Kaminski Myasthenia Gravis and Related Disorders

2. Auflage 2009
ISBN: 978-1-59745-156-7
Verlag: Humana Press
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 312 Seiten

Reihe: Current Clinical Neurology

Advances in the study and understanding of myasthenia gravis have led to the need for the publication of this important new edition. The goal of Myasthenia Gravis and Related Disorders, Second Edition is identical to the first -- to provide the clinician and the scientist with a common resource for understanding this complex disorder. This new edition begins with discussions of neuromuscular junction structure and function and follows with updated chapters covering a wide range of topics, such as the acetylcholine receptor, clinical presentation, diagnostic evaluation, and treatment. Importantly, new supplemental chapters have been added; these discuss rigorous clinical assessments of patients for research trials and the epidemiology and genetics of myasthenia gravis. The discussion of the most challenging aspects of myasthenia gravis, its impact on patients' psychological make-up, has been expanded as well. Myasthenia Gravis and Related Disorders, Second Edition retains the 'personal approach' of the authors regarding treatment and is a valuable resource for meeting the many and varied needs of patients with myasthenia gravis.

Autoren/Hrsg.

Kaminski, Henry J.

Inhaltsverzeichnis

1;Preface;6
2;Contents;7
3;Contributors;9
4;Series Editor Introduction;11
5;Color Plates;12
6;Neuromuscular Junction Physiology and Pathophysiology;13
6.1;1.1 INTRODUCTION;13
6.2;1.2 MOTOR NERVE PROPERTIES;13
6.2.1;1.2.1 Distal Motor Nerve Properties;13
6.2.2;1.2.2 The Nerve Terminal;14
6.2.2.1;1.2.2.1 Role of Ca2+ Channels in Transmitter Release;14
6.2.2.2;1.2.2.2 Synaptic Vesicle Fusion;15
6.3;1.3 THE SYNAPTIC CLEFT;16
6.3.1;1.3.1 Synatpic Cleft Acetylcholine Esterase;17
6.3.2;1.3.2 Alteration of AChE in Neuromuscular Diseases;17
6.3.3;1.3.3 Extracellular Matrix in the Synaptic Cleft;17
6.3.4;1.3.4 ACh-Binding Protein;18
6.4;1.4 POSTSYNAPTIC MEMBRANE SPECIALIZATION;18
6.4.1;1.4.1 How the NMJ Accommodates to Muscle Contraction;19
6.4.2;1.4.2 Postsynaptic Na+and AChR Channels;19
6.5;1.5 SAFETY FACTOR FOR NEUROMUSCULAR TRANSMISSION;20
6.6;REFERENCES;20
7;Acetylcholine Receptor Structure;25
7.1;2.1 INTRODUCTION;25
7.2;2.2 SIZE AND SHAPE OF ACHRS;26
7.3;2.3 STRUCTURES OF ACHR SUBUNITS;27
7.4;2.4 ORGANIZATION OF SUBUNITS IN ACHR SUBTYPES;31
7.5;2.5 ACETYLCHOLINE-BINDING SITES;33
7.6;2.6 CATION CHANNEL AND ITS GATE;35
7.7;2.7 ANTIGENIC STRUCTURE AND THE MAIN IMMUNOGENIC REGION (MIR);35
7.8;2.8 INDUCTION OF THE AUTOIMMUNE RESPONSE TO ACHRS IN MG;38
7.9;2.9 AUTOIMMUNE MECHANISMS WHICH IMPAIR NEUROMUSCULAR TRANSMISSION IN MG AND EAMG;39
7.10;2.10 EFFECTS OF ACHR MUTATIONS IN CONGENITAL MYASTHENIC SYNDROMES;40
7.11;2.11 NEURONAL ACHR SUBTYPES AND FUNCTIONAL ROLES;42
7.12;2.12 AUTOIMMUNE IMPAIRMENT OF NEURONAL ACHRS;43
7.13;2.13 EFFECTS OF HUMAN NEURONAL ACHR MUTATIONS;44
7.14;REFERENCES;45
8;Immunopathogenesis of Myasthenia Gravis;54
8.1;3.1 INTRODUCTION;54
8.2;3.2 ANTI-ACHR Ab IN MG AND IN EXPERIMENTAL AUTOIMMUNE MG (EAMG);54
8.3;3.3 EPITOPES RECOGNIZED BY ANTI-ACHR Ab IN MG AND EAMG;56
8.3.1;3.3.1 The MIR;56
8.3.2;3.3.2 The Cholinergic Site;56
8.3.3;3.3.3 Non-AChR Antigens;57
8.4;3.4 ANTI-ACHR CD4+ T-HELPER CELLS IN MG;58
8.4.1;3.4.1 Epitope Repertoire of Anti-AChR CD4+ T Cells in MG;59
8.4.2;3.4.2 CD4+ T Cells of MG Patients Recognize ‘‘Universal’’, Immunodominant AChR Epitopes;61
8.4.3;3.4.3 Unstable Recognition of AChR Epitopes by CD4+ T Cells of Ocular MG Patients;61
8.5;3.5 TCR Vbeta AND Valpha USAGE BY ANTI-ACHR CD4+ T CELLS OF MG PATIENTS;62
8.6;3.6 ROLES IN MG AND EAMG OF CYTOKINES SECRETED BY DIFFERENT CD4+ SUBSETS;64
8.7;3.7 CD8+ CELLS IN MG AND EAMG;67
8.8;3.8 THE THYMUS IN MG;68
8.8.1;3.8.1 AChR-Like Proteins Are Expressed in the Thymus;68
8.8.2;3.8.2 Thymus Cells That Express AChR Proteins;69
8.9;3.9 PATHOGENIC MECHANISMS OF MG;70
8.10;REFERENCES;72
9;Epidemiology and Genetics of Myasthenia Gravis;82
9.1;4.1 INTRODUCTION;82
9.2;4.2 EPIDEMIOLOGICAL ISSUES AND MYASTHENIA GRAVIS;82
9.2.1;4.2.1 Definition of Terms;82
9.2.2;4.2.2 Epidemiological Studies of Myasthenia Gravis;83
9.2.3;4.2.3 Current Trends in the Epidemiology of Myasthenia Gravis;83
9.2.4;4.2.4 Seronegative and Muscle-Specific Kinase Antibody-Related Myasthenia Gravis;85
9.2.5;4.2.5 Genetics of MG;86
9.2.6;4.2.6 Proof of Inheritance;86
9.3;4.3 CANDIDATE GENES;87
9.3.1;4.3.1 HLA Complex;87
9.3.2;4.3.2 AChR as a Self-Antigen and Other HLA Genes;87
9.3.3;4.3.3 Other Candidate Genes;88
9.4;REFERENCES;88
10;Clinical Presentation and Epidemiology of Myasthenia Gravis;90
10.1;5.1 DEFINITION AND CLASSIFICATION;90
10.2;5.2 CLINICAL MANIFESTATIONS;90
10.2.1;5.2.1 Ocular;90
10.2.2;5.2.2 Bulbar;91
10.2.3;5.2.3 Limb, Trunk and Respiratory;94
10.2.4;5.2.4 Muscle Atrophy;95
10.2.5;5.2.5 Clinical Classifications and Quantitative Tests;97
10.2.6;5.2.6 Cognitive Involvement;97
10.2.7;5.2.7 The Course of the Disease;98
10.2.8;5.2.8 Exacerbating Factors;99
10.3;5.3 EPIDEMIOLOGY;100
10.3.1;5.3.1 Incidence and Prevalence;100
10.3.2;5.3.2 Age, Gender and Classification;100
10.3.3;5.3.3 Acquired Infantile MG;101
10.3.4;5.3.4 Myasthenia Gravis in the Elderly;101
10.3.5;5.3.5 Myasthenia Gravis and Thymoma;101
10.3.6;5.3.6 The Incidence of Autoimmune Diseases in MG;101
10.3.7;5.3.7 Genetic Predisposition;102
10.3.8;5.3.8 Differential Diagnosis;102
10.4;REFERENCES;102
11;Ocular Myasthenia;106
11.1;6.1 INTRODUCTION;106
11.2;6.2 EPIDEMIOLOGY;106
11.3;6.3 BASIS FOR OCULAR MUSCLE INVOLVEMENT BY MYASTHENIA GRAVIS;106
11.4;6.4 CLINICAL PRESENTATION;107
11.5;6.5 DIAGNOSTIC TESTING;107
11.6;6.6 PROGRESSION TO GENERALIZED MYASTHENIA GRAVIS;110
11.7;6.7 TREATMENT;111
11.8;References;112
12;Thymoma-Associated Paraneoplastic Myasthenia Gravis;116
12.1;7.1 INTRODUCTION;116
12.2;7.2 HISTOPATHOLOGY OF THE THYMUS IN MG;117
12.2.1;7.2.1 Thymic Lympho-follicular Hyperplasia (TFH);117
12.2.2;7.2.2 Thymus Histology in Late-Onset MG (LOMG);118
12.2.3;7.2.3 Thymomas and Paraneoplastic MG;118
12.3;7.3 PATHOGENETIC CONCEPTS IN SEROPOSITIVE MG;118
12.3.1;7.3.1 Pathogenesis of MG in Thymic Lympho-follicular Hyperplasia (TFH);118
12.3.2;7.3.2 Pathogenesis of Thymoma-Associated (Paraneoplastic) MG;120
12.3.2.1;7.3.2.1 Genetic Features Contributing to Paraneoplastic MG;120
12.3.2.2;7.3.2.2 Molecular and Functional Features Contributing to Paraneoplastic MG;121
12.3.2.3;7.3.2.3 Shared Features Among MG-Associated Thymomas;121
12.3.3;7.3.3 A Pathogenetic Model of Paraneoplastic Myasthenia Gravis;121
12.3.4;7.3.4 Etiological Triggers of Paraneoplastic MG;122
12.3.5;7.3.5 Major Unresolved Questions in Paraneoplastic MG;123
12.4;REFERENCES;124
13;Electrodiagnosis of Neuromuscular Junction Disorders;129
13.1;8.1 INTRODUCTION;129
13.2;8.2 BASIC CONCEPTS OF NEUROMUSCULAR TRANSMISSION;129
13.2.1;8.2.1 Quantum;129
13.2.2;8.2.2 End-Plate Potential;129
13.2.3;8.2.3 Safety Factor;130
13.2.4;8.2.4 Calcium Influx into the Terminal Axon;130
13.2.5;8.2.5 Compound Muscle Action Potential;130
13.3;8.3 ELECTRODIAGNOSTIC TESTS IN NEUROMUSCULAR JUNCTION DISORDERS;130
13.3.1;8.3.1 Routine Motor Nerve Conduction Studies;130
13.3.2;8.3.2 Conventional Needle Electromyography;130
13.3.2.1;8.3.2.1 Moment-to-Moment Variation Instability of Motor Unit Action Potentials;130
13.3.2.2;8.3.2.2 Short-Duration, Low-Amplitude, and Polyphasic MUAPs;131
13.3.2.3;8.3.2.3 Fibrillation Potentials;131
13.3.3;8.3.3 Repetitive Nerve Stimulation;131
13.3.3.1;8.3.3.1 Principles;131
13.3.3.2;8.3.3.2 Techniques;131
13.3.3.3;8.3.3.3 Findings;132
13.3.3.4;8.3.3.4 Measurements;134
13.3.4;8.3.4 Single-Fiber EMG;136
13.3.4.1;8.3.4.1 Principles;136
13.3.4.2;8.3.4.2 Techniques;136
13.3.4.3;8.3.4.3 Measurements;138
13.3.4.4;8.3.4.4 Findings;139
13.4;8.4 NEUROMUSCULAR DEFECT FINDINGS IN NEUROMUSCULAR JUNCTION DISORDERS;140
13.4.1;8.4.1 Myasthenia Gravis;140
13.4.1.1;8.4.1.1 Baseline Motor Nerve Conduction Studies;141
13.4.1.2;8.4.1.2 Slow Repetitive Nerve Stimulation;141
13.4.1.3;8.4.1.3 Rapid Repetitive Nerve Stimulation and Post-exercise Facilitation;141
13.4.1.4;8.4.1.4 Single-Fiber EMG;142
13.4.1.5;8.4.1.5 Conventional Needle EMG;144
13.4.2;8.4.2 Lambert-Eaton Syndrome;144
13.4.2.1;8.4.2.1 Baseline Motor Nerve Conduction Studies;145
13.4.2.2;8.4.2.2 Rapid Repetitive Nerve Stimulation and Post-exercise Facilitation;145
13.4.2.3;8.4.2.3 Slow Repetitive Nerve Stimulation;145
13.4.2.4;8.4.2.4 Single-Fiber EMG;145
13.4.2.5;8.4.2.5 Conventional Needle EMG;145
13.4.3;8.4.3 Botulism;145
13.4.3.1;8.4.3.1 Baseline Motor Nerve Conduction Studies;147
13.4.3.2;8.4.3.2 Rapid Repetitive Nerve Stimulation and Post-exercise Facilitation;147
13.4.3.3;8.4.3.3 Slow Repetitive Nerve Stimulation;147
13.4.3.4;8.4.3.4 Single-Fiber EMG;147
13.4.3.5;8.4.3.5 Conventional Needle EMG;148
13.4.4;8.4.4 Congenital Myasthenic Syndromes;148
13.4.5;8.4.5 Electrodiagnostic Strategy in a Patient with Suspected Neuromuscular Junction Disorder;148
13.5;8.5 NEUROMUSCULAR DEFECT FINDINGS IN OTHER NEUROMUSCULAR DISORDERS;149
13.5.1;8.5.1 Amyotrophic Lateral Sclerosis;149
13.5.2;8.5.2 Miller-Fisher Syndrome;149
13.5.3;8.5.3 Guillian-Barré Syndrome;149
13.6;REFERENCES;150
14;Autoantibody Testing in the Diagnosis and Management of Autoimmune Disorders of Neuromuscular Transmission and Related Diseases;152
14.1;9.1 INTRODUCTION;152
14.2;9.2 SPECTRUM OF ANTIBODIES TO TARGETS AT THE NMJ AND ASSOCIATED MOLECULES;152
14.3;9.3 IDENTIFYING A PATHOGENIC ROLE FOR ANTIBODIES IN ANTIBODY-MEDIATED DISORDERS;153
14.4;9.4 DISEASE PHENOTYPES IN AUTOIMMUNE MYASTHENIC DISORDERS;153
14.5;9.5 HETEROGENEITY AND PATHOPHYSIOLOGICAL EFFECTS OF AChR ANTIBODIES;154
14.5.1;9.5.1 Binding Antibodies Measured by Immunoprecipitation;155
14.5.2;9.5.2 Blocking Antibodies;156
14.5.3;9.5.3 Assays to Detect Modulating Antibodies;156
14.5.4;9.5.4 Other Autoantibodies;156
14.6;9.6 AUTOIMMUNE MG IN ASSOCIATION WITH THYMOMA;156
14.6.1;9.6.1 Striated Muscle Antibody Assays;157
14.7;9.7 LATE-ONSET MG NOT ASSOCIATED WITH A DETECTABLE THYMOMA;157
14.8;9.8 ROLE OF ANTIBODIES IN DIAGNOSIS AND TREATMENT IN PATIENTS WITH MG;157
14.9;9.9 SERONEGATIVE (SN) MG;158
14.9.1;9.9.1 Plasma Exchange and Passive Transfer;158
14.9.2;9.9.2 Functional and Binding Studies;158
14.9.3;9.9.3 Antibodies to a Candidate Antigen;158
14.10;9.10 LAMBERT-EATON SYNDROME AND CEREBELLAR ATAXIA;159
14.10.1;9.10.1 Plasma Exchange and Passive Transfer;159
14.10.2;9.10.2 Functional and Binding Studies;160
14.10.3;9.10.3 Radioimmunoprecipitation Assays;160
14.11;9.11 ACQUIRED NEUROMYOTONIA;160
14.11.1;9.11.1 Plasma Exchange and Passive Transfer;160
14.11.2;9.11.2 Functional and Binding Assays;160
14.12;9.12 STIFF PERSON SYNDROME;162
14.13;9.13 CONCLUSIONS;162
14.14;REFERENCES;162
15;Treatment of Myasthenia Gravis;166
15.1;10.1 INTRODUCTION;166
15.2;10.2 PATIENT EDUCATION AND EVALUATION;167
15.3;10.3 TREATMENTS;168
15.3.1;10.3.1 Cholinesterase Inhibitors;169
15.3.2;10.3.2 Corticosteroids;170
15.3.3;10.3.3 Azathioprine;171
15.3.4;10.3.4 Cyclosporine;172
15.3.5;10.3.5 Mycophenolate Mofetil;173
15.3.6;10.3.6 Tacrolimus;173
15.3.7;10.3.7 Plasma Exchange;174
15.3.8;10.3.8 Intravenous Immunoglobulin;174
15.3.9;10.3.9 Other Immunosuppressive Treatments;175
15.4;10.4 SPECIFIC CLINICAL SITUATIONS;176
15.4.1;10.4.1 Myasthenia Gravis and Pregnancy;176
15.4.2;10.4.2 Treatment of the Myasthenia Gravis Patient with Thymoma;176
15.4.3;10.4.3 Juvenile Myasthenia Gravis;176
15.4.4;10.4.4 The Treatment-Resistant Patient;177
15.4.5;10.4.5 Experimental Treatments for Myasthenia Gravis;177
15.5;REFERENCES;178
16;Neurocritical Care of Myasthenic Crisis;183
16.1;11.1 INTRODUCTION;183
16.2;11.2 PATHOPHYSIOLOGY;183
16.2.1;11.2.1 Precipitants;183
16.2.2;11.2.2 Respiratory Abnormalities;184
16.2.3;11.2.3 Oropharyngeal Dysfunction;184
16.2.4;11.2.4 Clinical Presentation and Evaluation;184
16.2.5;11.2.5 Differential Diagnosis;186
16.3;11.3 MANAGEMENT;186
16.3.1;11.3.1 General;186
16.3.2;11.3.2 Ventilatory Management;187
16.3.3;11.3.3 Ventilator Weaning;187
16.3.4;11.3.4 Treatment of Neuromuscular Dysfunction;188
16.3.5;11.3.5 Outcome of Myasthenic Crisis;189
16.4;REFERENCES;190
17;Thymectomy for Non-thymomatous MG;192
17.1;12.1 INTRODUCTION;192
17.2;12.2 TOTAL THYMECTOMY IS INDICATED;192
17.3;12.3 SURGICAL ANATOMY OF THE THYMUS;193
17.4;12.4 RESECTIONAL POTENTIAL OF THE SURGICAL TECHNIQUES;194
17.4.1;12.4.1 Combined Transcervical and Transsternal Thymectomy;194
17.4.2;12.4.2 Transsternal Thymectomies;194
17.4.3;12.4.3 Transcervical Thymectomies;197
17.4.4;12.4.4 Videoscopic-Assisted Thymectomies;197
17.5;12.5 PROBLEMS IN THE ANALYSIS OF THYMECTOMY FOR MG;198
17.5.1;12.5.1 Data Analysis;198
17.5.2;12.5.2 Other Pitfalls of the Analysis of Results;199
17.6;12.6 THE RESULTS OF THYMECTOMY;200
17.6.1;12.6.1 Introduction;200
17.6.2;12.6.2 Thymectomy Versus Medical Management;201
17.6.3;12.6.3 Comparative Results Following Thymectomy;201
17.7;12.7 INDICATIONS FOR THYMECTOMY;203
17.8;12.8 SELECTING THE THYMECTOMY TECHNIQUE;204
17.9;12.9 RE-OPERATION;205
17.10;12.10 TRACHEOSTOMY: TIMING AND TECHNIQUE;206
17.11;12.11 SURGICAL MANAGEMENT OF THYMOMA;207
17.12;12.12 PERI-OPERATIVE PATIENT MANAGEMENT;207
17.13;12.13 HOSPITAL MORBIDITY AND MORTALITY;208
17.14;12.14 OUTCOMES RESEARCH;209
17.15;12.15 RECOMMENDATIONS;210
17.16;12.16 EPILOGUE;210
17.17;REFERENCES;211
18;Lambert-Eaton Syndrome;216
18.1;13.1 INTRODUCTION;216
18.2;13.2 HISTORY;216
18.3;13.3 PATHOGENESIS;217
18.3.1;13.3.1 Physiology of Neuromuscular Transmission;217
18.3.2;13.3.2 Pathophysiology of Neuromuscular Transmission in LES;218
18.3.3;13.3.3 Immunopathophysiology of LES;220
18.4;13.4 EPIDEMIOLOGY;221
18.5;13.5 CLINICAL PRESENTATION;222
18.5.1;13.5.1 Symptoms and Signs;222
18.5.2;13.5.2 Natural History;223
18.6;13.6 DIAGNOSIS;223
18.6.1;13.6.1 Clinical Manifestations;223
18.6.2;13.6.2 Electrodiagnostic Studies;224
18.6.3;13.6.3 Serological Tests;224
18.6.4;13.6.4 Differential Diagnosis;225
18.7;13.7 TREATMENT;226
18.7.1;13.7.1 Symptomatic Treatment;226
18.7.1.1;13.7.1.1 Cholinesterase Inhibitors;226
18.7.1.2;13.7.1.2 Guanidine;226
18.7.1.3;13.7.1.3 3,4-Diaminopyridine;226
18.7.2;13.7.2 Treatment of the Associated Neoplasm;227
18.7.3;13.7.3 Immunotherapy;227
18.8;REFERENCES;228
19;Acquired Neuromyotonia;233
19.1;14.1 INTRODUCTION;233
19.2;14.2 CLINICAL FEATURES OF NMT AND RELATED SYNDROMES;233
19.2.1;14.2.1 Clinical Manifestations;233
19.2.2;14.2.2 Electrophysiological Features;234
19.3;14.3 SERUM AND CEREBROSPINAL FLUID TESTS;235
19.4;14.4 PHYSIOLOGICAL BASIS OF EXCITABILITY OF MOTOR AXONS IN NMT PATIENTS;235
19.4.1;14.4.1 Clinical and Experimental Evidence for an Autoimmune Basis;236
19.4.1.1;14.4.1.1 Associated Autoimmune Syndromes;236
19.4.1.2;14.4.1.2 Response to Immunotherapies;236
19.4.1.3;14.4.1.3 Passive Transfer of Immunoglobulins to Mice;236
19.5;14.5 ANTIBODIES TO VGKC;237
19.5.1;14.5.1 Other Possible Autoantibodies in NMT;239
19.6;14.6 VGKC ANTIBODIES IN OTHER MUSCLE DISEASES;239
19.7;14.7 CENTRAL NERVOUS SYSTEM ABNORMALITIES IN NMT;240
19.7.1;14.7.1 Morvan’s Syndrome;240
19.7.2;14.7.2 Limbic Symptoms Without Overt Neuromyotonia;241
19.8;14.8 TREATMENT OF NMT;241
19.9;REFERENCES;242
20;Congenital Myasthenic Syndromes;245
20.1;15.1 INTRODUCTION;245
20.2;15.2 MOLECULAR GENETIC CLASSIFICATION;245
20.3;15.3 DIAGNOSTIC METHODS;246
20.4;15.4 PRESYNAPTIC CONGENITAL MYASTHENIC SYNDROMES;247
20.4.1;15.4.1 Congenital Myasthenic Syndrome with Episodic Apnea;247
20.4.1.1;15.4.1.1 Clinical Features;247
20.4.1.2;15.4.1.2 Molecular Basis;247
20.5;15.5 SYNAPTIC CONGENITAL MYASTHENIC SYNDROME;248
20.5.1;15.5.1 Endplate Acetylcholinesterase Deficiency;248
20.5.1.1;15.5.1.1 Clinical Features;248
20.5.1.2;15.5.1.2 Molecular Basis;248
20.6;15.6 POSTSYNAPTIC CONGENITAL MYASTHENIC SYNDROMES;249
20.6.1;15.6.1 Genetic Disorders of the AChR;249
20.6.2;15.6.2 AChR Deficiency due to Mutations in the AChR Subunits;249
20.6.2.1;15.6.2.1 Clinical Features;249
20.6.2.2;15.6.2.2 Molecular Basis;250
20.7;15.7 KINETIC ABNORMALITIES OF THE ACHR;250
20.7.1;15.7.1 Slow-Channel Congenital Myasthenic Syndrome;250
20.7.1.1;15.7.1.1 Clinical Features;250
20.7.1.2;15.7.1.2 Molecular Basis;250
20.7.2;15.7.2 Fast-Channel Congenital Myasthenic Syndrome;252
20.7.2.1;15.7.2.1 Clinical Features;252
20.7.2.2;15.7.2.2 Molecular Basis;252
20.8;15.8 MUTATIONS AFFECTING ACHR CLUSTERING AND SYNAPTIC STRUCTURE;252
20.8.1;15.8.1 AChR Deficiency due to RAPSN Mutations;252
20.8.1.1;15.8.1.1 Clinical Features;252
20.8.1.2;15.8.1.2 Molecular Basis;253
20.8.2;15.8.2 Congenital Myasthenic Syndrome with Proximal Weakness due to Mutations in DOK7;254
20.8.2.1;15.8.2.1 Clinical Features;254
20.8.2.2;15.8.2.2 Molecular Basis;254
20.8.3;15.8.3 Prenatal Hereditary Myasthenia due to Mutations in CHRNG;256
20.8.3.1;15.8.3.1 Clinical features;256
20.8.3.2;15.8.3.2 Molecular Basis;256
20.8.4;15.8.4 Rare Postsynaptic Congenital Myasthenic Syndromes;256
20.9;REFERENCES;257
21;Toxic Neuromuscular Transmission Disorders;260
21.1;16.1 INTRODUCTION;260
21.2;16.2 PHARMACOLOGICAL NEUROTOXICITY;261
21.2.1;16.2.1 Antibiotics;261
21.2.2;16.2.2 Cardiovascular Drugs;262
21.2.3;16.2.3 Cholesterol-Lowering Agents;263
21.2.4;16.2.4 Magnesium;263
21.2.5;16.2.5 Recreational Drugs;264
21.2.6;16.2.6 Rheumatologic Drugs;264
21.2.7;16.2.7 Other;264
21.2.7.1;16.2.7.1 Interferon Alpha;264
21.2.7.2;16.2.7.2 Botulinum Neurotoxin;265
21.3;16.3 BIOLOGICAL NEUROTOXINS;265
21.3.1;16.3.1 Botulism;265
21.3.2;16.3.2 Envenomation;266
21.3.2.1;16.3.2.1 Arthropods;266
21.3.2.2;16.3.2.2 Spider Bites;267
21.3.2.3;16.3.2.3 Tick Paralysis;267
21.3.2.4;16.3.2.4 Scorpion Bites;269
21.3.2.5;16.3.2.5 Snakebites;269
21.3.2.6;16.3.2.6 Marine Toxins;270
21.3.2.7;16.3.2.7 Plant Toxins;271
21.4;16.4 OCCUPATIONAL NEUROTOXINS;271
21.4.1;16.4.1 Heavy Metals;271
21.4.2;16.4.2 Organophosphate and Carbamate Poisoning;272
21.4.2.1;16.4.2.1 Pesticides;273
21.4.2.2;16.4.2.2 Agents of War and Terrorism;273
21.4.2.3;16.4.2.3 Pathophysiology;274
21.4.2.4;16.4.2.4 Treatment;274
21.5;REFERENCES;275
22;The Impact of Myasthenia Gravis on Mood, Cognitive Function, and Quality of Life;283
22.1;17.1 INTRODUCTION;283
22.2;17.2 THE EFFECTS OF PSYCHOLOGICAL HEALTH ON DISEASE;283
22.3;17.3 THE IMPACT OF MG ON THE PSYCHOLOGICAL AND SOCIAL HEALTH OF PATIENTS;285
22.3.1;17.3.1 Psychological Health in MG;285
22.4;17.4 COGNITION AND MENTAL FATIGUE IN MG;288
22.4.1;17.4.1 Neuropsychological Function in MG;289
22.4.2;17.4.2 Fatigue in Myasthenia Gravis;289
22.4.3;17.4.3 The Relationship Between Fatigue and Cognition in Myasthenia Gravis;290
22.5;17.5 FACTORS THAT SUPPORT PSYCHOLOGICAL HEALTH IN MYASTHENIA GRAVIS;291
22.5.1;17.5.1 Perceived Control;291
22.5.2;17.5.2 Uncertainty in Illness;292
22.5.3;17.5.3 Illness Intrusiveness;292
22.5.4;17.5.4 Social Support;293
22.6;17.6 SUMMARY;293
22.7;REFERENCES;294
23;Myasthenia Gravis: Classification and Outcome Measurements;297
23.1;18.1 INTRODUCTION;297
23.2;18.2 CLINICAL CLASSIFICATION OF MG;297
23.3;18.3 QUANTITATIVE MG SCORE (QMG);299
23.4;18.4 MYASTHENIA GRAVIS MANUAL MUSCLE TEST (MG-MMT);300
23.5;18.5 MYASTHENIC MUSCLE SCORE (MMS);300
23.6;18.6 MG ACTIVITY OF DAILY LIVING PROFILE (MG-ADL);301
23.7;18.7 FATIGUE TESTING;301
23.8;18.8 MGFA THERAPY STATUS;302
23.9;18.9 MGFA POSTINTERVENTION STATUS (PIS);303
23.10;REFERENCES;304
24;Index;307