Amyotrophic lateral sclerosis (ALS), a slowly progressive disease of variable presentation and rate of progress, has come into the limelight after a century of neglect. Recently, the pace of research has rapidly accelerated, stemming from several parallel lines of research: epidemiology and genetics, neurotrophic factors, excitotoxicity and its integral relation to energy metabolism, free radical homeostasis and its relation to apoptotic cell death, calcium metabolism and cytoskeletal proteins within the motor neuron. Moreover, striking advances in technology for biomedical research are also contributing. From these investigations, reclassification of ALS and motor neuron diseases syndromes is beginning. The introduction of an anti-excitotoxic drug, with an effect in slowing progression of the disease, has made the process of diagnosis and clinical management more important. All these factors have led to a surge in interest and understanding regarding therapy, the maintenance of quality of life in the disease and the ethical issues surrounding the progression of this disease. This book will be of great interest to clinical neurologists and trainees, and to all those concerned in the care of people with ALS.

Nine years have elapsed since the second edition of this book was published. In this time the principal advances in neuromuscular diseases have been in the application of molecular genetics to understanding the aetiology and pathogenesis of this group of disorders. As a result many previously unrecognised disorders have been charac terised. Some clinical syndromes, such as the limb girdle dystrophies, have become better defined. In many such instances the new genetic information has led to major advances in knowledge of the biology of cell structures, for example, the membrane structural and channel proteins. The clinical syndromes themselves, and their patho logical and electrophysiological characteristics, however, remain as important as ever, since they constitute the clinical problem itself and, indeed, the database from which all other concepts emerge. Knowledge of the pathogenesis, genetics, and molecular biology of neuromuscular disorders is essential both in developing and applying new therapies and preventive measures, and in formulating genetic and prognostic advice. However, this informa tion does not necessarily always define clinically useful syndromes. Myotonia, for example, is an electrophysiological finding in some syndromes in which it is un detectable by clinical examination, although the phenomenon itself was originally defined as a clinical entity. The limb girdle muscular dystrophy syndromes can be defined by severity, distribution of weakness, age of onset, sex distribution and other characteristics and many of these can be better understood by study of the under lying defect in cell structural proteins.

Hughlings Jackson, the noted English neurologist, fathered many ideas that today still underlie our understanding of common clinical phenomena. This is a reappraisal of Jackson's work, both within its historical framework and in light of modern concepts of neurology. The approach is new, combining historical, clinical and basic scientific information in one synthesis on the organization and function of the nervous system. The concept of levels of function is addressed, specifically with regard to areas of brain function; and the hierarchical strategy is considered as part of the current concept of a distributed system of neurons. Clinicians and scientists alike will find much food for thought in this modern treatise of Jacksonian concepts.

Amyotrophic lateral sclerosis or motor neurone disease is one of the most debilitating and devastating of the neurological diseases. The only comprehensive textbook available on the topic, this completely reorganized and expanded new edition examines all aspects of ALS from pathology to patient care and provides the reader with a ready reference to help with the difficulties encountered in patient diagnosis and treatment. Undoubtedly an important work in the field, this book will be of great interest to clinical neurologists and trainees, and to all those concerned with the care of people with ALS.

Here is the first book to provide a comprehensive overview of the clinical, pathological, and research aspects of motor neuron disease (MND). The text contains all essential features of the anatomy, physiology, pharmacology and toxicology of the motor system, a full description of MND and its variants, as well as historical developments and a review of the current concepts and controversies. This book comes at a time of increasing interest in neurodegenerative disorders and MND in particular. It will prove a key reference book with an integrated overview of the field, and will be indispensable to practicing neurologists, researchers, and all those with an interest in MND.

Museie biopsy is a long-established technique in clinical practice having been introduced by Duchenne in 1868 (Arch. Gen. Med., 11, 5-179). However, the needle method used by Duchenne was not generally adopted, although Shank and Hoagland described a similar technique in 1943 (Science, 98, 592), and open muscle biopsy has for long been preferred in clinical practice, even with the advent of newer needle biopsy methods (Bergstrom, 1962, Scand. J. Clin. Lab. Invest., 14, Suppl. 68, 1-110). The development of enzyme histochemical techniques has contributed greatly to knowledge of muscle pathology. More recently electron microscopy and immunocytochemistry have also been applied to clinical diagnosis of neuromuscular disease. This book is intended to serve as a practical guide in muscle pathology, particularly for histopathologists, and for those in training. As enzyme histochemistry has become more widely available, formalin-fixed methods have become less frequently used in muscle biopsy work. In this new edition of Muscle Biopsy Pathology we have taken account of the advances in classification and histological technique, and in knowledge of neuromuscular diseases, that have emerged since the first editionwas published in 1984. We hope that this book will continue to be used as a practical guide in the diagnosis and understanding of these disorders. 1. Introduction 1. 1 Generalfeatures of muscle The differentiation of musde into red and white types is a feature of all vertebrates and, indeed, of chordates.

Natural history and treatment outcome of disease are of critical importance to patients, clinicians and health care providers across the full range of medical disciplines. In many specialties, such as neurology and neurosurgery, this sort of information can be hard to obtain in the absence of extensive outcome studies and agreed measures of outcome in different conditions. This volume seeks to help inform about effective care and rehabilitation by providing a succinct review of whatever data is available for the majority of conditions encountered in clinical practice. Particular attention has been given to the evaluation of the severity and outcome of each disorder and to advise on comparing risks and benefits of treatment. This resource will prove invaluable to all involved in informing patients of treatment options and making important cost-efficient decisions on care. It should also be welcomed in the planning of clinical trials for potential new therapies and as a reference in medicolegal spheres.

Natural history and treatment outcome of disease are of critical importance to patients, clinicians and health care providers across the full range of medical disciplines. In many specialties, such as neurology and neurosurgery, this sort of information can be hard to obtain in the absence of extensive outcome studies and agreed measures of outcome in different conditions. This volume seeks to help inform about effective care and rehabilitation by providing a succinct review of whatever data is available for the majority of conditions encountered in clinical practice. Particular attention has been given to the evaluation of the severity and outcome of each disorder and to advise on comparing risks and benefits of treatment. This resource will prove invaluable to all involved in informing patients of treatment options and making important cost-efficient decisions on care. It should also be welcomed in the planning of clinical trials for potential new therapies and as a reference in medicolegal spheres.