Neuromuscular Junction Disorders: Diagnosis and Treatment PDF

Preface

Diseases of the neuromuscular junction (NMJ) include a large spectrum of acquired and inherited disorders mainly characterized by fluctuating muscle weakness and fatigability of ocular, bulbar or limb muscles. Remarkable progress has been made in our understanding of the pathogenesis of these disorders in recent years. Furthermore, our ability to diagnose these conditions has improved significantly due to the widespread availability of immunologic tests, the use of in vitro electrophysiologic and microstructural studies, and the refinement of sensitive clinical electrodiagnostic tests of neuromuscular transmission. Despite these advances, significant questions remain to be answered by the researcher and the clinician, and disagreement exists amongst specialists regarding therapy and management of patients. This lack of a ‘‘consensus opinion'' makes it difficult for the physician as well as the physician–trainee to approach these disorders in a systematic fashion. Unfortunately, existing textbooks covering this topic do not present a detailed and concise resource for diagnosis and management of these patients.

This book is directed toward advanced students, residents and practitioners of neurology, and in particular those who are involved in the evaluation and care of patients with neuromuscular junction disorders. In response to the ever-increasing mass of neuroscience information, we have attempted to present a monograph offering a concise, comprehensive and up-to-date resource covering all aspects of the diagnosis and clinical management of patients with diseases of the neuromuscular junction with an emphasis on the clinical aspects of this very interesting group of conditions. The basic physiology, anatomy, pathophysiology and immunology pertaining to these diseases are covered in only sufficient depth to allow the clinician to better understand the mechanism of signs and symptoms, the physiologic basis for diagnostic tests, and the rationale for specific treatments.

It is important for the reader to realize that there are a number of approaches to the treatment of the common disorders of neuromuscular transmission. The reason for this disagreement is apparent when one considers the surprising paucity of randomized, controlled, prospective therapeutic studies addressing treatment issues in these diseases. This is particularly apparent in the most common disorder of neuromuscular transmission, myasthenia gravis. For this reason, we present the commonly prescribed treatments for these disorders, the apparent rationale for their use, and the strength of scientific evidence for efficacy of a certain intervention based on the existing international literature. We attempt to explain why all physicians do not use a particular intervention in the same way or in all clinical situations. The reader may develop his/her own approach based on this evidence. The art of providing optimal medical care to this group of patients often lies in deciding when to treat aggressively and when to proceed cautiously and conservatively. The information provided in this book will assist the clinician in making this important therapeutic decision by presenting data regarding the natural history of the disease in question and by detailing the adverse effects of specific treatment modalities. As in other areas of medicine, therapeutic decision-making in disorders of the NMJ is a risk/benefit assessment.

The book is formatted into two main parts. The first part (Chapters 1–3) covers the basic anatomy, physiology, pathophysiology, and diagnosis of the NMJ. The features of presynaptic, synaptic and postsynaptic disorders of the NMJ are discussed in general as an introduction to the more specific coverage of the individual disorders.Abrief coverage of the immunology relevant to the immune-mediated disorders of the NMJ is also presented. Part I ends with a discussion of the diagnostic approach to NMJ disorders including immunologic, pharmacologic and electrophysiologic testing. The information presented in Part I provides a background for understanding concepts presented in Part II. Part II is comprised of the different individual disorders of neuromuscular transmission. Chapters examining myasthenia gravis, Lambert- Eaton syndrome, congenital myasthenic syndromes and human botulism, tetanus and venom poisoning are presented. The final chapter of the book covers the effects of pharmacologic agents on the NMJ. Tables and cross-referenced charts are used to facilitate understanding of the information and to allow for integration of the text.

It is our hope that this volume will aid 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.