[...]... the Neuromuscular Junction I Introduction II The Neuromuscular Junction: A Specialized Synapse III Anatomy of the Neuromuscular Junction IV Physiology of Neuromuscular Transmission References 1 1 1 3 14 30 2 Pathophysiology of Neuromuscular Junction Disorders I Introduction II Prejunctional (Neurogenic) Neuromuscular Transmission Failure III Presynaptic Disorders IV Synaptic Disorders V Postsynaptic Disorders. .. students and clinicians to gain a better understanding of the clinical evaluation, investigation, diagnosis and treatment of diseases of the NMJ, and that investigators and more experienced clinicians will find it a valuable resource Matthew N Meriggioli James F Howard, Jr C Michel Harper Contents Foreword Preface iii v PART I GENERAL ASPECTS OF DISORDERS OF THE NEUROMUSCULAR JUNCTION 1 Anatomy and Physiology... Pharmacological Neurotoxicology of Neuromuscular Transmission I Introduction II Pharmacologic Blockade of Neuromuscular Transmission References Index 263 263 263 283 291 1 Anatomy and Physiology of the Neuromuscular Junction I INTRODUCTION Clinicians who regularly care for patients with disorders of the neuromuscular junction (NMJ) realize the importance of understanding its anatomy and physiology A working... Epidemiology and Natural History IV Etiology and Immunopathogenesis V Clinical Presentation VI Diagnosis VII Treatment and Management VIII Clinical Management in Specific Situations IX Overview References 101 101 102 103 104 107 114 116 134 145 146 5 Lambert-Eaton Syndrome I Introduction II History III Epidemiology and Natural History IV Etiology and Immunopathogenesis V Clinical Presentation VI Diagnosis VII Treatment. .. VII Basic Immune Mechanisms in Disorders of the Neuromuscular Junction VIII Overview References 3 Diagnostic Tests for Neuromuscular Junction Disorders I Introduction II Physiology of Neuromuscular Transmission Revisited III Diagnostic Testing IV Comparison of Diagnostic Tests in Myasthenia Gravis V Overview References 48 52 55 55 59 59 59 60 94 94 95 PART II DISORDERS OF NEUROMUSCULAR TRANSMISSION 4... clinically relevant aspects of the anatomy and physiology of normal neuromuscular transmission follows A number of clinical examples are provided to illustrate the application of anatomic and physiologic concepts to the diagnosis and treatment of patients with NMJ disease II THE NEUROMUSCULAR JUNCTION: A SPECIALIZED SYNAPSE There are two main types of synapses: electrical and chemical At an electrical synapse,... metabolic demands of transmitter synthesis and Anatomy and Physiology of Neuromuscular Junction 5 Figure 1.4 Diagrammatic representation of the major components of the mammalian neuromuscular junction The nerve terminal is unmyelinated but is capped by a Schwann cell It is directly aligned with the endplate region of a muscle fiber A basement membrane overlies the Schwann cell laterally and becomes... medial rectus weakness and fatigable right ptosis with normal facial, bulbar, and extremity muscle strength AChR binding antibodies are negative, but electrodiagnostic studies confirm a defect in neuromuscular transmission Anatomy and Physiology of Neuromuscular Junction 11 His symptoms respond initially to treatment with AChE inhibitors but eventually recur despite dose escalation Treatment with high-dose... synaptic clefts are the spaces between the junctional folds (JF) A giant synaptic vesicle (G) is seen within the presynaptic nerve terminal (From Ref 1.) Anatomy and Physiology of Neuromuscular Junction 3 Figure 1.2 Diagrammatic representation of Fig 1.1 illustrating the components of the neuromuscular junction: (1) the presynaptic nerve terminal, (2) the synaptic space, and (3) the postsynaptic muscle membrane... of these receptors on the crests of the postsynaptic junctional folds is absolutely required for normal neuromuscular transmission Anatomy and Physiology of Neuromuscular Junction 13 At the endplate, individual AChRs are connected to each other and anchored to the muscle fiber cytoskeleton Rapsyn, a 43-kDa protein, connects AChRs to one another and also connects the clusters of AChRs to the muscle . and William C. Koller 60. Clinical Neurovirology, edited by Avindra Nath and Joseph R. Berger 61. Neuromuscular Junction Disorders: Diagnosis and Treatment, . ASPECTS OF DISORDERS OF THE NEUROMUSCULAR JUNCTION 1. Anatomy and Physiology of the Neuromuscular Junction 1 I. Introduction 1 II. The Neuromuscular Junction: