP) amplitude in nn Sensory loss in the sural nerve territory and plantar the sural sensory study, depending on the lesion site. aspect of the foot, depending on the lesion site. nn Conduction studies in adjacent nerves should be normal Sural deficits indicate a lesion at or proximal to the unless the lesion involves the distal sciatic nerve, peroneal knee nerve concurrently, or if polyneuropathy is present. nn Causalgia, complex regional pain syndrome type II, nn Needle EMG should show denervation in tibial may develop in the setting of tibial nerve injury supplied muscles of the lower leg and foot. Tibial Natural History innervated hamstring muscles and peroneal supplied muscles should be normal. nn May improve over weeks to many months, depending on the nature of and severity of the causative lesion Treatment nn Diagnosis Analgesic and antineuropathic pain medications may improve symptoms Differential diagnosis nn Appropriate management if causalgia, complex nn Sciatic neuropathy regional pain syndrome type II, is present nn L5 or S1 radiculopathy nn Physical therapy to maximize functional recovery nn Lumbosacral plexopathy nn Surgical exploration and decompression if a mass nn Tibial neuropathy at the ankle lesion is the etiology

40 Tibial Neuropathy–From Knee to Ankle 41

Prognosis Suggested Readings nn Improvement in sensory and motor deficits Katirji B, Wilbourn A. Mononeuropathies of the lower limb. over months to about 2 years depending on the In: Dyck PJ, Thomas PK, eds. Peripheral Neuropathy. 4th ed. (pp. 1500–1503). Philadelphia, PA: Elsevier; 2005. severity of the causative lesion. Stewart, John D. Focal Peripheral Neuropathies. 4th ed. (pp. 510–539). West Vancouver, BC, Canada: JBJ Publishing; 2010. I: Mononeuropathies I:

Trigeminal Neuralgia and Neuropathy John C. Kincaid MD

Description Risk Factors Syndromes due to lesions of the trigeminal nerve nn Facial trauma nn nn (tic douloureux) manifests as Dental extractions nn recurrent unilateral short-lived paroxysms of severe Multiple sclerosis, particularly in trigeminal facial pain neuropathy patients with onset below age nn nn Trigeminal neuropathy manifests as loss of sensation, 50 years nn often without a painful component Herpes Zoster involving the trigeminal nerve

Etiology Clinical Features Trigeminal neuralgia Trigeminal neuralgia nn Compression of the sensory root of the nerve proximal nn Unilateral paroxysms of intense “electric”- or to the Gasserian ganglion by branches of the superior “hot poker”-like pain lasting seconds cerebellar artery nn Pain is often provoked by facial or jaw movement or nn Inflammatory demyelination of the sensory axons cutaneous stimulation within the trigeminal sensory within the brainstem due to multiple sclerosis territory nn Idiopathic nn Attacks tend to not occur during sleep Trigeminal neuropathy nn The second or third divisions of the nerve are more nn Nerve trauma due to facial or mandibular fractures, often affected dental extractions, or skull base surgery nn Absence of persisting sensory loss in the affected nn Compression or invasion of the nerve by skull base or division of the nerve nasopharyngeal neoplasms Trigeminal neuropathy nn Local inflammation of the nerve due to Herpes nn Unilateral loss of sensation in the trigeminal Zoster attacks or connective tissue diseases, such as territory scleroderma or mixed connective tissue disease nn Pain is a less common feature except in cases nn Idiopathic occurring as component of a Herpes Zoster attack Epidemiology nn Motor deficits can occur if the mandibular division is nn Trigeminal neuralgia’s annual incidence is 4 to 25 involved cases per 100,000 of population with higher incidence occurring in older individuals Natural History nn Trigeminal neuropathies are much less common than nn Trigeminal neuralgia: recurring attacks of pain, trigeminal neuralgia although spontaneous remissions can occur nn Trigeminal neuropathy: persistent sensory deficits Pathogenesis nn Trigeminal neuralgia: local demyelination of the Diagnosis peripheral or central trigeminal sensory axons allows spontaneous generation of action potentials in Differential diagnosis nociceptive neurons nn Trigeminal neuralgia: migraine headache, cluster nn Trigeminal neuropathy: local demyelination and headache, temporomandibular joint dysfunction, axonal damage due to trauma, compression, or sinusitis, and dental disease inflammation of trigeminal sensory axons and at nn Trigeminal neuropathy: brainstem infarction, times motor axons sinusitis, and facial trauma

42 Trigeminal Neuralgia and Neuropathy 43

History Treatment nn Trigeminal neuralgia: paroxysmal unilateral Trigeminal neuralgia short-lived attacks of intense electric jabbing pain in nn Antiepileptic medications: carbamazepine or oxcarbazine the forehead, maxilla, or mandible often provoked by nn Gabapentin and baclofen can be used as adjunctive face or jaw movements medications nn Trigeminal neuropathy: persistent sensory loss in the nn Surgical decompression of the sensory root if medical territory of the trigeminal nerve Mononeuropathies I: treatment fails nn Physical examination Gamma-knife treatment is also a viable option for patients not fully responsive to medical management Trigeminal neuralgia nn Rhizotomy of the Gasserian ganglion by thermal or nn Normal sensory and motor functions of the trigeminal chemical means and adjacent cranial nerve territories Trigeminal neuropathy nn An attack of pain may be provoked by cutaneous nn Antibiotics for sinusitis stimuli in the affected division of the nerve nn Antibiotic and surgical management of dental infection Trigeminal neuropathy nn Immune suppressive/modulation for connective tissue nn Loss of sensation in the affected division(s) of the disease nn nerve Appropriate management of Herpes Zoster attack and nn Atrophy of the masseter and temporalis muscles may postherpetic neuralgia be present if the mandibular division is involved Prognosis Both conditions: absence of jaw crepitance during nn The pain of trigeminal neuralgia should be fully ­opening/closing motions. controllable in the vast majority of patients by medical or surgical means Testing nn The sensory loss due to trigeminal neuropathy tends nn Imaging of the brain stem and course of the trigeminal to persist nerve through the skull base nn Imaging of the sinuses Suggested Readings nn Connective tissue disease serologies: ANA, SS-A, Hughes R. Diseases of the fifth cranial nerve. In: Dyck PJ, Thomas PK, eds. Peripheral Neuropathy. 4th ed. and SS-B (pp. 1207–1217). Philadelphia, PA: Elsevier; 2005. nn Dental examination Love S, Coakham H. Trigeminal neuralgia, pathology and nn Blink reflex testing for trigeminal neuropathy pathogenesis.­ Brain 2001;124:2347–2360. Ulnar Neuropathy—At the Elbow John C. Kincaid MD

Description Diagnosis Syndrome due to a lesion of the ulnar nerve in the region Differential diagnosis of the elbow nn Medial epicondylitis nn Etiology Degenerative arthritis of the elbow nn Cervical radiculopathy involving the C8 or T1 nerve nn Entrapment by the proximal aspect of the flexor carpi roots ulnaris (cubital tunnel retinaculum) during elbow nn Lower trunk or medial cord brachial plexopathy flexion nn Neurogenic thoracic outlet syndrome nn Compression of the nerve just proximal to the medial nn Ulnar neuropathy at the wrist epicondyle during prolonged or repetitive flexion nn Focal manifestation of polyneuropathy (retro-epicondylar region) nn Entrapment due to osteoarthritis of the elbow joint History years to decades after an elbow fracture (tardy ulnar nn Paresthesias in digits IV to V, which worsens during palsy) elbow flexion nn Compression of the nerve during fracture of the distal nn Pain in the medial elbow region humerus or proximal ulnar nn Weakness in fine motions of the digits or hand nn Lacerations of the nerve due to penetrating injury (eg, page turning, finger nail clipping, buttoning) eg, glass shards, knife wounds Physical examination nn Compression of the nerve during or immediately nn Decreased sensation to light touch or pin prick in following surgery (intraoperative ulnar neuropathy) digits IV to V nn Epidemiology Decreased sensation to light touch or pin prick over the medial aspect of both the palmar and dorsal nn Second most common entrapment mononeuropathy aspects of the hand after carpal tunnel syndrome nn Two point discrimination threshold greater than 2 to nn Seen more commonly in men 3 mm on tip of digits IV to V nn Pathogenesis Weakness of abduction and adduction of ulnar- supplied hand muscles Local demyelination and then axonopathy, depending on nn Weakness of flexion of the distal interphalangeal the severity of the nerve compression joints of digits IV to V nn Risk Factors Atrophy of ulnar-supplied hand and medial forearm muscles in severe cases nn Prior elbow fracture with residual mal-alignment of nn Subluxation of the nerve over the medial epicondyle the humerus and ulna (tardy ulnar palsy) during elbow flexion (occurs in ~20% of normal nn Surgical procedures (intraoperative ulnar neuropathy) individuals) nn Clinical Features Tinel’s sign along the nerve around the elbow nn Reproduction of or worsening of sensory symptoms nn Tingling and/or numb-type paresthesias in digits by 30 seconds of full elbow flexion (elbow flexion test) IV to V nn Normal strength in non-ulnar C8 muscles, such as the nn Pain in the medial elbow abductor pollicis brevis and extensor pollicis longus nn Weakness in ulnar-supplied hand and forearm muscles Testing nn Motor nerve conduction studies show slowing of Natural History conduction velocity in the elbow segment with normal nn May improve over days to weeks with reduction of velocity in the forearm. Distal latency should remain repeated or prolonged periods of elbow flexion normal. 44 Ulnar Neuropathy—At the Elbow 45

nn In more severe cases that produce axon loss, the nn Observe the clinical status over 4 to 8 weeks and if forearm conduction velocity may also be slow and the improvement occurs, continue conservative treatment response amplitudes become reduced at stimulus sites nn If symptoms persist or worsen during conservative both proximal and distal to the elbow treatment, refer the patient for surgical consultation: nn Sensory responses from the fifth digit or the dorsal The surgical procedure may be decompression at the cutaneous branch will show reduced amplitudes level of the proximal flexor carpi ulnaris or anterior

with stimulation at the wrist when axonal damage is submuscular transposition of the nerve. Mononeuropathies I:

present nn Ulnar neuropathy occurring in the intraoperative or nn Sensory responses from wrist-level stimulation will immediately postoperative setting tends to respond remain normal if the elbow lesion is predominantly less well to surgical intervention demyelinating nn Median motor and sensory and radial sensory Prognosis conduction studies should remain normal unless an nn Improvement over weeks to 2 months with underlying polyneuropathy is present conservative treatment if the lesion is predominantly nn When the lesion causes axonal damage, needle EMG demyelinating will show abnormal resting activity and neurogenic- nn Improvement over weeks if surgery is performed for type motor unit potentials in ulnar-supplied hand patients not responding to conservative treatment and, in most instances, ulnar-supplied forearm nn Improvement over months in patients showing muscles but should be normal in non-ulnar C8- or predominantly axonal-type abnormalities on T1-supplied muscles. preoperative electrodiagnostic studies

Treatment Suggested Readings nn Limit elbow flexion voluntarily or via an elbow pad, Campbell WW, Carroll DJ, et al. Practice parameter for electrodiagnostic studies in ulnar neuropathy at the elbow. which secondarily impairs full elbow flexion Muscle Nerve. 1999;22:408–411. nn Occupational therapy evaluation for padding and Stewart, John D. Focal Peripheral Neuropathies. 4th ed. (pp. splinting of the elbow 260–313). West Vancouver, BC, Canada: JBJ Publishing; 2010. Ulnar Neuropathy—At the Wrist John C. Kincaid MD

Description Natural History nn Syndrome due to lesion of the ulnar nerve as it enters nn May improve over weeks to months with reduction of the hand (Guyon’s canal) the causative activity

Etiology Diagnosis nn Nerve trauma from recurring or sustained external Differential diagnosis pressure on the ulnar side of the hand nn Ulnar neuropathy at the elbow nn Compression by ganglia, synovial cysts, and benign nn C8 or T1 radiculopathy neoplasms nn Lower trunk brachial plexopathy, including neurogenic thoracic outlet syndrome Epidemiology nn Arthritis or other bony abnormality of the wrist Rare lesion: encountered approximately once in 5 years nn Tendinitis/ of the ulnar aspect of the in an 1800-patient study per year tertiary level electromy- wrist/hand ography (EMG) laboratory History nn Weakness of ulnar-controlled finger motions Pathogenesis nn Abnormal sensation in IV and V digits nn Compression of the ulnar nerve in the “Guyon’s canal” nn Hand or forearm pain is not a common feature region of the hand Physical examination Risk Factors nn Weakness of ulnar innervated hand muscles: nn Long-distance cycling on a “ram’s horn” handlebar hypothenar and intrinsic or intrinsic only nn type bicycle Atrophy of ulnar innervated muscles in moderate-to- nn Use of the ulnar side of the heel of the hand as a severe cases nn “hammer” Normal function of flexor digitorum profundus and nn Prolonged or recurrent leaning on the base of the hand flexor carpi ulnaris muscles nn Normal function of median and radial innervated muscles of the hand and digits Clinical Features nn Decreased sensation to light touch or pin prick of the nn Weakness of the ulnar innervated hand muscles palmar aspect of digits IV to V nn Sensory loss in digits IV and V with sparing nn Normal sensation over the ulnar area of the palmar of the palmar and dorsal ulnar sensory areas of the and dorsal ulnar area of the hand hand nn Tinel’s sign over the ulnar nerve at the wrist nn Depending on the lesion site as the nerve nn Inspect/palpate ulnar aspect of the wrist for mass enters the hand, four different clinical patterns lesion may occur: ––Weakness of all ulnar innervated hand muscles and Testing abnormal sensation in digits IV to V; nn Ulnar motor conduction studies, including distal ––Weakness in both hypothenar and ulnar intrinsic latency to the first dorsal interosseous muscle: hand muscles with normal sensation; ––Lesions of the ulnar nerve at the wrist should ––Weakness in ulnar intrinsic hand but not produce prolongation of motor distal latency to the hypothenar muscles with normal sensation hypothenar muscles and/or first dorsal interosseous (most common pattern); and muscle depending on the exact lesion site at the wrist ––Sensory loss in digits IV to V with normal function ––Forearm and across-elbow conduction velocities of ulnar supplied hand muscles should be normal

46 Ulnar Neuropathy—At the Wrist 47

nn Ulnar sensory conduction studies to the fifth digit and nn Surgical exploration/decompression of the nerve if the dorsal cutaneous branch improvement of function does not occur over several nn Median motor conduction study to evaluate for months of observation or if a space occupying lesion is abnormalities in non-ulnar C8/lower trunk plexus found on imaging studies supplied muscles nn Needle EMG of ulnar innervated hand and Prognosis

forearm muscles and median supplied thenar nn Improvement over weeks to months after elimination Mononeuropathies I:

muscles of external compressive activities or surgical excision nn Imaging of the hand by plain x-ray for fracture and by of space occupying lesions magnetic resonance imaging (MRI) or ultrasound for soft tissue-type lesions Suggested Readings Stewart, John D. Focal Peripheral Neuropathies. 4th ed. Treatment (pp. 297–313). West Vancouver, BC, Canada: JBJ Publishing; 2010. nn Reduce activities that produce pressure on the ulnar Wu J-S, Morris JD, Hogan GR. Ulnar neuropathy at the aspect of the base of the hand wrist: Case report and review of literature. Arch Phys Med nn Pad the base of the hand for activities such as bicycling Rehabil. 1985;66:785–788. Vagal (Laryngeal) Neuropathy John C. Kincaid MD

Description Clinical Features Syndromes due to lesions of the vagal nerve nn Hoarseness and impaired ability to increase the volume of the voice nn Abnormalities of laryngeal function: voice and nn Impairment raising the pitch of the voice laryngeal sensation nn Persistent cough nn Abnormalities of vagal autonomic function: heart nn Stridor when bilateral lesions are present rate regulation and gastrointestinal motility nn Syncope or enhanced tendency for syncope modulation Natural History Etiology Improvement in the majority of patients over several nn Nerve trauma, more commonly unilateral, during weeks to about 6 month time frame surgical procedures on thyroid, cervical spine, carotid artery, or skull base Diagnosis nn Nerve trauma during intrathoracic surgical procedures or during endotracheal intubation Differential diagnosis nn Compression or infiltration of the nerve by neoplasms nn Central nervous system lesion of the lateral in the neck or chest brainstem producing vagal dysfunction along with nn Idiopathic but presumably autoimmune inflammatory other signs, such as cerebellar ataxia and hemisensory neuritis loss nn Local manifestation of generalized polyneuropathy nn Dislocation of the arytenoid bone during trauma to the larynx Epidemiology History Rare lesions except in the postoperative setting: tempo- nn Abrupt onset of voice dysfunction in patients due to rary paresis occurs in 2% to 12% of thyroidectomies, 2% nerve trauma during a surgery to 6% of carotid endarterectomies, and 2% of cervical nn Gradual onset and progressive voice dysfunction spine surgeries done by the anterior approach in patients due to compression or infiltration of the nerve by neck or thoracic neoplasms Pathogenesis nn Persistent cough nn Local demyelination and axonal damage secondary to nn Enhanced tendency for syncope compression or traction during surgery Physical examination nn Nerve compression secondary to infiltration by nn Dysphonia of a hoarse, raspy nature neoplasms in the neck, or check along the course of nn Impairment of vocal cord motion (requires the nerve visualization of the vocal cord) nn Autoimmune inflammation of the nerve nn Findings of lateral medullary syndrome (unilateral nn Axonopathy and demyelination due to an underlying lower limb ataxia and impairment of pain and polyneuropathy temperature sensation along with vagal dysfunction) Risk Factors Testing nn Surgery on the neck, cervical spine, or intrathoracic nn Evaluation of vocal cord function by laryngoscopy structures nn Imaging of neck and chest to identify mass lesions nn Endotracheal intubation along the course of the vagal nerve nn Malignancy of the thyroid or chest along the course of nn Needle EMG of laryngeal muscles: abnormalities in the nerve both the cricothyroid and thyroarytenoid indicate a nn Presence of generalized polyneuropathy, such as lesion of the nerve proximal to the bifurcation of the Charcot-Marie-Tooth disease or diabetic neuropathy superior and recurrent laryngeal branches 48 Vagal (Laryngeal) Neuropathy 49

nn Assessment of swallowing function if dysphagia is a nn Several surgical procedures are available to partially manifestation of the dysfunction improve long-term vocal cord dysfunction nn Cardiac evaluation if new-onset syncope is a feature of nn Reinnervation phenomena such as spastic dysphonia the lesion can be treated by botulinum toxin injection into the nn Neurological evaluation if generalized neuropathy, thyroarytenoid muscle features of basal ganglia disease, or motor neuron Prognosis disease are present Mononeuropathies I: Most patients improve over 3 to 6 months Treatment Suggested Readings nn Tracheostomy may be required if airway Rosenthal L, Benninger M. Vocal fold immobility: A longitudinal compromise occurs due to bilateral lesions, analysis of etiology over 20 years. Laryngoscope 2007;117: which leave the vocal cords in an adducted 1864–1870. Thomas P, Mathias C. Diseases of the ninth, tenth, eleventh position and twelfth cranial nerves. In: Dyck PJ, Thomas PK, eds. nn Expectant observation over 3 to 6 months watching Peripheral Neuropathy. 4th ed. (pp. 1273–1293). Philadelphia, for recovery of nerve function PA: Elsevier; 2005.

II Polyneuropathies Acute Inflammatory Demyelinating Polyradiculoneuropathy (Guillain-Barré Syndrome) John C. Kincaid MD

Description nn Sensations of band-like tightness may be experienced Acquired, autoimmune polyneuropathy, which reaches in truncal areas maximum clinical deficit over a time course of 8 weeks nn Autonomic dysfunction manifesting as unstable blood or less pressure or cardiac arrhythmias may occur nn Urinary and rectal sphincter functions usually remain Etiology normal Autoimmune process, which attacks the myelin sheath and axons of the nerve roots and peripheral nerve trunks Natural History nn Improves over 3 to 12 months in most patients Epidemiology nn Severe persisting deficits occur in 5% to 10% Prevalence of one case per 100,000 population Diagnosis Pathogenesis Differential diagnosis nn Cellular rather than antibody-mediated autoimmune nn Acute polyneuropathy due to other causes such response, which cross reacts with antigens on the as porphyria; adverse effects of medication such peripheral myelin sheath or axons of the nerve roots as cancer chemotherapy, nitrofurantoin, or and nerve trunks metronidazole exposure, and/or arsenic poisoning nn Recent infection with Campylobacter jejuni (C. jejuni) nn Spinal cord lesion due to an inflammatory process is a potentially provoking factor in approximately 30% such as transverse myelitis or the initial attack of of cases multiple sclerosis nn Other cases may follow nonspecific respiratory nn Spinal cord compression due to spondylotic , initial HIV infection, vaccination, or surgical procedures with a typical interval of 8 to nn Spinal cord infarction 12 weeks or less between those events and the onset of nn Poliomyelitis the neuropathy nn West Nile virus infection History Risk Factors nn Paresthesias begin in the feet and spread proximally nn C. jejuni infection into the feet, legs, and upper extremities in a time nn Vaccination against seasonal influenza course extending over several days to a maximum of Clinical Features 8 weeks nn Weakness evolves in the same distal to proximal, nn “Ascending” (distal to proximal, lower extremity lower and upper extremity pattern described in somewhat earlier than upper extremity) pattern of clinical features motor and sensory deficits, with motor dysfunction nn Neuropathic pain tends to be a less prominent feature, usually being the more prominent feature but some patients report a “tight” or constrictive nn Maximum deficit is reached by 8 weeks or less after pattern in the thoracic/abdominal spinal areas onset, with 4 weeks or less being more typical nn Loss of muscle stretch reflexes Physical examination nn Neuropathic pain in the limbs may occur but is nn Symmetrical weakness in distal and proximal muscles usually not a prominent feature of the lower and upper extremities

52 Acute Inflammatory Demyelinating Polyradiculoneuropathy (Guillain-Barré Syndrome) 53 nn Weakness of facial muscles occurs in up to 50% and show fibrillations and positive waves by 4 to 8 weeks extraocular muscles may be affected in 5% to 10% of after onset, reflecting the development of axonal patients dysfunction nn Respiratory failure due to pharyngeal, diaphragmatic, or nn Cerebrospinal fluid (CSF) analysis for protein and cell chest wall muscle weakness occurs in 30% of patients count nn Loss of muscle stretch reflexes nn Consider porphyria screen and urine arsenic level nn Deficits in sensory function such as light touch, vibration, and pin prick sensation Treatment Testing nn Immune modulating therapy by plasma exchange or nn Motor nerve conduction studies show prolongation of intravenous infusion of gamma-globulin shortens the distal latencies and slowing of conduction velocities in duration of the deficits by 30% to 50%. the forearm and leg segments of the nerves. nn Corticosteroids by oral or intravenous routes do not II: Polyneuropathies II: nn Distal latencies greater than 125% of the upper limit have any beneficial affect. of normal, conduction velocities less than 70% of the low limit of normal and conduction block with Prognosis response amplitudes, dropping by more than 20% nn Improvement over a 2- to 12-month time frame between proximal and distal stimulus sites support nn 10% of patients may have a partial relapse after an the neuropathy being predominantly demyelinating initial period of improvement nn Sensory conduction studies also become abnormal nn 15% of patients are left with clinically significant by showing prolonged distal latencies and reduction deficits of response amplitudes but nerves that do not pass through potential entrapments sites such as the sural and superficial radial may remain normal. Suggested Readings Amato A, Russell J. Neuromuscular Disorders (pp 214–232). nn The latencies of the F-wave and H-reflex become McGraw Hill, New York; 2008. prolonged if they are recordable Griffin J, Sheikh K. The Guillain-Barré Syndromes. nn Needle EMG shows reduction of motor unit potential In: Dyck PJ, Thomas PK, eds. Peripheral Neuropathy. 4th ed. recruitment as the weakness begins and then may (pp. 2197–2219). Philadelphia, PA: Elsevier; 2005. Amyloid Neuropathies John C. Kincaid MD

Description Natural History Peripheral neuropathies due to accumulation of specific Gradual progression of the neuropathic and other organ proteins, which have a propensity to form insoluble deficits: extracellular fibrils in certain tissues nn Neuropathic deficits in the inherited forms may Etiology progress to a disabling degree nn Hematologic, cardiac, and renal deficits may progress The neuropathy occurs in two different settings: to a severe degree nn Sporadic (primary amyloid neuropathy) due to overproduction and tissue deposition of the light Diagnosis chain component of immunoglobulin Differential diagnosis nn Inherited (familial amyloid neuropathy) cases due to nn altered structure of a constituent protein resulting in Chronic inflammatory neuropathy nn an enhanced tendency for tissue deposition Idiopathic carpal tunnel syndrome followed some years later by polyneuropathy due to another cause Epidemiology nn Other dominantly inherited polyneuropathies Neuropathies due to amyloidosis are rare: History nn Sporadic cases are the more common type nn Sensory loss and paresthesias, beginning in feet of a myloidosis and occur in the setting of a nn Small fiber sensory functions, such as pain and lymphoproliferative disorder temperature, may be predominantly affected early nn Inherited cases show a dominant inheritance pattern on in some inherited varieties with large fiber-type dysfunction occurring later Pathogenesis nn Carpal tunnel syndrome is the initial manifestation in Overproduction of normal proteins, such as the gamma- some types of amyloidosis nn light chain component of immunoglobulin, or alteration Distal weakness usually occurs after sensory of the usual amino acid sequence of a constitutive protein, dysfunction nn such as prealbumin (transthyretin), cause the protein to Autonomic dysfunction manifesting as impotence, be less soluble than normal and to have an increased ten- diarrhea, sphincter dysfunction, orthostatic hypotension, dency to form deposits of a beta-sheet structure in certain and impaired sweating are features of some forms tissues, including the peripheral nerves. Physical examination nn Deficits in the sensory modalities of pin prick and Clinical Features temperature, light touch, vibration, and position nn Onset of deficits in the 30- to 50-year-old age group is sensation are the earliest findings in patients with typical polyneuropathy nn Gradual onset of sensory loss and paresthesia, nn Sensory deficits and signs of nerve irritability in the beginning in the toes and feet is the more median nerve territory may be found in patients with common pattern; lower extremity motor deficits carpal tunnel syndrome as an early manifestation may develop later as can hand sensory and motor nn Symmetrical distal weakness of the lower and later the deficits upper extremities nn Carpal tunnel syndrome can be the initial nn Loss of muscle stretch reflexes consistent with the presentation in some forms of amyloid neuropathy pattern of weakness with polyneuropathy developing years later nn Impaired pupillary reaction to light and orthostatic nn Autonomic, cardiac, renal, and hematologic hypotension if autonomic functions are impaired dysfunction occurs in some forms of amyloidosis nn Purpuric skin lesions

54 Amyloid Neuropathies 55

Testing nn Immune modulation with melphalan and steroids or nn Serum and urine protein electrophoresis to evaluate high-dose melphalan followed by autologous stem cell for the presence of a monoclonal protein or excessive rescue in primary amyloidosis production of gamma-light chains nn Liver transplantation in Familial Amyloid Neuropathy nn Bone marrow examination in patients with the may stabilize the peripheral nerve and cardiac primary form of amyloidosis components nn Biopsy of abdominal fat pad, rectal mucosa, or nn Treatment with protein-stabilizing agents such as peripheral nerve for demonstration of deposits, difunisal and tamifidis (the latter is not available in the which stain with the dye Congo Red and show pink United States currently) may stabilize the neuropathy to green color change when viewed under polarized nn Down regulation of amyloid protein production by light ribonucleic acid (RNA) interference mechanisms is nn Nerve conduction studies show an “axonal” pattern being investigated in familial amyloidosis II: Polyneuropathies II:

of abnormality: motor and sensory response amplitudes are low, conduction velocities are no Prognosis slower than the mid-30 meter per second range, and nn Hematologic, cardiac, and peripheral nerve components distal latencies remain normal except in the median of primary amyloid may stabilize with treatment nerve nn Peripheral nerve and cardiac components of familial nn Depending on the type of amyloid neuropathy, amyloidosis may stabilize with treatment nerve conduction studies may show findings typical nn The role of emerging therapies such as of median neuropathy at the wrist initially and protein-stabilizing medications and RNA interference polyneuropathy-type findings appear years later modulation of production of the abnormal proteins nn Cerebrospinal fluid values tend to be normal remains to be more fully established. nn Electrocardiogram and echocardiogram to evaluate cardiac conduction and contractile functions Suggested Readings Benson M, Kincaid J. The molecular biology and clinical features Treatment of amyloid neuropathy. Muscle Nerve. 2007;36:411–423. Kincaid J. Neuropathies due to amyloidosis. In: Donofrio P, ed. nn Symptomatic treatment for neuropathic pain Textbook of Peripheral Neuropathy (pp. 227–232). New York: nn Treat cardiac arrhythmias and heart failure Demos Medical; 2012. Cancer-Related Polyneuropathies John C. Kincaid MD

Description Syndrome 3: Generalized sensory-motor Neuropathies in the form of neuronopathy, multiple polyneuropathy mononeuropathy, or a generalized polyneuropathy can nn Occurs in patients who have cancer but have not yet occur in patients who have cancer. received chemotherapy or for which another etiology Neuropathy related to the treatment of cancer is cov- is definable ered in Chapter 36 on medication-related neuropathy. Risk Factors Etiology Having cancer: especially small cell lung, breast, colon, nn Indirect (remote) effect due to autoimmune attack nasopharyngeal, or leukemia against peripheral neurons Clinical Features nn Direct effect due to neoplastic cell infiltration of nn Syndrome 1: Abrupt to subacute onset of progressive peripheral nerves sensory loss in the limbs and at times truncal areas nn Indirect effect due to alteration of systemic and nerve producing impairment of standing and walking due metabolism to ataxia which may allow spontaneous movements of Epidemiology the hands or feet to develop (pseudoathetosis) Neuropathy is clinically evident in up to 5% of cancer ––Some patients with this syndrome may also develop patients but may be present in up to 30% of patients who an encephalopathy with features of memory loss and are evaluated by nerve conduction study and quantitative seizures sensory testing. nn Syndrome 2: Abrupt to subacute onset of progressive focal pain, sensory, and motor dysfunction in single Pathogenesis or multiple adjacent peripheral nerves or plexus Syndrome 1: Sensory neuronopathy territories nn The most classic cancer-related neuropathy, but is very nn Syndrome 3: Subacute onset of distal sensory and rare motor dysfunction in patients known to have or who nn An autoimmune attack against the Hu protein complex are found to have cancer but who have not yet received present on certain neoplastic cells and sensory neurons chemotherapy or is the presumed cause of this “paraneoplastic” or Natural History “remote effect of cancer” syndrome nn Syndrome 1: Progressive worsening over weeks to a nn Small cell lung cancer is the most common neoplasm few months producing this syndrome, but breast, ovarian, and nn Syndrome 2: Progressive worsening producing renal also have been associated more extensive focal deficits in the area of initial Syndrome 2: Multiple mononeuropathy, involvement plexopathy, or polyradiculopathy nn Syndrome 3: Initial worsening and then stabilization nn Infiltration of the nerve roots, brachial or lumbosacral Diagnosis plexi, or individual nerve trunks by neoplastic cells is the cause of this syndrome Differential diagnosis nn Leukemia or lymphoma is the more common source nn Polyneuropathies due to concomitant conditions such of infiltrating cells as diabetes nn Cranial nerve syndromes are most often related to nn Chemotherapy-induced peripheral neuropathy nasopharyngeal cancers nn Guillain-Barré syndrome or chronic inflammatory nn Brachial plexopathy is most often associated with neuropathy breast or lung cancers nn Spinal cord or brain lesions due to metastases nn Lumbosacral plexopathy is most often associated with nn Local nerve lesions such as Herpes Zoster due to colon or cervical cancers cancer-related immune system alteration 56 Cancer-Related Polyneuropathies 57

History nn Electrodiagnostic testing nn Syndrome 1: Subacute onset of progressive sensory ––Syndrome 1 shows absence of sensory loss in the limbs resulting in impaired use of the nerve responses but normal values for motor hands and feet plus truncal ataxia studies nn Syndrome 2: Acute to subacute onset in individual ––Syndrome 2 shows motor and sensory as well as or multiple cranial nerves or plexus dysfunction needle EMG abnormalities in the areas of producing pain, sensory loss, and weakness in the abnormality but may not show generalized affected nerve territories abnormality nn Syndrome 3: Subacute onset of length-dependent, ––Syndrome 3 shows a distal predominant axonal-type sensory-motor dysfunction; alternatively, signs of peripheral neuropathy peripheral neuropathy may be found on clinical nn Imaging studies to define local abnormalities in examination and electrophysiologic testing without cranial nerve, skull base, plexus, or multiple nerve II: Polyneuropathies II:

the patient being aware of the deficit root territories nn Physical examination Standard serum tests for peripheral neuropathy: fasting glucose, vitamin B12 level, serum protein Syndrome 1 electrophoresis for monoclonal gammopathy nn Decreased sensation to vibration, light touch, position, and pain stimuli in the limbs and at times the truncal Treatment areas nn Syndrome 1: Management of the neoplasm is the nn Absence or reduction of muscle stretch reflexes mainstay, immunologically based treatments such nn Muscle strength is normal but the sensory loss may be as plasmapheresis or intravenous immune globulin profound enough that the patient has to look directly probably do not improve the neuropathy at the body part being tested to be able to generate nn Syndrome 2: Local radiation therapy and intrathecal normal power chemotherapy nn Spontaneous movements of the toes, fingers, feet, nn Syndrome 3: Symptomatic management of sensory hands, and at times truncal areas of which the patient and motor deficits may be unaware (pseudoathetosis) can occur when the sensory impairment is severe Prognosis Syndrome 2 nn Syndrome 1: Defined by the course of primary nn Focal sensory and motor deficits corresponding to neoplasm but sensory deficits tend to not improve individual or multiple adjacent cranial nerves or to the nn Syndrome 2: Defined by the course of the primary brachial or lumbosacral plexus neoplasm, but local deficits may improve temporarily with focused treatment Syndrome 3 nn Syndrome 3: Stable to slowly worsening course nn Distal sensory loss to all modalities nn Weakness of toe, foot, and finger motions Suggested Readings nn Loss of muscle stretch reflexes distally Amato A, Russell J. Neuromuscular Disorders (pp. 313–332). Testing New York: McGraw Hill; 2008. Bosch P, Haberman T, Tefferi A. Peripheral neuropathy nn Anti-Hu antigen in serum and cerebrospinal fluid for ­associated with lymphoma, leukemia and myeloprolif- syndrome 1 erative disorders. In: Dyck PJ, Thomas PK, eds. Peripheral nn Cerebrospinal fluid analysis for low glucose level and Neuropathy. 4th ed. (pp. 2489–2503). Philadelphia, PA: presence of neoplastic cells in syndrome 2 Elsevier; 2005. Chronic Inflammatory Demyelinating Polyradiculoneuropathy John C. Kincaid MD

Description Natural History Acquired, autoimmune sensory and motor polyneuropa- nn Spontaneous improvement is uncommon thy, which reaches maximum clinical deficit over a time nn A relapsing remitting course occurs in about 50% of course of at least 8 weeks, often evolving over a many- patients month course of time Diagnosis Etiology Differential diagnosis Autoimmune process, which attacks the myelin sheath nn Subacutely evolving polyneuropathy due to diabetes, and axons of the nerve roots and peripheral nerve trunks alcoholism, amyloidosis, HIV infection, autoimmune Epidemiology conditions such as Sjögren syndrome or systemic erythematosus, and inherited neuropathies Prevalence of one case per 100,000 population nn Spinal cord compression due to cervical or Pathogenesis lumbosacral spondylotic myelopathy nn nn Cellular rather than antibody-mediated autoimmune Residual of prior lesions such as polio and post-polio response, which cross reacts with antigens on the syndrome peripheral myelin sheath or axons of the nerve roots History and nerve trunks nn Paresthesias begin in the feet and spread proximally nn Immunoglobulin M (IgM) monoclonal gammopathy into the legs and upper extremities in a time course with cross reaction against the myelin-associated extending over at least 8 weeks but more typically over glycoprotein component of peripheral nerve may many months produce this syndrome nn Weakness, which evolves in the same distal to proximal, lower, and upper extremity pattern Risk Factors described in clinical features nn IgM monoclonal gammopathy nn Neuropathic pain is not usually a prominent feature nn Antecedent events such as infectious illnesses before Physical examination the onset of neuropathy are much less common, in nn Symmetric weakness in distal and proximal muscles contrast to the situation for Guillain-Barré syndrome of the lower and upper extremities Clinical Features nn Weakness of facial muscles occurs in 15% of patients nn “Ascending” (distal to proximal, lower extremity and tends to be mild nn somewhat earlier than upper extremity) pattern of Papilledema can occur when cerebrospinal fluid motor and sensory deficits, with motor dysfunction protein is very high nn usually being the more prominent feature Respiratory insufficiency is unusual in this condition nn nn Maximum deficit is reached in a time course of more Loss of muscle stretch reflexes nn than 8 weeks; a time frame of many months to few Deficits in sensory functions such as light touch, years is more typical vibration, and pin prick sensation nn Loss of muscle stretch reflexes Testing nn Neuropathic pain is usually not a prominent feature nn Motor nerve conduction studies show prolongation of nn Autonomic dysfunction manifesting as unstable blood distal latencies and slowing of conduction velocities in pressure or cardiac arrhythmias may occur forearm and leg segments of the nerves. nn Urinary function is disturbed in approximately 25% of nn Distal latencies >125% of the upper limit of normal, patients conduction velocities <70% of the low limit of normal

58 Chronic Inflammatory Demyelinating Polyradiculoneuropathy 59

and conduction block with response amplitudes Treatment dropping by more than 20% between proximal and nn Immune-modulating therapy with corticosteroids, distal stimulus sites support the neuropathy being plasma exchange, or intravenous infusion of gamma- predominantly demyelinating globulin should produce improvement in 80% of nn Sensory conduction studies also become abnormal patients by showing prolonged distal latencies and reduction nn Ongoing treatment over months to years may be of response amplitudes, but nerves that do not pass required through potential entrapment sites such as the sural and superficial radial may remain normal. Prognosis nn The latencies of the F-wave and H-reflex become nn Spontaneous improvement is rare prolonged if they are recordable nn Immune-modulating treatment should produce nn Needle EMG shows reduction of motor unit potential improvement in up to 80% of patients but prolonged II: Polyneuropathies II:

recruitment as the weakness begins and then may treatment may be required show fibrillations and positive waves by 4 to 8 weeks after onset, reflecting the development of axonal Suggested Readings dysfunction Amato A, Russell J. Neuromuscular Disorders (pp. 233–260). New nn Cerebrospinal fluid (CSF) protein is elevated by cell York: McGraw Hill; 2008. count remains normal Hahn A, Hartung H, Dyck P. Chronic inflammatory demyelinat- ing polyradiculoneuropathy. In: Dyck PJ, Thomas PK, eds. nn Porphyria screen, vitamin B12 level, serum protein Peripheral Neuropathy. 4th ed. (pp. 2221–2253). Philadelphia, electrophoresis for monoclonal protein, especially IgM PA: Elsevier; 2005. Critical Illness Polyneuropathy Gentry Dodd MD ■ John C. Kincaid MD

Description nn Autonomic dysfunction is not a major feature or is not An acute, acquired, axonal polyneuropathy that develops clearly distinguishable from the effects of the primary during the treatment of some severely ill patients illness nn Urinary and rectal sphincter functions usually remain Etiology normal nn Occurs in conditions such as sepsis, severe trauma, or pancreatitis, which provoke the systemic inflammatory Natural History response syndrome (SIRS) Improves over 3 to 12 months in most patients who are able to be discharged from the hospital. Epidemiology nn Fifty-eight percent of patients with a prolonged Diagnosis intensive care unit (ICU) stay develop critical illness Differential diagnosis neuropathy nn Critical illness nn It has been found in some prospective studies that nn Acute polyneuropathy due to other causes such as 70% to 80% of patients with severe sepsis and multiple Guillain-Barré Syndrome, cancer chemotherapy, organ failure suffer from this disorder nitrofurantoin exposure, or porphyria ––It is seen in nearly 100% of patients with sepsis and nn Cervical spinal cord lesion due to an inflammatory coma process such as transverse myelitis or the initial attack nn Patients who end up developing critical illness neuropathy of multiple sclerosis have an increased organ dysfunction score and a number nn Spinal cord infarction of organs involved and are also ventilated longer nn Botulism

Pathogenesis History Proposed mechanisms include effects of inflammatory nn Weakness of the limbs and truncal muscles, which mediators such as cytokines, interleukins, and alteration develops while the patient is in ICU and most often of nitric oxide pathway functioning manifests as difficulty weaning the patient from the ventilator Risk Factors nn Dysesthesias in feet and hands with onset in the Sepsis, severe trauma, and conditions such as pancreati- same time frame as the motor deficits but tis, which result in the patient being ill enough to require which may not be apparent due to altered mechanical ventilation sensorium and impaired communication due to intubation Clinical Features nn Onset while the patient is in intensive care Physical examination nn Inability to wean from mechanical ventilation is nn Symmetrical weakness of the lower and upper usually the most prominent manifestation extremities affecting both distal and proximal muscles nn Weakness in a distal to proximal gradient but which and often to the degree of producing complete can be severe enough to produce complete limb and paralysis of the limbs respiratory muscle paralysis nn Respiratory failure due to pharyngeal, diaphragmatic, nn Loss of reflexes while in ICU or chest wall muscle weakness occurs in 30% of nn Abnormal sensation in a distal to proximal gradient patients (this feature may not be apparent if the patient has an nn Loss of muscle stretch reflexes altered sensorium) nn Deficits in sensory function such as light touch, nn Neuropathic pain in the limbs may occur but is vibration, and pin prick sensation if the patient’s usually not a prominent feature sensorium allows reliable examination 60 Critical Illness Polyneuropathy 61

Testing nn There is a paucity of evidence suggesting that early nn Conduction studies show an “axonal” pattern of rehabilitation beginning in the ICU enhances muscle abnormality: motor and sensory response amplitudes recovery: are low if present, conduction velocities are no slower ––Early physical therapy (PT) and occupational than the mid-30 meters per second range, and distal therapy (OT) have been shown to improve latencies remain normal functional independence nn Needle EMG shows fibrillations and positive waves ––Range-of-motion exercises during bed rest should be along with severely reduced motor unit potential established in ICU patients recruitment nn Cerebrospinal fluid values tend to be normal Modalities nn Spinal cord magnetic resonance imaging (MRI) does nn Functional electrical stimulation not show significant abnormalities of the canal or nn Electrical stimulation (E stim) II: Polyneuropathies II: spinal cord parenchyma Consults nn Creatine phosphokinase values may be elevated early nn Physical and occupational therapy in the course of the weakness nn Neurology Pitfalls nn Physiatry nn In some patients that present similarly to those with Complications of treatment critical illness neuropathy, may demonstrate reduced nn compound muscle action potentials with normal Hypoglycemic events are significantly increased with sensory amplitudes. In these cases, and the use of intensive insulin therapy nn disorders of neuromuscular transmission need to be Those patients receiving intensive insulin therapy considered have been shown to have a small increase in ––This can be done with creatine phosphokinase levels, mortality muscle biopsy, and repetitive stimulation studies Prognosis Red flags nn In a study from 1996, a third of patients died in the nn Administration of succinylcholine as a muscle relaxing acute phase, a third were ambulatory within anesthetic agent runs the risk of hyperkalemic cardiac 4 months, and the rest took 4 to 12 months to recover arrest or remained ventilated nn Many patients have profound muscle weakness and Treatment chronic disability Medical treatment nn Persistent disabilities often include reduced reflexes, nn Prevention of SIRS is the most effective way to reduce sensory loss, atrophic muscles, painful dysesthesias, the chance of developing critical illness neuropathy and foot drop nn Once critical illness neuropathy has been established, the only effective treatment is physical and Helpful Hint occupational therapy nn Examination of patients with possible critical illness nn The occurrence of critical illness neuropathy, however, polyneuropathy is often difficult to perform, given that has been shown to be reduced with intensive insulin the patient may be unresponsive, encephalopathic, or treatment sedated. ––Goal blood glucose level is 108–150 mg/dL ––This should only be implemented by an experienced Suggested Readings team Bolton C, Gilbert J, Hahn A. Polyneuropathy in critically Exercise ill patients. J Neurol Neurosurg . 1984;47:1223. Zochodne D. Neuropathies associated with renal fail- nn Once the patient is out of the ICU and able to tolerate ure, hepatic disorders, chronic respiratory disease and therapy, focus should be on preserving the residual critical Illness. In: Dyck PJ, Thomas PK, eds. Peripheral strength as well as preventing any type of Neuropathy. 4th ed. (pp. 2017–2037). Philadelphia, PA: from forming Elsevier; 2005. Hereditary Motor and Sensory Neuropathy/Charcot-Marie-Tooth Disease John C. Kincaid MD

Description nn Abnormalities in sensory function tend to be a less Inherited polyneuropathy, which most often causes motor prominent symptom, despite sensory deficits being dysfunction more prominently than sensory dysfunction present on clinical examination nn Neuropathic pain tends to not be a prominent feature Etiology in most patients Genetically based alteration of structural components of nn Reflexes are abnormal distally but may be preserved the Schwann cell, axon, or neuronal cell body of periph- proximally eral neurons nn Except for distal limb abnormalities in sweating, autonomic functions tend to be clinically spared Epidemiology nn Urinary and rectal sphincter functions usually remain nn Prevalence of one case per 100,000 population normal nn Dominant inheritance is the most common genetic nn A pattern of recurrent mononeuropathies, such as pattern but X-linked and recessive patterns also occur foot drop, , or ulnar deficits, which come on after prolonged position maintenance and then Pathogenesis improve over weeks to months, can be seen in the nn Charcot-Marie-Tooth (CMT) patients usually hereditary liability to pressure palsy variant of CMT segregate into demyelinating (CMT type 1) or axonal type 1 (CMT type 2) forms depending on the degree of nerve conduction velocity slowing Natural History nn Alerted structure in a growing list of proteins involved Gradual onset over years, most often in the late teens or in Schwann cell or axon function of peripheral early twenties, with very slow worsening over subsequent neurons is the basis of the clinical manifestation years to decades nn Abnormalities of Schwann cell proteins, such as peripheral membrane protein 22 (PMP-22) and myelin Diagnosis protein zero (MPZ), are the more commonly identified Differential diagnosis alterations in the demyelinating form of the disease nn Other slowly evolving neuropathies such as those due nn Abnormalities in a mitochondrial cell wall protein to diabetes or excessive alcoholic consumption (mitofusion-2) is the most common alteration found nn Late-onset, lower motor neuron disorders such as in CMT type 2 patients spinal muscular atrophy nn Abnormalities in a gap junction protein present in nn Spinocerebellar ataxias Schwann cell membranes (connexin 32) accounts for most of the X-linked varieties of CMT History nn Weakness in toe and ankle functions, which begins Risk Factors insidiously, manifesting as foot drop followed years nn A parent having the same condition: dominant later by onset of finger and hand weakness nn inheritance is the most common, but X-linked and Distal sensory symptoms such as numbness and recessive patterns also occur tingling, which appear in a similar time frame but which are often much less prominent than the motor Clinical Features manifestations nn Gradual onset, most often in the late teen age-group, Physical examination of a pattern of weakness involving the toes and feet nn Symmetrical weakness in distal muscles of the lower initially and then the fingers/hands years later and, to a lesser degree, upper extremities

62 Hereditary Motor and Sensory Neuropathy/Charcot-Marie-Tooth Disease 63 nn Atrophy of intrinsic foot and distal leg muscles nn The latencies of the F-wave and H-reflex become producing a “peroneal muscular atrophy” pattern prolonged if they are recordable (stork or inverted champagne bottle legs) nn Needle EMG shows fibrillations, positive waves, and nn Atrophy of intrinsic hand muscles, which becomes more enlarged motor unit potentials in patients who have prominent years after the foot weakness and atrophy been symptomatic for years or decades nn Abnormal foot structure is often present from nn Genetic testing for the commonly identified childhood: pes cavus, abnormally high-arched feet protein abnormalities such as PMP-22, MPZ, and nn Loss of muscle stretch reflexes distally connexin 32 nn Deficits in sensory functions of light touch, vibration, and pin prick sensation Treatment nn Superficial nerve trunks may be visually or palpably nn No direct treatment currently exists enlarged in some forms of the illness nn Ankle foot orthoses can improve stability in standing II: Polyneuropathies II: Testing and walking nn Physical and occupation therapy to maximize nn Motor nerve conduction studies most often show capabilities “demyelinating”-type abnormalities with prolongation nn Antineuropathic pain medications if paresthesias and of distal latencies and slowing of conduction velocities neuropathic pain are significant symptoms in leg and forearm segments of the nerves nn Distal latencies > 125% of the upper limit of normal, Prognosis conduction velocities < 70% of the lower limit of normal nn nn Axonal (CMT type 2) varieties show reduction Slow worsening over decades nn in response amplitudes but only mild slowing of Progression to a wheel chair–dependent state is conduction velocities uncommon nn Conduction block tends to not be found unless the patient has hereditary liability to pressure palsy Suggested Readings Amato A, Russell J. Neuromuscular Disorders. (pp 162–192). variant of neuropathy New York: McGraw Hill; 2008. nn Sensory conduction studies also become abnormal by Griffin J, Sheikh K. The Guillain-Barré Syndromes. In: showing prolonged distal latencies and reduction of Dyck PJ, Thomas PK, eds. Peripheral Neuropathy. 4th ed. response amplitudes (pp 2197–2219). Philadelphia, PA: Elsevier; 2005. Idiopathic Polyneuropathy John C. Kincaid MD

Description nn Neuropathy due to inflammatory connective tissue Sensory-motor polyneuropathy occurring in patients for diseases such as Sjögren’s syndrome whom an etiology has not been determined nn Genetic neuropathy when details of family history are limited Etiology nn Postgastric bypass-related neuropathy No etiology has been established despite an adequate nn Prior therapeutic radiation treatment workup. History nn Epidemiology Slow onset of numbness, paresthesias, and, at times, burning pain in the toes and feet About 30% of adults who develop polyneuropathy will nn Significant distal weakness or ataxia are usually not not have an etiology established. features of this type of neuropathy Pathogenesis Physical examination An axonal-type mechanism is presumed based on the nn Deficits in distal lower extremities in sensory characteristics of nerve conduction studies in this group modalities of light touch, vibration, pin prick, and hot of patients and cold sensation nn Mild symmetrical weakness of foot and distal lower Clinical Features extremity muscles may be present nn Insidious onset and slow progression is the most nn Loss of muscle stretch reflexes proportionate to the common pattern other clinical deficits nn A length-dependent sensory or sensory-motor pattern nn Toe and foot deformities suggestive of an inherited is expected etiology should be absent nn Reflex loss should be consistent with the clinical deficits Testing rather than being generalized when other clinical nn Biochemical and serological assessment, including deficits are still mild fasting glucose, renal function, hematologic nn Foot deformities such as hammer toes and pes cavus status, vitamin B12 level, serum and urine protein should not be present electrophoresis, connective tissue diseases, HIV, and nn Some patients will have a “small fiber neuropathy” hepatitis B and C pattern with abnormalities in pain and thermal nn Glucose tolerance testing should be considered if an sensory modalities only etiology remains unestablished nn Natural History Cerebrospinal fluid analysis will likely not be helpful and will be normal or show nonspecific abnormalities Onset over months to years with very slow progression such as mild elevation of protein over the following years is the most common pattern nn Conduction studies will usually show an “axonal” Diagnosis pattern of abnormality: motor and sensory response amplitudes are reduced if present, Differential diagnosis conduction velocities are no slower than the mid-30 nn Polyneuropathy related to glucose intolerance meters per second range and distal latencies remain nn Chronic inflammatory polyneuropathy normal nn Cervical or lumbar canal stenosis nn Needle EMG shows fibrillations and positive waves in nn Medication, toxin, or infection-related neuropathy foot and distal leg muscles along with abnormally large nn Neuropathy due to monoclonal gammopathy motor unit potentials in distal muscles

64 Idiopathic Polyneuropathy 65 nn Spinal cord magnetic resonance imaging (MRIs) do not Treatment show significant abnormalities of the neural foramina, nn Symptomatic treatment of paresthesias and neuropathic spinal canal dimensions, or the spinal cord parenchyma. pain nn Genetic screening and assessment for the presence of nn Continued neurological follow up antinerve antibodies should not be done unless the Prognosis clinical scenario is suggestive of an etiology in these

Most patients do not progress to significant levels of categories. impairment nn Nerve biopsy will usually not be helpful in establishing a specific diagnosis Suggested Readings nn Skin biopsy for quantitation of intraepidermal nerve Amato A, Russell J. Neuromuscular Disorders (pp. 361–370). fiber density should be considered if a “small fiber” New York: McGraw Hill; 2008. Hughes R, Umapathi T. A controlled investigation of the cause neuropathy pattern is present and the evaluation has of chronic idiopathic axonal polyneuropathy. Brain. 2004;127: II: Polyneuropathies II: not revealed a specific cause. (pp. 1723–1730). Medication-Induced Polyneuropathy John C. Kincaid MD

Description Natural History Acquired polyneuropathies arising as side effects from nn A pattern of subacute onset and progression, which medication usage then improves over months after exposure ends, is the most common syndrome Etiology nn The clinical pattern termed “coasting”, in which Disruption of cellular functions involved in the mainte- manifestations continue to worsen for several weeks nance of the axon and neuronal cell body after the exposure ends, can also be seen Epidemiology Most often encountered in patients undergoing treat- Diagnosis ment for cancer, cardiac arrhythmia, subacute to chronic Differential diagnosis infections, and rheumatologic disorders nn Acute to subacute polyneuropathy due to other Pathogenesis causes, such as Guillain-Barré, chronic inflammatory nn Disruption of axoplasmic transport neuropathy, porphyria, or spread of the neoplasm to nn Interference with mitochondrial and nuclear DNA the cranial nerves or nerve roots nn translation Spinal cord lesion due to an inflammatory process such nn Other incompletely understood mechanisms as transverse myelitis or the initial attack of multiple sclerosis Risk Factors nn Spinal cord compression due to spondylotic nn Exposure to any of the following medications, typically myelopathy or metastasis to the spinal column in a dose-related fashion: amiodarone, bortezomib, cis- or oxaliplantin, colchicine, cytosine arabinoside, History dapsone, etopside, chloroquine or hydroxychloroquine, nn Numbness, paresthesias, and pain beginning in the isoniazid, leflunomide, metronidazole, nitrofurantoin, toes and spreading proximally into the feet, legs, nucleosides for HIV, paclitaxel, phenytoin, pyridoxine and upper extremities over weeks to months during in excessive amounts, thalidomide and vincristine exposure to the medication nn Pre-existing inherited or diabetic polyneuropathy nn Weakness which evolves in a similar distal to may result in a more prominent neuropathy than proximal, lower and upper extremity pattern, to that attributable to medication exposure alone described for sensory dysfunction Clinical Features nn Length-dependent sensory-motor polyneuropathy Physical examination producing distal sensory loss, neuropathic pain, and nn Deficits in sensory function, such as light touch, weakness of toe and ankle musculature is the most vibration, pin prick and temperature sensations; more common manifestation prominent distally nn Sensory-only pattern of symptoms and signs such as nn Ataxia may be present if the sensory loss is severe paresthesia and ataxia may occur with medications nn Symmetrical weakness in distal muscles of the lower such as the platinum-based chemotherapeutic drugs and then upper extremities nn Subacute onset and progression related to cumulative nn Loss of muscle stretch reflexes in a length-dependent dosing is the most common clinical pattern but acute pattern onset can be seen, for example, nitrofurantoin exposure nn Deficits in cranial nerve function are uncommon nn Autonomic dysfunction manifesting as impaired and their presence suggests alternative bowel motility and urinary retention may occur with explanations such as spread of the neoplasm vincristine to the meninges

66 Medication-Induced Polyneuropathy 67

Testing nn Symptomatic management of the sensory nn Motor nerve conduction studies show reduced disturbances amplitudes of sensory and motor responses along with nn Physical and occupational therapy if significant motor mild slowing of conduction velocities in lower and and coordination deficits develop upper extremity nerves nn Reassurance that the deficits will likely improve over nn Distal latencies should remain normal and conduction months after the medication exposure ends block should not occur nn The latencies of the F-wave and H-reflex remain Prognosis normal or are only slightly prolonged, as long as they Improvement over months to about 2 years after expo- are still recordable sure to the medication ends nn Needle EMG may show fibrillations and positive waves if motor axons are affected. Abnormally large Suggested Readings II: Polyneuropathies II: motor unit potentials can occur months to years later Amato A, Russell J. Neuromuscular Disorders (pp. 323–349). as reinnervation occurs New York: McGraw Hill; 2008. Herskovitz S, Schaumburg H. Neuropathy caused by drugs. Treatment In: Dyck PJ, Thomas PK, eds. Peripheral Neuropathy. 4th ed. nn Neuroprotective agents that lessen the tendency for (pp. 2553–2583). Philadelphia, PA: Elsevier; 2005. development of the neuropathy do not yet exist Multifocal Motor Neuropathy John C. Kincaid MD

Description nn Sensory symptoms occur in some patients but tend to Acquired, autoimmune polyneuropathy, which produces be much less prominent than the motor dysfunction asymmetric dysfunction of multiple individual peripheral (Lewis-Sumner syndrome) nerves (multifocal), with motor deficits usually being nn Neuropathic pain is usually not a prominent feature predominant over sensory nn Autonomic dysfunction in a widespread fashion causing blood pressure, cardiac, or sphincter Etiology abnormalities does not occur nn Autoimmune process producing focal dysfunction of the myelin sheath and axons of multiple individual Natural History peripheral nerve trunks nn Spontaneous improvement is uncommon nn Classified by some as a variant of chronic nn Spread to additional individual nerves occurs over a inflammatory polyneuropathy many-month to many-year time frame

Epidemiology Diagnosis nn Annual incidence is 10 times less common than Differential diagnosis amyotrophic lateral sclerosis nn Amyotrophic lateral sclerosis, producing lower motor nn Male-female ratio of 3:1 neuron dysfunction nn Tends to occur in the adult age group nn Mononeuritis multiplex due to vasculitis affecting the vasa nervorum Pathogenesis nn Hereditary liability to pressure palsy due to genetic nn Autoimmune response against antigens thought abnormality in peripheral membrane protein (PMP)-22 to be localized to the peripheral myelin of motor axons History nn nn Humoral (antibody) mechanisms are thought to be the Motor dysfunction in a focal pattern: unilateral foot predominant mechanism, and serum immunoglobulin drop, wrist drop, elbow flexion M (IgM) antibodies directed against the GM1 nn Onset of individual lesions is usually insidious ganglioside component of the peripheral nerve are nn Spread to additional nerves occurs over months present in many patients with this syndrome nn Abrupt onset of paresthesias and neuropathic pain typical of vasculitic mononeuritis multiplex is not a Risk Factors prominent feature None have been identified nn Symptoms and signs of sensory dysfunction occur in some patients but tend to be much less prominent Clinical Features than the motor abnormalities nn Weakness, fasciculations, and cramping in multiple Physical examination individual peripheral nerve territories nn Focal weakness in multiple individual peripheral nn Muscle atrophy is present in cases of longer duration nerve territories nn Onset tends to be gradual and initially involves nn Atrophy can occur but early in the course of the a single nerve only, for example, radial, illness, weakness can be disproportionate to the musculocutaneous, or peroneal degree of atrophy nn Spread to other nerves in the same or other limbs nn Fasciculations can occur in the muscles of the affected occurs over months to years but evolution to a nerves symmetrical pattern of involvement is not typical nn Reflexes are reduced or absent in the affected nn Muscle stretch reflexes become abnormal in the nerves but generalized areflexia typical of chronic affected nerves but tend to not become diffusely inflammatory demyelinating polyradiculoneuropathy abnormal does not usually occur 68 Multifocal Motor Neuropathy 69 nn Signs of upper motor neuron dysfunction, as would nn Prophyria screen, vitamin B12 level, serum protein be expected in typical amyotrophic lateral sclerosis electrophoresis for monoclonal protein, especially IgM (ALS), are not present and serum glucose should be normal nn Deficits in light touch, vibration, and pin prick sensation may be found in the sensory territories of Treatment the affected nerves nn Immune-modulating therapy with intravenous infusion

of gamma-globulin is the mainstay of treatment Testing nn Ongoing treatment at monthly intervals for prolonged nn Motor nerve conduction studies show partial time frames may be required conduction block along the course of the affected nn Corticosteroids and plasma exchange do produce nerves, often at sites other than standard entrapment improvement or stabilization of this condition sites such as the ulnar at the elbow, the median at the nn Intravenous pulse cyclophosphamide may cause II: Polyneuropathies II: wrist, or peroneal at the fibular head improvement of the deficits nn Slowing of conduction velocity and prolongation nn The role of additional agents such as rituximab in the of distal latency is often present in affected nerves, long-term management of this condition remain to be whereas adjacent nerves remain electrically normal established nn Sensory conduction studies in the nerves showing nn Physical and occupational therapy to aid improvement motor abnormality can also become abnormal but are of function more often normal nn Needle EMG shows reduction of motor unit potential Prognosis recruitment early on while deficits present for many nn Spontaneous improvement is rare months produce signs of axonal damage such as nn Immune-modulating treatment should produce at fibrillation potentials and abnormally large voluntary least some improvement in up to 80% of patients, but motor unit potentials prolonged treatment may be required nn Cerebrospinal fluid protein tends to remain normal nn Sedimentation rate tends to remain normal nn Antibodies associated with peripheral vasculitides such Suggested Readings as polyarteritis nodosa or Wegener’s granulomatosis Amato A, Russell J. Neuromuscular Disorders (pp. 233–260). New York: McGraw Hill; 2008. should be absent Taylor B, Willison H. Multifocal motor neuropathy with nn S gM antibodies against the ganglioside GM1 or conduction block. In: Dyck PJ, Thomas PK, eds. Peripheral related components of peripheral myelin are present in Neuropathy. 4th ed. (pp. 2277–2298). Philadelphia, PA: 50% or more patients Elsevier; 2005. Neuropathy Due to Herpes Zoster (Shingles) John C. Kincaid MD

Description nn Most often only one cranial nerve sensory territory or Mononeuropathies and radiculopathies due to infection one spinal dermatome is unilaterally affected, the 5th with Herpes Zoster virus cranial and any of the thoracic levels being the more common sites Etiology nn Weakness in the associated myotome may be present Localized inflammatory process in sensory ganglion cells in up to 30% of patients and their peripheral axons resulting from reactivation of nn Up to 40% patients over 60 years may have persisting latent Herpes Zoster virus infection pain after the rash resolves: postherpetic neuralgia nn Lesions in the 5th cranial territory may be associated Epidemiology with a cerebral vasculitis, producing a stroke nn Occurs in patients who had prior infection with syndrome Herpes Zoster (Varicella or Chicken Pox) nn Lesions of the 7th nerve can produce Ramsay-Hunt nn Decades after the initial Varicella attack, reactivation syndrome: facial palsy and Herpetic rash in the of virus latent in sensory ganglia produces the attack external ear canal of Herpes Zoster nn Development of the typical pattern of pain without nn Attacks are 2 to 3 times more likely in otherwise appearance of the rash is possible: Zoster sine Herpete normal patients older than 60 years nn Attacks are more common in patients who Natural History have hematologic neoplasms or who are The dermatomal pain and skin rash resolve over about immunocompromised 4 to 6 weeks but patients older than 60 years may be left with pain, which does not improve. Pathogenesis nn Initial infection with Herpes Zoster occurs in Diagnosis childhood as Chicken Pox (Varicella) Differential diagnosis nn After resolution of the Chicken Pox, the virus persists nn Cervical, thoracic, or lumbar radiculopathy due to as a latent infection in the sensory neurons of cranial disk herniation and spinal nerves nn Idiopathic or postviral 7th nerve palsy nn The virus can reactivate when cell-mediated nn Trigeminal neuralgia immunity becomes compromised by age, nn Diabetic truncal neuropathy physiological stress, cancer, autoimmune disease, nn Carcinomatous meningitis producing cranial and or therapeutic immune suppression spinal nerve root lesions nn Genital Herpes outbreak if the pain and cutaneous Risk Factors lesion occurs in the perineal area nn Age over 60 years nn Compromise of normal immune function by History underlying disease or immune suppressive treatment nn Abrupt, unprovoked onset of persistent pain in a cranial nerve or spinal nerve root pattern Clinical Features nn Vesicular rash in the area of pain appearing days to a nn Dermatomal pain lasting 4 to 6 weeks week after pain onset nn Vesicular skin rash in the affected dermatome nn Localized weakness may occur in muscles supplied by appearing days to about 2 weeks after onset of the pain the affected nerve, including the abdominal wall

70 Neuropathy Due to Herpes Zoster (Shingles) 71

Physical examination nn Oral steroids along with the antiviral agents may nn Unilateral vesicular rash corresponding to the sensory lessen the tendency to develop postherpetic neuralgia territory of the affected cranial or spinal nerve: up to but the literature in support for this is not strong. three adjacent dermatomes may be affected nn The pain of the initial attack and of postherpetic nn Weakness in myotome of the affected nerve neuralgia may improve with antineuropathic Testing pain medications such as gabapentin, pregabalin, amitriptyline, analgesics, and topical lidocaine nn The diagnosis is usually able to be established by the patches. history and examination nn Brain and spinal magnetic resonance imaging (MRI) to evaluate for alternative causes of the clinical deficits Prognosis nn Sensory and at times motor nerve conduction studies nn In most patients, the pain and rash resolves within and needle EMG will be abnormal in the affected 2 months II: Polyneuropathies II: nerves, if those are accessible for testing nn Those with pain persisting beyond approximately 2 months will have persisting pain and sensory Treatment disturbances in the territory of the affected nerve Antiviral treatment may shorten the intensity and dura- tion of the attack: Suggested Readings nn Acyclovir 800 mg orally five times daily for 7 days Glidden D, Tyler K. Herpes virus infection and peripheral ­neuropathy. In: Dyck PJ, Thomas PK, eds. Peripheral nn Valacyclovir 1000 mg orally three times daily or Neuropathy. 4th ed. (pp. 2117–2127). Philadelphia, PA: famciclovir 500 mg three times daily for one week Elsevier; 2005. are alternative treatments but are about six times as Hirsch M. Herpes virus infections. In: Nabel E, ed. ACP Medicine expensive as acyclovir [Section 7, Ch XXVI]. Hamilton, ON, Canada: Decker; 2013. Neuropathy Due to Leprosy John C. Kincaid MD

Description Natural History Peripheral neuropathy syndromes occurring in patients nn Stabilization of the number of individual lesions may who have leprosy occur in the Tuberculoid variety of the disease, but progression occurs in the Lepromatous form Etiology Infection with Mycobacterium leprae Diagnosis Differential diagnosis Epidemiology Multiple mononeuropathy due to other causes, such as nn Rare syndrome in the United States, Canada, and diabetes, vasculitis, inherited liability to pressure palsy, Europe. Approximately 100 new cases per year in the neurofibromatosis, and Wartenburg’s sensory neuritis United States, which occur in immigrants from endemic areas such as India, Brazil, Nepal, and Mozambique History nn Insidious onset of patchy skin lesions, which produce Pathogenesis sensory loss within the area of involvement nn The bacterium infects the skin and then spreads to the nn Individual lesions may progress to involvement of Schwann cells of the peripheral nerves and produces individual territories such as the ulnar peroneal, deficits, most often in cooler body areas such as the greater auricular ear lobes, , knees, and lateral shins nn Neuropathic pain is not a feature and would be nn Resulting local inflammation may cause segmental expected in lesions due to vasculitis enlargement of the nerves, whereas demyelination of Physical examination nerves further enhances sensory deficits nn Patchy, multifocal skin lesions with raised, Risk Factors erythematous borders and hypopigmented nn Exposure to the bacterium, most often through nasal centers nn secretions of infected patients and less often via Loss of sensation in the center of these lesions nn skin-to-skin contact Larger areas of sensory loss and motor deficit can nn Patients who develop leprosy are thought to have a occur corresponding to individual nerve trunks nn genetically based deficit in cell-mediated immunity Nerves may become visually or palpably enlarged nn A multiple mononeuropathy or polyneuropathy Clinical Features pattern of involvement can occur in advanced infection characteristic of the Lepromatous form of nn Leprosy occurs in three forms: Tuberculoid in which the disease. skin lesions are present but infrequent, Lepromatous in which skin lesions are widespread, and Borderline Testing Lepromatous, which falls in between nn Skin biopsy of lesions in the Tuberculoid form shows nn In each of these forms, discrete areas of granuloma formation, presence of helper T cells and hypopigmented, anesthetic skin occur few bacilli nn The paucity or abundance of the lesions defines the nn Skin biopsy of lesions in the Lepromatous form shows type of leprosy the absence of granuloma formation, absence of helper nn Motor deficits may occur when the main nerve trunks T cells but the presence of suppressor T cells and are involved abundant bacilli nn Local anesthesia secondary to the nerve involvement nn When an individual nerve trunk is clearly abnormal, can allow trauma to the toes and fingers to be biopsy shows inflammation and the presence of undetected and result in mutilation of the affected areas bacilli

72 Neuropathy Due to Leprosy 73 nn Nerve conduction studies show reduction of sensory Prognosis and motor response amplitudes in individual nn Stabilization of the pattern of involvement but deficits peripheral nerves may persist long term

Treatment Suggested Readings nn Tuberculoid form: rifampin 600 mg once per month Leonard M, Blumberg H. Infections due to Mycobacterium

and dapsone 100 mg daily for 6 months leprae and nontuberculous mycobacteria. In: Nabel E, ed. nn Lepromatous and borderline Lepromatous forms: rifampin ACP Medicine. (Section 7, Chapter XXXIX). Hamilton, ON, 600 mg once per month, clofazimine 300 mg once per Canada: Decker; 2013. Sabin T, Swift T, Jacobson R. Neuropathy associated month, and dapsone 100 mg daily for 12 months with ­leprosy. In: Dyck PJ, Thomas PK, eds. Peripheral nn Insensate areas such as finger, toes, and feet, may Neuropathy. 4th ed. (pp. 2081–2108). Philadelphia, require protective splinting PA: Elsevier; 2005. II: Polyneuropathies II:

Polyneuropathy Due to Chemical Toxins and Metals John C. Kincaid MD

Description Clinical Features Polyneuropathy due to exposure to hexacarbons, arsenic, For lead-related neuropathy: lead, and thallium (also see the chapter on “Medication- nn Abdominal pain with constipation Induced Polyneuropathy”) nn Motor deficits, beginning in finger extensors then Etiology wrist extensors and then intrinsic hand muscles; lower extremity deficits manifest later Exposure to these chemical agents appears to disrupt cel- nn Sensory deficits are not prominent or do not occur lular functions involved in maintenance of the axon Schaumburg has suggested the following criteria For arsenic- and thallium-related neuropathy: to support the relationship of a suspected toxin to the nn Acute gastrointestinal illness followed several days neuropathy: to a week later by onset of distal lower and upper nn A characteristic clinic picture should be present extremity paresthesias followed by distal weakness nn A definite and dose-related exposure should be nn Skin changes of sloughing and then present hyperpigmentation of the palms and soles occur in nn The neuropathy should be reproducible in arsenic toxicity experimental animals nn Alopecia is a feature of thallium toxicity but may not be apparent for 2 to 3 weeks after exposure Epidemiology nn Mees’ lines occur in the fingernails and toe nails with Polyneuropathy due to any of these agents is profoundly exposure to arsenic or thallium rare but knowledge of their clinical presentation and For hexacarbon-related neuropathy: evaluation is important in differential diagnosis. nn Gradual onset of numbness in the toes, feet, and fingers Pathogenesis nn Distal weakness may appear with continued exposure The mechanism of action of each of these agents is not well established for the nervous system or other organ Natural History manifestations. nn Long-term improvement occurs with elimination of exposure Risk Factors nn The clinical pattern of “coasting” in which nn Exposure to hexacarbons (n-hexane or methyl n-butyl manifestations continue to worsen for several ketone) occurs in either an industrial setting in weeks to about 4 months after the exposure ends which factory or workshop ventilation is inadequate can also be seen or in a personal setting of sniffing (or huffing) glue, gasoline, hair spray, brake cleaner, or other similar Diagnosis products nn Exposure to arsenic and thallium most often Differential diagnosis currently occur in the setting of attempted suicide or nn Acute polyneuropathy due to other causes, such homicide as Guillain-Barré syndrome, medication reaction, nn Exposure to lead occurs in battery and other porphyria lead-containing product manufacturing, lead nn Spinal cord lesion due to an inflammatory process smelting, and perhaps lead ammunition remaining in such as transverse myelitis or the initial attack of the body after a gun shot multiple sclerosis

74 Polyneuropathy Due to Chemical Toxins and Metals 75

History nn Urine arsenic levels: normal <25 µg/dL in 24 hours or nn Validating exposure to the agent may require <125 µg/dL for fish eaters investigation by the physician nn Arsenic levels in hair or finger nails: <1 µg/g nn The historical details specific to each agent are given nn For all other than lead toxicity: motor nerve in the Clinical Features section conduction studies show reduced amplitudes of sensory and motor responses along with mild slowing

Physical examination of conduction velocities in lower and upper extremity For neuropathy due to lead toxicity: nerves nn Weakness of finger and wrist extensors, intrinsic hand nn Needle EMG may show fibrillations and positive muscles, and distal leg muscles waves and reduced motor unit potential recruitment nn Sensation tends to remain normal in the acute setting nn Mees’ lines on fingernails and toenails II: Polyneuropathies II:

Treatment For the other agents: nn Elimination of exposure to the toxic agent nn Deficits in sensory function such as light touch and nn The role of chelation therapy in patients with arsenic, vibration more so than pin prick and temperature lead, and thallium exposure is not fully established sensations in the toes, feet, and fingers nn Symptomatic management of the sensory nn Symmetric weakness in distal muscles of the lower disturbances and then upper extremities nn Physical and occupational therapy if significant motor nn Loss of muscle stretch reflexes in a length-dependent and coordination deficits develop pattern nn Mees’ lines, palmar hyperpigmentation, and alopecia Prognosis in thallium toxicity Improvement over months after exposure to the caus- ative agent ends. Testing nn Hemoglobin and hematocrit levels for anemia Suggested Readings nn Red cell morphology for basophilic stippling in lead Berger A, Schaumburg H. Neuropathy associated with and arsenic toxicity industrial agents, metals and drugs. In: Dyck PJ, Thomas PK, eds. Peripheral Neuropathy. 4th ed. (pp. 2505–2525). nn Serum levels for lead: normal <40 µg/dL or Philadelphia, PA: Elsevier; 2005. <70 µg/dL for industrial workers Windebank A. Metal neuropathy. In: Dyck PJ, Thomas PK, eds. nn Urine lead levels: normal <100 µg/dL in 24 hours Peripheral Neuropathy. 4th ed. (pp. 2527–2551). Philadelphia, or <300 µg/dL for industrial workers PA: Elsevier; 2005. Polyneuropathy Due to Nutritional Deficiency John C. Kincaid MD

Description Natural History Acquired polyneuropathy occurring in patients who develop nn Develops over months to years deficiencies in vitamins or other metabolic factors essential nn Does not improve without treatment for the maintenance of nerve structure and function Diagnosis Etiology Differential diagnosis Most often encountered in patients who have inadequate nn Diabetic polyneuropathy intake or inadequate absorption of the essential factor nn Chronic inflammatory polyneuropathy nn Cervical or lumbar canal stenosis Epidemiology nn Idiopathic sensory-motor polyneuropathies Occurs most often in alcoholism, prolonged vomiting, History following gastric bypass for weight loss, or in very restric- nn Slow onset of numbness, paresthesias, and burning tive diets pain of the toes, feet, and at times fingers nn Unsteady balance Pathogenesis nn Weakness of distal leg and at times finger muscles nn Deficiency of thiamine (B1), pyridoxine (B6), cobalamin (B12), alpha-tocopherol (E), or copper can Physical examination alter the metabolism of peripheral and at times central nn Distal lower and at times upper extremity deficits in axons sensory function, such as light touch, vibration, and nn Excessive intake of pyridoxine can also produce pin prick sensation polyneuropathy nn Loss of muscle stretch reflexes at the ankle nn Symmetric weakness of distal lower and, at times, Risk Factors distal upper extremity muscles nn nn Extensive gastrointestinal surgery, including gastric Signs of upper motor neuron dysfunction may also be bypass for weight loss present in cobalamin and copper deficiency nn Alcoholism Testing nn Antitubercular treatment with isoniazid increases nn Conduction studies show an “axonal” pattern of demand for pyridoxine abnormality: motor and sensory response amplitudes nn Excessive use of pyridoxine can also produce are reduced if present, conduction velocities are no polyneuropathy slower than the mid-30 meters per second range, and distal latencies remain normal Clinical Features nn Needle EMG shows fibrillations and positive waves in nn Slow onset foot and distal leg muscles along with abnormally large nn Sensory symptoms, which initially appear in the motor unit potentials in distal muscles distal lower extremities and migrate proximally if the nn Cerebrospinal fluid values tend to be normal condition worsens nn Spinal cord magnetic resonance imaging (MRI) does nn Weakness in distal lower and at times upper extremity not show significant abnormalities of the canal or muscles spinal cord parenchyma nn Ataxia nn Vitamin level testing

76 Polyneuropathy Due to Nutritional Deficiency 77

Treatment Suggested Readings nn Dietary supplementation of the deficient element Amato A, Russell J. Neuromuscular Disorders (pp. 303–311). nn Reduction or elimination of alcohol intake New York: McGraw Hill; 2008. nn Saperstein D, Barohn R. Neuropathy associated with nutritional Symptomatic treatment of paresthesias and neuropathic and vitamin deficiencies. In: Dyck PJ, Thomas PK, eds. pain Peripheral Neuropathy. 4th ed. (pp. 2051–2062). Philadelphia, nn Symptomatic management of ataxia PA: Elsevier; 2005.

Prognosis nn Some improvement over months to about 2 years II: Polyneuropathies II:

Polyneuropathy Due to Vasculitis John C. Kincaid MD

Description Natural History Peripheral neuropathy syndrome occurring most often nn Progressive worsening over weeks to months in a pattern of sequentially developing multiple mono- nn Spontaneous remission is not typical neuropathies Diagnosis Etiology Differential diagnosis Autoimmune vasculitis affecting the vasa nervorum nn Other acute to subacute progressive polyneuropathies Epidemiology such as Guillain-Barré syndrome or chronic inflammatory neuropathy Rare syndrome approximately five cases per 100,000 nn Multifocal motor neuropathy population per year nn Hereditary liability to pressure palsy nn Pathogenesis Brachial or lumbosacral plexopathy producing bilateral abnormality nn Vasculitis affecting arteries and capillaries, including those of the vasa nervorum, become involved due to History an inflammatory response nn Abrupt onset of mononeuropathic-type sensory and nn Other organ systems such as the sinuses, lungs, motor deficits, which progress in a stepwise fashion gastrointestinal tract, and kidneys may be involved to involve additional nerves in other limbs, the trunk concurrently, depending on the specific immune and at times, the cranial region responses nn Neuropathic abnormalities most often occur as part of nn Infectious processes such as hepatitis B or C or HIV a syndrome involving other organ systems, such as the may trigger the vasculitis sinuses, lungs, gastrointenstinal tract, kidneys, joints, nn May occur as a component of systemic lupus and skin, but the neuropathic manifestations may erythematosus (SLE), rheumatoid arthritis (RA), occur in isolation (nonsystemic vasculitic neuropathy) Sjögren’s syndrome or systemic sclerosis Physical examination nn Risk Factors Patchy, multifocal deficits in motor and sensory function, which correspond to individual peripheral nn Other autoimmune conditions such as SLE or RA nerve territories nn Hepatitis B or C infections nn Evidence of sinus, pulmonary, joint, and cutaneous Clinical Features involvement may be present, depending on the specific diagnosis nn Sensory disturbance with neuropathic pain and paresthesias occurring in a patchy, stepwise, Testing progressive (multiple mononeuropathic) pattern over nn Nerve conduction studies show reduction of sensory a many-week to several-month time frame and motor response amplitudes in individual nn Motor deficits that occur in the same stepwise pattern peripheral nerves with adjacent nerves initially nn Evolution to a symmetric pattern of involvement remaining normal may occur as additional individual nerves become nn Conduction velocities in affected nerves tend to involved remain normal or be only mildly slowed in an “axonal” nn Onset in a symmetrical pattern of involvement rather pattern of abnormality than the more typical progressive multi-focal one may nn Needle EMG shows denervation in muscles of the also occur affected nerves

78 Polyneuropathy Due to Vasculitis 79 nn Test for elevation of sedimentation rate, presence nn Symptomatic management of paresthesias and of antineutrophil cytoplasmic antibodies (p or c), neuropathic pain by antiepileptic, antidepressant, and cryoglobulinemia, and antibodies or antigens for at times analgesic medications hepatitis B or C nn Assessment of sinuses, pulmonary, gastrointestinal, Prognosis and renal systems to identify concurrent involvement nn Stabilization of the pattern of involvement is the nn Biopsy of a cutaneous nerve: sural, superficial peroneal, initial indication of responsiveness of the or radial, demonstrated to be abnormal by clinical condition examination or nerve conduction study to evaluate for nn Improvement in the motor and sensory deficits presence of vasculitis over months is expected, but motor, sensory, nn Biopsy of muscle in an abnormal nerve territory may and neuropathic pain deficits may persist increase the yield for diagnosis of vasculitis long term II: Polyneuropathies II:

Treatment Suggested Readings nn Immune modulation with corticosteroids, 1 mg/kg daily Amato A, Russell J. Neuromuscular Disorders (pp. 261–270). New York: McGraw Hill; 2008. nn Concurrent use of a nonsteroidal agent such as Collins M, Kissel J. Neuropathies with systemic vasculitis. cyclophosphamide given as monthly intravenous In: Dyck PJ, Thomas PK, eds. Peripheral Neuropathy. 4th ed. pulses improves the long-term course of the illness (pp. 2335–2404). Philadelphia, PA: Elsevier; 2005. Polyneuropathy in Diabetes Mellitus John C. Kincaid MD

Description nn Tight control of blood sugars lessens the tendency for Syndrome of symmetrical length-dependent polyneu- progression in type 1 diabetes ropathy, which occurs in patients with diabetes mellitus or in “prediabetic” states Diagnosis Differential diagnosis Etiology nn Plantar fascitis Alteration in the microenvironment of the peripheral nn (bilaterally) axons due to altered glucose metabolism nn Interdigital neuroma (Morton’s neuroma) bilaterally nn Other causes of polyneuropathy Epidemiology nn Produces symptoms in approximately 20% of diabetics History with disease duration of over 10 years nn 25% to 30% may be asymptomatic and the neuropathy nn Is present in approximately 50% of that same only be identified during physical examination or population based on physical examination and neurophysiological testing for another condition such neurophysiological assessment as lumbar radiculopathy nn Numbness in the toes, which progresses proximally Pathogenesis over years nn Accumulation of osmotically active sugars in the nn Pain and allodynia in the feet with or without other axons or Schwann cells (polyol pathway) disturbances of sensation nn Alteration of protein function by glycosylation nn Asymmetric involvement of the lumbosacral plexus nn Disturbance of microvascular functions in the peripheral and/or the thoracic or upper lumbar truncal nerves nerves may occur independent of the polyneuropathy (see the chapter on “Lumbosacral Plexopathy”) Risk Factors nn Autonomic dysfunction as manifest by erectile nn Persistently poor control of serum glucose dysfunction, impaired sweating in the distal limbs, nn Metabolic syndrome orthostatic hypotension, and disturbed gastrointestinal nn Impaired glucose tolerance without frank hyperglycemia motility Physical examination Clinical Features nn Decreased sensation to vibratory, light touch, pin nn Abnormal sensation in the toes, feet, distal legs, and prick, or monofilament-type stimuli in toes and distal fingers: numbness, tingling, pins, and needles in a aspect of the feet symmetrical pattern nn Absence of ankle muscle stretch reflexes nn Pain in the toes and feet (less common than the nn Weakness of toe abduction, flexion, or extension abnormal sensations listed earlier) with characteristics motions such as “deep in the bone” pressure, surface burning, nn Weakness of ankle extension and flexion plus weakness short sharp jabs of knife-like pain of intrinsic hand muscles in more severe cases nn Allodynia (painful sensation provoked by a nonpainful stimulus such as bed sheets), especially in the tips of Testing the toes nn Nerve conduction studies show reduction of sensory nn Ankle and hand weakness in more advanced cases response amplitudes in distal leg/foot nerves initially and then reduction of motor response amplitudes Natural History later. Conduction velocities become slowed but remain nn Slow worsening over years manifested by more above 70% of the low limit of normal, and distal proximal spread of the abnormal sensations latencies tend to not be abnormally prolonged.

80 Polyneuropathy in Diabetes Mellitus 81 nn Similar abnormalities may appear in hand nerves if Prognosis the overall condition worsens over the years nn Stable to slowly worsening symptoms and signs of the nn Abnormalities in autonomic control of the heart neuropathy (cardiovagal) as demonstrated by heart rate with deep nn Neuropathic pain, which begins after treatment of breathing testing hyperglycemia begins, may improve over months if improved sugar control is maintained Treatment nn Optimal control of serum glucose Suggested Readings Llewelyn J, Tomlinson D, Thomas P. Diabetic neuropathies. nn Daily visual inspection of the soles In: Dyck PJ, Thomas PK, eds. Peripheral Neuropathy. 4th ed. nn Symptomatic management of paresthesias and (pp. 2197–2219). Philadelphia, PA: Elsevier; 2005. neuropathic pain by antiepileptic, antidepressant, and Rajabally Y. Neuropathy and impaired glucose tolerance: An at times analgesic medications updated review of evidence. Acta Neurol Scand. 2011;124:1–8. II: Polyneuropathies II:

Polyneuropathy in Lyme Disease John C. Kincaid MD

Description Natural History Mononeuropathies and polyneuropathies due to infec- The initial cutaneous and systemic manifestations im­prove, tion with Borrelia (B.) burgdorferi. but the patient may develop longer-term effects such as The name Lyme is based on the features of the condi- arthritis, persistent fatigue, and encephalopathy. tion being characterized on a group of patients from the Diagnosis Lyme, Connecticut region. Differential diagnosis Etiology nn Idiopathic 7th nerve palsy Inflammatory process due to either direct invasion of nn Acute cervical, thoracic, or lumbar radiculopathy the affected nerves by the infectious agent or an immune nn Viral meningitis response against the agent, which attacks the myelin and nn Carcinomatous meningitis producing cranial and axons of peripheral nerve trunks or nerve roots. spinal nerve root lesions nn Autoimmune conditions producing multisystem Epidemiology symptoms and signs nn Occurs in specific regions of North America and History Europe: States of the New England area, Wisconsin, nn Development of an isolated skin lesion with features of Minnesota, and Northern California erythema migrans in concert with experiencing a tick nn May to August occurrence pattern bite a few days to a few weeks previously nn Onset of unilateral or bilateral 7th nerve palsy, Pathogenesis headache, or painful radiculopathy several weeks after nn Infection with B. burgdorferi and resulting humoral appearance of the skin lesion and cell-mediated immunological reaction to the agent nn Multijoint arthritis, especially in the knees, appearing nn The relative roles of direct invasion by the infectious several months after the skin lesion agent versus immune responses against it in the nn Late effects such as fatigue and cognitive impairment pathogenesis of the neurologic lesions has not been in a small percent of patients fully established. Physical examination Risk Factors nn Red papular lesion appearing about 1 week after the nn Living in or visiting an area of endemic infection tick bite, which enlarges over the next few days in a during the late spring to early fall red ring border-clear center nn nn Being bitten by a tick—typically Ixodes scapularis Unilateral or bilateral 7th nerve deficit nn (deer tick) or other Ixodes species—which carry Asymmetric “radicular” weakness and sensory loss B. burgdorferi with or without cranial nerve deficits nn Acute to subacute multijoint arthritis, especially in the Clinical Features knees nn Red papular skin lesion (erythema migrans) appearing Testing 7 to 10 days after the tick bite, which enlarges over nn Serology: Two-step testing of the antibody response days to a few weeks against B. burgdorferi antigens (note: these may be nn Low-grade fever, arthralgias, headache, and malaise negative in the first 2 weeks after onset) may occur while the skin lesion is present ––Enzyme-linked immunosorbent assay (ELISA) or nn 15% of patients develop signs of more clear cut immunofluorscence assay (IFA) for IgM and IgG neurologic involvement in the first 3 months after the antibodies tick bite: meningitis, cranial neuropathy, radiculitis ––If ELISA or IFA assay is positive, perform Western nn 10% develop cardiac arrhythmia in the first few immunoblot test for antibodies months of the illness ––If both are positive, infection has occurred 82 Polyneuropathy in Lyme Disease 83 nn Cerebrospinal fluid testing may show pleocytosis but nn Patients with arthritis: Oral antibiotics as listed above normal glucose levels for 2 months nn Motor and sensory nerve conduction studies show an “axonal” pattern of abnormalities in the affected nerves Prognosis nn With appropriate antibiotic treatment, the Treatment majority of patients resolve the systemic, neurologic, nn Patients with erythema migrans only: Oral and rheumatologic manifestations of the disease amoxicillin 500 mg tid, doxycycline 100 mg bid or cefuroxime axetil 500 mg bid for 2 to 3 weeks with Suggested Readings immune-modulating therapy by plasma exchange or Said G. Lyme disease. In: Dyck PJ, Thomas PK, eds. Peripheral Neuropathy. 4th ed. (pp. 2109–2116). Philadelphia, PA: intravenous infusion of gammaglobulin shortens the Elsevier; 2005. duration of the deficits by 30% to 50% Tompkins D, Luft B. Lyme disease and other spirochetal nn Polyneuropathies II: Patients with facial palsy as a component of Lyme ­zoonoses., In: Nabel E, ed. ACP Medicine. [Section 7, disease: Oral antibiotics as listed above for 30 days Chapter VII]. Hamilton, ON, Canada: Decker; 2013. Polyneuropathy Related to HIV Infection John C. Kincaid MD

Description nn Syndrome 3: Abrupt to subacute onset of lower Several syndromes of polyneuropathy or polyradiculopa- extremity motor and sensory dysfunction as well as thy can occur in patients infected with HIV bowel/bladder dysfunction is typical of the CMV-related polyradiculitis, which occurs late Etiology in the course, when AIDS has developed Infection with HIV and resulting alteration of immune- mediated responses, which then secondarily involve the Natural History peripheral nervous system nn Syndrome 1: Course typical for Guillain-Barré syndrome, including the response to customary therapies Epidemiology nn Syndrome 2: Slowly worsening deficits over years 20% to 30% of HIV-infected patients develop a clinically manifested by more proximal spread of the abnormal evident peripheral neuropathy related to the primary sensations condition or the treatment thereof. A higher percentage of nn Syndrome 3: Persisting, severe deficits, which only patients will be found to have neuropathy based on clinical partially respond to antiviral treatment and electrophysiological examinations rather than based on symptoms alone. Diagnosis Pathogenesis Differential diagnosis nn The virus does not directly infect the peripheral nerves nn Other acute to chronic peripheral neuropathies nn Syndrome 1: Immune response at the time of initial nn Polyneuropathy related to the medications used to infection is likely the cause of the Guillain-Barré-type treat the HIV infection neuropathy, which can occur early in the course of the nn due to transverse myelitis, multiple infection sclerosis, spondylosis, epidural abscess, or late HIV nn Syndrome 2: Immune response against the virus is the infection likely cause of the sensory-motor and often painful History neuropathy encountered late in the course of HIV nn Syndrome 1: Acute neuropathy developing over days infection when AIDS develops to about 4 weeks, with motor and sensory deficits nn Syndrome 3: Immune deficiency occurring in typical of Guillain-Barré syndrome advanced stages of the illness allows opportunistic nn Syndrome 2: Chronically evolving length-dependent infections with cytomegalovirus (CMV) to develop sensory, and to a much lesser degree motor dysfunction, and produce lumbosacral polyradiculitis which occurs late in the course of HIV infection or in Risk Factors its treatment with antiretroviral medications nn Infection with HIV virus nn Syndrome 3: Acute to subacute evolution of lower nn Lack of adequate antiretroviral treatment extremity weakness and sensory loss in the legs, accompanied by loss of urinary and rectal sphincter Clinical Features control nn Syndrome 1: Abrupt to subacute onset of motor and Physical examination sensory deficits in the lower and upper limbs is typical of Guillain-Barré syndrome, which occurs early in the Syndromes 1 and 2 course of HIV infection nn Decreased sensation to vibratory, light touch, pin nn Syndrome 2: Gradual onset of abnormal sensation prick, or monofilament-type stimuli in toes and distal in the toes, feet, distal legs, and fingers: numbness, aspect of the feet tingling, pins, and needles plus neuropathic pain is nn Absence of ankle muscle stretch reflexes typical of this neuropathy, which occurs later in the nn Weakness of toe abduction, flexion, or extension course of the infection when AIDS has developed motions

84 Polyneuropathy Related to HIV Infection 85 nn Weakness of ankle extension and flexion plus weakness nn Syndrome 3: Lower extremity conduction studies of intrinsic hand muscles in more severe cases show the pattern of a preganglionic lesion with motor Syndrome 3 studies showing low amplitude responses and only mildly slowed velocities. Sensory responses may nn Exam findings are those of a cauda equina syndrome remain normal. Needle EMG shows denervation in nn Loss of sensation in the feet, legs, and perineal area nn lower extremity muscles as well as the lumbar and

Weakness in foot and leg muscles, plus weakness of possibly the lower thoracic paraspinal muscles. CSF sphincters analysis shows elevated white blood cells; protein and nn Loss of reflexes in the legs glucose may be low Testing nn HIV antibody, HIV ribonucleic acid (RNA) titer (viral Treatment load), and CD4 count nn Syndrome 1: Same as Guillain-Barré syndrome not II: Polyneuropathies II: nn Hepatitis B antigen and antibody and hepatitis C related to HIV infection antibody nn Syndrome 2: Optimal antiretroviral treatment of the nn Fasting glucose and vitamin B12 levels HIV infection and symptomatic treatment of the nn Cerebrospinal fluid (CSF) analysis: Syndromes 1 and paresthesias and neuropathic pain; consider altering 3 show protein elevation typical of Guillain-Barré antiretroviral medications for 2 to 3 months to syndrome but also show an elevated white cell count distinguish neuropathy from HIV versus nn CSF viral cultures may be positive for CMV in medication-related etiology syndrome 3 nn Syndrome 3: CMV antivirals and rehabilitative nn Syndrome 1: Nerve conduction studies show a management of the resulting paraplegia “demyelinating pattern” with conduction velocity slowing below 70% of the low limit of normal and Prognosis distal latency prolongation beyond 125% of the upper nn Syndrome 1: Course typical of Guillain-Barré limit of normal. Lower and upper extremity nerves are syndrome not related to HIV infection involved nn Syndrome 2: Persistent to slowly worsening sensory nn Syndrome 2: Nerve conduction studies show an and motor deficits “axonal pattern” consisting of reduction of sensory nn Syndrome 3: Persistent, often severe, deficits in lower response amplitudes in distal leg/foot nerves initially extremity and sphincter dysfunction and then reduction of motor response amplitudes later. Conduction velocities become slowed but Suggested Readings remain above 70% of the low limit of normal and Amato A, Russell J. Neuromuscular Disorders (pp. 295–298). New York: McGraw Hill; 2008. distal latencies tend to not be abnormally prolonged. Hoffmann C, Gallant J. In: Nabel E, ed. ACP Medicine. [Section 7, Upper extremities show lesser degrees of abnormality Ch XXXIII]. Hamilton, ON, Canada: Decker; 2013. Porphyric Neuropathy John C. Kincaid MD

Description nn Acute onset of abdominal pain, which may simulate Acute and potentially recurring polyneuropathy due to an acute abdomen the metabolic disorder porphyria nn Psychiatric disturbance manifesting as agitation; hallucinations which appear in the same time frame Etiology as the abdominal pain Genetic abnormalities in the pathway for the hepatic nn Encephalopathy manifesting as seizures and at times synthesis of heme cause episodic overproduction of neu- coma rotoxic intermediate components of heme nn Peripheral neuropathy, which begins several days after the abdominal pain Epidemiology nn Sun sensitivity in hereditary coproporphyria and nn A very rare disorder in North America but knowledge variegated types, which produce blistering in sun of the condition is important due to it being frequently exposed areas considered in the differential diagnosis of acute neuropathy Natural History nn Dominant inheritance pattern with a gene prevalence nn Ten percent of attacks can be fatal of between 1 in 1,000 to 100,000 in the white nn The neuropathy improves over weeks to months after population for the acute intermittent variety of the acute attack but permanent deficits may occur porphyria and 1 in 3000 in South African population where the variegated variety is most often encountered Diagnosis Differential diagnosis Pathogenesis nn Guillain-Barré syndrome Genetic abnormality in three enzymes of the hepatic nn Drug-induced neuropathy: chemotherapy, heme synthesis pathway cause the porphyria syndromes nitrofurantoin exposure that can produce peripheral neuropathy nn Acute spinal cord syndrome: transverse myelitis or nn Porphobilinogen deaminase in the acute intermittent midline disk herniation form History nn Coproporphyrinogen oxidase in hereditary nn Abrupt onset of abdominal pain coproporphyria nn Psychiatric disturbances concurrent with or shortly nn Protoporphyrinogen oxidase in variegate prophyria following the onset of abdominal pain nn Abrupt onset of peripheral neuropathy with Risk Factors features of: Having the genetic mutation and encountering biological ––Initial proximal predominance of the motor deficits, conditions, which trigger overproduction of the prophy- which may worsen over the course of days; rin intermediates ––Cranial nerve involvement; and nn Medications which induce the cytochrome P450 system ––Autonomic dysfunction with sympathetic nn Fluctuation in gonadal hormone levels overactivity, urinary hesitancy, and constipation nn nn Biological or psychological stress Sensitivity to sun exposure with resulting blistering in nn Nutritional deprivation, which alters glucose metabolism the hereditary coproporphyria and variegated types Physical examination Clinical Features nn Weakness which may be asymmetric initially but nn Relapsing attacks which begin in late adolescence and which may progress to generalized involvement, early adulthood including the respiratory muscles

86 Porphyric Neuropathy 87 nn Loss of muscle stretch reflexes proportionate to the nn Spinal cord or brain magnetic resonance imaging (MRI) pattern of weakness rather than the early generalized does not show significant anatomical abnormalities loss of reflexes typical of Guillain-Barré syndrome nn Assay immediate family members for the presence of nn Deficits in limb and truncal sensory function such the biochemical abnormality as light touch, vibration, and pin prick sensation are present if the patient’s sensorium allows reliable Treatment examination nn Supportive care, including respiratory support nn Blistering skin lesions in sun exposed areas nn Elimination of potentially provocative medications Testing (see the second reference for a comprehensive list and also visit www.porphyriafoundation.com) nn Assay of urine for presence of abnormally high nn Morphine can be used for the abdominal pain concentrations of heme synthesis products: nn Haloperidol can be used to treat agitation ––Aminolevulinic acid nn Polyneuropathies II: Propofol can be used to treat seizures ––Porphobilinogen nn Intravenous glucose administration (300–500 g/24 hrs) nn Assay of urine and stool for the presence of without insulin to suppress overproduction of heme abnormally high concentrations of heme synthesis intermediates products: nn Intravenous infusion of hematin at a 2 to ––Coproporphyin 5 mg/kg/day dosing for 3 to 14 days suppresses ––Protophorphyrin production of aminolevulinic acid nn Observe urine for change to dark color during exposure to light Prognosis nn Nerve conduction studies show an “axonal” pattern of nn abnormality: motor and sensory response amplitudes Improvement over a 2- to 12-month time frame nn are low if present, conduction velocities are no slower Deficits in distal strength and sensory may persist than the mid-30 meters per second range and distal latencies remain normal Suggested Readings nn Needle EMG shows reduced motor unit potential Anderson K, Kappas A. The porphyrias. In: Nabel E, ed. ACP Medicine. (Section 9, Chapter VII). Hamilton, ON, Canada: recruitment initially and then signs of muscle Decker; 2013. membrane instability several weeks after onset Windebank A, Bonkovsky H. Porphyric neuropathy. nn Cerebrospinal fluid values tend to be normal or show In: Dyck PJ, Thomas PK, eds. Peripheral Neuropathy. 4th ed. only mild protein elevation (pp. 1883–1892). Philadelphia, PA: Elsevier; 2005.

Neuromuscular III Junction Botulism John C. Kincaid MD

Description Clinical Features Syndrome of acutely evolving weakness of skeletal m­ uscle nn Onset of symptoms and signs 12 to 36 hours after and impairment of autonomic function due to peripheral exposure to the toxin cholinergic deficiency resulting from the effects of the nn Gastrointestinal (GI) disturbance in the form of toxin released by Clostridium botulinum (C. botulinum) nausea and vomiting and then constipation are the initial manifestations, with the exception of wound Etiology botulism in which GI disturbance does not occur nn Exposure to the toxin produced by C. botulinum nn Impairment of visual focusing and then development nn The most common source of the toxin is improperly of diplopia sterilized homemade food products in which the nn Weakness of skeletal muscle, which may include bacteria grows and produces toxin muscles of respiration, that evolves over the next nn Ingestion of Clostridium spores by infants and 2 to 4 days subsequent proliferation of the bacteria in the nn Absence of sensory disturbance gastrointestinal tract may produce infantile botulism nn Wounds contaminated by soil can introduce the Natural History bacteria into the traumatized tissue and allow toxin nn Deficits evolve to maximum over several days and in the wound site then persist for several months

Epidemiology Diagnosis Rare but recognizable syndrome Differential diagnosis nn About 100 cases per year are reported in the nn Autoimmune myasthenia gravis United States nn Guillain-Barré syndrome nn Half of these come from western states where altitude nn Organophosphate poisoning and the resulting alteration of the boiling point of nn Periodic paralysis water may be a factor nn Tick paralysis History Pathogenesis nn Onset of gastrointestinal disturbance, followed nn Botulinum toxin degrades several proteins in hours to a few days later by somatic muscle cholinergic nerve terminals, which play important weakness, beginning several days after toxin roles in the docking of synaptic vesicles with the exposure terminal membrane and release of neurotransmitters nn Maximal autonomic and skeletal muscle deficits result into the synaptic cleft by 2 to 4 days after onset nn The impaired release of acetylcholine produces deficits in somatic motor and autonomic functions Physical examination nn Look for a tick attached to the skin Risk Factors nn The sensorium should be normal in teenagers and nn Exposure to food contaminated by C. botulinum adults; infants may appear lethargic due to the nn Penetrating and crush injuries contaminated weakness by soil nn Impaired pupillary reaction to light and nn Administration of illicit drugs by subcutaneous or accommodation intravenous route nn Diplopia and weakness of other cranial muscles, nn Ingestion of raw honey or other Clostridium followed hours to a few days later by weakness of the spore-containing foods by infants somatic muscles, including those of respiration

90 Botulism 91 nn The weakness may manifest with poor feeding and Treatment floppiness nn Supportive care, including intubation and ventilation nn Muscle stretch reflexes are reduced or absent nn The support may need to be maintained for weeks, nn Sensory examination is normal as recovery requires the regeneration of motor and Testing autonomic nerve terminals and synapses nn Trivalent antiserum to toxins A, B, and E should be nn Antiacetylcholine choline receptor antibodies will be administered when the diagnosis is strongly considered negative nn The antitoxin can be obtained from the Centers for nn The toxin may be present in serum, stool, or food Disease Control in Atlanta, GA, USA samples nn Verification of the absence of an to the nn Serum potassium, calcium, and magnesium levels antitoxin should be verified by intradermal testing should be normal

with horse serum, while monitoring for an allergic nn Motor nerve and sensory conduction studies show reaction normal conduction velocities and distal latencies but nn Acetylcholinesterase inhibitors such as pyridostigmine the motor response amplitude may be reduced may improve the weakness nn Repetitive motor nerve stimulation may produce a nn Occupational and physical therapy evaluation for decremental response at slow rates of stimulation but optimization of functional capacity faster rates such as 10 to 20 Hz may be required nn An incremental response may be shown by repetitive Prognosis stimulation at 30 to 50 Hz but if present, the nn Improvement and eventual recovery should occur

amount of increment tends to be less than seen in Neuromuscular JunctionIII: in the majority of patients who receive adequate Lambert-Eaton myasthenic syndrome; up to a 50% management, including intensive care unit level care increment can be found in normal subjects due to nn The duration of the need for highly supportive care pseudofacilitation may be weeks to a few months nn Needle EMG may show abnormal resting activity in severely weak muscles several weeks after onset and Suggested Readings may show somewhat small size motor unit potentials, Cherington M. Clinical spectrum of botulism. Muscle Nerve. which are unstable in configuration for one discharge 1998;21:701–710. to the next Chow A. Anaerobic Infections. In: Nabel E, ed. ACP Medicine nn Cerebrospinal fluid protein levels tend to be normal (Section 7, Chapter V). Hamilton, ON, Canada: Decker; 2013. Congenital Myasthenia Gravis John C. Kincaid MD

Description nn Fast channel syndrome is due to alteration of the Syndromes due to genetic-based abnormalities in neuro- normal amino acid sequence of the ion channel muscular junction structure and function, which present proteins in the acetylcholine receptor and results in in newborns, infants, or children as episodes of fatigable shorter than normal opening of the channel during weakness involving facial, limb, and respiratory muscles synaptic transmission

Etiology Risk Factors The congenital myasthenia gravis syndromes are classi- Dominant inheritance in the slow channel syndrome, fied by the site of functional abnormality: recessive inheritance in the others. nn Presynaptic Clinical Features nn Synaptic nn nn Postsynaptic Onset in newborn or infant years is the more common clinical pattern Epidemiology nn Fatigable weakness of facial, limb, and at times Very rare but recognizable syndromes: about 200 patients respiratory muscles nn with these syndromes had been reported in literature by Static weakness may also develop in some syndromes the mid-2000 time frame Natural History Pathogenesis nn Defined by the specific syndrome: some produce episodic weakness, which lessens in severity as the Presynaptic abnormality: patient enters teen to early adult years, whereas others nn Choline acetyltransferase deficiency impairs the produce a static to slowly progressive persistent packaging of acetylcholine into synaptic vesicles and weakness the replenishment of the vesicles during sustained muscle contraction Diagnosis nn This condition is also known as congenital myasthenic Differential diagnosis syndrome with episodic apnea nn Autoimmune myasthenia gravis Synaptic abnormality: nn Infantile or juvenile motor neuron disease nn nn Congenital end plate acetylcholinesterase deficiency Muscular dystrophy with distal myopathy impairs breakdown of acetylcholine after release manifestations nn and results in persistent or recurrent opening of the Botulism (for the initial episode of weakness) nn acetylcholine receptor ion channel and impairment of Periodic paralysis repolarization of the postsynaptic membrane History nn The deficiency of acetylcholinesterase arises due to an nn Recurring episodes of facial, limb, and at times, abnormality in collagen, which anchors the enzyme in respiratory weakness the proper location of the postsynaptic membrane nn Some attacks are precipitated by intercurrent illness Postsynaptic abnormality: such as infection nn A family history of similar attacks may be present nn These are the more common causes of congenital myasthenic syndrome Physical examination nn Slow channel syndrome is due to alteration of the nn Weakness of cranial and limb muscles which worsens amino acid sequence of the ion channel proteins in with sustained use the acetylcholine receptor and results in prolonged nn Persistent weakness of cranial, limb, and axial muscles opening of the channel during synaptic transmission in congenital acetylcholinesterase deficiency

92 Congenital Myasthenia Gravis 93 nn Episodic plus an underlying persistent weakness of nn Acetylcholinesterase inhibitors such as neck extensors and the extensors of the wrist and pyridostigmine may improve weakness in choline fingers in slow channel syndrome acetyltransferase deficiency and fast channel Testing syndrome nn nn Antiacetylcholine receptor and anti-muscle-specific 3,4-Diaminopyridine may improve weakness tyrosine kinase antibodies will be negative in fast channel syndrome due to its enhancing nn Motor nerve and sensory conduction studies show effects on acetylcholine release from the nerve normal conduction velocities and distal latencies terminal nn nn Needle EMG should show normal resting activity and Quinidine and fluoxetine may improve strength in normal to small size motor unit potentials, which are slow channel syndrome nn unstable in configuration Occupational and physical therapy evaluation for optimization of functional capacity nn Repetitive motor nerve stimulation often shows a decremental response to 2 to 3 Hz stimuli, but this may not be present in each condition Prognosis nn Patients with congenital acetylcholinesterase nn Improvement in the frequency and severity of the deficiency and slow channel syndrome demonstrate episodes of weakness often occur as the infant moves a repetitive (re-firing) component of the compound into teen or early adult years muscle action potential occurring 5 to 10 milliseconds nn Slowly worsening persistent weakness in neck after the negative phase of the potential following a extensors and wrist/finger extensor muscles occurs in single maximal stimulus

slow channel syndrome Neuromuscular JunctionIII: nn Definitive diagnosis of the specific condition may require referral to a center with experience in the Suggested Readings detailed analysis of these types of syndromes Engle A, Ohno K, Sine S. Congenital myasthenic syndromes in Treatment myology. In: Engle A, Franzini-Armstrong C, eds. 3rd ed. (pp. 1801–1844). New York: McGraw Hill; 2004. nn Management of recurring episodes of acute Engle A, Shen X, Selcen D, Sine S. New horizons for respiratory failure may be required in congenital ­congenital myasthenic syndromes. Ann NY Acad Sci. acetylcholinesterase deficiency 2012;1275:54–62. Lambert-Eaton Myasthenic Syndrome Cynthia L. Bodkin MD

Description nn Proximal leg more than arm weakness Lambert-Eaton Myasthenic Syndrome (LEMS) is an auto- nn Symptoms exacerbated by heat immune disorder involving antibodies against the pre- nn Stiffness and/or muscle aching is noted in one third of synaptic neuromuscular junction patients after physical activity nn Ocular and bulbar symptoms are not common Etiology/Types nn Autonomic dysfunction, such as constipation, blurred nn Idiopathic vision, decreased sweating, and impotence, is common nn About two thirds of cases are paraneoplastic disorder, nn Respiratory failure from LEMS is rare of which roughly 90% are associated with small cell lung cancer Natural History nn Symptoms often precede diagnosis of cancer by Epidemiology approximately 10 months (range 6 months to 4 years) nn Rare disorder nn Mean age of onset is 54 years, with more than 80% Diagnosis older than 40 years Differential diagnosis nn Women are more prone to the idiopathic form, nn Myasthenia syndrome whereas men are more common in the paraneoplastic nn Botulism form nn Dermatomyositis/polymyositis nn Amyotrophic lateral sclerosis Pathogenesis nn Electrolyte abnormality nn Antibodies against P/Q voltage-gated calcium channels on the presynaptic terminal in 85% to History 90% of patients nn Fluctuating weakness nn About 74% of patients with lung cancer and 40% nn Difficulty walking without cancer have antibodies to N-type calcium nn Dry mouth, eyes, or skin channels nn Constipation and/or urinary retention nn Acetylcholine release from the presynaptic terminal Examination is impaired, leading to decreased activation of nn Variable muscle weakness with proximal muscles postsynaptic acetylcholine receptors on the muscle more involved than distal nn With fewer receptors activated, the endplate potentials nn Decreased or absent deep tendon reflexes with initial may fall below threshold to generate an action testing, which improves with repetitive testing potential nn Mild ptosis or diplopia may be present in some patients nn Examination may be normal Risk Factors nn Autoimmune disease (rheumatoid arthritis, lupus, and Testing inflammatory bowel disease) nn P/Q voltage-gated calcium channels antibodies nn Small cell lung cancer nn N-type calcium channel antibodies nn Smoking nn Nerve conduction studies demonstrate decreased-to- normal absolute values of amplitude. Greater than Clinical Features 10% decrement can be seen at 2 to 3 Hz repetitive nn Fluctuating or fatigable weakness stimulation, whereas facilitation is noted with nn Temporary increased strength with short bursts of 20 to 50 Hz stimulation or short bursts of exercise exercise nn Needle EMG demonstrates normal motor unit nn Functional impairment out of proportion to objective duration and amplitude but varying potentials in weakness weak muscles 94 Lambert-Eaton Myasthenic Syndrome 95 nn Single-fiber electromyography demonstrates increase Surgical jitter and neuromuscular blocking nn Surgical removal or biopsy of underlying cancer, if found nn Chest computed tomography (CT) scan, Consults and positron emission tomography (PET) scan nn Neurology should be considered to evaluate for underlying nn Pulmonary cancer nn Oncologist nn Bronchoscope for patients at risk for lung cancer nn Physical medicine and rehabilitation Pitfalls Complications of treatment nn Delayed diagnosis nn Opportunistic infections nn Not screening for underlying cancer nn Osteoporosis, weight gain, hyperglycemia, cataracts, and peptic ulcer in patients on steroids Red flags nn Fasciculation and atrophy Prognosis nn Treatment Dependent on underlying cancer and other autoimmune conditions Medical nn Treat underlying cancer Helpful Hint nn 3,4-diaminopyridine nn Repeated screen for underlying cancer should be nn Anticholinesterase considered at interval periods

nn Neuromuscular JunctionIII:

Immunosuppressive agents: ––Corticosteroids Suggested Readings ––Azathioprine Amato AA, Russell JA. Neuromuscular Disorders (viii, pp. 457–528). New York: McGraw-Hill Medical; 2008. ––Cyclosporine Biller J. Practical Neurology. 4th ed. (pp. 559–569). Philadelphia, nn Plasmapheresis PA: Lippincott Williams & Wilkins, a Wolters Kluwer nn Intravenous immunglobulin ­business; 2012. Myasthenia Gravis Cynthia L. Bodkin MD

Description nn Symptoms tend to worsen later in the day and improve Myasthenia gravis (MG) is an autoimmune disorder involv- with physical rest ing antibodies against the neuromuscular junction nn Lack of autonomic dysfunction nn Urinary and bowl function usually remain normal Etiology/Types Natural History nn Idiopathic nn About 80% will develop ocular symptoms nn About 80% to 90% of patients have antibodies to nn 80% to 85% of patients with ocular myasthenia will acetylcholine (ACh) receptors (either modulating or develop generalized weakness, most within the 1st year blocking) nn In 70% of patients the maximum weakness usually nn About 25% of patients who do not have an antibody occurs within the first three years to (ACh) receptors will have antibodies to nn 10% to 15% can have a spontaneous remission muscle-specific kinase (MuSK) nn Remainder is seronegative Diagnosis Differential diagnosis Epidemiology nn Lambert-Eaton myasthenic syndrome nn Prevalence is approximately 1 in 10,000 to 20,000 nn Botulism nn Male-to-female ratio estimated 1:2 nn Congenital myasthenic syndromes nn Age of onset can be any age with a peak in the 2nd nn Compressive cranial neuropathies and 3rd decade in women and 5th and 6th decade nn Mitochondrial cytopathies in men nn Oculopharyngeal muscular dystrophy nn Bulbar onset amyotrophic lateral sclerosis (ALS) Pathogenesis nn Dermatomyositis/polymyositis nn Antibodies to postsynaptic ACh receptors on the History muscle decrease the number of receptors available nn The presentation can vary among patients but to bind to ACh during nerve impulse. With fewer includes the following: receptors available, the endplate potentials may fall ––Fluctuating weakness below threshold to generate an action potential ––Diplopia and/or ptosis ––Dysphagia and/or dysarthria Risk Factors ––Weakness in legs/trouble walking nn Autoimmune disease (rheumatoid arthritis, lupus, and ––Shortness of breath or respiratory failure pernicious anemia in about 5%) Examination nn Thyroid disease in about 10% nn nn Thymoma Variable muscle weakness with proximal muscles nn d-penicillamine and alfa-interferon therapy have more involved than distal and arms more than legs nn induced MG Fluctuating asymmetrical extraocular movements nn Ptosis Clinical Features nn Nasal speech nn nn Fluctuating or fatigable weakness Neck extension weakness nn nn Half of patients will have ocular symptoms, either Exam may be normal diplopia or ptosis Testing nn Roughly 10% will present with leg weakness, 10% with nn ACh receptor antibodies generalized weakness, 10% with bulbar (dysarthria nn Striated muscle antibody present in patients with or dysphagia) weakness, and less than 1% with thymoma respiratory failure nn MuSK antibody

96 Myasthenia Gravis 97 nn Nerve conduction studies demonstrate normal nn Plasmapheresis (common treatment with acute absolute values, but greater than 10% decrement can exacerbation) be seen at 2 to 3 Hz repetitive stimulation nn Intravenous immunoglobulin (common treatment nn Needle EMG demonstrates normal motor unit with acute exacerbation) duration and amplitude but varying potentials in nn Supportive: weak muscles ––Close monitoring in intensive care unit for patients nn Single-fiber EMG demonstrates increased jitter and in a crisis neuromuscular blocking ––Bi-level positive airway pressure nn Anticholinesterase tests with intravenous ––Intubation edrophonium can temporarily improve weakness. ––Feeding tube Patient must have an objective measurable Surgical abnormality on examination in order to measure nn Thymectomy for patients with a thymoma and can be improvement. Positive test can be seen in other considered in patients without a thymoma neuromuscular disorders nn Antinuclear antibody Consults nn Rheumatoid factor nn Neurology nn Thyroid stimulating hormone nn Pulmonary nn Chest computed tomography (CT) scan to evaluate for nn Speech pathology thymoma or thymic enlargement nn Dietitian nn Magnetic resonance imaging (MRI) of brain and orbits Complications of treatment III: Neuromuscular JunctionIII: for ocular myasthenia to evaluate for other potential nn Opportunistic infections causes nn Risk of lymphoproliferative malignancies Pitfalls nn Osteoporosis, weight gain, hyperglycemia, cataracts, nn Delayed diagnosis and peptic ulcer in patients on steroids nn Failure to recognize impending respiratory failure Prognosis nn Temporary worsening with start of steroids can lead nn to respiratory failure Variable: ––Mortality from MG is unusual due to the current Red flags advancements in medical care nn Pain nn In 70% of patients the maximum weakness usually nn Autonomic symptoms occurs within the first 3 years nn Fasciculation and atrophy nn 10% to 15% can have a spontaneous remission Helpful Hint Treatment nn Steroids may temporarily worsen weakness Medical nn Anticholinesterase Suggested Readings nn Immunosuppressive agents: Amato AA, Russell JA. Neuromuscular Disorders (viii, pp. 457–528). New York: McGraw-Hill Medical; 2008. –– Corticosteroids Biller J. Practical Neurology. 4th ed. (pp. 559–569). Philadelphia, ––Azathioprine PA: Lippincott Williams & Wilkins, a Wolters Kluwer ––Cyclosporine business; 2012. Organophosphate Poisoning John C. Kincaid MD

Description the degree of respiratory paralysis and central nervous Syndrome of acute overactivity of cholinergic synaptic system manifestations of agitation, encephalopathy, transmission due to blockade of acetylcholinesterase by and seizures organophosphate compounds, with resulting central nn Survivors of the acute exposure may develop ­nervous system, autonomic nervous system, and neuro- peripheral neuropathy and myelopathy weeks later muscular manifestations Natural History Etiology nn Prompt treatment in a hospital or military triage setting Exposure to the causative compounds by contact with permits survival excessive amounts of insecticides, contaminants of food nn Longer-term effects such as peripheral neuropathy or products, or exposure to nerve agent warfare compounds myelopathy may not be preventable in military or terrorist settings Diagnosis Epidemiology Differential diagnosis The most common source of this type of exposure is sui- nn Status epilepticus of other etiology cide attempts in which ingestion of insecticides occurs. nn Acute abdomen Pathogenesis nn Opioid withdrawal nn nn Carbamate and organophosphate compounds inhibit Myasthenic crisis nn the activity of acetyl cholinesterase, resulting in Attack of porphyria nn excess acetylcholine at synapses in the central and Encephalitis autonomic nervous system and at the neuromuscular History junction nn Acute onset of gastrointestinal disturbance nn Manifestations of the excess cholinergic activity shortly after exposure to or ingestion of the include encephalopathy, seizures, miosis, excessive compound salivation, bronchospasm, abdominal cramping, nn Seizures and muscular paralysis follow minutes later hyperhidrosis, fasciculations, and muscular weakness Physical examination nn Delayed manifestations of myelopathy or peripheral nn Signs of cholinergic excess: hyperhydrosis, miosis, neuropathy due to the compounds’ effects on sialorrhea, fasciculations structural proteins of central and peripheral nerves nn Altered sensorium may occur in survivors of the acute exposure nn Generalized convulsions Risk Factors nn Weakness of skeletal muscles Exposure to organophosphate compounds in the form Testing of high dose contact with insecticides such as malathion, nn Chest radiograph, blood gas, electrocardiogram, ingestion of food products contaminated by industrial electrolytes, calcium, and magnesium levels lubricating agents such as triorthocresyl phosphates, or nn Computed tomography (CT) of the head contact with nerve gas warfare agents such as soman, nn Electroencephalogram sarin, or VX in weapon storage, terrorist, or military action-type settings Treatment nn Clothing removal and decontamination of skin Clinical Features nn Protection of rescue and medical workers with nn Acute onset of abdominal cramps, vomiting, diarrhea, respirators, butyl rubber gloves rather than latex, hyperhidrosis, and excessive salivation butyl rubber aprons nn Depending on the compound, additional nn Supportive care, including intubation and ventilation manifestations may include muscular weakness up to nn Gastric lavage if ingestion has occurred 98 Organophosphate Poisoning 99 nn Administration of atropine and 2-PAM (1–2 g IV nn Peripheral neuropathy and myelopathy may develop immediately followed by 200–500 mg/hr) to counteract weeks after the acute event in survivors cholinergic excess nn Military personnel in war settings carry atropine and Suggested Readings 2-PAM injectors Holstege C, Kirk M, Sidell F. Chemical warfare nerve agent nn Seek input from a poison control center ­poisoning. Crit Care Clin. 1997;13:923–942. Prognosis Wiegland T, Patel M, Olson K. Management of poisoning and drug overdose. In: Nabel E, ed. ACP Medicine. nn Survival is possible if recognition of the scenario is (Section 8, Chapter I). Hamilton, ON, Canada: Decker; prompt and treatment is instituted 2013.

III: Neuromuscular JunctionIII:

Radiculopathies/ IV Plexopathies Brachial Plexopathy Gentry Dodd MD ■ Nathan D. Prahlow MD

Description Risk Factors A pathologic process affecting a group of nerves in the nn Trauma to the shoulder, causing a downward force, brachial plexus, usually distal to the dorsal root ganglion with possible movement of the head and neck to the and proximal to the peripheral nerves contralateral side, can cause traction to the upper brachial plexus Etiology nn Traction to the arm, such as attempting to catch nn Trauma: one’s self while falling, can lead to lower plexus ––Stretching of nerves injury ––Nerve transection nn Diabetes (although lumbosacral plexopathies are more ––Obstetric injuries common) ––Hemorrhage nn Tumors of the head, neck, and chest nn Cancer: nn History of radiation therapy to the upper chest, neck, ––Direct tumor invasion or shoulder ––Radiation therapy nn Idiopathic: Clinical Features ––Neuralgic amyotrophy nn Pain, either acute or progressive, in the shoulder or Types upper arm nn nn Upper plexus lesions Evolving arm, shoulder, or hand numbness nn ––For example, Erb’s palsy Weakness of the upper extremity nn nn Lower trunk lesions Atrophy, likely to not be appreciated until several ––For example, Klumpke’s palsy weeks after plexus injury nn Sympathetic changes can be seen with a C8, T1 lesion Epidemiology nn 0.4% of patients with cancer Natural History nn 2% to 5% of cancer patients treated with radiation nn Traumatic etiology: nn Traumatic brachial plexus injuries usually occur in ––Most natural improvements occur within 6 months young males (89%) ––In general, recovery is poor ––Age range is 14 to 63 years, with a mean of 29 years ––Injuries that have a degree of axonal continuity have nn Idiopathic brachial plexopathy (Neuralgic Amyotrophy) a more favorable outcome has an annual incidence of 2 to 3 per 100,000 nn Nerve pain may be severe and can persist for a long nn Iatrogenic causes are usually from positioning in time surgery or anesthesia Diagnosis Pathogenesis Differential diagnosis nn Nerve compression or traction from trauma, such nn Radiculopathy as would be experienced with a direct blow to the nn Rotator cuff disease shoulder during contact sports, can lead to nerve nn Shoulder dislocation damage or even transection nn Thoracic outlet syndrome nn Inflammatory, metabolic, and radiation-induced plexopathies often involve small vessel ischemia History nn Metabolic abnormalities, such as diabetes, can cause nn Trauma local inflammation and focal ischemia nn History of head/neck cancer with or without targeted nn Neoplasms can place direct pressure on the plexus radiation therapy but more often causes a plexopathy via direct nerve or nn Sensory disturbances connective tissue invasion nn Focal upper extremity weakness 102 Brachial Plexopathy 103

Exam Exercise nn Manual muscle testing nn Range-of-motion exercises to prevent contractures nn Sensory testing and secondary deformities, followed by gravity nn Deep tendon reflexes assisted exercise, then resistance exercise nn Evaluate for specific arm/hand positioning: nn Passive muscle stretching helps prevent muscle atrophy ––Erb’s palsy—extended arm, pronated forearm, flexed nn Electrical stimulation to the denervated muscles can hand: help prevent significant atrophy • • “Waiter’s tip” position Modalities •• C5, C6 injury nn Electrical stimulation (E-stim) for pain control ––Klumpke’s palsy—claw hand: nn Transcutaneous electrical nerve stimulation; although •• C8, T1 injury efficacy is questionable in chronic and neuropathic nn Look for signs of atrophy in the upper extremities pain Testing nn Ultrasound for deep pain and muscle spasm nn Computed tomography (CT) myelography Injections nn Magnetic resonance imaging (MRI) without nn Focal nerve block contrast Surgical treatment nn Plain films to look for bony structural abnormalities nn nn EMG—should be performed 3 to 6 weeks after injury Nerve/plexus reconstruction nn ––Sensory nerve action potentials may be normal if the Spinal cord stimulator placement nn lesion is preganglionic (proximal to the dorsal root Deep brain stimulator nn ganglion) Lesioning of the dorsal root entry zone ––Sensory potentials will be abnormal if the lesion is Consults postganglionic nn Physiatry ––EMG demonstrates normal paraspinal activity with nn Neurology peripheral abnormalities nn Pitfalls Complications of treatment nn deformities can develop and are difficult nn Surgery may not completely reverse symptomatology to treat nn Placement of spinal cord stimulators and deep brain IV: Radiculopathies/Plexopathies IV: Red flags stimulators are associated with the usual risks as well nn Once muscle atrophy is present, regaining full as intracranial/intradural infections functional capacity is difficult Prognosis Treatment nn A good recovery can be expected if the cause is Medical identified and treated appropriately ––For example, head/neck cancer nn Medications to control pain: nn Limited muscle movement may be seen months after ––Non-steroidal anti-inflammatory drugs (NSAIDs) the damage ––Anticonvulsants: nn Surgical intervention may not show significant results •• Gabapentin until 3 to 4 years after initial treatment and following •• Lyrica significant intensive therapy ––Tricyclic antidepressants: •• Nortriptyline Helpful Hint •• Amitriptyline nn If an EMG demonstrates normal sensory action ––Cymbalta is often used as an adjunctive therapy to potentials, there may still be a nerve root avulsion help treat neuropathic pain •• Opioids in general are not useful for the treatment Suggested Readings of neuropathic pain Simmons Z. Electrodiagnosis of brachial plexopathies and nn If the cause of plexopathy is due to diabetes or renal proximal upper extremity neuropathies. Phys Med Rehab Clin disease, the underlying comorbidities should also be N Am. 2013; 24(1):13–32. treated appropriately Wilbourn AJ. Plexopathies. Neurol Clin. 2007;25(1):139–171. Lumbosacral Plexopathy Gentry Dodd MD ■ Nathan D. Prahlow MD

Description nn Diabetes—lumbosacral plexopathies are more common A pathologic process affecting a group of nerves in the than brachial plexopathies as a result of diabetes lumbosacral plexus, usually distal to the dorsal root nn Tumors of the pelvis or hip ganglion and proximal to the peripheral nerves nn History of radiation therapy to the pelvis or thigh regions Etiology Clinical Features nn Trauma: nn Pain, either acute or progressive, in the pelvis, thigh, ––Stretching of nerves or lower extremity ––Nerve transection nn Evolving thigh, leg, calf, or foot numbness ––Hemorrhage/hematoma nn Weakness of the lower extremity nn Cancer: nn Atrophy, likely to not be appreciated until several ––Direct tumor invasion weeks after plexus injury ––Radiation therapy Natural History Types nn Traumatic etiology: nn Lumbar plexus lesions: ––Most natural improvements occur within 6 months ––Involves the anterior rami of L2–L4 ––In general, recovery is poor nn Sacral plexus lesions: ––Injuries having a degree of axonal continuity have a ––Involves the anterior rami of L5–S3 more favorable outcome Epidemiology nn Nerve pain may be severe and persist for a long time nn For diabetics, the incidence of a proximal neuropathy Diagnosis is 8 per 1000 nn In traumatic cases with a sacral fracture, there is a 2% Differential diagnosis incidence of lumbosacral plexopathy nn Radiculopathy ––With other pelvic fractures, the incidence is 0.8% nn Polyradiculopathy (cauda equina syndrome) nn One per 2000 to 6000 obstetric deliveries result in nn Anterior horn cell disease: lumbosacral plexopathies ––Painless, diffuse weakness nn Idiopathic cases of lumbosacral plexopathy are ––Muscular atrophy rare, with only a few hundred cases in the literature nn Myopathy

Pathogenesis History nn Nerve compression or transection from trauma nn Trauma nn Inflammatory, metabolic, and radiation induced nn History of lower abdominal/pelvic cancer plexopathies often involve small vessel ischemia with or without targeted radiation therapy nn Metabolic abnormalities, such as diabetes, can cause nn Sensory disturbances local inflammation and focal ischemia nn Focal lower extremity weakness nn Neoplasms can place direct pressure on the plexus Examination but more often causes a plexopathy via direct nerve or nn Manual muscle testing connective tissue invasion nn Sensory testing nn Hip dislocations can cause direct trauma to the plexus nn Deep tendon reflexes nn Retroperitoneal hematomas can place pressure on the nn Specific examination findings depend on which plexus portion of the plexus is involved Risk Factors ––Lumbar involvement: nn Trauma to the pelvis or hip, such as seen with motor •• Weakness of hip flexion, knee extension, vehicle accidents or gunshot wounds thigh adduction

104 Lumbosacral Plexopathy 105

•• Decreased sensation of the anteromedial thigh nn If the cause of plexopathy is due to diabetes, any •• Decreased patellar reflex underlying comorbidities should also be treated ––Sacral involvement: appropriately • • Weakness of hip extension, hip abduction, knee Exercise flexion, ankle plantar flexion and dorsiflexion nn Range-of-motion exercises to prevent contractures •• Decreased sensation in the posterior thigh and and secondary deformities plantar surface of the foot ––Followed by gravity-assisted exercise then resistance •• Decreased Achilles reflex exercise nn Look for signs of atrophy in the lower extremities nn Passive muscle stretching helps prevent muscle atrophy Testing nn Electrical stimulation to the denervated muscles can nn Computed tomography (CT) myelography help prevent significant atrophy nn Magnetic resonance imaging (MRI) without Modalities contrast nn Electrical stimulation (E-stim) for pain control nn Plain films to look for bony structural abnormalities ––Transcutaneous electrical nerve stimulation; nn EMG—should be performed 3 to 6 weeks postinjury although efficacy is questionable in chronic and ––Sensory and motor nerve action potential amplitudes neuropathic pain are reduced, indicating a lesion distal to the dorsal nn Ultrasound for muscle spasm and pain control root ganglion •• Sensory potentials will be abnormal if the lesion is Injections

postganglionic nn Focal nerve block ––EMG can demonstrate denervation, as evidenced Surgical treatment by fibrillations and positive sharp waves, as well as nn Nerve/plexus reconstruction reduced recruitment nn Spinal cord stimulator placement • • For the diagnosis, denervation needs to be nn Deep brain stimulator observed in muscles that are innervated by two nn Lesioning of the dorsal root entry zone different lumbosacral spinal levels that involve at least two different peripheral nerves Consults nn Pitfalls Physiatry nn Neurology nn Radiculopathies/Plexopathies IV:

Once muscle atrophy is present, regaining full nn Neurosurgery functional capacity is difficult Red flags Complications of treatment nn nn Cancer-related history must be elicited Surgery may not completely reverse symptomatology nn Placement of spinal cord stimulators and deep brain Treatment stimulators are associated with the usual risks as well as intracranial/intradural infections Medical treatment nn Medications to control pain: Prognosis ––Non-steroidal anti-inflammatory drugs (NSAIDs) nn A good recovery can be expected if the cause is ––Anticonvulsants: identified and treated appropriately •• Gabapentin nn Limited muscle movement may be seen months after •• Lyrica the damage ––Tricyclic antidepressants: •• Nortriptyline Helpful Hint •• Amitriptyline nn If an EMG demonstrates normal sensory action ––Cymbalta is often used as an adjunctive therapy to potentials, there may be a nerve root avulsion help treat neuropathic pain •• Opioids in general are not useful for the treatment Suggested Reading of neuropathic pain Wilbourn AJ. Plexopathies. Neurol Clin. 2007;25(1):139–171. Neuralgic Amyotrophy (Parsonage-Turner Syndrome) Gentry Dodd MD ■ Nathan D. Prahlow MD

Description ––An autoimmune response to a virus may directly Neuralgic amyotrophy, also known as Parsonage-Turner affect the brachial plexus Syndrome (PTS) and idiopathic brachial plexopathy, is a ––Vasculitic disease, such as polyarteritis nodosa, disorder consisting of a constellation of findings usually systemic lupus erythematosus, and temporal preceded by abrupt onset of upper extremity/shoulder arteritis, which are related to neuralgic amyotrophy pain followed by progressive motor weakness, dysesthesia, suggest that a vascular component is at play and numbness. ––Inflammatory or mechanically induced ischemia may be the cause of the sudden onset of pain Etiology •• Perineural thickening and neovascularization nn Can be triggered by the following: have been reported in nerve biopsies ––Infection nn Cases related to surgery are often thought to be due to ––Surgery/anesthesia either poor positioning that results in brachial plexus ––Rheumatic disease: traction or immune-mediated inflammation of the •• Connective tissue disorders brachial plexus •• Systemic lupus erythematosis •• Polyarteritis nodosa Risk Factors ––Trauma: nn The most commonly described risk factor is viral •• Remote from the shoulder girdle complex illness, with approximately 25% of patients with ––Immunizations: neuralgic amyotrophy having had a preceding viral •• Tetanus illness •• Diphtheria, pertussis, tetanus (DPT) nn Recent immunization is the second most commonly •• Smallpox cited risk factor: Up to 15% of patients with neuralgic Types amyotrophy had a recent immunization prior to the nn No specific types of PTS exist, but varying portions of development of this syndrome the plexus may be affected Clinical Features Epidemiology nn Sudden onset of constant, severe shoulder pain that nn Overall, the incidence of neuralgic amyotrophy is may extend to the trapezius, forearm, and hand 1.64 per 100,000; however, this may be underreported, ––Usually, no constitutional signs or symptoms are as this is a difficult clinical diagnosis associated with shoulder pain, although a viral nn The incidence is higher in men than women, with illness may precede the initial presentation ratios ranging from 11:9 to 11:1 ––The duration of pain usually lasts from days to nn There is no apparent left or right side preference; weeks bilateral involvement occurs in up to 30% of patients ––Pain is typically neuropathic in nature nn Affected age groups range from 3 months to 75 years, nn Muscle weakness, atrophy, and sensory loss develop as with the highest prevalence in the 3rd to 7th decades the pain subsides and can last up to years ––Subtle muscular weakness can be seen days to weeks Pathogenesis after initial symptom onset nn The pathology of this idiopathic disorder is not clearly ––Obvious weakness and atrophy is usually seen understood, but there are several theories as to the within a month cause of the sudden onset of acute shoulder pain ––Scapular winging may be seen if the long thoracic ––Viral illness may directly affect the brachial plexus nerve is involved

106 Neuralgic Amyotrophy (Parsonage-Turner Syndrome) 107

Natural History Pitfalls nn A study looking at functional strength revealed only nn If EMG abnormalities are seen in a nerve root 89% recovery within 3 years distribution only and not also in a peripheral nerve nn One-third of patients suffer from chronic pain distribution, the likely etiology of shoulder pain is and functional deficits up to 6 years after initial radiculopathy diagnosis Red flags nn Shooting arm pain is typically a sign of radiculopathy Diagnosis rather than neuralgic amyotrophy Differential diagnosis nn Rotator cuff disease Treatment nn Cervical disc disease Medical nn Bicipital tendonitis nn The best treatment at this time remains unknown nn Other causes of brachial plexopathy nn There is some evidence to suggest that oral History corticosteroids administered during the acute pain phase of neuralgic amyotrophy can shorten the nn Recent surgical intervention or anesthesia duration of intense pain and expedite motor recovery nn Viral illness preceding the onset of shoulder pain nn Because the acute pain phase of neuralgic amyotrophy nn Immunization shortly before shoulder pain began is usually short in duration—days to weeks— Examination

non-steroidal anti-inflammatory drugs (NSAIDs) nn Manual muscle testing and opioids are generally recommended over the use nn Sensory testing of tricyclics and anticonvulsants given their delayed nn Deep tendon reflexes onset in pain relieving effect nn Visual inspection looking for signs of muscle atrophy nn Immunotherapy has been used in the past as a potential Testing therapeutic agent, although there are a limited number of studies available to demonstrate its effectiveness nn The diagnosis is largely a clinical one nn Chest x-ray to rule out potential mass or Pancoast Exercise tumor nn Range-of-motion exercises to prevent contractures nn Cervical spine magnetic resonance imaging (MRI) and secondary deformities IV: Radiculopathies/Plexopathies IV:

is helpful in ruling out cervical disc disease as the ––Followed by gravity-assisted exercise and then potential etiologic agent resistance exercise ––This, however, can cloud the clinical picture given ––Strength training should be delayed until significant the many incidental, nonclinically important reinnervation of the affected muscles has developed findings that can be seen in advanced imaging nn Electrical stimulation to the denervated muscles can nn EMG—should be performed 3 to 6 weeks after help prevent significant atrophy injury Modalities ––Sensory and motor nerve action potential nn Electrical stimulation (E-stim) for pain control amplitudes of distal muscles are commonly normal nn Transcutaneous electrical nerve stimulation for pain as the proximal muscles are more often affected control ––EMG can demonstrate positive sharp wave and fibrillations, signs of acute denervation, 3 to 4 weeks Injections after symptom onset nn No specific injection techniques exist for the treatment •• This is seen in peripheral nerves and nerve of neuralgic amyotrophy root distributions, as opposed to just nerve root distribution (as seen in radiculopathy) Surgical Treatment ––EMG performed 3 to 4 months after symptom onset nn No specific surgical interventions exist for the may show chronic denervation with signs of early treatment of neuralgic amyotrophy, although chronic reinnervation (polyphasia) pain can be treated in several ways ––There may be contralateral EMG abnormalities even ––Spinal cord stimulator without symptoms ––Dorsal root entry zone lesioning 108 Neuralgic Amyotrophy (Parsonage-Turner Syndrome)

Consults ––This study looked only at functional recovery and nn Physiatry not EMG findings of reinnervation, so recovery nn Neurology may be exaggerated as there can be muscular Complications of treatment compensation nn Reinnervation usually begins 6 months to 1 year after nn If resistance exercises are begun before adequate initial injury reinnervation is begun, axonal regeneration and subsequent muscle reinnervation may be retarded Helpful Hint ––A follow-up EMG can help demonstrate the degree nn Diagnosis is made by the acute onset of severe pain, of reinnervation of the affected muscles followed by resolution of pain, which is in turn Prognosis followed by muscle weakness and atrophy nn Prognosis for functional recovery is usually good in Suggested Reading most cases Tjoumakaris FP, Anakwenze OA, et al. Neuralgic amyotrophy­ nn One study suggested an 89% functional recovery in (Parsonage-Turner syndrome). J Am Acad Ortho Surg. patients 3 years after symptom onset 2012;20(7):443–449. Radiculopathy Gentry Dodd MD ■ Nathan D. Prahlow MD

Description nn Noncompressive: Radiculopathies are pathologic processes that affect the ––Noncompressive causes can lead to nerve root spinal nerve at the root level that often present as pain infarction or invasion that usually affects the radiating into an extremity sensory portion of the nerve root nn Cervical radiculopathies are usually due to bony Etiology issues, whereas those of the lumbar spine are more nn Spondylosis often caused by disc herniation nn Disk herniation nn Diabetes Risk Factors nn Infection nn Trauma nn Tumor: lipoma, meningioma, neurofibroma nn History of degenerative disc or joint disease nn Infarction nn Arachnoiditis: from surgery, anesthesia, myelogram Clinical Features nn Pain in the neck, arms, trunk, legs, or back

Types nn nn Cervical Potentially atypical pain that presents as chest nn Thoracic pain, breast pain, or facial pain for cervical nn Lumbar radiculopathy nn Numbness or dysesthesia that occurs in a more-or-less Epidemiology typical nerve root distribution pattern nn nn Cervical: Weakness ––Mean age at diagnosis is 47.9 years ––Incidence rates of 63.5 and 107.3 per 100,000 for Natural History men and women, respectively nn In general, the majority of radiculopathy cases are

––Male:female ratio of 1.7:1 self-limited and respond well to conservative therapy IV Radiculopathies/Plexopathies : ––C7 accounts for roughly 70% of all cervical without the need for interventional or surgical radiculopathy cases, C6 20%, and the remaining treatment. 10% between C5, C8, and T1 nn Thoracic: Diagnosis ––Up to 5% of symptomatic herniated discs occur in the thoracic region Differential diagnosis ––Equal rates between men and women nn Peripheral entrapment neuropathy nn Lumbar: nn Brachial/lumbosacral plexopathy ––Equal rates between men and women nn Spinal stenosis ––Majority of lesions involve the L5 and S1 roots nn Cauda equina syndrome History Pathogenesis nn Abrupt onset of symptoms is seen more commonly nn Compressive: with a herniated disc ––Bony overgrowth and degenerative changes in nn If the radiculopathy is caused by spondylosis, the vertebral joints can lead to neuroforaminal symptom onset is more gradual narrowing and compression of the nerve roots Examination ––Disc herniation can also cause nerve root nn Sensory testing compression if the herniation occurs nn Upper and lower limb strength and reflex testing laterally nn Observation for atrophy

109 110 Radiculopathy nn Spurling’s maneuver—extend and rotate the neck nn Oral analgesics toward the symptomatic side with a downward nn Short course of oral steroid medication compression. This test is positive with a reproduction in radiating pain symptoms. Spurling’s maneuver is Exercise very specific, but not all that sensitive nn Physical therapy referrals should focus on range-of- nn Straight leg raise test with reproduction of radicular motion and strengthening exercises symptoms nn Bowstring sign is a relief of radicular pain with flexing Modalities of the knee during the straight leg raise test nn Traction to the cervical and lumbar spines can result in relief of nerve root compression Testing ––Traction is not recommended for cases nn Noncontrast magnetic resonance imaging (MRI), involving spinal cord compression or large disc most helpful when surgery is being considered protrusion, especially central cervical herniated nn Computed tomography (CT) myelography when discs MRI is contraindicated; certain cases may require in nn The efficacy of traction in the treatment of addition to MRI testing radiculopathy is unclear nn Plain films can help establish the extent of spondylosis Injections nn EMG: nn Epidural steroid infections are most effective when the ––Nerve conduction studies and EMG must be etiology is a herniated disc performed together nn Caudal epidural steroid injections are most beneficial ––Sensory nerve action potentials are normal for S1 nerve root lesions ––Motor action potentials may have decreased amplitudes Surgical treatment ––EMG should be performed in three muscles of the nn Should be reserved for cases that do not respond to an same myotome with different peripheral innervations adequate trial of conservative treatment (usually 6–12 •• Motor units may have increased duration, weeks) or if there is presence of progressive motor amplitude, and polyphasia with decreased weakness recruitment nn Cervical: •• Positive sharp waves and fibrillations appear in ––Anterior cervical discectomy and fusion the periphery in about 3 to 6 weeks ––Posterior laminoforaminotomy, used when a single Pitfalls lateral disc herniation is present nn Missing a conus medularis lesion or myelopathy nn Lumbar: nn Presence or absence of bowel and bladder complaints ––Laminectomy may be misleading ––Discectomy

Red flags Consults nn Progressive weakness nn Physiatry nn Difficulty walking and bowel/bladder dysfunction are nn Neurology suggestive of myelopathy nn Neurosurgery nn A history of fever, chills, unexplained weight loss, and intravenous drug abuse should cause concern that Complications of treatment tumor or infection is active nn Medication side effects nn An increase in symptoms when lying down is nn Potential for intravascular or intraspinal injections suggestive of a dural mass with interventional procedures nn Treatment Abnormalities seen on imaging do not always correlate with symptoms, and patients can be referred Medical for unnecessary surgery nn Avoidance of exacerbating activities nn Surgical complications: failed back surgery syndrome, nn Non-steroidal anti-inflammatory drugs (NSAIDs) chronic pain, and arachnoiditis Radiculopathy 111

Prognosis Suggested Readings nn In the absence of worsening symptoms, increasing Chiodo A, Haig AJ. Lumbosacral radiculopathies: Conservative muscle weakness, bowel or bladder dysfunction, the approaches to management. Phys Med Rehabil Clin N Am. 2002;13(3):609–621, viii. majority of cases resolve with conservative measures Wilbourn AJ, Aminoff MJ. AAEM minimonograph 32: The in 2 to 3 months electrodiagnostic examination in patients with radiculopathies. American Association of Electrodiagnostic Helpful Hint Medicine. Muscle Nerve. 1998;21(12):1612–1631. nn Until the diagnosis is confirmed by EMG, Wolff MW, Levine LA. Cervical radiculopathies: Conservative approaches to management. Phys Med Rehabil Clin N Am. fluoroscopically guided injection, or surgery, one should 2002;13(3):589–608, vii. describe the symptoms of “radiating limb pain,” rather than label the patient with the term “radiculopathy.”

IV: Radiculopathies/Plexopathies IV:

Thoracic Outlet Syndrome—Neurogenic Nathan D. Prahlow MD

Description History A disputed syndrome of upper limb symptoms, including nn Neck trauma radiating pain, paresthesias, and weakness, due to the nn Limb pain compression of the neurovascular bundle superior to the nn Paresthesias first rib and posterior to the clavicle nn Shoulder/arm/hand weakness nn Neck pain Etiology/Types nn Occipital headaches nn Neurogenic nn May have symptoms of Raynaud’s phenomenon nn Arterial Examination nn Venous nn Neck rotation with side-bending to elicit Epidemiology pain/paresthesias in contralateral limb nn Tenderness on palpation of scalene muscles nn 10 cases per 100,000 people nn Symptoms brought on within 60 seconds of placing nn >90% neurogenic arm in 90 degrees abduction and full external nn <1% arterial rotation nn Pathogenesis Modified Upper Limb Tension Test of Elvey: Abduct both shoulders to 90 degrees with extended elbows nn Brachial plexus compression from the scalene muscles (causes ipsilateral symptoms), then dorsiflex both Risk Factors wrists (may increase ipsilateral symptoms), then tilt head to side—ear to shoulder (causes contralateral nn Cervical rib found in <1% of the population symptoms) (70% seen in women); most are asymptomatic nn Check pulses—normal in neurogenic, may be absent nn Cervical rib predisposes to symptom development in arterial after neck trauma Testing Clinical Features nn Cervical plain films: rule out cervical rib nn Neck and arm pain nn EMG: typically normal, but may have nonspecific nn Arm paresthesias abnormalities. Medial antebrachial cutaneous sensory, nn Upper limb weakness median motor, ulnar motor, and ulnar sensory studies nn Occipital headaches may be abnormal Pitfalls Natural History nn Adson’s Test is of little to no clinical value in any type nn May develop after neck trauma, such as whiplash-type of TOS injuries Red flags Diagnosis nn Raynaud’s phenomenon may cause confusion with Differential diagnosis arterial TOS nn Cervical radiculopathy Treatment nn Brachial plexopathy nn Arterial thoracic outlet syndrome (TOS) Medical treatment nn Venous TOS nn Little evidence to support a specific treatment nn Posterior shoulder girdle myofascial pain syndrome nn Consider the options listed below, based on the nn Ulnar neuropathy physician and patient preference

112 Thoracic Outlet Syndrome—Neurogenic 113

Exercise nn Surgery: incisional pain, pneumothorax, nn Restore cervical spine range of motion and intercostalbrachial neuralgia, wound infection, shoulder/arm function wound hematoma nn Correct posture Modalities Prognosis nn Unknown nn Cervical traction nn Rare surgery nn Heat for muscle spasm/pain nn May require several opinions and consults from Injection TOS experts nn Botulinum toxin injection into scalene muscles Surgical Helpful Hint nn First cervical rib resection nn Specifically include the study of the medial nn Supraclavicular neuroplasty of the brachial plexus antibrachial cutaneous sensory nerve if referring for EMG/NCS Consults nn Electromyography Suggested Readings nn Thoracic surgery Povlsen B, Belzberg A, Hansson T, et al. Treatment for thoracic nn Neurosurgery outlet syndrome (Review). The Cochrane Collaboration. Complications of treatment Indianapolis, IN: J Wiley & Sons; 2010. Sanders RJ, Hammond SL, Rao NM. Diagnosis of nn Complications of therapies, modalities, and any thoracic outlet syndrome.­ J Vascular Surg. 2007;46(3): medications utilized 601–604. IV: Radiculopathies/Plexopathies IV:

Thoracic Outlet Syndrome—Vascular Nathan D. Prahlow MD

Description History A disputed syndrome of upper limb symptoms, includ- nn Neck trauma ing radiating pain, paresthesias, and weakness, due to the nn Limb pain, paresthesias, shoulder/arm/hand compression of the neurovascular bundle superior to the weakness, neck pain, and occipital headaches, as for first rib and posterior to the clavicle neurogenic TOS nn Arterial: pallor, coldness, paresthesias Etiology/Types nn Venous: arm swelling, cyanosis, aching pain, nn Neurogenic paresthesias worst in hand/fingers nn Arterial nn May have symptoms of Raynaud’s phenomenon nn Venous Examination Epidemiology nn Arterial: digital ischemia, pallor, coldness nn nn 10 cases per 100,000 people Venous: arm swelling and cyanosis, which may be nn >90% neurogenic worst distally nn nn <1% arterial Nerve tension tests and scalene palpation, as for neurogenic TOS Pathogenesis Testing nn Arterial: Emboli from aneurysm or subclavian artery nn Cervical plain films to evaluate for cervical rib stenosis nn Duplex ultrasound testing to evaluate vasculature nn Venous: Thrombosis or other subclavian vein nn Arteriography for planning obstruction Pitfalls Risk Factors nn Adson’s Test is of little to no clinical value in any type nn Cervical rib found in <1% of the population (70% seen of TOS in women); most are asymptomatic Red flags nn Most cervical ribs cause neurogenic thoracic outlet nn Raynaud’s phenomenon may cause confusion with syndrome (TOS) arterial TOS

Clinical Features Treatment nn Hand and forearm symptoms greater than neck and shoulder symptoms Medical nn Little evidence to support a specific treatment Natural History Exercise nn May develop spontaneously nn None indicated nn Venous TOS may develop after excessive use of the upper limb Modalities nn None indicated Diagnosis Injection Differential diagnosis nn None indicated nn Raynaud’s phenomenon Surgical nn Cervical radiculopathy nn First cervical rib resection nn Brachial plexopathy nn Surgical repair of artery if abnormalities seen nn Neurogenic TOS nn Posterior shoulder girdle myofascial pain syndrome Consults nn Sympathetic response nn Vascular surgery 114 Thoracic Outlet Syndrome—Vascular 115

Complications of treatment Helpful Hint nn Surgery: incisional pain, pneumothorax, nn Differentiate between arterial and venous causes, intercostobrachial neuralgia, wound infection, rather than lumping the two together as wound hematoma “vascular TOS”

Prognosis Suggested Readings nn Unknown Povlsen B, Belzberg A, Hansson T, et al. Treatment for thoracic outlet syndrome (Review). The Cochrane Collaboration. nn Rare surgery Indianapolis, IN: J Wiley & Sons; 2010. nn May require several opinions and consults from Sanders RJ, Hammond SL, Rao NM. Diagnosis of thoracic outlet TOS experts syndrome. J Vascular Surg. 2007;46(3):601–604.

IV: Radiculopathies/Plexopathies IV:

Motor Neuron V Diseases Amyotrophic Lateral Sclerosis Cynthia L. Bodkin MD

Description Natural History Amyotrophic lateral sclerosis (ALS) is a progressive nn Progressive weakness of skeletal muscles, including ­neurodegenerative disorder affecting the motor neurons respiratory muscles, leading to respiratory failure in the brain and spinal cord. Diagnosis Etiology/Types Differential diagnosis nn Approximately 10% is genetic nn Cervical spondylosis nn 90% sporadic with unknown cause nn Multifocal motor neuropathy with conduction block nn Progressive bulbar palsy—primarily affects bulbar nn Myasthenia gravis muscles nn Spinal muscular atrophy nn Progressive muscular atrophy—only lower motor History neuron findings nn nn Primary lateral sclerosis—only upper motor neuron Progressive painless weakness nn findings Twitching or fasciculations nn Cramps Epidemiology nn Muscle atrophy or wasting nn Prevalence estimated 6 per 100,000 nn Shortness of breath nn Incidence 2 per 100,000 nn Dysarthria nn White population more commonly affected nn Dysphagia nn Male-to-female ratio of 1.5:1 nn Falls nn Age of onset is most often between 40 and 70 years, Examination but can be any age nn Muscle weakness nn Atrophy Pathogenesis nn Spasticity nn Unknown in majority of cases nn Brisk reflexes nn Roughly 10% to 15% of the genetic cases are from nn Abnormal reflexes superoxide dismutase 1 mutation nn Fasciculations nn Other known genes TDP-43 (TAR DNA-binding nn Sensory generally preserved protein-43), FUS (fused in sarcoma/translated Testing in liposarcoma) gene, and valosin-containing nn protein Nerve conduction studies (NCS)—decreased motor amplitudes with normal sensory responses Risk Factors nn EMG—fibrillation and fasciculation potentials with nn Service in United States military large complex motor unit potentials nn Deployed in Gulf War nn Magnetic resonance imaging (MRI) brain and spine— rule out other causes Clinical Features nn Gene testing if family history exists nn Painless progressive weakness starts in one area and nn Rapid plasma reagin (RPR)—rule out syphilis spreads to rest of body nn B12 nn Lower motor neuron signs, such as fasciculations and nn HIV atrophy nn Anti-GM1 antibodies in pure lower motor neuron disease nn Upper motor neuron (corticospinal track) signs, nn Anti-acetylcholine receptor antibodies such as spasticity, brisk reflexes, and Babinski reflex nn Anti-muscle specific kinase (MuSK) antibodies nn Pseudobulbar affect nn Hexosaminidase A nn Frontotemporal dementia nn Lyme disease

118 Amyotrophic Lateral Sclerosis 119

Pitfalls Consults nn Delayed diagnosis nn Neurology nn Physical medicine and rehabilitation Red flags nn Pulmonary nn Gynecomastia suggests Kennedy’s disease nn Speech Pathology nn Physical Therapy Treatment nn Occupational Therapy Medical nn Dietitian nn Riluzole Complications of treatment nn Dextromethorphan/quinidine for pseudobulbar nn Nausea and elevated liver function test from riluzole affect nn Dextromethorphan/quinidine—arrhythmias in nn Supportive patients with prolonged QT interval nn Bilevel positive airway pressure nn Feeding tube Prognosis nn Progressive weakness until completely paralyzed or Exercises until respiratory failure nn Stretching nn Mean survival 2 to 5 years after onset of weakness nn Range of motion nn Avoid aggressive physical therapy or strengthening Helpful Hints Modalities nn Quality of life main treatment goal nn nn Active and/or passive range of motion Beware of painless weakness Surgical Suggested Readings nn Tracheostomy and ventilation depending on patient’s Amato AA, Russell JA. Neuromuscular disorders (pp. viii, 775). New York: McGraw-Hill Medical; 2008. wishes: Brown WF, Bolton CF, Aminoff MJ. Neuromuscular Function and ––Percutaneous endoscopic gastrostomy tube Disease: Basic, Clinical, and Electrodiagnostic Aspects. 1st ed. placement depending on patient’s wishes 2 volumes, (pp. xxiii, 1948). Philadelphia, PA: Saunders; 2002. V: MotorV: Neuron Diseases

Hereditary Spastic Paraplegia Gabriel Smith MD ■ Nathan D. Prahlow MD

Description Diagnosis A genetic, neurodegenerative disorder characterized by Differential diagnosis progressive spasticity and weakness of the lower limbs. nn Cerebral palsy nn Etiology/Types Multiple sclerosis nn Krabbe disease nn Hereditary Spastic Paraplegia (HSP) is a hereditary nn HIV/AIDS condition nn Vitamin deficiency (B12 and E) nn Autosomal dominant, autosomal recessive and nn Wilson’s disease X-linked recessive inheritance patterns nn Uncomplicated (pure) HSP History nn Complicated HSP: Pure HSP + other neurologic nn Family history of HSP dysfunction nn Weakness and spasticity of legs develops over months Epidemiology nn Walking impairment due to foot drop nn Prevalence is 3 to 10 cases per 100,000 nn Urinary urgency nn Male-to-female ratio of 1:2 nn Patients with complicated HSP demonstrate nn Age ranging from infancy to 70 years deterioration in cognitive function and other neurologic functioning Pathogenesis Examination nn Inheritance of mutations results in retrograde nn degeneration of the longest nerve fibers in the Lower extremity muscle weakness, increased tone, corticospinal tracts and dorsal columns and increased deep tendon reflexes nn Upper extremity muscle tone and strength are Risk Factors normal nn nn Family history of HSP Foot drop on gait examination Testing Clinical Features nn SPG4 and SPG3A (mutated genetic loci) nn Classically, pure HSP is characterized by subtle nn Venereal Disease Research Laboratory test—rule out development of leg stiffness, weakness, and increased syphilis tone with spared sensation nn HIV antibody nn Complicated HSP is comprised of pure HSP and nn Lumbar puncture—evaluate for multiple sclerosis additional neurologic and cognitive deficits, including nn Vitamins B12 and E ataxia, mental retardation, peripheral neuropathy, and nn Serum copper and ceruloplasmin epilepsy nn Galactosylceramide beta-galactosidase nn Severity of disease is highly variable nn EMG nn Magnetic resonance imaging (MRI)—rule out spine Natural History pathology nn Inherited mutations lead to protein dysfunction in various intracellular sites throughout nerve cells of the Pitfalls corticospinal tracts and dorsal columns nn Delayed diagnosis nn Impaired membrane trafficking and axonal transport lead to neurodegeneration Red flags nn Patients experience gradual stiffening and weakness in nn Development of further neurologic or cognitive the lower limbs with variable loss of function decline in HSP patients

120 Hereditary Spastic Paraplegia 121

Treatment Complications of treatment nn Medical Antispasticity medications may make walking more difficult because stiffness and spasticity may actually nn Baclofen (taken orally or intrathecally) help compensate for weakness nn Tizanadine and dantrolene also decrease spasticity nn Oxybutynin for urinary urgency Prognosis nn Selective serotonin reuptake inhibitors (SSRIs) for nn HSP is quite heterogeneous with variable prognoses depression due to loss of function nn In general, uncomplicated HSP is not associated with Exercises increased mortality nn Physical therapy—stretching, strengthening, and nn Complicated HSP is associated with greater morbidity walking exercises and mortality due to additional neurocognitive deficits Modalities nn Heat for muscle pain Helpful Hint nn Injection Obtaining a thorough family history is very important in making a correct diagnosis nn Botulinum toxin injections for spasticity Surgical Suggested Readings nn None Fink J. Advances in the hereditary spastic paraplegias. Exp Neurol. 2003;184:106–110. Consults Salinas S, et al. Hereditary spastic paraplegia: Clinical nn Neurology features and pathogenetic mechanisms. Lancet Neurol. 2008;7(12):1127–1138. nn Physical and occupational therapy nn Physical medicine and rehabilitation V: MotorV: Neuron Diseases

Poliomyelitis Gabriel Smith MD ■ Nathan D. Prahlow MD

Description nn Incubation of 3 to 6 days A viral disease affecting the anterior horn motor neurons nn Progressive inflammation of nerves leads to cell death of the spinal cord and the nerve cells within the bulbar and can result in paralysis if damage is sufficient region of the brainstem, leading to flaccid weakness or (>90% neuronal cell death) paralysis. Diagnosis Etiology/Types Differential diagnosis nn Poliomyelitis is caused by poliovirus, a member of the nn Guillain-Barré syndrome enterovirus group nn West Nile virus nn Spread is mainly by fecal-oral route nn Viral myositis nn Types include subclinical poliomyelitis, nonparalytic poliomyelitis, and paralytic poliomyelitis; may also History be divided by affected location: spinal poliomyelitis, nn Recent travel to endemic area bulbar poliomyelitis, and bulbospinal poliomyelitis nn Unavailability (or refusal) of polio vaccine nn Poor hygiene Epidemiology nn Fever, nn Very rare (<1500 cases worldwide) nn Asymmetric, proximal weakness nn Male-to-female ratio of 1:1 Examination nn Most common in children <5 years old: Minor Illness ––Bulbospinal poliomyelitis accounts for 19% of cases nn ––Bulbar poliomyelitis accounts for 2% of cases Nausea/vomiting nn Fever, abdominal pain Pathogenesis Major Illness nn Infection with poliovirus nn Exam consistent with aseptic meningitis nn Profound asymmetric weakness/paralysis Risk Factors nn Contractures nn Lack of immunization nn Age <5 years Testing nn Travel to endemic area nn Cerebrospinal fluid (pressure/cell count/protein) nn Complete blood count Clinical Features nn EMG nn Most infections with poliovirus are asymptomatic nn Throat, stool, blood samples for poliovirus (subclinical poliomyelitis) nn Polymerase chain reaction to distinguish wild-type nn Fever, malaise, sore throat, anorexia, and headache poliovirus from vaccine strains (nonparalytic poliomyelitis) Pitfalls nn Severe myalgias followed by flaccid, asymmetric nn Delayed diagnosis proximal weakness in legs (most common), arms or nn Vaccination of immunocompromised patients may muscles of the trunk lead to contraction of disease nn Irreversible paralysis, exceedingly dangerous when nn Poor compliance with vaccination, and difficulty muscles of respiration are involved with maintaining accurate records in endemic regions Natural History Red flags nn Poliovirus enters nervous system via axonal nn Respiratory distress/failure transport through peripheral nerves, or by crossing nn Muscle weakness or paralysis decades following polio the blood–brain barrier illness (post-polio syndrome) 122 Poliomyelitis 123

Treatment nn nn Medical nn Physical medicine and rehabilitation nn Supportive treatment as there is no cure nn Treatment is aimed at prevention Complications of treatment nn Vaccination with injected polio vaccine (inactive) or oral nn Much higher rate of vaccine-induced polio in polio vaccine (active, used mainly in endemic regions) immunocompromised patients Exercises Prognosis nn Physical therapy—passive range of motion and nn Infection is asymptomatic in most cases splinting help prevent contracture nn Patients with nonparalytic polio recover fully nn Frequent repositioning in paralyzed patients nn About 5% patients with paralytic polio die from nn Speech therapy to prevent aspiration in patients with respiratory failure cranial nerve involvement nn Post-polio syndrome may occur 20 to 40 years Modalities following bout with paralytic polio (prognosis is nn Heat for muscle pain good)

Injection Helpful Hints nn Injectable polio vaccine (IPV) is injectable form of nn Polio is nearly eradicated inactivated vaccine nn Goal is prevention with vaccination Surgical nn Be aware of post-polio syndrome in patients with nn Release of contractures history of paralytic polio Consults Suggested Reading nn Neurology Cohen JI. Enteroviruses and reoviruses. Harrison’s Principles of nn Infectious disease . 17th ed. New York: McGraw Hill; 2008. V: MotorV: Neuron Diseases

Post-Polio Syndrome Shangming Zhang MD FAAPMR

Description nn Sleep apnea Post-poliomyelitis syndrome (PPS) is a complex of late nn Swallowing or breathing problems onset of neuromuscular symptoms that occurs decades after a patient has recovered from the acute polio infec- Natural History tion. The common symptoms include fatigue, new muscle nn Slowly progressive with period of stability of 3 to weakness or atrophy, and musculoskeletal pain. Patients 10 years also frequently complain of difficulties with walking and stair-climbing. Diagnosis Differential diagnosis Etiology/Types nn Peripheral polyneuropathy nn Unclear. The most accepted hypothesis is that excess nn Myopathy metabolic demand on remaining motor neurons leads nn Multilevel radiculopathy to their eventual deterioration nn West Nile virus infection nn Amyotrophic lateral sclerosis Epidemiology nn Multiple sclerosis nn 29% to 64% of polio survivors nn Myasthenia gravis nn 200,000 to 640,000 PPS cases in the United States nn 12 to 20 million worldwide History nn Onset of PPS approximately 30 years after acute polio nn Confirmed history of acute paralytic polio with nn Affects women more than men residual muscle weakness and atrophy nn A period of partial or complete functional recovery Pathogenesis after acute polio, followed by interval of stable The precise cause of PPS remains unclear. Several hypoth- neurologic function for at least 15 years eses have been proposed as follows: nn Fatigue nn New onset or increased muscle weakness and nn Remaining healthy motor neurons cannot maintain new atrophy sprouts due to denervation exceeding reinnervation nn Muscle and or joint pain nn Chronic inflammation or cellular immunity-mediated nn Symptoms at least 1 year process nn Reactivation of persistent latent viruses causes motor Examination neuronal loss nn Progressive weakness in previously weak muscle nn Aging: the interval between acute polio and PPS is a groups or new weakness in previously clinically risk factor for PPS unaffected muscle groups nn Weakness Risk Factors nn Deep tendon reflexes absent nn Severe residual weakness nn Sensation intact nn Early bulbar respiratory difficulty in the acute phase nn Electromyographic evidence of denervation nn Aging Pitfalls nn Clinical Features Misdiagnosis for any of the conditions described in the differential diagnosis nn Muscle or joint pain nn Fatigue Red flags nn Muscle weakness and atrophy nn Occult fractures—may be overlooked in case of nn Poor endurance muscle pain

124 Post-Polio Syndrome 125

Treatment Consults nn Medical Interventional for nerve blocks nn Lamotrigine, bromocriptine, and pyridostigmine Complications of treatment reported to improve fatigue nn Fractures nn Modafinil and corticosteroids ineffective nn Falls nn IVIG 2 g/kg over 2 to 5 days in refractory cases nn Upper extremity entrapment neuropathy

Exercise Prognosis nn Rehabilitation management is the mainstay of nn Slowly progressive with period of stability of 3 to treatment 10 years nn Submaximal aerobic training and low-intensity muscular strengthening Helpful Hints nn Aquatic therapy has a positive impact on pain and nn PPS is essentially a diagnosis of exclusion made in muscle function polio survivors nn Due to high-risk group for fall and fracture, Modalities bone density assessment, review of fall risk, and nn Transcutaneous electrical nerve stimulation (TENS) therapeutic intervention should be considered for all unit, heat, ice can be used to manage pain PPS patients nn Pain is the most common complaint in >90% of cases. Injections Most frequently reported pain sites are shoulders, nn Nerve blocks effective to relieve pain lower back, legs, and hips Surgical Suggested Reading nn Joint deformities, contractures, and leg length Gonzalez H, Olsson T, Borg K. Management of postpolio discrepancy may require surgery syndrome. Lancet Neurol. 2010;9:634–642. V: MotorV: Neuron Diseases

Primary Lateral Sclerosis Cynthia L Bodkin MD

Description nn Spastic dysarthria Primary lateral sclerosis (PLS) is a progressive neurode- nn Falls generative disorder affecting the upper motor neurons in Examination the brain and spinal cord. nn Muscle weakness nn Spasticity Etiology/Types nn Brisk reflexes nn Unknown nn Abnormal reflexes Epidemiology Testing nn Unclear nn Nerve conduction studies (NCS)—normal nn Approximately 0.5% of patients with amyotrophic nn Magnetic resonance imaging (MRI) of brain and lateral sclerosis (ALS) spine—rule out other causes nn Male-to-female estimated ratio of 1:1 nn Rapid plasma reagin (RPR)—rule out syphilis nn Age of onset is similar to ALS nn B12 nn HIV Pathogenesis nn Cerebrospinal fluid—multiple sclerosis panel nn nn Unknown Lyme disease nn Gene testing for hereditary spastic paraparesis Risk Factors Pitfalls nn None known nn Delayed diagnosis Red flags Clinical Features nn Family history nn Progressive stiffness and weakness, usually starting nn Visual symptoms in the lower extremities then spreading to rest of the body Treatment nn Upper motor neuron (corticospinal track) signs, such Medical as spasticity, brisk reflexes, and Babinski reflex nn nn Can have pain due to spasticity Baclofen nn Tizanidine Natural History nn Benzodiazepines nn nn Progressive spasticity and weakness of skeletal muscles Supportive nn Bilevel positive airway pressure nn Diagnosis Feeding tube Exercises Differential diagnosis nn Stretching nn Cervical spondylosis nn Range of motion nn Hereditary spastic paraparesis nn Progressive multiple sclerosis Modalities nn ALS nn Active and/or passive range of motion nn B12 deficiency nn Massage nn Pool therapy History nn Progressive spasticity and weakness Injection nn Pain from spasticity nn Botulism toxin for spasticity management

126 Primary Lateral Sclerosis 127

Surgical nn Sedation nn Tracheostomy and ventilation depending on patient’s nn Confusion wishes Prognosis ––Percutaneous endoscopic gastrostomy tube nn placement depending on patient’s wishes Progressive weakness and stiffness until completely nn Baclofen pump for spasticity management paralyzed or until respiratory failure nn Average disease duration is 20 years Consults nn Some “PLS” patients may later develop lower motor nn Neurology neuron findings nn Physical medicine and rehabilitation Helpful Hint nn Pulmonary nn Quality of life main treatment goal nn Speech pathology nn Physical and occupational therapist Suggested Readings nn Dietitian Amato AA, Russell JA. Neuromuscular Disorders (pp. viii, 775). New York: McGraw-Hill Medical; 2008. Complications of treatment Brown WF, Bolton CF, Aminoff MJ. Neuromuscular Function and Disease : Basic, Clinical, and Electrodiagnostic Aspects. nn Nausea and elevated liver function test from 1st ed. 2 volumes (pp. xxiii, 1948). Philadelphia, PA: medications Saunders; 2002. V: MotorV: Neuron Diseases

Progressive Bulbar Palsy Cynthia L. Bodkin MD

Description nn Difficulty chewing Progressive bulbar palsy is a progressive neurodegen- nn Drooling erative disorder affecting the lower motor neurons to Examination the facial muscles involved in swallowing, chewing, and nn Bulbar muscle weakness speaking. nn Fasciculations in bulbar muscles nn Less prominent arm and leg weakness with upper and Etiology/Types lower motor neuron findings nn Unknown nn Abnormal reflexes

Epidemiology Testing nn Nerve conduction studies (NCS)—fasciculation and nn Unclear fibrillation potentials with large complex motor unit nn Approximately 25% of patients with amyotrophic potentials diffusely lateral sclerosis present with bulbar symptoms nn Magnetic resonance imaging (MRI) of brain and nn Age of onset usually between 50 and 70 years, but can spine—rule out other causes be seen in any age nn HIV nn Lyme disease Pathogenesis nn Acetylcholine receptor antibodies nn Majority unknown nn SOD1 mutation Pitfalls nn Delayed diagnosis Risk Factors Red flags nn Family history nn Visual symptoms such as double vision nn Eye movement abnormalities Clinical Features nn Progressive dysphagia and dysarthria Treatment nn Choking Medical nn Pneumonia nn Anticholinergic medication for drooling nn Emotional liability nn Supportive nn Bilevel positive airway pressure Natural History nn Feeding tube nn Progressive weakness of bulbar muscles leading to inability to speak or swallow Exercises nn Stretching and range of motion for limb symptoms Diagnosis Injection Differential diagnosis nn Botulism toxin to the parotid gland for saliva nn Myasthenia gravis management nn Brain stem stroke Surgical nn Ocularpharyngeal muscular dystrophy nn Tracheostomy and ventilation depending on patient’s History wishes nn Choking ––Percutaneous endoscopic gastrostomy tube nn Slurred speech placement depending on patient’s wishes

128 Progressive Bulbar Palsy 129

Consults Prognosis nn Neurology nn Progressive weakness of bulbar muscles until nn Physical medicine and rehabilitation respiratory failure from pneumonia nn Pulmonary nn Survival 1 to 3 years nn Speech pathology nn Physical and occupational therapist Helpful Hint nn Dietitian nn Quality of life main treatment goal Complications of treatment nn Nausea and elevated liver function test from medications Suggested Readings Amato AA, Russell JA. Neuromuscular Disorders (p. viii, 775). nn Sedation New York: McGraw-Hill Medical; 2008. nn Confusion Brown WF, Bolton CF, Aminoff MJ. Neuromuscular Function and nn Dry mouth Disease: Basic, Clinical, and Electrodiagnostic Aspects. 1st ed., nn Urinary retention 2 volumes (pp. xxiii, 1948). Philadelphia, PA: Saunders; 2002. V: MotorV: Neuron Diseases

Progressive Muscular Atrophy Cynthia L. Bodkin MD

Description Examination Progressive muscular atrophy is a progressive neurode- nn Muscle weakness generative disorder affecting the lower motor neurons nn Atrophy only. nn Fasciculations nn Sensation generally preserved Etiology/Types Testing nn Unknown nn Nerve conduction studies (NCS)—decreased motor nn Flail arm variant amplitudes with normal sensory responses nn Flail leg variant nn EMG—fibrillation and fasciculation potentials with large complex motor unit potentials Epidemiology nn Magnetic resonance imaging (MRI) of the brain and nn Estimated to be around 4% of amyotrophic lateral spine—rule out other causes sclerosis (ALS) cases nn Anti-GM1 antibodies nn Males more likely to be affected nn Hexosaminidase A nn Younger age of onset than typical ALS nn Lyme disease Pathogenesis Pitfalls nn Unknown nn Delayed diagnosis Red flags Risk Factors nn Gynecomastia suggests Kennedy’s disease nn None known Treatment Clinical Features Medical nn Painless progressive weakness starts in one area and nn Riluzole spreads to the rest of body nn Supportive nn Lower motor neuron signs such as fasciculations and nn Bilevel positive airway pressure atrophy nn Feeding tube Natural History Exercises nn Progressive weakness of skeletal muscles, including nn Stretching respiratory muscles, leading to respiratory failure nn Range of motion nn Avoid aggressive physical therapy or strengthening Diagnosis Modalities Differential diagnosis nn Active and/or passive range of motion nn Multifocal motor neuropathy with conduction block Surgical nn Spinal muscular atrophy nn Tracheostomy and ventilation depending on patient’s nn Classic ALS choice History nn Percutaneous endoscopic gastrostomy tube placement nn Progressive painless weakness depending on patient’s choice nn Twitching or fasciculations Consults nn Cramps nn Neurology nn Muscle atrophy or wasting nn Physical medicine and rehabilitation nn Shortness of breath nn Pulmonary nn Falls nn Speech pathology

130 Progressive Muscular Atrophy 131 nn Physical and occupational therapist Helpful Hints nn Dietitian nn Quality of life—main treatment goal nn Complications of treatment Beware of painless weakness nn Nausea and elevated liver function test from Riluzole Suggested Readings Amato AA, Russell JA. Neuromuscular Disorders (pp. viii, 775). Prognosis New York: McGraw-Hill Medical; 2008. nn Progressive weakness until completely paralyzed or Brown WF, Bolton CF, Aminoff MJ. Neuromuscular Function until respiratory failure and Disease: Basic, Clinical, and Electrodiagnostic Aspects. nn Similar to classic ALS (2–5 years) with possible 1st ed., 2 volumes (pp. xxiii, 1948). Philadelphia, PA: Saunders; 2002. slightly slower course Wijesekera LC, Mathers S, Talman P, Galtrey C, et al. Natural nn Flail limb variants’ 5-year survival ranges from history and clinical features of the flail arm and flail leg ALS 52% to 64% variants. Neurology. 2009;72(12):1084–1094. V: MotorV: Neuron Diseases

Spinal and Bulbar Muscular Atrophy (Kennedy’s Disease) Nathan D. Prahlow MD

Description nn Endocrine abnormalities, including gynacomastia, A progressive, X-linked, degenerative motor neuron reduced fertility rate, azoospermia, oligospermia, and disease, characterized by asymmetric weakness in the diabetes hip and shoulder girdle musculature and associated nn One-third of patients develop inguinal hernias muscle cramping, atrophy, and fasciculations. Speech nn The risk of androgenic alopecia is reduced and swallowing difficulties develop as the disease progresses. Natural History nn Age of onset ranges between 20 and 60 years Etiology/Types nn Median age to require a handrail to ascend stairs is nn Almost exclusively affects males 49 years nn Female carriers, because of lyonization, may have nn Median age requiring use of a cane for ambulation is mild muscle cramps and weakness, fasciculations, and 59 years elevated creatine kinase levels nn Median age requiring wheelchair for mobility is 61 years Epidemiology nn There may be a significant variability within affected nn X-linked recessive families for age of onset, rate of progression, and nn Prevalence of 3.3 per 100,000, but geographically severity of disease variable, with a prevalence of 13 per 85,000 near nn Severity ranges from asymptomatic (elevated Vaasa, Finland creatine kinase only), to severe muscle disease with bulbar involvement requiring mechanical Pathogenesis ventilation nn Expansion of the CAG trinucleotide repeat in the androgen receptor gene on chromosome Xq11-12 Diagnosis nn Affected subjects typically have repeat counts greater Differential diagnosis than 40; normal individuals have 11–33 repeats nn Amyotrophic lateral sclerosis nn Loss of anterior horn cells in the brainstem and spinal nn Primary lateral sclerosis cord nn Adult-onset spinal muscular atrophy nn Various muscular dystrophies Risk Factors nn Multifocal motor neuropathy nn Mother as a carrier of the abnormality nn Mitochondrial disorders Clinical Features History nn Weakness and wasting of limb, bulbar, and facial nn Family history muscles, in an asymmetric distribution nn Physical changes as described above nn Proximal flaccid weakness (initially lower limbs), Examination which progresses over time nn Examine for atrophy, weakness, bulbar abnormalities nn Bilateral Dupuytren’s contractures may be present nn Dysarthria and dysphagia are common; respiratory Testing difficulties may arise nn Serum creatine kinase may be mildly elevated; may be nn Postural tremor and easy fatigability may be seen detectable prior to other disease findings

132 Spinal and Bulbar Muscular Atrophy (Kennedy’s Disease) 133 nn EMG findings: Decreased compound muscle action Surgical potentials, sensory nerve action potentials, and nn Generally none indicated conduction velocities are present, with upper limb nn Percutaneous endoscopic gastrostomy tube placement abnormalities typically greater than lower limb might be needed in cases of severe dysphagia (has nn Scrotal skin biopsy shows high degree of nuclear never been reported) accumulation of mutant androgen receptor protein Consults nn Genetic testing, including demonstration of the nn Neurology expansion of the CAG repeat in the androgen receptor nn gene, is the gold standard Complications of treatment Pitfalls nn Side effects of any medication or intervention nn Variability of disease within known affected families attempted may confound the examiner Red flags Prognosis nn Severe bulbar symptoms require earlier respiratory nn One of the best prognoses and survival rates of motor intervention neuron diseases nn Some affected males remain asymptomatic for their Treatment entire lives nn Disease progression is generally slow; life expectancy Medical is normal or only minimally reduced nn Symptomatic treatment only nn Pneumonia and respiratory failure are common nn Research into androgen deprivation is ongoing causes of death Exercise nn Maintenance of range of motion Helpful Hint nn No specific recommendations exist, but avoidance of nn The greater the number of CAG repeats, the earlier the strenuous exercise may be appropriate onset of symptoms

Modalities Suggested Readings Finsterer J. Bulbar and spinal muscular atrophy (Kennedy’s nn Symptomatic treatment, as needed disease): A review. Eur J Neurol. 2009;16:556–561. nn For significant respiratory dysfunction, noninvasive Finsterer J. Perspectives of Kennedy’s disease. J Neurolog Sci. positive pressure ventilation may be indicated 2010;298:1–10. V: MotorV: Neuron Diseases

Spinal Muscular Atrophy Shangming Zhang MD FAAPMR

Description nn Type III SMA (Kugelberg-Welander disease): Spinal muscular atrophy (SMA) is the second most symmetric proximal weakness, independent standing common autosomal-recessive neuromuscular disorder. It and walking but trouble with going up and down is characterized by progressive symmetric muscle weakness stairs, with or without positive Gowers’ sign, calf due to degeneration and loss of lower motor neurons (ante- pseudohypertrophy, and normal intelligence rior horn cells in the spinal cord and cranial nerve nuclei). nn Type IV SMA: benign, similar to type III

Etiology/Types Natural History nn Due to mutations in survival motor neuron (SMN) nn Anterior horn motor neuron degeneration and death gene nn Peripheral denervation, muscular weakness, atrophy, nn Acute infantile (SMA type I or Werdnig-Hoffmann and pain disease): onset from birth to 6 months nn Respiratory failure and death in severe cases nn Chronic infantile (SMA II): onset between 6 and Diagnosis 12 months nn Chronic juvenile (SMA III or Kugelberg-Welander Differential diagnosis disease): onset after 12 months nn Becker muscular dystrophy nn Adult onset (SMA IV): onset of symptoms during nn Amyotrophic lateral sclerosis early adulthood with more favorable prognosis nn Congenital myopathies nn Myasthenia gravis Epidemiology nn Disorders of carpotonia nn Estimated incidence of approximately 1 in 10,000 to nn Disorders of carbohydrate metabolism 15,000 live births with a genetic carrier frequency of nn Botulism 1 of 50 to 80 nn Acid maltase deficiency nn Primary lateral sclerosis Pathogenesis History nn Thought to be caused by progressive degeneration nn Type I with poor sucking, difficulty swallowing, and loss of the anterior horn cells in the spinal cord frequent respiratory infections and failures due to mutation, deletion, or rearrangement of SMN nn Type II with developmental motor delay genes, which are essential for early pre-mRNA splicing nn Type III with slowly progressive proximal weakness, Risk Factors the pelvic girdle being more affected than the shoulder girdle nn Family history nn Type IV symptomatic in the mid-thirties nn Male gender Examination Clinical Features nn Muscle atrophy nn Type I SMA (Werdnig-Hoffmann disease): floppy nn Flaccid weakness baby/hypotonia, difficulty feeding, weak cry, failure to nn Fasciculations reach milestones, absent muscle stretch reflexes, nn Hypotonia and wasting frog-legged position, tongue fasciculations, nn Decreased or absent deep tendon reflexes extraocular and sphincter muscles spared nn Sensory examination normal nn Type II SMA: floppy baby/hypotonia, slowly nn Normal sensory nerve action potential (SNAP) progressive limb weakness, upper greater than nn Abnormal needle EMG lower, absent muscle stretch reflexes, kyphoscoliosis, nn Molecular genetic testing confirmatory independent sitting, standing, and walking with nn Increased creatine phosphokinase level assistive devices nn Electrocardiogram normal

134 Spinal Muscular Atrophy 135

Pitfalls Consults nn Delayed diagnosis nn Physical medicine and rehabilitation nn Genetic counseling and prenatal diagnosis should be nn Spine and orthopedic surgery for deformities offered to all families with SMA nn nn Red flags Pulmonology nn Dietary or nutrition nn Pulmonary infection and failure nn As symptoms progress, it is unsafe for patients Complications of treatment with SMA to drive or operate other machinery nn Exercise-caused pain or fatigue nn Increased risk of falls due to weakness in lower nn Infection from surgical intervention extremities Prognosis Treatment nn Children with SMA type I usually die from Medical respiratory failure within the first 2 years nn The lifespan of patients with SMA type II varies from nn Supportive 2 years to the third decade of life nn Knee-ankle-foot orthoses nn Many patients with SMA type III have a normal life nn Well-fitted wheelchair to prevent spinal deformities expectancy and joint contractures nn Patients with SMA type IV have a normal life expectancy Exercise nn Non–fatigue causing exercise Helpful Hints Modalities nn Facial muscles affected least nn nn Transcutaneous electrical nerve stimulation may help Extraocular muscles, bowel, and bladder spared nn symptomatic relief of pain Sensation normal nn Antibiotic treatment not affecting survival in SMA Surgical type I nn Spinal deformity correction and early orthopedic intervention if indicated Suggested Reading nn Noninvasive ventilation and percutaneous Prior T. Spinal muscular atrophy: Newborn and carrier screening. gastrostomy to improve quality of life Obstet Gynecol Clin N Am. 2010;37:23–36. V: MotorV: Neuron Diseases

VI Muscle Diseases Becker Muscular Dystrophy Matthew Axtman DO

Description nn Limb-girdle muscular dystrophy Becker muscular dystrophy is an inherited disorder of nn Emery-Dreifuss muscular dystrophy slowly progressive weakening of proximal limb and pelvic nn Spinal muscular atrophy muscles caused by a mutation of the dystrophin gene. History nn Etiology/Types Progressive difficulty with walking, running, jumping, climbing stairs nn X-linked recessive nn Frequent falls nn Epidemiology Loss of balance nn Difficulty breathing nn Incidence is 1 per 30,000 male births nn Mild learning and cognitive problems nn Females are carriers of the mutated dystrophin gene nn Fatigue Pathogenesis Examination nn Mutation of the dystrophin gene, causing a defect in nn Calf pseudohypertrophy the dystrophin protein nn Muscle atrophy nn The dystrophin gene is located on the short arm of nn Symmetrical proximal muscle weakness chromosome 21 (Xp21) nn Gowers Sign—a maneuver in which the patient starts in a 4-point stance on the hands and knees and slowly Risk Factors uses the hands to “walk up” the legs to a standing nn A positive family history of Becker muscular position. This is due to weak pelvic girdle muscles and dystrophy proximal hip weakness nn Waddling gait Clinical Features nn Toe walking nn nn Difficulty with ambulation and mobility Scoliosis nn Muscle weakness and symptoms usually develop Testing around the age of 11 years but can occur earlier or nn Creatine phosphokinase levels may be elevated 5 to later 100 times normal levels, but levels decrease as muscle nn Patients usually remain ambulatory until their late mass decreases twenties nn Muscle biopsy demonstrates variation of muscles’ sizes and proliferation of adipose or connective tissue Natural History nn Polymerase chain reaction nn Muscle atrophy in proximal muscles due to dystrophin nn Genetic testing for dystrophin abnormalities mutation nn Ultrasonography shows increased echogenicity in nn Proliferation of adipose and connective tissue within affected muscles the muscles nn 75% of patients show echocardiogram abnormalities nn Affects skeletal and smooth muscles, therefore both of right ventricular strain, tall R waves, deep Q waves, voluntary and cardiac tissues involved and inverted T waves nn EMG shows a myopathic pattern of decreased Diagnosis amplitude, polyphasic, short duration motor-unit Differential diagnosis action potentials nn Duchenne muscular dystrophy Pitfalls nn Congenital muscular dystrophy nn Not evaluating cardiac status—cardiac tissue may be nn Facioscapulohumeral dystrophy more affected than skeletal muscles

138 Becker Muscular Dystrophy 139

Red flags Complications of treatment nn Dilated cardiomyopathy—mild nn Effects of long-term steroids nn Respiratory infections nn Strenuous activity can cause muscle damage nn Respiratory failure Prognosis Treatment nn There is a high variability of disability in patients— Medical many patients maintain independence with assistive nn Patient and family education devices nn Short-term steroid treatment using prednisone has nn Early onset of symptoms is associated with more shown temporary increases in strength cardiac involvement and earlier difficulty with nn Creatine supplementation has been shown to enhance mobility athletic performance in up to 10% of individuals nn Patients will most likely need the use of a wheelchair nn Evaluation for bracing, walkers, and wheelchairs if or assistive device for mobility mobility becomes limited nn Life expectancy is into the 5th and 6th decades of life, but can live a normal lifespan Exercises nn Encourage moderate activity Helpful Hints nn Stretching nn Activity should be limited to moderate intensity due nn Physical therapy targeting range of motion to prevent to the possibility of muscle damage with strenuous the formation of contractures activity Modalities nn Calf pseudohypertophy is due to increased adipose nn None and connective tissue and not due to increased muscle mass Surgical nn Cognitive deficiencies are less severe than in nn Spinal fusion for scoliosis Duchenne muscular dystrophy nn Tendon release for joint contractures Consults Suggested Readings nn Physical medicine and rehabilitation Louis M, Lebacq J, Poortmans JR, Belpaire-Dethiou MC, et al. nn Beneficial effects of creatine supplementation in dystrophic nn Pulmonology patients. Muscle Nerve. 2003;27(5):604–610. Markert CD, Ambrosio F, Call JA, Grange RW. nn Orthopedic surgery for spinal deformities or tendon Exercise and Duchenne muscular dystrophy: Toward release evidence-based ­exercise prescription. Muscle Nerve. nn Genetic counseling 2011;43(4):464–478.

VI: Muscle Diseases Muscle VI:

Dermatomyositis Shangming Zhang MD FAAPMR

Description Natural History Dermatomyositis is an idiopathic inflammatory myopathy nn Striated muscle inflammation and weakness manifested by symmetrical proximal weakness, character- nn Cutaneous lesions istic skin lesions, and strong association with malignancy. nn Association with malignancy: ovarian, lung, pancreatic, stomach, and colorectal cancers, Etiology/Types and non-Hodgkin’s lymphoma nn Unknown etiology nn Type 1: primary idiopathic polymyositis; Diagnosis insidious onset; with dysphagia, dysphonia, and moderate-to-severe arthritis Differential diagnosis nn Type 2: primary idiopathic dermatomyositis; acute nn Polymyositis onset; with proximal muscle weakness, heliotrope nn Inclusion body myositis rash with periorbital edema and systematic symptoms, nn Systemic lupus erythematous including fatigue, fever, and weight loss nn Scleroderma nn Type 3: dermatomyositis or polymyositis; associated nn Plaque psoriasis with malignancy; seen in males > 40 years old; nn Sarcoidosis prognosis poor History nn Type 4: childhood dermatomyositis or polymyositis; nn Difficulty climbing stairs, walking, or rising from a more disabling due to severe joint contracture; rapidly sitting position progressive weakness nn Pruritic rash, scaly scalp, or diffuse hair loss nn Type 5: dermatomyositis or polymyositis overlapping nn Arthralgia, arthritis with collagen vascular disease nn Difficulty swallowing or speaking Epidemiology Examination nn Estimated prevalence 5.5 in 100,000 people nn Characteristic heliotrope (blue-purple discoloration) rash with periorbital edema Pathogenesis nn Proximal muscle weakness with or without tenderness nn Activation and deposition of complement causes lysis nn Joint swelling of endomysial capillaries and muscle ischemia nn Diffuse alopecia Risk Factors nn Gottron’s papules over bony prominences nn nn Male-to-female ratio 2:1 Periungual telangiectases, poikiloderma nn nn Two peak ages of onset: 5 to 10 years; 50 years Calcinosis cutis—calcium deposition in skin, seen in juvenile form Clinical Features Testing nn Generalized fatigue nn Elevated creatine kinase, aldolase, lactate nn Symmetric proximal weakness dehydrogenase (LDH) nn Characteristic skin lesions: nn Positive antinuclear antigen ––Gottron’s papules—erythematous scaly coating at nn Myopathic findings on EMG dorsal finger joints nn Biopsy: perifascicular atrophy, large nuclei, necrosis ––Heliotrope rash—violaceous coloration on upper eyelids Pitfalls ––Shawl sign—erythematous area in a “V” over the nn Misdiagnosis of skin disease as psoriasis or eczema upper back or chest nn Failure to screen malignancy associated with nn Dysphagia dermatomyositis nn Abnormal cardiopulmonary findings nn Delayed initiation of corticosteroid therapy

140 Dermatomyositis 141

Red flags Consults nn Presence of malignancy nn nn Cardiopulmonary involvement nn nn Neurology Treatment nn Medical and Surgical nn Medical Cardiology nn Internal Medicine nn Oral corticosteroids as the mainstay of therapy: prednisone 1 mg/kg/day for 4 to 6 weeks, then taper to Complications of treatment avoid relapse nn Side effects of corticosteroids nn Immunosuppressive agents as second line: azathioprine or methotrexate Prognosis nn Intravenous immunoglobulin (IVIg) in severe nn Depending on severity of myopathy, refractory cases coexistence of malignancy, and cardiopulmonary nn Sun protection cream involvement Exercise nn 20% cases have spontaneous remission and 5% have nn Encourage range-of-motion and isometric exercises rapid progressive course and death nn No strengthening exercises until inflammation controlled Helpful Hints nn Sun avoidance and protective measures in patients nn Mandatory screening for malignancy with skin lesions nn Heliotrope rash strongly suggestive of Modalities dermatomyositis nn Sun avoidance and protective measures necessary for nn Heat, cold, ultrasound can be tried in patients with patients with skin disease contractures Surgical Suggested Reading nn Surgery for resectable malignancy Dalakas MC, Hohlfeld R. Polymyositis and dermatomyositis. nn Surgical removal of calcinosis Lancet. 2003;362:971–982.

VI: Muscle Diseases Muscle VI:

Duchenne Muscular Dystrophy Shangming Zhang MD FAAPMR

Description Diagnosis Duchenne muscular dystrophy (DMD) is an X-linked Differential diagnosis recessive disorder caused by chronic muscle degeneration nn Becker muscular dystrophy due to dystrophin deficiency. DMD is severe, progressive, nn Myotonic muscular dystrophy (Steinert’s and the most common muscular dystrophy. disease) Etiology/Types nn Spinal muscular atrophy nn nn X-linked recessive (Xp 21.2) inherited Facioscapulohumeral dystrophy nn nn Spontaneous deletions or mutations Kennedy’s disease nn Limb-girdle muscular dystrophy Epidemiology nn nn Most common childhood-onset muscular dystrophy History nn Affecting 1 in 3600 to 6000 live male births nn Onset of symptoms in childhood Pathogenesis nn Weakness, fatigue, and poor endurance nn Dystrophin protein is essential to the structural nn Frequent falls, difficulty ascending stairs, or arising stability of myofibers. Dystrophin deficiency from the floor associated with DMD results in chronic inflammation nn Muscle cramps or stiffness and severe muscular degeneration. nn Focal enlargement of calf muscles nn Dystrophin deficiency also leads to cardiomyopathy nn Lordosis and scoliosis and possible mental retardation nn Family history Risk Factors Examination nn Family history nn Proximal muscle weakness nn Calf enlargement Clinical Features nn Abnormal deep tendon reflexes nn Delayed motor milestones nn Increased creatine phosphokinase with values up to 50 nn Waddling gait and Gower’s sign by age 3 to 5 years to 100 times normal nn Calf pseudohypertrophy with fatty and fibrous tissue nn Abnormal electrocardiogram replacement within 1 to 2 years nn EMG: sensory nerve action potential (SNAP) nn Toe walking and clumsy running normal, compound muscle action potential (CMAP) nn Gower’s sign (patient uses hands/arms to “climb” up small amplitude, needle exam with myopathic their body to arise from floor) is due to proximal findings muscle weakness nn Muscle biopsy: no dystrophin nn Lumbar lordosis and scoliosis nn X-ray to evaluate and screen the degree of spine nn Wheelchair bound by 12 years old deformities nn Possible mental retardation nn Molecular diagnosis nn Extraocular muscles spared Pitfalls Natural History nn Cardiac surveillance to be implemented at the time of nn Chronic progressive muscular degeneration diagnosis nn Weakness, contractures, scoliosis, wheelchair bound, decubitus ulcers, pulmonary complications, and Red flags cardiomyopathy to death nn Osteoporosis and fractures

142 Duchenne Muscular Dystrophy 143

Treatment Complications of treatment nn Medical Corticosteroids can cause cataracts, diabetes, hypertension, osteoporosis, behavioral changes, and nn Prednisone 0.75 to 1.5 mg/kg p.o. daily: extension weight gain of independent ambulation up to 3 years, delay in nn Infection and failures related to surgical development of scoliosis and cardiac and respiratory intervention complications nn H2 blocker to prevent corticosteroids—caused gastritis and ulcer Prognosis nn Onset at age 3 to 5 years Exercise nn Wheelchair bound by age of 12 years nn Gentle sports and activities under supervision nn Death by age of 20 years nn Daily stretching to delay contractures Modalities Helpful Hints nn Heat, cold, ultrasound may provide relief of nn Corticosteroid treatment has been proved to prolong contracture-related pain independent ambulation by up to 3 years, delays development of scoliosis, and improves cardiac and Surgical respiratory functions nn Scoliosis surgery before vital capacity less than 35% nn Coordinated multidisciplinary care needed nn Tendon lengthening surgery may prolong ambulation by up to 2 years Suggested Readings Consults Bushby K, Finkel R, Birnkrant DJ, Case LE, et al. Diagnosis nn Orthopedic surgery and management of Duchenne muscular dystrophy, nn Cardiology part 1: Diagnosis, and pharmacological and psychosocial management.­ Lancet Neurol. 2010;9:77–93. nn Pulmonology Bushby K, Finkel R, Birnkrant DJ, Case LE, et al. Diagnosis nn Neurology and management of Duchenne muscular dystrophy, nn Genetics part 2: Implementation of multidisciplinary care. Lancet nn Psychology Neurol. 2010;9:177–189.

VI: Muscle Diseases Muscle VI:

Emery-Dreifuss Muscular Dystrophy Nathan D. Prahlow MD

Description nn Fascioscapulohumeral dystrophy nn Emery-Dreifuss muscular dystrophy is characterized nn Limb-girdle muscular dystrophies by early formation of contractures and the presence of History cardiac issues. It is the third most common X-linked nn Upper limb functionality (biceps and triceps) recessive muscular dystrophy, although autosomal nn Palpitations, syncope recessive and dominant forms are also seen. Examination Etiology/Types nn Irregular cardiac rhythm nn X-linked nn Presence of contractures nn Autosomal dominant: variable features nn Marked humeral and peroneal muscle wasting, with nn Autosomal recessive relative sparing of deltoid nn Inability to heel-walk due to Achilles contracture and Epidemiology calf atrophy nn X-linked: 1 per 100,000 people; the most common nn May be unable to flex lumbar spine due to contractures form of Emery-Dreifuss muscular dystrophy nn Mild facial weakness nn Autosomal dominant: unknown nn Mild hand weakness nn Autosomal recessive: very rare Testing Pathogenesis nn Genetic testing nn nn Mutations in the EMD or LMNA genes affect proteins Muscle biopsy: nonspecific myopathic changes nn in the nuclear lamina of the cell Electrocardiogram (EKG): low amplitude/absent P waves, variable degree of conduction block, possible Risk Factors evidence of cardiomyopathy nn nn Family history positive for Emery-Dreifuss muscular EMG: myopathic features of low amplitude dystrophy compound muscle action potential (CMAP) in atrophic muscles Clinical Features nn Serum creatine kinase mildly elevated (<10 times nn Early formation of joint contractures normal) nn Muscle wasting in humeroperoneal distribution Pitfalls nn Cardiac conduction defects (bradycardia progressing to nn Carriers are at risk for sudden death due to arrhythmia complete heart block), with or without cardiomyopathy Red flags Natural History nn Cardiac arrhythmias, with or without cardiomyopathy nn Normal birth and early development nn Onset in early childhood/adolescence (<15 years) Treatment nn Slow progression Medical treatment nn Rare loss of ambulation nn Supportive nn Cardiac issues may develop before significant weakness nn May require powered mobility nn Cardiac involvement is almost always present by age nn Cardiac: annual EKG, Holter monitor, antiplatelet 30 years therapy, cardiac transplant Diagnosis Exercise nn Cardiac precautions necessary Differential diagnosis nn Duchenne muscular dystrophy Modalities nn Becker muscular dystrophy nn Ankle foot orthoses 144 Emery-Dreifuss Muscular Dystrophy 145

Injection Prognosis nn None indicated nn No effective treatment for the progressive weakness Surgical nn Pacemaker or automatic implanted cardiac defibrillator Helpful Hint nn nn Surgical release of contractures Annual cardiac screening of relatives is needed, as carriers are at risk for sudden death due to arrhythmia Consults nn Cardiology Suggested Readings nn Cardiac surgery Helbling-Leclerc A, Bonne G, Schwartz K. Emery-Dreifuss nn Orthopedic surgery ­muscular dystrophy. Eur J Human Genetics. 2002;10: nn Certified Orthotist 157–161. Zacharias AS, Wagener ME, Warren ST, et al. Complications of treatment Emery-Dreifuss muscular dystrophy. Semin Neurol. nn Complications of surgery 1999;19(1):67–79.

VI: Muscle Diseases Muscle VI:

Fascioscapulohumeral Dystrophy Matthew Axtman DO

Description History Fascioscapulohumeral dystrophy is a slowly progressive nn Difficulty whistling weakening of skeletal muscles, which usually starts in the nn Difficulty sucking through a straw face, shoulder girdle, and upper arms. nn Eye lids remain open while sleeping nn Shoulder weakness Etiology/Types nn nn Autosomal dominant in 70% to 90% of patients nn Muscle pain nn Sporadic mutation in 10% to 30% of individuals nn Problems with dorsiflexion of the feet

Epidemiology Examination nn Scapular winging nn Prevalence is 1 in 20,000 nn Weak facial muscles nn Higher frequency in males nn Weak tibialis anterior muscle resulting in foot-drop Pathogenesis nn Atrophy of the biceps and triceps nn Beevor’s sign (movement of the navel toward the head nn Caused by the deletion of D4Z4 at gene locus 4q35 on when flexing the neck) due to lower abdominal muscle chromosome 4 weakness Risk Factors nn Increased lumbar lordosis due to weak abdominal muscles nn A positive family history of fascioscapulohumeral nn High-frequency sensorineural hearing loss dystrophy Testing Clinical Features nn Creatine kinase—elevated nn Winged scapula nn Muscle biopsy—chronic myopathic changes nn Facial muscle weakness nn EMG—myopathic potentials nn Foot-drop nn Increased lumbar lordosis Pitfalls nn Coat’s syndrome: retinal vasculopathy with Natural History telangiectasia, exudation, and retinal detachment nn Symptoms develop in the 1st to 3rd decade of life Red flags nn 90% of patients demonstrate symptoms by the age of nn Vision changes 20 years nn Weakness typically begins in the facial muscles and Treatment slowly progresses caudally nn Scapular winging is the most common initial symptom Medical nn Evaluation for bracing, walkers, and wheelchair Diagnosis nn Visual screening Differential diagnosis Exercises nn Congenital muscular dystrophy nn Low-impact aerobic exercises nn Amyotrophic lateral sclerosis nn Gentle range of motion nn Limb-girdle muscular dystrophy nn Dermatomyositis Modalities nn Congenital myopathies nn Supportive

146 Fascioscapulohumeral Dystrophy 147

Surgical Prognosis nn Scapulothoracic arthrodesis if deltoid function is nn Life expectancy is normal preserved nn 20% of patients may require wheelchair assistance nn Tendon transfer for foot-drop nn Size of the deletion affects prognosis Consults Helpful Hints nn Physical medicine and rehabilitation nn Extraocular and pharyngeal muscles are spared nn Neurology nn Scapular winging is the most characteristic sign nn Ear/nose/throat nn Weakness may be asymmetric nn Pulmonology nn Orthopedics Suggested Readings nn Audiology Pandya S, King WM, Tawil R. Fascioscapulohumeral nn ­dystrophy. Phys Ther. 2008;88(1):105–113. nn Genetic counseling [Epub 2007 Nov 6]. van der Kooi EL, Vogels OJ, van Asseldonk RJ, et al. Complications of treatment Strength training and albuterol in facioscapulohumeral nn Overuse syndrome ­muscular dystrophy. Neurol. 2004;24;63(4): nn Pain 702–708.

VI: Muscle Diseases Muscle VI:

Hyperkalemic Periodic Paralysis Nathan D. Prahlow MD

Description History The periodic paralyses, of which hyperkalemic periodic nn Symptoms last from minutes up to 4 hours paralysis (HyperKPP) is a type, are characterized by epi- nn Limb, eye, throat, and trunk muscles most involved; sodes of flaccid muscle weakness. respiratory muscles are spared nn Attacks may occur with more frequency before Etiology/Types breakfast nn Primary (hereditary) nn Secondary (acquired) Examination nn Myotonia in facial, lingual, and hand muscles Epidemiology nn May have weakness and paresthesias nn Autosomal dominant nn 1 in 200,000 people Testing nn Genetic testing Pathogenesis nn Provocative testing with exercise (increases serum nn Mutation in the SCN4A gene, affecting the muscular potassium) followed by bed rest (immediate sodium channel decline, followed by increase after 20 minutes of rest) Risk Factors nn EMG: compound muscle action potential (CMAP) nn Family history of HyperKPP amplitude increases after 5 minutes of exercise, and declines within 20 minutes Clinical Features nn Attacks of mild-to-severe weakness, worsened by Pitfalls ingestion of potassium-rich foods, strenuous exercise, nn Serum potassium is low after a HyperKPP attack, emotional stress, cold, or medications mimicking hypokalemic periodic paralysis nn Symptoms may be isolated to a single muscle or widespread Red flags nn Usually complete recovery between attacks, but may nn Avoid potassium, depolarizing muscle relaxants, have stiffness and cholinesterase inhibitors in general anesthesia Natural History nn Onset younger than 10 years Treatment nn Frequency and severity of attacks increases gradually Medical as one ages nn nn Severity decreases after about age 50 years Genetic counseling nn nn Weakness may become permanent Ingestion of carbohydrates at onset of symptoms nn Prevent attacks with early awakening and Diagnosis eating of breakfast, frequent carbohydrate-rich meals, avoidance of potassium-rich foods and Differential diagnosis medications that increase serum potassium, nn Hypokalemic periodic paralysis and avoidance of fasting, strenuous exercise, nn Myotonia congenita and cold nn Paramyotonia congenita nn Myotonic dystrophy Exercise nn Schwartz-Jampel syndrome nn Mild exercise may help abort an attack

148 Hyperkalemic Periodic Paralysis 149

Modalities Helpful Hint nn None indicated nn Non-steroidal anti-inflammatory drugs (NSAIDs), Surgical heparin, spironolactone, angiotensin converting nn None indicated enzyme (ACE) inhibitors, trimethoprim, and oral/IV potassium may all cause hyperkalemia and induce a Consults secondary HyperKPP nn Neurology Complications of treatment Suggested Readings nn Side effects of medications Finsterer J. Primary periodic paralyses. Acta Neurol Scand. 2008;117:145–158. Prognosis Miller TM. Differential diagnosis of myotonic disorders. Muscle nn Lifespan is not affected Nerve. 2008;37:293–299.

VI: Muscle Diseases Muscle VI:

Hypokalemic Periodic Paralysis Nathan D. Prahlow MD

Description History The periodic paralyses, of which hypokalemic periodic nn Symptoms last from hours up to several days paralysis (HypoKPP) is a type, are characterized by epi- nn Ocular, bulbar, and respiratory muscles are usually sodes of flaccid muscle weakness not affected nn Attacks occur with more frequency upon awakening Etiology/Types and during/after vigorous exercise nn Primary (hereditary) Examination nn Secondary (acquired) nn Not associated with clinical myotonia nn Epidemiology Lower limb weakness may be episodic or due to the slowly progressive permanent weakness that may nn Autosomal dominant develop nn 1 in 100,000 people, the most common of the periodic paralyses Testing nn Genetic testing Pathogenesis nn Serum potassium levels do not correlate with the nn Mutation in the CACNA1S gene or SCN4A gene, severity of weakness, and may be decreased or normal affecting the voltage-gated sodium channel nn Serum creatine kinase levels rise during attacks nn EMG: compound muscle action potential (CMAP) Risk Factors amplitudes decrease during attack and increase after nn Family history of HypoKPP exercise; myotonic discharges typically absent nn Electrocardiogram: evidence of hypokalemia Clinical Features (flattened T-wave and ST-segment depression) nn Attacks of severe weakness, associated with a drop in Pitfalls serum potassium levels nn Aspiration pneumonia has caused death in several nn Usually complete recovery between attacks, but may persons with HypoKPP have subacute weakness Red flags Natural History nn Avoid volatile anesthetic agents and depolarizing muscle relaxants in general anesthesia due to risk of nn Onset younger than 20 years postanesthesia weakness and malignant hyperthermia nn Frequency and severity of attacks greatest between 15 and 35 years Treatment nn Frequency decreases after about age 35 years nn Frequency ranges from a single attack to rare attacks Medical to daily attacks nn Genetic counseling nn Weakness may become permanent, especially after nn Diet rich in potassium and low in sodium and attacks in close succession carbohydrates nn Oral (or IV) potassium supplementation Diagnosis Exercise Differential diagnosis nn Gentle exercise nn Hyperkalemic periodic paralysis Modalities nn Myotonia congenita nn None indicated nn Paramyotonia congenita nn Myotonic dystrophy Surgical nn Schwartz-Jampel syndrome nn None indicated

150 Hypokalemic Periodic Paralysis 151

Consults Helpful Hint nn Neurology nn Patients with diabetes should avoid acetazolamide, as Complications of treatment it increases potassium uptake into muscle cells nn Side effects of medications Suggested Reading Prognosis Finsterer J. Primary periodic paralyses. Acta Neurol Scand. nn Lifespan is generally not affected 2008;117:145–158.

VI: Muscle Diseases Muscle VI:

Limb-Girdle Muscular Dystrophies Nathan D. Prahlow MD

Description nn Cardiomyopathy The limb-girdle muscular dystrophies (LGMD) are a nn Respiratory status class of muscular dystrophies which predominantly nn Vision changes affect the muscles of the shoulder and hip regions. Examination Etiology/Types nn Proximal upper limb girdle weakness, including nn Autosomal dominant scapular winging nn Autosomal recessive nn Proximal posterior lower limb (hamstring/buttock) nn Can be a new mutation weakness nn Waddling gait Epidemiology nn Prominent contractures of Achilles, elbows, and nn Rare spine nn LGMD2A is the most common type nn Percussion-induced repetitive contractures—“rippling muscles” Pathogenesis nn May develop cataracts nn Over 20 chromosomal abnormalities are currently recognized, affecting many different muscle Testing proteins nn Serum creatine kinase nn Muscle biopsy with histology and immunoanalysis Risk Factors nn Genetic testing nn Family history positive for a limb-girdle muscular nn Forced vital capacity—preserved in the most common dystrophy type (LGMD2A) Clinical Features Pitfalls nn Proximal limb muscle weakness nn nn Dysarthria Misdiagnosis of polmyositis due to increased CK and nn Modestly elevated serum creatine kinase (CK) levels, inflammatory infiltrate on muscle biopsy nn although some may show extreme elevation Missing cardiac involvement Natural History Red flags nn Gradual progression of weakness over time nn Cardiac arrhythmias, cardiomyopathy, and nn Onset most common between age 8 and 15 years respiratory failure risk, especially in types LGMD1B, LGMD2C-2F, and LGMD2I Diagnosis Differential diagnosis Treatment nn Duchenne muscular dystrophy Medical treatment nn Becker muscular dystrophy nn Supportive nn Fascioscapulohumeral dystrophy nn Assistive devices nn Congenital myopathies nn Genetic counseling nn Polymyositis nn Family tree surveillance nn Autoimmune rippling muscle disease History Exercise nn Any age of onset, but most common between age nn Stretching groups 8 and 15 years nn Prevention of contractures

152 Limb-Girdle Muscular Dystrophies 153

Modalities Complications of treatment nn Supportive nn Complications of surgery Surgical Prognosis nn Automatic implanted cardiac defibrillator nn Patients with LGMD2A have normal lifespan placement nn Cataract removal Helpful Hint nn Although CK levels may be high, this disease is not Consults responsive to steroids nn Cardiology nn Ophthalmology Suggested Reading nn Neurology Bushby K. Diagnosis and management of the limb girdle nn Physical medicine and rehabilitation ­muscular dystrophies. Practical Neurol. 2009;(9):314–323.

VI: Muscle Diseases Muscle VI:

McArdle’s Disease (Glycogen Storage Disease Type V) Matthew Axtman DO

Description Diagnosis McArdle’s disease is a metabolic disorder caused by the Differential diagnosis inability to break down glycogen into glucose, resulting nn Tarui disease (glycogen storage disease type VII) in exercise intolerance. nn Glucose intolerance Etiology/Types nn Glucose-6-phosphatase deficiency nn nn Autosomal recessive Glucose-6-phosphate dehydrogenase deficiency nn nn Types: Hypoglycemia ––Classic History ––Late-onset (rare) nn Exercise intolerance ––Fatal infantile (rare) nn nn Epidemiology Muscle cramps nn Fatigue nn Frequency is 1 per 100,000 births nn Dark urine nn May be underdiagnosed due to mild symptoms in some patients Examination nn Muscle atrophy Pathogenesis nn Proximal muscle weakness after exercise nn Caused by the enzyme deficiency of myophosphorylase nn During exercise, glycogen is broken down into glucose Testing via the myophosphorylase enzyme for the production nn Elevated creatine kinase of adenosine triphosphate (ATP) nn Urinalysis demonstrates myoglobinuria nn In McArdle’s disease, initial energy is maintained nn Muscle biopsy shows excess glycogen and absence of by glucose in the blood, but once the blood-borne myophosphorylase stores are depleted, there is an inability to convert the nn Ischemic and nonischemic forearm exercise test: glycogen to glucose for utilization. Hand is exercised for 30 seconds, with baseline and serial laboratory studies drawn, measuring lactate and Risk Factors ammonia levels nn A positive family history of McArdle’s disease Pitfalls Clinical Features nn Delayed diagnosis that may cause rhabdomyolysis and nn Patients note the inability to perform activities at renal failure if the patient continues to exercise at a normal levels high level nn Disease severity can range from mild exercise Red flags intolerance to fixed muscle weakness with severely nn Rhabdomyolysis limited activities of daily living nn Renal failure nn Patients may display a “second wind” phenomenon in which they are able to resume activities at normal levels Treatment after a brief period of rest. This is due to the body’s ability to use other sources of energy, such as fatty acids. Medical nn High carbohydrate diet may improve exercise tolerance Natural History nn Recommend having glucose supplementation for nn Symptoms usually present in the 2nd to 3rd decade of energy replacement life nn Vitamin B6 supplementation 154 McArdle’s Disease (Glycogen Storage Disease Type V) 155

Exercises Prognosis nn Patients are recommended to participate in moderate nn Benign process if strenuous activity is avoided aerobic activity to improve exercise tolerance nn May develop acute renal failure if excessive exercise is nn Avoid strenuous isometric or sustained aerobic performed exercises, which may lead to rhabdomyolysis nn Older patients may develop fixed proximal muscle Modalities weakness nn None Helpful Hints Surgical nn The primary goal is activity and exercise modification nn None nn Educate the patient on “second wind” phenomenon Consults Suggested Readings nn Physical medicine and rehabilitation Lucia A, Nogales-Gadea G, Perez M, et al. McArdle disease: nn What do neurologists need to know? Nat Clin Pract Neurol. nn Internal medicine 2008;4(10):568–577. Quinlivan R, Buckley J, James M, Twist A, et al. McArdle Complications of treatment disease: A clinical review. J Neurol Neurosurg Psychiatry. nn None 2010;81(11):1182–1188. [Epub 2010 Sep 22].

VI: Muscle Diseases Muscle VI:

Myotonia Congenita Nathan D. Prahlow MD

Description History An inherited condition characterized by myotonia—the nn Developmentally “clumsy” slow relaxation of a muscle after a contraction nn Childhood gagging and difficulty swallowing nn Warm-up effect Etiology/Types nn Becker’s myotonia congenita: muscle stiffness and nn Thomsen’s myotonia congenita: autosomal dominant pain; temporary attacks of weakness inheritance Examination nn Becker’s myotonia congenita: autosomal recessive nn Clinical myotonia inheritance nn Delayed release of handshake nn Epidemiology Forceful eye closing: delay in opening initially, but improves with repetition nn 1 in 100,000 people nn Becker’s myotonia congenita: mild permanent Pathogenesis weakness nn May have increased muscle bulk nn Mutation in the CLCN1 gene, which encodes a protein found in the skeletal muscle chloride ion channels Testing nn Genetic testing Risk Factors nn EMG: electrical myotonia; decrement with repetitive nn Family history of myotonia congenita stimulation Pitfalls Clinical Features nn Patients appear normal, but may have difficulties with nn Myotonia some tasks and activities nn Stiffness, especially when first starting an activity nn After warm-up, muscles function may be normal Red flags nn “Little Hercules” presentation, with significant muscle nn None hypertrophy at a young age Treatment Natural History Medical nn Early childhood presentation, with parent noting nn Sodium channel blocker, such as mexiletine or weakness, clumsiness, and/or stiffness in child phenytoin (Becker’s myotonia congenita appears at a later age nn Medication use can be limited to times when the need than Thomsen’s myotonia congenita) for quicker action is predicted nn Symptoms may improve with age, but usually do not Exercise resolve nn Warm-up before a strenuous activity nn Diagnosis Therapy to address any activity of daily living or range-of-motion issues Differential diagnosis Modalities nn Myotonic dystrophy nn As needed nn Schwartz-Jampel syndrome nn Hyperkalemic periodic paralysis Injection nn Paramyotonia congenita nn None indicated

156 Myotonia Congenita 157

Surgical Helpful Hints nn None indicated nn Classic myotonia symptoms improve with physical Consults activity nn Both clinical and electrical myotonia are seen in this nn Physical medicine and rehabilitation disease process nn Neurology Complications of treatment Suggested Readings nn Side effects of medication Kurihara T. New classification and treatment for myotonic disorders.­ Intern Med, 2005:44(10):1027–1032. Prognosis Miller TM. Differential diagnosis of myotonic disorders. nn Normal longevity Muscle Nerve 2008;37:293–299.

VI: Muscle Diseases Muscle VI:

Myotonic Dystrophy Matthew Axtman DO

Description nn Vision changes Myotonic dystrophy [dystrophia myotonica (DM)] is a nn Learning disabilities slowly progressive, variable disease characterized by mus- cle weakness, muscle atrophy, and myotonia. The disease Natural History also involves disorders of the cardiac, respiratory, ocular, nn There is a significantly high rate of variability with neurologic, digestive, and endocrine systems. regard to age at symptom onset, severity of symptoms, and systems affected Etiology/Types nn The disease is slowly progressive over years nn Autosomal dominant nn Types: Diagnosis ––DM Type 1—Steinert’s disease Differential diagnosis ––DM Type 2—Proximal myotonic myopathy nn Paramyotonia congenita nn Epidemiology Congenital myotonia nn Limb-girdle dystrophy nn Type 1—1 in 8,000 individuals nn Polymositis nn Type 2—unknown nn Dermatomyositis Pathogenesis nn Mild tetanus nn Myotonic dystrophy type 1: History ––A trinucleotide (CTG) repeat disorder on nn Progressive weakening of facial, jaw, neck, hand, and chromosome 19 distal leg muscles in DM1 ––Mutation in the DMPK gene nn Progressive weakening of neck, shoulder, hip flexor, ––50 to 4000 repeats of the trinucleotide (healthy and upper leg muscles in DM2 individuals have 5–37 repeats) nn Muscle pain nn Myotonic dystrophy type 2: nn Difficulty relaxing grip after grabbing or holding ––A tetranucleotide (CCTG) repeat disorder on an object chromosome 3 nn Hypersomnia ––Mutation in the ZNF9 gene nn Coughing/choking while eating or drinking ––75 to 11,000 repeats of the tetranucleotide (healthy nn Heart palpitations individuals have fewer than 75 repeats) nn Developmental delays nn Weight loss Risk Factors nn Diarrhea nn Family history of myotonic dystrophy nn Constipation nn Clinical Features Behavioral difficulties nn Infertility nn Progressive weakness in distal muscles in DM1 and in nn Early menopause proximal muscles in DM2 nn Myotonia-delayed relaxation of skeletal muscles after Examination voluntary contraction nn Muscle weakness in the facial, neck, hand, distal leg nn Muscle atrophy muscles in DM1 nn Weight loss nn Muscle weakness in the neck, shoulder, hip flexor, and nn Swallowing difficulties proximal leg muscles in DM2 nn Breathing difficulties nn Muscle atrophy nn Cardiac arrhythmias nn Myotonia nn Abnormal facies—“Hatchet face,” with tented open nn Long face mouth and elongated face nn Bland facial expression 158 Myotonic Dystrophy 159 nn Temple balding nn Cough assist devices nn Stiff gait nn Pacemaker/implantable cardioverter defibrillator nn Dental malocclusion nn Continuous positive airway pressure nn Poor suck reflex nn Hormone replacement therapy nn Ptosis nn Antidiabetic drugs nn Cardiac arrhythmias—atrial fibrillation/flutter most nn Dietary management common nn Incentive spirometry nn Weak cough nn Mexiletine for disabling myotonia nn Muscle pain Exercises nn Gonadal atrophy nn Range of motion nn Dental caries nn Strengthening nn Pilomatrixoma tumors nn Aerobic exercise Testing nn Aquatic therapy nn DNA testing Modalities nn Creatine kinase nn Heat for muscle pain nn Electrocardiogram nn Patients may need heated gloves during cold weather nn Holter monitor to help prevent myotonia nn Echocardiogram nn Fasting blood glucose Surgical nn HgbA1c nn Cataract extraction nn Testosterone, luteinizing hormone, follicle stimulating nn Blepharoplasty hormone levels nn Pilomatrixoma removal nn Chest x-ray Consults nn Pulmonary function testing nn Cardiology nn Swallow assessment nn Pulmonology nn Muscle biopsy nn nn EMG nn Physical medicine and rehabilitation nn Neuropsychological testing nn Neurology nn Sleep study nn Ophthalmology nn Neuroimaging nn Gastroenterology nn Invasive electrophysiologic testing nn Neuropsychology Pitfalls Complications of treatment nn Patients may develop aspiration pneumonia if nn Vigorous activity should be avoided due to the risk of difficulty with swallowing is present sudden cardiac death nn Sudden cardiac death may occur in asymptomatic nn Antiarrhythmics and antimyotonic medication should

children be prescribed carefully due to proarrhythmic effects Red flags nn Cardiac and respiratory problems are the main causes Prognosis of mortality nn Disability is more severe, the earlier the symptoms nn Increased risk of mortality with anesthesia appear in life nn Increased sensitivity to drugs that decrease respiratory nn Increased length of the repeat disorder is associated VI: Muscle Diseases Muscle VI: drive with worse prognosis and earlier life expectancy nn Severity of the disease increases and prognosis worsens with successive generations Treatment Medical Helpful Hints nn Evaluation for orthoses, assistive devices, and adaptive nn Patients may have very mild symptoms and go equipment undiagnosed until a child is born and is diagnosed nn Non-steroidal anti-inflammatory drugs for pain with the disorder 160 Myotonic Dystrophy nn The symptoms are highly variable depending Suggested Readings on the number of associated repeats on the Kurihara T. New classification and treatment for myotonic chromosome disorders.­ Intern Med. 2005;44:1027–1032. Orngreen MC, Olsen DB, Vissing J. Aerobic training in patients nn Myotonic dystrophy is associated with with myotonic dystrophy type 1. Ann. Neurol. 2005;57:754–757. insulin resistance leading to diabetes Turner C, Hilton-Jones D. The myotonic dystrophies: ­diagnosis and mellitus management. J Neurol Neurosurg Psychiatry. 2010;81(4):358–367. Paramyotonia Congenita Nathan D. Prahlow MD

Description Testing Also known as Eulenberg syndrome. Characterized by nn Genetic testing paradoxical myotonia, in which the myotonic activity is nn Serum potassium moderately elevated; serum creatine heightened by activity kinase (CK) usually elevated nn EMG: plentiful myotonic discharges present during Etiology/Types cooling of the muscle nn Autosomal dominant Pitfalls Epidemiology nn Misdiagnosis nn 1 in 200,000 or rarer; locally may be more common Red flags due to founder effect nn None Pathogenesis Treatment nn Mutation in the a-subunit of the muscular sodium channel gene SCN4A Medical treatment nn Mexiletine, a sodium channel blocker, may be taken Risk Factors during cold-weather months nn Positive family history nn Chlorothiazide and acetazolamide have been shown to Clinical Features be helpful nn Cold-induced localized prolonged myotonia and Exercise weakness nn Strenuous exercise may trigger or worsen symptoms nn Increased myotonia with repetitive or continual activity Modalities nn Facial muscles and upper limb muscles more involved nn None indicated Natural History Injection nn Onset in childhood nn None indicated nn Nonprogressive nn Weakness from paramyotonia congenita is not Surgical permanent nn None indicated Diagnosis Consults nn Neurology Differential diagnosis nn Hyperkalemic periodic paralysis Complications of treatment nn Myotonia congenita nn Side effects of medication nn Myotonic dystrophy nn Schwartz-Jampel syndrome Prognosis nn No impact on lifespan History

nn Symptoms after cold exposure VI Helpful Hint Diseases Muscle : nn Symptoms after vigorous exercise nn Cold triggers also include swimming in cold water, nn Flaccid weakness may follow the episodes of myotonia cold drafts, and eating ice cream nn Symptoms may last minutes to several hours Examination Suggested Readings nn Paradoxical myotonia: rapidly repeated forcible eye Kurihara T. New classification and treatment for myotonic ­disorders. Intern Med. 2005;44(10):1027–1032. closure brings on the inability to open eyes Miller TM. Differential diagnosis of myotonic disorders. nn No muscular wasting or hypertrophy Muscle Nerve. 2008;37:293–299. 161 Polymyositis Gabriel Smith MD ■ Nathan D. Prahlow MD

Description nn Hypothyroidism An inflammatory myopathy characterized by symmetric nn Systemic lupus erythematosis proximal weakness nn Fibromyalgia History Etiology/Types nn Symmetric proximal muscle weakness, increasing nn Unknown over 3 to 6 months nn Epidemiology Many patients have prior history of connective tissue diseases nn Approximately 1 in 250,000 nn Myalgias nn Female-to-male ratio of 2:1 nn Fatigue, fever, anorexia nn Affects adults > 18 years old nn May have respiratory or gastrointestinal complaints nn Extremely rare in children depending on what muscle groups are involved Pathogenesis Examination nn Thought to be initiated by viral illness or an nn Symmetric weakness, proximal > distal autoimmune response, resulting in muscle nn Tenderness of involved muscles destruction nn Deep tendon reflexes and sensation preserved

Risk Factors Testing nn nn Age 40 to 60 years Erythrocyte sedimentation rate (ESR) nn nn Female Complete blood count (CBC) nn nn Presence of connective tissue diseases Anti-nuclear antibody (ANA) nn Anti Jo-1 antibodies Clinical Features nn Serum creatine kinase nn nn Gradual muscle weakness and myalgias EMG nn nn Systemic symptoms: fever, malaise, arthralgias Chest x-ray nn nn Dysphagia and/or dysphonia Muscle biopsy nn Pulmonary dysfunction Pitfalls nn Due to insidious onset, symptoms may be disregarded Natural History as mere fatigue, delaying treatment nn Unknown agent causes insult to muscles leading to release of autoantigens Red flags nn Antigens are presented to CD8+ T cells nn Respiratory distress/failure nn Activated CD8+ T cells directly damage muscles nn Dysphagia and dysphonia through release of cytokines nn Aspiration pneumonia nn Macrophages also contribute to inflammation nn Sufficient damage leads to muscle destruction and Treatment weakness over several months The typical sequence of treatment is: nn High-dose prednisone Differential diagnosis nn Azithropine or methotrexate for steroid sparing nn Dermatomyositis nn Intravenous immunoglobulin (IVIg) nn Inclusion body myositis nn Rituximab, cyclosporine, cyclophosphamide, or nn Polymyalgia rheumatica tacrolimus

162 Polymyositis 163

Exercises Prognosis nn Physical therapy—passive range of motion and nn Five-year survival is 95%, 10-year survival is 84% splinting help prevent contraction nn Worse prognosis with advanced age, female, nn Aerobic exercise during inactive phase presence of Anti-Jo-1 and Anti-SRP nn Speech therapy to prevent aspiration antibodies nn Modalities Also worse prognosis if associated with cardiac or pulmonary dysfunction nn Heat for muscle pain Surgical Helpful Hints nn None. nn Most patients improve with therapy Consults nn Many make full functional recovery nn Neurology nn Patients with associated interstitial lung disease nn Rheumatology greatly benefit from cyclophosphamide nn Cardiology nn Pulmonology Suggested Readings nn Physical medicine and rehabilitation Dalakas MC. Polymyositis, dermatomyositis, and nn Physical therapy/occupational therapy (PT/OT), inclusion body myositis. Harrison’s Principles of speech therapy Internal Medicine. 17th ed. New York: McGraw Hill; Complications of treatment 2008. Dalakas MC. Inflammatory muscle diseases: A critical review nn Steroids, immunosuppressants, and chemotherapeutic on pathogenesis and therapies. Curr Opin Pharmacol. agents are notorious for their side-effect profiles 2010;10(3):346–352.

VI: Muscle Diseases Muscle VI:

Pompe Disease (Glycogen Storage Disease Type II) Matthew Axtman DO

Description nn The late-onset-type progresses slowly and is highly Pompe disease is a metabolic disorder caused by the variable accumulation of glycogen within lysosomes causing nn Patients with the late-onset type may have a mild progressive muscle weakness. disability for years or develop the need for assistive devices for mobility and ventilation Etiology/Types nn Autosomal recessive Diagnosis nn Types: Differential diagnosis ––Infantile (4–8 months old) nn Duchenne muscular dystrophy ––Late onset (>1 year old) nn Spinal muscular atrophy nn Limb-girdle dystrophy Epidemiology nn Inflammatory myopathies nn Frequency is 1 per 138,000 births for infantile type nn Amyotrophic lateral sclerosis nn Frequency is 1 per 57,000 for late onset type History Pathogenesis nn Infants have difficulty lifting head or rolling over nn Caused by a deficiency of the lysosomal enzyme acid nn Failure to gain weight alpha-glucosidase (also called acid maltase) nn Delayed or failure to meet developmental milestones nn Progressive decrease in limb strength Risk Factors nn Recurrent respiratory infections nn A positive family history of Pompe disease nn Difficulty chewing and swallowing nn Frequent falls Clinical Features nn Difficulty climbing stairs or standing nn Patients with the infantile form present with nn Difficulty breathing, especially while lying down weakness, hypotonia, respiratory infections, delayed Examination milestones, feeding difficulties, and failure to thrive nn Hypotonia nn Patients with the late-onset form present with nn Head lag progressive muscle weakness, recurrent respiratory nn Weak suck reflex infections, difficulty swallowing, and delayed nn Weakness of leg and pelvic muscles milestones nn Hepatomegaly nn Young children may not be able to walk, run, and nn Enlarged tongue jump at the same age as their peers nn Waddling gait nn Natural History Loss of balance with ambulation nn Scoliosis nn The infantile form progresses quickly and patients nn Abnormal heart rhythm have a high mortality if left untreated nn There is a glycogen buildup within cardiac muscles Testing that causes cardiac hypertrophy in the infantile type nn Acid alpha-glucosidase enzyme levels nn There is a progressive weakness of respiratory nn Creatine kinase levels are elevated muscles that leads to an ineffective cough, difficulty nn Muscle biopsy—excessive glycogen accumulation in breathing, recurrent respiratory infections, and nn Chest x-ray—heart is enlarged respiratory failure nn Electrocardiogram

164 Pompe Disease (Glycogen Storage Disease Type II) 165 nn Echocardiogram—thickened cardiac tissue nn Pulmonology nn EMG nn Respiratory therapy nn Pulmonary function tests—decreased vital capacity nn Speech therapy nn Sleep study nn Genetic counseling nn Pitfalls Orthopedics nn Failure to monitor respiratory status Complications of treatment nn Failure to monitor nutritional status nn Physical therapy should not exceed exercise tolerance Red flags and compromise the patient’s cardiac or respiratory status nn Recurrent respiratory infections nn Failure to gain weight Prognosis nn Loss of vital capacity nn Variable, depending on the type, age of onset, and severity of symptoms Treatment nn Infantile type is usually fatal within the first 2 years of Medical life due to cardiorespiratory failure nn Enzyme replacement therapy using Alglucosidase alfa nn Without medical treatment, the disease is lethal in ––Myozyme is approved for infantile-type infants and young children Pompe disease nn Late-onset type is slowly progressive and ––Lumizyme is approved for late-onset type Pompe associated with significant morbidity and premature disease for patients 8 years and older who do not mortality have evidence of cardiac hypertrophy nn Prognosis is dependent on respiratory status nn Evaluation for bracing, orthotics, and assistive devices nn Ventilatory support Helpful Hints nn Respiratory status should be monitored every 3 to Exercises 6 months for decline of function nn Strengthening of weakened limb muscles nn Pompe disease is the only glycogen storage disease nn Strengthening of respiratory and oropharyngeal with a defect in lysosomal metabolism muscles nn Cardiac involvement in the late-onset type is lacking nn Range of motion and stretching to prevent contracture or mild compared with the infantile form formation nn Developing motor skills Suggested Readings Modalities Hirschhorn R, Reuser AJJ. Glycogen storage disease type II: Acid alpha-glucosidase (acid maltase) deficiency. nn None In: Scriver C, Beaudet A, Sly W, Valle D, eds. The Metabolic Surgical and Molecular Bases of Inherited Disease. 8th ed. (pp. 3389–3420). New York: McGraw-Hill; 2001. nn Spinal fusion for severe scoliosis Wang RY, Bodamer OA, Watson MS, Wilcox WR; nn Tendon release for contractures on behalf of the ACMG Work Group on Diagnostic Consults Confirmation of Lysosomal Storage Diseases. Lysosomal storage diseases: Diagnostic confirmation and nn Cardiology ­management of presymptomatic individuals. Genet Med. nn Neurology 2011;13(5):457–484. VI: Muscle Diseases Muscle VI:

Rhabdomyolysis Gabriel Smith MD ■ Nathan D. Prahlow MD

Description nn Damaged muscle cells retain water, resulting in Breakdown of striated muscle fibers with the release hypovolemia of potentially toxic cellular contents into the systemic nn Hypovolemia activates the sympathetic nervous system circulation and other systems resulting in renal vasoconstriction and renal ischemia Etiology/Types nn Myoglobin released from muscle cells is toxic to renal nn There are many causes of rhabdomyolysis tubules, resulting in AKI nn Major categories include drugs/toxins, trauma, exertion, immobilization, muscle hypoxia, genetic defects, Diagnosis infections, and extreme body temperature changes Differential diagnosis nn HMG-CoA reductase inhibitors—“Statins” nn Acute intermittent porphyria ––This class of medication has widespread use nn Sickle cell crisis ––Generally very safe and well tolerated nn Viral myopathy ––Subclinical muscle pain and weakness may affect nn Compartment syndrome 7% of patients on statin monotherapy nn Diabetic ketoacidosis ––Clinically detectable myopathy incidence of less than 0.1%, and only one fatal rhabdomyolysis case History per 5 million patients taking statins nn History depends on etiology nn Many patients notice dark urine Epidemiology nn Myalgias and weakness nn Accounts for 7% to 10% of acute kidney injury (AKI) nn Flu like symptoms nn Overall more common in adults nn Oliguria nn Somewhat higher prevalence in males Examination nn Ranges from benign to serious Pathogenesis nn Muscle tenderness or rigidity nn Muscle cell death releases toxic cell components, nn Fever or low body temperature resulting in end organ damage nn Signs of sepsis Risk Factors Testing nn nn See “Etiology” section Serum creatine kinase repeated every 6 to 12 hrs until peak is measured nn Clinical Features Urine dipstick for blood nn Fractional excretion of sodium nn Highly variable, subclinical to severe nn Basic metabolic panel nn Weakness, myalgias nn Cardiac troponins nn Dark urine nn Complete blood count nn Altered mental status if severe nn Coagulation studies nn Natural History Electrocardiogram nn Some insult results in muscle cell death Pitfalls nn Electrolyte disturbances result from release of nn May have insidious onset, especially in immobile intracellular contents hospitalized patients with other comorbidities

166 Rhabdomyolysis 167

Red flags Consults nn Cardiac arrhythmias nn Nephrology: nn Signs of compartment syndrome –– nn Signs of disseminated intravascular coagulation ––Internal Medicine Complications of treatment Treatment nn Aggressive hydration may result in fluid overload, Medical leading to respiratory complaints nn Treat underlying condition nn Vigorous hydration with isotonic crystalloids Prognosis nn Loop diuretics nn Prognosis depends on underlying etiology and any nn Mannitol may reduce compartment pressures other existing comorbidities nn Consider bicarbonate if serious acidosis exists nn Significantly worse if renal failure results nn Treat electrolyte imbalances appropriately Exercises Helpful Hints nn nn Avoid extreme exercise as this can precipitate Early intervention is important for preventing renal rhabdomyolysis failure nn Focus treatment on underlying cause of Modalities rhabdomyolysis nn Heat may relieve residual myalgias nn Always consider rhabdomyolysis as possible cause of Injection renal failure in chronic illness patients nn None Suggested Reading Surgical Bosch X, Poch E, Grau JM: Rhabdomyolysis and acute kidney nn Necessary in case of compartment syndrome injury. New Engl J Med. 2009;361:62–72.

VI: Muscle Diseases Muscle VI:

Schwartz-Jampel Syndrome Nathan D. Prahlow MD

Description History Also known as dysostosis enchondralis metaepiphysaria, nn Neonates/infants: feeding difficulty, choking, chondrodystrophic myotonia, and osteochondromuscular respiratory failure dystrophy, the Schwartz-Jampel syndrome (SJS) includes nn Motor developmental delay, especially ambulation features of muscle stiffness and mild weakness, charac- Examination teristic facies, and bony deformities nn Facies: small palpebral fissures (blepharophimosis), Etiology/Types low-set ears, small puckered mouth, micrognathia, and hypertrichosis of the eyelids (excess hair, or multiple nn Type IA: most common rows of eyelashes) nn Type IB: apparent at birth nn Short neck, pigeon breast, protuberant abdomen nn Type II: a separate disorder, known as nn Stuve-Wiedemann syndrome Sparse subcutaneous tissue nn Clinical myotonia with action and percussion Epidemiology nn Joint contractures of shoulders, elbows, wrists nn Unknown nn Muscle mass may be atrophic or hypertrophic Testing Pathogenesis nn Genetic studies nn Mutations of the HSPG2 gene, causing abnormalities nn EMG: usually normal nerve conduction study (NCS); in the basement membrane protein perlecan spontaneous high-frequency/low-voltage discharges Risk Factors at rest, which increase with needle movement, muscle percussion, or voluntary movement; may resemble nn Family history of SJS myotonic discharges Clinical Features nn Mild to moderate creatine kinase elevation nn Muscle stiffness and mild weakness nn Muscle biopsy: normal or nonspecific myopathic nn Characteristic facies: small, fixed facial features abnormalities nn Bony deformities: short stature, joint contractures nn Plain films to document bony abnormalities noted on nn Intelligence may be affected, but high intelligence may examination be seen nn Occasional electrocardiogram abnormalities Natural History Pitfalls nn Mistaken diagnosis nn Usually diagnosed before 3 years of age nn Motor developmental delay, particularly ambulation Red flags nn Gait becomes progressively stiff and wide based nn Type II (Stuve-Wiedemann syndrome) has a nn Slowly progressive, but may be static high-infant mortality rate Diagnosis Treatment Differential diagnosis Medical treatment nn Myotonia congenita nn Anticonvulsants and quinine nn Myotonic dystrophy nn Antiarrhythmics nn Muscular dystrophies nn Hereditary motor-sensory neuropathies Exercise nn Myasthenia gravis nn Maintenance of range of motion nn Periodic paralysis nn Massage nn Stiff man syndrome nn Gradual muscle warm-up

168 Schwartz-Jampel Syndrome 169

Modalities Complications of treatment nn As needed nn Side effects of medications Injection Prognosis nn Botulinum toxin for those unable to maintain nn Type IA does not significantly shorten lifespan an open eye nn 20% of patients are mentally retarded Surgical Helpful Hint nn Orbicularis oculi myectomy, levator aponeurosis nn Although 20% are mentally retarded, many patients resection, and lateral canthopexy for severe are of normal or superior intelligence blepharophimosis not amenable to botulinum toxin Suggested Readings nn Contracture release Ault J. Schwartz-Jampel syndrome treatment and management. (Updated February 2, 2010). http://emedicine.medscape.com Consults /article/1172013-treatment#a1128. Medscape, New York. nn Ophthalmology Pascuzzi RM. Schwartz-Jampel syndrome. Semin Neurol. nn Orthopedic surgery 1991;11(3):267–273.

VI: Muscle Diseases Muscle VI:

VII Movement Disorders Blepharospasm Susan X. Yu DO ■ Nathan D. Prahlow MD

Description nn Improved by concentrating on a specific task or by A focal dystonia characterized by excessive involuntary using sensory tricks (talking or touching the forehead repetitive blinking or sustained eyelid closure or the eyebrow)

Etiology/Types Natural History nn Also called benign essential blepharospasm nn With progression, spasms occur frequently during the nn Unknown etiology day, disappear in sleep, then reappear several hours nn Autosomal dominant disorder with reduced after waking penetrance of about 5% with genetic heterogeneity nn Further progression: spasms intensify to the degree nn Due to spasms of orbicularis oculi (OO) that the patient is functionally blind, as the eyelids nn Sometimes due to failure of levator palpebrae may remain forcibly closed for hours contraction: apraxia of eyelid opening Diagnosis Epidemiology Differential diagnosis nn Average onset age 50 to 60 years nn Blepharitis: eyelid inflammation nn 12 to 133 per million nn Blepharoptosis: drooping of the eyelid margin nn 2.3 times more frequent in women and with older nn Facial palsy: inability to close the upper lid and laxity onset age of the lower lid nn Third nerve palsy Pathogenesis nn Stroke nn Unknown. Likely due to pathology in the basal nn Dry eye syndrome ganglia, brainstem, and thalamus nn Orbital inflammatory syndrome nn Dry eye and photophobia suggest trigeminal system nn Thyroid eye disease (due to overactive thyroid gland) sensitization and/or sympathetically maintained pain nn Autoimmune diseases such as myasthenia gravis and multiple sclerosis Risk Factors History nn Increased risk: nn Clinical diagnosis ––prior head trauma with loss of consciousness ––family history of dystonia Examination nn ––prior eye disease Observation of delayed eye opening nn Reduced risk: Testing ––previous cigarette smoking nn EMG recordings of the pretarsal orbicularis oculi ––coffee drinking nn In eyelid apraxia, EMG shows levator muscle inactivity despite the patient’s attempt to open eyes Clinical Features Pitfalls nn Begins gradually with excessive blinking and eye nn Selective contraction of the pretarsal portion irritation (normal blink = once every 2 to 3 seconds) of the orbicularis oculi can be responsible for nn Eyelid spasms may occur with cervical dystonia, Meige eyelid closure syndrome, and other cranial dystonias (clenching or nn May be associated with a reactive depression mouth opening, grimacing, and tongue protrusion) nn Triggers: dry eyes on bright light exposure, watching Red flags television, reading, driving, fatigue, and emotional nn When accompanied by other symptoms of stroke, stress such as extremity weakness

172 Blepharospasm 173

Treatment nn Deep brain stimulation for patients also with cranial Medical dystonia—mild to 75% improvement nn Anticholinergics: trihexyphenidyl and benztropine Consults nn Antihistamine: diphenhydramine nn Neurology nn Benzodiazepines: clonazepam, diazepam, lorazepam, nn Ophthalmology alprazolam nn Neurosurgery nn Antispasticity agents: baclofen and tizanidine Complications of treatment nn Antipsychotics: haloperidol, thioridazine, amitriptyline nn Botulinum toxin: ptosis (21%), superficial punctate nn New-generation neuroleptics: tetrabenazine, keratitis (6%), and eye dryness (6%) risperdone, olanzapine, quetiapine, and clozapine nn Anticholinergics and antihistamine: constipation, dry nn Others: Carbidopa/levodopa, carbamazepine, mouth, difficulty in urinating, trouble concentrating, propranolol memory loss, and confusion. Use caution with Exercise glaucoma nn nn Occupational therapy to work on stress reduction Benzodiazepines and antispasticity agents: sleepiness, difficulty of thinking, fatigue, imbalance, Modalities dependency nn Use of a sensory trick: glasses fitted with wire loops to nn Antipsychotics: reversible parkinsonism, involuntary press against the brow or to lift the upper lid (Lundie movements loops) nn New-generation neuroleptics: sleepiness, insomnia, nn Reduction of photophobia with FL-41 rose-tint lenses constipation, fatigue, and confusion; Clozaril can Injection lower the white blood cell count nn Treatment of choice: botulinum toxin injection of the Prognosis eyelid muscles: nn Typically a chronic condition ––High efficacy for many years without side effect or nn 10% spontaneously remit in the first 5 years loss of efficacy nn More likely to spread past the head (31%) than ––Botox 27- to 30-gauge without EMG upper extremity dystonias, most during the first ––Start with 1.25 to 2.5 units (0.1 mL)/muscle: 5 years •• Upper lid: medial pretarsal OO • • Upper Lid: lateral pretarsal OO Helpful Hints •• Lower lid: lateral pretarsal OO nn Determine the contribution of lid opening apraxia ––Unless the pretarsal portion is injected with because it does not respond well to botulinum toxin botulinum toxin, treatment will fail, and the injections patient could be diagnosed with apraxia in error. nn Add oral medications slowly when botulinum toxin For proper diagnosis, inject Riolan’s muscle, at the injections are not effective, titrate to effective dosage lid margin to minimize side effects nn Doxorubicin chemomyectomy provides >10 years relief but has skin side effects Suggested Readings nn Superior sympathetic ganglion blockade with local Hallett M, Evinger C, Jankovic J, Stacy M, BEBRF International anesthetic to decrease photophobia Workshop. Update on blepharospasm: Report from Surgical the BEBRF International Workshop. Neurol. 2008; 71(16):1275. nn Myectomy of the eyelid protractors; shortening of the Hallett M. Blepharospasm: Recent advances. Neurol. levator tendon or frontalis sling 2002;59(9):1306–1312. VII: Movement Disorders

Dystonia Shashank J. Davé DO FAAPMR

Description Natural History Involuntary muscle contractions leading to abnormal nn May begin in the head/neck or a limb, then progress movement and posture to adjacent parts, such as the trunk nn Chronic, but some may spontaneously remiss Etiology/Types nn Primary dystonia: mostly inherited in autosomal Diagnosis dominant pattern Differential diagnosis nn Secondary dystonia: usually acquired and has an nn Brain injury: acquired and congenital associated neurologic impairment and ataxia nn Stroke nn Focal: for example, cervical dystonia, blepharospasm, nn Multiple sclerosis facial dystonia, occupational dystonia nn Seizures nn Generalized: involves one limb, trunk, and another nn Encephalitis body area nn Musculoskeletal disorders nn Spasmodic dysphonia–laryngeal muscles nn Drugs such as dopamine blockers nn Conversion disorder Epidemiology nn Wide range, based on few epidemiologic studies History nn 2 to 7500 per million, with cervical dystonia being the nn Abnormal contractions of the involved limb/body part most common focal dystonia during activity, which usually goes away with rest Examination Pathogenesis nn Depends on body part affected; for head and neck, nn Neurodegenerative disorder see Chapter 89 on “Torticollis” nn Type 1 (DYT1) dystonia: mutation in TOR1A gene nn Movement usually has a directional component which encodes an ATP-binding protein nn Geste antagoniste: sensory trick such as light touch nn May involve basal ganglia, motor cortex, and or brushing the involved area, which attenuates the cerebellum movement nn Decreased inhibition nn Neurotransmitter imbalance in dopamine and Testing acetylcholine nn Usually a clinical diagnosis nn Brain magnetic resonance imaging (MRI) to check Risk Factors for lesions in the basal ganglia, motor cortex, and nn Very few, but may be associated with stressful cerebellum, and to rule out other diagnoses listed above nn life-events Laboratories: comprehensive metabolic panel, complete blood count nn Clinical Features Wilson’s disease: ceruloplasmin nn Gene testing for hereditary dystonia, such as DYT1 nn Muscle spasm with involuntary sustained tonic or dystonia clonic contractions nn Levodopa trial: for dopa-responsive dystonia nn Co-contraction: simultaneous agonist and antagonist contraction Pitfalls nn Contractions may intensify with voluntary effort nn Conversion disorder nn Sensory trick: light touch over affected body region nn Essential tremor versus dystonia may attenuate dystonia nn Dystonia plus parkinsonism

174 Dystonia 175

Red flags Consults nn Neoplasm nn Movement disorder neurologist nn Cord compression: bilateral symptoms and lower limb nn Genetic counselor (if appropriate) involvement nn Physical medicine and rehabilitation

Treatment Complications of treatment nn Levodopa: dyskinesia, hypotension, hallucination Medical nn Trihexyphenidyl: xerostomia, blurred vision, nn Depends on etiology glaucoma nn Levodopa, if trial is successful nn Baclofen: sedation, dizziness; avoid sudden nn Trihexyphenidyl withdrawal nn Baclofen: oral, intrathecal nn Botulinum toxin: xerostomia, dysphagia, weakness nn Clonazepam nn Tetrabenazine Prognosis Exercises nn Treatment largely symptomatic nn Physical therapy for stretching and strengthening; gait nn No curative treatments available retraining nn Response rate to levodopa is 15% nn Occupational therapy for activities of daily living nn Generalized cardiovascular conditioning Helpful Hint nn Contracture prevention nn Generalized dystonia warrants generalized treatment, Modalities whereas focal dystonia warrants focal treatment nn Ice/heat for pain nn Electrical stimulation for weakness Suggested Readings Comella CL, Pullman SL. Botulinum toxins in neurological Injection disease. Muscle Nerve. 2004;29:628. nn Botulinum toxin for focal muscle overactivity Geyer HL, Bressman SB. The diagnosis of dystonia. Lancet Neurol. 2006;5:780. nn Gene therapy: for DYT1 dystonia, which involves Janovic J. Treatment of dystonia. Lancet Neurol. 2006;5:864. inhibiting gene expression; preclinical studies are Simpson DM, Blitzer A, Brashear A, et al. Assessment: promising Botulinum neurotoxin for the treatment of movement ­disorders (an evidence-based review): Report of the Surgical Therapeutics and Technology Assessment Subcommittee nn Neurosurgical for deep brain stimulation of internal of the American Academy of Neurology. Neurol. 2008; globus pallidus or less commonly, subthalamic nucleus 70:1699. VII: Movement Disorders

Essential Tremor Susan X. Yu DO ■ Nathan D. Prahlow MD

Description nn Enhanced physiologic tremor: Progressive movement disorder, characterized by a rhyth- ––Postural tremor, 10 to 12 Hz, low amplitude mic, involuntary, oscillatory shaking of body parts ––Sudden onset nn Drug and metabolic-induced tremor: Etiology/Types ––Postural tremor, 10 to 12 Hz, low amplitude nn 50% are autosomal dominant ––Sudden onset nn Orthostatic tremor, 15 to 20 Hz Epidemiology nn Parkinsonism: nn 0.4% to 6% prevalence; 5% of those over age 65 years ––Resting tremor, 4 to 6 Hz, “pill-rolling” nn Incidence increases with age ––Gradual onset in older patients nn Affects both genders, all ages, all ethnicities ––Micrographia Pathogenesis ––Gait: narrow-based and shuffling nn Cerebellar tremor/brain tumors: nn Unknown. Lewy bodies found in the brainstem (locus ––Intention and postural tremor, low frequency ceruleus) along with degenerative changes in the ––Ipsilateral to lesion cerebellum ––Abnormal finger-to-nose and heel-to-shin Risk Factors ––Gait: wide-based and ataxic nn nn Each child of an affected parent has a 50% chance of Psychogenic tremor: inheritance ––Changing tremor frequency and amplitude nn No known environmental risk factor ––Abrupt onset, extinction with distraction nn Dystonic tremor: Clinical Features ––Age younger than 50 years nn An action tremor which is usually postural, but ––Irregular, jerky tremors occasionally kinetic ––Abnormal wrist flexion nn Action tremors occur during voluntary muscle nn Wilson’s disease: contraction ––Age younger than 40 years ––Postural tremors occur while maintaining a position ––“Wing-beating” tremor against gravity, such as when holding hands nn Fragile X syndrome outstretched History ––Kinetic tremors (intention tremors) occur during nn Hand tremors noticeable by patient and family target-directed movements nn Handwriting change—view old handwriting samples nn Commonly affects wrists and hands, but also affects to compare the head, lower extremities, and voice nn Precipitating and relieving factors, such as caffeine, nn Either high or low tremor frequency, without other alcohol, medications, exercise, fatigue, or stress neurologic findings nn Relieved with alcohol (two drinks per day) Examination nn Examine for tremors at rest and with activity: Natural History ––Head: nod and shake head nn Any age of onset, often in early adulthood ––Jaw, tongue Diagnosis ––Voice: Reciting a standard paragraph and enunciating a sustained vowel Differential diagnosis ––Limbs: nn Essential tremor is a diagnosis of exclusion: •• Outstretching arms with wrist supination and ––4 to 8 Hz, low amplitude (less than 1 cm movement) pronation

176 Essential Tremor 177

•• Apposing index fingers one inch apart in front of nn Bilateral DBS more effective for voice tremors, but the face dysphagia and dysarthria are more likely as side •• Performing finger-to-nose, shin-to-heel effects •• Drinking or pouring from a paper cup nn Thalamotomy: nn Handwriting samples: large, tremulous, angulated ––Radiofrequency ablation loops; Archimedes spirals ––Gamma knife nn Normal gait, Romberg, and muscle tone Consults Testing nn Neurology nn Laboratories: Rule out potential metabolic or toxin nn Neurosurgery causes with thyroid stimulating hormone, serum Complications of treatment ceruloplasmin, 24-hour urinary copper, complete nn blood count with differential, comprehensive Medications: metabolic profile ––Propranolol: bradycardia, syncope, fatigue, and nn Imaging: Rule out other potential causes such as erectile dysfunction Parkinson’s disease with brain computed tomography/ ––Primidone: drowsiness, dizziness, and magnetic resonance imaging (CT/MRI), single photon disequilibrium emission computed tomography (SPECT) to visualize ––Topiramate: weight loss, extremity paresthesias, and the dopaminergic pathways memory disturbance nn Deep brain stimulation: Pitfalls ––Dysarthria 3% to 18%, paresthesias 6% to 36%, nn Sleep disorders may cause fatigue, which amplifies dystonia 2% to 9%, balance disturbance 3% to 8%, physiologic tremors ataxia 6%, and limb weakness 4% to 8% nn Polyneuropathy may cause small involuntary nn Hardware complications 25% movements that mimic tremors Red flags Prognosis nn Seizures, fever, and anemia may indicate other causes nn Progressive disorder of tremor nn Tremor amplitude increases with age nn Tremor frequency decreases with age Treatment nn 25% of patients retire early or modify their career path Medical nn Propranolol: 50% of patients benefit Helpful Hints nn Primidone: 50% of patients benefit nn Tremor are categorized by activating condition nn Topiramate: 50% of patients benefit (kinetic/intention, postural, resting, and isometric), nn The above can sometimes be used in combination topographical distribution (head, voice, and limbs), nn Gabapentin and frequency (low <4 Hz, medium 4 to 7 Hz, and Exercises high >7 Hz) nn None nn Many medications can influence or cause tremors by Modalities increasing adrenergic activity nn nn Weighted utensils may help dampen tremor for Physiological states, such as anxiety, excitement, self-feeding fright, muscle fatigue, thyrotoxicosis, fever, and pheochromocytoma, may influence tremor Injection severity nn Botulinum toxin is effective for head tremors nn Botulinum toxin has varying results for voice tremors Suggested Readings Surgical Crawford P, Zimmerman EE. Differentiation and diagnosis of tremor. Am Fam Physician. 2011;83(6):697–702. nn Deep brain stimulation (DBS): (Review). ––Nucleus ventrointermedius of the thalamus and Deuschl G, Raethjen J, Hellriegel H, Elble R. Treatment of neighboring subthalamic structures highly effective, patients with essential tremor. Lancet Neurol. 2011;10(2):

but gradual loss of tremor control 148–161. (Review). VII: Movement Disorders

Friedreich’s Ataxia (Primary Spinocerebellar Degeneration) Susan X. Yu DO ■ Shashank J. Davé DO FAAPMR

Description nn Within 5 years of onset, patients develop “scanning” An inherited disease that causes progressive degenera- dysarthria, lower limb weakness, and decreased tion of the nervous system resulting in ataxia, muscle joint-position, and vibration distally. This is due weakness, areflexia, and heart disease to degeneration of the dorsal root ganglia, posterior columns, corticospinal tracts, dorsal spinocerebellar Etiology/Types tracts, and the cerebellum. nn Hereditary: autosomal recessive nn Defect in chromosome 9 with hyperexpansion of GAA Diagnosis repeats in intron 1 of frataxin gene Differential diagnosis nn Amyotrophic lateral sclerosis Epidemiology nn B12 deficiency nn Ratio of 1:50,000 white nn Syphilis nn Ratio of 1:60 to 1:100 carrier frequency nn Peripheral neuropathy nn Hereditary motor sensory neuropathies Pathogenesis nn Spinal cord compression nn Mitochondrial protein frataxin is severely reduced due nn Ovarian cancer to the mutation nn Mitochondrial disorders nn Frataxin deficiency results in abnormal nn Ataxia with vitamin E deficiency intramitochondrial iron accumulation, defective nn Slow virus (Creutzfeldt-Jakob disease) mitochondrial respiration, free radical overproduction, nn Phenytoin intoxication and oxidant-induced intracellular damage History nn Cells of the nervous system, heart, and pancreas with nn high metabolic needs are particularly susceptible to Diagnostic criteria: free radical damage ––Disease duration >5 years ––Disease onset age <25 years (96%) Risk Factors ––Progressive ataxia of gait and limbs nn Family history of Friedreich’s ataxia ––Absent lower limb muscle stretch reflexes (88%) ––Extensor plantar response Clinical Features Examination nn Slowly progressive lower limb ataxia starting at age 10 nn General: kyphoscoliosis to 15 years nn Head, eyes, ears, nose, and throat (HEENT): nystagmus nn Followed by dysarthria and upper limb ataxia nn Cardiac: murmurs nn Muscle weakness, lower limb spasticity, scoliosis, nn Extremities: pes cavus (short foot, high arch, hammer bladder dysfunction, absent lower limb reflexes, loss of toes), limb weakness, spasticity position, and vibration sense nn Neuro: ataxia of four limbs, cerebellar dysarthria, loss nn 67% have hypertrophic cardiomyopathy with chest of vibratory and position sense, high steppage gait, pain, shortness of breath, and heart palpitations positive Babinski reflex, absent lower limb reflexes nn 30% have diabetes mellitus Testing Natural History nn Molecular genetic testing nn Average onset age of 10 to 15 years, with most before 25 nn Targeted mutation analysis by polymerase chain years, with gait ataxia the first symptom (spinocerebellar reaction and/or Southern blot analysis of the GAA degeneration leads to proprioception loss) repeat

178 Friedreich’s Ataxia (Primary Spinocerebellar Degeneration) 179 nn EMG/nerve conduction study (NCS) with motor Modalities nerve conduction velocities >40 m/sec, with reduced nn Bracing for pes cavus and kyphoscoliosis or absent sensory nerve action potentials and absent nn Prostheses: walking aids or wheelchairs for mobility H-reflex Injection nn Electrocardiogram and echocardiogram for a baseline nn Botulinum toxin for spasticity of cardiomyopathy nn Blood tests: fasting glucose, vitamin E, and B12 levels Surgical nn Magnetic resonance imaging (MRI) of the brain nn Correct foot deformities and scoliosis and spine to rule out other brain and spinal cord nn Gastrostomy for dysphagia neurologic conditions nn Pacemaker insertion Consults Pitfalls nn Neurology nn 25% of individuals homozygous for GAA expansion nn Genetics have atypical findings: nn Physical medicine and rehabilitation ––Late onset at age 26 to 39 years, at times >40 years ––Retained reflexes Complications of treatment ––Spastic paraparesis without ataxia nn Medications for spasticity: includes sedation and central nervous system depression Red flags Prognosis nn Shortness of breath on exertion, dizziness, syncope, nn Larger GAA expansions are associated with earlier chest pain, or arrhythmias disease onset, increased frequency of cardiomyopathy and upper limb areflexia, and more rapid disease Treatment progression Medical nn Most patients are wheelchair-bound 15 to 20 years nn Idebenone (analog of coenzyme Q10, free after symptom onset nn radical scavenger) 5 mg/kg improves left Average age of death is 37 years, often due to cardiac ventricular heart mass, no significant effect on failure and aspiration pneumonia nn ataxia Average interval from symptoms onset to death is nn Erythropoietin (frataxin expression upregulator)— 36 years in more recent studies ongoing research Helpful Hints nn Medications for spasticity, arrhythmias, diabetes, nn First symptom is usually unsteady gait; later, ataxia bladder dysfunction gradually worsens, affecting the arms and then the trunk nn Psychological support nn Genetic counseling of the family is important Exercises Suggested Readings nn Muscle-strengthening exercises not effective Bidichandani SI, Delatycki MB. Friedreich Ataxia. GeneReviews; nn Physical therapy/occupational therapy (PT/OT) 1998 Dec 18 [updated 2009 Jun 25]. [Internet]. Pagon RA, Bird TD, Dolan CR, et al., eds. Seattle, WA: University for spasticity, to maintain flexibility, and prevent of Washington, Seattle; 1993–2011. contractures www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part nn Speech therapy for dysphagia management =friedreich VII: Movement Disorders

Huntington’s Disease Gabriel Smith MD ■ Nathan D. Prahlow MD

Description nn Difficulty with chewing, swallowing, speaking, and Huntington’s disease (HD) is a progressive, fatal, autoso- ambulating all progress over time mal dominant disorder characterized by motor, behav- nn Cognitive abilities decline progressively ioral, and cognitive dysfunction. nn Full-time care is eventually required nn Life expectancy is approximately 20 years after the Etiology/Types onset of symptoms nn Autosomal dominant hereditary increase in Diagnosis polyglutamine (CAG) repeats in the gene coding sequence of the Huntingtin gene Differential diagnosis nn Westphal variant (~10% of HD cases)—onset at age nn Neuroacanthocytosis <20 years, characterized by Parkinsonian features nn Multiple sclerosis with little or no choreiform movements nn Systemic lupus erythematosus nn HIV Epidemiology nn Cocaine or other central nervous system stimulants nn Prevalence of two to eight cases per 100,000 History nn Onset is typically between 25 and 45 years (range of nn Gradually increasing, unintentional choreiform 3–70 years) movement over months to years nn Male-to-female ratio is 1:1 nn Dysarthria and dysphagia are common nn Personality changes Pathogenesis nn Poor memory and intellectual dysfunction nn Genetic disorder resulting in abnormal protein nn Depression, psychosis, and suicidal ideation are production and cell death in the basal ganglia common ––Genetic anticipation occurs resulting in Examination increasing numbers of repeats with subsequent nn Generalized choreiform movements, often disguised generations by the patient as purposeful actions nn CAG repeats result in Huntingtin protein dysfunction nn Manifestations of mood disorder (variable) nn Dysfunction of protein (unknown function) leads to nn Dysphonia disturbed homeostasis within neurons nn May appear parkinsonian in later disease nn Neurodegeneration in the basal ganglia results in clinical features of HD Testing nn Head computed tomography/magnetic resonance Risk Factors imaging (CT/MRI) looking for caudate atrophy nn nn Positive family history Genetic testing for CAG repeats nn nn Age 25 to 45 years May consider genetically testing children nn HIV testing nn Clinical Features Antiphospholipid antibodies nn Urine drug screen nn Progressive, involuntary choreiform movements nn Changes in behavior Pitfalls nn Changes in personality nn Delayed diagnosis nn Dementia nn Patients with HD often need 24-hour care as disease progresses Natural History Red flags nn Symptoms may begin at any age and are progressive nn Loss of coordination, leading to frequent falls nn Chorea: jerky, random, uncontrollable movements nn Suicidal ideation or behavior

180 Huntington’s Disease 181

Treatment nn Genetic Counseling nn Medical Physical therapy/occupational therapy (PT/OT) nn Speech therapy nn Benzodiazepines nn Physical medicine and rehabilitation nn Valproic acid nn Tetrabenazine—dopamine depleting agent Complications of treatment nn Selective serotonin re-uptake inhibitors (SSRIs) for nn Standard side-effect profiles of medications depression nn Atypical antipsychotics preferred for treatment of Prognosis psychosis nn Progression of disease and death is inevitable Exercises nn Earlier age of onset in subsequent generations nn Core strengthening for posture nn Coordination improvement Helpful Hints nn Speech therapy to prevent aspiration nn Clinical diagnosis of HD can be strongly suspected in cases of chorea with a positive family Modalities history nn None nn Open communication with genetic counselors is vital Surgical if children of HD patients are considering being tested nn None for the disease Consults Suggested Reading nn Neurology Sturrock A, Leavitt B. The clinical and genetic features nn Psychiatry, with individual, group, and family therapy of Huntington disease. J Geriatr Psychiatry Neurol. sessions 2010;23(4):243–259. VII: Movement Disorders

Parkinson’s Disease Shangming Zhang MD FAAPMR

Description nn Wilson’s disease Parkinson’s disease (PD) is the most common movement nn Normal pressure hydrocephalus disorder. It occurs as a result of degeneration of brain nn Brain tumors stem nuclei, especially the dopaminergic cells of substan- History tia nigra. Hyperactivity of the cholinergic neurons in the nn Resting “pill-rolling” tremor suppressed by activity or caudate nuclei is also thought to contribute to PD. The sleep common clinical features include resting tremor, rigidity, nn Smooth resistance to passive movement and joint postural instability, and bradykinesia. range of motion Etiology/Types nn Festinating gait, with small, shuffling steps nn Frequent falls or tripping nn Due to lack of dopamine-producing cells in the basal nn Masked facies ganglia nn Small handwriting (micrographia) Epidemiology nn Depression nn Dementia nn Prevalence: 160 per 100,000 nn 1% of the population over 50 years of age Examination nn Mask-like facies Pathogenesis nn Muscle rigidity nn Dopamine depletion leads to imbalance between nn Resting tremor dopaminergic input and cholinergic input nn General slowing of movements nn Postural instability Risk Factors nn Olfactory dysfunction nn Age: 5 per 100,000 in the population younger nn Micrographia than 40 years versus 300 to 700 per 100,000 in the Testing population at 70 years of age nn nn Male-to-female ratio of 3:2 Plasma ceruloplasmin and copper to rule out Wilson’s disease Clinical Features nn Brain magnetic resonance imaging (MRI) to rule nn Resting tremor (the most common presentation) out normal pressure hydrocephalus, tumor, multiple nn Lead pipe rigidity (constant increase in tone resisting strokes, subdural hematoma movement) Pitfalls nn Cogwheel rigidity (jerky increases in tone resisting nn Driving evaluation movement) nn Fall prevention: home evaluation nn Postural instability nn Aspiration pneumonia: swallowing evaluation nn Bradykinesia Red flags Natural History nn Orthostatic hypotension nn Chronic progressive debilitating neurodegenerative nn Aspiration pneumonia central nervous system disease Treatment Diagnosis Medical Differential diagnosis nn l-dopa: levodopa/carbidopa nn Drug-induced parkinsonism nn Dopamine receptor agonists: pergolide, bromocriptine nn Toxin-induced parkinsonism nn Anticholinergics: amantadine, benztropine nn Multiple strokes nn Dopamine metabolism inhibitors: selegiline 182 Parkinson’s Disease 183

Exercise nn Psychiatry for management of depression and dementia nn Physical exercises improve physical functioning, nn Neurosurgery for surgical treatment in advanced cases health-related quality of life, strength, balance, and Complications of treatment gait for patients with PD nn Side effects of medications nn Treadmill training beneficial nn Infection or failure of surgery Modalities nn Deep brain stimulator effectively reduces tremor, Prognosis rigidity, and bradykinesia nn Positive prognostic indicators: early tremor, rigidity, nn Biofeedback for sialorrhea and a family history of Parkinson’s disease nn Injections Negative prognostic indicators: bradykinesia, akinesia, postural instability, gait dysfunction, cognitive nn Chemodenervation with botulinum toxin to treat deficits, dysphagia, and late age of onset spasticity and tremor nn Mortality rate from PD is threefold that of the general Surgical population matched for age, gender, and race nn Destructive surgeries: thalamotomy and pallidotomy nn Deep brain stimulation Helpful Hint nn To be used to treat rigidity, dyskinesia, and tremor nn l-dopa is currently a keystone of treatment and has in advanced PD patients who are unresponsive to or shown to reduce mortality by 50% intolerant of oral medications Consults Suggested Reading Doherty J, Fried G, Saulino M. Degenerative movement dis- nn Neurology for medication options orders of the central nervous system. In: Braddom RL, ed. nn Physical and occupational therapy Physical Medicine & Rehabilitation. 4th ed. (pp. 1223–1232). nn Speech language pathology Philadelphia, PA: Elsevier Saunders; 2011. VII: Movement Disorders

Torticollis Shashank J. Davé DO FAAPMR

Description nn Cervical myelopathy Abnormal head/neck muscle contraction resulting in aber- nn Soft tissue strain rant movement or posture of the head, neck, or shoulders nn Stroke nn Brain injury Etiology/Types nn Medication side effects (dopamine antagonists) nn Sagittal plane: anterocollis–forward flexion nn Multiple sclerosis nn Sagittal plane: retrocollis–backward extension History nn Coronal plane: laterocollis–sidebending nn Neck pain (50%) nn Transverse plane: torticollis–rotation nn Functionally limiting neck range of motion nn Usually involves combinations of the above nn Head/neck tremor nn May worsen with stress Epidemiology nn Focal dystonia: cervical dystonia is the most common Examination type nn Extremities: nn Prevalence of focal dystonia 295 per million ––May have associated tremor/dystonia if progression nn Incidence of focal dystonia 24 per million ––Usually normal strength and reflexes nn Neurologic: Pathogenesis ––Neck muscle tenderness nn Lesions within the basal ganglia, motor cortex, and ––Asymmetric head/neck position and/or range of cerebellum motion in sagittal, coronal, or transverse plane, or nn Neurotransmitter imbalance in dopamine and combination of all the three acetylcholine ––Associated trigger points Testing Risk Factors nn Cervical spine x-ray and magnetic resonance imaging nn Neck injury (eg, motor vehicle collision) (MRI) to rule out other causes and structural nn Stressful life events abnormalities nn Clinical Features Needle EMG to determine which muscles are involved in torsion pattern nn Head/neck muscle spasm with involuntary sustained nn Brain MRI to rule out other conditions tonic or clonic contractions nn Co-contraction: simultaneous agonist and antagonist Pitfalls contraction nn Missing myofascial pain syndrome nn Contractions may intensify with voluntary effort Red flags nn Sensory trick: light touch over affected body region nn Cervical cord compression (eg, chin) may attenuate dystonia nn Malignancy Natural History Treatment nn Average onset age 30 to 50 years nn Usually waxes and wanes, but may spontaneously remit Medical nn May progress to other body regions, such as the face nn Muscle relaxants: baclofen, tizanidine nn Analgesics Diagnosis Exercises Differential diagnosis nn Isotonic neck strengthening nn Cervical radiculopathy nn Muscle energy/proprioceptive neuromuscular facilitation nn Myofascial pain syndrome nn Multiplanar range of motion 184 Torticollis 185

Modalities Prognosis nn EMG biofeedback nn May very rarely spontaneously remit, but cervical nn Heat/ultrasound dystonia is considered a lifelong neurodegenerative nn Ice disorder

Injection Helpful Hints nn Botulinum toxin nn On examination, break down torsion pattern into Surgical three cardinal planes to determine which muscles may nn Deep brain stimulation be involved (transverse plane/toricollis may involve contralateral sternocleidomastoid and ipsilateral Consults splenius capitis) nn Neurology nn Needle localization techniques with botulinum toxin nn Physical medicine and rehabilitation injections include EMG and ultrasound nn Neurosurgery Complications of treatment Suggested Readings Comella CL. The treatment of cervical dystonia with botulinum tox- nn Oral muscle relaxants: drowsiness and dizziness ins. J Neural Transm. 2008;115(4):579–583. [Epub 2007 Nov 12]. nn Botulinum toxin: neck muscle weakness, dysphagia, Stacy M. Role of botulinum toxin in the treatment of cervical xerostomia dystonia. Neurol Clin. 2008;26(Suppl 1):23. VII: Movement Disorders

Tourette’s Syndrome Susan X. Yu DO ■ Shashank J. Davé DO FAAPMR

Description nn Boys are more likely to have tics with attention deficit A chronic childhood-onset condition characterized by hyperactivity disorder (ADHD) motor and vocal tics lasting for more than 1 year. Motor nn Girls are more likely to have tics with OCD tics include simple (twitching, eye blinking), dystonic (slow twisting movements), tonic (isometric co­ ntractions), com- Natural History plex motor (touching, tapping), and echopraxia ­(mimicking nn Average onset age 5.6 years gestures of others). Vocal/phonic tics include simple (throat nn Tics most severe at age 10 years clearing, sniffing, coughing), complex (words or partial nn Tics start to resolve at age 13 years words), coprolalia (shouted obscenities), and echolalia nn One-third resolve in adulthood (repeating words of others) nn Tics may not resolve until age 30 years

Etiology/Types Diagnosis nn Primary: unknown Differential diagnosis nn Secondary: nn ––Inherited: majority of cases, but no gene identified A diagnosis of Tourette’s syndrome includes each of ––Infection: Streptococcus infection (not yet proven) the following: ––Toxins: hypothesized ––Onset younger than 18 years ––Traumatic brain injury ––Both a motor tic and a phonic tic present for over 1 year Epidemiology ––Tics occurring many times a day—usually in nn 1% prevalence bouts—and nearly every day; however, some may be nn Rare in African descent present only intermittently ––Not due to the direct physiological effects of a Pathogenesis substance (stimulants) or general medical condition nn Unclear. May be due to a developmental defect in the (Huntington’s disease or postviral encephalitis) migration of the GABAergic neurons in the basal nn ganglia creating an imbalance in the cortico-striato- nn Asthma thalamic circuit. Tics are hypothesized to be a result nn Hyperactivity, nervousness of failure of cortical inhibition of unwanted motor nn Dystonia programs that are generated in the basal ganglia nn Myoclonus nn Postulated autoimmune reaction after streptococcal nn Chorea infection; however, no temporal link has been found nn Compulsions Risk Factors History nn Comorbid Obsessive-Compulsive Disorder (OCD) nn Tics decreased by sleep, alcohol, orgasm, fever, nn Maternal prenatal use of coffee, cigarettes, and relaxation and concentrating on an enjoyable task alcohol nn Suppression of tic in public places, until an irresistible nn Nonspecific maternal life stress during pregnancy impulse to release the tic nn Forceps delivery nn Waxing and waning of tics nn Low birth weight nn Premonitory sensation localized at the site of the tic nn Likely bilineal (maternal and paternal) transmission Examination nn Except for tics, neurologic exam is usually normal Clinical Features nn Involuntary, sudden, rapid, brief, repetitive head, neck Testing movements, gestures and vocalizations during times nn Clinical diagnosis of stress, anxiety, excitement, fatigue, or boredom nn Neuroimaging and laboratory tests not needed 186 Tourette’s Syndrome 187 nn Magnetic resonance imaging (MRI) shows overall Exercises larger amygdala and hippocampus volume (but nn None decreases with age) Modalities nn Electroencephalography and evoked responses not nn None helpful Injection Pitfalls nn Botulinum toxin for eye blinking, neck and nn Assess for coexisting psychiatric conditions, especially shoulder tics ADHD and OCD nn Need to rule out benign common tic disorder that Surgical lasts <1 year in 3% to 24% of school children nn Deep brain stimulation of the thalamus, globus nn Vocal tics may be due to upper respiratory disorders pallidus, putamen, subthalamic nucleus Red flags Consults nn Seizures nn Neurology nn Fever/infection nn Allergy nn Head trauma nn Ophthalmology Complications of treatment Treatment nn Atypical antipsychotics: marked weight gain, glucose Medical intolerance nn All antipsychotics: sedation, depression, increased nn Education about the condition is key in order to appetite, parkinsonism maintain and strengthen the child’s self-confidence and self-esteem Prognosis nn Habit-reversal treatment to suppress tics nn In one-third of children, tics resolve in adulthood nn Commonly used medications may or may not be nn In one-third of children, tics become much less Food and Drug Administration approved for severe treatment of Tourette’s syndrome nn In one-third of children, there is no change in tics nn Tics alone: nn Tic severity stabilizes by age 25 years ––First line: guanfacine, tetrabenazine ––Second line: fluphenazine, risperidone, atypical Helpful Hints antipsychotics (haloperidol, pimozide), clonzaepam, nn Best time to look for tics is when the patient is walking topriamate, botulinum toxin into or out of the exam room ––Third line: deep brain stimulation nn Tetrabenazine causes less weight gain and less tardive nn With OCD: dyskinesia than antipsychotic medications ––First line: cognitive behavioral therapy, selective nn Methylphenidate is effective for ADHD and does not serotonin re-uptake inhibitors (SSRIs) exacerbate tics ––Second line: atypical antipsychotics (haloperidol, pimozide) ––Third line: deep brain stimulation Suggested Readings nn With ADHD: Jankovic J, Kurlan R. Tourette syndrome: Evolving concepts. Mov Disord. 2011;26(6):1149–56, May. ––First line: behavioral therapy, guanfacine Kurlan R. Clinical practice. Tourette’s syndrome. N Engl J Med. ––Second line: clonidine, methylphenidate, other 2010;363(24):2332–2338. (Review). (Erratum in: N Engl J Med. central nervous system stimulants, atomoxetine 2011 Feb 3;364(5):490). VII: Movement Disorders

Writer’s Cramp Susan X. Yu DO ■ Nathan D. Prahlow MD

Description Natural History A focal task-specific dystonia, an involuntary spasm, flex- nn Some patients progress from simple to dystonic writer’s ion, extension, and or rotation of fingers, wrist, elbow and cramp or shoulder, causing writing difficulties Diagnosis Etiology/Types Differential diagnosis nn Etiology unknown, autosomal dominant gene with nn incomplete penetrance Benign essential tremor nn nn Simple: writing difficulty without difficulty Parkinson’s disease nn performing other manual motor tasks Multiple sclerosis nn nn Progressive: writing difficulty along with difficulty Spinocerebellar degeneration nn with other motor tasks such as hair combing and Spinal muscular atrophy nn lifting utensils Dopamine-responsive dystonia nn nn Dystonic: involuntary hand spasm that interferes with Wilson’s disease many manual motor functions History nn Progressive writing difficulty Epidemiology nn Pain is rare, but may have finger, forearm, arm, or nn 69 per million shoulder discomfort nn Most common in the age group 30 to 50 years nn Male-to-female ratio is 1.3:1 Examination nn Occupations that involve writing nn Flexion and wrist ulnar deviation, elbow elevation when writing Pathogenesis nn Compensatory maneuvers: excessive gripping; or nn Unknown holding pen vertically, in a closed fist, or between nn Likely a disorder of a motor subroutine in the index and long fingers cortex-basal ganglia-thalamus-cortex loop nn Normal muscle strength, muscle stretch reflexes, and nn Spinal reciprocal inhibition, a process that inhibits sensation the antagonist muscles when the agonist muscles are nn Decreased range of motion and increased muscle active, is reduced tone in the flexor and extensor muscles of the nn Multichannel EMG of the affected side shows upper limb excessive simultaneous contraction of agonist nn One-third of patients with large-amplitude hand and antagonist active hand muscles when writing, tremor during writing or when arm is outstretched with abnormally prolonged EMG activation bursts, especially in the triceps Testing nn EMG of both extremities to rule out nerve injury Risk Factors nn Magnetic resonance imaging (MRI) of the brain to nn 5% with positive family history rule out a structural lesion nn 25% with relatives with dystonia Pitfalls nn Higher risk with history of local trauma nn A small number of patients may have pain and Clinical Features paresthesias due to carpal tunnel syndrome, caused by repeated dystonic wrist spasms nn Excessive co-contraction of agonist and antagonist active hand muscles when writing (normal: alternating Red flags contraction of agonist and antagonist muscles when nn A focal dystonia can sometimes be the first writing) manifestation of a generalized dystonia 188 Writer’s Cramp 189

Treatment Consults nn Medical Neurology nn Neurosurgery nn Anticholinergic: Trihexyphenidyl, effective in 5%: nn Physical medicine and rehabilitation ––Reduces dystonia by blocking cholinergic innervation of the basal ganglia, which in turn Complications of treatment increases the dopaminergic output nn Trihexyphenidyl: dry mouth, blurred vision, memory nn Beta-adrenergic blockers: propranolol: loss, confusion ––Reduce hand tremor nn Botulinum toxin: temporary weakness and pain at Exercises injection sites nn None Prognosis Modalities nn 33% attempt to change hands for writing nn Occupational therapy—adaptive devices: nn 50% continue to use dominant hand for writing ––Alter pen grip, increase pen diameter, use a writing nn 20% to 25% develop same symptoms on the devise that mounts a pen on a gliding or ball-bearing contralateral hand and forearm tripod frame (Blackburn writing devise) nn 15% discontinue writing with dominant hand nn Sensory discrimination therapy nn 5% have spontaneous remission for months or years, nn Transcutaneous electrical nerve stimulation (TENS) but with eventual recurrence of forearm flexors improves writing time and decrease nn 7% develop carpal tunnel syndrome tremor nn Cooling and warming of arm with various modalities Helpful Hint may allow better writing performance nn Writer’s cramp is more likely to cause coordination Injection deficits rather than to cause pain, as in overuse nn Botulinum toxin with EMG guidance to weaken syndromes overactive muscles: effective in 67% Surgical Suggested Readings nn Stereotactic thalamotomy Gordon NS. Focal dystonia, with special reference to writer’s cramp. Int J Clin Pract. 2005;59(9):1088–1090. nn Deep brain stimulation of the ventral thalamic Rhoad RC, Stern PJ. Writer’s cramp—a focal dystonia: Etiology, nucleus (Voa and Vop: nucleus ventrooralis anterior diagnosis, and treatment. J Hand Surg Am. 1993;18(3): and posterior) 541–544. VII: Movement Disorders

Index 191

acute inflammatory demyelinating polyradiculoneuropathy, 52 differential diagnosis, 138 clinical features, 52 epidemiology, 138 description, 52 etiology, 138 diagnosis, 52–53 natural history, 138 differential diagnosis, 52 pathogenesis, 138 epidemiology, 52 prognosis, 139 etiology, 52 risk factors, 138 natural history, 52 treatment, 139 pathogenesis, 52 Bell’s palsy, 4–5 prognosis, 53 blepharospasm, 172 risk factors, 52 clinical features, 172 treatment, 53 description, 172 ALS. See amyotrophic lateral sclerosis diagnosis, 172 amyloid neuropathies, 54 differential diagnosis, 172 clinical features, 54 epidemiology, 172 description, 54 etiology, 172 diagnosis, 54–55 natural history, 172 differential diagnosis, 54 pathogenesis, 172 epidemiology, 54 prognosis, 173 etiology, 54 risk factors, 172 natural history, 54 treatment, 173 pathogenesis, 54 botulism, 90 prognosis, 55 clinical features, 90 risk factors, 54 description, 90 treatment, 55 diagnosis, 90–91 amyotrophic lateral sclerosis (ALS), 118 differential diagnosis, 90 clinical features, 118 epidemiology, 90 description, 118 etiology, 90 diagnosis, 118–119 natural history, 90 differential diagnosis, 118 pathogenesis, 90 epidemiology, 118 prognosis, 91 etiology, 118 risk factors, 90 natural history, 118 treatment, 91 pathogenesis, 118 brachial plexopathy, 102 prognosis, 119 clinical features, 102 risk factors, 118 description, 102 treatment, 119 diagnosis, 102–103 axillary neuropathy, 2 differential diagnosis, 102 clinical features, 2 epidemiology, 102 description, 2 etiology, 102 diagnosis, 2 natural history, 102 differential diagnosis, 2 pathogenesis, 102 epidemiology, 2 prognosis, 103 etiology, 2 risk factors, 102 natural history, 2 treatment, 103 pathogenesis, 2 bulbar muscular atrophy, 132 prognosis, 3 clinical features, 132 risk factors, 2 description, 132 treatment, 3 diagnosis, 132–133 differential diagnosis, 132 Becker muscular dystrophy, 138 epidemiology, 132 clinical features, 138 etiology, 132 description, 138 natural history, 132 diagnosis, 138–139 pathogenesis, 132

191 192 Index bulbar muscular atrophy (cont.) pathogenesis, 60 prognosis, 133 prognosis, 61 risk factors, 132 risk factors, 60 treatment, 133 treatment, 61 cancer-related polyneuropathies, 56 dermatomyositis, 140 clinical features, 56 clinical features, 140 description, 56 description, 140 diagnosis, 56–57 diagnosis, 140–141 differential diagnosis, 56 differential diagnosis, 140 epidemiology, 56 epidemiology, 140 etiology, 56 etiology, 140 natural history, 56 natural history, 140 pathogenesis, 56 pathogenesis, 140 prognosis, 57 prognosis, 141 risk factors, 56 risk factors, 140 treatment, 57 treatment, 141 carpal tunnel syndrome, 19–20 DMD. See Duchenne muscular dystrophy chemical toxins and metals, polyneuropathy, 74 Duchenne muscular dystrophy (DMD), 142 clinical features, 74 clinical features, 142 description, 74 description, 142 diagnosis, 74–75 diagnosis, 142 differential diagnosis, 74 differential diagnosis, 142 epidemiology, 74 epidemiology, 142 etiology, 74 etiology, 142 natural history, 74 natural history, 142 pathogenesis, 74 pathogenesis, 142 prognosis, 75 prognosis, 143 risk factors, 74 risk factors, 142 treatment, 75 treatment, 143 chronic inflammatory demyelinating polyradiculoneuropathy, 58 dystonia, 174 clinical features, 58 clinical features, 174 description, 58 description, 174 diagnosis, 58–59 diagnosis, 174–175 differential diagnosis, 58 differential diagnosis, 174 epidemiology, 58 epidemiology, 174 etiology, 58 etiology, 174 natural history, 58 natural history, 174 pathogenesis, 58 pathogenesis, 174 prognosis, 59 prognosis, 175 risk factors, 58 risk factors, 174 treatment, 59 treatment, 175 Clostridium botulinum, 90 dystrophia myotonica (DM). See myotonic dystrophy congenital myasthenia gravis, 92 clinical features, 92 Emery-Dreifuss muscular dystrophy, 144 description, 92 clinical features, 144 diagnosis, 92–93 description, 144 differential diagnosis, 92 diagnosis, 144 epidemiology, 92 differential diagnosis, 144 etiology, 92 epidemiology, 144 natural history, 92 etiology, 144 pathogenesis, 92 natural history, 144 prognosis, 93 pathogenesis, 144 risk factors, 92 prognosis, 145 treatment, 93 risk factors, 144 critical illness polyneuropathy, 60 treatment, 144–145 clinical features, 60 essential tremor, 176 description, 60 clinical features, 176 diagnosis, 60–61 description, 176 differential diagnosis, 60 diagnosis, 176–177 epidemiology, 60 differential diagnosis, 176 etiology, 60 epidemiology, 176 natural history, 60 etiology, 176 Index 193

natural history, 176 clinical features, 62 pathogenesis, 176 description, 62 prognosis, 177 diagnosis, 62–63 risk factors, 176 differential diagnosis, 62 treatment, 177 epidemiology, 62 etiology, 62 facial neuropathy, 4 natural history, 62 clinical features, 4 pathogenesis, 62 description, 4 prognosis, 63 diagnosis, 4 risk factors, 62 differential diagnosis, 4 treatment, 63 epidemiology, 4 hereditary spastic paraplegia (HSP), 120 etiology, 4 clinical features, 120 natural history, 4 description, 120 pathogenesis, 4 diagnosis, 120 prognosis, 5 differential diagnosis, 120 risk factors, 4 epidemiology, 120 treatment, 4 etiology, 120 fascioscapulohumeral dystrophy, 146 natural history, 120 clinical features, 146 pathogenesis, 120 description, 146 prognosis, 121 diagnosis, 146 risk factors, 120 differential diagnosis, 146 treatment, 121 epidemiology, 146 HSP. See hereditary spastic paraplegia etiology, 146 Huntington’s disease (HD), 180 natural history, 146 clinical features, 180 pathogenesis, 146 description, 180 prognosis, 147 diagnosis, 180 risk factors, 146 differential diagnosis, 180 treatment, 146–147 epidemiology, 180 femoral neuropathy, 6 etiology, 180 clinical features, 6 natural history, 180 description, 6 pathogenesis, 180 diagnosis, 6 prognosis, 181 differential diagnosis, 6 risk factors, 180 epidemiology, 6 treatment, 181 etiology, 6 hyperkalemic periodic paralysis (HyperKPP), 148 natural history, 6 clinical features, 148 pathogenesis, 6 description, 148 prognosis, 7 diagnosis, 148 risk factors, 6 differential diagnosis, 148 treatment, 6–7 epidemiology, 148 Friedreich’s ataxia, 178 etiology, 148 clinical features, 178 natural history, 148 description, 178 pathogenesis, 148 diagnosis, 178–179 prognosis, 149 differential diagnosis, 178 risk factors, 148 epidemiology, 178 treatment, 148–149 etiology, 178 HyperKPP. See hyperkalemic periodic paralysis natural history, 178 hypokalemic periodic paralysis (HypoKPP), 150 pathogenesis, 178 clinical features, 150 prognosis, 179 description, 150 risk factors, 178 diagnosis, 150 treatment, 179 differential diagnosis, 150 epidemiology, 150 genitofemoral nerves, 8 etiology, 150 glycogen storage disease type II, 164–165 natural history, 150 glycogen storage disease type V, 154–155 pathogenesis, 150 Guillain-Barré syndrome, 52–53 prognosis, 151 Guyon’s canal. See ulnar neuropathy risk factors, 150 treatment, 150–151 HD. See Huntington’s disease HypoKPP. See hypokalemic periodic paralysis hereditary motor and sensory neuropathy, 62 (HypoKPP) 194 Index idiopathic polyneuropathy, 64 etiology, 21 clinical features, 64 natural history, 21 description, 64 pathogenesis, 21 diagnosis, 64–65 prognosis, 22 differential diagnosis, 64 risk factors, 21 epidemiology, 64 treatment, 22 etiology, 64 LEMS. See Lambert-Eaton myasthenic syndrome natural history, 64 leprosy, 72 pathogenesis, 64 clinical features, 72 prognosis, 65 description, 72 risk factors, 64 diagnosis, 72–73 treatment, 65 differential diagnosis, 72 iliohypogastric nerves, 8 epidemiology, 72 ilioinguinal nerves, 8 etiology, 72 inflammatory demyelinating polyradiculoneuropathy. See acute natural history, 72 ­inflammatory demyelinating ­polyradiculoneuropathy; pathogenesis, 72 ­chronic inflammatory demyelinatingp­ olyradiculoneuropathy prognosis, 73 inguinal neuropathies, 8 risk factors, 72 clinical features, 8 treatment, 73 description, 8 LGMD. See limb-girdle muscular dystrophies diagnosis, 8 limb-girdle muscular dystrophies (LGMD), 152 differential diagnosis, 8 clinical features, 152 epidemiology, 8 description, 152 etiology, 8 diagnosis, 152 natural history, 8 differential diagnosis, 152 pathogenesis, 8 epidemiology, 152 prognosis, 8 etiology, 152 risk factors, 8 natural history, 152 treatment, 8 pathogenesis, 152 intercostobrachial neuropathy, 9 prognosis, 153 clinical features, 9 risk factors, 152 description, 9 treatment, 152–153 diagnosis, 9 long thoracic neuropathy, 12 differential diagnosis, 9 clinical features, 12 epidemiology, 9 description, 12 etiology, 9 diagnosis, 12 natural history, 9 differential diagnosis, 12 pathogenesis, 9 epidemiology, 12 prognosis, 9 etiology, 12 risk factors, 9 natural history, 12 treatment, 9 pathogenesis, 12 prognosis, 12 Kennedy’s disease, 132–133 risk factors, 12 Kiloh-Nevin syndrome, 15–16 treatment, 12 lumbosacral plexopathy, 104 Lambert-Eaton myasthenic syndrome (LEMS), 94 clinical features, 104 clinical features, 94 description, 104 description, 94 diagnosis, 104–105 diagnosis, 94–95 differential diagnosis, 104 differential diagnosis, 94 epidemiology, 104 epidemiology, 94 etiology, 104 etiology, 94 natural history, 104 natural history, 94 pathogenesis, 104 pathogenesis, 94 prognosis, 105 prognosis, 95 risk factors, 104 risk factors, 94 treatment, 105 treatment, 95 Lyme disease, polyneuropathy in, 82 laryngeal neuropathy, 48–49 clinical features, 82 lateral antebrachial cutaneous neuropathy, 21 description, 82 clinical features, 21 diagnosis, 82–83 description, 21 differential diagnosis, 82 diagnosis, 21 epidemiology, 82 differential diagnosis, 21 etiology, 82 epidemiology, 21 natural history, 82 Index 195

pathogenesis, 82 risk factors, 19 prognosis, 83 treatment, 20 risk factors, 82 medication-induced polyneuropathy, 66 treatment, 83 clinical features, 66 description, 66 McArdle’s disease, 154 diagnosis, 66–67 clinical features, 154 differential diagnosis, 66 description, 154 epidemiology, 66 diagnosis, 154 etiology, 66 differential diagnosis, 154 natural history, 66 epidemiology, 154 pathogenesis, 66 etiology, 154 prognosis, 67 natural history, 154 risk factors, 66 pathogenesis, 154 treatment, 67 prognosis, 155 meralgia paresthetica, 10–11 risk factors, 154 MG. See myasthenia gravis treatment, 154–155 mononeuropathies medial antebrachial cutaneous neuropathy, 13 axillary neuropathy, 2–3 clinical features, 13 facial neuropathy (Bell’s palsy), 4–5 description, 13 femoral neuropathy, 6–7 diagnosis, 13 inguinal neuropathies, 8 differential diagnosis, 13 intercostobrachial neuropathy, 9 epidemiology, 13 lateral antebrachial cutaneous neuropathy, 21–22 etiology, 13 lateral femoral cutaneous neuropathy, 10–11 natural history, 13 long thoracic neuropathy, 12 pathogenesis, 13 medial antebrachial cutaneous neuropathy, 13–14 prognosis, 14 median neuropathy risk factors, 13 anterior interosseous neuropathy, 15–16 treatment, 13–14 in arm to mid-forearm, 17–18 median neuropathy at wrist, 19–20 anterior interosseous neuropathy, 15 musculocutaneous neuropathy, 21–22 clinical features, 15 obturator neuropathy, 23 description, 15 peroneal (fibular) neuropathy, 24–25 diagnosis, 15–16 phrenic neuropathy, 26 differential diagnosis, 15 pudendal neuropathy, 27 epidemiology, 15 radial neuropathy etiology, 15 in arm, 28–29 natural history, 15 posterior interosseous neuropathy, 30–31 pathogenesis, 15 superficial radial sensory neuropathy, 32 prognosis, 16 sciatic neuropathy, 33–34 risk factors, 15 spinal accessory neuropathy, 35 treatment, 16 suprascapular neuropathy, 36–37 in arm to mid-forearm, 17 tibial neuropathy clinical features, 17 in ankle and foot, 38–39 description, 17 from knee to ankle, 40–41 diagnosis, 17–18 trigeminal neuralgia and neuropathy, 42–43 differential diagnosis, 17 ulnar neuropathy epidemiology, 17 at elbow, 44–45 etiology, 17 at wrist, 46–47 natural history, 17 vagal (laryngeal) neuropathy, 48–49 pathogenesis, 17 motor neuron diseases prognosis, 18 amyotrophic lateral sclerosis, 118–119 risk factors, 17 bulbar muscular atrophy, 132–133 treatment, 18 hereditary spastic paraplegia, 120–121 at wrist, 19 poliomyelitis, 122–123 clinical features, 19 post-polio syndrome, 124–125 description, 19 primary lateral sclerosis, 126–127 diagnosis, 19–20 progressive bulbar palsy, 128–129 differential diagnosis, 19 progressive muscular atrophy, 130–131 epidemiology, 19 spinal muscular atrophy, 132–135 etiology, 19 movement disorders natural history, 19 blepharospasm, 172–173 pathogenesis, 19 dystonia, 174–175 prognosis, 20 essential tremor, 176–177 196 Index movement disorders (cont.) diagnosis, 158–159 Friedreich’s ataxia, 178–179 differential diagnosis, 158 Huntington’s disease, 180–181 epidemiology, 158 Parkinson’s disease, 182–183 etiology, 158 torticollis, 184–185 natural history, 158 Tourette’s syndrome, 186–187 pathogenesis, 158 writer’s cramp, 188–189 prognosis, 159 multifocal motor neuropathy, 68 risk factors, 158 clinical features, 68 treatment, 159 description, 68 neuralgic amyotrophy, 106 diagnosis, 68–69 clinical features, 106 differential diagnosis, 68 description, 106 epidemiology, 68 diagnosis, 107 etiology, 68 differential diagnosis, 107 natural history, 68 epidemiology, 106 pathogenesis, 68 etiology, 106 prognosis, 69 natural history, 107 risk factors, 68 pathogenesis, 106 treatment, 69 prognosis, 108 muscle diseases risk factors, 106 Becker muscular dystrophy, 138–139 treatment, 107–108 dermatomyositis, 140–141 neuromuscular junction Duchenne muscular dystrophy, 142–143 botulism, 90–91 Emery-Dreifuss muscular dystrophy, 144–145 congenital myasthenia gravis, 92–93 fascioscapulohumeral dystrophy, 146–147 Lambert-Eaton myasthenic syndrome, 94–95 hyperkalemic periodic paralysis, 148–149 myasthenia gravis, 96–97 hypokalemic periodic paralysis, 150–151 organophosphate poisoning, 98–99 limb-girdle muscular dystrophies, 152–153 neuropathy due to Herpes Zoster, 70 McArdle’s disease, 154–155 clinical features, 70 myotonia congenita, 156–157 description, 70 myotonic dystrophy, 158–160 diagnosis, 70–71 paramyotonia congenita, 161 differential diagnosis, 70 polymyositis, 162–163 epidemiology, 70 Pompe disease, 164–165 etiology, 70 rhabdomyolysis, 166–167 natural history, 70 Schwartz-Jampel syndrome, 168–169 pathogenesis, 70 musculocutaneous. See lateral antebrachial cutaneous neuropathy prognosis, 71 myasthenia gravis (MG), 96 risk factors, 70 clinical features, 96 treatment, 71 description, 96 nutritional deficiency, polyneuropathy, 76 diagnosis, 96–97 clinical features, 76 differential diagnosis, 96 description, 76 epidemiology, 96 diagnosis, 76 etiology, 96 differential diagnosis, 76 natural history, 96 epidemiology, 76 pathogenesis, 96 etiology, 76 prognosis, 97 natural history, 76 risk factors, 96 pathogenesis, 76 treatment, 97 prognosis, 77 myotonia congenita, 156 risk factors, 76 clinical features, 156 treatment, 77 description, 156 diagnosis, 156 obturator neuropathy, 23 differential diagnosis, 156 clinical features, 23 epidemiology, 156 description, 23 etiology, 156 diagnosis, 23 natural history, 156 differential diagnosis, 23 pathogenesis, 156 epidemiology, 23 prognosis, 157 etiology, 23 risk factors, 156 natural history, 23 treatment, 156–157 pathogenesis, 23 myotonic dystrophy, 158 prognosis, 23 clinical features, 158 risk factors, 23 description, 158 treatment, 23 Index 197 organophosphate poisoning, 98 PLS. See primary lateral sclerosis clinical features, 98 poliomyelitis, 122 description, 98 clinical features, 122 diagnosis, 98 description, 122 differential diagnosis, 98 diagnosis, 122 epidemiology, 98 differential diagnosis, 122 etiology, 98 epidemiology, 122 natural history, 98 etiology, 122 pathogenesis, 98 natural history, 122 prognosis, 99 pathogenesis, 122 risk factors, 98 prognosis, 123 treatment, 98–99 risk factors, 122 treatment, 123 paramyotonia congenita, 161 polymyositis, 162 clinical features, 161 clinical features, 162 description, 161 description, 162 diagnosis, 161 diagnosis, 162 differential diagnosis, 161 differential diagnosis, 162 epidemiology, 161 epidemiology, 162 etiology, 161 etiology, 162 natural history, 161 natural history, 162 pathogenesis, 161 pathogenesis, 162 prognosis, 161 prognosis, 163 risk factors, 161 risk factors, 162 treatment, 161 treatment, 162–163 Parkinson’s disease (PD), 182 polyneuropathies clinical features, 182 acute inflammatory demyelinating polyradiculoneuropathy, 52–53 description, 182 amyloid neuropathies, 54–55 diagnosis, 182 cancer-related polyneuropathies, 56–57 differential diagnosis, 182 Charcot-Marie-tooth disease, 62–63 epidemiology, 182 chronic inflammatory demyelinating polyradiculoneuropathy, etiology, 182 58–59 natural history, 182 critical illness polyneuropathy, 60–61 pathogenesis, 182 in diabetes mellitus, 80–81 prognosis, 183 due to chemical toxins and metals, 74–75 risk factors, 182 due to HIV infection, 84–85 treatment, 182–183 due to nutritional deficiency, 76–77 Parsonage-Turner syndrome (PTS), 106–108 due to vasculitis, 78–79 PD. See Parkinson’s disease hereditary motor and sensory neuropathy, 62–63 peroneal (fibular) neuropathy, 24 idiopathic polyneuropathy, 64–65 clinical features, 24 in Lyme disease, 82–83 description, 24 medication-induced polyneuropathy, 66–67 diagnosis, 24–25 multifocal motor neuropathy, 68–69 differential diagnosis, 24 neuropathy epidemiology, 24 due to Herpes Zoster (shingles), 70–71 etiology, 24 due to leprosy, 72–73 natural history, 24 porphyric neuropathy, 86–87 pathogenesis, 24 sensory neuropathy, 62–63 prognosis, 25 polyneuropathy, in diabetes mellitus, 80 risk factors, 24 clinical features, 80 treatment, 25 description, 80 phrenic neuropathy, 26 diagnosis, 80–81 clinical features, 26 differential diagnosis, 80 description, 26 epidemiology, 80 diagnosis, 26 etiology, 80 differential diagnosis, 26 natural history, 80 epidemiology, 26 pathogenesis, 80 etiology, 26 prognosis, 81 natural history, 26 risk factors, 80 pathogenesis, 26 treatment, 81 prognosis, 26 polyneuropathy related to HIV infection, 84 risk factors, 26 clinical features, 84 treatment, 26 description, 84 plexopathies. See radiculopathies/plexopathies diagnosis, 84–85 198 Index polyneuropathy related to HIV infection (cont.) epidemiology, 128 differential diagnosis, 84 etiology, 128 epidemiology, 84 natural history, 128 etiology, 84 pathogenesis, 128 natural history, 84 prognosis, 129 pathogenesis, 84 risk factors, 128 prognosis, 85 treatment, 128–129 risk factors, 84 progressive muscular atrophy, 130 treatment, 85 clinical features, 130 Pompe disease, 164 description, 130 clinical features, 164 diagnosis, 130 description, 164 differential diagnosis, 130 diagnosis, 164–165 epidemiology, 130 differential diagnosis, 164 etiology, 130 epidemiology, 164 natural history, 130 etiology, 164 pathogenesis, 130 natural history, 164 prognosis, 131 pathogenesis, 164 risk factors, 130 prognosis, 165 treatment, 130–131 risk factors, 164 PTS. See Parsonage-Turner syndrome treatment, 165 pudendal neuropathy, 27 porphyric neuropathy, 86 clinical features, 27 clinical features, 86 description, 27 description, 86 diagnosis, 27 diagnosis, 86–87 differential diagnosis, 27 differential diagnosis, 86 epidemiology, 27 epidemiology, 86 etiology, 27 etiology, 86 natural history, 27 natural history, 86 pathogenesis, 27 pathogenesis, 86 prognosis, 27 prognosis, 87 risk factors, 27 risk factors, 86 treatment, 27 treatment, 87 post-polio syndrome (PPS), 124 radial neuropathy clinical features, 124 in arm, 28 description, 124 clinical features, 28 diagnosis, 124 description, 28 differential diagnosis, 124 diagnosis, 28 epidemiology, 124 differential diagnosis, 28 etiology, 124 epidemiology, 28 natural history, 124 etiology, 28 pathogenesis, 124 natural history, 28 prognosis, 125 pathogenesis, 28 risk factors, 124 prognosis, 29 treatment, 125 risk factors, 28 PPS. See post-polio syndrome treatment, 29 primary lateral sclerosis (PLS), 126 posterior interosseous neuropathy, 30 clinical features, 126 clinical features, 30 description, 126 description, 30 diagnosis, 126 diagnosis, 30–31 differential diagnosis, 126 differential diagnosis, 30–31 epidemiology, 126 epidemiology, 30 etiology, 126 etiology, 30 natural history, 126 natural history, 30 pathogenesis, 126 pathogenesis, 30 prognosis, 127 prognosis, 31 risk factors, 126 risk factors, 30 treatment, 126–127 treatment, 31 primary spinocerebellar degeneration, 178–179 superficial radial sensory neuropathy, 32 progressive bulbar palsy, 128 clinical features, 32 clinical features, 128 description, 32 description, 128 diagnosis, 32 diagnosis, 128 differential diagnosis, 32 differential diagnosis, 128 epidemiology, 32 Index 199

etiology, 32 SJS. See Schwartz-Jampel syndrome natural history, 32 SMA. See spinal muscular atrophy pathogenesis, 32 spinal accessory neuropathy, 35 prognosis, 32 clinical features, 35 risk factors, 32 description, 35 treatment, 32 diagnosis, 35 radiculopathies/plexopathies differential diagnosis, 35 brachial plexopathy, 102–103 epidemiology, 35 lumbosacral plexopathy, 104–105 etiology, 35 neuralgic amyotrophy, 106–108 natural history, 35 thoracic outlet syndrome pathogenesis, 35 neurogenic, 112–113 prognosis, 35 vascular, 114–115 risk factors, 35 radiculopathy, 109 treatment, 35 clinical features, 109 spinal muscular atrophy (SMA). See also bulbar muscular atrophy, 134 description, 109 clinical features, 134 diagnosis, 109–110 description, 134 differential diagnosis, 109 diagnosis, 134–135 epidemiology, 109 differential diagnosis, 134 etiology, 109 epidemiology, 134 natural history, 109 etiology, 134 pathogenesis, 109 natural history, 134 prognosis, 111 pathogenesis, 134 risk factors, 109 prognosis, 135 treatment, 110 risk factors, 134 rhabdomyolysis, 166 treatment, 135 clinical features, 166 suprascapular neuropathy, 36 description, 166 clinical features, 36 diagnosis, 166–167 description, 36 differential diagnosis, 166 diagnosis, 36 epidemiology, 166 differential diagnosis, 36 etiology, 166 epidemiology, 36 natural history, 166 etiology, 36 pathogenesis, 166 natural history, 36 prognosis, 167 pathogenesis, 36 risk factors, 166 prognosis, 37 treatment, 167 risk factors, 36 treatment, 36–37 Schwartz-Jampel syndrome (SJS), 168 clinical features, 168 thoracic outlet syndrome (TOS) description, 168 neurogenic, 112 diagnosis, 168 clinical features, 112 differential diagnosis, 168 description, 112 epidemiology, 168 diagnosis, 112 etiology, 168 differential diagnosis, 112 natural history, 168 epidemiology, 112 pathogenesis, 168 etiology, 112 prognosis, 169 natural history, 112 risk factors, 168 pathogenesis, 112 treatment, 168–169 prognosis, 113 sciatic neuropathy, 33 risk factors, 112 clinical features, 33 treatment, 112–113 description, 33 vascular, 114 diagnosis, 33–34 clinical features, 114 differential diagnosis, 33 description, 114 epidemiology, 33 diagnosis, 114 etiology, 33 differential diagnosis, 114 natural history, 33 epidemiology, 114 pathogenesis, 33 etiology, 114 prognosis, 34 natural history, 114 risk factors, 33 pathogenesis, 114 treatment, 34 prognosis, 115 sensory-motor polyneuropathy, 64 risk factors, 114 sensory neuropathy, 62–63 treatment, 114–115 200 Index tibial neuropathy ulnar neuropathy in ankle and foot, 38 at elbow, 44 clinical features, 38 clinical features, 44 description, 38 description, 44 diagnosis, 38–39 diagnosis, 44–45 differential diagnosis, 38 differential diagnosis, 44 epidemiology, 38 epidemiology, 44 etiology, 38 etiology, 44 natural history, 38 natural history, 44 pathogenesis, 38 pathogenesis, 44 prognosis, 39 prognosis, 45 risk factors, 38 risk factors, 45 treatment, 39 treatment, 45 from knee to ankle, 40 at wrist, 46 clinical features, 40 clinical features, 46 description, 40 description, 46 diagnosis, 40 diagnosis, 46–47 differential diagnosis, 40 differential diagnosis, 46 epidemiology, 40 epidemiology, 46 etiology, 40 etiology, 46 natural history, 40 natural history, 46 pathogenesis, 40 pathogenesis, 46 prognosis, 41 prognosis, 47 risk factors, 40 risk factors, 46 treatment, 40 treatment, 47 tic douloureux. See trigeminal neuralgia torticollis, 184 vagal (laryngeal) neuropathy, 48 clinical features, 184 clinical features, 48 description, 184 description, 48 diagnosis, 184 diagnosis, 48–49 differential diagnosis, 184 differential diagnosis, 48 epidemiology, 184 epidemiology, 48 etiology, 184 etiology, 48 natural history, 184 natural history, 48 pathogenesis, 184 pathogenesis, 48 prognosis, 185 prognosis, 49 risk factors, 184 risk factors, 48 treatment, 184–185 treatment, 49 TOS. See thoracic outlet syndrome vasculitis, polyneuropathy, 78 Tourette’s syndrome, 186 clinical features, 78 clinical features, 186 description, 78 description, 186 diagnosis, 78–79 diagnosis, 186–187 differential diagnosis, 78 differential diagnosis, 186 epidemiology, 78 epidemiology, 186 etiology, 78 etiology, 186 natural history, 78 natural history, 186 pathogenesis, 78 pathogenesis, 186 prognosis, 79 prognosis, 187 risk factors, 78 risk factors, 186 treatment, 79 treatment, 187 trigeminal neuralgia and neuropathy, 42 clinical features, 42 writer’s cramp, 188 description, 42 clinical features, 188 diagnosis, 42–43 description, 188 differential diagnosis, 42 diagnosis, 188 epidemiology, 42 differential diagnosis, 188 etiology, 42 epidemiology, 188 natural history, 42 etiology, 188 pathogenesis, 42 natural history, 188 prognosis, 43 pathogenesis, 188 risk factors, 42 prognosis, 189 treatment, 43 risk factors, 188 trigeminal neuropathy. See trigeminal neuralgia and neuropathy treatment, 189