Surgical Disorders of the Peripheral Nerves, Second Edition

Surgical Disorders of the Peripheral Nerves Second Edition

Rolfe Birch

Surgical Disorders of the Peripheral Nerves Second Edition

Author Rolfe Birch M. Chir, FRCP&S (Glas), FRCS (Edin), FRCS (Eng) by election Professor in Neurological Orthopaedic Surgery, University College, London and Visiting Professor, Department of Academic Neurology, Imperial College, London and Honorary Orthopaedic Consultant, Hospital for Sick Children Great Ormond Street, London and The National Hospital for Nervous Diseases, Queen Square, London and Raigmore Hospital, Inverness and Honorary Orthopaedic Surgeon to the Royal Navy and Consultant in Charge, War Nerve Injuries Clinic at the Defence Medical Rehabilitation Centre, Headley Court, Leatherhead, Surrey

ISBN  978-1-84882-107-1 e-ISBN  978-1-84882-108-8 DOI  10.1007/978-1-84882-108-8 Springer London Dordrecht Heidelberg New York British Library Cataloguing in Publication Data A catalogue record for this book is available from the British Library Library of Congress Control Number: 2010933604 © Springer-Verlag London Limited 2011 1st edition by R. Birch, G. Bonney and C.B. Wynn Parry published in 1998 by Churchill Livingstone, ISBN 978-0-443-04443-4 Apart from any fair dealing for the purposes of research or private study, or criticism or review, as permitted under the Copyright, Designs and Patents Act 1988, this publication may only be reproduced, stored or transmitted, in any form or by any means, with the prior permission in writing of the publishers, or in the case of reprographic reproduction in accordance with the terms of licenses issued by the Copyright Licensing Agency. Enquiries concerning reproduction outside those terms should be sent to the publishers. The use of registered names, trademarks, etc., in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant laws and regulations and therefore free for general use. Product liability: The publisher can give no guarantee for information about drug dosage and application thereof contained in this book. In every individual case the respective user must check its accuracy by consulting other pharmaceutical literature. Cover design: xxxxxx Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com)

In memoriam George Bonney

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Preface to the First Edition

“Opportunity comes to the mind prepared.” Opportunity came in full measure to H.J. Seddon with his appointment as surgeon in charge of the Medical Research Coucil’s (MRC) Peripheral Nerve Injury Unit in Oxford during the Second World War (1939–1945). It was after all in the Oxford of those days that J.Z. Young was doing the work on the nervous system that was to be the beginning of so many of the later developments in neuroanatomy and neurophysiology. The rewards of the MRC’s far sighted planning were abundant: to Seddon in particular was due that happy result. He was, however, the first to acknowledge the fortunate circumstances that enabled him to undertake the work in the company of so many doctors and scientists distinguished in the fields of anatomy, physiology and pathology of the peripheral nerves. He acknowledged too his debt to two great colleagues in clinical medicine: Hugh Cairns and George Riddoch. It was also fortunate that the Oxford unit was not allowed to die away at the end of the War, and that Seddon was able to continue at the Royal National Orthopaedic Hospital and the Institute of Orthopaedics the work that had begun and flourished at Oxford. After Seddon’s retirement his close colleague Donal Brooks and others developed and extended his work in London, while in other centres those who had worked with these men made their own contributions. Sadly, the bright hope that with introduction of the National Health Service the planning that contributed so much to the earlier success would be continued, has withered and died. Seddon’s belief that “the necessity for this segregation, this concentration of cases” would be recognised has been proved wrong. The hope may finally have been extinguished in this country by the introduction through the National Health Service Act of 1990 of an artificial internal market in health care, with competition between “providers of health care” and by the necessary corollary of the forced Gleichschaltung of the medical profession. Seddon’s firmness of purpose, clarity of thought, immense capacity for sustained hard work and powers of organisation were shown in “Peripheral Nerve Injuries” (1954) presented by the Nerve Injuries Committee of the Medical Research Council under his chairmanship. These characteristics were complemented by the qualities of those who collaborated in the work at Oxford. In the preface to the first edition of Surgical Disorders, Seddon paid generous tribute to J.Z. Young, P.B. Medawar, Graham Weddell and others. A special prominence was accorded to the contribution made by Donal Brooks. One who knew and worked with both has recorded the view that even that recognition was inadequate. He has made the disrespectful comparison of Brooks and Seddon with Jeeves and Wooster, and others who shared that experience may recognise the origins of the impious thought. Seddon’s character was of course the antithesis of that of Wooster, but those who saw these men at work cannot doubt that the calm guidance from the Irish Jeeves greatly influenced Seddon’s work and actions. Both editions of Surgical Disorders bear the mark of Seddon’s personality: the ordered thought; the meticulous observation and recording; the awareness of the ambient scientific field; the occasional dogmatic assertion; the love of tabulation. No one can read the book and vii

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not admire its depth and scope; no one can read it without astonishment at the comprehensive manner in which the subject is treated. One finds in it flashes of insight which, thought by the reader to have originated with him or her, turn out to be the subliminal origins of that thought. Some may consider it too bold an undertaking to attempt the revision of a work which is a classic of British clinical science and an abiding monument to Seddon’s work and leadership. However, things have moved on since 1975. Advances have been made in this country. In the field of disorders of peripheral nerves by Eames, Fullerton, Gamble, Gilliatt, Thomas, Urich and others. In continental Europe the work of Brunelli, Carlstedt, Gilbert, Hagbarth, Landi, Lundborg, Millesi, Morelli, Narakas, Slooff, Torebjörk, Wallin and others has opened new possibilities and destroyed old certainties. In the USA, Gelberman, Kline, Leffert, Omer, Spinner, Terzis, Wilbourn and many others have made massive contributions. In Canada, Hudson and Mackinnon have made great clinical and experimental contributions. In Australia, the doctrine of primary repair of injuries in the upper limb and hand was developed by Rank, O’Brien and others. In China, where the feasibility of “replantation” was first demonstrated, Professor Gu of Shanghai has made and continues to make advances in the field. The development of neurotisation was largely due to work in Japan, where Nagano and Sugioka and many others continue that and other work. In particular, ideas about all types of lesion of the brachial plexus have changed; conceptions of pain mechanisms have developed, and much enlightenment has come to the understanding of the pathology of tumours. Lastly, and most sadly the incidence of “iatrogenic” lesions has greatly increased, though in this connection great advances have been made in the treatment of birth injuries of the brachial plexus. The authors of the present work hope that they may have succeeded in restoring Surgical Disorders to its place as the British text on the present state of affairs in the field. George Bonney had the privilege and pleasure and occasional pain, of working with Seddon; Christopher Wynn Parry came to the Royal National Orthopaedic Hospital at the time of its Renaissance under the leadership of Lipmann Kessel when new fields in neurophysiology, in the treatment of pain and in the surgery of the brachial plexus were being explored; Rolfe Birch came to the field at St Mary’s and the Royal National Orthopaedic Hospitals armed with experience in microsurgery, and in histological and electron-microscopic techniques. Most of the work on the results of which we have drawn was done at St Mary’s and the Royal National Orthoapaedic Hospitals. The original layout of the book has largely been retained, but the text has been entirely rewritten. Chapters on “iatrogenic” lesions, on birth injuries of the brachial plexus and on recovery of sensibility after repair have been added. The subjects of pain and of tumours are considered in more depth than formerly. The subject of electrophysiological examination is considered by an expert in the field, Dr. Shelagh Smith. Rather more attention is given to anatomical considerations than was formerly the case. As Last (1949) remarked with some asperity “restatement of the facts appears to be warranted by the misconceptions shown by many postgraduate students.” Not just by students. Evidently, we have tried to keep abreast of continuing advances in this developing field, but we shall inevitably be overtaken by the march of events. One does what one can. As was shown by his magisterial reorganization of a then famous London medical library, Seddon saw a clear separation between “medicine” and “surgery.” As the title of this book suggests, we have aimed to deal mainly with disorders which are generally amenable to treatment by operation, and with the appropriate techniques of operation. However, we maintain a belief in the unity of medicine. The book is aimed at surgeons in training and in practice, at physicians in general and at neurologists in particular. We even hope that undergraduates will come to no great harm through reading it. The aim has been determined by observation over the years in the clinic and in the courts of a general lack of knowledge and want of interest in conditions of peripheral nerves. These defects in medical education have generally been unhelpful to patients: injuries of nerves have been “missed” in accident departments; the delay so

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produced is compounded by a lack of appreciation of the urgency of the situation and of the possibilities of repair; tumours of nerves too often go unrecognised until at operation a junior practitioner is confronted by a tumour occupying, or in close proiximity to, a major nerve. We hope that this book may help in stimulating interest in conditions affecting peripheral nerves, that it may aid in enhancing the quality of treatment of such lesions, and that it may bring the field of study to the notice of clinicians highly placed in surviving teaching institutions. Lesions of peripheral nerves are indeed very useful in teaching the interpretation of physical signs, which is after all the main business of the clinician. It has not been possible to treat exhaustively every aspect of the now large subject, but we hope that sufficient and sufficiently well chosen references have been given to open avenues for further reading. We had hoped to include a chapter on disorders of selected cranial nerves, and in particular of the facial nerve. That hope was, alas, born to die: we have in the event restricted the cranial nerve study to one which is really a spinal nerve – the spinal accessory – and to some aspects of damage to the fifth, seventh, tenth and twelfth nerves. Rashly, perhaps, we have proposed one or two new terms for varieties of nerve injury and for pain arising from the nerve injury. We have also revived an old suggestion for a term to replace that commonly used to designate injury inflicted by doctors. We do not hope to escape criticism for this presumption, but we hope that, at least, our derivations will be found by classicists to be correct. We hope that those derivations do no discredit to the august institution where their principles were imparted. All who work in this field owe a debt of gratitude to the late Sir Herbert Seddon, and to the late Sir Sydney Sunderland. The extent of their contribution is overwhelming: no list of references, however long, can indicate its magnitude. Any book on this subject must draw heavily on Peripheral Neuropathy, and in particular on the third edition (1993). We are glad to acknowledge our debt to the editors and authors contributing to that majestic work. The late Professor Roger Gilliatt was foremost amongst those who after the Second World War made advances in the field and stimulated the interest of his colleagues and juniors at Queen Square and in other centres. No-one contributed more to the study and treatment of lesions of the brachial plexus than did the late Professor Algimàntas Narakas of Lausanne. We gratefully acknowledge the contribution of these two men and the lasting influence of their work. 

Rolfe Birch George Bonney† Christopher Wynn Parry

Preface to the Second Edition

This work is dedicated to George Bonney who began preparation of the second edition of Surgical Disorders of the Peripheral Nerves shortly after the publication of the first. The structure of the book was well advanced by the time of his death. One main reason for undertaking this task was the rising tide of iatrogenous injuries. It became clear that it was no longer reasonable to assume that modern medical education provides graduates with a sound grasp of the anatomical and physiological principles of the peripheral nervous system. The work has been almost entirely rewritten with much greater emphasis upon the causes and manifestations of injuries to nerves, particularly iatrogenous injuries and the effects of ischaemia. Shelagh Smith and Ravi Knight have rewritten the chapter on electrodiagnosis which now takes its proper place in the central part of the book rather than at the end. Tara Renton has provided a welcome addition about the risks to the branches of the trigeminal nerve during facio-maxillary and dental work. The field of entrapment neuropathy has been reduced to a discussion about how to avoid error in diagnosis and in execution. With considerable reluctance the field of tumours of peripheral nerves has been approached in the same way. Information about cause, course and outcome in more than 6000 nerve injuries are summarised. The immense task of collation of data was undertaken by the staff of the Peripheral Nerve Injury Unit under the direction of the research coordinator, Margaret Taggart. Sanjay Patel provided exceptional skills in the development of different data bases and he analysed the extensive material about the birth lesion of the brachial plexus. Dirk de Camp, photographer of the Institute of Orthopaedics undertook all of the photographic work and developed an archive of several thousand images with particular precision. This involved the retrieval of much earlier material and he showed extraordinary patience in preparing the final order of the photographs for the different chapters. All of the drawings in this edition were done by Philip Wilson, who took on the constant revision and alteration without demur. We have indeed been fortunate in the close collaboration with distinguished colleagues in two other Institutions. Praveen Anand, now at the Hammersmith Hospital (Imperial College), has, with his team, provided extensive information from investigations of tissues obtained from patients with nerve injuries or suffering from neuropathic pain and these findings have been matched with those drawn from clinical examination and quantitative sensory testing performed in the Joint Clinics held with him, and with Peter Misra, at the Hammersmith Hospital. Uma Anand provided beautiful illustrations from the successful culture of neurones from human dorsal root ganglia. Nicholas Murray, Shelagh Smith, Peter Misra, and Carla Cordivari of the Department of Neurophysiology at the National Hospital for Nervous Diseases, Queen Square examined more than 1000 patients seen in our Joint Diagnostic Clinics. Susan Standring provided a great deal of her own original material and, through her good offices, Martyn Cooke curator and John Carr photographer, went to great lengths to provide photographs of specimens held in the Wellcome Museum of the Royal College of Surgeons of England. xi

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A number of colleagues undertook the laborious task of reading the manuscripts. The first four chapters were read by Susan Standring, Praveen Anand and Peter Misra who made many cogent suggestions and important corrections. Frank Horan, Editor Emeritus of the Journal of Bone and Joint Surgery, and Michael Laurence of the Editorial Board of that Journal undertook the arduous task of reading the entire work. Their contribution went far beyond the detection of innumerable blemishes. Their highly informed and meticulous criticism strengthened the structure and concept of the work. The responsibility for errors remains with the author. Margaret Taggart indexed and catalogued all references and transcribed the entire manuscript as well as developing and implementing methods within the Peripheral Nerve Injury Unit for the prospective collection of data for all patients. Thomas Carlstedt joined us in 1995, transferring his work from the Karolinska Institute, Stockholm and he shared his thoughts and work in the fields of injuries to the lumbo sacral plexus, reconnection between the central and the peripheral nervous systems in cases of avulsion of spinal nerves, entrapment of the pudendal nerve and in aspects of nerve tumours. Marco Sinisi, who joined us five years ago generously provided material from his experience with peripheral nerve tumours, neuropathic pain and prolonged conduction block. For many years our house surgeons and registrars have made important contributions by reviewing both case notes and patients and going to great lengths to retrieve classical references. We have been extremely fortunate in our many visiting colleagues, who brought with them new ideas and who undertook much original work. Without their contributions the work could not have gone forward and wherever possible those contributions have been acknowledged in the text. Particular thanks are due to the many hundreds of colleagues, for the most part orthopaedic surgeons, by whose acumen and professional authority so many patients have been sent to us with a clear and accurate diagnosis at the best possible time for their treatment. Particular thanks too go to our editors, Melissa Morton and Denise Roland of Springer. They provided so much encouragement and interest throughout but also offered highly critical reviews of earlier drafts which ensured some clarity of purpose. Rolfe Birch

Contents

1  The Peripheral Nervous System: Gross Anatomy . . . . . . . . . . . . . . . . . . . . . . . . . 1.1 The Cranial Nerves. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2 The Spinal Nerves. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2.1 The Anterior Primary Rami. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2.2 Thoracic Anterior Primary Rami. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2.3 Lumbar and Sacral Anterior Primary Rami. . . . . . . . . . . . . . . . . . . . . . . . 1.2.4 The Posterior Primary Rami. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.3 The Autonomic Nervous System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.3.1 The Sympathetic System. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.3.2 The Parasympathetic Nervous System. . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.3.3 Afferent Autonomic Pathways. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.4 Nerves at Risk from Musculo Skeletal Injury. . . . . . . . . . . . . . . . . . . . . . . . . . . . References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1 4 7 7 18 18 32 33 34 36 37 37 41

2  The Microscopic Structure of the Nervous System: Its Function . . . . . . . . . . . . . 2.1 The Neurotrophins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1.1 Nerve Growth Factor. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 The Peripheral Nerve Fibres. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2.1 Conduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2.2 The Basis of the Action Potential: Ion Channels. . . . . . . . . . . . . . . . . . . . 2.2.3 Axonal Transport. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2.4 The Blood Supply of Nerves. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2.5 The Nervi Nervorum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2.6 Changes in Nerves with Ageing. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3 The Somatic Motor System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4 The Somatic Sensory System. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4.1 Cutaneous Sensibility. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4.2 The Skin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4.3 Cutaneous Sensory Receptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4.4 Deep Sensibility. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4.5 The Muscle Spindles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4.6 The Golgi Tendon Organs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4.7 Central Connections. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4.8 Visceral Afferents. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.5 Cortical Maps. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.6 Synaptic Activity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

43 44 44 46 54 56 57 58 59 59 61 62 62 64 65 66 66 68 69 70 71 72 72

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Contents

3  Reactions to Injury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1 Axonotmesis – Neurotmesis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2 The Cell Body and Proximal Stump. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2.1 Wounds of the Perineurium. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2.2 Contralateral Effects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3 The Distal Stump . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4 Types of Lesion Produced by Different Physical Agents. . . . . . . . . . . . . . . . . . . 3.4.1 Acute Ischaemia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4.2 Ischaemia from Tamponade. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4.3 Ischaemia and Acute Compression Within Neurovascular Fascial Compartments. . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4.4 Ischaemia by Acute Compression from Swollen Muscle . . . . . . . . . . . . . 3.4.5 Ischaemia Caused by Traction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4.6 Reperfusion Injury. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4.7 Chronic Ischaemia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4.8 Crush . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4.9 Compression – Acute. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4.10 Chronic Nerve Compression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4.11 Traction or Stretch Injury. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4.12 Thermal Injury. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4.13 Electric Shock . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4.14 Percussion Injury. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4.15 Injection Injury. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4.16 Vibration Injury. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.5 The Perineurium and Neoplasm or Infiltration. . . . . . . . . . . . . . . . . . . . . . . . . . . 3.6 Radiation and Peripheral Nerves. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.7 Envenomation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.8 The Peripheral Effects of Denervation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.9 Changes at the Higher Levels: The Phantom Limb . . . . . . . . . . . . . . . . . . . . . . . References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

90 92 95 96 97 97 98 99 100 103 104 106 106 107 107 108 108 109 110 111

4  Regeneration and Recovery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1 The Response of the Nerve and Axon to Transection. . . . . . . . . . . . . . . . . . . . . . 4.2 The Repair of Large Gaps. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2.1 Other, Non Neural, Material for Grafts: Entubation . . . . . . . . . . . . . . . . . 4.3 Nerve Transfer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3.1 Recovery of Cutaneous Sensation after Nerve Transfer . . . . . . . . . . . . . . 4.3.2 Recovery of the Deep Afferent Pathways after Nerve Transfer. . . . . . . . . 4.3.3 Complications of Regeneration. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.4 Regeneration after Intradural Injury. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.5 Recovery of Function after Nerve Repair. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.5.1 Methods. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.6 Factors in Prognosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.7 Severity of Injury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.8 Delay. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

115 116 123 126 128 130 130 132 135 137 138 139 140 140 140

5  Clinical Aspects of Nerve Injury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1 Associated Symptoms and Signs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.2 Recognition of the Level and the Depth of Injury . . . . . . . . . . . . . . . . . . . . . . . . 5.3 Signs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.4 Tinel’s Sign. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.5 Eliciting the Tinel Sign in Closed Lesions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

145 148 151 154 156 159

77 81 82 84 85 85 87 87 89

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5.6 5.7 5.8 5.9

Tinel’s Sign and Recovery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Examination of Sensibility. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Quantitative Sensory Testing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Examination of Muscles. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.9.1 Some Pitfalls . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.9.2 Our Methods. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.9.3 Clinical Examination. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.9.4 The Lower Limb. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.9.5 Late Signs of Nerve Injury. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.9.6 Signs of Reinnervation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.10 Records. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.11 Aids to Diagnosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

161 161 163 166 166 168 168 174 177 180 182 185 188

6  Clinical Neurophysiology in Peripheral Nerve Injuries . . . . . . . . . . . . . . . . . . . . Shelagh Smith and Ravi Knight 6.1 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.2 Electrodiagnostic Techniques. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.2.1 Glossary of Electrodiagnostic Procedures. . . . . . . . . . . . . . . . . . . . . . . . . 6.2.2 Intra-operative Neurophysiological Procedures. . . . . . . . . . . . . . . . . . . . . 6.2.3 Electrodiagnostic Techniques and Localisation. . . . . . . . . . . . . . . . . . . . . 6.3 Limitations and Pitfalls of Electrodiagnostic Investigation . . . . . . . . . . . . . . . . . 6.4 Safety Aspects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.5 Pathophysiological Correlates. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.5.1 Types of Nerve Lesion: the Electrophysiological Consequences . . . . . . . 6.5.2 Regeneration and Reinnervation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.6 Clinical Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.6.1 Upper Limb Neuropathies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.6.2 Lower Limb Neuropathies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6.6.3 Diffuse Problems. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

191

7  Operating on Peripheral Nerves . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.1 Indications and Objects of Intervention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.1.1 Special Units: Their Role. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2 General Principles of Operation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2.1 Control of Bleeding. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.3 Apparatus and Instruments. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.4 Methods of Repair. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.4.1 The Vascular Repair. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.4.2 The Nerve Operations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.5 The Nerve Repair . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.5.1 Methods of Suture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.5.2 Grafting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.5.3 Indications For and Methods of Nerve Transfer . . . . . . . . . . . . . . . . . . . . 7.5.4 Immobilisation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.6 Approaches to Individual Nerves. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.6.1 The Transverse Supraclavicular Approach: (Anterior, or Anterolateral). . 7.6.2 The Transclavicular Exposure. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.6.3 The Postero-Lateral Route. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.7 Repair of the Roots of the Spinal Nerves in an Avulsion Lesion. . . . . . . . . . . . . 7.7.1 The Spinal Accessory Nerve. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.7.2 The Suprascapular Nerve. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.7.3 The Infraclavicular Part of the Brachial Plexus. . . . . . . . . . . . . . . . . . . . .

231 231 232 233 233 234 239 239 241 244 245 247 249 252 254 254 256 259 262 264 265 265

191 191 192 197 199 199 201 201 202 205 206 206 219 223 225

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7.7.4 7.7.5 7.7.6 7.7.7 7.7.8 7.7.9 7.7.10 7.7.11 7.7.12

The Circumflex Nerve . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Median and Ulnar Nerves in the Arm and the Axilla. . . . . . . . . . . . . . . . The Radial Nerve. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . The Posterior Interosseous Nerve. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . The Lower Part of the Median Nerve. . . . . . . . . . . . . . . . . . . . . . . . . . . . The Lower Part of the Ulnar Nerve . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Nerves in the Abdomen and Pelvis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . The Sciatic Nerve. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . The Tibial and Common Peroneal Nerves in the Popliteal Fossa and Below. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  7.7.13 The Lower Tibial Nerve and the Plantar Nerves . . . . . . . . . . . . . . . . . . . 7.8 Entrapment Neuropathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.8.1 The Thoracic Outlet Syndromes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.8.2 The Suprapleural Membrane (Sibson’s Fascia). . . . . . . . . . . . . . . . . . . . 7.8.3 The First Rib. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.8.4 The Seventh Cervical Rib. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.8.5 Considerations About Operation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.8.6 Carpal Tunnel Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.8.7 Technique of Operation (Open Method) . . . . . . . . . . . . . . . . . . . . . . . . . 7.8.8 Operations for Ulnar Neuropathy at the Elbow. . . . . . . . . . . . . . . . . . . . 7.8.9 The Less Common Entrapment Syndromes – Upper Limb. . . . . . . . . . . 7.8.10 Some Entrapment Neuropathies in the Lower Limb . . . . . . . . . . . . . . . . 7.8.11 Meralgia paraesthetica. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.8.12 Entrapment of the Pudendal Nerve. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.8.13 The Piriformis Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.8.14 The Tarsal Tunnel Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.8.15 “Morton’s Metatarsalgia”. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.9 Pitfalls in Operating on Tumours of Peripheral Nerves. . . . . . . . . . . . . . . . . . . . 7.9.1 The Solitary Benign Schwannoma (Neurolemmoma, Neurinoma). . . . . 7.9.2 The Intraneural Ganglion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.9.3 The Solitary Neurofibroma. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.9.4 Malignant Peripheral Nerve Sheath Tumours (MPNST). . . . . . . . . . . . . References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

266 266 266 267 267 269 270 271

8  Compound Nerve Injury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.1 The Wound. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.1.1 War Wounds: Current Practice. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.2 The Vascular Lesion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.2.1 The Shoulder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.2.2 The Elbow. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.2.3 The Knee . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.2.4 The False Aneurysm and Arteriovenous Fistulae. . . . . . . . . . . . . . . . . . . 8.2.5 Ischaemia and the Nerve. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.2.6 Iatrogenous Ischaemic Injury. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.3 Skin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.4 Penetrating Missile Injuries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.4.1 Suture and Grafting During World War Two: The MRCR Evidence. . . . 8.4.2 Grafts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.4.3 Experience from St Mary’s and the Royal National Orthopaedic Hospitals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  8.4.4 The Brachial Plexus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.4.5 Pain. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.4.6 The Peripheral Nerves . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8.4.7 Recent Experience . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

303 304 305 306 309 312 312 313 316 319 320 322 323 324

272 273 273 275 276 276 276 280 282 282 284 284 285 285 285 286 286 287 287 287 289 290 293 298

326 326 328 328 330

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8.5 Neurovascular Injuries: Amputation Revascularisation. . . . . . . . . . . . . . . . . . . . 332 8.5.1 The Brachial Plexus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 333 8.5.2 The Closed Infraclavicular Lesion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 334 8.6 Nerves and Bone and Joint Injuries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 339 8.6.1 The Nerve and the Pattern of Fracture. . . . . . . . . . . . . . . . . . . . . . . . . . . 341 8.6.2 The Shoulder Girdle and Gleno-Humeral Joints. . . . . . . . . . . . . . . . . . . 343 8.6.3 The Clavicle. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 344 8.6.4 Dislocation of the Gleno-Humeral Joint . . . . . . . . . . . . . . . . . . . . . . . . . 345 8.6.5 The Radial Nerve and Fractures of the Humerus. . . . . . . . . . . . . . . . . . . 351 8.6.6 Incidence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 351 8.6.7 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355 8.6.8 The Musculocutaneous Nerve. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 355 8.6.9 Elbow. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 356 8.6.10 Iatrogenous Injuries in the Adult. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 359 8.6.11 The Forearm. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  359 8.7 The Lower Limb. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 360 8.7.1 The Femoral Nerve . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 360 8.7.2 The Lumbo Sacral Plexus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 361 8.7.3 The Hip. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363 8.7.4 The Common Peroneal and Tibial Nerves. . . . . . . . . . . . . . . . . . . . . . . . 365 8.7.5 More Recent Experience at the Royal National Orthopaedic Hospital. . 367 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 369 9  The Closed Supraclavicular Lesion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.1 Mechanisms of Injury. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.2 Anatomy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.2.1 Course in the Neck. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.2.2 Micro Anatomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.2.3 Functional Distribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.3 Lesions of the Spinal Cord. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.4 The Evolution of Our Policy of Treatment of Closed Traction Lesions of the Brachial Plexus. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.5 The Definition of Pre and Postganglionic Lesion: Prognosis for Recovery. . . . . 9.6 Epidemiology. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.7 Diagnosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.7.1 Conduction studies: The Current Situation . . . . . . . . . . . . . . . . . . . . . . . 9.7.2 The Operation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.8 Some of the Techniques Used for Repair. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.9 Strategies of Repair. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.9.1 The Upper Lesion: Rupture or Avulsion of C5, C6 (C7) with Intact (C7) C8, T1. . . . . . . . . . . . . . . . . . . . . . . . . . 9.9.2 The Lower Lesion: Intact C5, C6 (C7), Rupture or Avulsion C8, T1. . . 9.9.3 The Middle Group. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.9.4 The Complete Lesion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.9.5 Free Functioning Muscle Transfer (FFMT). . . . . . . . . . . . . . . . . . . . . . . 9.9.6 The Bilateral Lesion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.10 Results. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.10.1 Methods. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.10.2 Definitions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.10.3 Conventional Nerve Transfers. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.10.4 Repair of Avulsed Ventral Roots. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.11 Recovery of Function by Patients. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.11.1 Age. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

375 376 378 378 379 379 380 384 385 388 389 392 398 398 399 399 404 404 404 406 407 409 409 409 410 410 411 415

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9.12 Relief of Pain by Repair. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 416 9.12.1 Return to Work. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 420 9.13 Reimplantation of Avulsed Spinal Nerves. . . . . . . . . . . . . . . . . . . . . . . . . . . . 421 9.13.1 The First Clinical Case – George Bonney, 1977 (from the first edition of this work) . . . . . . . . . . . . . . . . . . . . . . . . . . 421 9.13.2 Subsequent Work by Thomas Carlstedt. . . . . . . . . . . . . . . . . . . . . . . 423 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 425 10  Birth Lesions of the Brachial Plexus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 429 10.1 The Lesion of the Spinal Nerve in Birth Lesion of the Brachial Plexus (BLBP)����������������������������������������������������������������������������������������430 10.1.1 The Central Affect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 431 10.2 Methods of Study. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 432 10.2.1 Diagnosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 432 10.3 Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 436 10.3.1 Incidence. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 436 10.3.2 Risk Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 437 10.4 Recovery in the Complete Lesion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 444 10.4.1 Group 3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 445 10.4.2 Group 4. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 445 10.5 Treatment. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 447 10.6 Supplementary Investigations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 448 10.6.1 Neurophysiological Investigations (NPI). . . . . . . . . . . . . . . . . . . . . . 448 10.6.2 Imaging. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 453 10.7 Nerve Operations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 453 10.8 The Indications for Operation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 453 10.8.1 The Incomplete Lesion: Groups 1 and 2 . . . . . . . . . . . . . . . . . . . . . . 454 10.9 The Operation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 454 10.9.1 Methods of Repair . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 456 10.9.2 Post-operative Care. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 456 10.10  Results of Nerve Operations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 457 10.10.1  Experience at St Mary’s – Royal National Orthopaedic Hospital . . . 458 10.10.2  Late Reinnervation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 462 10.10.3  Cocontraction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 463 10.11  Deformities. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 463 10.12  Posterior Subluxation (PS) and Posterior Dislocation (PD) of the Gleno-humeral Joint with Related Contractures . . . . . . . . . . . . . . . . . . 466 10.12.1  Onset and Progression of the Secondary Deformities. . . . . . . . . . . . 467 10.12.2  Diagnosis and Classification. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 469 10.12.3  Medial Rotation Contracture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 470 10.12.4 The Development of Our Preferred Operation for Posterior Subluxation or Dislocation of the Gleno-Humeral Joint. . . . . . . . . . 471 10.12.5 The Operation for Reduction of the Posterior Subluxation and Dislocation of the Gleno-Humeral Joint. . . . . . . . . .  473 10.12.6  Deformities at the Elbow and Forearm. . . . . . . . . . . . . . . . . . . . . . . . 478 10.13  Conclusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 479 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 479 11  Iatrogenous Injuries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Part 1: General Considerations Rolfe Birch 11.1 Incidence and Audit. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.2 Causes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.2.1 Generalised Disorders. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.2.2 Alcohol. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

483

485 486 486 487

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11.2.3 Diabetes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.2.4 Connective Tissue Disease. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.2.5 Warning and consent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.2.6 Teaching and Training. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.2.7 Specialisation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.2.8 Continuity of Care: Timing of Operation. . . . . . . . . . . . . . . . . . . . . . . 11.3 Nerve Lesions in Total Hip Arthroplasty. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.3.1 The Nerve Lesion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.3.2 Findings in the 110 Patients Seen Between 2001 and 2007. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.3.3 Indications for Urgent Reexploration . . . . . . . . . . . . . . . . . . . . . . . . . 11.4 Radiation Neuropathy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.4.1 The Place of Operation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.5 Prevention of Iatrogenous Lesions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.5.1   Teaching and Training. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.5.2   Audit and Consent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.5.3   Conduct of Affairs. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.5.4   Recognition and Action. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

487 488 490 492 493 493 494 494

Iatrogenous Injuries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  Part 2: Minimising and Managing Iatrogenous Trigeminal Nerve Injuries in Relation to Dental Procedures Tara Renton 11.6 Introduction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.6.1   Signs and Symptoms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.7 Mechanisms of Nerve Injuries. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.7.1   Local Analgesic Related Trigeminal Nerve Injuries . . . . . . . . . . . . . . 11.7.2 Implant Related Nerve Injuries . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.7.3   Management of Implant Related Nerve Injuries . . . . . . . . . . . . . . . . . 11.7.4   Endodontic Related Nerve Injury. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.7.5   Third Molar Surgery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.7.6   Dental Extraction of Other Teeth Proximal to IAN Canal. . . . . . . . . . 11.7.7   Socket Medications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.7.8   Post Operative Infection Related Nerve Injuries. . . . . . . . . . . . . . . . . 11.7.9   Management of Trigeminal Nerve Injuries . . . . . . . . . . . . . . . . . . . . . 11.7.10  Evaluation of Trigeminal Nerve Injuries. . . . . . . . . . . . . . . . . . . . . . . 11.7.11  Possible Interventions and Timing. . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.7.12  Possible Management Tools. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.7.13  Reassurance Counselling/Cognitive Behavioural Therapy. . . . . . . . . 11.7.14  Medical Intervention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.7.15  Surgical Intervention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.7.16  Reasoning for Early Nerve Repair. . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.7.17  Surgical Technique. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.7.18  Medico Legal Issues. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.7.19  Improved Consent . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 11.7.20  Improved Management of These Injuries . . . . . . . . . . . . . . . . . . . . . . 11.7.21  Can We Prevent These Injuries? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

501

12  Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12.1 Nocicipient. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12.1.1 The Gate Theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12.1.2 Events After Nerve Injury . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12.1.3 Central Pain: The Preganglionic Injury of the Brachial Plexus. . . . . . 12.1.4 The Sympathetic Nervous System and Pain . . . . . . . . . . . . . . . . . . . .

527 528 530 530 533 534

494 496 497 498 499 499 499 499 500

501 503 503 503 504 505 507 509 513 513 513 513 513 515 515 515 516 516 517 517 518 521 521 521 521

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12.2 Complex Regional Pain Syndrome (CRPS) Type 1 and (CRPS) Type 2. . . . . . 534 12.2.1 CRPS Type 2 (Causalgia). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 535 12.2.2   The Painful, Stiff, Swollen Part After Fracture or Soft Tissue Injury (CRPS Type I, Reflex Sympathetic Dystrophy). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  536 12.3 Diagnosis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 538 12.3.1 Drugs and Other Measures Short of Operation. . . . . . . . . . . . . . . . . . 538 12.3.2 Indications for Operation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 542 12.3.3 Causalgia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 542 12.3.4 Neurostenalgia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 549 12.3.5 Post Traumatic Neuralgia. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 551 12.4 Interventions upon the Central Nervous System. . . . . . . . . . . . . . . . . . . . . . . . 555 12.4.1 Interventions on the Central Nervous System: Stimulation. . . . . . . . . 556 12.4.2 Interventions upon the Central Nervous System: Ablation. . . . . . . . . 557 12.5 Summary. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 558 References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 558 13  Reconstruction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.1 Requirements. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.1.1 The Tension of Transfer. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.1.2 Fixed Deformity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.1.3 Correction of Fixed Deformity. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.2 Principles of Operation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.2.1 The Equino-varus Deformity of Ankle and Foot. . . . . . . . . . . . . . . . . 13.2.2 Flexor Muscle Slide, by the Technique of Books . . . . . . . . . . . . . . . . 13.2.3 Fixed Extension at the Metacarpo-phalangeal Joints. . . . . . . . . . . . . . 13.2.4 Release of Contracted Small Muscles of the Hand. . . . . . . . . . . . . . . 13.3 Methods of Reconstruction. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.3.1 The Shoulder Girdle. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.3.2 Extension of the Elbow . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.3.3 Flexion of Elbow. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.3.4 The Operations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.4 Paralysis of the Extensors to the Wrist and Fingers, and of the Abductors and Extensors to the Thumb. . . . . . . . . . . . . . . . . . . . . . . 13.4.1 Pre and Post-operative Care. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.4.2 The Operations. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.5 The High Median Palsy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.5.1 Abduction and Opposition of the Thumb. . . . . . . . . . . . . . . . . . . . . . . 13.6 The High Ulnar Palsy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.7 Combined Nerve Lesions and the Hand. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.8 The Lower Limb. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.8.1 The Insensate Foot. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.8.2 Abduction and Flexion at the Hip . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.8.3 The Knee . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.8.4 Foot and Ankle: The Drop Foot from Common Peroneal Palsy. . . . . 13.9 Vascularized Bone and Muscle Transfer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.10 Amputation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13.11 Conclusion. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

563 565 568 569 571 572 573 573 574 575 576 576 580 580 582 584 586 587 589 589 591 593 594 596 596 597 598 601 601 602 603

14  Rehabilitation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 607 14.1 Communication. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 608 14.2 History. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 609

Contents

xxi

14.3 The Rehabilitation Team. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.4 The Method of Work. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.5 Some Technical Aspects. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.6 Motivation. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.7 Rehabilitation in Progressive Neurological Disease. . . . . . . . . . . . . . . . . . . . . 14.8 The Choice of Intervention. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.9 Patients with Neuropathic Pain. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.10 Paralysis not Physically Determined. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.10.1 Conversion Paralysis. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.10.2 The Munchausen Syndrome. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.10.3 Malingering. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.11 Rehabilitation in the War Wounded . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .  14.11.1 Outcomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14.12 The Future. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

610 611 612 616 624 624 625 626 626 627 628 628 629 630 630

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 631

Contributors

Ravi Knight, MB BS MD MRCPCH   Department of Clinical Neurophysiology, John Radcliffe Hospital, Oxford, UK Tara Renton, PhD MDSc BDS FRACDS(OMS) FDSRCS MHEA  Oral Surgery Department, King’s College London, London, UK Shelagh Smith, BSc MBChB FRCP  Department of Clinical Neurophysiology, National Hospital for Neurology and Neurosurgery, London, UK

xxiii

1

The Peripheral Nervous System: Gross Anatomy

Restatement of the facts appears to be warranted by the misconceptions shown by many post graduate students (Last 1949). Definition of the nervous system; separation of the central and peripheral nervous system; gross anatomy of the peripheral nervous system, including cranial and spinal nerves and the autonomic nervous system; nerves particularly at risk from skeletal injury and bleeding. The nervous system is the mechanism through which the organism is kept in touch with its internal structures and external environments and reacts to changes in them. The central nervous system – the brain and its caudal prolongation the spinal cord – is connected to the periphery by the peripheral nervous system. The latter includes the cranial nerves, the spinal nerves with their roots and rami, the peripheral nerves and the peripheral components of the autonomic nervous system, the sympathetic, parasympathetic and enteric divisions (Gardner and Bunge 2005). The peripheral nerves contain motor fibres (to end plates in skeletal muscle), sensory fibres (from organs and endings in skin, muscle, tendon, periosteum, and bone and joint), efferent autonomic fibres (to blood vessels, sweat glands and arrectores pilarum muscle), and visceral afferent fibres. In no other system is so much functional and relay capacity concentrated in so small a volume of tissue. The cervical spinal cord, with a width of about 2 cm and a depth of about 1.5 cm, contains all the apparatus transmitting control of somatic function from the neck down, together with that of control of much visceral function. Because of their greater content of connective tissue, the peripheral nerves have proportionately a lesser functional content, yet severance in an adult’s arm of the median nerve of 5 mm diameter effectively ruins the function of the hand and forearm (Fig. 1.1).

Phrenic n.

Dorsal root ganglion C5 Dorsal root ganglion C6

Fig. 1.1  The fifth, sixth cervical nerves avulsed from the spinal cord. The ventral root is easily distinguishable from the dorsal rootlets. Note the dorsal root ganglion, the dural sleeve merging into the epineurium and the spinal nerve itself. The small pieces of tissue on the proximal ends of the dorsal rootlets (below) are probably portions of the spinal cord.

Ventral root C5 Ventral root C6 Dorsal roots C5

R. Birch, Surgical Disorders of the Peripheral Nerves, DOI: 10.1007/978-1-84882-108-8_1, © Springer-Verlag London Limited 2011

Dorsal roots C6

1

2

Surgical Disorders of the Peripheral Nerves

The cranial and spinal nerves: Twelve pairs of cranial nerves arise from the brain and brain stem. The second of these, the optic nerves, are in fact prolongations of the central nervous system. Thirty-one pairs of spinal nerves – 8 cervical, 12 thoracic, 5 lumbar, 5 sacral and 1 coccygeal – arise from the spinal cord. Each spinal nerve leaves or enters the cord by a ventral, largely motor, root, and a dorsal sensory root (Figs. 1.2 and 1.3). Each sensory root splits into several rootlets as it approaches the spinal cord; these enter the cord along the line of the postero lateral sulcus. The division of the anterior roots into rootlets is less obvious and takes place nearer the cord. Because in the adult the spinal cord extends caudally only so far as the first lumbar vertebral level, the obliquity of the emerging and entering roots in the theca increases from above downwards (Figs. 1.4 and 1.5). The theca below the first lumbar level is occupied by the lumbar, sacral and coccygeal roots forming a leash whose appearance has been likened to that of a horse’s tail (cauda equina). The cell bodies of the fibres forming the anterior roots are mostly situated in the anterior horn of the grey matter of the spinal cord; those of the fibres of the dorsal root are in the dorsal root ganglion, situated in or near the intervertebral foramen. As they approach the foramen, the two roots join to form the spinal nerve, which outside the foramen divides into anterior and posterior primary rami (Fig. 1.6). The autonomic nervous system: Three divisions of the autonomic nervous system – the sympathetic, the parasympathetic and the enteric – are usually described. In each, pre-ganglionic fibres arise from cells in the brain stem or spinal cord. These relay in ganglia to post-ganglionic fibres innervating cardiac muscle, smooth muscle and glands. Most viscera are supplied by both sympathetic and parasympathetic divisions; the cell bodies of the enteric system are confined to the wall of the bowel (Gardner and Bunge 2005). Dorsal root

Dura mater Arachnoid Pia mater

Dorsal root ganglion

Fig. 1.2  The origin of the roots from the cord, their junction just distal to the dorsal root ganglion, and the emergence of the nerve from the spinal cord.

Ventral root

Posterior primary ramus

Fig. 1.3  The division of the spinal nerve (cervical region) into anterior and posterior primary rami.

Anterior primary ramus

Dorsal root ganglion

Spinal cord Dura mater

The Peripheral Nervous System: Gross Anatomy Fig. 1.4  The spine and spinal cord, seen from the front (a) and behind (b). Some of the dorsal bone has been excised. There is increasing obliquity of the roots in relation to the spinal cord from above down. Below the first lumbar level the spinal canal is occupied by the cauda equina. The dorsal root ganglia lie within the intervertebral foramina. The posterior primary rami are generally smaller than the anterior primary rami. The thoracic sympathetic chain is seen (a). The formation of the sacral plexus and the origin of the sciatic nerve is shown (b).

a

Fig. 1.5  The left side of the spinal cord exposed by hemilaminectomy. The cord has temporarily been rotated by stays passed through the denticulate ligaments. The upper most roots (left) are those of the fifth cervical nerve: they emerge at an angle of about 45° to the cord. The lowest roots (right) are those of the seventh cervical nerve, emerging at a very oblique angle to the cord.

3

b

4

Surgical Disorders of the Peripheral Nerves

1.1 The Cranial Nerves (Figs. 1.6–1.9, 1.12 and 1.14–1.16) The first, olfactory, mediates the sense of smell; the second, optic, mediates that of sight. The latter nerve is a prolongation of the central nervous system. The third, fourth and sixth nerves control the muscles concerned with movement of the eye. The fifth, (trigeminal) nerve has an extensive motor and sensory function, controlling the muscles of the jaw and conveying sensation from the skin of the face and the mucosa of the mouth and nose, and probably from the superficial muscles of the face. The lingual branch which conveys sensation from the tongue and buccal mucosa is, with the inferior alveolar nerve, particularly at risk during operations upon the mouth and jaws. Compression of the trigeminal sensory root by branches from the superior cerebellar artery is a common cause of trigeminal neuralgia (Hughes 2005). The seventh (facial) nerve innervates the superficial muscles of the face and neck. It is remarkable for its vulnerability to damage in each of the three parts of its course – intra-cranial, intra-osseous (in the petrous part of the temporal bone) and extra-temporal. The eighth (auditory) nerve mediates the senses of hearing and of balance. The ninth (glosso-pharyngeal) nerve conveys sensibility from the pharynx and from the back of the tongue and has a small motor function. The tenth (vagus) nerve has, as its name suggests, wide ranging branches and functions, most of the latter being parasympathetic. Motor branches innervate the muscles of the larynx, and sensory branches convey sensation from it. Its recurrent laryngeal branch is in the ascending part of its course in close relationship with the trachea and oesophagus and with the thyroid and parathyroid glands (Fig. 1.16a and b).

Spinal accessory n.

Vertebral a.

Dorsal roots C3, C4 and C5 Superior cervical sympathetic ganglion Vagus n. Dorsal root ganglia C5 and C6

Posterior primary ramus of C7

Fig. 1.6  The brainstem and cervical cord exposed by laminectomy. The spinal accessory nerve passes anterior to the dorsal roots, and emerges through the jugular foramen accompanied by the vagus and glosso-pharyngeal nerves. The vertebral artery courses anteriorly to the spinal nerves.

The Peripheral Nervous System: Gross Anatomy Fig. 1.7  The formation of the 11th cranial (cranial and spinal accessory) nerve. Note the temporary “cranialisation” of the spinal component of the nerve.

5

Pons

Vagus n.

Abducens n.

Jugular foramen

Cranial root

Spinal root C1

Accessory n. Foramen magnum

C2

C3 Spinal cord C4

C5

Trigeminal (V) n. Facial (VII) and vestibulocochlear (VIII) n.n. Glossopharyngeal (IX), vagus (X) and accessory (XI) n.n. Spinal part of accessory n.

Vertebral a. Posterior primary ramus C2 Anterior primary ramus C2 Dura Dorsal root ganglion C3

Fig. 1.8  The junction between the spinal cord and the brain stem shown by excision of a posterior bony element. The first cervical nerve passes away from the spinal cord at almost a right angle.

6 Fig. 1.9  (a) The terminal branches of the facial nerve emerging from deep to the parotid gland. The greater auricular nerve courses obliquely across the sternocleidomastoid. (b) The deeper course of the facial nerve is shown after excision of parotid, the spinal accessory nerve is seen crossing the floor of the posterior triangle.

Surgical Disorders of the Peripheral Nerves

a

Greater occipital n. Lesser occipital n. Parotid gland and facial n. branches at anterior border

Great auricular n. External jugular v. Transverse cervical n.

Marginal mandibular branch of facial n. Cervical branch of facial n.

b

Spinal accessory n.

The Peripheral Nervous System: Gross Anatomy

7

The spinal part of the eleventh (accessory) nerve arises from cells in the accessory nucleus, “a column of cells of the somatic efferent type, extending from the second to the fifth and sixth cervical segments of the cord” (Brodal 1981). These cells are in the dorsolateral part of the anterior horn of the grey matter. The fibres emerge segmentally from each side of the cord, to unite to form on each side a nerve which passes rostrally, posterior to the denticulate ligament, into the cranial cavity through the foramen magnum. In the cranial cavity the nerve unites briefly with its cranial part, derived mainly from the cells in nucleus ambiguus, before passing out of the skull with it through the jugular foramen. Outside the skull the two parts separate, the cranial portion going to join the vagus nerve and the spinal part passing obliquely down the neck to innervate the sternocleidomastoid and trapezius muscles. The spinal accessory nerve is particularly at risk to the activities of surgeons in the posterior triangle of the neck yet its course here is consistent. It emerges from beneath the sternocleidomastoid muscle at about 5 mm cephalad to the point where the greater auricular nerve begins its upward course over the anterior face of the muscle. The course of the nerve distal to the posterior triangle has been described by Pereira and Williams (1999). The innervation of the trapezius has been described by Brown (2002) and by Kierner et al. (2001) who showed that the middle and lower parts of the muscle may be partially supplied by branches from the cervical plexus whereas the upper one-third is innervated solely by the spinal accessory nerve. Although Bremner-Smith et al. (1999) thought that 60% of the individual nerve fibres were unmyelinated or finely myelinated, and that many of these were afferent fibres, this observation was not confirmed by Bunting and Standring (2000), who did not detect unmyelinated axons in immunofluorescence light microscopic studies. The 12th (hypoglossal) nerve leaves the skull through the hypoglossal canal in the occipital bone to supply the intrinsic and all but one of the extrinsic muscles of the tongue. Although there are receptor organs in the muscles of the human tongue (Cooper 1953), it is likely that most of the impulses from them travel in the lingual nerve (Weddell et al. 1940). The sensation of taste is mediated by fibres in the facial nerve (anterior two-thirds of the tongue) and by fibres in the glossopharyngeal nerve (posterior one-third of the tongue). In the upper part of the neck the hypoglossal nerve is joined by fibres from the anterior rami of the uppermost two cervical nerves. These soon leave the nerve to form the ansa hypoglossi from which the infrahyoid muscles are supplied.

1.2 The Spinal Nerves 1.2.1 The Anterior Primary Rami The anterior primary rami of the uppermost four cervical nerves unite and branch to form the cervical plexus, through which the skin of the neck and part of the face and some of the muscles of the neck are innervated. A branch of the fourth cervical anterior ramus, with contributions from the third and fifth rami, passes caudally into the thorax as the phrenic nerve, to supply motor fibres to the diaphragm and sensory fibres to the related pleura, fibrous pericardium and peritoneum (Figs. 1.10–1.12). The anterior primary rami of the lowest four cervical nerves and most of that of the first thoracic nerve unite and branch to form the brachial plexus in the lower part of the neck and behind the clavicle (Figs. 1.13–1.16). The upper limb receives its innervation through the branches of this important plexus. The most proximal muscles are supplied by branches from the rami; the intermediate muscles by branches from the trunks and cords; the muscles of the limb itself by branches from the main terminal nerves – the median, ulnar, musculo-cutaneous, radial and circumflex (axillary). There is a segmental pattern to this innervation: the most proximal muscles are supplied by branches of the uppermost rami; the most distal muscles are supplied by branches derived from the eighth cervical and first thoracic nerves. The segmental pattern of innervation is shown more clearly in the cutaneous supply (Figs. 1.17 and 1.18). The cervical root supply has been, as it were, extruded from the supply to the trunk. Thus, in the transition of innervation from the skin of the neck to that of the trunk there is anteriorly a change from the fourth cervical to the second thoracic segment; posteriorly, from the fifth cervical to the first thoracic segment. An important anatomical and functional differentiation of the plexus takes place with the division of the trunks into anterior and posterior divisions. From the anterior divisions the lateral and medial cords are formed; from the posterior divisions the posterior cord is formed. The lateral and medial cords innervate pre-axial (flexor) musculature; the posterior cord innervates post-axial (extensor) musculature. The plexus and the distribution of its nerves vary considerably from one individual to another: the contributions made by the component nerves vary; the origin and method of formation of the main nerves vary; in some cases the contribution of the fifth nerve is large and that of the first thoracic nerve is small, while in others the reverse is the case. The truly autonomous area of cutaneous supply of each main component nerve is small and variable in extent and location. The contributions made

8

Surgical Disorders of the Peripheral Nerves

Fig. 1.10  The right cervical plexus and its (mainly sensory) branches.

C1 Hypoglossal (XII n.) Lesser occipital

C2

Great auricular Transverse cervical

C3

Superior root of ansa cervicalis Inferior root of ansa cervicalis

C4

C5

Supraclavicular n.n.

Phrenic

Ramus to n. to serratus anterior

by the fourth cervical and second thoracic nerves vary: usually their contributions are small, but occasionally the fourth cervical nerve makes an important contribution to the innervation of scapulo-humeral muscles (Figs. 1.19–1.29). The supply of the skin and of the hand is divided between the median, ulnar and radial nerves. The first two supply the palmar aspect; all supply the dorsal aspect. The median nerve supplies the skin of the radial side of the palm, the palmar aspects of the thumb, index and middle fingers and of the radial part of the ring finger, and the terminal parts of the dorsal aspect of these digits. The ulnar nerve supplies the skin of the ulnar side of the palm, the palmar aspects of the little finger and the ulnar part of the ring finger, the dorsal aspect of the ulnar half of the hand, the little and ring fingers and the ulnar side of the proximal part of the middle finger. The radial nerve supplies the radial side of the dorsum of the hand, of the proximal parts of the thumb and index fingers and of the radial side of the middle finger. Damage to the terminal branches of these nerves of cutaneous sensation, which is usually caused by a needle or scalpel, often leads to pain which is quite out of proportion to the functional importance of the nerve. Mok et al. (2006) studied the cutaneous innervation of the dorsum of the wrist and of the hand; Tindall et al (2006) describe a “safe zone” which avoids damage to the dorsal cutaneous branch of the ulnar nerve; Beldner et al. (2005) studied the relations between the lateral cutaneous nerve of the forearm and the superficial radial nerve and MacAvoy et al. (2006) offer practical advice about avoiding damage to the posterior cutaneous nerve of the forearm (Fig. 1.29). Gruber (1870) having dissected the forearm of 125 cadavers, reported an incidence of 15.2% of branches between the median and ulnar nerves in the forearm . Most commonly, a branch runs from the anterior interosseous branch of the median nerve to the ulnar nerve, but Srinivasan and Rhodes (1981) recognize six varieties of this anomaly, the “Martin-Gruber” anastomosis. Bhadra et al. (1999) displayed, by dissection, important variations in the innervation of the flexor digitorum profundus, whilst Branovovacki et al. (1998) and Mahakkanukrauh and Somsarp (2002) reveal different patterns of distribution of the radial nerve. Whilst the variations of the distribution of the peripheral nerves are significant we have found that the variations in the distribution of the spinal nerves forming the brachial plexus are much more important. At least one-third of patients with complete lesions of C5, C6 and C7 retain powerful extension of the digits and this is seen in some patients in whom only the first thoracic nerve has survived.

The Peripheral Nervous System: Gross Anatomy

9

Fig. 1.11  The course of the phrenic nerve. Note the small branch to the pericardium.

Great auricular n. Transverse cervical n. Spinal accessory n. Cervical n. passing to accessory Supraclavicular n.n.

Omohyoid m. Internal jugular v. Nerve to serratus anterior Phrenic n. Lateral pectoral n.

Fig. 1.12  The cervical and brachial plexus. The right supraclavicular nerves are shown. The left brachial plexus is exposed after excision of sternocleidomastoid and the clavicular head of pectoralis major.

10

Surgical Disorders of the Peripheral Nerves

Fig. 1.13  The right brachial plexus. Note the sequence: the anterior primary rami; trunk; divisions; cord; nerves. Note that the trunks are upper, middle and lower, and that the cords are lateral, medial and posterior from their position in relation to the axillary artery which is, in fact, variable.

C3 C4 C5

Supraclavicular n.

C6

Upper trunk

Lateral cord Posterior cord Medial cord Lateral pectoral n. Circumflex n.

C7

Dorsal scapular n. Middle trunk Suprascapular n. Lower trunk

C8 T1 Phrenic n. Nerve to serratus anterior Medial pectoral n.

Axillary a. Thoracodorsal n. Medial cutaneous n. of forearm Radial n. Musculocutaneous n. Median n. Ulnar n.

Vagus n. Transverse cervical a. Suprascapular a. Thoraco-acromial a.

Phrenic n. Suprascapular n.

Fig. 1.14  The brachial plexus revealed by excision of both clavicles. The right subclavian vein has been removed, both left subclavian vessels have been excised.

The Peripheral Nervous System: Gross Anatomy

11

a

b Stellate ganglion Vertebral a.

Suprascapular n. Phrenic n. Vagus n. Recurrent laryngeal n.

Suprascapular a. Subclavian a.

Subclavian a. Common carotid a.

Subclavian v.

Brachiocephalic v.

Fig.  1.15  The right brachial plexus and the great vessels. (a) Left: showing the relations of the brachiocephalic vein and its branches. (b) Right: the subclavian vein has been excised, revealing the subclavian artery passing deep to scalenus anterior.

a

b

Internal carotid a. Vagus n.

Phrenic n. Thyrocervical a.

Superior cervical sympathetic ganglion

Spinal accessory n. Internal jugular v.

Subclavian a. Vagus n. Recurrent laryngeal n.

Thoracic duct

Common carotid a.

Common carotid a.

Thoracic duct

Subclavian a. Recurrent laryngeal n.

Fig. 1.16  The left brachial plexus. (a) Left: sternocleidomastoid has been excised. (b) Right: the clavicle and part of pectoralis major has been removed.

12

Surgical Disorders of the Peripheral Nerves

C3

C3

C4

C4 T2 T3 T4 T5 T6 T7

T3 T4 T2

T2

T10 T11

T5 T6

T8 T9

T2

C5

C5

T1

C6

C6

T7 T1

T8 T9

T12

C6

L1

T10

C6

T11 T12 L1

C8

C7

Fig.  1.17  Approximate distribution of dermatomes on the posterior aspect of the right upper limb (From Aids to the Examination of the Peripheral Nervous System, 4th edition. By kind permission of Dr. Michael O’Brian and Elsevier Ltd).

C7

C8

Fig.  1.18  Approximate distribution of dermatomes on the anterior aspect of the right upper limb (From Aids to the Examination of the Peripheral Nervous System, 4th edition. By kind permission of Dr. Michael O’Brian and Elsevier Ltd).

Upper subscapular n.

Musculocutaneous n.

Circumflex n. Lower subscapular n. Thoracodorsal n.

Latissimus dorsi tendon Median n.

Nerves to triceps

Ulnar n. Nerve to brachialis

Lateral cutaneous n. forearm

Fig. 1.19  The main nerves in the right axilla and arm.

Nerve to medial head triceps

The Peripheral Nervous System: Gross Anatomy Fig. 1.20  The right circumflex (axillary) and suprascapular nerves.

13

Suprascapular n.

Superior transverse scapular ligament

Supraspinatus

Suprascapular n. Joint capsule Infraspinatus

Deltoid Circumflex n.

Teres minor Branches of radial n. to triceps Teres major

Radial n.

Triceps brachii

Suprascapular a. Suprascapular n.

Acromioclavicular joint

Medial head Long head Lateral head

CIRCUMFLEX (AXILLARY) NERVE

Deltoid RADIAL NERVE UPPER CUTANEOUS NERVE OF THE ARM

Posterior circumflex humeral a.

Teres minor

Circumflex n.

Fig. 1.21  The posterior aspect of the right shoulder after excision of trapezius and most of deltoid showing the course of the suprascapular and the circumflex nerves and their vessels.

Fig. 1.22  The right (axillary) circumflex nerve (From Aids to the Examination of the Peripheral Nervous System, 4th edition. By kind permission of Dr. Michael O’Brian and Elsevier Ltd).

14

Coracobrachialis MUSCULOCUTANEOUS NERVE

Surgical Disorders of the Peripheral Nerves

CIRCUMFLEX (AXILLARY) NERVE Triceps, long head Triceps, lateral head

Biceps Triceps, medial head Brachialis

Brachioradialis

RADIAL NERVE

Extensor carpi radialis longus Extensor carpi radialis brevis Supinator

POSTERIOR INTEROSSEOUS NERVE (deep branch)

Extensor carpi ulnaris Extensor digitorum Lateral cutaneous nerve of the forearm

Extensor digiti minimi Abductor pollicis longus Extensor pollicis longus Extensor pollicis brevis Extensor indicis

Fig.  1.23  The right musculocutaneous nerve (From Aids to the Examination of the Peripheral Nervous System, 4th edition. By kind permission of Dr. Michael O’Brian and Elsevier Ltd).

SUPERFICIAL RADIAL NERVE

Fig. 1.24  The right radial nerve (From Aids to the Examination of the Peripheral Nervous System, 4th edition. By kind permission of Dr. Michael O’Brian and Elsevier Ltd).

The Peripheral Nervous System: Gross Anatomy

15

Fig. 1.25  The anterior aspect of the right elbow. Lateral cutaneous n. of the forearm

Brachioradialis m. Posterior interosseous n.

Superficial radial n. Flexor digitorum superficialis m. (radial head cut) Anterior interosseous n. Nerve to flexor pollicis longus

Ulnar n. Brachial a. Median n. Nerve to pronator teres Nerve to palmaris longus, flexor dig. sublimis and flexor carpi radialis Nerve to flexor carpi ulnaris Nerve to flexor digitorum profundus Nerves to flexor digitorum sublimis

Nerve to flexor digitorum profundus Ulnar n. and a.

Flexor pollicis longus

Flexor carpi ulnaris Flexor digitorum profundus

16

Surgical Disorders of the Peripheral Nerves

Sensory Dorsal cutaneous branch

MEDIAN NERVE

ANTERIOR INTEROSSEOUS NERVE

Flexor carpi radialis Palmaris longus Flexor digitorum superficialis

Deep motor branch Superficial terminal branches

Flexor digitorum profundus I & II Flexor pollicis longus

Flexor pollicis brevis Opponens pollicis

Flexor carpi ulnaris Flexor digitorum profundus III & IV MEDIAL CUTANEOUS NERVE OF THE FOREARM

Motor Abductor pollicis brevis

MEDIAL CUTANEOUS NERVE OF THE ARM

Palmar cutaneous branch

Pronator teres

Pronator quadratus

ULNAR NERVE

Palmar branch Motor

Flexor retinaculum

Adductor pollicis Flexor pollicis brevis

Abductor Opponens digiti Flexor minimi

1st Dorsal interosseous

First lumbrical

1st Palmar interosseous

Second lumbrical

Third lumbrical

Fourth lumbrical

Sensory

Fig. 1.26  The right median nerve (From Aids to the Examination of the Peripheral Nervous System, 4th edition. By kind permission of Dr. Michael O’Brian and Elsevier Ltd).

Fig. 1.27  The right ulnar nerve (From Aids to the Examination of the Peripheral Nervous System, 4th edition. By kind permission of Dr. Michael O’Brian and Elsevier Ltd).

The Peripheral Nervous System: Gross Anatomy

17

Fig. 1.28  The median and ulnar nerves in the left hand. Inset shows the normal course of median nerve at the wrist and also the palmar cutaneous nerve.

Common palmar digital n. Median n. dividing into common palmar digital branches Recurrent branch of median n. Flexor carpi radialis m. Radial a.

Superficial palmar arch Nerve to hypothenar m.m. Deep branch of ulnar n. Superficial branch of ulnar n. Ulnar n. Ulnar a. Flexor carpi ulnaris m.

Median n.

Recurrent branch of median n.

Flexor retinaculum

Palmar cutaneous branch of median n. Median n. Flexor carpi radialis m. Flexor digitorum superficialis m.

18 Fig. 1.29  The terminal branches of the superficial radial and lateral cutaneous nerves of forearm seen during operation at the right wrist.

Surgical Disorders of the Peripheral Nerves Superficial radial n.

Extensor carpi radialis longus

Lateral cutaneous n. forearm

Extensor carpi radialis brevis

1.2.2 Thoracic Anterior Primary Rami The second to the sixth thoracic anterior primary rami innervate the intercostal muscles and the skin of the anterior and lateral chest wall. Most of the first nerve goes to join the brachial plexus; most of the second goes as the intercosto-brachial nerve to innervate the skin of the axilla and of the medial side of the arm. The lower six thoracic anterior rami continue from the intercostal spaces to the anterior wall of the abdomen, innervating its skin and muscles. The lowest nerves supply sensory fibres to the lateral part of the diaphragm. The lowest (12th) thoracic ventral ramus, sometimes called the subcostal nerve, is larger than the others and connects with the ilio-hypogastric branch of the first lumbar nerve.

1.2.3 Lumbar and Sacral Anterior Primary Rami (Fig. 1.30) The first lumbar anterior primary ramus gives rise to two mainly cutaneous nerves and part of a third. The iliohypogastric, iloinguinal and genitofemoral nerves supply respectively the skin of part of the buttock, of the groin and the greater part of the external genitalia. The second, third and fourth lumbar anterior rami unite and branch to form the lumbar plexus from which arise the nerves innervating the skin of the thigh and its anterior and medial muscles. The plexus is formed in the anterior part of the psoas major muscle, in the posterior wall of the abdomen. Its terminal branches lie under the parietal peritoneum. Some of these emerge lateral and some medial to the psoas major. The most important terminal branch is the femoral nerve, which passes, lateral to the psoas major and femoral vessels, under the inguinal ligament to reach the upper part of the thigh (Figs. 1.31 1.32 and 1.39). Through its anterior and posterior divisions it supplies the skin of the anterior surface of the thigh and the quadriceps and sartorius muscles. The saphenous branch of the posterior division descends with the femoral artery to emerge from the femoral canal above the knee and supply the skin of the medial side of the leg and foot. The obturator nerve emerges medial to the psoas major and, passing along the lateral wall of the pelvis, emerges into the thigh through the obturator foramen. Through anterior and posterior branches the adductor muscles and the skin of the medial side of the thigh are supplied. Part of the fourth lumbar ramus and all the fifth ventral ramus join to form the lumbo-sacral trunk, which emerges medial to the psoas major to enter the pelvis and join the first, second and third sacral nerves to form the sacral plexus on the posterolateral wall of the pelvis (Figs. 1.33 and 1.34).

The Peripheral Nervous System: Gross Anatomy

19

Ganglionated chain

L1

L1

L2

L2

Iliohypogastric n. L3

L3

Ilioinguinal n. L4

L4

Genitofemoral n. Psoas muscle

L5

L5

Femoral n. Lumbosacral trunk

S1

Lateral cutaneous n. thigh Femoral n.

S2

Obturator n.

S3 S4

Pudendal n.

Fig. 1.30  The femoral and sacral plexuses and the ganglionated sympathetic chain.

Sciatic n.

20

Surgical Disorders of the Peripheral Nerves

Fig. 1.31  The left femoral nerve. Lateral cutaneous n. of thigh

Femoral n. Femoral a. Medial circumflex femoral a. Lateral circumflex femoral a. Anterior branch of obturator n. Medial cutaneous nerve of thigh 2nd perforating a. 3rd perforating a. Saphenous n. Femoral a. (cut)

Femoral a. (cut) Ascending branch of lateral circumflex femoral a. Profunda femoris 1st perforating a. Intermediate cutaneous nerve of thigh Descending branch of lateral circumflex femoral a.

The Peripheral Nervous System: Gross Anatomy

21

Fig. 1.32  The left femoral nerve.

Femoral n.

Nerves to iliacus

External iliac a. External iliac v. Obturator n.

a

1st sacral n.

Lumbosacral trunk Genitofemoral n.

Sympathetic trunk 2nd sacral n. 3rd sacral n.

Femoral n.

4th sacral n. Pudendal n.

Fig. 1.33  The relations of the left sacral plexus. (a) The female pelvis. (b) The male pelvis.

Obturator n.

22 Fig. 1.33  (continued)

Surgical Disorders of the Peripheral Nerves

b

1st sacral n.

Lumbosacral trunk Genitofemoral n.

Sympathetic trunk 2nd sacral n. Femoral n.

3rd sacral n. 4th sacral n.

Obturator n.

Pudendal n.

Union of ventral rami of S2 and S3

Ventral ramus of S1

Ventral ramus of S4

Fig. 1.34  The left sacral plexus.

Sacrospinous ligament

Lumbosacral trunk

The Peripheral Nervous System: Gross Anatomy

23

The innervation of the perineum and most of the lower limb is derived from the branches of this plexus (Figs. 1.37 and 1.38). The sciatic nerve, the largest in the body, leaves the pelvis through the greater sciatic foramen and passes behind the hip joint into the back of the thigh. This great trunk has two main components, which are functionally and often anatomically quite distinct (Figs. 1.35, 1.36, 1.39 and 1.40). The tibial nerve innervates the medial hamstrings, it descends in the midline through the popliteal fossa into the back of the leg, to supply its superficial and deep muscles. It has an important and frequently useful branch, the sural

Gluteus maximus (reflected) Superior gluteal n. Inferior gluteal n. Pudendal n. Sciatic n. Posterior cutaneous n. of thigh

Tibial n. Common peroneal n. Nerves to lateral and medial gastrocnemius Nerve to popliteus Nerves to soleus Sural n.

Sural communicating branch

Tibial n.

Medial calcaneal n.

Fig. 1.35  The right sciatic nerve and its major components in the lower limb.

24

Surgical Disorders of the Peripheral Nerves

Superior gluteal n.

T10

Common peroneal division of sciatic trunk

L1 T11

L2 T12

Inferior gluteal n.

L1

S5

S4

S3

S3

Pudendal n.

S4

Posterior cutaneous n. of thigh

L2

L2 S2

L3

L3

Tibial division of sciatic trunk

S2 L4

Fig. 1.36  The right sciatic nerve and its two main components, the common peroneal and tibial nerves. The CPN is quite distinct and in this specimen it passes separately through piriformis muscle, a not uncommon variation.

L5 L4 L5

S1

L3

L3

S2

S1 L5

S2

S1 L5

S4 S3

S3 S5

L2

L2

L2

L2

Fig.  1.38  Approximate distribution of dermatomes on the perineum (From Aids to the Examination of the Peripheral Nervous System, 4th edition. By kind permission of Dr. Michael O’Brian and Elsevier Ltd).

Fig. 1.37  Approximate distribution of dermatomes on the right lower limb (From Aids to the Examination of the Peripheral Nervous System, 4th edition. By kind permission of Dr. Michael O’Brian and Elsevier Ltd).

The Peripheral Nervous System: Gross Anatomy Fig. 1.39  The nerves on the anterior aspect of the right lower limb (From Aids to the Examination of the Peripheral Nervous System, 4th edition. By kind permission of Dr. Michael O’Brian and Elsevier Ltd).

25

Iliacus FEMORAL NERVE

LATERAL CUTANEOUS NERVE OF THE THIGH

OBTURATOR NERVE

Cutaneous branch Adductor brevis MEDIAL CUTANEOUS NERVE OF THE THIGH

Rectus femoris Quadriceps Vastus lateralis femoris Vastus intermedius Vastus medialis INTERMEDIATE CUTANEOUS NERVE OF THE THIGH

Adductor longus Gracilis

Adductor magnus

COMMON PERONEAL NERVE SUPERFICIAL PERONEAL NERVE Peroneus longus Peroneus brevis LATERAL CUTANEOUS NERVE OF THE CALF Peroneus tertius

Extensor digitorum brevis

DEEP PERONEAL NERVE Tibialis anterior Extensor digitorum longus Extensor hallucis longus SAPHENOUS NERVE

26 Fig. 1.40  The nerves on the posterior aspect of the right limb (From Aids to the Examination of the Peripheral Nervous System, 4th edition. By kind permission of Dr. Michael O’Brian and Elsevier Ltd).

Surgical Disorders of the Peripheral Nerves

Gluteus medius Gluteus minimus SUPERIOR GLUTEAL NERVE Piriformis

SCIATIC NERVE

Tensor fasciae latae INFERIOR GLUTEAL NERVE Gluteus maximus

Semitendinosus Semimembranosus Adductor magnus

TIBIAL NERVE

POSTERIOR CUTANEOUS NERVE OF THE THIGH Biceps, long head Biceps, short head

COMMON PERONEAL NERVE

Gastrocnemius, medial head Soleus

Gastrocnemius, lateral head

Tibialis posterior Flexor digitorum longus

Flexor hallucis longus

TIBIAL NERVE SURAL NERVE CALCANEAL BRANCH

MEDIAL PLANTAR NERVE to: Abductor hallucis Flexor digitorum brevis Flexor hallucis brevis Cutaneous branches

LATERAL PLANTAR NERVE to: Abductor digiti minimi Flexor digiti minimi Adductor hallucis Interossei Cutaneous branches

The Peripheral Nervous System: Gross Anatomy

27

nerve, which arises in the upper part of the popliteal fossa, descends between the two heads of gastrocnemius and pierces the deep fascia in the proximal part of the leg (Figs. 1.41 and 1.42). Usually, a branch from the common peroneal (or fibular) nerve joins the sural nerve; at times, it is larger than the contribution from the tibial nerve. Rarely, the sural nerve arises wholly from the common peroneal division. The nerve then descends to pass lateral to the tendo Achilles to supply the skin on the lateral side of the foot. The tibial nerve continues into the foot behind the medial, tibial, mallelous and through its terminal medial and lateral plantar branches supplies the intrinsic muscles of the foot and the skin of the sole (Fig. 1.44a). The common peroneal nerve innervates the lateral hamstring muscles in the thigh. It diverges laterally from the mid line to pass behind the head of the fibula and lateral to its neck. Here it divides into deep and superficial peroneal nerves. The former passes into the anterior compartment of the leg to innervate the anterior muscles and finally to supply the extensor digitorum brevis and the skin of the dorsum of the first interdigital space (Figs. 1.43 and 1.44b). The superficial peroneal (musculocutaneous) nerve passes deep to the upper part of the peroneus longus muscle to supply both peronei. Its continuation pierces the deep fascia in the distal part of the leg to supply the skin of the dorsum of the foot and anterolateral part of the ankle.

Popliteal a.

Sciatic n.

Tibial n. Common peroneal n. Superior lateral genicular a. Superior medial genicular a. Saphenous n. Inferior medial genicular a.

Sural communicating branch Inferior lateral genicular a. Nerve to popliteus

Tibial n.

Sural n.

Fig. 1.41  The right popliteal fossa.

28

Surgical Disorders of the Peripheral Nerves

Fig. 1.42  The right popliteal fossa.

Tibial n. Sartorius m. Gracilis m. Semitendinosus m. Nerve to medial gastrocnemius m.

Common peroneal n. Plantaris m. Lateral head of gastrocnemius m.

Semimembranosus m. Popliteal a.

Medial head of gastrocnemius m.

Sural n.

The more proximal branches of the sacral plexus supply the gluteal muscles and the skin and muscles of the perineum (Figs. 1.35, 1.36 and 1.38). The superior gluteal nerve, emerging above the piriformis muscle supplies the short gluteus medius and minimus and the tensor fasciae latae. The inferior gluteal nerve, emerging below the piriformis muscle, supplies the gluteus maximus muscle. Kampa et al. (2007) have described an internervous “safe zone” for exposure of the capsule of the hip. The pudendal nerve leaves the pelvis through the greater sciatic foramen and, entering the pudendal canal through the lesser sciatic foramen, passes into the perineum to innervate its skin and muscles. As in the case of the upper limb, there is a segmental innervation of the muscles and, more easily seen, of the skin. Again, the segments innervating the limb have been extruded from the innervation of the trunk and perineum, so that in the transition from trunk to perineum there is posteriorly a segmental change from the third lumbar to the third sacral dermatome. The skin of the foot is supplied by all the main nerves of the lower limb save the obturator (Figs. 1.44–1.46). The plantar surface is supplied by the tibial nerve through its plantar branches; the medial side by the saphenous branch of the femoral nerve; the lateral side by the sural branch of the tibial nerve, and the dorsum by the superficial and deep divisions of the common peroneal nerve. Apparently trivial injuries to the terminal branches of the nerves of cutaneous sensation sometimes cause even more trouble in the lower than in the upper limbs. Tennent et  al. (1998) describe painful neuromas of the infrapatellar branch of the saphenous nerve whilst MacNicol and Kelly (2002) provide an ingenious method for preventing this by transillumination during arthroscopic work. Solan et  al. (2001) advise against the conventional dorsal incision over the hallux because of the constant dorso medial branch which arises from the superficial peroneal nerve.

The Peripheral Nervous System: Gross Anatomy

29

Fig. 1.43  The course relations and branches of the right common peroneal nerve.

Lateral sural cutaneous n. Common peroneal n. Lateral sural cutaneous n.

Deep peroneal n. Superficial peroneal n.

Sural n. Deep peroneal n. Superficial peroneal n.

Fascia of the leg

Lateral calcaneal branches

Dorsal branch of plantar digital n. of great toe

Deep peroneal n., cutaneous branch

30 Fig. 1.44  (a) Above: the medial aspect of the right ankle. (b) Below: the lateral aspect of the left ankle and heel.

Surgical Disorders of the Peripheral Nerves

a Posterior tibial a. Medial calcaneal n.n.

Tibialis posterior m. Flexor digitorum longus m. Flexor hallucis longus m. Medial plantar n.

Lateral plantar n.

b Short saphenous v. Sural n.

Superficial peroneal n.

Peroneus longus m. Anterior tibial a. and deep peroneal n.

Peroneus brevis m.

The Peripheral Nervous System: Gross Anatomy

Dorsal branch of plantar digital n. of great toe

31

Proper plantar digital n.n.

Common plantar digital n.n. Flexor hallucis longus Flexor digitorum longus

Medial plantar n.

Lateral plantar n., superficial branch Lateral plantar n., deep branch

Lateral plantar n.

Dorsal branches of plantar digital n. great toe

Flexor hallucis longus Flexor digitorum longus

Medial plantar n. Lateral plantar n. Flexor digitorum brevis Tibial n.

Fig. 1.45  The sole of the left foot.

Plantar aponeurosis

Fig. 1.46  The sole of the left foot.

32

Surgical Disorders of the Peripheral Nerves

1.2.4 The Posterior Primary Rami The posterior primary rami are usually smaller than the anterior. Most divide into medial and lateral branches to supply the muscles and skin of the posterior part of the neck and trunk. They do not enter the limbs. The posterior primary rami of the uppermost three spinal nerves differ from those of the lowest five in extending their supply to the back of the head (Fig. 1.47). The posterior ramus of the first nerve, actually larger than the anterior ramus, chiefly supplies muscles between the atlas and occiput. The posterior ramus of the second cervical nerve is the largest of the cervical posterior rami and larger than its anterior ramus. Emerging between the posterior arch of the atlas and the lamina of the axis, it divides into a large medial and a smaller lateral branch. The former goes on as the greater occipital nerve to innervate the skin of the back of the scalp. At its beginning, it is in close relationship with the back of the atlanto-axial joint. The third cervical posterior ramus provides a third occipital branch. The posterior rami of the lowest five cervical nerves innervate the posterior vertebral muscles; the medial branches of the fourth and fifth rami also innervate the skin. The thoracic posterior primary rami similarly pass posteriorly close to the posterolateral (zygapophyseal) intervertebral joints to supply posterior vertebral muscles and the skin of the back of the chest. The lumbar posterior rami are similarly disposed, but only the uppermost three reach the skin. The sacral posterior rami are small, having a small distribution to muscle and to the skin over the sacrum.

Vertebral a.

Atlantoaxial facetal joint

Greater occipital n.

Fig. 1.47  The uppermost right three cervical vertebrae and the greater occipital nerve.

Lower articular process of C3

Vertebral a.

The Peripheral Nervous System: Gross Anatomy

33

1.3 The Autonomic Nervous System Conventionally, the autonomic nervous system is divided into two parts – the sympathetic and the parasympathetic nervous systems. Langley (1903, 1926) proposed the enteric nervous system as a third component. Indeed, the complexity and extent of the innervation of the viscera are such as to make this further division attractive (Furness and Costa 1980). Both systems are characterized by having relays between their cells of origin and their terminations: in the case of the sympathetic system the relays are in paravertebral or axial ganglia; in the case of the parasympathetic system they are in or near the organs innervated (Fig. 1.48).

Afferent Dorsal root Sympathetic chain Dorsal horn (sensory neurone) ganglion and ganglion

Blood vessel

Ventral horn Fig. 1.48  Efferent (red) and afferent (green) autonomic paths in the spinal cord and ganglionic chain.

Ventral Efferent (motor neurone) root

Grey ramus

Skin

Intestine

Splanchnic ganglion (coeliac) White ramus

34

Surgical Disorders of the Peripheral Nerves

1.3.1 The Sympathetic System The pre-ganglionic cells of the efferent fibres of the sympathetic system are in the lateral horn of the grey matter of the spinal cord from the first thoracic to the second lumbar level. Most of the ganglia are in the paravertebral sympathetic chains extending from the top to the bottom of the spinal column; others lie in autonomic plexi in the abdominal cavity. Usually there are on each side 2 cervical, 1 cervico-thoracic (stellate), 11 thoracic, 4 lumbar and 5 sacral or pelvic ganglia. Preganglionic myelinated fibres enter the cervico-thoracic, thoracic and upper two lumbar ganglia in white rami from the first thoracic to the second lumbar spinal nerve. These fibres relay in the corresponding ganglia or proceed up or down the chain to relay in other ganglia of the chain or in one of the ganglia of the autonomic plexi. The distribution to the spinal nerves is by way of grey rami, which contain unmyelinated fibres, from the corresponding paravertebral ganglia. Fibres pass directly from the autonomic plexi to their destinations. Afferent fibres have their cells in the posterior root ganglia; their sites of relay are not clearly identified. The sympathetic supply to the head and neck arises mainly from the uppermost three thoracic segments, passes cranially, and relays in the cervical ganglia to be distributed to vessels and sweat glands and in particular to the dilator of the pupil, and the smooth muscle fibres in orbitales and levator palpebrae superioris muscles. Most of the supply to these muscles of the eye arises from the first thoracic segment. The sympathetic supply to the upper limb arises principally from the second to the sixth thoracic segments. Fibres pass up the chain to the middle cervical and cervicothoracic stellate ganglia, where they relay to be distributed by grey rami to the nerves of origin of the brachial plexus (Figs. 1.49 and 1.50). The sympathetic supply to the lower limbs arises from the lowest three thoracic and uppermost two lumbar segments. Fibres enter the first and second lumbar ganglia by white rami, descend in the chain, relay in the lumbar and sacral ganglia and are distributed by grey rami to the lumbar and sacral nerves (Figs. 1.51 and 1.52).

Stellate ganglion

8th cervical n. Lower trunk of plexus

C7

1st intercostal n. 1st posterior intercostal vessels

T1

Kuntz n. Rib 1 T2

T3

Ventral ramus T1

Rib 2

Ventral ramus C8

Rib 3

Lower trunk

Sympathetic chain and ganglion

T4 Rib 4 Superior intercostal v.

Superior costotransverse ligament

Fig. 1.49  The relations of the cervico thoracic (stellate) ganglion.

Unusually large communication between T2 and T1

Fig. 1.50  The relations of the cervico thoracic (stellate) ganglion.

The Peripheral Nervous System: Gross Anatomy Fig. 1.51  The autonomic nerves in the chest and abdomen.

35

Common carotid a. Internal jugular v. Vagus n. Thoracic duct Subclavian v. Intercostal n.n.

Arch of aorta

Azygos v. Sympathetic trunk and ganglia Branches from sympathetic trunk to the greater splanchnic n.

Thoracic duct

Aorta

Greater splanchnic n.

Coeliac plexus Superior mesenteric plexus

Inferior mesenteric plexus

Superior hypogastric plexus

36

Surgical Disorders of the Peripheral Nerves Coeliac plexus

Superior mesenteric plexus Subcostal n. Iliohypogastric n. Inferior mesenteric plexus

Ilioinguinal n. Genitofemoral n.

Superior hypogastric plexus

Inferior hypogastric plexus and pelvic splanchnic n.

Fig. 1.52  The autonomic nerves in the abdomen and pelvis.

1.3.2 The Parasympathetic Nervous System The efferent outflow of the parasympathetic nervous system arises from nuclei in the mid-brain and part of the hind brain and the sacral part of the spinal cord. The pre-ganglionic fibres are distributed by the third, seventh, ninth and tenth cranial nerves and by the second to the fourth sacral spinal nerves. From the last arise the pelvic splanchnic nerves (nervi evigentes) which supply the ganglia in which the pre-ganglionic fibres relay are in or near the organs supplied. The effect of parasympathetic activity is inhibitory in the heart, motor to the muscle of the bladder and bowel and dilator in small vessels. The central control of both sympathetic and parasympathetic function is exercised from nuclei in the hypothalamus which themselves receive input from higher centres. The fibres from the hypothalamus almost certainly descend in a column in the lateral part of the white matter of the spinal cord (Nathan and Smith 1987). Parasympathetic fibres to the papillary and ciliary muscles pass with the oculomotor (III) cranial nerve via the ciliary ganglion, those to the lacrimal, submandibular and sublingual salivary glands travel with the facial (VII) cranial nerve via the submandibular ganglion. Those to the parotid gland are conveyed by the glossopharyngeal (IX) cranial nerve. The main visceral plexi are the cardiac, pulmonary oesophageal, coeliac, mesenteric and hypogastric (Fig. 1.52). They are fed from the cervical and cervico-thoracic ganglia, from the middle and lower thoracic ganglia (the thoracic splanchnic nerves), from the lumbar ganglia (the lumbar splanchnic nerves) and from the sacral ganglia. Both sympathetic and parasympathetic systems contribute to these plexi, the vagus (tenth cranial) nerve being the principal source of parasympathetic fibres to the chest and abdomen, and the second, third and fourth sacral nerves to the pelvis. The effect of efferent sympathetic activity is to cause sweating, to constrict small vessels and to cause contraction of the arrectores pilarum muscle. The visceral actions are to stimulate the action of the heart and to cause sphincteric contraction.

The Peripheral Nervous System: Gross Anatomy

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1.3.3 Afferent Autonomic Pathways Autonomic afferent fibres have their cells of origin in the dorsal root ganglia and in some cranial ganglia. Their peripheral processes run with efferent fibres, terminating in receptor endings in the walls of viscera and vessels. Impulses from these endings do not necessarily obtrude on consciousness, but evidently mediate sensations such as hunger, distension of the bladder and perhaps pain. Most, presumably, are concerned with the initiation of visceral reflexes. Schott (1994) re-examined the role of afferent autonomic pathways in the transmission of painful impulses, and has proposed a return to Langley’s (1903) concept of the unitary nature of the sensory system. In particular, he proposes the inclusion of autonomic afferents from the peripheral organs such as blood vessels with those from organs in the head, neck, thorax and abdomen under the general head “visceral afferents.” Edgar (2007) reviewed the considerable evidence showing that there is dual innervation to the lumbar intervertebral disc. The somatic afferent pathway enters the adjacent dorsal root segmentally via the sinu-vertebral nerves. The other pathway is non segmental and sends fibres through the paravertebral sympathetic chain which re enter through the thoraco lumbar white rami communicantes (Suseki et al. 1998). The nociceptor terminals from the spine have been mapped by Bucknill et al. (2002) by detecting sodium channels Nav 1.8 and Nav 1.9 which are associated with pain fibres. The afferent component of the enteric division is described by Furness (2006).

1.4 Nerves at Risk from Musculo Skeletal Injury The anatomical arrangements of some of the peripheral nerves make them particularly vulnerable to damage from skeletal injury. The sacral nerves are particularly at risk in fractures involving the sacral foramina. The proximity to bone of the main nerves at the elbow render all three vulnerable to skeletal injury (Fig. 1.53). The sciatic trunk is damaged by the posterior displaced head of the femur. Fleming et al. (2004) showed, by “video extensometry” that strain on the sciatic nerve was increased by 26% with the hip flexed to 45° and the knee extended. The course of the circumflex nerve is described by Coene (1985) “in the axillary region the nerve has a free course in loose fatty tissue, but when it turns around the subscapularis muscle, it is captured in a tunnel formed by the fascia of the subscapularis muscle cranially, the teres major muscle caudally and the coraco-brachialis muscle laterally. The fascii of these muscles join at the entrance to the quadrilateral tunnel, where they firmly surround the hitherto independent axillary nerve and posterior circumflex vessels which meet the nerve at this point. This neurovascular complex turns around the inferior border of the subscapular tendon, it passes cranially over the superior border of the teres major tendon, and enters a horizontal ‘tube’.” This arrangement puts the nerve at risk by forward displacement of the head of humerus and bleeding from the posterior circumflex vessels strangles the nerve. The radial nerve is at risk from fractures of the shaft of the humerus between the two relatively fixed points of the nerves to the lateral head of triceps and the tunnel through the inter muscular septum (Lambert 2005). The common peroneal nerve, which passes above or through the piriformis in as many as 30% of cases, is tethered above in relationship to the piriformis and below at the neck of the fibula. The fascia surrounding the biceps femoris muscle and tendon sweeps around to embrace the nerve. The deep peroneal nerve passes rather acutely forward to enter the anterior compartment of the leg. Sleeves of fascia surround main nerves and main vessels in some regions, an arrangement which predisposes the nerve to injury from ischaemia or compression or both, from bleeding. The anterior primary rami of C7, C8, and T1 are enclosed in quite a rigid space after they enter the posterior triangle of the neck. This is bounded, posteriorly, by the dorsal part of the first rib, the transverse processes of the cervical vertebrae and by the fascia of the levator scapulae muscle. The nerves are embraced by the scalenus anterior and scalenus medius muscles, both of which are invested in an unyielding fascia. This is one envelope of the prevertebral fascia which also serves to bind the phrenic nerve down to the anterior face of scalenus anterior. The prevertebral fascia is particularly well developed in front of the vertebral column and also at the base of the posterior triangle where it envelops C7, C8, and T1, the phrenic nerve, the cervical sympathetic chain, and the subclavian and vertebral arteries. Infusion of relatively large volumes of fluid, from 10 to 20 mL, deep to the prevertebral fascia for the

38

Surgical Disorders of the Peripheral Nerves

purpose of inducing regional block may cause tamponade of the radicular vessels which enter the spinal canal and contribute to the anterior spinal artery. Wilbourn (2005) has described the medial brachial fascial compartment which extends from the axilla to the elbow, and is bounded by the tough medial intermuscular septum and the axillary sheath. Wilbourn suggests that bleeding into this compartment is responsible for the majority of infraclavicular plexopathies following regional block and possibly for many of the neurovascular injuries which result from closed or penetrating missile injuries into this region. The anterior interosseous nerve and its accompanying artery may be damaged by compression because of swelling in the deepest part of the flexor compartment of the forearm. The ulnar nerve is accompanied by the ulnar artery, in a discrete fascial compartment in the distal two-thirds of the forearm. Donaghy (2005) suggests that the femoral nerve is more seriously damaged by haematoma where it passes deep to the thick fascia over the iliacus muscle. The nerve is especially at risk from bleeding into the femoral triangle (Fig. 1.54). The deep peroneal nerve is accompanied by the anterior tibial artery, an end artery, throughout most of the anterior compartment of the leg. The tibial nerve is accompanied by the posterior tibial artery in the distal one-half of the leg in a sheath of fascia similar to the arrangements for the ulnar vessels and nerve. The collateral circulation at the knee is particularly poor (Figs. 1.55 and 1.56).

Superior ulnar collateral a.

Brachial a.

Radial recurrent a.

Common interosseous a.

Anterior ulnar recurrent a.

Radial a.

Ulnar a.

Fig. 1.53  The collateral vessels at the elbow accompany the nerves. They must be compromised if the nerves are injured. The specimen is the left elbow.

Anterior interosseous a.

The Peripheral Nervous System: Gross Anatomy

39

Fig. 1.54  The femoral nerve and vessels deep to the inguinal ligament. The drawing shows the left inguinal region.

Lateral femoral cutaneous nerve Inguinal ligament Femoral nerve Femoral branch of genitofemoral nerve Iliacus m. Femoral artery Femoral vein Femoral canal Pectineus m. Psoas major m.

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Surgical Disorders of the Peripheral Nerves

Fig. 1.55  The collateral circulation about the knee is poor. The drawing shows the left knee.

Descending genicular a. Articular branch of descending genicular a. Saphenous branch of descending genicular a. Medial superior genicular a.

Descending branch of lateral circumflex femoral a.

Lateral superior genicular a.

Common peroneal n.

Patellar tendon

Lateral inferior genicular n.

Medial inferior genicular a.

Circumflex fibular a.

Anterior tibial a.

Anterior tibial recurrent a. Deep peroneal n. Superficial peroneal n.

a

Superior lateral genicular a.

b

Superior medial genicular a. Popliteal a. Popliteal a.

Superior lateral genicular a. Inferior lateral genicular a.

Anterior tibial a. Anterior tibial a.

Inferior lateral genicular a.

Tibiofibular trunk

Inferior medial genicular a.

Fig. 1.56  The popliteal and the anterior tibial arteries. Lateral view (a) (left) posterior view (b) (right). In this specimen the anterior tibial artery passes above the popliteus muscle. Other variations are common. The specimen is the right knee.

The Peripheral Nervous System: Gross Anatomy

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References Beldner S, Zlotolow DA, Melone CP, Agnes AM, Jones MH (2005) Anatomy of the lateral antebrachial cutaneous and superficial radial nerves in the forearm: a cadaveric and clinical study. J Hand Surg 30A:1226–1230 Bhadra N, Keith MW, Peckham PH (1999) Variation of innervation of flexor digitorum profundus muscle. J Hand Surg 24A:700–703 Branovovacki G, Hanson M, Cash R, Gonzalez M (1998) The innervation pattern of the radial nerve at the elbow and in the forearm. J Hand Surg 23B:167–169 Bremner-Smith AT, Unwin AJ, Williams WW (1999) Sensory pathways in the spinal accessory nerve. J Bone Joint Surg 81B:226–228 Brodal A (1981) The spinal accessory nerve. In: Neurological anatomy. Oxford University Press, New York/Oxford, p 458 Brown H (2002) Anatomy of spinal accessory nerve plexus: relevance to head and neck cancer and atherosclerosis. Exp Biol Med 227:570–578 Bucknill AT, Coward K, Plumpton C, Tate S, Bountra C, Birch R, Sandison A, Hughes SP, Anand P (2002) Nerve fibres in lumbar spine structures and injured spinal roots express the sensory neurones specific sodium channels SNS/PN3 NaN/SNS2. Spine 27:135–140 Coene LNJEM (1985) Axillary nerve lesions and associated injuries. Thesis, University of Leiden Cooper S (1953) Muscle spindles in the intrinsic muscles of the human tongue. J Physiol 67:1–13 Donaghy M (2005) Lumbosacral plexus lesions. In: Dyck PJ, Thomas PK (eds) Peripheral neuropathy. 4th edn. Philadelphia, Elsevier, Chapter 56. pp 1375–1390 Edgar MA (2007) The nerve supply of the lumbar intervertebral disc. J Bone Joint Surg 89B:1135–1139 Fleming P, Lenehan B, Sankar J, Folan-Curran P, Curtin W (2004) One third, two thirds: relationship of the radial nerve to the lateral intermuscular septum in the arm. Clin Anat 17:26–29 Furness JB (2006) Novel gut afferents: intrinsic afferent neurones and intestinofugal neurones. Auton Neurosci 125:81–85 Furness JB, Costa M (1980) Types of nerves in the enteric nervous system. Neuroscience 5:1–20 Gardner E, Bunge RP (2005) Gross anatomy of the peripheral nervous system. In: Dyck PJ, Thomas PK (eds) Peripheral neuropathy, 4th edn. Saunders Elsevier, Philadelphia, pp 11–34 Gruber W (1870) Über die Verbindung des Nervus medianus mit dem Nervus ulnaris am Unterarme der Menschen und der Säugethiere. Archive Anatomie Physiologie Medizin (Leipzig) 37:501–522 Hughes RAC (2005) Disease of the fifth cranial nerve. In: Dyck PJ, Thomas PK (eds) Peripheral neuropathy, 4th edn. Elsevier Saunders, Philadelphia, pp 1207–1218, Chapter 49 Kampa RJ, Prasthofer A, Lawrence-Watt DJ, Pattison RM (2007) The internervous safe zone for incision of the capsule of the hip. J Bone Joint Surg 89B:971–976 Kierner AC, Zelenka I, Burian M (2001) How do the cervical plexus and the spinal accessory nerve contribute to the innervation of the trapezius muscle? Arch Otolaryngol Head Neck Surg 127:1230–1232 Lambert SM (2005) Further opinion: radial nerve palsy associated with fractures of the shaft of the humerus. Doi: 10.1302/0301-620X. 87B12.17720 Langley JN (1903) The autonomic nervous system. Brain 26:1–26 Langley JN (1926) The autonomic nervous system. Part 1. Heffer, Cambridge Last RJ (1949) Innervation of the limbs. J Bone Joint Surg 31B:452–464 MacAvoy MC, Rust SS, Green DP (2006) Anatomy of the posterior antebrachial cutaneous nerve: practical information for the surgeon operating on the lateral aspect of the elbow. J Hand Surg 31A:908–911 MacNicol MF, Kelly M (2002) Identification of the saphenous nerve at arthroscopy. Arthroscopy 14:312–314 Mahakkanukrauh P, Somsarp V (2002) Dual innervation of the brachialis muscle. Clin Anat 15:206–209 Mok D, Nikolis A, Harris PG (2006) The cutaneous innervation of the dorsal hand: detailed anatomy with clinical implications. J Hand Surg 31A:563–574 Nathan PW, Smith MC (1987) The location of descending fibres to sympathetic pre-ganglionic vasomotor and sudomotor neurones in man. J Neurol Neurosurg Psychiatry 50:1257–1262 Pereira MT, Williams WW (1999) The spinal accessory nerve distal to the posterior triangle. J Hand Surg 24B(3):368–369 Schott GD (1994) Visceral afferents: their contribution to “sympathetic-dependent” pain. Brain 117:397–413 Solan MC, Lemon M, Bendall SP (2001) The surgical anatomy of the dorsomedial cutaneous nerve at the hallux. J Bone Joint Surg 83B:250–252 Srinivasan R, Rhodes J (1981) The median-ulnar anastomosis (Martin Gruber) in normal and congenitally abnormal fetuses. Arch Neurol 38:418–419 Standring SM, Bunting S (2000) The fibre content of the spinal accessory nerve. Personal Communication Suseki K, Takahishi Y, Takahishi K, Chiba T, Yamagata M, Moriya H (1998) Sensory nerve fibres from lumbar intervertebral discs pass through rami communicates. J Bone Joint Surg 80B:737–742 Tennent TD, Birch NC, Holmes MJ, Birch R, Goddard NJ (1998) Knee pain and the infrapatellar branch of the saphenous nerve. J R Soc Med 91:573–575 Tindall MA, Patel M, Frost A, Parkin I, Shetty A, Compson J (2006) The anatomy of the dorsal cutaneous branch of the ulnar nerve – a safe zone for positioning of the 6R portal in wrist arthroscopy. J Hand Surg 31B:203–205 Weddell G, Harpman JA, Lambley DG, Young L (1940) The innervation of the musculature of the tongue. J Anat 74:255–267 Wilbourn AJ (2005) Brachial plexus injuries. In: Dyck PJ, Thomas PK (eds) Peripheral neuropathy, 4th edn. Elsevier Saunders, Philadelphia, Chapter 55. pp 1339–1373

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The Microscopic Structure of the Nervous System: Its Function

The neurone and neurotrophins; transitional zone and roots; the Schwann cell and myelin; the connective tissue sheaths; conduction; axonal transport; blood supply; nervi nervorum; changes with aging; motor path with central and peripheral connections; sympathetic outflow; sensory path with superficial and deep peripheral connections and with central connections; the role of visceral afferents; neurotransmitters. The essential component of the system is the nerve cell with its dendrites and its prolongation, the axon (Figs.  2.1–2.3). Young (1945) characterized the axon as “a very long cylinder of a semi fluid nature.” It is a column of neuronal cytoplasm, the axoplasm enclosed by a cell membrane, the axolemma. Thomas et  al. (1993a) described the axoplasm as a “fluid cytosol in which are suspended formed elements.” The most conspicuous of the latter is the cytoskeleton consisting of neurotubules, neurofilaments and matrix. In addition, there are mitochondria, axoplasmic reticulum, lamellar and multivesicular bodies, and membranous cisterns, tubes and vesicles. It is the cytoskeleton that provides the apparatus for axoplasmic transport. Berthold et al. (2005) describe the axolemma as a three-layered unit membrane about 8  nm thick and consider that it: “conveys signals between the neurone and its Schwann cells that control the proliferative and myelin

producing functions of the Schwann cells and partly regulate axon size.” The glial cells of the peripheral nervous system are essential for the development, maturation, survival and regeneration of the neurone. The relationship between the axon and the Schwann cell is lifelong. The myelinating and non myelinating Schwann cells are the main peripheral glial cells. There are others, which include the satellite cells surrounding cell bodies in the dorsal root and autonomic ganglia, the glia of the enteric system; the teloglia (terminal Schwann cells) at the terminals of somatic motor axons and the glia associated with sensory terminals such as the Pacinian corpuscle. Mirsky and Jessen (2005) observe: “evidence to date suggests that the molecular and morphological differences between these various cells depend on the specific location and cellular environment in which they are found and that the glial cells of the PNS retain unusual plasticity throughout

Fig. 2.1  Cultured human dorsal root ganglion neurone immunostained for Gap 43 (growth associated protein) showing the cell body and neurites arising from the cell body, x40 (Courtesy of Dr. Uma Anand).

Fig. 2.2  Phase contrast image of a single DRG neurone showing the large rounded cell body, x63 (Courtesy of Dr. Uma Anand).

R. Birch, Surgical Disorders of the Peripheral Nerves, DOI: 10.1007/978-1-84882-108-8_2, © Springer-Verlag London Limited 2011

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Surgical Disorders of the Peripheral Nerves

2.1 The Neurotrophins 2.1.1 Nerve Growth Factor

Fig.  2.3  Cultured human DRG neurones immunostained for Gap 43 (green) and for the vanilloid receptor TRPV1 (red), the nuclei of satellite cells are stained blue (DAPI). Bar = 25 mm (Courtesy of Dr. Uma Anand).

life.” King (Berthold et al. 2005) estimated that about 10% of nuclei within the endoneurium of a normal peripheral or spinal nerve root are fibroblasts, and that endogenous macrophages account for between 2% and 9%. Most of the remainder are Schwann cells. Whilst mast cells are also seen their function is not well understood. “Neuron theory” Cajal (1954) asserts that “the neuron, a nerve cell with its processes, is the structural unit of nervous tissue, and the neurons are the only elements in the nervous system which conduct nervous impulses” (Brodal (1981b)). There is no continuity between nerve cells: the termination of the axon on a cell is no more than a contact, a contact to which Sherrington (1897) gave the name, synapse. Brodal (1981b) goes on: “not only is the neuron a structural unit; it also, in most cases, behaves as a trophic unit”; but the neurone itself requires trophic support during maturation and for survival after injury to the axon (Fig. 2.4).

Fig. 2.4  NGF immuno reactivity in neurones in a human dorsal root ganglion which was avulsed from spinal cord six weeks earlier. Immuno reactivity, identified by green fluorescence staining, is localized to cells of the small type. The yellow intracellular granules are lipofucsin deposits which exhibit auto fluorescence. Indirect immunofluorescence method, x50 (Courtesy of Professor Praveen Anand).

Cajal (1928) proposed that there was no autogenous regeneration of the peripheral stump. His belief in the presence of some neurotrophic factor in the distal stump is expressed in the phrase “The penetration into the peripheral stump implies a neurotrophic action, or the exercise of electrical influence by the latter.” He named contact guidance “tactile adhesion.” Young (1942) seemed to conclude that “successful nervous regeneration must depend mainly on the chances provided for adequate numbers of outgrowing fibers to establish connections resembling their original ones.” A hint of belief in neurotrophins had, however, been given in his work with Holmes (Young and Holmes 1940). It was during the 1940s that Hamburger and his colleagues (Hamburger and Keefe 1944) showed that the removal of a limb bud from a chick embryo led to a reduction in the number and size of the neurones destined for that limb whereas addition of extra target tissue during embryonic development was followed by an increase in the number and the size of the relevant neurones. “These observations led directly to the discovery of nerve growth factor (NGF)” (Windebank and McDonald 2005). Levi-Montalcini et  al. (1954) and Cohen et  al. (1954), described an agent found in mouse sarcomata which markedly promoted growth in the sympathetic and posterior root ganglia of chick embryos. They found that treatment with snake venom enhanced the activities of this agent, and that snake venom itself contained a potent growth promoting agent. The results of partial purification and characterisation of this nerve growth factor (NGF) were presented and suggested that the active material was a protein or bound to a protein. Levi-Montalcini and Angeletti (1968) indicated the specific action of NGF on sensory and sympathetic nerve cells: “the control exerted by the NGF on sensory and sympathetic nerve cells stands out by virtue of the magnitude of its effects, its target specificity, and the plurality of its actions.” Windebank and McDonald (2005) defined growth factors as “soluble extracellular macromolecules that influence the proliferation, growth and differentiation of target cells by a cell surface receptor mediated mechanism.” Most neurotrophins are polypeptides which are produced in ­tissues such as skin or muscle from whence they are transported to the neuronal cell body by the fast centripetal component of axonal transport. Three major families of growth factors are recognized. 1. The classic neurotrophins include nerve growth factor (NGF), brain derived nerve factor (BDNF) and the neurotrophins 3–7 (NT3, 4, 5, 6, 7). NGF is produced by cells including keratinocytes, melanocytes, vascular and smooth muscle cells, testis and ovarian cells, and endocrine and exocrine tissue. NGF interacts with the high

The Microscopic Structure of the Nervous System: Its Function

affinity ­receptor p140 tyrosine receptor kinase (TrkA) which is expressed by sympathetic neurones and by small diameter neurones in the dorsal root ganglia. After nerve injury, cells in other tissues, including Schwann cells and fibroblasts, synthesize and release NGF. Mice experimentally engineered to be deficient in TrkA do not develop thermoceptive or nociceptive neurones. BDNF apparently supports the development of motor neurones and their survival after axonotomy. After nerve transection, BDNF messenger RNA increases in muscle and the messenger RNA of one of the receptors to this nerve growth factor, tyrosine receptor kinase B (TrkB) increases in motor neurones. Neurotrophin 3(NT3) is mainly expressed in muscle spindles, Merkel cells and the Golgi tendon organs. This neurotrophin specifically binds to tyrosine receptor kinase C (TrkC). Mice which have been genetically engineered to lose this receptor lack proprioceptive organs. 2. Other neurotrophins are synthesized by the glial cells. It is likely that these factors support the embryonic midbrain and motor neurones in the spinal cord. The glial derived nerve factor (GDNF) binds with its high affinity receptor, also the tyrosine kinase receptor c-Ret. The ciliary neurotrophic factor (CNTF) first binds to its receptor and also the leukemia inhibitory factor receptor beta (LIFR ß). CNTF supports neurones in the ciliary ganglion, dopaminergic neurones, retinal rods and sympathetic and motor neurones. 3. The third family include the insulin growth factor (Igf) which structurally resembles insulin and binds with the tyrosine kinase IGF-I receptor, which is itself homologous to the insulin receptor. This receptor is expressed throughout the nervous system. Nerve growth factors are synthesized by the target organs of the nerves and are conveyed centrally to the neuronal cell bodies. This transport ceases after axonotomy. The interruption of this flow contributes to cell death amongst central neurones, an effect which is more severe in the immature nervous system and after axonotomy close to the neuronal cell bodies (Figs. 2.5 and 2.6). Anand and his colleagues have extensively investigated neurotrophic factors and their receptors in the normal human nerve, and in nerves affected by diabetes, leprosy, and injury. These studies have been extended to neurones from human dorsal root ganglia, (Anand et  al. 1996, Bar et  al. 1998,Saldanha et al. 2000, Yiangou et al. 2000, Durrenberger et  al. 2004, Chessell et  al. 2005, Facer et  al. 2007). More recently, Uma Anand and her colleagues have perfected methods in vitro for the study of living neurones from human dorsal root ganglia and this has permitted close study of the effects of neurotrophins and molecular mechanisms. (Anand et al. 2006, Sanchez et al. 2007, Anand et al. 2008a, Anand et al. 2008b, Anand et al. 2008c) Anand et al. (2006) summarize the effect of neurotrophin factors on the morphology and expression of some receptors in cultured human dorsal

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Fig. 2.5  Brain derived neurotrophic factor (BDNF) immunoreactivity in medium sized neuronal cell bodies and associated axons in human dorsal root ganglion 6  weeks after avulsion of spinal nerves, x40 (Courtesy of Professor Praveen Anand).

Fig. 2.6  Glial derived nerve factor (GDNF) receptor Cret immunoreactivity in neuronal cell bodies of human dorsal root ganglion two weeks after avulsion of spinal roots, x40 (Courtesy of Professor Praveen Anand).

root ganglion sensory neurones: the factors NGF, NT3 and GDNF are produced by peripheral target tissues such as epidermal keratinocytes and affect the phenotype of cultured sensory neurones. In the mature nervous system neurotrophins switch from providing trophic support for neuronal survival to maintenance of a specific neuronal phenotype thereby facilitating modality specific sensory function. For example GDNF and NGF regulate the normal function of two distinct classes of nociceptors via their receptors Ret and TrkA respectively. The levels of these factors are altered by injury. Administration of NGF induces thermal and mechanical hyperalgesia, it is upregulated by inflammation and plays a key role in the pathophysiology of nociception (Figs. 2.7–2.10). Evidently, important questions regarding the role of neurotrophic factors both in regeneration of peripheral nerves and in causation of pain and cutaneous hyperaesthesia and

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Fig. 2.7  Neurotrophin 3 (NT3) immunostaining in suprabasal epithelial cells of human glabrous arm skin, x40 (Courtesy of Professor Praveen Anand).

Surgical Disorders of the Peripheral Nerves

Fig. 2.10  Subepithelial fascicles of NGF positive axons in the tongue of patient with burning mouth syndrome (BMS), x40 (Courtesy of Professor Praveen Anand).

hyperalgesia are raised by the continuing work in this field. Although trials using factors for the treatment of amyotrophic lateral sclerosis and diabetic neuropathy failed, their therapeutic roles continue to be explored and developed.

2.2 The Peripheral Nerve Fibres

Fig. 2.8  Nerve growth factor (NGF) immunostaining of basal epithelial cells in human glabrous arm skin, x40 (Courtesy of Professor Praveen Anand).

Fig. 2.9  GDNF immunoreactivity in Schwann cells of healthy human sural nerve, x150 (Courtesy of Professor Praveen Anand).

In the central nervous system the neurones are supported in a network of oligodendrocyte and astrocyte processes, with very little extracellular space. The structure of peripheral nervous tissue is one of nerve fibres (axons – Schwann cell units) suspended in a collagen rich extra cellular space (Berthold et al. 1984, 1993). The transition from central to peripheral nervous structures takes place in the rootlets or less often in the roots of the spinal nerves. This is the transitional region or transitional zone (TZ). The development of the transitional region in dorsal rootlets was described by Carlstedt in 1981. The extension of CNS structure into the base of the rootlet is cone-shaped. Thus, “each transitional region can be subdivided into an axial CNS compartment and a surrounding PNS compartment” (Berthold et al. 1993) (Figs. 2.11 and 2.12). The myelin sheath distal to the transitional zone is formed by the transitional Schwann cell and that central to it by the transitional oligendendrocyte. The basal lamina of the axon remains continuous through the TZ. Some myelinated nerve fibres become nonmyelinated centrally. Fraher (2005) states that during development: “the CNS-PNS interface oscillates and continually changes its form and position as the two tissue classes establish their mutually exclusive territories.” The astrocyte barrier, which is at first flush with the glia limitans becomes pushed

The Microscopic Structure of the Nervous System: Its Function

peripherally by the central tissue process. Myelination is delayed in the transitional zone and that in the proximal rootlet segment lags behind the rest of the root. The ventral root

47

of the rat has a rich blood supply unlike the dorsal root; in the cat the blood vessels do not accompany the axons in the dorsal root, instead they deviate from the endoneurial space and join vessels on the surface of the cord. Fraher suggests that this arrangement causes the dorsal roots to be more susceptible to ischemia than ventral roots. His findings that the mechanical arrangements lead to rupture at the rootlet rather than in the transitional zone has been confirmed in the human by Schenker (Schenker and Birch 2001) who examined biopsies of the tips of avulsed roots in 12 patients by light and by transmission electron microscopy. Of the ten biopsies taken within 4 weeks of injury the level of rupture was central to the TZ in two of the roots and peripheral to it in the remaining eight (Figs.  2.13 and 2.14). Schenker also studied the corpora amylacea (CA), round homogenously staining

Fig. 2.11  Morphology of the normal human spinal cord. A transverse light microscopic section at C7 showing a ventral root. A single large root in transition is demonstrated with central islands of autolysed glia. Numerous corpora amylacea are seen on the central side of the transitional zone. Toluidine blue, x100 (Courtesy of Editor Journal of Bone and Joint Surgery [British]).

Fig. 2.13  Transverse section of the tip of an avulsed dorsal root at C6 4 days after injury showing a central avulsion. The tissue in the centre of the section is CNS tissue in which glial cells show post traumatic lytic changes. Corpora amylacea are indicated by arrows. Toluidine blue, x100 (Courtesy of Editor Journal of Bone and Joint Surgery [British]).

Fig. 2.12  Normal anatomy of the transitional zone. Schwann cell processes are seen above, astrocyte processes lie closely to an unmyelinated axon (arrows) which is surrounded by a basal lamina(arrow head) Electron microscopy by Michael Kayser, Institute of Orthopaedics (Courtesy Michael Schenker).

Fig.  2.14  Avulsed ventral root of C6 4 days after injury showing a peripheral intradural rupture. The nerve tissue at the site of the rupture showed no CNS features. The tip is covered by organized blood clot and erythrocytes which interweave with fibrin strands. The myelinated fibres show early signs of Wallerian degeneration. Toluidine blue, x200.

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Surgical Disorders of the Peripheral Nerves

bodies 15–50 mm in diameter, which are found in the subpial zone of the spinal cord in post mortem material. The CA mark the watershed between the central and the peripheral nervous systems. The basal lamina surrounding the Schwann cell – axon unit extends into the spinal cord and cannot be used as a reliable indicator of peripheral nervous tissue. Most of the fibres of the ventral roots have their cells in the ventral horn of the grey matter. They can, perhaps, be regarded as outposts of the peripheral system in the central system. The fibres of the dorsal roots have their cells in the dorsal root ganglion: possibly, outposts of the central in the peripheral nervous system? These neurones are “unipolar in form with a single axon and no true dendrites” (Thomas et  al. 1993b). Each axon bifurcates into peripherally and centrally directed axons after leaving the cell body at a variable distance from the cell. The centrally directed branch is of smaller caliber than the peripheral one. The central processes enter the spinal cord along the posterolateral sulcus. In the cord the fibres bifurcate into ascending and descending branches. The branches of the smaller fibres in the lateral part of the root reach the dorsal horn of the grey matter, where both soon terminate having traversed between three and five segments. The branches of the larger fibres in the medial part of the root, mostly myelinated, similarly bifurcate after entering the white matter just medial to the dorsal horn. Some ascending fibres reach as high as the gracile and cuneate nuclei in the caudal part of the medulla. Other fibres of this group have short ascending and descending branches which enter the grey matter of the dorsal horn to establish synapses with nerve cells in its different laminae (Fig. 2.15). Sherrington (1894) showed that ventral roots of cats and monkeys contained intact myelinated nerve fibres after

transection of both the ventral and dorsal roots and he concluded that some afferents reached the spinal cord the “wrong way” through the ventral roots. Unmyelinated afferent fibres certainly enter the spinal cord in the ventral roots (Coggeshall et al. 1974). They may be concerned with the transmission of painful impulses (Clifton et  al. 1976) though White and Sweet (1969) failed to produce pain in man by stimulation of ventral roots. On the other hand, Brindley (1986) described three paraplegic patients who experienced pain whilst stimulating the ventral roots of S2 and S3 or of S3 and S4 to induce micturition by an implanted stimulator. Brindley says: “the Bell-Magendie law is certainly nearly true, but on published evidence it seems likely that it is not exactly true,” pointing out that pain could be evoked by antidromic impulses in efferent fibres. We were able to take advantage of the opportunity offered by intradural damage to nerves of the brachial plexus to demonstrate the presence of afferent fibres in the ventral roots of man. Stephen Gschmeissner examined by electron microscopy the ventral root of the eighth cervical nerve avulsed with its dorsal root and found with it at operation for exploration of the plexus in the posterior triangle of the neck. He found several surviving small myelinated and unmyelinated axons (Fig. 2.16). Clearly, the cell bodies of these axons must have been in the nerve or in the dorsal root ganglion; the fibres must have belonged to the afferent system. These findings were confirmed by Schenker (Schenker and Birch 2000) who examined biopsies from the tip of the avulsed rootlets in nine patients. The tips of the dorsal and of the ventral rootlets of 5 spinal nerves were examined within 8 days of injury, the other patients were operated at intervals ranging between 4 and 50 weeks from injury. Schenker found intact myelinated fibres in all ventral root specimens. The majority of those Direct ascending tract Lissauer’s tract I

Lateral corticospinal tract

X

II III IV V VI VII VIII

Fig. 2.15  The paths of the afferent fibres entering and efferent fibres leaving the spinal cord. Note (right) the laminae of the grey matter.

IX

Crossed ascending tract

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Fig. 2.16  Afferent and efferent fibres in the ventral root. Large healthy myelinated axons in the ventral root of the 8th cervical nerve avulsed from the spinal cord 6 weeks previously. The myelinated efferent fibres have undergone Wallerian degeneration and there is much collagenisation (Electron microscopic study by Mr. Stephen Gshmeissner, x5000).

identified in the later biopsies were regenerating, perhaps signifying collateral sprouting from the intact cell bodies of the adjacent avulsed dorsal root ganglion. There were a small number of intact fibres in the early specimens and Schenker suggests that: “it is therefore likely that these few fibers of the ventral root represent afferent fibers in continuity with the cell body in the DRG.” Less than 5% of the central processes of all dorsal afferents survive the traction injury and it was assumed that “wrong way” ventral afferents do just the same so that the few surviving ventral root afferents that were observed may represent only a very small proportion of the population. Based on this assumption Schenker proposed that the proportion of afferent fibres in the ventral root of man is similar to that found by Loeb (1976) who, by microelectrode recordings in cats, calculated that 3.9% of all afferent fibres reached the cord through the ventral root (Fig. 2.17). In the peripheral nervous system the axons are closely associated with the Schwann cells (Schwann 1839). Sanders (1942) established the central role of Schwann cells in regeneration through grafts: “autografts remain alive and myelin fragmentation and Schwann multiplication go on very much as in a normal peripheral stump.” Sanders rejected methods of repair which do not enrich the environment with Schwann cells. Schwann cells arise from the neural crest, from the same cells that differentiate into peripheral neurones; they provide essential trophic support to the neurone during development and also during regeneration. Our present understanding of the part played by these cells in repair owes a

great deal to the work of Susan Hall of Guy’s Hospital, and now editor of Gray’s Anatomy. (Hall 1997, 1999, 2001, 2005, Li et al. 1998) (Fig. 2.18). Mirsky and Jessen (2005) described how two important growth factors, neuregulin 1 and endothelin regulate early Schwann cell development. The Schwann cell separated from its axon survives for rather longer in the mature than in the immature nervous system. The most important component of the basal lamina is laminin which interacts with receptors in the plasma membrane of the Schwann cell which include the integrins and alphadystroglycan. Laboratory mice which have been genetically engineered to produce defective laminin or a defective receptor for laminin, develop profound nerve pathology and muscle dystrophy (Uziyel et al. 2000). Schwann cells provide another important protein, the tumor suppressor protein, Merlin (schwannomin), which links membrane proteins to the actin cytoskeleton in epithelia and other cell types. Mutations in the gene controlling Merlin lead to an increased frequency of schwannomas. In leprosy, components of the cell wall of M.leprae interact with laminin 2, the major isoform of laminin, and this interferes with the normal interaction between laminin and alphadystroglycan leading to demyelination and to axonal degeneration. During myelination Schwann cells radically transform their phenotype in response to signals from the larger axons; as Mirsky and Jessen (2005) say: “this response represents one of the most striking examples of cell-cell interaction that is known.”

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Surgical Disorders of the Peripheral Nerves

Fig. 2.19  A large myelinated nerve fibre within the posterior root of a 7th cervical nerve which had been avulsed from the spinal cord six weeks previously. The axoplasm contains neurofilaments and a few microtubules. The Schwann cell cytoplasm it is enveloped by a well defined basal lamina. There are processes from fibroblasts from within the endoneurium, x16,200. Fig. 2.17  Rupture of the ventral root of C5 peripheral to the transitional zone examined 5 months after avulsion. Two thinly myelinated axons are seen. x 17,000 (Electron microscopic study by Mr. Michael Kayser, Institute of Orthopaedics. By courtesy editor Journal of Anatomy).

Fig. 2.18  In vitro cultures of mouse DRG neurones and Schwann cells. The Schwann cells are immunostained for S100 (red) the neurones for nerve growth factor (green), x50 (Courtesy of Professor Susan Standring).

Scherer and Arroyo (2002) provide an extensive review of the molecular organisation of myelinated axons. The larger axons are enwrapped along their length by a continuous series of contiguous Schwann cells into which they are invaginated. The nodes of Ranvier represent the points of contiguity of adjacent Schwann cells (Fig. 2.19). The fibre is contained within a basal lamina. The basal lamina separates nerve fibres from the endoneurial space and it runs without interruption from the central nervous system to the termination of the axon. Thomas (1963) defined this structure in an electron microscope study. Schwann cells are surrounded by a basal lamina approximately 250 Å in thickness which is separated from the plasma membrane of the Schwann cell by a gap of 250 Å. The endoneurium is organized in two layers which surround the basal lamina. The inner layer is composed of collagen fibres of smaller diameter than those in the outer layer which run longitudinally, circularly and obliquely. This layer is inflected at the nodes with the basement membrane. The outer layer consists solely of longitudinal collagen fibres and it is not inflected at the node. Bunge et  al. (1986) considered the basal lamina essential in the linkage

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51

Fig. 2.20  Clusters of unmyelinated axons (long arrows), enveloped by Schwann cell cytoplasm. Short arrows indicate basal lamina, x26,220.

between the Schwann cell and the axon and with the extracellular matrix. The smaller fibres are contained in bundles by columns of Schwann cells. Eames and Gamble (1970) showed the ensheathing arrangement of successive Schwann cells which overlapped and interdigitated: the Schwann cells of unmyelinated axons in these nerves give off multiple cytoplasmic processes, which form close relationships with axons, with other processes, and with bundles of collagen. A ramifying “network” system of Schwann processes is thereby present throughout the endoneurium.

Eames and Gamble recognize areas of specialisation of the Schwann membranes which consisted of “a short length of increased plasma membrane thickness and electron density.” Later studies using scanning electron microscopy and freeze fracture replication have generally confirmed these earlier observations (Stolinski and Breathnach 1982). It is at times very difficult to distinguish between a nonmyelinated axon and a Schwann cell process in histological sections of regenerating peripheral nerves! (Fig. 2.20). The diameter of the axon is one important factor which determines whether the Schwann cells will lay down a myelin sheath around it. Webster (1993) proposes that the sheath is laid down in spiral layers by the Schwann cell, or part of its surface, moving around the axon (Webster 1993). The multilamellar sheath has a high lipid content and some protein components. Suter and Martini (2005) say that the major component of the protein components of myelin is Po myelin protein zero (MPZ), which accounts for 50–60% of all myelin protein. Peripheral myelin protein 22 (PMP 22) comprises from 2% to 5% of myelin proteins and mutations of the controlling gene lead to inherited myelin disorders. Suter and Martini comment that mutation of this gene was: “the first identified culprit gene for inherited neuropathies of Charcot-Marie Tooth (CMT) type.” Myelin basic protein

(MBP) accounts for 5–15% of myelinated proteins. The myelin associated glycoprotein (MAG), which forms no more than 0.1% of the myelin proteins, may play a pivotal role during myelination because of its early expression and because of its location to the axon-Schwann cell interface. Mice genetically engineered to be deficient in MAG showed extensive axonopathy and degeneration of myelin in motor fibres. The myelin sheath is traversed by cytoplasmic channels – the incisures of Schmidt-Lanterman (Hall and Williams 1970) (Fig.  2.21). The meeting points of consecutive Schwann cells are the nodes of Ranvier. These are short, about 1 micron in length and the axon here is constricted,

Fig. 2.21  A widened Schmidt-Lanterman incisure in a teased mouse sciatic nerve. Normal saline in vitro, x100 (Courtesy of Professor Susan Standring).

52

free of myelin but enveloped by projections of Schwann cytoplasm. The node is bordered by an adjacent paranode, which is dilated and which contains an increasing amount of mitochondrial rich Schwann cell cytoplasm outside a more or less crenated myelin sheath. Berthold et al. (2005) characterize the node thus: “these parts of the myelinated nerve fibers, the paranode-node-paranode (PMP) regions, constitute, structurally as well as functionally, the most spectacular parts of a myelinated nerve fiber.” The PMP regions are responsible for the generating and propagation of the action potential and they are the centers for activity in the early phases of Wallerian degeneration and collateral sprouting (Figs. 2.22–2.24). The axon-myelin sheath–Schwann cell complexes are arranged in bundles otherwise known as fascicles or funiculi. In so small a nerve as the fourth cranial there may be as many as 3,400 fibres. In the roots inside the spinal canal endoneurial collagen is scanty in contrast with the abundant content in the nerves outside the foramen (Gamble 1964; Eames and Gamble 1964) The surgeon who has had dealings with nerves inside and outside the spinal canal will appreciate the distinction: the spinal roots and rootlets are fine and fragile and very susceptible to trauma; the peripheral nerves are strong and have much greater resistance to handling. Outside the intervertebral foramina the three supporting structures, epi, peri, and endoneurium are clearly established. The epineurium, in effect the prolongation of the dural sleeve of the nerve roots, is composed of longitudinally directed collagen fibres, fibroblasts and fat cells. (Gamble and Eames 1964). The perineurium, which ensheaths the bundles, is composed of flattened cell processes alternating with layers of collagen. It provides a barrier to diffusion (Thomas 1963). The perineurium is strong; the intrafascicular pressure can be raised to more than 300  mmHg before it ruptures (Selander and Sjostrand 1978). The contents of the perineurium are under tension so that when it is cut they are extruded, rather like

Fig. 2.22  Node of Ranvier, mouse sciatic nerve in vivo, oblique incident illumination, x400(Courtesy of Professor Susan Standring).

Surgical Disorders of the Peripheral Nerves

toothpaste. This is most clearly seen on the day of injury in nerves which have been transected or ruptured and it is one of the indications that the level of section of the stump is adequate. The outflow rapidly diminishes over the course of several days. In the endoneurium, supporting the fibres

Fig. 2.23  Longitudinal section through a node of Ranvier, showing a remyelinated heminode (left) adjacent to a normal heminode (right). Compare the complexity of the paranodal fingers of the normal myelin sheath with the simple arrangement of the paranodal loops of the thinner, remyelinated sheath, x5,000 (Courtesy of Professor Susan Standring).

Fig.  2.24  Double immunostaining of sural nerve showing nodes of Ranvier (black) stained with antibodies to junction adhesion molecule (JAM – c) and axons (red) stained with antibodies to neurofilaments, x40 (Courtesy of Professor Praveen Anand).

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53

themselves, there is a return to longitudinal direction of cells and fibres; there are abundant collagen fibrils (Thomas 1963; Gamble and Eames 1964). Stolinski (1995) describes the epineurium as an outer layer of alveolar connective tissue and a more compact inner layer containing collagen and elastic fibres which are arranged in a wavy pattern. Perineurial cells are also arranged in a wavy manner and Stolinski suggested that the spiral bands of Fonata represent the wavy or zig zag organisation of nerve fibres. These arrangements provide a degree of protection to the nerve against traction. The nerve can be stretched by as much as 20% before the wavy arrangement is converted into a linear array. Tillett and her colleagues (2004) offer the concept of a distinct core and sheath in the rat sciatic nerve, and proposed that the interactions between the core and the sheath involve physical connections rather than a viscous fluid interface. The anatomical features of this interface were characterized using transmission electron microscopy and it appeared that the sheath was derived from the epineurium and most of the perineurium, whilst the core consisted of the endoneurium and a small proportion of perineurium: the plane of cleavage involved the innermost perineurial cell layer. A normal peripheral nerve trunk exposed at operation is enveloped in a well defined translucent envelope. This is the external epineurium (Fig.  2.25). Normal nerve trunks are easily distinguished from other longitudinal structures by the appearance of white spiral bands on their surface, the spiral bands of Fontana (Clarke and Bearn 1972, Stolinski 1995). The individual bundles or fascicles are seen within. These are enclosed by the perineurium with some condensation of the innermost epineurium forming a white, opaque layer (Fig.  2.26). The tissues surrounding the bundle form the epineurium, rather loose in texture, and rich in blood vessels which pass longitudinally along the axis of the nerve. However, the observer will see adventitial material outside the epineurium which is more clearly defined in some nerves

than in others and in different locations within the limb. There are, for example, translucent connective tissue arcades accompanying the median nerve in the forearm where it passes between the superficial and the deep flexor muscles of the fingers. Such vessels provide an alternative collateral pathway to the part; they also supply the nerve trunk so permitting the use, for example, of the ulnar nerve as a free vascularized graft. This tissue plane not only conveys vessels to the nerve but it also permits gliding of that nerve across joints and against the adjacent tissues. Thomas (1963) has estimated that 45% of nuclei seen in transverse sections of nerves are those of fibroblasts. Sunderland (1968) mapped the arrangement of bundles along the course of nerve trunks, showing branching, fusion and changes in number. He further showed that the cross-sectional area of the nerve occupied by connective tissue was variable, ranging from 60% to 85% (Fig. 2.27). These findings, especially those concerning re-arrangement of bundles, have been used to cast doubt on the feasibility of achieving accurate co-aptation of the ends of divided nerves. However topographical organisation is one essential quality of the nervous system and this is shown by the considerable topographical segregation of neurones involved in the somatic afferent pathways in the dorsal root ganglia, dorsal horn of the spinal cord, the thalamus and the sensory cortex. Perhaps predictably injury anywhere in the nervous system provokes considerable reorganisation. Sunderland himself recognized that there was a degree of topographical segregation of nerve fibres according to function over considerable lengths of the median and ulnar nerves. Micro­neurographic studies (Torebjörk and Ochoa 1980) confirmed these findings. Specific organisation (aggregation) of sensory and motor fibres occurs in the median nerve in the arm, so it does in all peripheral nerves. This segregation permits transfers such as that of Oberlin et  al. (1995), in which one bundle of the ulnar nerve

Fig. 2.25  The extrinsic epineurial vessels of the ulnar nerve, x40.

Fig. 2.26  The bundles and epineurial vessels of the ulnar nerve after displacing the adventitia, x40.

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Surgical Disorders of the Peripheral Nerves

Fig. 2.27  Sural nerve undergoing Wallerian degeneration 4 days after a proximally sited crush lesion showing macrophages stained positively for ED1, x100 (Courtesy of Professor Susan Standring).

is anastomosed to the nerve to the biceps. Stimulation of individual bundles, whose number ranges from 6 to 12, permits separation of those passing to the flexor muscles of the wrist and fingers from those passing to the small muscles of the hand. The ability to “map” the stump of a divided nerve allied to the ease of matching individual bundles by their size and disposition is but one of the great advantages of urgent repair of nerves (Fig. 2.28).

2.2.1 Conduction The special property of the nerve fibre is that of conducting a signal in the form of a propagated action potential (Landon 1985). Rasminsky (1985) opens the subject thus: “Nerve fibres are specialized processes of nerve cells that have the unique property to propagate action potentials, the currency of information in the nervous system.” The action potential is a brief, self propagating reversal of membrane polarity and it depends on an initial influx of sodium ions which cause a reversal of polarity to about +40  mV followed by a rapid return towards the resting potential as potassium ions flow out. In the unmyelinated fibre, a wave of depolarisation spreads continuously along the axon, attenuated by the large capacitance of the axolemma, which limits the velocity of conduction to about 1m/s. Standring (2008) likens this to: a flame moving along a fuse. Just as each segment of the fuse is ignited by its upstream neighbor, each segment of axon membrane is driven to threshold by the depolarization of neighboring membrane. Sodium channels within the newly depolarized ­segment

open and positively charged sodium ions enter, driving the local potential inside the axon towards positive values. This inward current in turn depolarizes the neighboring, downstream, non depolarized membrane, and the cyclic propagation of the action potential is completed.

The action potential is evoked by a stimulus which exceeds threshold by the all or nothing law of Adrian (1928); the cell body, on the other hand, responds in a graduated manner to stimuli transmitted across synapses which either inhibit or facilitate by raising or lowering the threshold respectively. In the myelinated fibre the myelin sheath acts as a capacitor and limits radial resistance at the internode, so that most of the current flows axially along the fibre. It is, says Bostock (1993) “powered by inward ‘kicks’ of inward membrane current at the nodes of Ranvier.” This method of “saltatory” conduction was so named by Tasaki and Takeuchi (1941; 1942), and further confirmed by Huxley and Stämpfli (1949). The myelin sheath thus enables the fibre to conduct rapidly without the necessity for a very large increase in axonal diameter. The caliber of unmyelinated axons varies from 0.4 to 1.25 mm (Gasser 1955); that of myelinated fibres from 2 to 22 mm (Ranson 1915; Greenfield and Carmichael 1935; Sunderland et al. 1949). The largest, fastest conducting elements are the myelinated fibres of around 20 mm diameter concerned with somatic afferent and efferent activity; the smallest and slowest conducting are the fibres of around 1 mm diameter that subserve autonomic activity and delayed pain sensibility (Galbraith and Myers 1991). Conduction velocity ranges from about 0.7 m/s in small unmyelinated fibres to about 80 m/s in the largest

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Fig. 2.28  Fascicular arrangement of nerve fibres and their supporting structures, the vascular systems of the peripheral nerve.

Epineurium Extrinsic vessel

Perineurium

Endoneurium Regional feeding vessel

Unmyelinated fibres

Node of Ranvier

Schwann cell nucleus

Myelin sheath

Axon

Myelinated fibre

56

myelinated fibres. Omer (1980) gives a range of 40–75 m/s in large myelinated fibres. The electrical changes associated with the wave of depolarisation can be measured through electrodes placed on the skin over the nerve, on the nerve, in the nerve or in individual fibres. These reactions form the basis for electrophysiological examination and for microneurography.

2.2.2 The Basis of the Action Potential: Ion Channels Hodgkin and Huxley (1939) made the first intracellular measurements of the resting potential across the cell membrane in the unmyelinated giant axon of the squid. In 1952 Hodgkin and Huxley described the cycle of depolarisation and repolarisation which underlies the high speed transmission of nerve action potentials and showed that the reversal of polarity was brought about by the influx and efflux of sodium and potassium ions across the axon membrane through individual parallel pathways which are controlled by independent gating particles or charges. Conduction of an action potential was blocked by pressure or by cold (Hodgkin 1937a, 1937b) Chiu (2005) defines the ion pathways, now known as channels: “voltage gated ion channels are like membrane lodged proteins that mediate rapid ion flux (106 ions/s) across cell membranes.” Chiu describes some of the methods that have been developed to define these entities. The patch clamp technique permitted study of the electrical events associated with the opening and the closing of a single ion channel. Later came the cloning of ion channels which permitted the recognition of 50 potassium channel genes and 10 sodium channel genes (by 2005). Later still the pore structure of potassium channels was studied by x-ray crystallography at a resolution of between 2.4 and 3.2 Å. Scholz, Reid, Vogel and Bostock (1993) were amongst the first to study, by patch clamping, sodium and potassium channels in the human nerve. The voltage-gated sodium ion channels are uniformly distributed along the membrane of nonmyelinated axons but they are densely concentrated at the nodes of Ranvier in the myelinated nerve axons. The potassium channels, on the other hand, are concentrated in the membrane at the juxta paranode. Ion channel function is energy dependent, it is ATP driven and this function is curtailed or altogether blocked by anoxia. Distortion of the myelin sheath adjacent to the node of Ranvier may unmask the potassium ion channels to such an extent that prolonged conduction block ensues. Evidently, demyelination is bound to lead to decrease of conduction velocity (McDonald 1963; McDonald and

Surgical Disorders of the Peripheral Nerves

Sears 1970) and eventually to conduction block. These facts will not escape the attention of the clinician faced with an ischaemic limb or with a deepening nerve lesion caused by expanding haematoma or entrapment. Once again we are indebted to Praveen Anand and his colleagues who have provided us with illustrations of sodium and potassium channels in the normal and in the injured nerve. Their extensive studies on the behavior of the ion channels in the injured nerve and in painful lesions of nerves are described in Chaps. 3 and 12. One of their observations reveals an important difference between the immature and the mature peripheral nerve in the human. Two voltage-gated sodium channels, Nav 1.8 and Nav 1.9 play a key role in neuropathic pain. The sodium channel Nav 1.9 could not be demonstrated in the nerves of infants (Yiangou et al. 2000) (Figs. 2.29 and 2.30).

Fig. 2.29  Sodium channel staining normal sural nerve, x40 (Courtesy of Professor Praveen Anand).

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Fig. 2.30  Nerve fibres within the mucosa and submucous plexus in human rectum stained with antibody to Protein Gene Product 9.5 (PGP9.5), a pan neuronal marker, x10 (Courtesy of Professor Praveen Anand).

2.2.3 Axonal Transport The axon functions as part of the neurone as a whole in transporting materials to and from the cell body. Lasek (1982) goes further than this: neurones exhibit a remarkable form of locomotion when they extend axons over great distances without moving the cell body. This capacity of neurones to extend axons independently of the movement of the perikaryon is one of the distinctive properties of the neuronal linkage because it distinguishes neurones from other migratory cell types.

Lasek (1982) further proposes that the unusual feature of neurones – their ability to translocate the axonal skeleton independently of the perikaryon – is accomplished by the continuous addition of cytoskeletal proteins at the proximal end of the cytoskeleton in the perikaryon. So, the neurone is able to extend its process “without towing the cell body along.” Ochs and Brimijoin (1993) define axonal transport as: “a system of intra cellular motility enabling nerve cells to deliver essential proteins and membrane components to the periphery, and to receive from these chemical signals and materials for disposal.” Two forms of transport, fast and slow, are recognized (Brimijoin 2005). The former may be orthograde (centrifugal) or retrograde (centripetal). The fast retrograde (centripetal) component conveys material to the cell body in microvesicles at the rate of 150– 300  mm/day. The fast orthograde (centrifugal) component

transports proteins, peptides, and neurotransmitters from the cell body at a rate of 200–400 mm/day. All systems are ATP dependant, and the microtubules are critical for fast axonal transport. Landon (1985) puts it this way: fast transport “is concerned with the orthograde transport of particular constituents of the axoplasm and materials such as some transmitter synthesizing enzymes, glycoproteins and membrane components, and the retrograde transport of membranous prelysosomal structures, and extra cellular materials such as nerve growth factor ingested at the axon terminal.” The process is sensitive to temperature; it is sensitive to deprivation of oxygen. Slow transport is uni-directional, orthograde (centrifugal). Rates of transport are from 1 to 4 mm daily; it is concerned with the transport of the neurotubule-neurofilament network of the cytoskeleton. Brimijoin recognizes two distant components: 1. Slow component A (SCa averaging about 1 mm/day) 2. Slow component B (SCb averaging 2–10 mm/day) The rate of transport of the SCa component is of course about the same as the rate of peripheral regeneration after axonotomy. The significance of axonal transport in disorders of peripheral nerves is plain: interference with the centrifugal process is likely to lead to defect or cessation of conduction; interference with the centripetal process will ultimately lead to degeneration of the nerve cell.

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2.2.4 The Blood Supply of Nerves Nerves have a very good blood supply: they need it. The surgeon notes the segmental blood supply from without and the axial vessels within the nerve. There are indeed (Lundborg 1979,1988) intrinsic epineurial perineurial and endoneurial plexuses, and extrinsic regional vessels in the “paraneurium.” These form “separate but extensively interconnected microvascular systems” providing a wide margin of safety. As McManis and colleagues (1993) remark: “these anastomotic vessels confer a resistance to ischemia in peripheral nerves so that nerve suffers functional or structural changes only when there is widespread vascular or microvascular damage.” Dyck et al. (2005) show that arterioles and small arteries are detectable only in the epi- and perineurium, and that these vessels may range in diameter from 50 to 400 mm. The arteries penetrating the perineurium are small, only rarely do they exceed 15  mm in diameter and small arteries are rarely detectable within the endoneurium. Lymphatics have not been detected within the perineurium. The endothelial junctions of the endoneurial vessels are tight, unlike those in the epineurium (Low 1976). Some nerves are better supplied than others. Kadiyala and his colleagues (2005) showed that the common peroneal nerve at the knee has far fewer extrinsic vessels than the tibial nerve at that level. Seddon (1975) commented on the extent to which it was permissible to mobilize the nerve in order to facilitate suture. His rather sanguine views of the effect on the blood supply are not confirmed by the later injection studies of Bell and Weddell (1984); indeed, later clinical experience has shown that it is preferable to bridge a gap by interposition than by mobilisation.

Surgical Disorders of the Peripheral Nerves

Weerasuriya (2005) proposed the concept of a “bloodnerve interface” instead of the “blood-nerve barrier.” Weerasuriya comments: “the structure of the perineurium combines features of the dura mater in terms of mechanical strength and the arachnoid with respect to impermiance.” Endoneurial fluid is in contact with the cerebro-spinal fluid through the subarachnoid angle. Flow is proximal to distal, the hydrostatic pressure of cerebro-spinal fluid is 10 mmHg, it is 3.5  mmHg in the dorsal root ganglion and it drops to between 1 and 2  mmHg within the peripheral nerves. Endoneurial hydrostatic pressure (EHP) rises in the aged nerve and it is possible that external pressure increases EHP by obstructing flow. This may be one factor underlying the effect of entrapment or compression. Hill and Hall (1999) suggest that the aggregation of Renaut bodies at sites of potential entrapment represents a response to local injury to the endoneurial capillaries. The blood supply to the roots of the spinal nerves is much less robust (Figs.  2.31a–c and 2.32). Two distinguished Cambridge anatomists, Woollam and Millen (1958), considered that: “man has just as much nervous system as he can supply with oxygen and no more.” The most important spinal vessel, the anterior spinal artery, was studied in the fetus and in the guinea pig and rat. Relatively few radicular arteries survived into adult life, the average number of those so doing was eight. Two of these seemed to be particularly important: a cervical vessel, arising from the vertebral artery and entering into and sustaining the anterior spinal artery at C6, C7 or C8, and the artery of Adamkiewicz 1881a,b, in the upper lumbar region. Figure 1 in Woollam and Millen’s paper shows, in a 24 week human fetus, that the radicular vessel adjacent to

Fig. 2.31  The dorsal vessels to the spinal cord and cauda equina: (a) upper thoracic segment (b) thoraco lumbar junction, (c) cauda equina.

The Microscopic Structure of the Nervous System: Its Function

a

59

b

Fig. 2.32  Resin cast of the blood vessels of the neck, seen from the front (a) and from the side (b). The arteries are shown red, the veins blue showing the segmental arrangement of vessels. The anterior spinal artery is shown (arrow) with an important segmental feeder vessel.

the seventh cervical nerve was the major supplier for the anterior spinal artery (Fig.  2.33). Dommisse (1974, 1975) confirmed that the number of radicular arteries (which he termed the medullary feeders) reinforcing the anterior longitudinal arterial channel was eight and that those reinforcing the dorsal arterial columns were 17. Only 8% of those passing to the cervical spinal cord arose from the vertebral artery. The pattern was variable: “but the principle of a rich supply for the cervical and lumbar enlargements was confirmed” (Dommisse 1975). In the 6 drawings from cadaver dissections a total of 12 vessels are described, 4 of these at the level C6, C7 and 4 more at C4. The anterior spinal artery is the most important of the longitudinal channels. Its central branches, which are end arteries, supply about two-thirds of the cross-sectional area of the cord. The rest of the dorsal grey and the white columns are supplied by branches arising from the dorsal arterial system. Occlusion of the anterior spinal artery leads to the catastrophe of infarction of the anterior cord, the anterior spinal cord syndrome. The significance of damage to major feeder arteries is emphasized by the work of Svensson (2005) who addressed the risk of severe cord lesion after aortic surgery. Svensson achieved a rate of paralysis of 3.8% on patients most at risk, those with complex thoracoabdominal aneurysms, by a number of measures which included: “sequential segmental repair with repositioning and moving the clamp upon the grafts sequentially downwards

and reattaching intercostal and lumbar arteries.” Disruption of the radicular arteries entering the spinal canal with the spinal nerves which form the brachial plexus probably underlies the partial Brown Séquard syndromes which are seen in cases of avulsion. Occlusion of flow through those vessels by tamponade explains the catastrophe of spinal cord infarction or even death complicating spinal nerve or interscalene block.

2.2.5 The Nervi Nervorum Curiously but perhaps predictably, nerves have their own nerve supply in the shape of the nervi nervorum, derived from their own fibres. There are free endings in the epi-, peri- and endoneurium, and some encapsulated endings of Pacinian type in the endoneurium. (Hromada 1963). These are probably one factor underlying the exquisite sensitivity of nerves trapped in fibrosis after operations for “entrapment” neuropathy.

2.2.6 Changes in Nerves with Ageing Corbin and Gardner (1937) examined the dorsal and ventral roots of the eighth and ninth thoracic spinal nerves of 34

60

Surgical Disorders of the Peripheral Nerves Posterior spinal aa.

Posterior segmental medullary a. Spinal branch Anterior segmental medullary a.

Posterior segmental medullary a. Spinal branch Anterior segmental medullary a.

Anterior spinal a.

Fig. 2.33  The segmental medullary (radicular) arteries and the anterior spinal artery in the lower cervical cord (after Woollam and Millen 1958).

cadavers whose ages ranged from 1 day to 89  years. The highest number of myelinated fibres, found in persons in their second and third decades, was 187% larger than that found in the nerves of a 1 day old infant. They found that after the third decade there was a gradual loss of myelinated fibres, up to 32% for the person of 89 years. Cottrell (1940) examined the median, femoral, sciatic and common peroneal nerves of 30 persons coming to necropsy at ages ranging from 3 h to 81 years. She found changes in the vessels and the connective tissue, with “alteration and loss of the nerve fibers.” Ochoa and Mair (1969) examined portions of the sural nerves of seven volunteers aged 5–59, and were the first to show that active destruction of unmyelinated fibres started early in life, whereas loss of myelinated fibres was found only in the 59-year-old. Tohgi and colleagues (1977) examined the sural nerves of 79 persons coming to necropsy after “acute death,” whose ages ranged from 1 week to 88 years. The average density of small myelinated fibres decreased rapidly from the age of 1 week (26,300/mm2) to the second decade (9,560/mm2), and continued to decrease gradually with age, to reach at the eighth decade an average of 74% of that at the second decade. There seems to be an error in the printing of the figure for the eighth decade. Large myelinated fibres appeared first in an infant aged 3 months. Their density increased rapidly, to reach at 3 years the level found in the young adult. The average of the

third decade was 6,480/mm2; at the ninth decade it was 3,480/ mm2. In this extensive study there is mention of the ageing changes in the vasa nervorum and the perineurium. Jacobs and Love (1985) made a qualitative and quantitative study of 27 sural nerves obtained within 24 h of death from human subjects without history of disease or of ingestion of drugs known to affect peripheral nerve. Densities of myelinated and unmyelinated fibres decreased from birth to the end of the eighth decade, because of increasing size and separation of fibres during the first decade, and an increase in endoneurial collagen in the older persons. Also, the slope of the internodal length-fibre diameter increased progressively during the first decade, but then remained virtually constant until the age of 60. Then, degeneration, regeneration, demyelination and remyelination caused increasing variation in internodal length. Thomas et al. (1993b), summarising previous findings, refer to “mild peripheral neuropathy” of older humans. Norris and colleagues (1953) examined age changes in the maximum conduction velocity of motor fibres of the ulnar nerves of 175 ambulatory male patients, employees and staff members of the Baltimore City Hospitals. There was steady reduction in conduction velocity from the third to the ninth decade. They canvassed possible causes for this regression. Taylor (1984) studied the effects of age on conduction and amplitude in motor and sensory fibres of adult nerves. He indicated that tables of normal data of the rise and

The Microscopic Structure of the Nervous System: Its Function

fall of conduction and amplitude could be constructed for use in clinical investigation. Kimura (1993) stated that: “nerve conduction velocities are roughly half the adult value in fullterm infants, but increase rapidly, reflecting the process of myelination, to the adult value at age 3–5 years.” He noted the slow decline of conduction velocity after the fourth decade, and drew attention to the contemporaneous increase of the latencies of the F wave and somatosensory evoked potentials. Cowen et al. (2005) describe the greater vulnerability with increasing age of large, long, myelinated nerve fibres, and of larger sensory neurones. There also appears to be selective vulnerability of some autonomic neurones, notably within the enteric system. Evidence is provided to support the proposal that “interactions between sensory neurones and their receptor targets are crucial initiators of an age related nervous deterioration.” These changes must evidently concern clinicians treating the very young and the rather old: in the former, they may have a bearing on diagnosis; in the latter, they may be relevant to the susceptibility of a nerve or nerves to damage by pressure or traction.

61 V

Re

V

C Re Ru

2.3 The Somatic Motor System The motor pathway begins in the neurones in the pre-central gyrus of the cerebral cortex. Their axons pass by the internal capsule to the mid-brain and to the pyramids of the medulla. From each side most fibres cross the mid line at the decussation of the pyramids to descend in the lateral part of the white matter of the cord as the lateral corticospinal tract. At various segmental levels impulses from this tract activate, through internuncial neurones, the motor cells in the anterior part of the grey matter (Fig. 2.34). “Extrapyramidal” tracts from the red nucleus, the vestibular nuclei and the reticular formation also influence the activity of the ventral horn neurones. Brodal (1981c) prefers to discard the designation “extrapyramidal,” on the grounds that “those cortical regions which give rise to fibers in the pyramidal tract also give rise to fibers to a number of nuclei which project further caudally….” The cell bodies of the motor neurones are in Lamina IX (Rexed 1954) of the ventral horn of the grey matter. There are large (alpha) and small (gamma) cells (Fig. 2.35). They are acted on by primary sensory fibres and by fibres descending from the cortex and from nuclei in the brain stem. The axons from the large cells are destined for the extrafusal fibres. By correlating the distribution of paralysis with the sites of loss of cells in the ventral horn, Sharrard (1955) was able to show how the cells were grouped in the grey matter. Broadly, the medial group supply the muscles of the trunk and neck; the lateral group supply the muscles of the limbs.

Fig. 2.34  The major descending tracts in the spinal cord and their overlapping zones of termination in the grey matter. C corticospinal, V vestibulospinal, Re reticulospinal, Ru rubrospinal.

Thus, cells of the latter group are present chiefly in the cervical and lumbar enlargements, whereas those of the medial group are found throughout the length of the cord. Nathan and Smith (1958) studied the spinal cord in patients who had earlier undergone cordotomy, and defined the descending

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Fig. 2.35  Motor neurone cell bodies in the ventral horn of human spinal cord stained with antibodies to TRPV 4, a novel ion channel, x40 (Courtesy of Professor Praveen Anand).

pathways for the control of the bladder: “in man, the majority of descending fibers concerned with micturition lie in the lateral column, on an equatorial plane passing through the central canal. This location remains the same in the cervical, thoracic, lumbar and sacral segments.” The distribution of nerves within the muscles of the upper limb has been described by Lim and his colleagues (2004). The staining technique of Sihler was used which renders muscle translucent and stains the myelin in the nerves a dark blue. The intramuscular distribution of the nerves was then mapped by photographing the superficial and deep surfaces of the muscle using a back light technique. In flat, triangular or trapezoid muscles (class 1) the main nerve runs perpendicular to the muscle fibres giving off side branches that run parallel with them. The spindle shaped or fusiform muscles (class 2) were subdivided into unipennate or bipennate muscles. In the bipennate muscles the aponeurosis of the tendon splits the muscle into two compartments and in these the primary nerve divided into two secondary branches passing each side of the tendon. In muscles with more than one head of origin (class 3) the pattern of innervation is more complex. The pattern of innervation is determined by three factors: “the shape of the muscle, its position and orientation in relation to the passage of the nerve, and the muscle tendon morphology.” These findings support the idea of transfer of part of a muscle and they emphasize the requirement for the repair of intramuscular nerves in lacerated muscles. Contact with, and transmission to muscle is effected through the motor end-plates (see Fig. 2.42). There are two components of each end plate: neural and muscular. They are separated by a cleft of about 30 nm. The muscular soleplate contains a number of muscle cell nuclei; it is not itself

Surgical Disorders of the Peripheral Nerves

contractile. There are two types of neural endings: the en plaque terminal on extrafusal (alpha nerve fibre) muscle fibre, and the plate endings on intrafusal (gamma nerve fibre) muscle fibres. Transmission at en plaque endings initiates action potentials which are rapidly conducted to all parts of the muscle fibres, whereas transmission at plate endings of “trail” and “en grappe” types excites the fibres at several points. Acetylcholine released at the nerve ending interacts with receptors to produce depolarisation of the muscle membrane and trigger the action potential in the muscle. The ventral roots from the first thoracic to the second lumbar segments of the spinal cord contain also the efferent pre-ganglionic fibres of the sympathetic nervous system: those of the second to fourth sacral nerves contain the efferent pelvic parasympathetic outflow.

2.4 The Somatic Sensory System The afferent pathways of the peripheral nervous system considerably exceed the efferent pathways in numbers and in complexity of organisation. By no means all lead to conscious sensation. Amongst the somatic afferents the Golgi organs and the muscle spindles are examples; the whole array of the visceral afferents is one more.

2.4.1 Cutaneous Sensibility The long debate about the mechanism of cutaneous sensibility begun by Blix (1884) and Goldscheider (1884) and continued by von Frey (1894, 1896), Head et  al. (1905), Head and Sherrin (1905), Head (1920),Adrian and Zotterman (1926), Adrian (1928), Zotterman (1939), Weddell (1941), Sinclair (1955) and many others is now drawing to its close: as Iggo (1985) remarks “the long-standing argument of ‘specificity’ versus ‘pattern’ in the operation of cutaneous receptors has been settled in favor of the ‘specificity’ hypothesis.” Iggo also states that: “it is now clear that no cutaneous receptors have an absolute specificity; they have a high degree of selective sensitivity, that is, a much reduced threshold to one form of stimulation” (Fig.  2.36). Adrian pioneered methods in Cambridge in the 1920s (Adrian and Zotterman 1926) which enabled electrophysiological studies of single afferent units. This led to work with microelectrodes and with intraneural microstimulation done by, among others, Hallin and Torebjörk (1973), Torebjörk and Ochoa (1980), Vallbo and Hulliger (1981) Hagbarth et  al. (1993), and Torebjörk Schmelz (2005). However, as Wall

Fig. 2.36  Cutaneous sensory receptors: glabrous skin (left) and hairy skin (right). Aα Aδ C

‘G’ unit ‘D’ unit Cutaneous (C) unit

Aδ/C

Aα

Field receptor

Thermoceptors

Aα

Lanceolate

Aδ/C

Aα

Aα

Aα

Aα

Paciniform

Type II (Ruffini)

Type I (Merkel)

Vibrissa

Nociceptors

Rapidly adapting mechanoreceptors

Slowly adapting mechanoreceptors

Hairless skin

Aα

Aδ/C

Aα

Meissner

Thermoceptors

Aα

Pacinian

Aδ/C

Aα

Type II (Ruffini)

Nociceptors

Aα

Type of ending: Type I (Merkel)

Type of fibre:

Rapidly adapting mechanoreceptors

Slowly adapting mechanoreceptors

The Microscopic Structure of the Nervous System: Its Function 63

Hairy skin Guard hair Down hair

Touch dome

64

(1961) pointed out: “specific modality and patterning theories are supplementary. The recognition of receptor specialisation for transduction of particular kinds and ranges of cutaneous stimulation does not preclude acceptance of the concept that information is coded in a pattern of impulses.” Mountcastle (1980) assigns to the specialized receptors a role as transducers responsible for amplification. He points out that in areas of skin subjected to sensory testing and later marked and excised, histological examination has shown only free nerve endings. No specialized mechanosensor transducers transmitting through unmyelinated fibres have been identified yet; the same is not so for nociceptors and most thermoreceptors, where the transient receptor potential (TRP) channels have been identified as transducing specific ranges of temperature. All these receptors seem to be represented in fine branching unmyelinated nerve endings in the cell layers of the epidermis (Fig. 2.37). The basis of stereognosis is a combination of stimuli from skin, tendons, muscles and joints relaying sensory information centrally where comparison is made from memories of movement. The role of movement is vital: a blindfolded person cannot identify the nature of a material if it is simply placed on the finger. Identification is aided if the material is drawn across the finger tip. Recognition is, however, immediate if the subject is allowed to create temporal and spatial patterns by feeling the texture between the moving finger and thumb (Melzack and Wall 1962). The fibres of afferent neurones are classed by their conduction velocity. Afferent fibres from the skin are divided into A-ab, A-d and C; muscle afferents are classed I, II, III and IV (Light and Perl 1993, Lawson 2005). There is some correlation between fibre diameter and the characteristics of the soma within the dorsal root ganglion. These are classed as large light (neurofilament rich) and small dark (neurofilament poor) neurones.

Surgical Disorders of the Peripheral Nerves

Fig. 2.38  Small diameter nociceptor cell bodies from a human dorsal root ganglion 2 weeks after avulsion stained with antibodies for prostaglandin receptor sub type EP1, x40 (Courtesy of Professor Praveen Anand).

Fig. 2.39  Small diameter nociceptor cell bodies and axons in the human dorsal root ganglion immunoreactive for the heat and capcaicin receptor TRPV1 2  weeks after avulsion injury, x20 (Courtesy of Professor Praveen Anand).

The neurones of C-fibres are small; those with Ad fibres are small to medium size; those with A-ab fibres are medium to large (Lawson 2005) (Figs. 2.38 and 2.39).

2.4.2 The Skin The introduction of immunohistochemical staining of nerve antigens has provided new insights into innervation of the skin (Kennedy et al. 2005). Kennedy says: Fig.  2.37  PGP9.5 immunoreactive somatic nerves in skin of patient with small fibre neuropathy, x 40 (Courtesy of Professor Praveen Anand).

bundles of nerves enter the skin deep in the dermis and course towards the skin surface, giving off axons to innervate the associated end organs. Unmyelinated nerve fibers comprise the vast

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morphologically unidentified receptors responding to very slow displacement of hair or skin are innervated by small slowly conducting C fibres. The principal mechano-sensor in hairy skin is the hair follicle receptor; in hairless (glabrous) skin the two principal types are the Meissner corpuscle, rapidly adapting, and the Merkel receptor, slowly adapting. Beneath the skin the rapidly adapting organ is the Pacinian corpuscle; the slowly reacting organ is the Ruffini’s corpuscle which is found in deep dermal layers and is characterized by large diffuse receptive fields. The Ruffini corpuscles provide information about finger position by responding to stretching of the skin (Lundborg 2004b). Stark et al. (1998) studied the distribution of Pacinian corpuscles in the hand: the total number identified was around 300 and most were located in the pulp skin of the fingers. Fig. 2.40  PGP9.5 immunoreactive autonomic nerve fibres surrounding sweat glands in the skin of a patient with small fibre neuropathy, x40 (Courtesy of Professor Praveen Anand).

majority of cutaneous innervation to the above dermal structures. The few myelinated nerve fibers terminate at hair follicles, Meissner corpuscles and Merkel complexes. The vertically orientated nerve bundles form a horizontal sub epidermal neural plexus. Epidermal nerve fibers branch from this plexus and, while penetrating the dermal-epidermal basement membrane to enter the epidermis, they lose their Schwann cells ensheathment and collagen collar.

The sweat glands are carpeted by a dense pattern of autonomic nerves (Fig. 2.40). Fine unmyelinated nerve endings form a network covering larger arteries in the deep dermis. The density of innervation of the epidermis is greatest in the proximal segment of the limb. There is little change between the 20th and 80th year.

2.4.3 Cutaneous Sensory Receptors

2.4.3.2 Thermoreceptors So long ago as 1884 Blix postulated that there were two types of thermoreceptor in the human skin: one for cooling and one for warming. Cooling receptors are served by unmyelinated and fine myelinated fibres, usually serving receptor fields about 100 mm in diameter (Light and Perl 1993). They are very sensitive to decrease in skin temperature from the normal or “neutral” level of 30–35°C. Fowler and colleagues (1988) indicate a conduction velocity of up to 2.1 m/s. Davis and Pope (2002) found that the sensation of cooling is replaced by an ache below 17.5°C and by pain below 14°C. Warming receptors, less common than cooling receptors, have receptive fields of less than a millimetre in diameter. Warm sense is a function of unmyelinated fibres within the epidermis; as we have seen the TRP channels transduce specific ranges of temperature. Temperatures above 43°C induce firing in C-fibre polynociceptors. Temperatures above 53°C evoke responses in fast conducting myelinated mechano-heat fibres (Light and Perl 1993, Lawson 2005).

Three types of cutaneous receptor are defined: low threshold mechano-sensors; thermoreceptors; nociceptors. 2.4.3.3 Nociceptors 2.4.3.1 Low Threshold Mechanosensors The distinction is made between slowly adapting receptors responding to sustained displacement such as continuous pressure; rapidly adapting receptors responding to the beginning or withdrawal of a stimulus or by a moving stimulus, and receptors responding to brief mechanical disturbances such as vibration and tapping. The first group includes the Merkel cells; the second includes the Meissner corpuscles and the third, the Pacinian corpuscles. Most are innervated by large and medium sized fibres conducting at rates of from 20 to 90  m/s. A few

The term is applied to primary afferent units which “uniquely signal stimuli intense enough to threaten physical damage to the tissue” (Light and Perl 1993). Some respond to intense mechanical stimuli; some to strong thermal stimulation, and some are polymodal. Impulses travel in myelinated fibres in the Ad to Aab ranges and in unmyelinated C fibres. Nociceptor fibres are widely distributed in the skin, muscle, joints, the epineurium of trunk nerves and the wall of blood vessels as an extensive plexus of free nerve endings. These pass to fine myelinated and non myelinated fibres and also to the largest (Aab) fibres (Light and Perl 1993, Lawson 2005). Ad nociceptors are high threshold mechano-sensors.

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Some respond to damaging heat. They conduct impulses from receptive fields of about 5 mm2 at about 20 ms. Many of the C-fibres are polymodal, responding to a range of noxious stimuli including histamine and other chemicals, heat, cutting and crushing. C-fibres are responsible for the triple response of Lewis and they are the basis of the axon reflex. They are less than 2 mm in diameter and conduct at between 0.5 and 2  m/s from fields which range from 1 to 10  mm2. Microneurography has clarified the physiological characteristics of the nociceptors in humans. Sharp, well localized pain follows stimulation of Ad afferents. Stimulation of single C-afferents induces dull, burning, poor localized and delayed pain (Torebjörk and Ochoa 1980). Head (with Rivers and Sherrin in 1905) observed two types of pain after the division and suture of his own superficial radial and lateral cutaneous nerves of the forearm. There was epicritic pain which was sharp and localized and protopathic pain which was dull, burning, delayed and unpleasant. It is tempting to relate these two pain types to the now proven characteristics of the two main groups of nociceptors. The reader can experience the two modalities of pain by stimulating the skin on the front of the wrist with a sharp pin. First, and almost immediately, a sharp, well localized pain is experienced. A little later the delayed response–slightly unpleasant, a little longer lasting and a little diffuse – is felt. The A-ß and A-d nociceptors have punctate superficial receptive fields and respond to noxious mechanical or noxious mechanical and thermal stimuli (Mechano-heat units) (Lawson 2005).

2.4.4 Deep Sensibility Sensation is conveyed from muscles, ligaments and tendons from specialized receptors and from free nerve endings in those structures. The receptor organs are: in muscle, muscle spindles and free nerve endings; in tendons, the Golgi organs, and in capsules and ligaments various endings, some similar to Ruffini endings, Pacinian corpuscles and Golgi organs. There are also plexuses of unmyelinated fibres (Fig. 2.41). Joints are innervated by a network of rapidly conducting myelinated fibres some of which are associated with encapsulated mechanosensors and by high threshold, slowly conducting fibres many of which are perhaps nociceptors (Takebayashi et  al. 1997, Petrie et  al. 1997, Hogervorst and Brand 1998, Chen et al. 2000). Takebayashi et al. (2006) recognized sympathetic afferents innervating the lumbar intervertebral discs. Tomita et al. (2007) investigated the distribution of nerve endings in the human dorsal radio-carpal ligament by fluorescence immunohistochemistry, with confocal laser microscopy and by Kontron image analysis “to rebuild” the endings, so providing data about morphological characteristics as well as incidence, density and distribution.

Surgical Disorders of the Peripheral Nerves

2.4.5 The Muscle Spindles It is over a 100 years since Sherrington (1894) demonstrated by ventral root section that “in a muscular nerve-trunk from one-third to one-half of the myelinated fibers are from cells of the spinal root-ganglion.” The size of these fibres was from 1.5 to 20 mm; they were not the largest fibres in the nerve; the largest came from the ventral root. On the other hand, the largest of these fibers were larger than any fibres in the cutaneous nerves. “It was shown that about two-thirds of all the afferent fibers measure above 7 mm. Of these I imagine that considerably more than one-half may be apportioned to the muscle spindles, the majority of the rest belonging to Golgi’s tendon organs.” Sherrington found too that “the smallest myelinated fibers in the muscular nerve are for the most part, perhaps entirely, root ganglion fibers.” Sherrington further showed that there were “recurrent” (afferent) fibres in the ventral roots. He identified the special end-organs of the afferent fibres in the muscle-spindles (muskel-spindel) of Kühne (1864). Ruffini (1897), in his observations on sensory nerve endings in muscles, defined the “sensorial” end organs of muscle as (1) the muscle spindles; (2) the tendon organs (Golgi organs) and (3) the Pacinian corpuscles. He concluded: “in my opinion it is upon these three levels of sense organ that physiology must turn its attention if it will resolve the problem of the muscular sense.” Batten (1897) further examined the muscle spindle and its behavior in various pathological conditions including injury to the brachial plexus. Horsley (1897) noted their “preservation in conditions of extreme muscular atrophy.” Since Sherrington’s time, a very great deal of work has been done on the structure and function of the muscle spindles (Banks et al. 1982; Boyd 1962, 1966, Boyd and Smith 1984; Goodwin and colleagues 1972; Cooper and Daniel 1963; Matthews 1981). Their behavior after nerve injury and on their regeneration is described in Chaps. 3 and 4. Boyd and Smith (1984) state that “The whole human body must contain about 20,000 spindles, each of them a marvel of micro-engineering.” Most spindles lie deep in muscle near branches of its nerve or blood vessels. Each contains small muscle fibres (intrafusal fibres) within a cellular and connective tissue capsule. Banks (2005) says: “there are two principle kinds of encapsulated sense organs in skeletal muscle.… the tendon organ, which senses the force of contraction and the muscle spindle which responds to muscle length.” Both have a copious innervation by large afferent fibres and the muscle spindle and the Golgi tendon organ account for nearly all group 1 afferent axons from muscles. There are three types of specialized intrafusal muscle fibres: the nuclear bag fibres (bag 1, bag 2), with a central accumulation of nuclei, and nuclear chain fibres, smaller and with a single row of nuclei. The spindles vary in length from a few millimeters to a centimeter. Each spindle receives up to 25 terminal branches

The Microscopic Structure of the Nervous System: Its Function

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Ib afferent

Golgi tendon organ

Primary (annulospiral) Ia afferent

Secondary (flower spray) II afferent

Aα efferent Muscle sole plate

Aγ efferent Motor end-plate with synaptic vesicles Muscle spindle

Fig. 2.41  The afferent and efferent innervation of skeletal muscle.

Motor end-plate

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of motor and sensory axons, together with autonomic innervation. The motor axons are the b and g axons of the ventral root; the sensory axons are myelinated fibres of groups I and II. The combination of motor and sensory innervation is reflected in the complexity of the function of the spindles. The conception of a servo action is evidently too simple; rather, it is evident that the spindles play several roles in the “feedback” mechanism for regulating muscle contraction and for appreciation of body position. Stacey (1969) reckoned that in a “motor” nerve of the cat the distribution of fibres was one-third myelinated motor, one-third myelinated sensory and one-third unmyelinated sensory. Banks (2005) studied the nerve to the soleus muscle of the cat. The nerve contains 180 myelinated sensory and 270 myelinated motor fibres. Most of the myelinated afferents arose from 56 spindles and 45 tendon organs. There were 115 fusimotor gamma efferent fibres, which means that the 25,000 extrafusal skeletal muscle fibres are innervated by only one-third of the total of myelinated nerve fibres. The human longissimus capitis is the most densely spindled muscle and the density of muscle spindles is 25 times more in the lumbrical muscles than in the gastrocnemius (Cooper and Daniel 1963). The other afferent endings in skeletal muscle are free endings innervated by unmyelinated and small myelinated fibres. Iggo (1961) found that these responded to sustained pressure but not to stretch or contraction. They responded to hypertonic saline, but that stimulus was sufficient to excite the spindles too. Other studies of these organs and their afferent fibres were made by Mense and Schmidt (1974) and by Mense (1977) who studied the response to chemical noxious stimulation by single fibre recording. Pomeranz and colleagues (1968) traced fine myelinated afferents from viscera, muscle and skin to Lamina V of the dorsal horn of the spinal cord.

2.4.6 The Golgi Tendon Organs Scott (2005) characterizes the second of the two encapsulated mechano-sensors in muscle. The Golgi organ senses length of muscle and impulses project from it to the cerebellum and cortex. Stimulation of the fibres from the Golgi apparatus in hand muscles causes cortical potentials and “illusions of muscle stretch.” The Golgi organ is about 0.1 mm in diameter and between 0.2 and 1.5 mm in length. It contains collagen strands which continue into muscle fibres at one end and into the tendon at the other. There are between 3 and 50 of these organelles in each muscle, and Scott says that the ratio of Golgi organs to spindles is less than 0.3. The myelinated afferent fibre is a little smaller than the largest afferent from the muscle spindle, and in the cat it conducts at the rate of 60–110 m/s. The terminals interweave amongst the collagen strands as sprays or spirals. The capsule contains capsular cells which

Surgical Disorders of the Peripheral Nerves

are continuous with the Schwann cells. The receptor is slowly adapting; it responds to the whole range of muscle contraction and the firing rate is proportionate to active tension. In humans the fibres are silent at physiological rest and there are progressive steps in the firing rate with increasing steps in muscle contraction. Recovery is virtually complete after a crush lesion inducing axonotmesis, it is very much worse after repair of divided nerves. The poor recovery of the two main encapsulated mechano-sensors in muscle after repair of divided nerves may account for the common complaints of weakness, lack of stamina, and poor coordination and also for the failure of musculotendinous transfer using reinnervated muscles. As MacQuillan (2006) says: “the normal function of muscles is dependent on their sensory apparatus.” Up to now, most clinical work on sensation and on recovery of sensibility after nerve injury and repair has been directed to cutaneous sensibility. Yet function such as stereognosis and proprioception must depend principally on signals from endings in muscle, tendons and ligaments. It is perhaps inadequately appreciated that there may be good recovery of sensory function of the hand with very imperfect cutaneous reinnervation, and that pain is just as likely to follow damage to a “purely motor” nerve as it is to follow damage to a “mixed” or “sensory” nerve. There is in fact no such entity as a “purely motor” nerve, except perhaps for the hypoglossal or facial. The signals from the muscles supplied by those nerves probably proceed by other cranial nerves: the lingual in the case of the hypoglossal nerve and the trigeminal and the auricular branch of the vagus in the case of the facial nerve. There are indeed a few peripheral nerves without a cutaneous sensory component: the spinal accessory; the phrenic; the anterior and posterior interosseous; the deep branch of the ulnar; the suprascapular. The content of afferent fibres in all such nerves is about 30%. Laviano (1992/93) in his thesis on “transfer of the spinal accessory nerve for the suprascapular in avulsions of the brachial plexus” shows EM photographs of portions of the suprascapular nerve taken at operation as long as 94  days after injury (Fig.  2.42). There are numerous medium-sized and small myelinated fibres in good condition: evidently, the distal processes of dorsal root ganglia. Our work along the same lines also suggests a proportion of myelinated afferent fibres for the “motor” nerve of around 30%. Laviano’s work confirms the earlier supposition (Bonney 1959) that the dorsal root ganglion cells survive for a long time the interruption of their central processes. As to the last: in a case of extensive intradural damage to the plexus we examined a specimen of suprascapular nerve taken at the time of “neurotisation” well after the period required for degeneration, and found that it contained not less than 30% of myelinated fibres. It is perhaps best to drop the terms “purely motor” and “purely sensory,” and even drop the term “mixed” applied to nerves with both motor and cutaneous sensory components. The terms

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2.4.7 Central Connections

Fig. 2.42  Intact (afferent) myelinated and unmyelinated fibres in the suprascapular nerve after avulsion lesion of the brachial plexus. Specimen taken 6 weeks after injury, when efferent fibres had degenerated, x6,600(Electron microscopic study by Mr Stephen Gshmeissner).

“nerves with motor and cutaneous sensory components” and “nerves without somatic motor components” are, unfortunately, cumbersome, but they do say what they mean.

The great array of sensory receptors in the skin and deep tissues sends back to the centre the signals of the stimuli received. Most afferent fibres, with their cell bodies in the dorsal root ganglia, enter the cord by the dorsal roots. Others, with cell bodies in the dorsal root ganglia or actually in the ventral roots, enter the cord by the latter (Fig. 2.43). The first analysis of incoming signals takes place in the spinal cord and medulla where all fibres terminate. Most of the large myelinated fibres ascending in the dorsal columns terminate in the gracile and cuneate nuclei in the medulla. Some smaller fibres of the dorsal columns terminate and relay in the cord: these are the propriospinal fibres. Although the classical view of the function of the dorsal column has been challenged (Wall 1970) it is broadly true that, as Brodal (1981d) states, they “mediate sensory signals necessary for rather complex discrimination tasks” (Nathan et al. 1986). Other afferent fibres terminate and relay in the grey matter of the dorsal horn. Each lamina (Rexed 1952, 1954; Price and Meyer 1974) of the grey matter receives afferents of specific functional modalities; each has a particular neuronal structure. Small myelinated nociceptor and thermoreceptor fibres terminate in lamina I; C fibres, nocithermo- and mechanosensors, in lamina II (substantia gelatinosa). Larger mechano-sensor fibres terminate in laminae III and IV. These relay to cells whose axons either ascend in the dorsal columns or reach the dorsal column nuclei by the dorsolateral fasciculus. Some fibres pass through the dorsal horn to relay with the large cells in the motor apparatus in lamina IX. Some unmyelinated and small myelinated fibres enter the dorsolateral fasciculus (Lissauer’s tract) just lateral to the tip of the dorsal horn to join fibres from cells in the substantia gelatinosa. Direct ascending tract

Lissauer’s tract Lateral corticospinal tract

III IV V VI

II

Dorsal root ganglion

I

X VII VIII

Fig. 2.43  The laminae of the grey matter with direct ascending, crossed ascending and internuncial tracts.

Crossed ascending tract

IX

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Surgical Disorders of the Peripheral Nerves

Fig. 2.44  Ascending tracts in the cord, brain stem and cortex. Note the relay of the directly ascending tracts in the gracile and cuneate nuclei in the medulla (after Brodal 1981a).

Leg

Trunk

Gyrus post. centr. Arm Caps. int. Face

Pes. pedunculi Nucl. ruber Subst. nigra Nucl. sens. princ. n. v.

Nucl. vent. post. lat. thalami (VPL) Mesencephalon

Pons Lemn.med.

Nucl. fun. gracil. Nucl. fun. cun. N. tract. spin. n. v. Tr. sp. cereb. dors. Tr. sp. cereb. ventr.

Med. obl. Tr. spinothal.

Med. spin.

Some fibres cross the midline to terminate in laminae I and V of the contralateral dorsal horn. There is a complex network of interconnecting fibres in the dorsal horn and in the substantia gelatinosa in particular. Sensory input is first analyzed and modified here. Secondary neurones in the dorsal horn give rise to fibres which ascend or descend for a few segments in the cord. They give rise principally to the fibres that, crossing the midline, ascend in the long tracts in the anterolateral segment of the spinal cord (Fig. 2.44). The transmission of impulses from the nuclei of the dorsal column is influenced by fibres descending from the sensory motor cortex (Gordon and Jukes 1964). This influence is predominantly inhibitory. The ascending fibres of those nuclei form the medial lemniscus of the brainstem, crossing the midline in the medulla to end in the thalamus. The final resolution of sensory impulses takes place in the somatosensory areas of the cerebral cortex (Mountcastle 1957). Not

even in this last analysis are afferent functions separated completely from motor function: stimulation of any of these areas produces motor effect (Woolsey 1964).

2.4.8 Visceral Afferents Schott’s (1994) principal proposition was that “sympathetically determined” pain was so determined because the afferent pathways were in the autonomic nerves. He noted the finding by Varro and colleagues (1988) of calcitonin generelated peptide (CGRP) in visceral afferents, admitting that selective histochemical markers for specifically pain-serving afferents were not, at that time, available. In developing his thesis Schott reverted to the conception of a system of visceral afferents which comprised not only fibres from organs

The Microscopic Structure of the Nervous System: Its Function

Fig. 2.45  Afferent fibres in the enteric division of the autonomic system. Nerve fibres within the mucosa and submucous plexus of human rectum stained with antibodies to sensory sodium channel (Nav1.7), x10 (Courtesy of Professor Praveen Anand).

generally classed as “viscera” but also afferents from blood vessels (Fig. 2.45) The evidence for the presence of a system for conveying from all viscera sensations both perceived and unperceived rests largely on indirect observations: the truly autonomic functioning of viscera: the production of pain by mechanical stimulation of peripheral arteries and veins; the operation of “referred pain” mechanisms; pain after operations on the sympathetic chain; the lack of “visceral sensibility” when the function of visceral afferents is impaired by age. There is evidence from the work of Sugiura and colleagues (1989) that visceral afferents terminate in laminae IV, V and X of the dorsal horn as well as in laminae I and II. They were also traced up and down in the cord and crossing the midline. In their final “conclusion,” Sugiura and colleagues (1989) proposed that their morphological observations suggested that “the somato-visceral convergence could occur in the superficial dorsal horn of the spinal cord,” and that “the scattered and extensive distribution of the terminal fields of single visceral C-afferent fibres may be one basis for the poor localisation of visceral sensation.”

2.5 Cortical Maps The fact that individual movements were controlled by specific areas of the cerebral cortex was recognized in the latter part of the nineteenth century and a “body map” of the sensory cortex was developed by Penfield and Boldrey (1937). The extensive observations made by these early workers do not support the notion of a rigid motor and sensory homunculus. Graham Brown and Sherrington (1912) and Sherrington and Leyton (1917) recognized the functional instability of

71

cortical motor points. A motor response might be elicited by stimulation of the post central cortex after preliminary stimulation of the precentral gyrus, a process that they termed facilitation. Repeated stimulation of the face area of the motor cortex in chimpanzees was followed by swift expansion of the region to embrace the territory originally representing the hand. Repeated stimulation sometimes induced a change from flexion to extension, a phenomena that they termed “reversal.” A third phenomenon, of “deviation of response” was recognized: “a cortical point can also influence the motor response of another whose response is neither diametrically opposed to nor identical with or very closely similar to its own” (Graham Brown and Sherrington 1912). Penfield and Boldrey (1937) mapped the areas of motor function by direct stimulation of the cerebral cortex during operations in 163 patients which were conducted under local anesthetic for the purpose of removing tumor or epileptogenic foci. Localisation was sharply defined for finger movements but very much less so for movements of the tongue and the jaws. Stimulation of the post central gyrus usually evoked a sensory response but this was by no means sharply defined. Even in the best defined map of finger sensation over one-sixth of the 158 points of stimulation actually lay in the pre central gyrus (Fig. 13 in the original paper). On 11 occasions stimulation of the cortex evoked a sensation of pain and in 13 more a sensation of cold. Patrick Wall (Wall 1977) provided clear evidence of plasticity within the adult somatosensory system by recording from single neurones and dorsal column nuclei and finding striking changes in the size of the receptive fields soon after partial deafferentation. Wall suggested that these changes might be caused by the unmasking of synapses normally ineffective or silent. The concepts of brain plasticity are reviewed by Lundborg (2004a) in his excellent monograph . Lundborg says that: brain plasticity implies the capacity of cortical synapses to change their function as circumstances require. In a short term perspective, they may rapidly alter their function, as a result of unmasking or potentiation of already existing synapses. In a more extended perspective, the synapses may increase or decrease in actual numbers and new dendrites may be formed.

(Lundborg 2004c). He continues: “cells that fire together, wire together i.e. neurones become involved in accomplishing the same function and learn to work together efficiently. This phenomenon is named Hebbian learning. Conversely, cells that fire apart, wire apart – i.e. neurones that are not involved in accomplishing the same function learn to ignore each other.” (Hebb 1947) We touch upon other aspects of brain “plasticity” in later chapters but should not forget the salutary observations of Ramachandran and Hirstein (1998): “it is an embarrassing fact that despite five decades of single unit physiology in animals, studied in excruciating detail, we still have no clear idea of how the brain works or why cortical maps exist.”

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2.6 Synaptic Activity The transmission of impulses at synapses is chemical, by the release of neurotransmitters causing a change in the permeability and hence the electrical polarisation of the post-synaptic membrane. Such changes may be excitatory or inhibitory; they are usually short-lived, because of early inactivation of the neurotransmitter. This is not of course the whole process: the effect of some neurotransmitters may be more prolonged or even permanent. In addition, some substances released at synapses may simply modify the response of the post-synaptic membrane to neurotransmitters. The general term “neuromediators” has been applied to substances released at synaptic endings; “neurotransmission” implies a direct effect on post-synaptic membrane; “neuromodulation” implies alteration of its response to a neuromediator ( Wigley et al. 2008). The best-known mediator and the one that has longest been known, is of course acetylcholine, synthesized by motor neurones and released at the motor terminals in skeletal muscle and at the synapses in sympathetic and parasympathetic ganglia. The other well-known mediators belong to the monoamine group: they are noradrenaline, adrenaline, dopamine, serotonin and histamine. Noradrenaline is the chief transmitter at the endings of sympathetic ganglionic neurones. Adrenaline too is present in peripheral neural pathways. Nitric oxide (NO) mediates smooth muscle relaxation at autonomic synapses. The other monoamines are chiefly present in the central nervous system. Gamma amino butyric acid (GABA) is a major inhibitory transmitter which is released at the terminal of such local circuit neurone systems as the inhibitory Renshaw loop. Glycine is another example of an inhibitory transmitter which is particularly prominent in the lower brain stem and spinal cord. Glutamate and aspartate are widely distributed excitatory transmitters. The range of neuropeptide modulators is very wide, including those associated with the function of the hypothalamus and hypophysis, corticotrophin, beta-endorphin, the enkephalins, calcitonin-related gene peptide and nerve growth factors. In the field of peripheral nerves, the last is of great and growing importance; the beta-­endorphins and enkephalins are important in the consideration of the mechanism and treatment of pain.

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The Microscopic Structure of the Nervous System: Its Function Omer G (1980) Range of conduction velocities. In: Omer GE, Spinner M (eds) Management of peripheral nerve problem. WB Saunders, Philadelphia, pp 6–7 Penfield W, Boldrey E (1937) Somatic motor and sensory representation in the cerebral cortex of man as studied by electrical stimulation. Brain 60:389–443 Petrie S, Collins J, Solomonow M, Wink C, Chuinard R (1997) Mechano receptors in the palmar wrist ligaments. J Bone Joint Surg 79B: 494–496 Pomeranz B, Wall PD, Weber WV (1968) Cord cells responding to fine myelinated afferents from viscera, muscle and skin. J Physiol (Lond) 199:511–532 Price DD, Meyer DJ (1974) Physiological laminar organisation of the dorsal horn of M. Mulatta. Brain Res 79:321–325 Ramachandran VS, Hirstein W (1998) The perception of phantom limbs. The DO Hebb lecture. Brain 9(121):1603–1630 Ranson SW (1915) Unmyelinated nerve fibres as conductors of protopathic sensation. Brain 38:381–389 Rasminsky M (1985) Conduction in normal and pathological nerve fibres. In: Swash M, Kennard C (eds) Scientific basis of clinical neurology, vol 28. Churchill Livingstone, Edinburgh, pp 390–399 Rexed B (1952) The cytoarchitectonic organisation of the spinal cord in the cat. J Comp Neurol 96:415–495 Rexed B (1954) A cytoarchitectonic organisation of the spinal cord in the cat. J Comp Neurol 100:297–379 Ruffini A (1897) Observations on sensory nerve-endings in voluntary muscle. Brain 20:367–374 Saldanha G, Bar K, Yiangou Y, Anand P, Birch R, Carlstedt T, Burrin JM (2000) Marked increase of interleukin – 6 in injured human nerves and dorsal root ganglia. J Neurol Neurosurg Psychiatry 69:693–694 Sanchez D, Anand V, Gorelik J, Benham CD, Bountra C, Lab M, Klenerman D, Birch R, Anand P, Korchev Y (2007) Localized and non-contact mechanical stimulation of dorsal root ganglion sensory neurons using scanning ion conductance microscopy. J Neurosci Methods 159:26–34 Sanders FK (1942) The repair of large gaps in the peripheral nerves. Brain 65:281–337 Schenker M, Birch R (2000) Intact myelinated fibres in biopsies of ventral spinal roots after preganglionic traction injury to the brachial plexus. A proof that Sherrington’s “wrong way afferents” exist in man? J Anat 197:383–391 Schenker M, Birch R (2001) Diagnosis of level of intradural ruptures of the rootlets in traction lesions of the brachial plexus. J Bone Joint Surg 83B:916–920 Scherer SS, Arroyo EJ (2002) Recent progress on the molecular organisation of myelinated axons. 3 rd Bunge Memorial lecture. J Peripher Nerv Syst 7:1–12 Scholz A, Reid G, Vogel W, Bostock H (1993) Ion channels in human axons. J Neurophysiol 70:1274–1279 Schott GD (1994) Visceral afferents: their contribution to “sympatheticdependent” pain. Brain 117:397–413 Schwann T (1839) Mikroskopiche Untersuchungen über die Übereinstimmung in der Strukter und dem Wachstum der Tiere und Pflanzen. Sander, Berlin Scott JJA (2005) The Golgi tendon organ. In: Dyck PJ, Thomas PK (eds) Peripheral neuropathy, 4th edn. Elsevier Saunders, Philadelphia, Chapter 7, pp 151–161 Seddon HJ (1975) Surgical disorders of peripheral nerves. Churchill Livingstone, 2nd edn. Edinburgh, London/New York, pp 267–270 Selander D, Sjostrand J (1978) Longitudinal spread of intraneurally injected local anaesthetics. An experimental study of the initial distribution following intraneural injections. Acta Anaesthesiol Scand 22:622–634 Sharrard WJW (1955) The distribution of the permanent paralysis in the lower limb in poliomyelitis. J Bone Joint Surg 37B:540–558

75 Sherrington CS (1894) On the anatomical constitution of nerves of skeletal muscles: with remarks on recurrent fibres in the ventral spinal nerve-root. J Physiol 17:211–258 Sherrington CS (1897) The synapse in: the central nervous system. In: Foster M, Sherrington CS A textbook of physiology, vol 3, 7th edn. Macmillan, London, p 929 Sherrington CS, Leyton ASF (1917) Observations on the excitable cortex of the chimpanzee, orang-utan and gorilla. Quart J Exp Physiol 11:135–222 Sinclair DC (1955) Cutaneous sensation and the doctrine of specific energy. Brain 78:584–614 Stacey MJ (1969) Free nerve endings in the skeletal muscle of the cat. J Anat 105:231–254 Standring S (2008) Conduction of nervous impulses. In: Standring S (ed in chief) Gray’s anatomy, 40th edn. Churchill Living stone, Elsevier, pp 63–64 Stark B, Carlstedt T, Hallin RG (1998) Distribution of human pacinian corpuscles in the hand. J Hand Surg 25B:370–372 Stolinski C (1995) Structure and composition of the outer connective tissue sheaths of peripheral nerve. J Anat 186:123–130 Stolinski C, Breathnach AS (1982) Freeze-fracture replication of mammalian peripheral nerve – a review. J Neurol Sci 57:1–28 Sugiura Y, Terui N, Hosoya Y (1989) Difference in distribution of central terminals between visceral and somatic unmyelinated (C) primary afferent fibres. J Neurophysiol 62:834–840 Sunderland S (1968) Intraneural topography. In: Sunderland S Nerve and nerve injuries. E & S Livingstone Edinburgh, London. … Median nerve pp 758–769; ulnar nerve pp 816–825; radial nerve pp 905–914; sciatic nerve pp 1029–1046 Sunderland S, Lavarack JO, Ray LJ (1949) The caliber of nerve fibers in human cutaneous nerves. J Comp Neurol 91:87–101 Suter U, Martini R (2005) Myelination. In: Dyck PJ, Thomas PK (eds) Peripheral neuropathy, 4th edn. Elsevier Saunders, Philadelphia, Chapter19, pp 411–431 Svensson LG (2005) Paralysis after aortic surgery: in search of lost cord function. The James IV lecture. Surgeon 3:396–405 Takebayashi T, Yamashita T, Minakiy, Ushii S (1997) Mechano sensitive afferent units in the lateral ligament of the ankle. J Bone Joint Surg 79B:490–493 Takebayashi T, Cavanagh JM, Kallukuri S, Chen C, Yamashita T (2006) Sympathetic afferents from lumbar intervertebral discs. J Bone Joint Surg 88B:554–557 Tasaki I, Takeuchi T (1941) Der am Ranvierschen Knoten entstehende Aktionström und seine bedeutung für die Erregungsleitung. Pflügers Archiv 244:696–711 Tasaki I, Takeuchi T (1942) Weiters Studien über den Aktionsstrom der markhältigen Nervenfäser und über die elektrosaltatorische. Uberträgung des Nervenimpulses. Pflügers Archiv 245:764–782 Taylor PK (1984) Non-linear effects of age on nerve conduction in adults. J Neurol Sci 66:223–234 Thomas PK (1963) The connective tissue of peripheral nerve; an electron microscope study. J Anat 97:35–42 Thomas PK, Berthold C-H, Ochoa J (1993a) Microscopic anatomy of the peripheral nervous system. In: Dyck PJ, Thomas PK, Griffin JW, Low PA, Poduslo JF (eds) Peripheral neuropathy, 3rd edn. WB Saunders, Philadelphia, Chapter 3, pp 28–92 Thomas PK, Scaravilli J, Belai A (1993b) Pathological alterations in cell bodies of peripheral neurons in neuropathy. In: Dyck PJ, Thomas PK, Griffin JW, Low PA, Poduslo JF (eds) Peripheral neuropathy, 3rd edn. WB Saunders, Philadelphia, Chapter 29, pp 476–513 Tillett RL, Afoke A, Hall SM, Brown RA, Phillips JB (2004) Investigating mechanical behaviour at a core-sheath interface in peripheral nerve. J Peripher Nerve Syst 9:255–262 Tohgi H, Tsukagoshi H, Toyokura Y (1977) Quantitative changes with age in normal sural nerves. Acta Neuropathol (Berlin) 38: 213–220

76 Tomita K, Berger EJ, Berger RA, Kraisarin J, An KN (2007) Distribution of nerve endings in the human dorsal radio carpal ligament. J Hand Surg 32A:466–473 Torebjörk HE, Ochoa JL (1980) Specific sensations evoked by activity in single identified sensory units in man. Acta Physiol Scand 110:445–447 Torebjörk E, Schmelz M (2005) Single-unit recordings of afferent human peripheral nerves by microneurography. In: Dyck PJ, Thomas PK (eds) Peripheral neuropathy, 4th edn. WB Saunders, London, Chapter 38, pp 1003–1014 Uziyel Y, Hall S, Cohen J (2000) Influence of laminin-2 on Schwann cell-axon interactions. Glia 32:109–121 Vallbo AB, Hulliger M (1981) Independence of skeletomotor and fusimotor activity. Brain Res 223:176–180 Varro A, Green T, Holmes S, Dockray GJ (1988) Calcitonin generelated peptide in visceral afferent nerve fibres: quantification by radio immunoassay and determination of axonal transport rated. Neuroscience 26:927–932 Von Frey M (1894) Beitrage zur Physiologie der Schmerzsinns. Berichte der Königliche Sächsiche Gesellschaft der Wissenschaften 46:185–196 Von Frey M (1896) Untersuchungen uber die Sinnesfunktionen der menschlichen Haut. 1. 1. Druckempfindung und Schmertz. Berichte der Köningliche Sächsiche Gesellschaft der Wissenschaften 48:175–264 Wall PD (1961) Two transmission systems for skin sensation. In: Roseblith WA (ed) Sensory communication. MIT press, Cambridge, pp 475–496 Wall PD (1970) The sensory and motor role of impulses travelling in the dorsal columns towards the cerebral cortex. Brain 93:505–524 Wall PD (1977) The presence of ineffective synapses and the circumstances which unmask them. Philos Trans R Soc Lond B278: 361–372 Webster HdeF (1993) Development of peripheral nerve fibers. In: Dyck PJ, Thomas PK, Griffin JW, Low PA, Poduslo JF (eds)

Surgical Disorders of the Peripheral Nerves Peripheral neuropathy, 3rd edn. WB Saunders, Philadelphia, pp 243–266 Weddell G (1941) The pattern of cutaneous innervation in relation to cutaneous sensibility. J Anat 75:346–366 Weerasuriya A (2005) Blood-nerve interface and endoneurial homeostasis. In: Dyck PJ, Thomas PK (eds) Peripheral neuropathy, 4th edn. Elsevier Saunders, Philadelphia, Chapter 29, pp 651–665 White JC, Sweet WH (1969) Pain and the neurosurgeon: a forty year experience. Charles C Thomas, Springfield, pp 895–896 Wigley C, Felts P, Standring S (2008) Mechanism of synaptic activity. In: Standring S (ed in Chief) Grays anatomy, 40th edn. Churchill Livingstone, Elsevier, pp 46–48 Windebank AJ, McDonald ES (2005) Neurotrophic factors in the peripheral nervous system. In: Dyck PJ, Thomas PK (eds) Peripheral neuropathy, 4th edn. Elsevier Saunders, Philadelphia, Chapter 17, pp 377–386 Woollam DHM, Millen JW (1958) Discussion on vascular disease of the spinal cord. Proc R Soc Med 51:540–543 Woolsey CN (1964) Cortical localization as defined by evoked potential and electrical stimulation studies. In: Scaltenbrand G, Woolsey CN (eds) Cerebral localization and organisation. University of Wisconsin Press, Madison, pp 17–32 Yiangou Y, Birch R, Sangeswaram L, Eglen R, Anand P (2000) SNS/PN3 and SNS2/NaN sodium channel like immunoreactivity in human adult and neonate injuries of sensory nerves. FEBS Lett 467:249–252 Young JZ (1942) Functional repair of nervous tissue. Physiol Rev 22:318–374 Young JZ (1945) The history of the shape of a nerve fibre. In: Le Gros Clark WE, Medawar PB (eds) Essays on growth and form. Oxford University Press, Oxford, p 41 Young JZ, Holmes W (1940) Nerve regeneration. Lancet 2:128–130 Zotterman Y (1939) Touch, pain and tickling: an electrophysiological investigation on cutaneous sensory nerves. J Physiol 95: 1–28

3

Reactions to Injury

Reactions to injury: the reaction of the nerve cell and myelin/Schwann cell complex; differential reaction of fibres of different sizes; two main types of nerve injury, degenerative and non-degenerative; Wallerian degeneration; the special case of the brachial plexus; reactions to various physical agents; the effects of denervation. Nerves can be damaged in a number of ways: (1) ischaemia; (2) physical agents such as traction or stretching which may be sudden, intermittent or prolonged, pressure, distortion, cold, heat, severance, electric shock, injection of noxious substances, ionising radiation; (3) infection and inflammatory processes; (4) ingestion of drugs and metals; (5) infiltration by or pressure from tumours; (6) the effects of systemic disease. The damage to the nerve may be “closed,” or “open” through a wound of the skin. Damage may be acute or chronic; single, repeated or continuing. The lesion may affect the whole nerve or only part of it. The depth of affection may vary from fibre to fibre or from one part of the nerve to another. The nerve affected may be entirely healthy or may be the subject of a neuropathy from hereditary or systemic causes or from a more proximal affection. Nerve injury may be associated with damage to one or more important structures: artery, vein, viscus, bone, muscle or ligament. It is helpful to the clinician to bear in mind two facts: (1) a nerve which has been transected or ruptured cannot recover until it is repaired; (2) a lesion of a peripheral nerve which remains in continuity but which continues to be subjected to the cause of that lesion will deepen until the cause is removed (Fig. 3.1a, b). The speed of that deepening is related to the cause. A nerve crushed by a plate or by an encircling suture may recover if that cause is removed within a minute or two. It is unlikely to recover if it is not relieved for more than 2 or 3 h. A nerve subjected to continuing traction and ischaemia from an expanding haematoma will recover if the situation is corrected within 6–8 h. After that recovery will probably be imperfect and may not occur at all. The nerve subjected to compression and ischaemia within a swollen ischaemic limb will almost certainly recover if the cause is corrected within 4 h; the chances of full spontaneous recovery diminish with the passage of every hour after that time. It may be years before the situation becomes irretrievable for a nerve subjected to radiotherapy or exposed to continuing traction from a malunited fracture. The cardinal symptom of the persistence of a noxious agent is pain (Fig. 3.2).

a

b

Fig. 3.1  Deepening of lesion. (a) Median nerve extricated from supracondylar fracture in a 9 year old girl at 3 days from injury. There was complete recovery. (b) Median nerve extricated from supracondylar fracture in a 13 year old girl 8 weeks after injury. There was no recovery.

In the mildest form of damage – that produced by transient ischaemia – there is transient failure of conduction affecting principally the large myelinated fibres. Lewis et al. (1931) described this form of centripetal paralysis produced by the application round the arm of a cuff inflated to suprasystolic pressure. First, there is loss of superficial sensibility. This is succeeded by a gradual loss of motor power. The first

R. Birch, Surgical Disorders of the Peripheral Nerves, DOI: 10.1007/978-1-84882-108-8_3, © Springer-Verlag London Limited 2011

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Fig. 3.2  Conduction block. The radial nerve shown tented over the tip of the screw 10 days after operation for fracture. There was a painful deep radial palsy. Conduction in the distal segment was preserved but there was no conduction across the lesion. Conduction in the nerve to brachioradialis (left hand sling) was preserved. Stimulation of the radial nerve above the level of lesion did not evoke response through the nerve to extensor carpi radialis longus (right hand sling). The screw was shortened. Recovery was complete by 24 h.

pain response is lost soon after superficial sensibility fails, but the delayed pain response can still be elicited after 40 min of ischaemia. Pilomotor and vasomotor functions are scarcely affected. This differential paralysis reflects, of course, the differing reactions of the fibres of different sizes. Large myelinated fibres are first affected; C fibres and autonomic fibres escape. Recovery of all modalities occurs within a few minutes of release of the cuff. By a simple but ingenious method Lewis and his colleagues demonstrated that the lesion was caused by ischaemia of the segments of the nerves underlying the cuff. MacKinnon and Dellon (1988) rightly suggest that all those intending to take up peripheral nerve work should try this experiment on themselves. The experience gives a very clear indication of what is meant by the depth of a nerve injury. That knowledge is certain to be important in clinical practice. Further, the experience of the unpleasant quality of the residual delayed pain sensation gives a good insight into the feelings of patients affected by dysaesthesia. It is interesting to note Merrington and Nathan’s (1949) observation that the paraesthsiae occurring during recovery arise not from the periphery but from the nerve trunks recovering from ischaemia. The effect of temporary ischaemia is particularly well illustrated by the behaviour of the main nerves during emergency repair of a main artery. Conduction persists for about an hour whilst the artery is being controlled and repaired. Then, conduction diminishes before altogether ceasing. Conduction returns within a few minutes after removal of clamps and restoration of flow. The conduction block caused by the penetrating missile wounds of war was recognised by Mitchell et al. 1864: “this condition of local shock is very curious. A man is shot in the thigh, the ball passes near the sciatic nerve, and instantly the

Surgical Disorders of the Peripheral Nerves

limb is paralysed; within a few minutes or at the close of a day or a week the volitional control in part returns, but finally they may be left with some single group of muscles permanently paralysed.” Seddon (1943) observed the characteristic features: paralysis exceeds loss of sensation; the nerves responsible for proprioception are more deeply affected than those conveying light touch sensation; vasomotor and sudomotor function is least affected. It is likely that this lesion is provoked by a momentary displacement, or stretching, of the nerve trunks. This explanation cannot account for the conduction block of blast injuries in which the patient is exposed, at close range, to the shock wave of an explosion without any wound, or fracture and with no signs of significant injury to the soft tissues. Case Report: A rocket propelled grenade landed 5 ft from an infantryman who was thrown through the air by the blast, landing heavily on his left side. He immediately noted loss of sensation of the whole of the left forequarter including the skin of the neck and of the chest wall. There was complete paralysis of the whole of the left upper limb. There was no local injury to the posterior triangle, the shoulder or to the cervical spine. Sensation started to recover after 3 days, the muscles started to work after 5 days. Recovery was nearly complete by about 3 weeks although subsequent QST revealed elevated warm thresholds. The mechanism underlying this increasingly common form of conduction block is now under investigation. It is possible that the shock wave causes distortion of the paranodal myelin and the membrane of the axon at the node of Ranvier. As Lewis et al. (1931) noted, the differential response of nerve fibres is reversed in the conduction block produced by infiltration of local anaesthetic agent. Here, the first sign of developing paralysis is the drying and warming of the extremity. It is probable that here conduction block is caused by interference with axonal conduction: so, the small unmyelinated fibres are the most susceptible and the first to succumb. By contrast compression of nerves by haematoma or aneurysm produces a characteristic pattern: autonomic paralysis is early and deep; loss of power extends over hours or days; deep position sense and limited joint position sense persist. With severe and prolonged pressure there is local demyelination and more prolonged conduction block (Fowler et al. 1972; Gilliatt 1981) (Fig. 3.3). The pressures used by

Proximal

Cuff

Distal

Axon

Fig. 3.3  Effect of pressure on nerve: squeezing of myelin with invagination at the node of Ranvier. Narrowing of axon with extrusion of its contents (After Ochoa J et al.1972).

Reactions to Injury

Gilliatt could not reasonably be used in experiments on human subjects. The myelin is squeezed proximally and distally from underneath the tourniquet so as to invaginate into the proximal and distal sheaths of the nodes of Ranvier. The structural affects of focal compression were analysed by Dyck et al. (2005a) in a series of experiments on the peroneal nerve of the rat. The nerve was subjected to a compression force of 300 mmHg for periods ranging from 2 min to 2 h, after which the nerve was rapidly stabilised by perfusion fixation. There was a sequence of events deep to the cuff: (1) the endoneurial fluid was squeezed out so that the nerve fibres and cells became more closely apposed; (2) fluid was squeezed from out of the axon leading initially to compaction of the formed elements and later to their being expressed from out of the axon at the margins of the zone of compression, and (3) the internodes were lengthened with shearing between the lamellae of the myelin sheath. Additional changes occurred at the edges of the cuff, at the intersection between the compressed and the non compressed nerve fibres. Here the area of the endoneurium increased, the axons became distended, especially at the nodes of Ranvier because of the increase of axonal fluid and loops of myelin which had been sheared off and came to overlap the nodes. The structural alterations revealed by this method cannot be caused by ischaemia, for these take several hours to develop and are, in appearance, quite different. A conduction block which may last for weeks or months results. If, in the clinical situation, the cause of the local demyelination persists in the form of (say) a bony projection causing pressure and distortion or of external pressure by haematoma, the block persists. This was so in the three cases reported by Birch and St Clair Strange (1990): in these, removal of the external pressure was rapidly followed by recovery in lesions which had persisted for up to 3 years. The bestowal of the name axonamonosis on this type of lesion by Birch and St Clair Strange, abetted by Bonney, was sharply criticised by Gilliatt in a communication which he was kind enough to keep private. In the experimental situation conduction recovers and motor and sensory functions are restored, though not necessarily in an orderly manner. In this type of paralysis, the autonomic fibres are usually spared, though not necessarily so. We have seen lesions of the median, the tibial and the common peroneal nerves produced by prolonged pressure in which there was prolonged vasomotor and sudomotor paralysis. All these forms of paralysis are examples of neurapraxia (Seddon 1943); all are examples of the non-degenerative lesion. Seddon gave the credit for the naming of his three types of nerve lesion to Sir Henry Cohen, later Lord Cohen of Birkenhead. “Neurapraxia” is perhaps the most admirable but potentially the most misleading of the three: derived from neuron (neuron – nerve or tendon) and apraxia (apraxia – non function), it signifies loss of nerve function – no more and no less. It will not do as a diagnosis unless the clinician using it is aware that it never signifies a degenerative lesion.

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The use of the negating a (alpha) is or should be familiar to clinicians, since it occurs in terms in common use such as aphasia, aphonia, astigmatism, anorexia, amyotrophy and so on. It is all the sadder that declining standards of literacy have combined with rising looseness of thought to render the use of the term neuropraxia a commonplace even in formerly reputable Journals and text books. Punishment should be reserved for clinicians using this meaningless neologism; lawyers using it should lose their fees; classicists using it should suffer an appropriate loss. The situation is wholly different when the lesion is serious enough to cause interruption of the axon. Then follow the changes of a degenerative lesion, caused by the damage to the neurone itself. The changes were first described by Waller (1850) and have since that time been known as those of Wallerian degeneration. We know now that they affect not only the axon but also the cell body; not only the neurone but also its Schwann cell ensheathment and its myelin sheath. There are changes too in the endoneurial cells and, over longer periods of time, in the motor and sensory end-organs. Distal to the site of injury the axon degenerates; there is a granular disintegration of the cytoskeleton and axoplasm, which are converted over succeeding days into amorphous debris (Figs. 3.4a–c and 3.5). Although Adrian (1916, 1917) and Pollock et al. (1946) thought that peripheral neural conduction might survive for up to a month after nerve section in man, Landau (1953) found that the motor response after section persisted for a much shorter period. The interval between injury and the last observation of a neuromuscular response ranged from 66 to 121 h. Gilliatt and Taylor (1959) investigated motor response after section of the facial nerve in man, and found that visible twitch in response to stimulation disappeared within 3–4 days; though an electrical response persisted for a further 48–72 h. Our own observations on motor conductivity after pre-ganglionic injury to the brachial plexus suggest that the motor response ceases about 3 days after injury. In one case stimulation of the ventral roots of spinal nerves which had been avulsed from the spinal cord evoked a motor response 132 h after the injury. The detection of persisting conduction in the distal segment of a nerve which has been ruptured or detached from the spinal cord excludes a more distal lesion of the nerve and excludes ischaemia of the nerve in cases where the axial artery has been damaged. Conduction may cease first in the most proximal part of the fibres. Gilliatt and Hjorth (1972) studied the matter in baboons. The motor response to stimulation disappeared after 4–5 days, but ascending nerve potentials could be recorded for a further 2 or 3 days. Evidently, failure of transmission at the neuromuscular junction precedes failure of conduction along the degenerating axon. Landau (1953) made the perceptive comment that “the distinction between complete Wallerian degeneration and less severe injury can be made on the basis of the disappearance of excitability in the peripheral nerve segment at this

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a

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b

c

Fig. 3.4  Changes in the distal stump of ulnar nerve transected 3 weeks previously. The gap between the proximal and distal stumps was 5 cm. (Electronmicroscopic studies prepared by Mr Stephen Gshmeissner.) (a) Disintegration of the axon and the myelin sheath. Axoplasm and

neurofilaments are seen in the lower fibre ×2,210. (b) Another part of the same specimen. Myelin debris within a macrophage (asterisk), probable Schwann cell processes (arrows) ×5,525. (c) Another part of the same specimen. Many Schwann cells, some with active nuclei ×5,525.

time,” that is, the time of disappearance of neuromuscular function. Many misdiagnoses of “neurapraxia” could have been and could be avoided if this simple procedure were more widely used. The essential difference between neurapraxia and the different types of degenerative lesion is the persistence of conduction in the distal segment of the nerve in the former and

its disappearance in the latter. Conduction disappears within 1 h of an ischaemic lesion but persists for hours or even days after transection or rupture. The early disappearance of conduction is, of course, the hall mark of impending or actual “critical” ischaemia. It is unwise to make a diagnosis of neurapraxia in the presence of persisting pain for that pain signifies that the

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Node of Ranvier

Fig. 3.5  Wallerian degeneration in the distal stump of fifth cervical nerve ruptured 3 weeks previously. The axon is collapsing and it is surrounded by a macrophage although the myelin sheath appears intact x 1,100.

noxious agent is continuing to act. A diagnosis of neurapraxia should not be made in the presence of a strong Tinel sign for this indicates that axons have been ruptured. A diagnosis of neurapraxia should never be made in limb rendered pulseless by injury: conduction block may prove to be but the first step towards something much worse.

3.1 Axonotmesis – Neurotmesis So long as the lesion is not severe enough to interrupt the continuity of the Schwann cell basal laminae from proximal to distal segment the original pathways for re-growth of axons remain (Young 1949; Causey and Palmer 1952; Thomas 1964; Haftek and Thomas 1967) (Fig.  3.6). As Gutmann and Sanders (1943) noted in their experimental work, “only after crushing (as opposed to section) was the nerve fully reconstituted.” Seddon (1943) described the appearance of axonotmesis in rabbits following firm squeezing of a nerve with fine smooth bladed forceps: “the immediate lesion is of striking appearance: the central and peripheral parts are united only by a fine ribbon of translucent connective tissue. The main substance of the nerve is broken and separated by an appreciable interval. Within a few minutes it flows together again, and the fine connecting ribbon is filled out so that the gap is no longer visible.” Seddon described similar experiments, which were performed with JZ Young, in patients in whom part of a limb required amputation: “on several occasions patients have allowed us to crush or divide a nerve, in the part to be sacrificed, at an appropriate interval before the final operation.” The general pattern of the nerve was retained: “the axons were completely interrupted and the conjugating tissue

Basal lamina

Schwann cell nucleus

Myelin sheath

Axon

Fig. 3.6  Axonotmesis (centre) and neurotmesis (bottom) at the moment of injury. Note the preservation of the Schwann cell basal lamina in axonotmesis.

appeared to consist of collapsed endoneurial tubes. In all but one case the lesion had been allowed to proceed to some measure of regeneration; there was a noticeable absence of the axonal branching and crisscrossing that are always found after suture. As Fig.  3.4b shows, the fibres have grown without hindrance into their old paths, exactly as described by Stroebe, Cajal and Langley.” Seddon and Young recognised that the integrity of the Schwann tubes provided important support for regeneration: “if, as we believe, the process of regeneration is a protoplasmic outflow from the central stump (Holmes and Young 1942) progress will be faster when the flow is confined to one main channel and not dissipated in many separate protoplasmic streams.” (Seddon 1975). It is the difference between preservation and destruction of continuity that underlies the division of degenerative lesions between those with the potential for spontaneous recovery and those that will not recover unless action is taken. Seddon (1943) named the first axonotmesis, from azwnw (axono – shaft, or axon) and TmhsiV (tmesis, cutting). That term is still valuable, indicating as it does the vital element of the degenerative lesion: the interruption of the axon and the consequent damage to the neurone. Seddon (1943) named lesions in which interruption of the axon was associated with interruption of the basal lamina, neurotmesis. He, of course derived the term from neuron (neurone, nerve or tendon) and TmhsiV (tmesis, cutting). It rightly indicates interruption of continuity of all elements of the nerve. As our colleague Gereis (2005) points out it is never easy to distinguish between paralysis (par lnsiV) an unrecoverable nerve lesion, and a palsy or paresis (paaresiV), a lesion which may recover spontaneously.

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Table 3.1  Classification of focal mechanical nerve injury. I. Focal conduction block Transient Ischaemic Other More persistent Demyelinating Axonal constriction II. Axonal degeneration With preservation of basal laminal sheaths of nerve fibers With partial section of nerve With complete transection of nerve From Thomas and Holdorff (1993). With permission.

Sunderland (1951) introduced a rather more elaborate system of classifying injury. Five degrees of severity were named, ranging from simple conduction block to loss of continuity. The views of this pioneer in the field command respect; it may well be, that some clinicians find Sunderland’s classification an improvement on Seddon’s and of more practical use than the earlier method. We, on the contrary, have tended towards a further simplification: to classification as “degenerative” and “non-degenerative.” This, we think, is the manner in which clinicians should regard nerve injuries: the first question to be asked is “is this lesion degenerative or non degenerative?” Thomas and Holdorff (1993) elaborate this conception of “degenerative” and “non-degenerative” lesions in a manner helpful to clinicians and experimentalists. We reproduce by permission their table  52–1, in which the subdivisions of “focal conduction block” and “axonal degeneration” are set out Table 3.1. We think that the question mark placed against “axonal constriction” is removed by the case shown to one of us by Campbell Semple (personal communication) (Fig. 3.7). In that case of hour-glass constriction of a main nerve trunk external neurolysis and decompression was followed by early and complete recovery, there must have been axonal constriction. Nagano et al. (1996) and Nagano (2003) studied “spontaneous” paralysis of the anterior interosseous nerve. They found during interfascicular neurolysis of the median nerve that there was “hourglass” constriction of the fascicles belonging to the anterior interosseous nerve. There was no external compression. Recovery after interfascicular neurolysis alone was “generally good.” Akira Nagano has summarised his experience in a personal communication (Nagano 2008). He has identified “hourglass” like fascicular constriction involving the median nerve near the elbow in 24 patients. Five of these presented with symptoms and signs suggestive of a diagnosis of neuralgic amyotrophy. Oberlin et al. (2006) describe a similar lesion involving the circumflex nerve. The possibility that this represents a twisting or torsion of the bundles is raised. Dyck et al. (2005a) show that

Fig.  3.7  Hour glass “constriction” of the lateral root of the median nerve, the result of traction injury. There was full spontaneous recovery (Mr Campbell Semple’s case).

the axon itself may be damaged or even transected by infolded loops of the myelin sheath thrust in by external pressure or other processes. Is it possible that this occurs in cases of “hour glass” constriction? In clinical practice, most injuries of nerves short of transection inflict damage of all three grades of severity. The lesion is pure only in cases of transient ischemia or complete transection. Seddon based his classification on a study of 650 nerve lesions. The injury was in continuity in 537 of these amongst which only 117 cases of “pure” lesions could be indentified; the rest were mixed. This is the usual pattern for the sciatic nerve stretched but not ruptured by dislocation of the femoral head and for the cords of the brachial plexus stretched but not ruptured by anterior dislocation of the head of the humerus. The decision about exploration in cases such as these is never easy but the difficulties may be eased if the clinician bears in mind the possibility that removal of the cause of the lesion may prevent deepening or deterioration and that it may convert a situation inimical to spontaneous recovery to one that is more favourable. The persistence of pain is an important indication for exploration of the nerve.

3.2 The Cell Body and Proximal Stump The central and the peripheral effects of Wallerian degeneration are profound and they are ultimately irreversible. The cell body is separated from the supply of neurotrophins and it may be drained or exhausted by the process of regeneration. The sooner the cell body is reconnected with the periphery the better. Proximal to the lesion changes occur in the axon, the myelin sheath, and in the nerve cells. Within a few days there is a reduction in the calibre of the proximal axon; there may be atrophy of the whole axonal “shaft.” Gutmann and Sanders (1943) thought that this might be caused by the

Reactions to Injury

outflow of axoplasm during regeneration. Aitken and Thomas (1962) showed that the reduction in the diameter of the fibre was still evident 300  days after suture of the nerve. Cragg and Thomas (1961) found that nerve conduction velocity in the proximal segment fell to between 60% and 70% of normal by 200 days and it did not improve in nerves which had not been repaired. Hoffer et al. (1979) recorded nerve conduction potentials in the roots of spinal nerves in cats whose leg nerves had been cut and prevented from regrowing. A progressive decline in nerve conduction velocity from the dorsal root fibres was demonstrated; the decline for the motor fibres stabilised. A clear correlation between the reduction in the calibre in the larger myelinated nerve fibres and a drop in the peak to peak amplitude of the nerve compound action current was demonstrated by Walbeehm et al. (2003). In the cell body itself there may be chromatolysis, a process characterised by Groves and Scaravilli (2005) as one associated with a regenerative and not a degenerative response to an insult. Curiously enough, transection of the central branches going to the central nervous system does not produce such clear cut changes in the cell bodies in the dorsal root ganglia. Lawson (2005) describes changes in the behaviour and in the expression of ion channels in the dorsal root ganglion (DRG) cell bodies which can be detected within a few minutes of an injury to the nerve. Anand and his colleagues (Rabert et al. 2004) studied the expression of genes in the neurones within adult human dorsal root ganglia in cases of avulsion lesions of the brachial plexus, taken at intervals ranging from 1 to 100  days after injury. There was a clear alteration in the expression of 91 genes particularly for those known to be involved in neurotransmission, trophism, cytokine function, signal transduction, myelination, transcription regulation and apoptosis. In other studies of the behaviour of human DRG neurones Boettger et al. (2002) measured the changes in potassium channel behaviour and the influence of neurotrophic factors, Bar et  al. (1998) recorded significantly higher levels of GDNF and Saldhana et al. (2000) found a remarkable increase in interleukin-6 (IL-6), which is a member of the neuropoietic cytokine family (Fig. 3.8). The chromatolysis following axonotomy1 may continue to actual dissolution of the cell body: “the nucleus becomes unidentifiable, all basophilia has disappeared and what remains is a seemingly empty sac containing the condensed remnants of neuronal DNA, a so-called ghost cell” (Groves and Scaravilli 2005). On the other hand rhizotomy scarcely affects the neurone, it “does not produce any observable morphological change in the perikarya of the affected neurones.” Chromatolysis does not occur in newborn mammals, instead the affected neurones become smaller, more intensely stained and many die. Groves and Scaravilli go on to define apoptosis

1

 he common usage is of course axotomy, but we believe that axonotomy T is the more correct term

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Fig. 3.8  TRPV1 (the heat and capsaicin receptor) in a human dorsal root ganglion 6 weeks after avulsion showing immunostaining in small diameter neuronal cell bodies and axons ×40 (Courtesy of Professor Praveen Anand).

as a controlled and deliberate form of neurone destruction that is largely a secondary effect of an insult. The loss of cells is more severe in more proximal axonotomy; axonotomy in the neonate produces a more rapid and much greater incidence of sensory and motor neurone death than in the adult and it is particularly severe after avulsion of the ventral root: “ventral root avulsion being the most severe and acute form of injury, because of the significant trophic support being supplied by surrounding glia and neurones in the adult spinal cord which is disrupted in avulsion” (Fig. 3.9a, b). The loss of sensory neurones was studied in the rat by Ygge (1989a,1989b) and by Schmalbruch (1987). Romanes (1946) observed the changes in the anterior horn cells of mice after permanent axonotomy by amputation. Dyck et al. (1984) were able to study the effect of permanent axonotomy on the spinal cords of two patients who had undergone respectively, partial and total amputation of a lower limb. They found that “loss of target tissue by axotomy leads to atrophy and then loss of motor neurones.” Suzuki et  al. (1993) examined the cervical cord and the roots and ganglia of the spinal nerves in a patient who died 38  years after amputation of the upper limb. They demonstrated a loss of neurones in the DRG, in the anterior horn, and a diminution of the large myelinated nerve fibres in the ventral and dorsal roots. Perhaps the electrophysiological findings in a cohort of old polio survivors described by Sorenson et  al. (2006) represent an attrition of surviving neurones in the anterior horn. Carlstedt (2007) says that: “motor neurones are rapidly killed by ventral root avulsions. Disconnection from the periphery means that interrupted supply of neurotrophic factors, together with vascular trauma leading to cytotoxicity drastically reduces the number of motor neurones up to about 90% of the normal population.” Carlstedt reckons that about one half of all motor neurones in the affected spinal cord segment have disappeared by 2 weeks after avulsion of the ventral root and he suggests that “a swift intervention to re

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a

b

Fig. 3.9  Delay: the proximal stump of C5 ruptured at the same level, 1 cm distal to the foramen, but exposed at operation at different intervals. (a) Six weeks after injury. Clusters of myelinated and unmyelinated nerve fibres forming minifascicles. Bar = 20 mm, (b) Eight months

after injury. Some unmyelinated axons lie within debris laden Schwann cell cytoplasm. There is extensive fibrosis. Fibroblast processes surround the Schwann cell- axon units ×3,000.

establish contact between the injured nerve cells and the periphery with its supply of neurotrophic substances would counteract nerve cell loss in these injuries.” The same phenomenon, of central cell death, follows more peripheral axonotomy although not to the same degree. One example of the depletion of neurotrophins is provided by Anand et  al. (1997) who showed, in human nerves, depletion of NGF proximally and rapid depletion of CNTF both proximally and distally after section of a nerve. As long ago as 1913 Cajal (1928) noted

intradural damage to the roots of the brachial plexus. At delayed operation (hemi laminectomy) the ipsilateral cord is seen to be atrophic, doubtless from the damage to the motor and sensory pathways. Further, magnetic resonance imaging plainly shows atrophy of the cord after birth injury of the brachial plexus. It is a matter of interest that, despite the degeneration of the proximal process of the cells of the dorsal root ganglion, those cells appear to retain for a long time their ability to sustain their distal processes, apparently without serious functional impairment (Bonney and Gilliatt 1958) (Fig. 3.10).

as shown by the older observations of Dickinson (1868) and by the more modern ones of Gadden, Ford and Monakow (1882), there are cases where the neuron whose axon is mutilated or even functionally isolated shows morbid changes, and may even die.

In the words of McComas et al. (1978) “the periphery is essential for the functional integrity of motor and sensory nerve axons.” Further evidence about the changes in proximal neural structures is available from studies of the spinal cord after

3.2.1 Wounds of the Perineurium Wounding of the perineurium causes demyelination and Wallerian degeneration (Thomas and Jones 1967). Spencer et  al. (1975) studied the process of demyelination and

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3.2.2 Contralateral Effects

Fig. 3.10  Right side of the spinal cord at the level C5 to C8 seen at hemilaminectomy 6 months after intradural lesion of the plexus. Note the shrinking of the middle part of the cord at the level of the emergence of the seventh cervical root and the mouths of the pseudo meningocoele.

For some years it has been our impression that the regenerative capacity of the central nervous system is diminished by the most severe injuries to the brachial plexus and we attributed this to an affect extending beyond the injured segments of the spinal cord. A dramatic example of the involvement of regions beyond the area of injury is provided by Suzuki et al. (1993) who, in addition to the ipsilateral effects already described, also demonstrated atrophy of the contralateral anterior horn, where there was a loss of the medium size cells and a reduction in the numbers of the medium and small myelinated nerve fibres in the contralateral ventral roots. This phenomenon has been closely examined by Oaklander and Brown (2004) who used the pan neuronal marker protein (PGP9.5) to measure the density of innervation in the skin of the paws of the rat after transecting one tibial nerve. There was almost complete loss of innervation within the plantar skin in the injured limb. However, a persisting loss of innervation, in excess of 50%, was noted in the skin of the contralateral hind paw. The significance of these findings will not be lost on the clinicians treating patients with nerve injuries.

3.3 The Distal Stump

Fig. 3.11  Injection injury. The tip of the needle lacerated the lateral part of median nerve at the elbow and a neuroma occupied about four of the bundles. Small fascicles of thinly myelinated axons and Schwann cells occupy the proximal stump of one bundle ×2,000.

subsequent remyelination induced by making a window in the perineurium and Thomas and Bhagat (1978) scrutinised the effects of performing a window in the perineurium and extracting its contents at that level. The perineurial cells separated from one another and also from their basal lamina and came to resemble fibroblasts. Regrowth occurred by bundles of axons and Schwann cells which became surrounded by fibroblasts which later developed into perineurial cells leading to the formation of many small fascicles, otherwise known as mini fascicles. This process may occur when the perineurium is lacerated by the tip of a needle and it leads to the formation of a small neuroma within the nerve trunk. The initiation of degeneration is inevitable after lacerating the perineurium which is, of course, deliberately incised during “end to side” repair or during transfer of one bundle from one undamaged nerve to the distal stump of another (Fig. 3.11).

Waller (1850) described the microscopical changes in the hypoglossal and glossopharyngeal nerves of the frog following division. He noted no change for the first 4 days but then progressive varicosity and irregularity of the myelin sheath. About the twentieth day the medullary particles are completely reduced to a granular state…. where we found a presence of the nervous element indicated by numerous black granules, generally arranged in a row like the beads of a necklace. In their arrangement it is easy to detect the wavy direction characteristic of the nerve.

Hall (2005) conceives Wallerian degeneration as an active process in which the environment of a normal nerve so inimical to regeneration of axons is transformed into one which is actively receptive to that regeneration, at least for a limited period. The earliest changes affect the cytoskeleton: “the earliest evidence of fibre alteration is the dissolution and clumping of the neurofilaments and microtubules of axons” (Dyck et al. 2005a). Schwann cells in the distal nerves, both in myelinated and unmyelinated fibres, begin a process of proliferation and the fact that the Schwann cells of undamaged unmyelinated fibres seem to share the proliferation of Schwann cells of damaged myelinated fibres suggest that diffusible, trophic factors are the stimulants for this proliferation(Archer and Griffin 1993, Griffin and Hoffman 1993). Within 48 h of injury, denervated

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myelinating Schwann cells down regulate expression of those genes encoding myelin associated proteins and other proteins which are important for maintaining the organisation of nodes, paranodes, and incisures (Hall 2005). The denervated Schwann cell columns lie within the original basal lamina forming Schwann tubes, formerly known as bands of Büngner. There is proliferation too of endoneurial fibroblasts in the distal nerve. The last important feature is the increase of macrophages; some derived from “resident” cells, others “recruited from the circulation” (Stoll et  al. 1989, Griffin and Hoffman 1993). Omura et  al. (2005a) estimated that the increase in macrophages reached a peak of 150-fold by day 14 after breaking down of the blood brain barrier. Macrophages clear the debris of myelin and axoplasm during which process a Schwann cell mitogen is liberated from the debris. Significantly, they remove proteins such as the myelin associated glycoprotein (MAG) which normally inhibit axonal growth (Hall 2005). Omura et al. (2005b) measured the changes in expression of BDNF, NT3 and NT4 in muscle and nerve after different types of injuries to the peripheral nerves. The significant changes occurred only after transection of the nerve. By 7 days there was a dramatic increase in the expression of messenger RNA for BDNF in muscle and the distal nerve. The messenger RNA for NT-4 decreased. Durrenberger et al. (2004, 2006) measured increase in the expression of chemical mediators of inflammation by macrophages and glial cells after injury to human nerves. Thomas (1964) examined by electronmicroscopy the distal stumps of nerves transected 7 days earlier and found that cords of Schwann cells, often several cells thick and surrounded by a common basal lamina, extended from the distal stump into the outgrowth by about 2  mm. The endoneurial tubes shrink, more collagen is deposited within the endoneurium and there is progressive fibrosis within the distal stump (Holmes and Young 1942). As time passes the number of Schwann cells in the distal stump diminishes and they become less receptive to regenerating axons because of the decrease in the expression of receptors which are normally important in Schwann cell-axon signalling (Li et al. 1997, 1998, Hall 1999, 2005). Calder and his colleagues (Terenghi et  al. 1998) examined the distal stumps from ten patients in whom the delay before repair ranged from 8 to 53  months: “denervated S-100 positive Schwann cells remained within the distal stumps for at least 53 months, organised into typical bands of Büngner, i.e. delicate processes of densely staining Schwann cell cytoplasm enclosed by a basal lamina.” Axons were demonstrated in all specimens; some of these were myelinated (Fig.  3.12). The effects of delay on the behaviour of the Schwann cell is summarised by Niels et  al. (2007) who write: “the reduced capacity to regenerate seems to be

Surgical Disorders of the Peripheral Nerves

Fig. 3.12  Distal stump of median nerve in a 25 year old man, transected 6 months previously by bullet from military rifle. Numerous pale processes of Schwann cell cytoplasm and occasional axonal sprouts. Extensive endoneurial collagenisation ×3,245 (Electronmicroscopic studies by Mr Michael Kayser).

linked to progressive inability of chronically denervated Schwann cells to respond to axonally-derived signals, a response that has been shown to decrease significantly after only two months of denervation” (Li et al. 1998). It is now established that delay before repair is harmful not only because of the effects upon the target organs, not only because of the effects upon the neurones themselves but also because of the falling away of the capacity of the Schwann cells, the essential supporting cells of peripheral nerves, to support regeneration. These facts will not escape the attention of clinicians (Fig. 3.13a–c). The special case of the brachial plexus – A wholly different system of thought has to be employed in lesions of the brachial plexus,