Frontispiece: Electron micrograph, x 48000. Longitudinal section of normal muscle. The sarcomeres, with Z bands arranged in series, and M, H and I bands, are clearly seen in this contracted muscle. Glycogen granules are prominent. The mitochondria and T-tube triads are placed near the Z bands, and a few small clear lipid droplets are present.

Michael Swash . Martin S. Schwartz

Neuromuscular Diseases A Practical Approach to Diagnosis and Management

Second Edition

With 202 Figures

Springer-Verlag Berlin Heidelberg GmbH

Michael Swash MD (London), FRCP (London), MRCPath Consultant Neurologist, The London Hospital, London El and St Mark's Hospital, LondonECI Senior Lecturer in Neuropathology, The London Hospital Medical College, London E 1, UK

Martin Schwartz MD (Maryland) Consultant Clinical Neurophysiologist, Atkinson Morley's Hospital (St Georges's Hospital), London SW20, UK

ISBN 978-1-4471-3528-9

British Library Cataloguing in Publication Data Swash, Michael, 1939-

Neuromuscular diseases: a practical approach to diagnosis and management. 1. Man. Muscles. Nerves. Diseases 1. Title II. Schwartz, Martin S. (Martin Samuel), 1941-616.7'4 ISBN 978-1-4471-3528-9 ISBN 978-1-4471-3526-5 (eBook) DOI 10.1007/978-1-4471-3526-5

Library of Congress Cataloging-in-Publication Data Swash, Michael. Neuromuscular diseases. Bibliography: p. Includes index. 1. Neuromuscular diseases. 1. Schwartz, Martin S. (Martin Samuel), 1941-Diseases-diagnosis. 2. Neuromuscular Diseases-therapy. WE 550 S973nj 616.7'4 87-32185 ISBN 978-1-4471-3528-9

. II. Title [DNLM: 1. Neuromuscular RC925.s951988

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© Springer-Verlag Berlin Heidelberg 1981,1988 Originally published by Springer-Verlag Berlin Heidelberg New York in 1988 Softcoverreprint of the hardcover 2nd edition 1988

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Product liability: The publisher can give no guarantee for information about drug dosage and application thereof contained in this book. In every individual case the respective user must check its accuracy by consulting other pharma­ceuticalliterature.

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To Caroline,for countless encouragements, conversations and splendid dinners

Preface to the Second Edition

In the seven years since the first edition of this book was published there have been many important developments in knowledge of neuromuscular diseases. These are reflected in this new edition. We have taken the opportunity to add much new clinical and scientific material to the book, particularly in relation to metabolic myopathies and neuropathies, and to include more information on genetic aspects of neuromuscular diseases, quantitative electromyo­graphic techniques, plexus and root lesions and cardiomyopathies. The aim of the book remains unchanged, but we have rearranged some of the material so that there are several new chapters. The illustrations have also been extensively revised and there are many new references. We hope that it will continue to provide a convenient source of practical and theoretical information that will not only be useful in managing patients with neuromuscular diseases, but will stimulate research.

London, May 1987 Michael Swash Martin S. Schwartz

Preface to the First Edition

Neuromuscular diseases are common in clinical practice. Patients with these disorders may be referred to neurologists, rheumatologists, orthopaedic surgeons, paediatricians or to general physicians, and their investigation, utilising electromyography (EM G) and muscle biopsy, often requires the help of the clinical neurophysiologist and of the pathologist. Investigation must be co-ordinated and interpreted in relation to the clinical findings, but it is rare for the clinical neurophysiologist, pathologist and referring physician to confer together in considering diagnosis and management - an attitude which reflects an underlying fragmentation of opinion and of research. This is evident, also, in most textbooks dealing with neuromuscular disorders, which conventionally emphasise either physiological, pathological or clinical aspects of these diseases. As a result of this restricted approach EMG and pathological investigation are often only used to establish a diagnosis, and their potential value in assessing the functional and structural disturbance in affected muscles remains unrealised. Neuromuscular disorders affect different muscles, or groups of muscles, in varying degrees, and they may progress at different rates in individual patients. Since electrophysiological investigations can be repeated with com­paratively little discomfort during the course of a neuromuscular disorder and its treatment, EMG and nerve conduction studies are particularly useful in assessing the distribution and rate of progress of any given disorder. Pathological studies, particularly nerve and muscle biopsy, can be repeated less frequently, although the advent of needle muscle biopsy may enable this investigation, like EMG, to be repeated in the quadriceps and perhaps in the biceps.

Electromyographic and pathological studies can therefore be used not only to indicate the diagnosis itself, but also to assess the overall distribution of the disease process, the effectiveness of compensatory processes and, therefore, the prognosis. Further, in some disorders, for example in polymyositis, myasthenia gravis and certain polyneuropathies, they may be used to assess the effectiveness of treatment. However, they cannot be used as a substitute for careful clinical evaluation.

It is the purpose of this book to describe and correlate the clinical, electromyographic, patho­logical and, when relevant, the biochemical features of neuromuscular disorders. Particular attention is paid to variations in these features during phases of progression or improvement. The effects of treatment, and of the various compensatory factors, such as reinnervation by axonal sprouting, muscle fibre regeneration, and myopathic changes in chronic neurogenic disorders, are described since these produce important and clearly recognisable changes in the course of these disorders. The role of EMG and pathological studies in this approach is emphasised since if investigation of patients with neuromuscular problems is planned as a logical progression, management becomes more effective.

Both of us have a particular interest in neuromuscular disorders. In addition to experience in clinical neurology one of us (M.S.) has a special interest in muscle and nerve pathology

x Preface

and the other (M.S.S.) in clinical neurophysiology. In our clinical practice and research we have approached neuromuscular problems jointly so that it has been possible for us to compare the EMG and pathological data. This approach is used in this book to show how the problems of individual patients can be assessed clinically, physiologically and pathologically. This com­bined approach can provide an overall understanding of the mechanisms of damage and repair of tissues in neuromuscular disorders.

London, June 1981 Michael Swash Martin S. Schwartz

Acknowledgements

We wish to thank the many people who have helped us in preparing this book. The histological preparations were made by Mrs Kathleen Fox, Mrs Margaret Sergeant and Mrs Elaine Cox at the Institute of Pathology, The London Hospital, and by Mr Peter Dalton at the Department of Pathology, St George's Hospital. The illustrations were prepared by Mr Ivor Northey and his colleagues in the Photographic Department at the Institute of Pathology, The London Hospital Medical College. The manuscript was faultlessly typed by Mrs Adrienne Raine.

The histological and electrophysiological investigations which have led to the production of this book were supported, in part, by grants from The Wellcome Trust, The Medical Research Council, The London Hospital Research Fund, St Mark's Research Foundation, The Motor Neurone Disease Association and The Amyotrophic Lateral Sclerosis Association (USA). A number of the illustrations are taken from our previous publications in Brain, Journal of Neurological Sciences, Journal of Neurology, Neurosurgery and Psychiatry, Journal of Anatomy, Gut, Neuropathology and Applied Neurobiology, Annals of Neurology, Muscle and Nerve, Clinical Neuropathology, and in Muscle Biopsy Pathology (published by Chapman and Hall, London 1984).

Finally, we thank our publisher, Michael Jackson, and the staff at Springer-Verlag in Wimbledon for their help during the preparation of this book.

Contents

Section 1 Principles ofInvestigation and Management

Chapter 1 Clinical Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3

General Aspects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Clinical Findings. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4

Weakness.............................................................. 4 Quantitative Assessment of Strength .................................... 6

Wasting and Hypertrophy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Fatiguability. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Tone and Reflexes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Pain and Cramps ................. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 Fasciculation, Myotonia, Myokymia and Myoedema. . . . . . . . . . . . . . . . . . . . . . . . . . 9 Sensory Disturbances in Neuromuscular Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 Examination of Peripheral Nerves. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 Involvement of Other Systems ............................................. 10 Family History. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

The Approach to Investigation ................................................ 10 Biochemical Tests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11

Blood Creatine Kinase Levels. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11 Creatine Kinase Levels in Neuromuscular Diseases ........................ 12

Other Serum Enzyme Tests. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 Other Biochemical Tests on Blood. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 Urinary Protein Excretion Tests. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13

Imaging. . . . . . . . . . . . .. . . . ... . . . . . .... . . . . . . . .. . . . . . . . . . . . .. . . . . . . . ... .. . . . . 13 Nuclear Magnetic Resonance Spectroscopy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13 Ultrasound Imaging of Muscle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 CT X-ray Scanning of Muscle . . . . . ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 Radionuclide Scanning of Muscle .......................................... 14

Chapter 2 Electromyography, Nerve Conduction and Other Neurophysiological Techniques. . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

Electromyographic Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15

xiv Contents

Recording Electrodes ..................................................... . . . 15 Surface Electrodes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 Concentric Needle Electrodes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 Monopolar Electrodes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 Single-Fibre EMG Electrodes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16 Macro EM G Electrodes .................................................. 16 Wire Electrodes ......................................................... 17 Sterilisation ofEMG Electrodes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 Signal Amplification ................................................. . . . . 17

Concentric Needle Electromyography .......................................... 18 Clinical Technique. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 EMG Activity in Relaxed Muscle. . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18

Insertional Activity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 End-plate Noise. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 End-plate Spikes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 18 Fibrillation Potentials. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 Fasciculation Potentials. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 Positive Sharp Waves. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 Complex Repetitive Discharges. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 Myokymia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 Neuromyotonia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 Myotonia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21

Motor Unit Potential Analysis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 Double Discharges . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . 25

Quantitative Concentric Needle EMG Studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 Manual Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 Automatic Analysis of Motor Unit Potentials. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 Automatic Analysis of the Interference Pattern. . . . . . . . . . . . . . . . . . . . . . . . . . . . 26 Motor Unit Counts. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26

Single-Fibre EMG. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 Surface EMG. . .. . . .. . . . . . . ... . .. . . . ... .. .. ... .. . .. ... . . . . . . . . . . . . . . . . . . . . . . 28 Macro EMG ............................................................... 28 Scanning EM G .................................................... . . . . . . . . . 28 Multielectrode Studies ....................................................... 29 Repetitive Stimulation ....................................................... 29 Nerve Conduction Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29

General Principles of Nerve Conduction Velocity Studies. . . . . . . . . . . . . . . . . . . . . . . 30 Motor Conduction Velocity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 Sensory Conduction Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 Nerve Action Potential Recording . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 H Reflex Studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 The F Response .................................... . . . . . . . . . . . . . . . . . . . . . 32 Motor Nerve Conduction Velocity Distribution. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 Motor and Sensory Nerve Refractory Period Studies. . . . . . . . . . . . . . . . . . . . . . . . . . . 34 Blink Reflex ............................................................ 34 Somatosensory Evoked Responses. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 Stimulation of Central Motor Pathways . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35

Chapter 3 Muscle and Nerve Biopsies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37

Muscle Biopsy. . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 Preparation of the Biopsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38

Contents xv

Histological Methods. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39 Structure of Skeletal Muscle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40

Muscle Fibres. . .. . .. . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . 40 Fibre Types and Motor Units .......................................... 42 Distribution of Muscle Fibres. .. . . . . . . . . . . .. . . . . . . . . . . . . . . . . .. .. . . . . . . . 42 Effects of Training and Exercise ........................................ 43 Effects of Age. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44 Muscle Spindles. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44

Indications for Muscle Biopsy .......................................... -'. . .'.-.' _45 Muscle Biopsy Pathology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45

Statistical Methods ...................................................... 46 Fibre-Type Predominance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 Fibre Size . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 46 Fibre-Type Atrophy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 Fibre Hypertrophy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 47 Fibre-Type Grouping . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 48 Central Nucleation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49

Histological Features. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 Degenerative Changes ................................................ 49 Regenerative Changes ................................................ 54

Muscle Spindles. .. . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . .. . . . . . . . 55 Terminal Motor Innervation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56 Motor End-Plates. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56 Blood Vessels ........................................................... 56

The Normal Nerve...... ....... .............. .... .. . ....... ............... .. 56 Nerve Biopsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60

Indications for Nerve Biopsy .............................................. 60 Identification of Neuropathies by Nerve Biopsy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60

Chapter 4 Pathophysiological Correlations and Compensatory Mechanisms . . . . . . . . . . . . 63

Pathophysiological Correlations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 Acute Neurogenic Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63 Chronic Neurogenic Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64 Rapidly and Slowly Progressive Neurogenic Disorders . . . . . . . . . . . . . . . . . . . . . . . . . 65 Axonal and Demyelinating Neuropathies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 Myopathic Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 67 End-Plate Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . 69

Compensatory Mechanisms. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 70 Fibre Splitting in Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71 Electromyographic Evidence .............................................. 74 Implications of Fibre Splitting. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75

Splitting and Fibre-Type Grouping. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 75 Splitting as a Compensatory Process. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 76 Relation of Fibre Splitting to "Myopathic" Changes in Denervated Muscle. . . . 76

Section 2 Classification

Chapter 5 Classification of Neuromuscular Disorders 81

Neurogenic Disorders. . . . . . . . . . . . . . . . .. . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . .. . . . . . . 81 Myopathic Disorders ........................................................ 82

xvi Contents

Section 3 Neurogenic Disorders

Chapter 6 Diseases of Anterior Horn Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 85

The Spinal Muscular Atrophies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85 Clinical Presentation of Types Ito IV SMA .................................. 87

Type I SMA (Werdnig-Hoffman Disease) ................................ 87 Type II SMA (Intermediate Type). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88 Type III SMA (Kuge1berg-Welander Disease). . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89 Type IV SMA (Adult-onset Type). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90 Other Types of SMA. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90

Clinical Investigation of Spinal Muscular Atrophies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92 Electrophysiological Investigation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92 Pathology .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 93 Management and Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 97 Genetics and Genetic Counselling ......................................... , 97

Motor Neuron Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 98 Epidemiology ................................ : . . . . . . . . . . . . . . . . . . . . . . . . .. 99 Clinical Features ......................... :.............................. 99 Familial Motor Neuron Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 101 Differential Diagnosis ................................................... , 101 Aetiology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 101 Laboratory Investigations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 102 Electrophysiological Assessment ........................................... 103 Muscle Biopsy .......................................................... 106 Other Pathological Aspects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 107 Management and Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 108

Other Anterior Horn Cell Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 109 Degenerative Conditions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 109 Syringomelia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 109 Viral and Transmissible Conditions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 110

Muscle Biopsy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 111 Herpes Zoster . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 111 Creutzfe1dt-Jakob disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 111 Intoxications. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 112 Post-irradiation Syndromes ............................................... 112

Chapter 7 A Clinical Approach to the Neuropathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 113

Clinical Features of Neuropathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 114 Clinical Evaluation ...................................................... 114 Progression. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 115

Pathological Correlation in Peripheral Neuropathies ............................. , 116 Axonal Transection ..................................................... , 116 Neuronopathy .......................................................... 116 Distal Axonopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 117 Myelinopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 117 Clinico-Pathological Correlations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 117 Electrophysiological Correlations .......................................... 118

Positive and Negative Symptoms in Neuropathies ................................ , 119 Sensory Symptoms ...................................................... , 120

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Motor Symptoms ........................................................ 120 ClinicalInvestigation of Polyneuropathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 121

Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 121 Nerve Biopsy ........................................................... 122 Outcome ofInvestigation of Polyneuropathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 122

Principles of Management of Polyneuropathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 122

Chapter 8 Nerve Entrapment and Compression Syndromes, and Other Mononeuropathies. 125

Injuries to Nerves ........................................................... 125 Entrapment Neuropathies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 126

Pathogenesis ........................................................ 126 General Principles of Electrophysiological Assessment ..................... 128

Compression Neuropathies. . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . .. 129 Pathophysiology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 130 Clinical Implications .............. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 130 Electrophysiological Assessment .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 130

Upper Limb Syndromes ...................................................... 131 Median Nerve Syndromes ................................................. 131

Carpal Tunnel Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 131 Anterior Interosseous Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 135 Other Median Nerve Syndromes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 136

Ulnar Nerve .. ". .. . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 136 Ulnar Nerve Lesion at the Elbow ....................................... 136 Ulnar Nerve Lesions at Wrist and Hand ................................. 138

Radial Nerve ............................................................ 138 Compression Injuries in the Upper Arm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 138 Posterior Interosseous Nerve Lesions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 139 Superficial Branch of the Radial Nerve. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 139

Musculocutaneous Nerve. . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 140 Notalgia Paraesthetica. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 140 Rectus Abdominis Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 140

Lower Limb Syndromes ...................................................... 140 Nerves ofthe Pelvic Girdle. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 140

Electrophysiological Assessment and Management ........................ 140 Sciatic Nerve Syndromes. . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 142

Sciatic Neuropathies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 142 Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 142

Common Peroneal Syndromes ............................................. 142 Electrophysiological Assessment and Management ........................ 143

Tibial Nerve Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 143 Electrophysiological Assessment and Management ........................ 144

Tarsal Tunnel Syndrome. . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . .. 144 Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 144 Management ........................................................ 144

Morton's Metatarsalgia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 145 Electrophysiological Assessment and Management ........................ 145

Double-Crush Syndrome ..................................................... 145 Adequate Electrophysiological Studies in Entrapment Neuropathies. . . . . . . . . . . . . . . .. 145 Other Mononeuropathies. . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 146

Bell's Palsy ............................................................. 146 Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 146

xviii Contents

Pathology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 147 Management. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 147

Hemifacial Spasm. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 148 Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 148 Management .......... , ............................................. 148

Other Cranial Nerve Syndromes .............................................. , 148 Mononeuritis Multiplex and Multiple Mononeuropathies ......................... , 148

Chapter 9 Brachial and Lumbar Nerve Root and Plexus Lesions. . . . . . . . . . . . . . . . . . . . .. 151

Brachial Root Lesions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 151 Clinical Features ........................................................ 152 Electromyography in Root Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 152 Other Electrophysiological Tests ...................... . . . . . . . . . . . . . . . . . . . .. 153 Radiological Investigations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 154

Brachial Plexus Lesions ...................................................... 154 Clinical Features ........................................................ 154 Electrophysiological Studies in Brachial Plexus Lesions ........................ 155

Thoracic Outlet Syndromes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . .. 156 New Electrophysiological Methods for the Diagnosis of Brachial Root and Plexus

Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 157 Treatment of Brachial Plexus Lesions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 157

Lumbo-Sacral Root and Plexus Lesions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 157 Lumbo-Sacral Canal Stenosis ............................................. , 158

Investigation ....................................................... , 158 Management.. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 159

Cauda Equina Lesions. . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 159 Conus Medullaris Lesions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 159 Lumbo-Sacral Disc Prolapse. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 159

Investigation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 160 Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 160 Management ........................................................ 160

Lumbo-Sacral Plexus Lesions. ............................................. 160 Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 161 Management. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 161

Chapter 10 Genetically Determined Neuropathies ............ . . . . . . . . . . . . . . . . . . . .. 163

The Syndrome of Peroneal Muscular Atrophy. .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 164 Hereditary Motor and Sensory Neuropathies of Unknown Cause. . . . . . . . . . . . . . . . . . .. 164

HMSN Type I (Hypertrophic Form of Peroneal Muscular Atrophy). . . . . . . . . . . . .. 165 Investigations ....................................................... 166 Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 166 Muscle Biopsy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 167 Peripheral Nerve Biopsy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 167 Other Pathological Features ........................................... 168 Prognosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 168

HMSN Type II (Neuronal Type of Peroneal Muscular Atrophy). . . . . . . . . . . . . . . .. 168 Investigations ....................................................... 168 Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 168 Muscle Biopsy. . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 169

Contents xix

Nerve Biopsy. . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 169 Prognosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 169

Management of Charcot-Mar ie-Tooth Syndrome (HMSN Types I and II) . . . . . . .. 169 Diagnosis of HMSN Types I and II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 170 Type III (Hypertrophic Neuropathy of Infancy: Dejerine-Sottas Disease) . . . . . . . .. 170

Investigations ....................................................... 170 Nerve Biopsy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 170 Course ............................................................. 170

Other FormsofHMSN ................................................... 171 Hereditary Sensory and Autonomic Neuropathies (HSAN) . . . . . . . . . . . . . . . . . . . . . . . .. 171

Type I HSAN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 171 Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 172 Pathology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 172

Type II HSAN .......................................................... 172 Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 173 Pathology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 173

Type III HSAN, Riley-Day Syndrome (Familial Dysautonomia) . . . . . . . . . . . . . . .. 173 Laboratory Assessment .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 173 Pathology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 173

Type IV HSAN . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 174 Type V HSAN .......................................................... 174 Congenital Universal Insensitivity to Pain. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 174 Management of HSAN Syndromes ......................................... 174

Treatment and Management of HSAN Type III (Riley-Day Syndrome) ....... 175 Neuropathy in Hereditary Spino-Cerebellar Ataxia. . . . . . . . . . . . . . . . . . . . . . . . . . .. 175 Friedreich's Ataxia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 175

Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 175 Pathology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 176 Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 176

Other Neuropathies Associated with Genetic Diseases. . . . . . . . . . . . . . . . . . . . . . . . . . . .. 176 Giant Axonal Neuropathy ................................................ 176 Chediak-Higashi Disease .................................. . . . . . . . . . . . . . .. 176 Chorea-Acanthocytosis Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 176 Hereditary Liability to Pressure Palsies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 176

Laboratory Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 177 Hereditary Brachial Plexus Palsies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 177

Treatment and Prognosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 177 Migrant Sensory Neuritis of Wart en berg . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 177

Hereditary Neuropathies with Specific Metabolic Defects .......................... 177 Familial Amyloid Polyneuropathy (F AP) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 177

Type I (Andrade) ..................................................... 178 Type II (Rukavina) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 178 Type III (Van Allen) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 179 Type IV (Meretoja) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 179 Other Forms of Hereditary Amyloidosis ................................. 179

Primary Amyloidosis with Neuropathy: Sporadic Forms. . . . . . . . . . . . . . . . . . . . . .. 179 Cause of the Neuropathy in Amyloidoses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 179 Porphyric Neuropathies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 180

Laboratory Investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 181 Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 181 Nerve Biopsy. . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 181 Course and Management .............................................. 181

xx Contents

Hypertrophic Neuropathy with Phytanic Acid Storage: Refsum's Disease. . . . . . . .. 182 Laboratory Investigations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 182 Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 182 Nerve and Muscle Biopsy. . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 182 Other Pathological Aspects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 183 Treatment and Outcome .............................................. 183 Screening for Susceptibility. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 183

Other Genetically Determined Neuropathies with Metabolic Defects. . . . . . . . . . . .. 183

Chapter 11 Acquired Polyneuropathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 187

Diabetic Neuropathy ........................................................ 187 Distal Symmetrical Polyneuropathy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 187 Focal and Multifocal Neuropathies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 188 Proximal Motor Neuropathy (Diabetic Amyotrophy) . . . . . . . . . . . . . . . . . . . . . . . . .. 188 Cranial Mononeuropathies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 189 Intercostal Mononeuropathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 189 Laboratory Investigations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 189 Electrophysiological Assessment ............................ . . . . . . . . . . . . . .. 190 Pathological Correlations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 191 Pathogenesis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 192 Management of the Diabetic Neuropathies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 192

Uraemic Neuropathy ........................................................ 193 Electrophysiological Assessment ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 193 Pathological Correlations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 194

Hepatic Neuropathy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 194 Neuropathies Associated with Alcoholism, Malnutrition, Hypovitaminosis and Malab-

sorption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 194 Alcoholic Neuropathy. . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 194

Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 194 Pathological Correlations ............................................. 195 Management ........................................................ 195

Malnutrition. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 196 Neuropathies Associated with Hypovitaminosis .............................. 196

Thiamine Deficiency. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 196 Vitamin B12 Deficiency. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 196 Other B Group Vitamin Deficiencies .................................... 197 Vitamin E Deficiency. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 197

Tropical Ataxic Neuropathy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 198 Hypothyroid Neuropathy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 198 Acromegalic Neuropathy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 198 Neuropathies Associated with Malignant Disease and Dysproteinaemias ... . . . . . . . . .. 198

Sensory Neuropathy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 199 Mixed Sensorimotor Neuropathy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 199 Types of Neoplasm ...................................................... 199 Incidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 200 Laboratory Investigations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 200 Electrophysiological Assessment ........................................... 200 Pathological Features .................................................... 201 Pathogenesis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 201 Management ............................................................ 201 Infiltration of Nerve Roots and Nerves. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 201

Contents xxi

Neuropathy Associated with Myeloma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 202 Laboratory Investigations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 202 Electrophysiological Assessment .... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 203 Nerve Biopsy ........................................................... 203 Course and Prognosis .................................................... 203 Pathogenesis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 203

Other Neuropathies Associated with Paraproteinaemia . . . . . . . . . . . . . . . . . . . . . . . . . . .. 204 Electrophysiological and Other Assessment ....... . . . . . . . . . . . . . . . . . . . . . . . . . .. 204 Management ......................................................... _ ... 204

Neuropathies Associated with Collagen-Vascular Disease. . . . . . . . . . . . . . . . . . . . . . . . .. 204 Polyarteritis Nodosa .............. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 205 Other Forms of Polyarteritis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 205 Rheumatoid Arthritis .................................................... 205 Systemic Lupus Erythematosus ............................................ 206 Wegener's Granulomatosis ................................................ 206 Scleroderma .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 206 Cranial Arteritis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 206 Mixed Connective Disease ................................................ 206 Assessment, Pathology and Management of Neuropathies Associated with

Collagen-Vascular Disease .............................................. 206 Laboratory Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 206 Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . .. 206 Pathology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 206 Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 207

Inflammatory Polyradiculoneuropathy (Guillain-Barre Syndrome) .................. 207 Acute Guillain-Barre Syndrome ........................................... 207 Relapsing Form of Guillain-Barre Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 208 Chronic Inflammatory Polyradiculoneuropathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 208 Unusual Variant Forms of Guillain-Barre Syndrome .......................... 208 Electrophysiological Assessment ........................................... 208 Pathological Correlations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 209 Pathogenesis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 210 Management. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 211 Prognosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 212

Neuropathy of the Critically III . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 212 Neuropathies due to Infection. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 212

Diphtheria. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 212 Laboratory Investigations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 212 Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 213 Pathology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 213 Course ............................................................. 213

Tetanus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 213 Herpes Zoster. . . . . . . . . . . . . . ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 213

Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 214 Nerve Biopsy ........................................................ 214 Management ........................................................ 214

Herpes Simplex .......................................................... 214 Rabies ................................................................. 214 Poliomyelitis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 214 Botulism. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 214 Leprosy ................................................................ 214

Indeterminate Leprosy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 215

xxii Contents

Lepromatous Leprosy ................................................ 215 Tuberculoid Leprosy ................................................. 216 Dimorphous Leprosy ................................................. 216 Laboratory Assessment of Leprosy ...................................... 216 Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 216 Pathology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 217 Management of Leprosy .............................................. 217

Granulomatous (Sarcoid) Neuropathy .......................................... 218 Drug-Induced and Toxic Neuropathies ......................................... 218

Clinical Features ........................................................ 219 Mechanisms of Neurotoxic Effects of Drugs and Other Substances ............... 219

Role of the Liver. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 219 Role of the Vascular Bed ............................... . . . . . . . . . . . . . .. 220 Dying Back Change .................................................. 220 Effects on Energy Metabolism. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 220 Effects on Cell Constituents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 220

Drug-Induced Peripheral Neuropathies ......................................... 220 Antineoplastic Drugs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 221 Antimicrobial Drugs .................................................. 221 Antirheumatic Drugs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 221 Anticonvulsant Drugs ................................................ 223 Cardiovascular Drugs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 223 Other Drugs ..................................................... '. . .. 223

Peripheral Neuropathy Due to Toxic Chemicals and Metals .. . . . . . . . . . . . . . . . . . . . . .. 223 Acrylamide ......................................................... 223 Arsenic. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 224 Carbon Disulphide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 224 Ethylene Oxide ...................................................... 224 Hexacarbon . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 224 Lead ............................................................... 224 Organophosphates ............................. . . . . . . . . . . . . . . . . . . . . .. 224 Toxic Oil ........................................................... 225

Electrophysiological and Laboratory Assessment .......... . . . . . . . . . . . . . . . . . .. 225 Screening for Low Level Toxic Effects in Industry. . . . . . . . . . . . . . . . . . . . . . . . . . . .. 225

Subacute Myelo-Optico-Neuropathy (SMON) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 225

Section 4 Disorders of the Neuromuscular Junction

Chapter 12 Myasthenia Gravis and Other Myasthenic Syndromes . . . . . . . . . . . . . . . . . . .. 229

Myasthenia Gravis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 229 Adult-Onset Myasthenia Gravis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 230 Special Features . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 233 Associated Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 233 Pathophysiology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 233 Circulating ACh Receptor Antibody. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 234 Experimental Autoimmune Myasthenia Gravis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 235 Other Immunological Features of Myasthenia Gravis .......................... 235 Pathology of the Thymus in Myasthenia Gravis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 236 Muscle Pathology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 237

Contents xxiii

Diagnosis .............................................................. 237 Pharmacological Tests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 237 Electrophysiological Tests . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 238 Other Diagnostic Tests. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 241

Management ............................................................ 241 Anticholinesterase Drugs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 241 Thymectomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 242 Immunosuppressant Therapy .......................................... 243 Plasma Exchange .................................................... 244

Recommended Treatment of Myasthenia Gravis .......................... ~ ... 244 Penicillamine-induced Myasthenia Gravis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 245 Lambert-Eaton Myasthenic Syndrome (LEMS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 245

Pathophysiology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 246 Laboratory Investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 246 Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 247 Muscle Biopsy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 247

Management. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 247 Differential Diagnosis ............. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 248

Congenital Myasthenic Syndromes ............................................. 248 Botulism . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . .. 248

Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 249 Pathophysiology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 249

Management. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 249 Tick Paralysis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 249 Cobra Envenomisation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 249 Hypermagnesaemia .......................................................... 250 Drug-induced Disorders of Neuromuscular Transmissions . . . . . . . . . . . . . . . . . . . . . . . .. 250

Section 5 Myopathies and Muscular Dystrophies

Chapter 13 Inflammatory Myopathies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 253

Idiopathic Polymyositis and Dermatomyositis in Adults ........................... 253 Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 254 Acute Polymyositis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 254 Subacute Polymyositis and Dermatomyositis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 255 Slowly Progressive (Chronic) Polymyositis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 256 Juvenile (Childhood-Type) Dermatomyositis ................................. 256 Myositis Associated with Autoimmune Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . .. 256

Myositis Associated with Mixed Connective Tissue Disease ................. 257 Myositis Associated with Systemic Lupus Erythematosus . . . . . . . . . . . . . . . . . .. 257 Myositis Associated with Rheumatoid Arthritis . . . . . . . . . . . . . . . . . . . . . . . . . .. 257 Myositis Associated with Scleroderma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 257 Myositis Associated with Other Autoimmune and Connective Tissue Diseases. 257

Association of Polymyositis and Dermatomyositis with Malignancy .............. 257 Subacute Necrotising Myopathy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 258

Aetiology ofInflammatory Muscle Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 258 Laboratory Investigations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 259 Electrophysiological Assessment ........................................... 260 Muscle Biopsy .......................................................... 262

xxiv Contents

Clinical Variants ofInflammatory Myopathy .................................. " 266 Inclusion Body Myositis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 267 Clinical Criteria for Diagnosis of Polymyositis ................................... 267

Differential Diagnosis .................................................. " 268 Treatment and Prognosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 268

Immunosuppressant Drugs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 269 Complications of Steroid Therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 269

Viral Myositis .............................................................. 270 Post-viral Fatigue Syndromes ................................................. 270 Bacterial and other Infections and Infiltration of Muscle . . . . . . . . . . . . . . . . . . . . . . . . . .. 270 Drug-Induced Myositis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 271 Polymyaglia Rheumatica and Giant Cell Arteritis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 271

Chapter 14 Muscular Dystrophies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 273

X-Linked Muscular Dystrophies ............................................... 273 Duchenne Muscular Dystrophy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 273

Incidence and Inheritance ............................................. 274 Laboratory Investigations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 274 Prenatal Diagnosis ................................ . . . . . . . . . . . . . . . . . .. 275 Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 275 Muscle Biopsy ....................................................... 276 Pathological Features in Other Organs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 281 Carrier Detection and Genetic Counselling . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 281 Genetic Locus for Duchenne Dystrophy ................................. 282 Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 282

Becker-Type Muscular Dystrophy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 283 Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 283 Muscle Biopsy ....................................................... 283 Management and Carrier Detection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 284

Other X-linked Muscular Dystrophies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 284 Limb-Girdle Muscular Dystrophy .............................................. 285

Laboratory Investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 286 Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 286 Muscle Biopsy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 287 Differential Diagnosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 288 Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 288

Congenital Muscular Dystrophy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 288 Investigations ....................................................... 289 Muscle Biopsy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 289 Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 289

Quadriceps Myopathy ....................................................... 289 Facio-Scapulo-Humeral Muscular Dystrophy .................................... 289

Laboratory Investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 291 Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 291 Muscle Biopsy ....................................................... 291 Differential Diagnosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 291 Management ........................................................ 292

Scapulo-Peroneal Muscular Dystrophy ......................................... 292 Laboratory Investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . . . .. 292 Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 292 Muscle Biopsy ...................................................... , 293

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Differential Diagnosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 293 Distal Muscular Dystrophy (Welander Type) .................................... 293

Investigations ....................................................... 294 Muscle Biopsy ..................................................... " 294

Ocular Myopathies ........................................................ " 294 Oculo-Pharyngeal Muscular Dystrophy ..................................... 294

Investigations ....................................................... 294 Management ........ " .............................................. 296

Progressive Ocular Myopathy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 296 Oculo-Cranio-Somatic Neuromuscular Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 296

Laboratory Investigations in Ocular Myopathies . . . . . . . . . . . . . . . . . . . . . . . . .. 296 Electrophysiological Assessment in Ocular Myopathies. . . . . . . . . . . . . . . . . . . .. 296

Chapter 15 Myotonic Syndromes . ............................................ " 299

The Phenomenon of Myotonia ................................................ 299 Pathophysiology of Myotonia ............................................. 299 Clinical Tests for Myotonia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 301

Myotonic Dystrophy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 302 Neonatal Myotonic Dystrophy ........................................... " 303 Genetic Aspects .................. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 303 Laboratory Investigations ............................................... " 304 Electrophysiological Assessment ........................................... 304 Muscle Biopsy .......................................................... 306 Management. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 308

Inherited Myotonic Syndromes .............................................. " 309 Myotonia Congenita ................................................... " 310 Recessive Generalised Myotonia ........................................... 310 Paramyotonia Congenita ................................................. 311 Paralysis Periodica Paramyotonica ......................................... 311 Laboratory Investigations in Inherited Myotonic Syndromes .................... 312 Electrophysiological Findings in Inherited Myotonic Syndromes. . . . . . . . . . . . . . . .. 312 Muscle Pathology ...................................................... " 313

Treatment of Myotonic Syndromes ............................................. 313 Differential Diagnosis ............................... . . . . . . . . . . . . . . . . . . . .. 314

Schwartz-Jampel Syndrome .................................................. 314 Electrophysiological Assessment ........................................... 314 Muscle Biopsy .......................................................... 314 Management ...... " ... '" .............................................. 315

Drug-Induced Myotonia ..................................................... 315 Muscle Contracture Induced by Exercise ...................................... " 315

Chapter 16 Benign Childhood Myopathies . ...................................... 317

Central Core Disease ....................................................... " 317 Laboratory Investigations ............................................. 318 Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 318 Muscle Biopsy ..................................................... " 318

Causation and Associated Features ......................................... 319 Multicore Disease ......................................................... " 320

Investigations ....................................................... 320 Pathology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 320

xxvi Contents

Management of Central Core and Multicore Disease .............................. 320 Nemaline Myopathy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 321

Investigations ....................................................... 321 Muscle Biopsy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 321 Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 323

Myotubular (Centronuclear) Myopathy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 323 Investigations ....................................................... 323 Muscle Biopsy ....................................................... 323 Outcome ........................................................... 324

Controversies in Aetiology '" . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 324 Congenital Fibre-type Disproportion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 324

Laboratory Investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 325 Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 325 Muscle Biopsy ....................................................... 325 Differential Diagnosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 325 Management ........................................................ 325

Arthrogryposis Multiplex Congentia ........................................... 325 Rigid Spine Syndrome ....................................................... 326 Other Syndromes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 326

Chapter 17 Metabolic Myopathies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 327

Glycogenoses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 327 Acid Maltase Deficiency (Pompe's Disease) .................................. 327

Laboratory Investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 329 Electrophysiological Assessment ................. '. . . . . . . . . . . . . . . . . . . . . .. 329 Muscle Biopsy ........................... '. . . . . . . . . . . . . . . . . . . . . . . . . . .. 329 Other Pathological Features ........................................... 330 Genetics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 330 Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 330

Debranching Enzyme Deficiency (Limit Dextrinosis) .......................... 331 Laboratory Investigations ............................................. 331 Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 331 Muscle Biopsy ....................................................... 331 Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 331

Type IV Glycogenosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 331 Myophosphorylase Deficiency (McArdle'S Disease) ........................... 332

Biochemical Basis of the Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 332 Laboratory Investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 333 Electrophysiologica1 Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 334 Muscle Biopsy ....................................................... 334 Management ........................................................ 334

Phosphofructokinase Deficiency ........................................... 334 Other Defects of Glycolysis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 334

Myoadenylate Deaminase Deficiency ................... , . . . . . . . . . . . . . . . . . . . . . .. 335 Mitochondrial Myopathies and Related Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 335

Mitochondrial Metabolism. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 336 Ragged-Red Fibres ..................................................... , 336 Clinical and Biochemical Features of Mitochondrial Disorders Affecting Muscle .. , 337 Defects of Substrate Utilisation ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 337

Defects ofCarnitine Utilisation ......................................... 339

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Other Lipid Storage Myopathies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 342 Carnitine Palmityl Transferase (CPTase) Deficiency ....................... 342

Defects in the Respiratory Chain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 343 Multisystem Syndromes ............................................... 343 Myopathic Syndromes ................................................ 343 Investigation of Respiratory Chain Defects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 343 Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 343 Defective Energy Function ............................................ 344

Periodic Paralyses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 344 Laboratory Abnormalities in Spontaneous Attacks .. . . . . . . . . . . . . . . . . . . . . .. 345 Provocative Diagnostic Tests. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 345 Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 346 }'.1uscle Biopsy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 346 Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 346

Thyrotoxic Periodic Paralysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 348 Other Forms of Hypokalaemic Myopathy ................................... 348

Malignant Hyperpyrexia Syndrome ............................................ 348 Screening for Susceptibility .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 349 Pathophysiology of the Rise in Temperature .............................. 349 Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 349 Muscle Biopsy ....................................................... 349 Management of Hyperpyrexia .......................................... 350

Neuroleptic-Malignant Syndrome .............................................. 350 Management. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 351

Myoglobinuria and Rhabdomyolysis ........................................... 351 Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 352 Muscle Biopsy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 352 Management ........................................................ 352

Nutritional and Toxic Myopathies ............................................. 352 Alcoholic Myopathy .............. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 352

Biochemical Features. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 353 Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 353

Carcinoid Myopathy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 353 Hypermagnesaemia ...................................................... 354 Whipple's Disease Myopathy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 354 Vitamin E Deficiency. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 354 Tropical Sprue and Coeliac Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 355 Osteomalacia ........................................................... 355

Chapter 18 Endocrine Myopathies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 357

Thyroid Myopathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 357 Hyperthyroid Myopathy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 358

Investigations ....................................................... 359 Muscle Biopsy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 359 Pathophysiology of Hyperthyroid Myopathy . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 359 Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 360

Hypothyroidism. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 360 Laboratory Investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 360 Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 360

xxviii Contents

Muscle Biopsy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 361 Nerve Biopsy ........................................................ 361 Management and Course ........... '" ................................ 361

Parathyroid Disorders and Osteomalacia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 361 Hyperparathyroidism and Osteomalacia ..................................... 361

Clinical Features. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 362 Laboratory Investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 362 Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 362 Muscle Biopsy ....................................................... 362 Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 363

Hypoparathyroidism. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 363 Adrenal Disorders and Steroid Myopathy ....................................... 363

Hyperadrenalism and Steroid Myopathy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 363 Laboratory Investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 363 Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 364 Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 364

Hypoadrenalism (Addison's Disease) ....................................... 364 Conn's Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 365

Pituitary Disorders .................. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 365 Acromegaly. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 365

Laboratory Investigations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 366 Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 366 Muscle Biopsy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 366 Nerve Biopsy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 367 Course ............................................................. 367

Chapter 19 Drug-Induced and Toxic Myopathies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 369

Muscle Pain, Stiffness and Cramp .............................................. 369 Necrotising Myopathy ....................................................... 369 Inflammatory Myopathy .......................................... . . . . . . . . . .. 370 Acute Hypokalaemic Paralysis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 370 Injection (Focal) Myopathy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 371 Subacute or Acute Painful Myopathy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 371 Chronic Painless Myopathy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 371 Toxic Myopathies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 371

Chapter 20 Cardiomyopathy in Neuromuscular Disorders. . . . . . . . . . . . . . . . . . . . . . . . . .. 373

Friedreich's Ataxia ... . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 374 Refsum's Disease ............................................................ 374 Hereditary Amyloid Neuropathy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 374 Guillain-Barre Syndrome .................................................... , 375 Diphtheria ................................................................ , 375 Duchenne Muscular Dystrophy ................................................ 375 Emery-Dreifuss Muscular Dystrophy ........................................... 375 Limb-Girdle Muscular Dystrophy .............................................. 375 Facio-Scapulo-Humeral Dystrophy ............................................ 375 Scapulo-Peroneal Syndrome. . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 375 Myotonic Dystrophy ........................................................ , 375 Periodic Paralysis ........................................................... 376

Contents xxix

Glycogenoses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 376 Kearns-Sayre Syndrome ..................................................... 376 Polymyositis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 376 Alcoholic Myopathy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 376 Endocrine Myopathies ....................................................... 377

Section 6 Other Clinical Problems

Chapter 21 Miscellaneous Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 381

Stiff Man Syndrome ......................................................... 381 Laboratory Tests. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 381 Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. . . . . . . .. 382 Pathology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 382 Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 382

Continuous Muscle Fibre Activity Syndrome (Isaacs' Syndrome) .................... 382 Laboratory Tests. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 382 Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 382 Nerve and Muscle Biopsy .............................................. 383 Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 383

Neuromyotonia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 383 Restless Legs Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 383 Excessive Fatiguability. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 384 Hysterical Weakness ......................................................... 385

Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 385 Effort Syndromes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 385 Primary Fibromyalgia and Overuse Syndromes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 386 Disuse ..................................................................... 386 Cachexia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 386 Ageing .................................................................... 387

Electrophysiological Assessment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 387 Muscle Biopsy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 387

Changes in Nerves with Age ............................................... 388

References ................................................................. 389

Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 449