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| Contributors | |
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| The Anatomy and Molecular Architecture of the Neuromuscular Junction | |
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| Basic Concepts | |
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| The Innervation of Muscle | |
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| The Presynaptic Region | |
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| The Nerve Terminal | |
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| Giant Synaptic Vesicles | |
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| Coated Vesicles | |
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| Dense-core Vesicles | |
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| Small Clear Synaptic Vesicles | |
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| Vesicular ACh Uptake | |
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| Synaptic Vesicle Pools | |
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| Synaptic Vesicles Move to and Dock at die Active Zones | |
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| Exocytotic Machinery | |
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| SNARE Complex | |
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| Priming of Docked Synaptic Vesicles | |
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| Synaptotagmin-1 | |
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| Steps in Exocytosis | |
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| Other Proteins Modulating Exocytosis | |
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| Presynaptic Cytoskeletal Components | |
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| The Active Zone and die Voltage-Gated Ca<sup>2+</sup> Channels | |
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| Voltage-gated K<sup>+</sup> Channels of die Presynaptic Membrane | |
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| Endocytotic Events and die Formation of New Synaptic Vesicles | |
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| The Synaptic Space | |
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| Synaptic Basal Lamina | |
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| Asymmetric AChE | |
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| Collagen XIII | |
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| Synaptic Laminins | |
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| The Postsynaptic Region | |
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| The Junctional Folds and Their Cytoskeletal Components | |
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| AChRs on the Junctional Folds | |
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| The Saturating Disk Model of Neuromuscular Transmission | |
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| Regulation of die Distribution and Subunit Composition of AChR | |
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| The Postsynaptic Cytoskeleton | |
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| The Junctional Sarcoplasm | |
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| AChR Syndiesis and Degradation | |
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| Signaling Mechanisms at the Neuromuscular Junction | |
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| Agrin, MuSK, and LRP4 | |
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| Dok-7 and Its Downstream Activators Crk, Crk-L, and Tidl | |
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| The Neuregulin/ARIA Signaling Pathway | |
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| Electrodiagnosis of Myasthenic Disorders | |
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| Introduction | |
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| Standard Motor Nerve Conduction Studies | |
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| Repetitive Compound Muscle Action Potentials | |
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| Repetitive Nerve Stimulation Studies | |
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| The Safety Margin of Neuromuscular Transmission | |
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| Pseudofacilitation vs. True Facilitation | |
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| Drug Effects | |
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| Choice of Muscles and Stimulation Sites | |
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| Troubleshooting Technical Problems | |
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| Special Considerations in Infants and Young Children | |
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| What Constitutes an Adequate Repetitive Stimulation Examination? | |
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| Needle Electromyography | |
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| The Properties of Motor Unit Potentials | |
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| MUP Changes Observed in Myasthenic Disorders | |
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| Single-Fiber Electromyography | |
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| Electrodiagnostic Findings in Specific Myasthenic Disorders | |
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| Autoimmune Myasthenia Gravis | |
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| Lambert-Eaton Syndrome | |
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| Botulism | |
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| Congenital Myasthenic Syndromes | |
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| The Immunopathogenesis of Myasthenia Gravis | |
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| Introduction | |
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| Immunological Principles | |
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| Basic Properties of B Cells and T Cells | |
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| The Intrathymic Differentiation of T Cells | |
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| Tolerance and Autoimmunity | |
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| Antigen Recognition by B Cells and Antibodies | |
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| Antigen Recognition by T Cells | |
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| Cooperation of B Cells and Helper T Cells | |
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| Myasthenia with Thymic Hyperplasia | |
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| Early Notions on the Role of the Thymus in MG | |
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| Intrathymic Myoid Cells and AChR | |
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| Key Tenets of "Intrathymic Pathogenesis" | |
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| Intrathymic Antigen Presentation | |
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| Thymic Autoantibody Production | |
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| Intrathymic Germinal Centers and B Cells | |
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| Human MG Thymus Grafted into SCID Mice | |
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| Two-Step Model of Intrathymic Autosensitization | |
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| "Promiscuous" Expression of Autoantigens by Medullary Thymic Epithelial Cells | |
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| Role of Regulatory T Cells (Treg) | |
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| Possible -Role of Viruses | |
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| Myasthenia Gravis with Thymoma | |
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| Epidemiology | |
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| Classification of Thymomas | |
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| Thymoma Features Associated with MG | |
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| Autoantibodies in Thymoma-Associated MG | |
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| Pathogenesis of Thymoma-Associated MG | |
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| Models of Tolerance Breakdown in TAMG | |
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| B Cell Responses In Myasthenia Gravis | |
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| General Features of Anti-AChR Antibodies | |
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| Epitopes Recognized by Anti-AChR Antibodies | |
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| Anti-Striational Antibodies | |
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| "MuSK-positive" and "Seronegative" Myasthenia | |
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| T Cell Responses in Myasthenia Gravis | |
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| AChR-Specific T Cells | |
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| Antigenic Epitopes Recognized by AChR-Specific T Cells | |
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| Cooperation Between B Cells and T Cells In MG | |
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| Pathogenic Effects of the Anti-Achr Antibodies | |
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| Summary | |
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| Natural History of Myasthenia Gravis | |
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| The History and "Natural" History of Myasthenia Gravis | |
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| Epidemiology | |
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| Onset | |
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| Ocular Myasthenia | |
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| Generalized Myasthenia Gravis | |
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| Time Between Onset and Generalized Manifestations | |
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| Signs and Symptoms | |
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| Exacerbation | |
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| Remission | |
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| Course | |
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| Mortality | |
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| Specific Clinical Situations | |
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| MuSK-Myasdienia Gravis | |
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| Pregnancy | |
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| Neonatal Myasthenia Gravis | |
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| Age-Related Issues for Myasthenia Gravis | |
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| Familial Incidence of Myasthenia Gravis | |
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| Disorders Associated with Myasthenia Gravis | |
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| Thymoma | |
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| Thyroid Disorders | |
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| Odier Autoimmune Diseases | |
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| Summary | |
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| The Diagnosis of Myasthenia Gravis and Other | |
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| Disorders of Neuromuscular Transmission | |
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| Introduction and Historical Background | |
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| Clinical Presentation | |
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| Myasthenia Gravis | |
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| MG Caused by Antibodies to Muscle-Specific Protein Kinase (MuSK-MG) | |
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| Physical Findings | |
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| Myasthenia Gravis | |
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| MuSK-MG | |
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| Differential Diagnosis | |
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| Differential Diagnosis of Ptosis | |
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| Differential Diagnosis of Diplopia | |
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| Differential Diagnosis of Dysarthria and Dysphagia | |
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| Differential Diagnosis of Isolated Respiratory Muscle Weakness | |
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| Differential Diagnosis of Fatigue | |
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| Differential Diagnosis of Mimicking Disorders | |
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| Diagnostic Studies for Myasthenia Gravis | |
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| Edrophonium Test | |
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| Antibody Tests | |
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| Electrodiagnostic Testing | |
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| Ocular Cooling (Ice-Pack Test) | |
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| Comparison of Diagnostic Techniques | |
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| Other Diagnostic Tests | |
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| 6. Therapy of Myasthenia Gravis | |
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| Introduction | |
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| Pathogensis of MG | |
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| Immune Pathogenesis of MG | |
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| Origin of MG | |
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| Treatment of MG | |
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| Prehminaries | |
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| Treatment Strategies | |
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| Treating MG in Special Situations | |
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| Ocular Myasthenia | |
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| Management of Associated Conditions Co-morbidities | |
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| Drug Interactions | |
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| Pregnancy and Neonatal MG | |
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| Myasdienic Crisis | |
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| Future Prospects for Treatment of MG | |
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| The Paradox of Difficulty in Obtaining Approval of MG Treatments | |
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| Conclusions | |
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| The Lambert-Eaton Myasthenic Syndrome | |
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| History | |
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| Clinical Features | |
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| Symptoms | |
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| Physical findings | |
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| Cancer-Associated Lems (Ca-Lems) | |
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| Non-Cancer Associated or Autoimmune Lems (Nca-Lems) | |
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| Epidemiology | |
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| Pathophysiology and Immunopathology | |
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| Electrodiagnostic Findings | |
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| Repetitive Nerve Stimulation Testing Needle Electromyography (EMG) | |
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| Single-fiber Electromyography | |
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| Electromyograpbic Quantitation of severity | |
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| Serological Testing | |
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| Voltage-gated Calcium Channel Antibodies | |
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| SOX1 Antibodies | |
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| Other Tests | |
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| Differential Diagnosis | |
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| MG/LEMS Overlap | |
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| Treatment | |
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| Cancer | |
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| Symptomatic Treatment | |
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| Immunotherapy | |
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| Agents That May Worsen Lems | |
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| Prognosis | |
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| Summary | |
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| Congenital Myasthenic Syndromes | |
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| A Brief History of the Congenital Myasthenic Syndromes | |
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| Mechanisms Compromising the Safety Margin of Neuromuscular Transmission | |
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| The Classification of Congenital Myasthenic Syndromes | |
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| The Investigation of Congenital Myasthenic Syndromes | |
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| Clinical Observations | |
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| Morphology <sup>125</sup>I-�-bgt Binding Sites per Endplate | |
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| In Vitro Electrophysiology Studies | |
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| Molecular Genetic Studies | |
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| Presynaptic CMS | |
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| CMS Caused by Defects in Choline Acetyltransferase (ChAT) | |
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| Paucity of Synaptic Vesicles and Reduced Quantal Release | |
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| Congenital Myasdienic Syndrome Resembling the Lambert-Eaton Syndrome | |
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| Synaptic Basal-Lamina-Associated CMS | |
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| Endplate Acetylcholinesterase Deficiency | |
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| Defects in �2-Laminin | |
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| Postsynaptic CMS Caused by Mutations in Achr | |
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| Slow-Channel Syndromes | |
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| Fast-Channel Syndromes | |
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| AChR Deficiency Caused by Recessive | |
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| Mutations in AChR Subunits | |
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| Escobar Syndrome | |
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| CMS Caused by Defects in Rapsyn | |
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| Defects in Mechanisms Governing Endplate Development and Maintenance | |
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| CMS Caused by Defects in Agrin | |
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| CMS Caused by Defects in MuSK | |
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| CMS Caused by Defects in Dok-7 | |
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| CMS Caused by Defects in die Hexosamine Biosynthetic Pathway | |
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| Miscellaneous Rare Congenital Myasthenic Syndromes | |
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| Sodium-Channel Myasdienia | |
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| CMS Caused by Plectin Deficiency | |
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| CMS Associated widi Centronuclear Myopatliy (CNM) | |
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| Endplate Acetylcholine Receptor, A Target for Myasthenic Disorders: Structural and Mechanistic Essentials | |
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| Introduction | |
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| AChR Structure | |
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| AChR Structure at die Atomic Scale | |
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| Pore Domain | |
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| Ligand-binding Domain | |
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| Interface Between Ligand-binding and Pore Domains | |
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| Mechanism of AChR Activation | |
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| Intermediate State Between Closed and Open States | |
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| Links Between Agonist Binding and Channel Opening | |
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| AChR Disease Mechanisms | |
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| Slow-channel CMS | |
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| Fast-channel CMS | |
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| Perspective | |
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| 10. Peripheral Nerve Hyperexcitability Syndromes | |
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| Background | |
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| Clinical and Electrodiagnostic Features of Hyperexcitability Syndromes | |
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| Pathophysiology | |
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| Hyperexcitability of die Motor Nerve Terminal | |
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| Hyperexcitability of Neuromuscular Junction | |
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| Inherited Myokymia (Potassium-Channel Mutations) | |
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| Autoimmune PNH | |
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| Neuromyotonia (Isaacs Syndrome) | |
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| Morvan Syndrome | |
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| Cramp-fasciculation | |
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| Syndrome | |
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| Antibodies against Voltage-gated Potassium Channel Complex Proteins | |
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| Other Antibodies | |
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| PNH Secondary to Toxins | |
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| Hyperexcitability due to Peripheral Nerve Disorders | |
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| Other Peripheral Hyperexcitability Syndromes | |
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| Treatment Options for Hyperexcitability Syndromes | |
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| Summary | |
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| Effects of Anti-Ganglioside Antibodies at the Neuromuscular Junction | |
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| Neuronal Gangliosides | |
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| Structure and Synthesis | |
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| Localization | |
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| Physiological Functions | |
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| Peripehral Nerve Disorders Associated With Anti-Ganglioside Antibodies | |
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| Experimental Evidence for Anti-Ganglioside Antibody-Mediated Attack of NMJs | |
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| Clinical Evidence for Nmj Synaptopathy in Anti-Ganglioside Antibody-Mediated Human Neuropathy | |
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| Comparing Clinical and Experimental Electrophysiological Findings | |
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| Therapeutic Considerations | |
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| Index | |