Handbook of Clinical Neurology, Vol. 115 (3rd series)Peripheral Nerve DisordersG. Said and C. Krarup, Editors© 2013 Elsevier B.V. All rights reserved

Chapter 1

Prelude to the peripheral neuropathies

ARTHUR K. ASBURY1 AND MICHAEL J. AMINOFF2

1Department of Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA2Department of Neurology, School of Medicine, University of California, San Francisco, CA, USA

Recognition of, and interest in, peripheral neuropathiesbegan to evolve almost two centuries ago, mainly inthe UK and the rest of Europe, and then in the USA.The newly developing techniques of histopathology dur-ing the 19th century made it possible to study peripheralnerves and nerve roots at autopsy and in experimentalstudies in animals. Clinicopathological studies, notablyby Jean-Martin Charcot and his students in Paris but alsoby others, allowed correlation with the clinical findingsrecorded during life. Even persons who had recoveredfrom a nerve root or nerve trunk neuropathy with min-imal or no persisting symptoms or findings, and whothen lived for many years, were often found at autopsyto have residual pathological findings in the previouslyaffected neural structures. The clinicopathologicalapproach of correlating the clinical features with thepostmortem neuropathological findings has now beenin place for over 150 years. It has formed the base ofmuch of the knowledge of peripheral neuropathy, butit has not indicated how to diagnose, manage, and ulti-mately reverse all such disorders.

The remarkably insightful clinical studies by SilasWeir Mitchell and his colleagues on casualties of theAmerican Civil War in the latter half of the 19th centuryalso led to further interest in the peripheral nervous sys-tem, at least for a time. Mitchell’s work with GeorgeMorehouse and William Keen was summarized in theirpioneering bookGunshot Wounds, and Other Injuries ofNerves (1864), which contained the first descriptions ofcausalgia. Mitchell subsequently extended this into hisdefinitive Injuries of Nerves and Their Consequences(1872), the first substantive work detailing the symp-toms, signs, treatment, and outcome of nerve injuries.

Despite these advances on both sides of the Atlantic,there was little interest in the peripheral nervous systemfor many years. Indeed, until the 1950s, peripheral neu-ropathies were of relatively minor interest to most neu-rologists, who were occupied principally with the many

disorders affecting the central nervous system. As such,peripheral nerve disorders were not given the attentionthey deserved, and patients with these disorders wereoften managed by other physicians, particularly inter-nists and general physicians.

This situation in 1950 was particularly evident in theUSA. There, physicians who wished to specialize in thedisorders of the nervous systemgenerally received 2 yearsof training, 1 year of neurology and 1 year of psychiatry,and often became skilled in neither. Those specialists ofyesteryear were little interested in, and poorly knowledge-able of, disorders of the peripheral nervous system. Sincethat time, however� with the advent of precise, objectivemethods of studying peripheral nerve function � thesedisorders have assumed greater importance.

In the 19th and 20th centuries, basic and clinical neuro-physiologists began to develop techniques that allowedfor a greater understanding of peripheral nerve functionand led to quantitative methods for evaluating neuromus-cular function in health and disease. GuillaumeDuchennede Boulogne in Paris, Emil Heinrich du Bois-Reymond inBerlin, and Wilhelm Erb of Heidelberg were early (19thcentury) pioneers in the field of electrodiagnosis or elec-trophysiology, followed later by Charles Sherrington andEdgar Adrian in Britain and by Joseph Erlanger, HerbertGasser, and George Bishop in the USA, who worked onthe selective functions of single nerve fibers and relatedissues. The mechanism of nerve conduction and theevents at the neuromuscular junction only became clearerin the latter half of the 20th century, however, with thefundamental studies of J. Z. Young, Alan Hodgkin,Andrew Huxley, Bernard Katz, Ricardo Miledi, andmany other physiologists and scientists. Adrian andBronkrecorded the electrical activity of motor units with a con-centric needle electrode in 1929, allowing the recruitmentpattern of motor units and regulation of muscle force tobe studied. Within 10 years, Derek Denny-Brown haddescribed the electrophysiological hallmark of fibrillation

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and fasciculation potentials in muscle, and shortly there-after Fritz Buchthal in Copenhagen began describingthe electrophysiological features of a number of neuro-muscular diseases, often in a quantitative manner. ErikKugelberg in Stockholm, Roger Gilliatt and P.K. Thomasin London, and Edward Lambert in Rochester, Minne-sota, were other pioneers in clinical neurophysiology,and their work led to the widespread clinical applicationof objective techniques for measuring peripheral nervefunction and permitted the characterization and localiza-tion of disordered function, even when the disorder hadnot yet become manifest clinically.

Detailed pathological, ultrastructural,microbiological,immunological, and genetic studies soon followed. Thesewere important, but as many of the leaders in these fieldsare still living � and indeed have contributed to thesevolumes � they will not be named individually here.The reader will be able to recognize their contributionsin the chapters that follow. Through the application ofthese various techniques, many new disorders have cometo be recognized, as is discussed in later chapters. Thesedevelopments aroused the interests of young trainees inneurology, and the subspecialty of neuromuscular dis-eases is now one of the most popular areas in neurology,with neuromuscular specialists making up somethingmore than 15% of all fully-trained neurologists.

The body of knowledge concerning neuromuscularmedicine in general and peripheral neuropathies in

4 A.K. ASBURY A

particular has grown exceptionally rapidly over the pastfive or six decades, as can be seen from the breadth ofthis book, and this already large body of knowledge willsurely continue to grow. More than 50 chapters follow-ing this one set forth in great detail the most modernways of evaluating, characterizing, distinguishing, andmanaging the numerous specific neuropathic syndromesthat have been described. Some disorders are related tosystemic disorders such as porphyria, uremia, sarcoido-sis, systemic amyloidosis, diabetes mellitus, or vasculi-tis. Others are due to exogenous toxins such as alcoholor other drugs such as long-term anti-epileptic medica-tion. The list of possible causes underlying a given poly-neuropathy is large. It is easy for physicians to overlookthe responsible culprit in individual cases. Many neurop-athies are amenable to treatment or avoidance of theresponsible cause. Virtually all of the irreversible neu-ropathies can be managed by specialists to lessen thesymptoms andminimize the difficulties of everyday life.

The editors of this two-volume work have taken on anenormous task in organizing and summarizing present-day knowledge of the peripheral nervous system and themyriad disorders that affect it. Their work will benefitnot only the medical and scientific community, forwhom these volumes will serve as a useful reference,but also members of the general public who will benefitby the application of this knowledge in an individual set-ting. They are to be congratulated on their achievement.

M.J. AMINOFF