Motor Neuron Disease in Adults

369 Pages·2014·24.79 MB·English

by  Mark Bromberg

MOTOR NEURON DISEASE IN ADULTS
SERIES EDITOR
Sid Gilman, MD, FRCP
William J. Herdman Distinguished University Professor of Neurology
University of Michigan
Contemporary Neurology Series
70 THE NEUROLOGY OF EYE 78 THE NEURONAL CEROID
MOVEMENTS LIPOFUSCINOSES (BATTEN DISEASE)
Fourth Edition Second Edition
R. John Leigh, MD, FRCP, and Sara E. Mole, PhD, Ruth D. Williams, MD,
David S. Zee, MD and Hans H Goebel, MD, Editors
71 PLUM AND POSNER’S DIAGNOSIS 79 PARANEOPLASTIC SYNDROMES
OF STUPOR AND COMA Robert B. Darnell, MD, PhD, and
Fourth Edition Jerome B. Posner, MD
Jerome B. Posner, MD, 80 JASPER’S BASIC MECHANISMS
Clifford B. Saper, MD, PhD, OF THE EPILEPSIES
Nicholas D. Schiff, MD, and Fred Plum, MD Jeffrey L. Noebels, MD, PhD,
72 PRINCIPLES OF DRUG THERAPY Massimo Avoli, MD, PhD,
IN NEUROLOGY Michael A. Rogawski, MD, PhD,
Second Edition Richard W. Olsen, PhD, and
Michael V. Johnston, MD, and Antonio V. Delgado-Escueta, MD
Robert A. Gross, MD, PhD, Editors 81 MYASTHENIA GRAVIS AND
73 NEUROLOGIC COMPLICATIONS MYASTEHNIC DISORDERS
OF CANCER Second Edition
Second Edition Andrew G. Engel, MD
Lisa M. DeAngelis, MD, and 82 MOLECULAR PHYSIOLOGY
Jerome B. Posner, MD AND METABOLISM OF THE
74 NEUROLOGIC COMPLICATIONS NERVOUS SYSTEM
OF CRITICAL ILLNESS Gary A. Rosenberg, MD
Third Edition 83 SEIZURES AND EPILEPSY
Eelco F.M. Wijdicks, MD, PhD, FACP Second Edition
75 CLINICAL NEUROPHYSIOLOGY Jerome Engel, Jr., MD, PhD
Third Edition 84 MULTIPLE SCLEROSIS
Jasper R. Daube, MD, and Moses Rodriguez, MD,
Devon I Rubin, MD, Editors Orhun H. Kantarci, MD,
76 PERIPHERAL NEUROPATHIES and Istvan Pirko, MD
IN CLINICAL PRACTICE 85 FRONTOTEMPORAL DEMENTIA
Steven Herskovitz, MD, Bruce L. Miller, MD
Stephen N. Scelsa, MD, 86 AUTONOMIC NEUROLOGY
and Herbert H. Schaumburg, MD Eduardo E. Benarroch, MD
77 CLINICAL NEUROPHYSIOLIOGY 87 EVALUATION AND TREATMENT
OF THE VESTIBULAR SYSTEM OF MYOPATHIES
Fourth Edition Second Edition
Robert W. Baloh, MD, FAAN, and Emma Ciafaloni, MD, Patrick F. Chinnery,
Kevin A. Kerber, MD and Robert C. Griggs, MD, Editors
MOTOR NEURON DISEASE
IN ADULTS
Edited By
Mark B. Bromberg, MD, PhD
Professor of Neurology
University of Utah
Salt Lake City, Utah
1
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Library of Congress Cataloging-in-Publication Data
Motor neuron disease in adults / edited by Mark Bromberg.
p. ; cm.
Includes bibliographical references.
ISBN 978–0–19–978311–3 (alk. paper)
I. Bromberg, M. B. (Mark B.), editor.
[DNLM: 1. Motor Neuron Disease. 2. Adult. WE 550]
RC376.5
616.8′3—dc23
2014008930
The science of medicine is a rapidly changing field. As new research and clinical experience broaden our knowledge,
changes in treatment and drug therapy occur. The author and publisher of this work have checked with sources believed
to be reliable in their efforts to provide information that is accurate and complete, and in accordance with the standards
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on acid-free paper
Contents
Preface xxi
Contributors xxiii
Introduction to “Motor Neuron Disease” xxv
Abbreviations xxvii
1. HISTORY OF THE RECOGNITION OF MOTOR NEURON DISEASE 1
Mark B. Bromberg
BACKGROUND AND NEW POINTS 1
HISTORICAL SETTING 1
HISTORICAL RECOGNITION OF MND 2
Bell • Aran • Duchenne and Cruveilhier • Charcot • Erb • Dejerine • Gowers • Brain
FAMILIAL MND 4
2. NOMENCLATURE AND CLASSIFICATION OF MOTOR NEURON DISEASE 5
Mark B. Bromberg
BACKGROUND AND NEW POINTS 5
INTRODUCTION 5
LOU GEHRIG 7
WFN RESEARCH CLASSIFICATION 7
PMA 9
PLS 10
ALS BY PHENOTYPES 10
3. CLINICAL ANATOMY, PHYSIOLOGY, AND PATHOLOGY OF MOTOR
NEURON DISEASE 12
Mark B. Bromberg
BACKGROUND AND NEW POINTS 12
INTRODUCTION 12
ANATOMY 13
UMNs • LMNs
v
vi Contents
PATHOLOGY 14
ALS • PLS • PMA
PHYSIOLOGY AND PATHOPHYSIOLOGY 15
ALS • PLS • Frontotemporal Lobe
4. CLINICAL FEATURES OF MOTOR NEURON DISEASE 18
Mark B. Bromberg
BACKGROUND AND NEW POINTS 18
INTRODUCTION 18
COGNITIVE DYSFUNCTION IN NONDEMENTED PATIENTS WITH MND 18
FRONTOTEMPORAL LOBE DYSFUNCTION AND DEMENTIA 19
PSEUDOBULBAR AFFECT AND INCREASED YAWNING 21
BULBAR DYSFUNCTION 21
Dysarthria • Dysphagia
UPPER EXTREMITY DYSFUNCTION 23
LOWER EXTREMITY DYSFUNCTION 24
RESPIRATORY DYSFUNCTION 25
EYE MOVEMENT ABNORMALITIES 25
5. FRONTOTEMPORAL DYSFUNCTION AND DEMENTIA IN AMYOTROPHIC
LATERAL SCLEROSIS 27
Lauren Elman and Zachary Simmons
BACKGROUND AND NEW POINTS 27
INTRODUCTION 27
EPIDEMIOLOGY 28
CLINICAL FEATURES 28
DIAGNOSTIC CRITERIA AND CATEGORIZATION 29
ASSESSMENT OF COGNITIVE AND BEHAVIORAL DEFICITS 29
Cognitive Instruments • Behavioral Instruments • Combined Cognitive and 
Behavioral Instruments
IMAGING 31
GENETICS AND PATHOLOGY 32
BIOMARKERS 34
CLINICAL RELEVANCE 35
EFFECT OF FTD ON COURSE AND PROGNOSIS 35
Contents vii
IMPLICATIONS OF FTD FOR THE CAREGIVER 35
NONPHARMACOLOGIC MANAGEMENT OF FTD 36
PHARMACOLOGIC MANAGEMENT OF ALS-FTD 36
CONCLUSION 38
6. LABORATORY TESTS FOR MOTOR NEURON DISEASE 42
Mark B. Bromberg
BACKGROUND AND NEW POINTS 42
INTRODUCTION 42
NERVE CONDUCTION TESTING 43
NERVE CONDUCTION TESTS FOR UMN LOSS 43
NEEDLE EMG TESTING 43
EMG ABNORMALITIES IN INDIVIDUAL MUSCLES 44
Cervical and Lumbosacral Muscles • Cranial Muscles • Diaphragm • Thoracic and Rectus 
Abdominis Muscles
MUSCLE BIOPSY 45
SEROLOGIC AND SPINAL FLUID LABORATORY STUDIES 45
Serum Creatine Kinase • Cerebrospinal Fluid
CENTRAL NERVOUS SYSTEM IMAGING 46
MUSCLE IMAGING 46
MRI • Ultrasound
FRONTOTEMPORAL LOBE TESTING 48
7. BIOMARKERS FOR MOTOR NEURON DISEASE 50
Shafeeq Ladha, Christina Chrisman, and Robert Bowser
BACKGROUND AND NEW POINTS 50
INTRODUCTION 50
GENETIC BIOMARKERS 51
PROTEIN BIOMARKERS 53
METABOLIC BIOMARKERS 57
NEUROPHYSIOLOGIC BIOMARKERS 58
MUNE • MUNE in ALS Studies • EIM • TMS
IMAGING BIOMARKERS 65
Conventional MRI • MRS • DTI • Voxel-based Morphometry • fMRI
CONCLUSIONS AND FUTURE DIRECTIONS 67
viii Contents
8. IMAGING IN MOTOR NEURON DISEASE 75
Martin R. Turner
BACKGROUND AND NEW POINTS 75
INTRODUCTION 75
TYPES OF NEUROIMAGING 76
NEUROIMAGING FOR DIAGNOSTIC EXCLUSION 77
NEUROIMAGING AS A BIOMARKER 80
CORE CEREBRAL MOTOR PATHOLOGY 80
Voxel- and Surface-based Morphometry • DTI • Spectroscopy
EXTRAMOTOR CEREBRAL PATHOLOGY 84
Radionuclide Imaging • VBM • DTI • Spectroscopy • fMRI
MECHANISTIC IMAGING 86
Loss of Cortical Inhibitory Influence • Neuroinflammation • Serotonergic Involvement
FUTURE DIRECTIONS 88
Imaging in Animal Models • Spinal Cord • Presymptomatic Pathology • Network-based 
Approaches
CONCLUSION 89
9. DIAGNOSTIC CRITERIA FOR MOTOR NEURON DISEASE 94
Mark B. Bromberg
BACKGROUND AND NEW POINTS 94
INTRODUCTION 94
TIME TO DIAGNOSIS 94
ALS 95
El Escorial Criteria • Airlie House Criteria • Awaji Criteria • Pending El Escorial Review
WORLD FEDERATION OF NEUROLOGY CRITERIA PERFORMANCE
REVIEWS 97
PLS 98
PMA 100
10. DIFFERENTIAL DIAGNOSIS OF MOTOR NEURON DISEASE 102
Mark B. Bromberg
BACKGROUND AND NEW POINTS 102
DIFFERENTIAL DIAGNOSIS OF ALS 102
KENNEDY DISEASE 102
MULTIFOCAL MOTOR NEUROPATHY 103
INCLUSION BODY MYOSITIS 105
Contents ix
SPONDYLOTIC RADICULOPATHY AND MYELORADICULOPATHY 105
MONONEUROPATHIES 106
MYASTHENIA GRAVIS 106
HEREDITARY SPASTIC PARESIS 106
LYME DISEASE 107
VIRAL DISEASES 107
RETROVIRAL DISEASES 107
HEAVY METAL TOXICITY 107
CANCER AND PARANEOPLASTIC SYNDROMES 107
11. MOTOR NEURON DISEASE PROGRESSION 109
Mark B. Bromberg
BACKGROUND AND NEW POINTS 109
INTRODUCTION 109
CLINICAL PROGRESSION 110
ALS • PBP • PMA • PLS
CLINIMETRIC SCALES 112
Composite Scales • Motor Unit Number Estimation • Motor Unit Number Index • CMAP 
Scan • Neurophysiologic Index • Electrical Impedance Myography • Muscle 
Ultrasound • MRI • ALSFRS
QUANTITATING PROGRESSION 115
ALS STAGING 116
PREDICTION OF PROGRESSION AND SURVIVAL 116
12. EPIDEMIOLOGY OF AMYOTROPHIC LATERAL SCLEROSIS 119
Adriano Chiò and Giancarlo Logroscino
BACKGROUND AND NEW POINTS 119
INTRODUCTION 119
DESCRIPTIVE EPIDEMIOLOGY 120
Methodologic Considerations • Incidence • Prevalence • Mortality
ALS TIME TRENDS 122
GENETIC EPIDEMIOLOGY 123
COGNITIVE CHANGES AND MOTOR NEURON DEGENERATION IN
POPULATION-BASED STUDIES 125
FTD: NEW END OF THE ALS SPECTRUM? 126
ALS PROGNOSTIC FACTORS 127