Neuromuscular Junction Disorders: Handbook of Clinical Neurology Vol 91 (Series Editors: Aminoff, Boller and Swaab)

Foreword......Page 1
Preface......Page 2
List of contributors......Page 4
History of human botulism......Page 30
Ham, 1897......Page 31
The motor unit......Page 32
Fish and seafood, 1936......Page 33
Wounds, 1951......Page 34
Infants, 1976......Page 35
Other forms of hyperexcitability......Page 202
Serologic tests......Page 36
Early symptomatic treatments for MG, 1900-1954......Page 37
Thymus involvement, from thymoma to thymectomy, 1901-1950......Page 39
Acetylcholine receptor antibodies......Page 262
But why is the MG patient weak? (1934-1972)......Page 42
Lambert-Eaton myasthenic syndrome, 1951-1989......Page 44
Thymectomy......Page 287
References......Page 48
An introduction to neuromuscular transmission......Page 55
Radioimmunoprecipitation of BuTx-AChR......Page 241
Inherited myokymia (potassium channel mutations)......Page 459
The motor neuron......Page 56
Immunopathology......Page 57
Diagnostic procedures......Page 59
Early evidence for quantal release......Page 60
Spatial aspects of quantal release......Page 61
The SNARE complex......Page 137
Frogs......Page 62
Slow channel congenital myasthenic syndrome......Page 65
Evidence for serum antibodies in SNMG......Page 208
Number of release sites and efficiency of release......Page 66
Statistical aspects of quantal release......Page 68
Diffusion of ACh in the cleft......Page 69
Properties of ACh-gated channels......Page 70
Introduction to the cable properties of the muscle fiber......Page 71
The threshold......Page 73
Folds and their electrical effects......Page 74
Safety factor of neuromuscular transmission: definition and measurement......Page 75
Origin of the concept of a safety factor in excitable cells......Page 76
Blocking action potential generation......Page 77
Estimating transmitter release using electrophysiology......Page 78
Estimating quantal content......Page 79
Comparison of reported values of safety factor at rat NMJs......Page 80
The effects of repetitive activity on release......Page 81
Decreases in quantal content......Page 82
Vesicle pools and their dynamics......Page 83
Mitochondria as modulators of quantal release......Page 84
Autocrine effects on release: purinergic......Page 86
NO as a modulator of release......Page 87
Modulation of quantal release by peptides and proteins......Page 88
Conclusions......Page 89
Release mechanism......Page 90
Postsynaptic specializations......Page 91
Matching NMJ size to muscle fiber size......Page 92
Matching of functional properties of NMJs to activity patterns......Page 93
Development of the motor neuron......Page 94
Synapse formation and elimination......Page 95
Molecular maturation of the developing NMJ......Page 97
Changes in the NMJ affecting safety factor during normal aging......Page 99
Structural reinnervation of the muscle......Page 101
Axon sprouting and muscle fiber type conversion......Page 102
Muscle damage......Page 103
Introduction to the toxins......Page 104
Presynaptic toxins that block release......Page 107
Presynaptic toxins that damage the nerve......Page 108
Overview......Page 109
Reduced quantal content of the EPP......Page 110
Conditions influencing transmitter action......Page 111
Inherited AChR deficiency......Page 112
Prolonged ACh action due to AChE deficiency......Page 113
Conditions influencing NMJ size......Page 114
Post-polio syndrome......Page 115
Many levels of organization contribute to the reliability of neuromuscular transmission......Page 117
Different factors may determine reliability in different species and different stages of development......Page 118
References......Page 119
Patterns of motor innervation......Page 130
Current classification and use of OPs......Page 425
The acetylcholine receptor......Page 280
Acetylcholinesterase......Page 131
Mental status......Page 132
The nerve terminal......Page 133
Coated vesicles......Page 134
Dense-core vesicles......Page 135
Diagnosis......Page 282
Movement of synaptic vesicles......Page 136
Priming of the docked synaptic vesicles......Page 138
Previous reports......Page 139
Systemic distribution of BoNT......Page 140
Histopathology......Page 264
References......Page 193
Intracellular mechanisms of BoNT-LCs......Page 142
Morphologic correlates of quantal transmitter release......Page 143
Endocytotic events and the formation of new synaptic vesicles......Page 144
Noncholinesterase mechanisms of neurotoxicity......Page 145
Synaptic laminins......Page 146
Functional significance of the junctional folds......Page 147
The acetylcholine receptor......Page 149
Structure-function correlations......Page 150
Postsynaptic cytoskeletal components......Page 151
AChR synthesis and degradation......Page 153
The structural development of the NMJ......Page 154
Agrin, MuSK, Rapsyn, and Dok-7......Page 156
References......Page 294
Regulation of synapse specific transcription......Page 158
The metabolic stability of NMJ AChR......Page 159
AChE expression at the NMJ......Page 160
Nerve sprouting......Page 161
References......Page 162
Introduction......Page 176
Endplate potentials and the safety margin of NMT......Page 178
Standard motor NCS......Page 179
Foodborne botulism......Page 312
Repetitive stimulation technique......Page 180
Differential diagnosis......Page 182
Concentric and single fiber EMG......Page 183
Autoimmune myasthenia gravis......Page 184
Seronegative autoimmune myasthenia gravis......Page 185
Prognosis......Page 186
Congenital myasthenic syndromes......Page 187
Original description......Page 188
Endplate acetylcholine esterase deficiency......Page 189
Congenital AChR deficiency......Page 192
AChR-specific T-cell lines......Page 211
Clinical findings of OPIDP in man......Page 444
Immunological principles......Page 196
General overview......Page 240
Pattern recognition receptors of the innate immune system......Page 197
Cholinesterase inhibitors as warfare agents......Page 242
The adaptive immune system: T-cell receptor and antigen presentation......Page 198
T-cell-B-cell cooperation......Page 200
Peripheral tolerance, immunoregulatory mechanisms and autoimmunity......Page 204
Experimental evidence for antibodies in SNMG......Page 205
Functional effects of AChR antibodies......Page 206
Properties of AChR antibodies......Page 207
Antibodies in the Lambert-Eaton myasthenic syndrome......Page 210
Regulation of the T-cell response......Page 212
Morphologic features......Page 213
Cellular responses of the innate immune system in MG......Page 214
Immunogenetics of myasthenia gravis......Page 215
Early notions of the role of the thymus in MG......Page 216
AChR structure......Page 324
Severe combined immunodeficiency mice as a model of MG pathogenesis......Page 218
Pathogenesis of MG with thymic lymphofollicular hyperplasia......Page 219
Pathogenesis of thymoma-associated MG......Page 220
Generalized tetanus......Page 406
Acute EAMG......Page 222
Risk factors for myasthenia gravis and association with other immunological diseases......Page 223
References......Page 224
Pathogenicity and characteristics of AChR antibodies......Page 243
Epidemiological studies based on serological studies......Page 244
Antibodies in seronegative MG......Page 246
Characteristics and mechanisms of action of MuSK antibodies......Page 247
Antibodies to AChRs in SNMG......Page 249
References......Page 466
Clinical presentation......Page 255
Physical findings......Page 256
Oropharyngeal and facial muscle examination......Page 257
Course......Page 258
Infant botulism......Page 363
Pathophysiology of MG......Page 259
Quinine and quinidine......Page 398
Diagnosis......Page 260
Iatrogenic botulism......Page 365
Edrophonium (Tensilon) test......Page 261
Azathioprine......Page 263
Recreational drugs......Page 401
Trafficking and internalization of BoNT-LCs into the neuronal cytosol......Page 376
Genetics of MG......Page 265
Thymoma......Page 266
Hypertension......Page 267
Childhood myasthenia gravis......Page 268
Differential diagnosis of childhood myasthenia......Page 269
``Seronegative´´ MG......Page 270
New immunosuppressive agents......Page 271
Pregnancy in MG......Page 272
Therapeutic strategies......Page 293
Interferon-induced MG......Page 273
References......Page 307
The neuromuscular junction in MG......Page 279
Background......Page 457
Anesthetics, local......Page 281
Bretylium......Page 397
Search for associated conditions......Page 283
Medications that exacerbate LEMS......Page 284
Hormones......Page 285
Adrenal corticosteroids......Page 286
Refractory MG: ``rebooting´´ the immune system with high dose cyclophosphamide......Page 289
Diabetes......Page 290
Pregnancy and neonatal MG......Page 291
Leflunomide......Page 292
Symptoms......Page 299
Pathophysiology......Page 300
Electrodiagnostic tests......Page 302
Voltage-gated calcium channel antibodies......Page 303
Treatment of LEMS......Page 304
MG/LEMS overlap syndrome......Page 306
Events after release of a single ACh quantum......Page 310
Antibiotics......Page 395
Transmitter release by repetitive nerve stimulation......Page 311
Cramp-fasciculation syndrome......Page 314
Clinical features......Page 315
Molecular studies......Page 316
Therapy......Page 317
Severe CMS with reduced quantal release......Page 318
Electrophysiologic features......Page 319
Central effects of botulinum neurotoxins......Page 380
Molecular pathogenesis......Page 321
Diagnosis......Page 322
Mechanisms of receptor activation by ACh......Page 325
Electrophysiologic features......Page 326
Pathogenetic mechanisms......Page 327
Molecular pathogenesis......Page 329
Therapy......Page 330
Fast-channel syndromes......Page 331
Arthropods......Page 332
Fast-channel syndromes due to unstable (mode-switching) kinetics......Page 333
Clinical features......Page 334
Endplate studies......Page 335
Molecular pathogenesis......Page 336
Rapsyn function and structure......Page 337
Clinical features......Page 339
Molecular pathogenesis......Page 340
Clinical features......Page 341
Morphologic features......Page 342
Molecular pathogenesis......Page 343
Diagnosis......Page 344
Clinical features......Page 345
Molecular pathogenesis......Page 346
Relation to other sodium channel disorders......Page 347
Therapy......Page 348
References......Page 349
Introduction......Page 357
Clinical and electromyographic features......Page 358
Carbamates......Page 360
General properties of botulinum neurotoxin......Page 361
Types of botulism......Page 362
Intestinal botulism in adolescents and adults......Page 364
Trimethaphan......Page 366
Diagnosis of botulism......Page 368
Differential diagnosis......Page 370
Pathophysiology of botulism and cellular mechanisms of botulinum neurotoxins......Page 371
Adsorption of botulinum toxin into the lymphatic system......Page 372
Receptors for BoNTs in neuronal cells......Page 374
Synaptic and postsynaptic effects......Page 378
References......Page 381
Pharmacological blockade of neuromuscular transmission......Page 393
Analgesics......Page 394
Anticonvulsants......Page 396
Magnesium......Page 399
Neuromuscular blocking drugs......Page 400
Miscellaneous......Page 402
Botulism......Page 403
Differential diagnosis......Page 404
Pathogenesis......Page 405
Management......Page 407
Spider bites......Page 408
Tick paralysis......Page 409
Snake bites......Page 410
Marine toxins......Page 411
Heavy metals......Page 412
References......Page 413
Use of AChE inhibitors in human medicine......Page 427
Inhibition of cholinesterases by OPs and CMs......Page 428
Reactivation of inhibited cholinesterases by oximes......Page 430
Electrophysiological aspects in peripheral neurotoxicity......Page 431
Electromyography in patients with OP and CM intoxication......Page 432
Clinical presentation......Page 433
Measurement of cholinesterase activity in acutely poisoned patients......Page 435
The necrotizing myopathy......Page 436
Introduction......Page 437
Observations in patients......Page 439
Comparison with other human diseases with impaired neuromuscular transmission......Page 441
Therapeutic considerations......Page 443
Role of OPs and CMs in the Gulf War Syndrome......Page 446
Atropine......Page 447
References......Page 448
PNH secondary to toxins......Page 460
Neuromyotonia (Isaacs syndrome)......Page 461
Morvan syndrome......Page 462
Voltage-gated potassium channel antibodies......Page 463
Hyperexcitability of the motor nerve terminal......Page 464
Summary......Page 465
Index......Page 468