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, or for that matter of the lumbo-sacral plexus, in which there is intradural damage to the roots (Fig. 3.14). In spite of the damage to the proximal branches, the axons, whose cells of origin are outside the cord in the posterior root ganglion, remain healthy for a long time when they are avulsed from the cord or ruptured intradurally. Such axons include all those in the dorsal root; also, of course, many

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a

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b

c

Fig.  3.13  The results of rupture complicated by sepsis. Electron­ microsopic study of serial (2 cm interval) biopsies of proximal stump of sciatic nerve of 34  year old man examined 8 months after rupture

c­ omplicated by fracture and subsequent sepsis. (a) 2 cm from the tip of the proximal stump ×2,340. (b) 4  cm from the tip of the proximal stump ×3,000. (c) 6 cm from the tip of the proximal stump ×1,500.

“recurrent” fibres in the anterior root whose cells of origin are in the dorsal root ganglion. These axons, their Schwann cells and myelin sheaths remain intact and functional, detached not only from central connection but also from Seddon’s, Sunderland’s, Thomas and Holdorff’s and even our systems of classification (Figs.  3.15–3.17). This is in fact, so far as afferent neurones are concerned, a lesion of the central nervous system. Somatic efferent fibres undergo degeneration, being separated from their cells; post ganglionic autonomic efferent fibres also degenerate, because of damage to their grey rami communicantes. We did think of applying the term neuradetosis (from neuron: neurone; nerve and a etoV : adetos; unbound, loose, free) to the lesion of the afferent fibres in avulsion of the plexus. However, we suffered so severe a mauling from the late Roger Gilliatt in connection with our previous attempt at naming that we have decided not to press the point.

3.4 Types of Lesion Produced by Different Physical Agents 3.4.1 Acute Ischaemia The first effect of ischaemia upon peripheral nerves is the loss of conduction caused by anoxic block of fast axoplasmic transport systems and the paralysis of ion channel function. We have seen the effect of transient ischaemia from a short period of pressure from a suprasystolic cuff and this can be observed during exposure of limb nerves with an inflated cuff in position. For about the first 20 min stimulation of the nerve evokes a brisk muscular response by transmission through the neuromuscular junction. This response diminishes and disappears after about 30 min. Conduction within the nerve itself can still be detected for up to another 20 min.

88 Fig. 3.14  The nerve and roots detached from the spinal cord. Note the intact dorsal root ganglion cell, with healthy axons in the detached parts of the roots, the degeneration of the efferent fibre in the ventral root and of the central projections of the afferent fibres.

Surgical Disorders of the Peripheral Nerves Direct ascending tracts

Dorsal root ganglion

Dorsal root ganglion

Cells and sensory nerves

Degenerate efferent Ventral horn cell and axon

Fig. 3.15  Dorsal root ganglion 6 months after avulsion from the spinal cord. The two neuronal cell bodies appear healthy and there are numerous myelinated fibres. Solochrome cyanin ×960.

On the other hand direct stimulation of the muscle provokes a twitch which can be elicited for up to several hours. Indeed, it is the loss of that direct response which signifies impending death of the muscle, and with it, the death of the limb. Whilst it is hard to separate the effects of acute ischaemia from those of other physical agents there are examples of the effects of ischaemia alone upon conducting tissue. Harriman (1977) examined the lower limb soon after amputation in a case where femoral embolectomy successfully restored flow but failed to relieve severe pain. There were areas of muscle infarction but these were confined to the thigh, the muscles below the knee were normal in colour. The nerves in the leg were infarcted. The stump of the sciatic nerve appeared normal but as the nerves passed distally they became soft and

Afferent fibre in ventral root

grey and sections showed swelling of the myelin sheaths and axons with only a scanty cellular reaction in the epineurium. Case report: In October 1993 a man then aged 73 underwent an injection of steroid into the right forearm. There was instant severe pain and loss of function in the distribution of the right ulnar nerve. Persistence of pain and alteration of sensibility combined with failure to detect sensory nerve action potentials led to exploration (August 1995). There were slight localised changes in the flexor carpi ulnaris muscle. The ulnar nerve appeared healthy, but the ulnar artery was tortuous, calcified and distally occluded. Evidently, steroid had been injected into the ulnar artery which at this point was the principal nutrient of the ulnar nerve. An ischaemic nerve lesion had followed, chiefly affecting the larger myelin fibres with very little and much circumscribed affection of muscle. The necrotising angiopathy which complicates disorders such as rheumatoid arthritis and polyarteritis nodosa illustrate the effects of occlusion of smaller vessels in the epineurium. Dyck et al. (2005b) show that many of the epineurial arterioles become occluded and this leads to: “quite dramatic multifocal fibre degeneration, fibre loss and regeneration, extending to involve the perineurium.” Sander (1999) described the case of a diver returning from a depth of 195 ft who developed a lesion of the deep peroneal nerve affecting the sensory fibres and suggested that there had been an infarction of part of the nerve by gas bubbles within the vasa nervorum. The cases of cranial nerve palsies reviewed by Greer (1997) were thought to be caused by compression of the facial and the trigeminal nerves by gas bubbles within the osseous canals.

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89

Fig. 3.16  Rupture and avulsion of the spinal nerves forming the brachial plexus: response to intradermal injection of histamine. (left) There is a flare, mediated by the axon reflex in the territory of the avulsed first thoracic nerve. (right) There is a wheal but no flare in the dermatome of C7 which was ruptured.

Fig. 3.17  Wallerian degeneration in the ventral root of the eighth cervical nerve 6  weeks after avulsion from the spinal cord. A degenerate efferent myelinated fibre (right) compared with a non degenerated myelinated afferent fibre (left) ×11,115 (Electron microscopic studies by Mr Stephen Gshmeissner).

3.4.2 Ischaemia from Tamponade The most dramatic examples of this are provided by the catastrophic cases of infarction of the spinal cord and the roots of the spinal nerves by the injection of local anaesthetic and other agents into the invertebral foramina. Flow through radicular vessels passing into the spinal canal to the anterior

spinal artery is occluded. One such case (Brouwers et  al. 2001) was caused by a diagnostic block of the right sixth cervical nerve in a 58 year old man. Under radiological control a 22 gauge needle was positioned in the posterior caudal corner of the foramen of C6 so that the tip of the needle lay well within the foramen. No cerebrospinal fluid was aspirated and radio contrast medium showed spreading alongside the nerve root. A mixture of 0.5 ml of bupivicaine and 0.5 ml triamcinolone was injected around the nerve root over a 1 min period. At about 1 min after this the patient suddenly developed flaccid paralysis and severe breathing difficulties. It soon became clear that there was a complete lesion of the cord from C3. An MR scan at 6 h showed increased signal intensity from C2 to T1 and a further MR scan at 24 h confirmed infarction of the spinal cord. There was, later, some recovery in the function of dorsal column but little else. The patient later died. In an informed and extensive comment on this paper Nash (2001) describes other cases of severe cord ischaemia following radiofrequency lesioning of dorsal root ganglia and root sleeve injection and he emphasised the importance of the blood vessels passing with the spinal nerves through the intervertebral foramina. “The intervertebral foraminae are of critical value in the blood supply of the cord, as the feeder vessels pass through the foraminae alongside the nerve root.” Similar cases of infarction mainly of the anterior part of the cord but without a fatal outcome, are described by Houten and Errico (2002) and Somayaji et al. (2005). These cases are thoroughly presented and it seems more likely that ischaemia was caused by tamponade of the radicular vessels rather than by direct damage. We believe that a

90

similar mechanism underlies the cases of anterior cord infarction following interscalene block in which the infusion of relatively large volumes of fluid deep to the unyielding prevertebral fascia disturbs flow within the radicular vessels accompanying the spinal nerves. The permanent defects in eight patients are set out in Table 3.2. We are aware of five more cases. Case Report: A 48 year old woman underwent arthroscopic decompression for her painful left shoulder. An interscalene block was performed after induction of anaesthetic using 20  ml of 0.5% bupivicaine under stimulator control. She developed hypotension and was slow to breathe spontaneously. On awakening she had numbness and weakness in all four limbs. There was flaccid paralysis in the left upper limb and of the C5/6 and C7 muscles in the right upper limb. There were severe defects in light touch and temperature sense in the left forequarter with lesser abnormalities in the right hand. Joint position and vibration sense were maintained. There was vasomotor and sudomotor paralysis in the right hand. There was no Bernard Horner syndrome. There was some affection of both lower limbs with weakness of the muscles about the hip and defects in light touch and temperature sense in the right lower limb. Her reflexes were brisk but there was no clonus. A dissociated sensory loss was evident on the right side of the trunk, the level for light touch was T4, that for pinprick sense was T6. An MR scan done on the day after injury was reported as normal but when this was repeated at 5 days bilateral linear patchy areas of high signal were seen, extending from C3 to T5. Somatosensory evoked potentials (SSEPs) at 11 days were normal; sensory action potentials were maintained in all four limbs and motor conduction in both lower limbs was preserved. Motor conduction was absent in the median and ulnar nerves in both upper limbs. By 6 months the lower limbs had recovered. There was complete paralysis of C8 and T1 muscles on the right and of C7,C8 and T1 muscles on the left. By now she experienced severe burning pain in the shoulder girdles and chest. Quantitative sensory testing revealed normal vibration sense in all four limbs, a marked elevation of thermal thresholds especially so in the left forequarter and reduced sweating in both hands. It seems that motor neurones in the anterior horns of the segment C7, C8 and T1 were infarcted, that there was some involvement of the sympathetic outflow to both of the upper limbs and that there was a primary spinothalamic syndrome. She remains in severe pain. Case Report: a previously fit 4 year old boy fell 3 or 4 ft from the steps of a slide sustaining a fracture through the extreme lateral end of the right clavicle. There was no loss of consciousness. The clavicular fragments were markedly displaced with dropping of the forequarter, but there was no evidence of neural affection. Six days after injury, operative reduction and internal fixation were done. The distal clavicular fragments had pierced the trapezius and platysma; after

Surgical Disorders of the Peripheral Nerves

reduction the fragments were united by two sutures. A right interscalene injection of 10  ml of 0.5% bupivicaine was done. It was clear early that there was a lesion of the cord and brain stem with palsies of right cranial nerves III, IV, V, VI, VII, VIII, IX, X, XI, XII, right phrenic palsy and right sided Claude Bernard Horner syndrome. There was flaccid paralysis in the right upper limb but sweating was present in the hand. Light touch sensation was present. Magnetic resonance imaging 2 days after operation showed swelling of the right side of the brain stem and cervical spinal cord. Vertebral angiography showed no abnormality. Neurophysiological investigations were done at 16 days after the operation and showed sensory conduction in the nerves of the upper limbs whilst motor conduction was absent in the right median and ulnar nerves. Somatosensory evoked potentials were recorded at Erb’s point and also from electrodes placed over the lower cervical vertebrae by stimulating the median and ulnar nerves but the higher cervical potentials and all cortical responses were absent, suggesting a lesion at the root entry level of the cervical cord (Dr. Steven Jones, Queen Square). By 5 months the cranial nerves and the phrenic nerve had recovered but the Bernard Horner sign persisted. There was complete paralysis of the muscles innervated by the right eighth cervical and first thoracic nerves. Quantitative sensory testing 1 year after the event revealed preservation of dorsal column function and of light touch and cotton wool sensation in both upper limbs but the thresholds for cooling and warming were very elevated in the right upper limb and also in the contralateral T3 and T4 dermatomes. Sweating in both palms was normal. It seems likely, in view of the absence of abnormal findings on angiography, that the responsible lesion here was a true spasm of the right vertebral artery, causing ipsilateral lesion of the cervical cord and brain stem and that there was also occlusion of flow through the radicular artery accompanying C8. The state of this boy’s hands, 7 years after the event, is illustrated in Fig. 3.18. Evidently, interscalene block is not lightly to be undertaken: the price of avoidance of general anaesthesia or relief of pain after operation may be too high. The increasing use of ultrasonography is likely to reduce the risk to the vertebral artery but it is unlikely to remove altogether the risk of tamponade of critical radicular vessels. The blocks were given with the patient awake in two of our cases.

3.4.3 Ischaemia and Acute Compression Within Neurovascular Fascial Compartments This is caused by bleeding or infusion of fluid into a fascial compartment which encloses the nerve and axial vessels but not muscle. Nerves especially at risk include the femoral

F

F

F

M

F

55

46

46

60

4a

48

R

L

R

R

L

R

L

No

No

Yes

Yes

No

No

Yes

a

The bulbar palsy had recovered by 5 months in case 4.

F

F

60

C7,8, T1

C7,8, T1

C7,8,T1

C5,6,7,8,T1

C7,8

C5,6,7,8,T1

C5,6,7,8,T1

C4,5,6

C8,T1

T1

–

–

–

C6,7

C5

No

Yes

No

No

No

Yes

No

No

Bilateral

No

Bilateral

No

No

Bilateral

No

No

Yes

M

52

R

Upper limb sympathetic

Table 3.2  Permanent defects in eight patients after interscalene block, followed for at least 3 years. Age Sex Side Phrenic palsy Lower motor neurone Cervical sympathetic Ipsilateral Contralateral

C5,6,7,8,T1

C5,6,7,8,T1

C5,6,7,8,T1

–

–

C6,7,8,T1

C7,8,T1

C5,6,7

C7,8,T1

T3,T4

Upper limb C7,8,T1 Lower limb

–

–

Upper and lower limbs

Lower limb

Spinothalamic tract Ipsilateral Contralateral

PNI3:VAS8 Shoulders and neck

No

PNI3: VAS 8 Neck. Shoulders and right hand

PNI 3: VAS 8 neck and shoulder

No

PNI 3: VAS 8 neck and shoulders

Resolved by day 7

Neck and shoulders PNI 3; VAS 8

Pain

Reactions to Injury 91

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Surgical Disorders of the Peripheral Nerves

Fig. 3.18  The hands of an 11 year old boy 7 years after anterior cord infarction caused by interscalene block.

nerve in the groin, the ulnar nerve in the forearm and the tibial nerve in the leg (Fig. 3.19). The syndrome is a common complication of skeletal injury, of nerve blocks and of vessel puncture. The anatomical arrangements putting certain nerves at risk are outlined in Chap. 1 and examples are described in Chap. 8. The medial brachial fascial compartment syndrome (Tsao and Wilbourn 2003) is an important example, for as Wilbourn (2005) suggests it is responsible for the majority of infraclavicular plexopathies following axillary regional block and also for many of the neurovascular injuries which result from closed or penetrating injuries in this region. The progression of the lesion is characteristic: there is, almost always, pain accompanied by dysaesthesiae; loss of sensation soon follows and then, over the next 2–3 h, paralysis ensues. Wilbourne’s comment bears repeating: “distal pulses are normal as they are with most compartment syndromes because the elevated pressure, although sufficient to collapse the vasae nervori, is far below mean arterial pressure. Ultrasound, MR and CT may reveal the vascular lesion, but, considering the very brief time available for surgical decompression before irreversible nerve damage occurs, obtaining these is rarely justified.” The 16 patients described by Stenning et  al. (2005) probably fall into the syndrome described by Wilbourn. There was, in all of these cases, an injury to the axillary artery or one of its offsets caused by dislocation of the shoulder or fracture of the proximal humerus. The diagnosis of continuing bleeding into the axillary sheath was made by the delayed onset of nerve palsy or the deepening of the lesion whilst under observation. There were 87 nerve palsies. A favourable outcome was seen in all cases where urgent repair of the artery and decompression of the axillary sheath was performed (see Table  8.5). The

Fig. 3.19  Recovering femoral palsy from haematoma in the femoral triangle in a 69 year old farmer who was taking warfarin after aortic valve replacement. Two months previously he had injured his thigh whilst vaulting a gate. He experienced severe pain for 24 h but this recovered spontaneously. The area of sensory loss is outlined and the site of the Tinel sign marked. Recovery was good but not complete by 6 months.

outcome for function within the hand in another patient in whom the diagnosis was delayed by 8 weeks is shown in Fig. 3.20.

3.4.4 Ischaemia by Acute Compression from Swollen Muscle The effect upon the nerves is at least as rapid as it is in cases of compression within a neurovascular sheath. The response to correction within 3 hours is almost always gratifying and the consequences of delay before that correction are particularly severe. The vascular arrangements of nerves are such that injuries of main arteries are more likely to produce infarction of muscle than necrosis of nerve trunks. Even when ischaemic degeneration of myelinated fibres was produced by multiple arterial ligation (Hess et al. 1979) Schwann cells and their lamina tubes and fibroblasts survived and provided conditions for recovery. The evidence is distorted by

Reactions to Injury

93

Fig. 3.21  Volkmann’s ischaemic contracture. Below: the ulnar nerve exposed during flexor muscle slide 8 weeks after supracondylar fracture. The epineurial vessels and also the ulnar recurrent collateral vessels are occluded and the nerve is compressed by the swollen infarcted muscle. Above: the appearance of the hand 14 years later.

Fig.  3.20  Fracture of left proximal humerus was complicated by expanding haematoma in a 63 year old man. Two attempts to occlude the torn posterior circumflex artery by interventional radiology failed. He was seen at 8 weeks by which time he was in right heart failure, in great pain and he had a complete infraclavicular plexopathy on the left side. Six litres of altered blood were removed from the axilla. His pain was relieved. Recovery was particularly poor in the radial and median nerves. (a) MR angiogram before operation. (b) The left hand 4 years after operation.

the circumstance that ischaemia is rarely complete. Even nerves which have been seriously ischaemic for 36 h have been seen to recover adequate function. In one case of ischaemia after supracondylar fracture of the humerus complicated by thrombosis of the brachial artery, the median nerve was seen at operation to lack all vascular pedicles from elbow to wrist. It lay in the middle of the completely infarcted flexor muscles of the forearm. Three years later there was recovery of sweating and of impaired sensation in its area of distribution. The effect of increasing pressure within the osseo-fascial compartment upon the vessels running with the nerves at the elbow is illustrated in Fig.  3.21. These vessels provide the main pathway for collateral circulation at the elbow after cessation of flow through the axial artery; the consequences

of neglect are especially severe. We shall return to this serious, and as it seems, increasingly common problem in Chap. 8. It is somewhat reassuring that adequate decompression, even when delayed for some months, usually leads to relief of pain and considerable improvement in sensation. Leonard (1967) described five such cases and he observed that: “ the vasa nervorum were seen to fill upon release of the tourniquet” (Fig. 3.22). Case Report: A 33  year old man suffered injury to the popliteal artery in the course of arthroscopic meniscectomy. We saw him 5 months later when he complained of severe pain. There was a vicious equino varus deformity of the ankle and foot. Below knee amputation had been recommended. The deep flexor compartment was exposed and wide step elongation of the heel cord and the flexor tendons brought the foot into a plantigrade position. The tibial nerve and posterior tibial artery were strangled within a thickened sheath. Both were narrowed to less than one half their normal diameter, the artery was not pulsatile and was there was no flow through the epineurial vessels. They were widely decompressed. Pulsatile flow returned at the end of the procedure. The patient reported relief of his pain and a sensation of warmth in the sole of his foot on the first post operative day. Over the next

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Surgical Disorders of the Peripheral Nerves

Fig. 3.22  The popliteal artery was lacerated during arthroscopic reconstruction of the posterior cruciate ligament. There was 24 h delay before the vessel was repaired. This was followed by rhabdomyolysis and acute renal failure. Most of the muscle in the leg was excised. Nine months later step elongation of the flexor tendons improved the posture of the foot and the decompression of the tibial nerve was followed by considerable recovery of sensation and some recovery into the small muscles of the foot.

few days he regained cutaneous sensibility in the skin of the sole of the foot. Recovery into the small muscles of the foot was apparent by 6 months and some recovery of vasomotor and sudomotor function in the plantar skin was observed 2 months later. Some nerve fibres were affected by conduction block; the greater number sustained a degenerative lesion. The strangulation of nerves by scar tissue is a common occurrence in war wounds, especially when damaged or repaired nerves are covered by split skin graft. “Nothing less than a full thickness flap or tune-pedicle graft will suffice since it is important that the nerve graft should lie, a far as possible, in healthy, well vascularised tissue” (Seddon 1954). Case Report: A 38 year old soldier sustained severe soft tissue damage to the right posterior triangle from bomb fragments. The wound was closed with split skin graft. He experienced significant pain and much loss of function from a deep palsy of the spinal accessory nerve. Operation was performed 4 years later in the hope of easing his pain. The scar was excised then the cervical plexus and the spinal accessory nerves were exposed. The spinal accessory nerve appeared as a narrowed cord from the posterior margin of the sternocleidomastoid to three fingers breadth above the clavicle. The epineurial circulation was almost nonexistent. Stimulation of the nerve above, when it was first exposed, evoked no distal response. After the nerve had been liberated from scar stimulation evoked an increasingly powerful muscular response in the fibres of the upper trapezius. A free full thickness skin flap was used to cover the defect (Roderick Dunn, Salisbury).

On the day after operation the patient demonstrated powerful activity in his right trapezius (Fig. 3.23). This case is by no means exceptional. It seems there must have been prolonged conduction block involving a significant number of the efferent fibres in the spinal accessory nerve. This type of lesion is common in nerves strangled in scar. Phang et al. (2009) described the case of a 26 year old woman who developed pain in her left hip. This was attributed to previously undiagnosed bilateral hip dysplasia. Pelvic osteotomy of both hips was done. The pain in the left hip became much worse and both hips were resurfaced 6 years later. The pain in her left hip deepened so that she could walk only with crutches. When she was reviewed 10 years after the onset of her symptoms it was clear that there was a focal lesion of the left femoral nerve. There was a strong and painful Tinel sign over the nerve at the groin crease, motor and sensory conduction was impaired and electromyography confirmed a mild degree of degenerative lesion of the fibres to the quadriceps muscle. The femoral nerve was exposed (Marco Sinisi RNOH). It was tethered and sharply compressed by scar tissue over a 4 cm segment. The nerve was liberated. Her pain was improved, there was, later, improvement in the range of movement at the hip and improvement to the power of extension of the knee. By 1 year she was able to walk freely without any aid. Hindsight is always easy but it does seem that the lesion of the nerve occurred during the operation of pelvic osteotomy and her description of the new symptoms which occurred after that operation indicated neuropathic pain.

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95

Fig.  3.23  The spinal accessory nerve after excision of scar during operation 4 years after missile injury. The transverse cervical nerve (1) and the proximal accessory (2) and distal accessory (3) are exposed. A full thickness skin flap was inserted. Recovery of function was evident on the day after operation (Courtesy of Mr Roderick Dunn, Salisbury).

Fig.  3.25  A 20  year old man developed staphylococcal septicaemia after an operation for pilonidal sinus. Rhabdomyolysis led to multiple organ failure. Early fasciotomy and wide excision of the muscles of the anterior compartment of both legs was performed. There was recovery of sensation and sympathetic function in the foot: the small muscles also recovered.

Fig. 3.24  An 18 year old man with Marfan’s syndrome suffered severe and extensive rhabdomyolysis with organ failure after an operation for aortic valve replacement. Urgent and extensive fasciotomies were performed. There was considerable recovery in the peripheral nerves of both lower limbs so that he was able to walk independently by 3 years after operation.

“Critical illness neuropathy” may develop in patients who develop multi organ failure or sepsis. (Donaghy 2009a). It is possible that the intense compression of nerve trunks within oedematous and swollen limbs contributes to this disorder (Figs. 3.24 and 3.25).

3.4.5 Ischaemia Caused by Traction Lundborg and Rydevik (1973) showed that 8% elongation of a segment of a nerve could cause impairment to vascular flow and that an elongation of 10–15% could arrest all blood

flow. Relaxation within 30 min would, in most cases, lead to restoration of flow and conductivity. Nerves which are stretched over an expanding haematoma sustain the most severe lesions, especially so when the false aneurysm is pulsatile. This type of injury is associated with causalgia. Recovery for nerves embedded within the wall of the sac is generally poor (Stewart and Birch 2001). Gardiner et  al. (2006) reported a fatal outcome in a 71 year old man with a 3 month history of “sciatica.” The pain increased in severity and it was attended by rapidly deteriorating function in the lumbar plexus. The underlying cause was an aneurysm of the common iliac artery (Fig. 3.26). Ischaemia is the common factor in many of the lesions inflicted upon nerves in continuity. The situation can usually be retrieved by urgent and accurate action. The recovery of some function through nerves strangled by fibrosis for months or even years, provides an indication of their resilience: on the other hand relief of the cause within 3 or 4 h offers the only real prospect for complete recovery. The

96

Fig.  3.26  A 68  year old woman developed an intensely painful and rapidly deepening lesion of the sciatic nerve on the evening of operation for total hip arthroplasty. The nerve was exposed 3 months later and it was found stretched over an organised haematoma. Her pain improved but the nerve did not recover.

different responses evoked by acute compression of a nerve trunk within a fascial sheath versus the insidious effect of a haematoma is illustrated by the following example. Case report: A healthy 28 year old woman suffered a fracture of her left tibia and fibula. This was treated by open reduction, internal fixation and bone graft from the ipsilateral iliac crest 7 days later. A femoral nerve block was given before induction of general anaesthesia. In spite of her complaints of intense searing, shooting pain radiating down the front of her thigh and leg the anaesthetist persisted with the infusion of local anaesthetic into the groin crease. Upon awakening the patient continued to experience intense pain which required high doses of morphine during the next 3 days. She became aware that she could not feel the sole of her foot and could not move her ankle. Her haemoglobin was measured at less than 8 g per dL on the third post operative day but the significance of this was not grasped. By 7 months it was appreciated that she had developed not only a significant femoral neuropathy but also a profound sacral plexopathy. The femoral neuropathy remained very painful and she continued to experience dynamic mechanical allodynia to stimulation of the skin of the front of the thigh. She was unable to walk because of pain, weakness and loss of position sense throughout the left lower limb. NPI were performed 9 months after her injury. Sensory and motor conduction studies were normal. Electromyo­ graphy revealed a few small polyphasic motor units in the right vastus medialis, otherwise the motor units were normal. QST found that joint position sense was very poor throughout the left lower limb, indeed it could not be detected for the hip. On the other hand vibration thresholds at the left great toe were within normal limits. The thresholds to monofilament stimulation and warm sensation were

Surgical Disorders of the Peripheral Nerves

increased throughout the left lower limb and there was a rather patchy loss of pinprick sense. The pain was exacerbated by extension at the hip. The femoral nerve was explored 11 months after her injury. The fascia surrounding the nerve was greatly thickened. The nerve was narrowed, and inflamed with a much diminished epineurial circulation. There was no sign of injury to any of the individual bundles within the trunk. The nerve was decompressed over some 10 cm. A tissue catheter was placed for the infusion of local anaesthetic about the proximal part of the femoral nerve for 48 h. There was considerable improvement in her pain and in her ability to walk. By 9 months after operation the muscles about both hips and knees were graded 5 by the MRC system but she still had extremely poor joint position sense throughout the left lower limb. It seems likely that the injury to the femoral nerve was provoked by injection of bupivicaine into the epineurium but not, in all likelihood, into the perineurium and that the nerve became strangled within its fascial sheath. The chief effect of this injury was pain, a pain so severe that the more insidious and painless lesion of the sacral plexus caused by continuing bleeding from the donor site at the ipsilateral iliac crest escaped attention. The effect of the haematoma was particularly severe for the largest myelinated afferent fibres: some never recovered. The myelinated efferent fibres and the smaller myelinated afferent fibres recovered over the course of 3 months: in these the lesion was one of conduction block. The experience of severe pain at the beginning of the femoral nerve block should have led to instant cessation of the injection.

3.4.6 Reperfusion Injury Bywaters et al. (1941) described the fatal outcome after freeing people whose limbs had been crushed for some hours by the debris of bombed houses. The renal failure was caused by the release of myoglobin from ischaemic muscle. The effects upon the nerves of reperfusion are of lesser consequence than the systemic effects but as McManis et  al. (2005)point out reperfusion aggravates the ischaemic injury to the nerve fibre. Nukada et al. (1997) described the stages of reperfusion injury of nerves. The blood nerve barrier (BNB) breaks down at about 3 h; then follows oedema, demyelination and axonal degeneration. There is an infiltration of polymorphonuclear leucocytes which peaks at about 24 h. This is followed by an increase in macrophages which invade the Schwann cell and the myelin sheaths. McManis et al. (2005) consider the function of the BNB as a physiological index of oxidative injury, which causes microvascular permeability and an environment in which there is generation of oxygen free radicals.

Reactions to Injury

3.4.7 Chronic Ischaemia Eames and Lange (1967) studied clinically and by light and electron microscopy of biopsy specimens, the effect of chronic ischaemia on the sural nerves of 30 patients with arteriosclerotic obliterative disease and two with Buerger’s disease. There was a good correlation between the severity of the arterial disease and the incidence of neuropathy. The incidence of neuropathy was high: 87.5%. There was found extensive segmental demyelination and remyelination in addition to Wallerian degeneration and regeneration. The unmyelinated fibres were least affected. In all cases – not only in those with Buerger’s disease – there were marked occlusive changes in the small arterial vessels of the epineurium. The relation of these changes to “ischaemic pain” and “trophic” changes in the skin was canvassed.

3.4.8 Crush Crush injuries stand with inadvertent transection, traction or neglected ischaemia as one of the four main causes of iatrogenous lesions. Although a crush injury might be considered as an extreme form of compression the clinical evidence suggests that it is rather more than that. Unless the cause is relieved swiftly the lesion of the nerve rapidly becomes a neurotmesis. The most extreme examples of this of course is when a nerve is encircled by a suture. Much depends on the material used and the tightness of the strangulation. We have seen nerves divided by stainless steel wire used for the fixation of displaced fragments of bone. Whilst recovery might be anticipated after removal of a braided suture, within an hour or two, nerves do not recover after this time (Fig. 3.27).

Fig. 3.27  A 48 year old woman experienced severe pain and an incomplete lesion of the sciatic nerve after operation of total hip arthroplasty. The nerve was exposed 8 weeks later. It had been transfixed by a braided suture. There was some moderation in her pain but little recovery for the nerve.

97

Not only do catgut sutures crush, they also provoke a brisk inflammatory response. Not only does an encircling suture strangle a nerve it also tethers it so that there is the added element of stretch. Severe pain is usual and it is often related to posture. Attempted stretching of the limb against the tethered nerve provokes intense pain (Fig. 3.28). We have seen more than 40 patients in whom main nerves had become inadvertently strangled by a suture passed around, or through, the nerve. When the suture was removed within hours of the operation there was instant relief of pain and a high level of recovery. Relief of pain was usual after removal of the suture up to about 2 weeks. In these cases recovery was always incomplete and when the ligature was removed later there was very little useful recovery. Hindsight suggests that that the better course might have been resection and suture of the relatively short damaged segment. Nerves entrapped within fractures or joints certainly pass through a period of ischaemic conduction block which may last for as long as 2 or 3 days. After that there is demyelination but recovery may be anticipated if the nerve is set free within 7–10 days. The situation is made very much worse if a compression plate or tension band is applied to the fracture without extricating the nerve. The resected material in such cases shows transection of normal structures with an interposed zone of dense fibrosis. The effect of compression between the bone and the plate is illustrated by a case treated by an alert surgeon who, drawing to the close of a difficult operation of internal fixation of a fractured shaft of humerus, realised that the hitherto protected radial nerve had inadvertently slipped between the plate and the bone. The nerve was

Fig. 3.28  A 38 year old woman experienced intense pain and a partial lesion of the ulnar nerve after repair of the capsule of the joint using an arthroscope. Her pain was worsened by attempted extension at the elbow. The nerve was exposed 4 days later, it had been caught by a clip. The clip was removed and her pain was relieved. There was considerable recovery in the ulnar nerve but she did not recover vasomotor and sudomotor control and there was lasting weakness of the small muscles.

98

Fig.  3.29  The appearance of a radial nerve after extrication from beneath a compression plate 48 h after first operation. There was relief of pain but only incomplete recovery so that later flexor to extensor transfer was necessary (Courtesy of Marco Sinisi, RNOH).

at once extricated. The duration of compression was, at the most, 5 min. The nerve was re-explored at that surgeon’s insistence some 6 weeks later even though an advancing Tinel sign offered the prospect of spontaneous recovery. The nerve had reconstituted, the epineurium was thickened but the epineurial vessels were patent and the bundles within had not been severed. Recovery proceeded uneventfully as an axonotmesis. Other examples of a good outcome after urgent correction of the situation are outlined in Chap. 8. Nerves extricated from within a fracture 2 or 3 days of the injury usually recover. There is certainly some narrowing of the nerve trunk in these cases but the perineurium is not breached. All may not be well within the perineurium: the lesion is mixed with elements of ischaemic and demyelinating conduction block interspersed with varying degrees of axonal degeneration (Fig. 3.29).

3.4.9 Compression – Acute Thomas and Holdorff (1993) consider crush and compression separately. It is likely that in the latter type of injury the lesion is localised – a mixture of demyelination and axonal interruption (Richardson and Thomas 1979). Certainly, with more severe pressure there is axonal interruption but that interruption is within the Schwann cell basal lamina tubes. Thomas and Holdorff show a figure which well illustrates this point. Dyck, Dyck and Engelstad (2005a) reserve the term compression for a “monophasic application of force exerted to the nerve from the outside so that it is compressed against a rigid underlying structure. Acute compression may also occur repeatedly.” They rightly point out that “entrapment” should be reserved for a nerve passing through an opening that is too small for it. This effectively tethers the

Surgical Disorders of the Peripheral Nerves

nerve so that it becomes subject to stretch. Platt (1928) described precisely this lesion in relation to the radial nerve stretched over an ununited fracture of the humeral shaft. Closed compression lesion, in which an external force is applied to the limb of a conscious patient usually leads to a conduction block. Such is the event in radial palsy caused by a badly applied plaster of Paris splint or the older style of crutch favoured by the cook in Treasure Island. Case report: A fit 23 year old woman fell deeply asleep lying on her left side for about 2 h and awoke with a complete left sided radial palsy. She had no pain, there was no Tinel sign and there was some preservation of cutaneous sensibility within the distribution of the nerve. She was fitted with a dynamic extension splint and at 6 weeks the first evidence of recovery into the extensor muscles of the wrist was apparent. Neurophysiological investigations were performed 9 weeks later which revealed normal conduction and a normal recruitment to a full pattern of motor units of normal appearance. Her recovery was complete by 12 weeks from the incident. The lesion was one of pure conduction block. More sustained compression leads to deeper lesions (Tait and Danton 1991). Case Report: A slim healthy 22 year old woman sustained a mid shaft right femoral fracture through an area of fibrous dysplasia. The operation of internal fixation was difficult and lasted for 7 h during which time the contralateral left leg was kept in a flexed abducted position to permit the use of an image intensifier. A muscle relaxant (Rocuronium) was used. She awoke with a complete left sciatic palsy. There was no bruising in the left thigh or the buttock. NPI at 2 months after operation showed a complete degenerative lesion of the nerves and muscles of the leg and foot with extensive denervation in the hamstring muscles. She was examined again 8 months after the incident, when she reported increasingly severe pain but some recovery of feeling into her foot. Recovery of power of the knee flexor muscles was measured at MRC Grade 4 and there was perceptible activity in the flexor muscles of the heel. There was complete vasomotor and sudomotor paralysis in the foot. There were strong Tinel signs for both divisions of the sciatic nerve in the leg indicating a rate of regeneration of a little more than 2 mm per day. By 14 months all muscle groups in the leg and foot were recovering and she could localise light touch to the skin of the foot. There was still sympathetic paralysis in the sole of the foot and she still had pain. NPI were repeated. No sensory conduction could be demonstrated in the nerves of the leg nor was motor conduction demonstrable for the tibial nerve. Motor conduction in the common peroneal nerve was reduced and slowed. Electromyography of the leg muscles revealed persisting denervation with reinnervation by collateral sprouting with many wide polyphasic units and irregular recruitment. By 18 months she showed further recovery and some improvement of her pain. Quantitative sensory testing (Praveen Anand Imperial College) showed elevated thermal

Reactions to Injury

thresholds in the plantar skin but the threshold to cooling fell within normal limits. The threshold to monofilament sensation was elevated and pinprick was felt as an unpleasantly sharp sensation from the mid calf down. Sweating in the left sole was reduced to about one half of that on the right. The threshold to vibration was markedly elevated. It seems that the largest and the smallest fibres suffered most. Such lesions can prove very serious in the growing child because of the disturbance of growth. Case Report: A 12 year old boy fell from a swing and experienced much pain. There was deep bruising in the left buttock and he presented with a high sciatic palsy which involved the superior gluteal nerve. The common peroneal nerve was more severely affected, NPI at 6 weeks revealing loss of conduction and denervation of all of the muscles innervated by that nerve. Sensory conduction was diminished in the tibial division and there were signs of partial denervation of all tibial muscles. There was considerable muscular recovery by 1 year. Sensory conduction in the tibial nerve had recovered. There was no sensory conduction in the common peroneal nerve and motor conduction was slowed and reduced in amplitude to just under 10% of the uninjured side. At 2 years the nerve had recovered but the left lower limb was shorter by 1.5 cm and the heel was fixed in equino varus deformity. The lesion in the more severe compression injuries is usually much more than a conduction block. The tempo of recovery varies from one population of nerve fibres to another

Fig. 3.30  A 50 year old man who required crutches developed “carpal tunnel syndrome” in his right hand. Two operations were performed with no lasting relief of his symptoms. His symptoms were improved after modification of his crutches and by the use of a silicone pad.

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and it is not unusual to see poor recovery for somatic unmyelinated fibres. As a rule, the sympathetic efferent fibres suffer least. Some nerves never recover.

3.4.10 Chronic Nerve Compression Entrapment syndromes provide most of the examples of chronic nerve compression, though the latter is one of the causes of neuropathy after ionising radiation and in other conditions in which a nerve is deformed over a tumour or bony abnormality (Fig. 3.30). Clearly, there are a number of mechanisms. Episodic ischaemia accounts for the nocturnal paraesthesiae in “carpal tunnel syndrome,” and possibly continued ischaemia accounts for the continuous symptoms (Hongell and Mattson 1971). Evidence about the size of fibres affected comes from Thomas and Fullerton (1963), and of segmental demyelination from Neary and Eames (1975). The systematic studies of MacKinnon and her colleagues (MacKinnon et al. 1985; Dellon and MacKinnon 1988; MacKinnon and Dellon 1986) showed that the earliest changes occurred in the small vessels of the endo- and perineurium. The presence of numerous Renaut corpuscles (Renaut 1881; Jefferson et al. 1981) was also observed, consistent with the observation made by Hill and Hall (1999) that these aggregate at sites of entrapment, and represent a response to local injury to the endoneurial

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Fig. 3.31  Intraneural ganglion of the common peroneal nerve. Top left: the patient presented with a painful foot drop of 9 months duration. The area of sensory loss is shown. Top right: magnetic resonance scan

shows the extent of the lesion and the communication with the proximal tibio-fibular joint. Below left: the ganglion is shown at operation. Below right: the resected specimen includes the articular branch.

capillaries. Later, there is perineurial and epineurial fibrosis, followed by loss of fibres and thinning of myelin sheaths. At the end of the process there is damage to unmyelinated fibres. Compression may be intermittent as it was in the case described by Mannan et al. (2008). A 25 year old woman experienced intense but intermittent sciatica which was closely related to the menstrual cycle. She endured this for many months and became dependent upon crutches and even a wheel chair. Her pain was relieved by removal of a focus of endometrial cysts which had infiltrated the sciatic nerve in the upper thigh. Bendszus et al.(2003) described two cases of severe but intermittent sciatica, provoked by sitting or lying and eased by standing or walking, which were caused by varicose veins enveloping the sciatic nerve. Pain was relieved by excision of the varicosities. The perineurium and the intraneurial ganglion. This rather mysterious disorder is often a source of needless maiming. Spinner et  al. (2003), Spinner et  al. 2006) have shown that the pedicle of the ganglion is, in fact, the articular branch of the nerve and that this is a pathway for synovial

fluid passing from an adjacent joint into the trunk of the nerve. It seems that the pathway is epineurial, and the perineurium acts as a barrier between the endoneurium and the increasing volume of synovial fluid. The perineurium, with its contents, is subjected to prolonged and varying compression. This may explain the high success following successfully conducted operations which involve not only decompression of the nerve but also excision of the articular branch through which synovial fluid tracks. The early recovery after months or even years of pain and weakness is remarkable indicating that the lesion of the nerve fibres is predominantly one of conduction block (Fig. 3.31).

3.4.11 Traction or Stretch Injury Peripheral nerves outside the spinal canal have considerable tensile strength, but their function is damaged by an elongation of 12% or more, the extent of damage varying with the

Reactions to Injury

suddenness and the length of time during which that elongation is maintained. Lundborg and Rydevik (1973) showed that venous flow was blocked when a nerve was stretched by 8% of its resting length, and that stretching by 15% produced ischaemia. At first, elongation is permitted by the elongation of the epineurium and the straightening of the irregular course of the fibres within the fascicles (Haftek 1970; Clarke and Bearn 1972). The latter drew attention to the significance of the “spiral bands of Fontana,” confirming his conclusion that the banding appearance of the peripheral nerve is due to the wave-like alignment of its individual nerve fibres. As the fibres are straightened the banding disappears. It is difficult to separate the effects of stretch upon the conducting tissue from those imposed upon the vessels. Ochs et al. (2000) studied the effects of stretch upon isolated segments of nerve placed within an oxygen chamber. A very light stretch straightened out the zig zag disposition of the nerve fibres. The spiral bands of Fontana were erased when the nerve was elongated to about 15%. This effect was achieved with an applied tension of less than 0.1 g. An applied tension of 2 g or more induced beading of the nerve fibres which was maximal at 4–5 g of tension. The change in the nerve was rapid and it was also rapidly reversible. The compound nerve action potential was actually augmented in the earliest stages before it fell away. Haftek (1970) added the observation that “before rupture of the perineurium the damage to the nerve fibres is either neurapraxia or axonotmesis, because the endoneurial sheaths and Schwann fibres remain intact.” Next, the calibre of the fibres is diminished, the endoneurial space is diminished and myelin is disrupted (Chalk and Dyck 1993). Then rupture starts: first the epineurium and lastly the nerve fibres. The longitudinal extent of damage is considerable. The process of damage by a bullet passing through soft tissue near a nerve is comparable. Such lesions are usually conduction blocks. Seddon (1975) illustrates one such case, where the epineurium was split by the passage of a bullet but the bundles were intact. It is usual, in closed traction lesion, to see that the epineurium has ruptured but the perineurium within remains intact, albeit stretched. These injuries are usually complicated by bleeding into the epineurium, extending over many centimetres. However we have encountered cases where the perineurium was ruptured even though the epineurium remained intact in nerves sharply angulated over a fragment of bone. It is much easier to recognise this pattern when the nerve is explored within 24 h of the injury (Figs.  3.32a–c). In the extreme traction injury the nerve is ruptured or avulsed from muscle. The wide recoil of the stumps be reduced only by urgent operation. We have seen nerves destroyed over a length of 15 cm by the action of a drill during operation. The manipulation of any joint which has been fixed for some time in a position of deformity always carries the risk of damage to nerves and vessels passing across it and accustomed to the position of deformity. In one case of attempted correction of long standing flexion deformity of both knees

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in an adult with cerebral palsy loss of pulses at the ankles was recognised by the staff of the recovery ward. No action was taken and above knee amputation of one lower limb proved necessary. Aspden and Porter (1994) reported a case in which the sciatic nerve was damaged by straightening knees that had long been flexed because of spastic diplegia. Birch et  al. (1991) described three cases in which the brachial plexus was damaged during manipulation of the shoulder for “frozen shoulder.” In one of these cases, manipulation had caused anterior dislocation. The plexus was explored in this case; there was no interruption of continuity, and recovery followed. Case report: A fit man, in age 64 years, developed severe osteoarthritis in his right knee complicated by severe fixed flexion deformity. Capsulotomy was done to regain extension as the first step in total arthroplasty of the joint. The surgeon avoided a suprasystolic cuff because of anticipated difficulties. A complete lesion of the tibial and common peroneal nerves was recognised on the evening of operation. Neurophysiological investigations at 22 months revealed no sensory or motor conduction. Considerable reinnervation of the tibial muscles was demonstrated and the distal muscles of the anterior compartment were also recovering (EHL, EDC) However, tibialis anterior was fibrosed, the muscle was silent and the concentric needle met with the characteristic, gritty resistance. In addition to the traction injury of the nerves it is likely that flow through the anterior tibial artery was interrupted. The patient had been discharged from the first hospital in spite of severe disability and continuing pain. Case report: A 13 year old girl with severe cerebral palsy was treated by anterior transfer of the hamstring muscles of the left knee with the object of correcting flexion deformity. On the day of operation she developed intense pain in the leg and foot. This did not respond to opiates and neither the child nor her mother were able to sleep for 8 weeks. The child lost a good deal of weight. We saw her at 8 weeks when it was clear that the nerve lesion, although deep, was not complete. The child had causalgia. The extent of discoloured skin matched the areas of intense mechanical allodynia. At operation both tibial and common peroneal nerves were found stretched and compressed, indeed strangled, by fascia and by scar in the popliteal fossa. The common peroneal nerve was reduced to about one half of normal diameter and the epineurial vessels were obliterated. The tibial nerve was inflamed and embedded in vascular adhesions. An external neurolysis was done, and a tissue catheter placed to permit infusion of local anaesthetic for 48 h after operation. The pain from the tibial nerve was improved, the pain from the common peroneal nerve persisted. Both nerves recovered. By about 9 months the child was able to tolerate shoes and weight bearing. Her mother described how vasomotor and sudomotor disturbance in the foot persisted even after pain had improved. In this case stretching of the nerves damaged the epineurial vessels, the myelin sheath and the axons, and this was compounded by compression from

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a

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b

c

Fig.  3.32  Traction injury. (a) The circumflex nerve exposed 4  days after anterior dislocation of shoulder. The bundles had ruptured and retracted within the intact epineurium. (b) Traction injury of the common peroneal nerve from varus injury at the knee. There was extensive recovery over the course of 9 months (axonotmesis). (c) A more violent

traction injury of the right upper limb. The median nerve was elongated by more than 100%. Over the course of the next 3 years there was recovery of cutaneous sensation in the hand, and some recovery of the flexor muscles of the forearm. The sympathetic fibres never recovered.

bleeding and by the persistence of inflammation induced by haematoma. A wide range of drugs had been used in an attempt to control the pain without considering the possibility of a persisting focal noxious agent at work. There may be a case, not only for monitoring of nerve conduction, but also the flow through adjacent main arteries before, during and after operations for the correction of severe flexion deformity at the knee and other joints as recommended by Martin et al. (2006). Somewhat similar circumstances obtain in limb lengthening operations, even though it is usual to effect a change slowly, over a period of weeks. It has been argued that, if during the process, signs or symptoms of actual or impending neural damage appear, the process can be stopped to permit recovery. Galardi et al. (1990) are less reassuring: they studied events in the limbs of five patients whose tibiae were lengthened at the rate of 1  mm per day over a period of 53–107  days. The ages of the patients ranged from 3 to 24 years. The conduction velocity of nerves and the electrical activity in muscles during lengthening were examined

and evidence of damage to myelin sheaths and axons was found in all cases. These findings evidently raise the question of whether nerve function should always be monitored during correction of major deformities of long standing. This concept was used by Nogueira et al. (2003) who used a pressure sense monitoring device during 814 limb lengthening procedures. Seventy-six (9.3%) nerve lesions occurred. Nerves were most at risk in double level lengthening of the tibia and in skeletal dysplasia. Most of the affected nerves were decompressed; 74 of the 76 recovered. Clear conclusions are drawn from this admirable work: the rate of lengthening should be slow; affected nerves should be decompressed as soon as possible; monitoring of nerve function by a pressure sense device is more sensitive than clinical examination and the largest myelinated fibres are the most vulnerable. Paley (1990) provides sound advice about prevention. Analysis of the deformity provides information about the potential distortion of neurovascular bundles; the drill hole for the frame screws should be made opposite to the bundle and neuromuscular blocking agents should not be used.

Reactions to Injury

Severe pain indicates damage to a nerve or vessel or both. If a Tinel sign is evoked by tapping the transfixion wire then it has certainly passed through, or close to, a trunk nerve. Polo et al. (1997) lengthened the lower limbs in 14 patients with achondroplasia and found that the common peroneal nerve was most vulnerable and that the lesion was detectible in the first days of elongation. The prognosis for nerves injured during correction of deformity or limb elongation is poor. Case report: A 12 year old child with Stüve-Weidemann syndrome had osteotomy of the femur for flexion deformity of the lower limb. The operation was done under epidural anaesthetic and a suprasystolic cuff was placed about the upper part of the thigh. There was a complete, but painless, sciatic palsy. NPI confirmed deep axonopathy without any evidence of generalised neuropathy. The tibial and common peroneal nerves were exposed 5 months later. They were unblemished. The amplitude of CNAP’s across the presumed level of lesion was diminished. At 36  months, there was some recovery for the tibial nerve but very little for the common peroneal nerve. Case report: A 35 year old woman with severe deformity at the knee and in the leg after operations for Blount’s disease, was treated by two level osteotomy of the tibia and fibula stabilised by an Ilizarov frame. This was followed by a deep, but painless, palsy of the tibial and common peroneal nerves. The nerves were exposed at 14 days to exclude the possibility of haematoma. They were unblemished. There was little recovery for either nerve at 18 months.

3.4.12 Thermal Injury The effects of cold have been studied extensively (Franz and Iggo 1968; Lundberg 1948; Douglas and Malcolm 1955; Dodt 1953; Denny Brown et  al. 1945). Bickford (1939)), cooling the ulnar nerve, found a sequential loss of the different modalities of sensation: first, appreciation of cold, and last, sensibility to pain, touch and warmth. As Thomas and Holdorff (1993) remark “observations on non freezing cold injury of nerve have largely stemmed from the exigencies of war”.

In the First World War “trench foot” was a common cause of disablement; in the Second World War “immersion foot” was a more common occurrence (Ungley et al. 1945). Donaghy (2009b) describes the freezing injury of frost bite, in which there is tissue necrosis often with a clear demarcation between living and dead tissue. Wallerian degeneration is an early feature of these injuries. One of us experienced this injury to a relatively minor degree and noted the loss of sensation in the affected toes which persisted for more than 10 years, a

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sensory loss which increased and became painful when the foot was exposed to mild cooling. The terrible pain which often complicates more severe frost bite is described by Maurice Herzog from his experience with the French expedition to Annapurna. The second type of cold injury recognised by Donaghy follows prolonged immersion in cold water or prolonged exposure to cold around freezing point. Irwin et al. (1997) had the opportunity of investigating the neural damage in a case of “trench foot” or “non freezing cold injury.” A 40 year old Asian man, homeless in the UK through the operation of free market principles, was subjected to exposure lasting 19 days, during 8 of which the ambient temperature was below 0°c. He lost all function and sensibility in his feet, and, ultimately, several toes. Sensory nerve function was carefully measured and recorded; at the time of removal of dead tissue, 4 weeks after admission, a biopsy of viable tissue was taken from the plantar surface of the right great toe. There was evidence of damage to both myelinated and unmyelinated nerve fibres, possibly, the authors’ speculate, “in a cycle of ischaemia and reperfusion.” In civil practice at the present time, it is rather the effects of heat that concern the clinician, principally because of damage to the sciatic nerve by the heat of polymerising cement during arthroplasty of the hip. The effects of heat seem to have received little attention. Nerves can be destroyed by extremes of heat, or by diathermy during operation. Hoogeveen et al. (1991) investigated the effect of heating a 5 mm segment of the sciatic nerve of the rat for 30 min at 45°C. They found that this produced swelling of the endothelium of the neural blood vessels and Wallerian degeneration of all the nerve fibres. There was of course total loss of motor function. The process in the nerves was, however, reversible: regeneration occurred over 4–5 weeks. The vascular changes were not apparently reversible. Xu and Pollock (1994) examined physiologically and morphologically the effect of heat ranging from 47°C to 58°C on rat sciatic nerve. Unmyelinated fibres showed a greater direct vulnerability to hyperthermia, first manifest as a reversible conduction block and at higher temperatures by immediate and selective axonal degeneration. Lower grade thermal injury caused a delayed selective loss of myelinated fibres. Xu and Pollock remark in relation to the latter effect: “Evidence from this study suggests that this is secondary to a heat-induced angiopathy, immediately and diffusely manifest in the vasa nervorum and giving rise to a progressive and ultimately severe reduction in nerve blood flow.” The relative sparing of unmyelinated fibres was attributed to their greater resistance to ischaemia. It is necessary in considering risk to the sciatic nerve in operation for hip replacement, to recall that the temperature of polymerising cement rises to 95°C about 15 min after mixing, and remains above 70°C for another 12 min. Birch et al. (1992) had the opportunity of examining a length of sciatic nerve damaged by the heat of polymerising cement. They later took the

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a

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a

b b

Fig. 3.33  A case of damage to the sciatic nerve by cement during operation for arthroplasty of the hip. (a) The sciatic nerve seen at operation a year after initial operation. The extruded cement can be seen in relation to the nerve. (b) The severely damaged common peroneal component was resected and grafted. The proximal stump appeared to be relatively healthy at 1 cm proximal to the cement. Toluidine blue ×100.

opportunity of studying the effect of the heat of polymerising cement on the median nerve of an arm recently amputated because of a complete pre-ganglionic injury of the brachial plexus. The remarkable feature was the localised nature of the lesion: although at the site of burning there was destruction of axoplasm and disruption of myelin, a normal pattern of myelinated and unmyelinated fibres was found 10  mm from the margin of the cement (Figs. 3.33a, b and 3.34 a, b). Wilkinson and Clarke (1992) reported two cases of burns to the brachial plexus in patients who fell asleep with their arms draped over the back of heated towel rails. Later decompression was performed in one case, revealing extensive fibrosis of the nerves and adjacent tissues. Recovery was poor in both these cases. Tubiana (1988) made rather sombre observations on the evolution of the treatment of these injuries during a long and illustrious career, noting little significant improvement. Salisbury and Dingeldein (1988) and Salzberg and Salisbury (1991) provide extensive reviews emphasising the necessity for early incision of the encircling eschar (Fig. 3.35). A clear description of the technique, with

Fig.  3.34  Thermal damage to the median nerve after exposure to the heat of setting cement, showing the limited longitudinal extent of the neural lesion. (Electronmicroscopic studies by Mr Stephen Gschmeissner.) (a) Virtual destruction of axoplasm and cellular elements at the site of the lesion ×3,600. (b) Healthy axons and collagen 10 mm from site of injury ×3,000.

emphasis on avoiding damage to underlying nerves, is given. Chalain and Clarke(2000) review the field of thermal injuries, their pathophysiology and the treatment of the consequences in children. Bonney (2002) describes the tragic consequences of the flash burns incurred during the Battle of Jutland which affected the face and the hands and were caused by the momentary flame of high explosives.

3.4.13 Electric Shock Hobby and Laing (1988) recognised four groups of electrical injury in 169 cases from a total of 3,300 patients: true electrical injury, from current passing from the conductor through

Reactions to Injury

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Fig. 3.35  Urgent and extensive division of the skin and fascia in a full thickness burn from petrol fire (Courtesy of Major K Brown RAMC).

the skin to the tissues; “arc” burn, where a current passes external to the body to the ground; secondary flame burn, from ignited clothing; and direct burn, from a hot electrical element. Reasonable spontaneous recovery occurred in those cases where the blood supply to the adjacent tissues was not destroyed. Di Vincenti et al. (1969) reported 69 cases of electrical burns, mostly from high tension injuries. The median and ulnar nerves were the most frequently damaged and the lesions were often severe and irreparable. Because nerves are good conductors the neurovascular bundles may be destroyed. Clifton et al. (2000) advise immediate repair of trunk nerves charred in electrical burns using nerve grafts which are covered by free full thickness skin flaps or by a vascularised nerve graft, such as the lateral cutaneous nerve of forearm within a free lateral arm flap. When electrical contact is brief there may be little burning but the passage of electrical current causes break down of the cell membranes. Clifton and colleagues describe this process of electroporation which is caused: “by polar water molecules being driven into molecular scale defects in the lipid bilayer component of the cell membrane, causing the defects to enlarge, with an increase in permeability, and the membrane to rupture.” Muscle and nerve cells are particularly susceptible to this injury which is responsible for some of the immediate clinical signs such as muscle spasms and episthotonus. The case described by Thaventhiran et al. (2001) provides one example of this phenomenon. The patient was injured by contact with a 20,000 voltage AC supply, the current entering at the right arm and exiting through the left elbow. He was completely paralysed below the neck but over

the subsequent 5 years there was extensive recovery although he remained doubly incontinent: “the remarkable degree of peripheral nerve regeneration and recovery seen in this patient suggests that the axons were selectively injured, leaving the surrounding tissue including the Schwann cells intact to enable subsequent regeneration.” The recovery of the very severe and generalised sensory motor polyneuropathy unmasked the extent of the myelopathy. There are some similarities between this case that of a 34 year old man who was struck by lightning. He suffered immediate loss of consciousness and cardiac arrest but was successfully revived. He was wearing a heavy gold chain at the time and a deep entry burn was seen on the right side of his neck with an exit burn on the left side. There were second degree flash burns to the chest, groin, upper and lower legs and there were superficial burns over the whole of his torso which formed a feathery or fern leaf pattern. He had a C5 tetraplegia with both urinary and faecal incontinence. His rehabilitation was directed by Dr Lal Landham (Rochester) and we were given the opportunity to examine him on several occasions. By 2 years after injury he had regained considerable recovery of power in all four limbs so that he could walk and he had regained urinary and faecal control. Quantitative sensory testing showed normal sensory thresholds for all modalities in all four limbs except for an elevated vibration threshold in the right lower limb. Neurophysiological investigations confirmed normal sensory and motor conduction but persisting denervation of the C5 and C6 myotomes. He had sustained a severe, diffuse sensory motor neuropathy. The permanent defect lay with the anterior horn cells at C5

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findings did nothing to explain the transient interruption of nerve function after percussive injury described by DennyBrown and Brenner (1944).

3.4.15 Injection Injury

Fig.  3.36  Function in the upper limbs 2 years after lightning strike. Note the atrophy of the muscles of the shoulder and in the arm.

and C6 and it seems likely that the site of the entry and exit burns in the neck is relevant. Perhaps these neurones were destroyed by electroporation? (Fig. 3.36). Quantitative sensory testing may reveal abnormalities which cannot be detected by classical neurophysiological investigations. A 40 year old man was electrocuted (AC current), by a faulty fuse in his house. The current passed through his right ear down to his right hand. He experienced very considerable pain and was unable to use his right upper limb. NPI were performed, first, 1 month after the injury and then again after 6 months which showed no disturbance either of sensory or motor conduction. Electromyography showed a pattern consistent with conduction block. However, QST at 6 months revealed diminished pinprick sensation in the right forearm and hand but also in the right trunk. Thermal thresholds were elevated in the right thenar eminence, with paradoxical burning on cooling by 7.2°C. There was also a suggestion of elevated thresholds in his right T2 region. Vibration thresholds were elevated at the right thumb and middle finger. In the same area there was elevation of monofilament threshold. Cotton wool sensation was reduced in the same distribution as pinprick sense. His sweating was preserved.

3.4.14 Percussion Injury Richardson and Thomas (1979) studied the effects of percussion injury. The clinical application in the peripheral nerve field is perhaps slight, but the authors indicate that their results could give some indication of events in injury of the spinal cord, in spite of the difference in structure between central and peripheral nervous tissue. The lesion appears principally to be a localised axonal interruption with later degeneration. Richardson and Thomas noted that their

The perineurium may be lacerated by the point of a needle an event which causes severe pain in the conscious patient. If that complaint of pain is ignored and through an injection into the nerve, the consequences may be severe. The damaging substances commonly injected into nerves are: steroid preparations; anaesthetic agents for intravenous use such as thiopentone; non steroidal anti-inflammatory drugs; anxiolytic agents such as diazepam; antibiotics; and local anaesthetics. The nerves most commonly affected are the brachial plexus in the neck and axilla, the radial nerve in the arm, the median at the elbow and the sciatic in the buttock. Usually, the occurrence of severe local and radiated pain makes it plain that the drug has been injected into the nerve. The onset of later and sensory paralysis may, however, be delayed for some hours. Although Hudson (1984) suggested that the ill effects arise from intraneural injection rather than from injecting near the nerve and later diffusion, it is hard to resist the speculation that the latter must sometimes be the responsible mechanism, a suggestion which is supported by Kline and Hudson (1995). The response of the nerve to the needle and to the substances injected is illustrated by some cases that we have treated. 1. A 40 year old man of slender physique came to operation which required exposure of the common peroneal nerve at the knee. After induction of general anaesthesia the line of incision was infiltrated with 0.25% bupivicaine. This provoked a twitch in the extensor muscles of the ankle indicating that the needle had been passed too deeply. The nerve was then exposed and the epineurium was greatly distended by the injected fluid. The bundles within were intact but the epineurial circulation had disappeared over a segment of some 4 cm. The epineurium was incised to decompress the nerve; the operation was then completed. On awakening he had a foot drop with sensory loss but no pain. By 6 h, sensation had recovered and there was the first evidence of recovery into the dorsiflexor muscles. Recovery was complete by 36 h. 2. A 45 year old woman with rheumatoid arthritis, for which she was taking prednisolone, experienced sudden severe shooting pain into her hand during venepuncture at the elbow. Pain persisted and sensation remained abnormal in the index and middle fingers whereas muscle power and sympathetic function remained intact. At 24 months the amplitude and velocity of sensory conduction from the affected digits was reduced to less than one half of

Reactions to Injury

normal. The median nerve was explored at the level of lesion which was marked by a strong Tinel sign. The epineurium was thickened and adherent to adjacent structures; epineurotomy revealed a neuroma of two bundles. After external neurolysis local anaesthetic was infused about the nerve by catheter for 24 h. Her pain was greatly improved. 3. The sciatic nerve of a 60 year old woman was blocked by 30 ml of 0.5% bupivicaine during operation for total knee replacement. Numbness and weakness were apparent within a few minutes but pain did not develop until 7 days had passed, increasing in intensity for the next 14 days. This was expressed as burning pins and needles in the sole of the foot and as shooting or electrical pain to the dorsum of the foot. The common peroneal nerve recovered by 6 weeks but the lesion of the tibial nerve remained dense. NPI at 14 weeks confirmed loss of conduction for the tibial nerve but recovery of motor conduction in the common peroneal nerve. Normal motor units were demonstrated in gastrocnemius but there were fibrillations in the abductor hallucis. Pain resolved spontaneously by 16 weeks, recovery was extensive by 36 weeks and by this time conduction was now detectable in the sural nerve, but the tibial nerve action potential was still absent and sympathetic paralysis persisted. It seems that recovery was better for the larger myelinated fibres than it was for the finely myelinated and non myelinated fibres. 4. A 6 year old boy was given an injection of antibiotics into the buttock and he experienced instantaneous and severe pain. When he was seen 2 years later there was a severe equinovarus deformity with shortening of the femur, the tibia and the foot on the ipsilateral side. Neurophysiological investigations at that time revealed an extensive degenerative lesion. There was no motor or sensory conduction in the common peroneal nerve, sensory conduction was preserved in the sural nerve. Denervation of the muscles was widespread, but rather deeper for the common peroneal nerve than it was for the tibial divisions. The posture of the foot was improved by an extensive operation which included elongation of the tendo Achillis, slide of the plantar muscles, shortening of the lateral column of the foot, calcaneal osteotomy and anterior transfer of tibialis posterior (Mr Fergal Monsell, RNOH). Experience with injection injuries in human beings does not always match with that of injection into the nerves of rats, just as the behaviour of the former is not regularly matched by that of the latter. Full recovery is by no means invariable; noxious injection is often followed by epineurial fibrosis and sometimes by dense intraneural scarring. Persistence of pain following an injection of steroid for carpal tunnel syndrome led to exploration of the median nerve in four patients at intervals ranging from 2 weeks to 8 weeks after injection. The nerves were found inflamed and swollen over a length of some 3 cm and they were surrounded by filmy adhesions, but

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there were no signs of penetration of the trunk by the needle. Injection of steroids into the buttock of a 64 year old man with psoriasis and scleroderma was followed, at about 1 hour, by complete common peroneal palsy and a painful partial lesion of the tibial nerve. The pain resolved spontaneously at about 3 months. Neurophysiological investigations at 1 year showed extensive demyelination with some axonopathy. Sensory conduction was absent: motor conduction was reduced in amplitude and in velocity. Polyphasic potentials were widespread in the muscles sampled but there were no fibrillations. It is possible that diffusion of the agent provoked vasculitis within and about the nerve in this case. The prognosis is not at all good. Pandian et al. (2006) followed 65 lesions of sciatic nerve and radial nerves caused by intramuscular injections of various drugs. Axonopathy was confirmed in all cases, and reinnervation was demonstrated in only one third. Pain was usual. The consequences for the growing limb were particularly severe.

3.4.16 Vibration Injury Extensive studies from the Department of Hand Surgery in Malmo have improved understanding of this difficult and controversial field (Stromberg 1997). The regular use of hand held vibrating tools may lead to a complex of symptoms, the hand–arm vibration syndrome. Stromberg defines three groups of symptoms: sensory-neural; vasospastic, and a combination of both. Cold intolerance presents as a significant symptom in one half of the patients with sensoryneural symptoms. There was impairment of nerve conduction, vibro tactile sense, and temperature sense in all patients, changes which were more strongly expressed in the median nerve. Biopsies of the dorsal interosseous nerve revealed demyelination, endoneurial and perineurial fibrosis, and loss of axons.

3.5 The Perineurium and Neoplasm or Infiltration Tumours arising from cells within the endoneurium are contained within the perineurium which acts as a compartment. The tumour may be a benign schwannoma but malignant peripheral nerve sheath tumours whose cell of origin is the Schwann cell, are contained within the perineurium, at least initially, and spread within it. We have seen intraneural spread of malignant tumours extending up to 18 cm from the main tumour (Fig.  3.37). The brachial and lumbo sacral plexus are common sites for malignant invasion by direct spread or by metastases through the lymphatics. However

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3.6 Radiation and Peripheral Nerves

Fig. 3.37  Malignant peripheral nerve sheath tumour in the medial cord of the brachial plexus in a patient with NF1. A biopsy of C8, 15  cm proximal to the main tumour mass, shows one bundle replaced by tumour and some degenerative changes in adjacent bundles. Haemotoxylin and eosin ×160 (Courtesy of Dr Jean Pringle).

there are no lymphatics within the endoneurium and the two cases of lumbosacral radiculoplexopathy in prostate cancer, described by Ladha et al. (2006a) at the Mayo Clinic, represent, in all likelihood, direct extension of the tumour within nerves from the prostate. Both patients had experienced worsening pain with a deepening sensory motor loss for a number of years. In one case this led to an increasing defect of bladder and bowel control. Biopsy of the affected nerves showed tumour cells organised into a glandular appearance, surrounded by S-100 positive cells which were contained within the perineurium. These workers comment that magnetic resonance imaging is extremely helpful in localising the disease and defining its extent and they observe that: “the clinician should always consider the entity of neoplastic radiculoplexopathy in the differential diagnosis of progressive, painful, lower extremity weakness as treatments such as radiotherapy may be palliative and spare further neurological decline.” Ladha et  al. (2006b) described two cases of isolated amyloidosis presenting as lumbosacral radiculoplexopathy. The first patient experienced a painless progressing sensory and motor loss. There was no systemic disease. Biopsy revealed diffuse infiltration of the endoneurium and perineurium. The MR scan in this case showed enlargement of the sciatic nerve with a denervation signal in the gluteal muscles. In the second case the lesion was more severe, with incontinence of bladder and bowel. This patient had successfully been treated for a lymphoma some years previously and there were no signs of active disease when he presented to the Mayo Clinic. Biopsy of the cauda equina was performed which revealed replacement by amyloid, and his neurological state was stabilised by excision of an “amyloidoma” from L3. The neurological effects of generalised amyloidosis are protean, the subject is reviewed by Kyle et al. (2005).

The statement by Janzen and Warren (1942) that “nerve tissue is extremely resistant to radiation” is, alas, true only so far as the function of conducting an impulse is concerned, and in so far as doses up to 10,000R (100 Gy) “do not cause overt damage to this normally static cell population” Vujaskovic (1997) found that peripheral nerves were damaged by exposure exceeding 20 Gy. The more deeply seated larger fibres were worst affected: the first changes occurred within the axon, where there was increased density of microtubules and neurofilaments. The lesion is perhaps best considered as (1) a lesion from external compression exerted by fibrosis of soft tissue and (2) an intrinsic lesion of the nerve. The latter affects the axon, the Schwann cells and the myelin sheath; it is associated with vasculitis, which leads eventually to fibrosis (Spiess 1972) (Fig.  3.38a, b). The affection may extend to the main vessel (Fig. 3.39). It seems likely that the dose of radiation tolerated by neural tissue depends broadly on the total dose and the period of time over which it is given, but evidently there are individual variations and there may indeed be individual susceptibilities.

3.7 Envenomation In the singular case reported by Laing and Harrison (1991) a young man’s right ulnar nerve was affected by the venom expressed from the tentacle of a box jellyfish (Chironex fleckeri) and presumably conveyed transcutaneously. The nerve was explored and found to be oedematous, but the period elapsing between injury and exploration is not related. There was spontaneous recovery. The case evokes echoes of that of the Lion’s Mane (1909), though because of the absence of Dr Watson from the latter we are condemned to remain in the dark about the presence of neuropathy in the surviving victim of Cyanea capillata. The fascinating field of poisons and evanomation is reviewed by Donaghy (2009a). The active agents cause death by interfering with ion channel function, by blocking the neuromuscular junction and by blocking synaptic transmission within the central nervous system. Cicutoxin, the agent in water hemlock, blocks ion channels and also receptors to gamma amino butyric acid (GABA) in the brain and the symptoms bear little relation to those attributed to Socrates in the Phaedo. The Puffer fish contains tetradotoxin which blocks sodium channels, a phenomenon which has enabled the analysis of these channels. The Krait injects bungarotoxins which block the post synaptic acetyl choline receptors at the neuromuscular junction; whereas the venom injected by the Mamba and the Taipan block pre synaptic nerve endings.

Reactions to Injury

109

a

Fig. 3.39  Radiation induced thrombosis of the third part of subclavian artery. A 38 year old woman developed severe pain, swelling and paralysis 6 weeks after completing a course of radiotherapy for breast cancer. She lost all sensation in the tips of her fingers. She could recognise light touch but could not localise it in the palm of the hand. Sensation was normal proximal to the wrist crease. There was no recovery of skeletal muscle or of smooth muscle function in her forearm and hand.

b

Fig. 3.38  Radiation neuropathy. Electron microphotographs of specimens from biopsy of the lateral trunk of the brachial plexus taken two and a half years after radiotherapy for cancer of the breast. (a) Extensive collagenisation, loss of axons and myelin ×4,125. (b) Extensive demyelination and Schwann cell loss ×4,125 (Electron micrographs prepared by Mr Michael Kayser).

3.8 The Peripheral Effects of Denervation These effects follow degenerative lesions in which recovery fails or is long delayed. If regeneration of axons into the distal stump fails, changes, which over time become

irreversible, develop in the target organs and in the proximal neurone. Motor end-plates atrophy and disappear (Bowden and Gutmann 1944); the denervated muscles undergo fibrosis. Bowden and Gutmann (1944) recorded that after 3 months denervation it became increasingly difficult to identify the end plates. From 3 years on they found fragmentation of structures, and reckoned that this represented irreversible change. Luco and Eyzaguirre (1955) found that the nearer the lesion was to the point of denervation the more rapidly did the changes in the end plates appear. Cutaneous sensory end-organs atrophy more slowly. Dellon (1981) found that they degenerate and eventually atrophy. The reaction of muscle spindles to denervation has been studied extensively. Sherrington (1894) found the spindles “very obvious amid atrophied extrafusal muscle fibres five months after denervation.” Batten (1897) found in a case of complete paralysis after a lesion of the brachial plexus that atrophy of spindles occurred but took place much later than was the case in ordinary muscle fibres. Tower (1932) found that the nuclear bag fibres showed only a slight reduction in diameter after denervation, whereas the chain fibres atrophied almost as rapidly as did the extrafusal fibres. Tower noted in particular the thickening of the capsule. De Reuck (1974) reported rather similar findings. Swash and Fox (1974) noted capsular thickening and atrophy of intrafusal fibres after sensorimotor denervation and Myles and Glasby (1992) conclusively showed that atrophy of muscle spindles followed uncorrected denervation. Loss of nervous control of the small peripheral blood vessels leads to defects of nutrition and atrophy in the subcutaneous tissues. This is compounded by unnoted injury, which can lead to the loss of part or the whole of the limb or even death as is seen in congenital insensitivity to pain, in leprosy

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or in septicaemia from an unnoted sore in neglected cases of sciatic palsy. The effects of denervation are particularly severe in the growing child especially so where there is persisting imbalance of muscle forces acting across a joint (Fig.  3.40). It is our impression that the shortening of the limb is more severe after complete lesions of main trunk nerves such as the sciatic than it is in cases of poliomyelitis.

3.9 Changes at the Higher Levels: The Phantom Limb

Fig. 3.40  Atrophy of the left foot in an 11 year old boy 4 years after transection of the tibial and common peroneal nerves at the knee. The repair of the common peroneal nerve was successful, that of the tibial nerve failed.

The changes in the functional organisation of the somatosensory cortex are rapid and extensive. Structural or, at least, synaptic reorganisation at a subcortical level was probably shown by Banati et al. (2001) who demonstrated changes in the activity of glial cells in the thalamus in patients with intractable pain after injury to the brachial plexus or peripheral nerves (Fig. 3.41). Ramachandran and Hirstein (1998) described their findings in a patient (DS) who had his arm amputated 1 year after an avulsion lesion of the brachial plexus. Stimulating the skin of the face evoked a sensation which was referred to the amputated digits: “when the cotton swab was moved continuously from the angle of the mandible to the symphysis menti, the referred sensation felt as if ‘it was moving from the ball of the thumb to the tip in an arc like motion’. This observation was replicated several times.” Ramnachandran and Hirstein suggest that the sensory input from the face is being received in two different cortical areas: the original face area and the area that previously only received information from the arm. Kew et al. (1997) studied

Fig. 3.41  Positron emission tomographic scan showing an in vitro marker of increased glial cell activity indicating synaptic reorganisation in the thalamus in a patient with persisting pain 4 years after brachial plexus lesion (Courtesy of Professor Praveen Anand).

Reactions to Injury

two patients with avulsion lesions of the brachial plexus using positron emission tomographic (PET) scanning. Both of these patients had referred sensations on the anterior and posterior chest wall where stimulation evoked a response in the amputated hand. PET scans showed a precise correlation between the finger where the referred sensation was felt and the disposition of the cortical maps. The phenomena of the “phantom” limb provides opportunities for analysis of the changes in the somatosensory cortex after injury. Mitchell (1872) wrote: “nearly every man who loses a limb carries about with him a constant or inconstant phantom of the missing member, a sensory ghost of that much of himself and sometimes a most inconvenient presence, faintly felt at times, but ready to be called up to his perception by a blow, a touch or a change of wind.” To Lord Nelson the severe phantom limb pain which he experienced in his right arm, lost during the attack at Santa Cruz provided a “direct proof of the existence of the soul” (Riddoch 1941). One extraordinary example of the persistence of a painful phantom is provided by a patient treated by our colleague, Christopher Wynn Parry, in the Rehabilitation Unit of the Royal National Orthopaedic Hospital. A 33 year old woman presented with persistent and severe phantom pain following amputation of her right arm in a road traffic accident at the age of 11 years. She described her clenched fist tightly holding a florin, for she had been going shopping at the time of her accident. There was a dramatic response to transcutaneous nerve stimulation and she described that, as the pain diminished, she felt the fingers of her clenched fist open and the coin dropped from her hand. The transcutaneous nerve stimulator was used on several occasions, ultimately with lasting relief. On the last occasion she described how she “saw” the coin disappearing down a drain. There are a number of possible explanations for this result; we might add that Christopher Wynn Parry often succeeded in relieving pain in patients otherwise abandoned.

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112 Denny Brown D, Adams RD, Brenner G, Doherty MM (1945) The pathology of injury to nerve induced by cold. J Neuropathol Exp Neurol 4:305–323 Denny-Brown D, Brenner C (1944) The effect of percussion on nerve. J Neurol Neurosurg Psychiatry 7:76–95 Di Vincenti FC, Moncrieff JA, Pruitt BA (1969) Electrical injuries: a review of 65 cases. J Trauma 9:497–507 Dodt E (1953) Differential sensitivity of mammalian nerve fibres. Acta Physiol Scand 29:91–108 Donaghy M (2009a) Polyneuropathy. In: Donaghy M (ed) Brain’s diseases of the nervous system, 12th edn, Oxford University Press, Oxford Chapter 21, pp 541–602 Donaghy M (2009b) Toxic and environmental disorders. In: Donaghy M (ed) Brain’s diseases of the nervous system, 12th edn, Oxford University Press, Chapter 5, pp 141–164 Douglas WW, Malcolm JL (1955) The effect of localized cooling on conduction in cat nerves. J Physiol 130:63–71 Durrenberger PF, Facer P, Gray RA, Chessell IP, Naylor A, Bountra C, Banati RB, Birch R, Anand P (2004) Cyclooxygenase – 2 (COX-2) in injured human nerve and a rat model of nerve injury. J Peripher Nerv Syst 9:15–24 Durrenberger PF, Facer P, Casula MA, Yiangou MY, Gray RA, Chessell IP, Day NC, Collins SD, Birnham S, Wilson AW, Elliot D, Birch R, Anand P (2006) Prostanoid receptor EP1 and COX-Z in injured human nerves and a rat model of nerve injury: a time course study. BMC Neurol 6:1 Dyck PJ, Nukada H, Lais CA, Karnes J (1984) Permanent axotomy: a model of chronic neuronal degeneration produced by axonal atrophy, myelin remodelling and regeneration. In: Dyck PJ, Thomas PK, Lambert EH, Bunge R (eds) Peripheral neuropathy, 2nd edn. WB Saunders, Philadelphia, pp 660–690 Dyck PJ, Dyck J, Engelstad PJB (2005a) Pathological alterations of nerves. In: Dyck PJ, Thomas PK (eds) Peripheral neuropathy, 4th edn. Elsevier Saunders, Philadelphia, pp 733–829, Chapter 32 Dyck PJB, Engelstad J, Dyck PJ (2005b) Microvasculitis. In: Dyck PJ, Thomas PK (eds) Peripheral neuropathy, 4th edn. Elsevier Saunders, Philadelphia, pp 2405–2414, Chapter 106 Eames R, Lange LS (1967) Clinical and pathological study of ischaemic neuropathy. J Neurol Neurosurg Psychiatry 30:215–236 Fowler TJ, Danta G, Gilliatt RW (1972) Recovery of nerve conduction after a pneumatic tourniquet: observations in the hind limb of a baboon. J Neurol Neurosurg Psychiatry 35:638–647 Franz DN, Iggo A (1968) Conduction failure in myelinated and nonmyelinated axons at low temperatures. J Physiol 199:319–345 Galardi G, Comi G, Lozza L, Marchettini P, Novarina M, Facchini R, Paronzini A (1990) Peripheral nerve damage during limb lengthening. J Bone Joint Surg 72B:121–124 Gardiner MD, Mangwani J, Williams WW (2006) Aneurysm of the common iliac artery presenting as a lumbosacral plexopathy. J Bone Joint Surg 88B:1524–1526 Gereis V (2005) Paresis and paralysis, pers com Gilliatt RW (1981) Physical injury to peripheral nerves. Mayo Clin Proc 56:361–370 Gilliatt RW, Hjorth RJ (1972) Nerve conduction during Wallerian degeneration in the baboon. J Neurol Neurosurg Psychiatry 35:335–341 Gilliatt RW, Taylor JC (1959) Electrical changes following section of the facial nerve. Proc Royal Soc Med 52:1080–1083 Greer HD (1997) Neurological consequences of diving. In: Bove AA, Davis JC (eds) Diving medicine. WB Saunders, Philadelphia, pp 258–269 Griffin JW, Hoffman PN (1993) Degeneration and regeneration in the peripheral nervous system. In: Dyck PJ, Thomas PK, Lambert EH, Bunge R (eds) Peripheral neuropathy, 3rd edn. WB Saunders Company, Philadelphia, pp 361–376 Groves MJ, Scaravilli F (2005) Pathology of peripheral neurone cell bodies. In: Dyke PJ, Thomas PK (eds) Peripheral neuropathy, 4th edn. Elsevier Saunders, Philadelphia, pp 683–732, Chapter 31

Surgical Disorders of the Peripheral Nerves Gutmann E, Sanders FK (1943) Recovery of fibre numbers and diameters in the regeneration of peripheral nerves. J Physiol 101:489–518 Haftek J (1970) Stretch injury of peripheral nerve. J Bone Joint Surg 52B:354–365 Haftek J, Thomas PK (1967) An electron-microscopic study of crush injuries to peripheral nerves. J Anat 102:154–155 Hall S (1999) The biology of chronically denervated Schwann cells. Ann NY Acad Sci 883:215–233 Hall S (2005) The response to injury in the peripheral nervous system. J Bone Joint Surg 87B:1309–1319 Harriman DGF (1977) Ischaemia of peripheral nerve and muscle. J Clin Pathol 30(supplII):94–99 Hess K, Eames RA, Darveniza P, Gilliatt RW (1979) Acute ischaemic neuropathy in the rabbit. J Neurolog Sci 44:19–43 Hill S, Hall S (1999) Microscopic anatomy of the posterior interosseous and median nerves at sites of potential entrapment in the forearm J Hand Surg 24B: 170–176 Hobby JAE, Laing JE (1988) Electrical injuries of the upper limb. In: Tubiana R (ed) The hand, vol III. WB Saunders Company, Philadelphia, pp 779–787 Hoffer JA, Stein RB, Gordon T (1979) Differential atrophy of sensory and motor fibres following section of cat peripheral nerves. Brain Res 178:347–361 Holmes W, Young JZ (1942) Nerve regeneration after immediate and delayed suture. J Anat 77:63–96 Hongell A, Mattson HS (1971) Neurographic studies before, after and during operation for median nerve compression in the carpal tunnel. Scand J Plast Reconstr Surg 5:103–109 Hoogeveen JF, Wondergem J, Troost D, van der Kracht AHW, Haveman O (1991) Blood vessel damage followed by Wallerian degeneration in the rat sciatic nerve after local hyperthermia. Neuropathol Appl Neurobiol 17:250–251 Houten JK, Errico TJ (2002) Paraplegia after lumbosacral nerve root block: report of three cases. Spine 2:70–75 Hudson AR (1984) Injection injuries of nerves. In: Dyck PJ, Thomas PK, Lambert EH, Burge R (eds) Peripheral neuropathy, 2nd edn. WB Saunders, Philadelphia. pp 429–431 Irwin MS, Gilbert SEA, Terenghi G, Smith RW, Green CJ (1997) Cold intolerance following peripheral nerve injury. Brit J Hand Surg 22:308–316 Janzen AH, Warren S (1942) Effect of roentgen rays on peripheral nerves of rats. Radiology 38:333–337 Jefferson D, Neary D, Eames RA (1981) Renaut body distribution at sites of human peripheral nerve entrapment. J Neurolog Sci 49:19–29 Kew JJ, Halligan PW, Marshall JC, Passingham RE, Rothwell JC, Ridding MC et  al (1997) Abnormal access of axial vibrotactile input to deafferented somatosensory cortex in human upper limb amputees. J Neurophysiol 77:2753–2764 Kline DG, Hudson AR (1995) Nerve injuries,WB Saunders, Philadelphia Injection injury p 46–50 Kyle RA, Kelly JJ, Dyck PJ (2005) Amyloidosis and neuropathy. In: Dyck PJ, Thomas PK (eds) Peripheral neuropathy, 4th edn. WB Saunders, Philadelphia. Chapter 108, pp 2427–2452 Ladha SS, Spinner RJ, Suarez GA, Amrami KK, Dyck PJB (2006a) Neoplastic lumbosacral radiculoplexopathy in prostate cancer by direct perineurial spread: An unusual entity. Muscle Nerve 34: 659–665 Ladha SS, Dyck PJB, Spinner RJ, Perez DG, Zeldenrust SR, Amrami KK, Solomon A, Klein CJ (2006b) Isolated amyloidosis presenting with lumbosacral radiculopathy: description of two cases and pathogenic review. J Peripher Nerv Syst 11:346–352 Laing JHE, Harrison DH (1991) Envenomation by the box-jellyfish - an unusual cause of ulnar nerve palsy. J Royal Soc Med 64:115–116 Landau WM (1953) The duration of neuromuscular function after nerve section. Neurosurgery 10:64–68 Lawson SN (2005) The peripheral sensory nervous system: dorsal root ganglion neurones. In: Dyck PJ, Thomas PK (eds) Peripheral

Reactions to Injury neuropathy (in two volumes), 4th edn. Elsevier Saunders, Philadelphia, pp 163–202, Chapter 8 Leonard MH (1967) Immediate improvement of sensation on relief of extraneural compression. J Bone Joint Surg 51A:1282–1284 Lewis T, Pickering GW, Rothschild P (1931) Centripetal paralysis arising out of arrested bloodflow to the limb. Heart 16:1–32 Li H, Terenghi G, Hall SM (1997) Effects of delayed reinnervation on the expression of C-er6B receptors by chronically denervated rat Scwann cells in vitro. Glia 20:333–347 Li H, Wigley C, Hall SM (1998) Chronically denervated rat Schwann cells respond to GGF in vitro. Glia 21:1–14 Luco JV, Eyzaguirre C (1955) Fibrillation and hypersensitivity to ach in denervated muscle: effects of length on degenerated nerve fibers. J Neurophysiol 18:65–73 Lundberg A (1948) Potassium and the differential thermosensitivity of membrane potential, spike and negative after potential in mammalian A and C fibres. Acta Physiol Scand Suppl 50(15):1–67 Lundborg G, Rydevik B (1973) Effects of stretching the tibial nerve of the rabbit: preliminary study of the intraneural circulation of the barrier function of the perineurium. J Bone Joint Surg 55B:390–401 MacKinnon SE, Dellon Al (1986) Experimental study of chronic nerve compression. Hand Clin 2:639–650 MacKinnon SE, Dellon AL (1988) Ischaemia of nerve: loss of vibration sensibility. In: Surgery of the peripheral nerve. Thieme Medical, New York, Georg Thieme Verlag Stuttgart New York p 57 MacKinnon SE, Dellon AL, Hudson AR, Hunter DA (1985) A primate model for chronic nerve compression. J Reconstr Surg Microsurg 1:185–195 Mannan K, Altaf F, Maniar S, Tirabosco R, Sinisi M, Carlstedt T (2008) Cyclical sciatica. J Bone Joint Surg 90B:98–101 Martin JN, Vialle R, Denormande P, Sorriaux G, Gad H, Harding I, Dizien O, Judet T (2006) Treatment of knee flexion in contracture due to central nervous system disorders in adults. J Bone Joint Surg 88A:840–845 McComas AJ, Sica REP, Banarjee S (1978) Long term effects of partial limb amputation in man. J Neurol Neurosurg Psychiatry 41: 425–432 McManis PG, Low PA, Lagerlund TD (2005) Nerve blood flow and microenvironment. In: Dyke PJ, Thomas PK (eds) Peripheral neuropathy. Elsevier Saunders, Philadelphia, pp 671–680, Chapter 30 Merrington WR, Nathan PW (1949) A study of post-ischaemic paraesthesiae. J Neurol Neurosurg Psychiatry 12:1–18 Mitchell SW (1872) Injuries of nerves and their consequences. JB Lippincott, Philadelphia Mitchell SW, Morehouse GR, Keen WW (1864) Gunshot wounds and other injuries to nerves. JB Lippincott, Philadelphia Myles M, Glasby MA (1992) The fate of muscle spindles after various methods of nerve repair in the rat. Neuroorthopaedics 13:15–23 Nagano A (2003) Spontaneous anterior interosseous nerve palsy review article. J Bone Joint Surg Br 85B:313–318 Nagano A (2008) “Hour glass” like fascicular constriction. Pers com Nagano A, Shibata K, Tokimura H, Yamamoto S, Tajiri Y (1996) Spontaneous anterior interosseous nerve palsy with hourglass-like fascicular constriction within the main trunk of the median nerve. Hand Surg 21A:266–270 Nash TP (2001) Comment on: “A cervical anterior spinal artery syndrome after diagnostic blockade of the right C6-nerve root” Browers PJAM et al. Pain 91:397–399 Neary D, Eames RA (1975) The pathology of ulnar nerve compression in man. Neuropathol Appl Neurobiol 1:69–88 Niels OB, Thomsen, Lars Dahlin B (2007) Injury to the radial nerve caused by fracture of the humeral shaft: timing and neurobiological aspects related to treatment and diagnosis. Scand J Plast Reconstr Surg Hand Surg 41:153–157 Nogueira MP, Paley D, Nave A, Herbert A, Nolente C, Herzenburg JE (2003) Nerve lesions associated with limb lengthening. J Bone Joint Surg 85A:1502–1510

113 Nukada H, Anderson GM, McMorran PD (1997) Reperfusion nerve injury: pathology due to reflow and prolonged ischaemia. J Peripher Nerv Syst 2:60–69 Oaklander AL, Brown JM (2004) Unilateral nerve injury produces bilateral loss of distal innervation. Ann Neurol 55:639–644 Oberlin C, Shafi M, Diverres JP, Silberman O, Adle H, Belkheyar Z (2006) Hourglass like constriction of the axillary nerve. J Hand Surg 31A:1100–1104 Ochoa J, Fowler TJ, Gilliatt RW (1972) Anatomical Changes in peripheral nerves compressed by pneumatic tourniquet. J Anat 113:433–455 Ochs S, Pourmand R, Si K, Friedman RN (2000) Stretch of mammalian nerve in  vitro: effect on compound action potentials. J Peripher Nerv Syst 5:227–235 Omura T, Omura K, Sano M, Sawada T, Hasegawa T, Nagano A (2005a) Spatio temporal quantification of recruit and resident macrophages after crush nerve injury utilizing immuno-histo chemistry. Brain Res 1057:29–36 Omura T, Sano M, Omura K, Hasegawa T, Doi M, Sawada T, Nagano A (2005b) Different expressions of BDNF, NT3 and NT4 in muscle and nerve after various types of peripheral nerve injuries. J Peripher Nerv Syst 10:293–300 Paley D (1990) Problems, obstacles and complications of limb lengthening by the Ilizarov technique. Clin Orth Rel Res 250:81–104 Pandian JD, Bose S, Daniel V, Singh Y, Abraham AP (2006) Nerve injuries following intramuscular injections: a clinical and neurophysiological study from North West India. J Periph Nerve Syst 11:165–171 Phang IS,Biant LC, Jones TS (2009) Neurostenalgia of the femoral nerve A treatable cause of intractable hip pain in a young adult. J Arthroplasty. PMID: 19577882 Platt H (1928) On the peripheral nerve complications of certain fractures. J Bone Joint Surg 10:403–414 Pollock LJ, Golseth JG, Arieff AJ (1946) The response of muscle to electrical stimuli during degeneration, denervation and regeneration. Military Neurophysiol 25:236–257 Polo A, Aldegheri R, Zambito A (1997) Lower limb lengthening in short stature. J Bone Joint Surg 79B:1014–1018 Rabert D, Xiao Y, Yiangou Y, Kreder D, Sangameswaran L, Segal MR, Hunt CA, Birch R, Anand P (2004) Plasticity of gene expression in injured human dorsal root ganglia revealed by gene chip oligonucleotide microarrays. J Clin Neuroscience 11:289–299 Ramachandran VS, Hirstein W (1998) The perception of phantom limbs. The DO Hebb lecture. Brain 9(121):1603–1630 Renaut J (1881) Systéme hyalin de souténement des centres nerveux et de quelques organes de sens. Archives de Physiologie Normale et Pathologique 8:845–860 Richardson PM, Thomas PK (1979) Percussive injury to peripheral nerve in rats. J Neurosurg 51:178–187 Riddoch G (1941) Phantom limbs and body shape. Brain 64:197–222 Romanes GJ (1946) Motor localization and the effects of nerve injury on the ventral horn cells of the spinal cord. J Anat 80:117–131 Saldhana 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, Psychiatr 69:693–694 Salisbury RE, Dingeldein GP (1988) The burnt hand and upper extremity. In: Green DP (ed) Operative hand surgery, vol II, 2nd edn. Churchill Livingstone, New York, pp 2135–2164 Salzberg CA, Salisbury RE (1991) Thermal injury of peripheral nerve. In: Gelberman RH (ed) Operative nerve repair and reconstruction. JB Lippincott, Philadelphia, pp 671–677 Sander HW (1999) Mononeuropathy of the medial branch of the deep peroneal nerve in a scuba diver. J Periph Nerv Syst 4:134–137 Schmalbruch H (1987) Loss of sensory neurones after sciatic nerve section in the rat. Anat Rec 219:323–329 Seddon HJ (1943) Three types of nerve injury. Brain 66:237–288 Seddon HJ (1954) Nerve grafting. In: Peripheral nerve injuries by the Nerve Injury Committee of the Medical Research Council MRC Special Report Series 282. London HMSO, pp 402–403

114 Seddon HJ (1975) Surgical disorders of peripheral nerves, 2nd edn. Churchill Livingstone, Edinburgh, pp 67–88 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 Somayaji HS, Saifuddin A, Casey ATH, Briggs TWR (2005) Spinal cord infarction following therapeutic computed tomography-guided left L2 nerve root injection. Spine 30:E106–E108 Sorenson J, Daube JR, Windebank AJ (2006) Electrophysiological findings in a cohort of old polio survivors. J Peripher Nerv Syst 11:241–246 Spencer PS, Weinberg HJ, Raine CS, Prineas JW (1975) The perineurial window – a new model of focal demyelination and remyelination. Brain Res 96:323–329 Spiess H (1972) Schädigungen am peripheren Nervensystem durch iioniserende Strahlen. In: Schriftenreihe neurologie, Band 10. Springer Verlag, New York Spinner RJ, Atkinson JLD, Teil RL, Birch R et al (2003) Peroneal intraneural ganglia: the importance of the articular branch. A unifying theory. J Neurosurg 99:330–343 Spinner RJ, Amrami KK, Kliot M, Johnston SP, Casanas J (2006) Suprascapular intraneural ganglia and glenohumeral joint attachments. J Neurosurg 104:551–557 Stenning M, Drew S, Birch R (2005) Low energy arterial injury at the shoulder with progressive or delayed nerve palsy. J Bone Joint Surg 87B:1102–1106 Stewart M, Birch R (2001) Penetrating missile injuries. J Bone Joint Surg 83B:517–524 Stoll G, Griffin JW, Li CY, Trapp BD (1989) Wallerian degeneration in the peripheral nervous system: participation of both Schwann cells and macrophages in myelin degeneration. J Neurocytol 18:671–683 Stromberg T (1997) Vibration induced neuropathy in the hand. Doctoral thesis. Wallin and Dalholm Boktryckeri AB ISBN. 91-628-2539-9 Sunderland S (1951) A classification of peripheral nerve injuries producing loss of function. Brain 74:491–516 Suzuki H, Oyanagi K, Takahishi H, Kono H, Yokoyama M, Ikjta F (1993) A quantitative pathological investigation of the cervical cord, roots and ganglia after long term amputation of the unilateral upper arm. Acta Neuropathol (Berl) 85:666–673 Swash M, Fox P (1974) The pathology of the human muscle spindle: effect of denervation. J Neurol Sci 22:1–24 Tait GR, Danton M (1991) Contralateral sciatic nerve palsy following femoral nailing. J Bone Joint Surg 73B:689–690 Terenghi G, Calder JS, Birch R, Hall SM (1998) A morphological study of Schwann cells and axonal regeneration in chronically transected human peripheral nerve. J Hand Surg 23B:583–587 Thaventhiran J, O’leary MJ, Coakley JH, Rose M, Nagendran K, Greenwood R (2001) Pathogenesis and recovery of tetraplegia after electrical injury. J Neurol Neurosurg Psychiatry 71:535–537

Surgical Disorders of the Peripheral Nerves Thomas PK (1964) Changes in the endoneurial sheaths of peripheral myelinated nerve fibres during Wallerian degeneration. J Anat 98:175–182 Thomas PK, Bhagat S (1978) The effect of extraction of the interfascicular contents of peripheral nerve trunks in perineurial structure. Acta Neuropathol (Berl) 43:135–141 Thomas PK, Fullerton PM (1963) Nerve fibre size in the carpal tunnel syndrome. J Neurol Neurosurg Psychiatry 26:520–527 Thomas PK, Holdorff B (1993) Neuropathy due to physical agents. In: Dyck PJ, Thomas PK (eds) Peripheral neuropathy, 3rd edn. WB Saunders, Philadelphia, pp 990–1014 Thomas PK, Jones DG (1967) The cellular response to nerve injury. 2. Regeneration of the perineurium after nerve section. J Anat 101:45–55 Tower SS (1932) Atrophy and degeneration in the muscle spindles. Brain 55:77–90 Tsao BE, Wilbourn AJ (2003) The medial brachial fascial compartment syndrome following axillary arteriography. Neurology 61:1037 Tubiana R (1988) Burns. In: Tubiana R (ed) The hand, 3rd edn. WB Saunders, Philadelphia Ungley CC, Channell GB, Richards RL (1945) The immersion foot syndrome. Br J Surg 33:17–31 Vujaskovic Z (1997) Structural and physiological properties of peripheral nerves after intra-operative irradiation. J Peripher Nerv Syst 2:343–349 Walbeehm ET, von Heel EBM, Kuypers PDL, Terenghi G, Hovius SER (2003) Nerve compound action current (NCAC) measurements and morphometric analysis in the proximal segment after nerve transection and repair in a rabbit model. J Peripher Nerv Syst 8:108–115 Waller A (1850) Experiments on the section of the glossopharyngeal and hypoglossal nerves of the frog, and observations of the alterations produced thereby in the structure of their primitive fibres. Philos Trans R Soc Lond 140:423–429 Wilbourn AJ (2005) Brachial plexus injuries. In: Dyck PJ, Thomas PK (eds) Peripheral neuropathy, 4th edn. Elsevier Saunders, Philadelphia, pp 1339–1373, Chapter 55 Wilkinson M, Clarke J (1992) Thermal Injuries to the brachial plexus. Injury 23:342–343 Xu D, Pollock M (1994) Experimental nerve thermal injury. Brain 117:375–384 Ygge J (1989a) Neuronal loss in lumbar dorsal root ganglia after proximal compared to distal sciatic nerve resection: a quantitative study in the rat. Brain Res 47B:193–195 Ygge J (1989b) Central projections of the rat radial nerve investigated with transganglionic degeneration and transganglionic transport of horse radish peroxidase. J Com Neurol 279:199–211 Young JZ (1949) Factors influencing the regeneration of nerves. Adv Surg 1:165–220

4

Regeneration and Recovery

Regeneration: the cellular proliferation; importance of integrity of the basal lamina; neurotropins and neurotrophins; regeneration after intradural injury; regeneration of end organs; predictors of recovery. But the journey of the axon tip to an end organ is only the most dramatic of the phases in the process of regeneration, and its arrival is alone no guarantee of the return of useful function. J.Z. Young 1942

Much of what is now known about the regeneration of nerves is based on the work of Ramon Y. Cajal (1928) who developed concepts about the regrowth of divided axons, the formation of growth cones, the re-ordering of growing axons into new fascicles (Cajal 1928a, Cajal 1928b), and the guidance of new axons to their target tissues. He postulated the existence of “allowing or attracting substances” (Cajal 1928c) and gave credit to Forsmann (1900) for introducing the term neurotropism. Cajal described neurotropism as an effect which was initially one of general attraction emanating from the distal stump which later became more individual and specific as the new axon approached its end organ and in particular, the muscle spindle or the Golgi tendon organ. He also outlined the likelihood of a neurotrophic influence provided by the Schwann cells: “the nutritive and tutorial functions of the cells of Schwann had already been recognized by the embryologists, many of whom believed that the success of the thickening of young fibres and the development of the medullary sheath were the principal functions of these cells. We may especially cite Graham Kerr (1904) who studied the behaviour of these cells in the normal development of nerves, and Mott and Halliburton (1901), who attributed to the bands of Büngner of the peripheral stump of cut nerves the function of feeding and protecting recently arrived sprouts. There is only a step between the recognition of these cells as a nutritive placenta and the admission in them of secretions capable of stimulating and orientating the sprouts that are wandering in the scar.”(Cajal 1928c) These concepts have, in effect, been confirmed by later work. Early in the Second World War a Nerve Injuries Committee was again appointed by the Medical Research Council. George Riddoch was appointed chairman and Hugh Cairns, then Professor of Surgery in Oxford, was placed in charge of injuries to the nervous system. Five hospitals were designated for the treatment of nerve injuries. A team was set up in the Zoology Department of Oxford University which included,

amongst others, Young, Medawar, Holmes, Sanders, Gutmann, Guttmann and Ruth Bowden. Young (1993) summarized some of this work. Nerve grafting in all its forms was studied. The first evidence of axonal transport was revealed. The rate of nerve regeneration, the effects of disuse, the regeneration of proprioceptors, the maturation of regenerated fibres and the significance of retrograde influence were amongst the fields of enquiry. Collectively this work marked a most important stage in improving understanding of regeneration and of applying those lessons to clinical practice: here is an example of what has become known, in fashionable circles, as “translational research.” The decades since the appearance of the MRC report in 1954 have seen extensive advances in understanding cellular and molecular mechanisms. These include the role of neurotrophic factors; the dramatic and urgent changes in the expression of genes which transform, at least in the early days, an environment from one which inhibits new axonal growth to one which protects the cell body and facilitates new growth. The functions of the Schwann cell and its basal lamina, and the mechanisms of guidance, selection, and discarding of new axons have been illustrated. Much of this new work is reviewed in the comprehensive and excellent works of Hall (2005a, b), and of Lundborg (2003, 2004). For an authoritative description of the cellular and molecular events which underlie the process of Wallerian degeneration and regeneration the reader is referred to Dyck and Thomas (2005). It is important to remember the differences between the laboratory investigation, in which a controlled, precise and limited lesion is inflicted upon a nerve and the situation faced by the clinician presented with a patient with a massive wound involving the soft tissues, the skeleton, the vessels and sometimes by other injuries which threaten life and limb. The demonstration of regenerating axons across a lesion of a nerve inflicted in the laboratory does not necessarily translate

R. Birch, Surgical Disorders of the Peripheral Nerves, DOI: 10.1007/978-1-84882-108-8_4, © Springer-Verlag London Limited 2011

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to the recovery of function in the human. The phenomena of pain and recovery of sensation are rather poorly revealed by experiments upon small mammals or for that matter by barely justifiable experimentation upon primates. “The proper study of man is man.” We have been singularly fortunate over the years in the work of colleagues who meticulously examined tissues removed from injured nerves in more than 1,000 patients. At St Mary’s Hospital all biopsies were examined by Dr Arthur Boylston, later Professor Boylston at Leeds and at the Royal National Orthopaedic Hospital material was examined by Dr Jean Pringle. Dr Yusuf Ali, of the Institute of Orthopedics actively encouraged study of material by transmission electronmicroscopy in investigations performed by Mr Stephen Gshmeissner and by Mr Michael Keyser. The work of the joint diagnostic clinic in the Department of Neurophysiology at Queen Square is related in Chaps. 5 and 6. From 1990 Professor Praveen Anand and his colleagues at the Royal London Hospital and then later at Imperial College investigated, by novel techniques, changes in expression of nerve growth factors and of ion channels, correlating these with the measurement of small and large fibre function using methods which are described in Chap. 5. There is no doubt that the fundamental cellular processes which underlie regeneration are similar in the laboratory, in the injuries of civilian practice and in the wounds of war, but they are modified by the violence of the injury, by the effects of injury on associated tissues and in particular by ischemia and by delay before repair. We offer some general conclusions which are based on our clinical and laboratory investigations. 1. The extent of longitudinal damage of the nerve is greater in a rupture caused by traction that it is in “tidy” transections caused by knife or glass and this effect rapidly worsens with increasing delay before repair. If healing has been complicated by sepsis then it is often necessary in a late repair to resect 3 cm or more from both proximal and distal stumps of the divided nerve before reaching a recognizable architecture and even then microscopic examination reveals considerable abnormality. The concept of retrograde degeneration of the axon extending to the first internode applies only to the most benign lesions, that of crushing the nerve between the tips of a jeweller’s forceps. 2. As time goes by the cellular response in both stumps changes from one friendly to regeneration to one less favorable. Dense collagenisation and a profusion of fibroblasts are characteristics of the distal stump in late cases. 3. The normal architecture of the nerve is most closely restored to normal in a well executed primary suture (Birch 1989). 4. It seems that regeneration through a graft falls away along its length and not solely at the suture lines. 5. Delay before repair leads to increasing fibrosis and to shrinking of the distal segment so that it becomes impossible to ensure an accurate topographical match.

Surgical Disorders of the Peripheral Nerves

4.1 The Response of the Nerve and Axon to Transection The cellular response. The cellular process of regeneration involves both proximal and distal stumps and any gap between them. Wallerian degeneration is an essential preliminary to regeneration in peripheral nerves for it is a process which transforms the environment of the peripheral nerve from one which is actively hostile to the sprouting and growth of axons into one which actively supports that process. The disappearance of the distal axon is more than a withering away, rather it is an active self destructive process, “triggered by events which occur before any morphological or electrophysiological changes can be detected” (Hall 2005a). These very early events, which lead to cytoskeletal disintegration, were likened to the lighting of a fuse by Tsao et al. (1999). Within a few hours the transected axon seals off. The proximal end is transformed into a growth cone which has been defined by Lundborg (2004a) as: “a swelling at the tip of the regenerating axon and possesses multiple needlelike extensions, filopodia and broader sheet like extensions, lamellopodia.” The filpodia are rich in actin, and they may extend or retract within a matter of minutes. The axon forms new branches or sprouts: collateral sprouts arise from nodes of Ranvier at levels at which the axons are still intact; terminal sprouts arise from the tip of the surviving axon. Seddon (1975a) described this process: “the individual outgrowing streams of axoplasm – even when confined, as they may sometimes be, within one Schwann tube – have been referred to as fibers or even axons. They are, in fact, only parts of the axon or nerve fibres. The Nile is still the Nile even when the body of water, diversified by rocks or islands, breaks up into many streams.” The axon response is followed, within a few days, by a dramatic increase in the numbers of supporting cells. The influx of haematogenous macrophages into the endoneurium is accompanied by intense mitotic activity within the Schwann cells and the fibroblasts so that the number of nuclei increases by as much as six times or more (Griffin and Hoffman 1993, Dyck et al. 2005) (Figs. 4.1–4.4). The beautiful work of Mirsky and Jessen (2005) describes the development of Schwann cells from the neural crest to Schwann cell precursors, then to immature Schwann cells and finally to myelinating and nonmyelinating cells. This work provides important insights into the behaviour of the Schwann cell after nerve transection. A remarkable feature of the Schwann cell is the rapid reversibility of the last stage of differentiation following separation of the Schwann cells from the axon. This “can be achieved either by injuring nerves in vivo or by dissociating cells from adult nerves and placing them in culture without neurons. Both in  vivo and in vitro, the process entails the developmental regression and dedifferentiation of individual Schwann cells and myelin

Regeneration and Recovery

Fig. 4.1  Wallerian degeneration in the ulnar nerve at 3 weeks after section. (Electronmicroscopic study by Stephen Gshmeissner) Distal stump. Macrophage (top left) clears myelin debris. A degenerating large myelinated axon (bottom left). Schwann cells x 2880.

Fig. 4.2  Distal stump. Degenerating large myelinated axons with proliferating Schwann cells x 11340.

breakdown. The characteristic molecular markers and structural features of myelinating and nonmyelinating cells are lost and the cells reenter the cell cycle and regress to a phenotype similar to that of immature Schwann cells. Such denervated Schwann cells redifferentiate readily on reassociation with axons during nerve regeneration” (Mirsky and Jessen 2005). This redifferentiation is associated with the renewed expression of phenotypes which are specific to myelinated and non myelinated axons and also to motor and sensory axons (Hall 2009, Höke et al. 2006). The proliferation, indeed the survival, of Schwann cells is modified by the severity of

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Fig. 4.3  Proximal stump. Retrograde degeneration of one large myelinated axon, proliferating Schwann cells and sprouting axons, forming a regenerating unit x 6960.

Fig. 4.4  Wallerian degeneration in the ulnar nerve at 3 weeks after section (Electronmicroscopic study by Stephen Gshmeissner). Distal stump. Schwann cell proliferation x 6840.

the injury to the distal trunk. Examination of biopsies taken during late repairs, especially when the injury was complicated by arterial injury or by sepsis, often show remarkably few Schwann cells. Instead it seems that the cellular population is largely composed of fibroblasts, surrounded by much collagen. Myelin fragments are detectable in such cases many months after the injury (Figs. 4.5 and 4.6). Transection of neonatal sciatic nerves in the rat results in the death of teloglia at the neuromuscular junction (Tra­ chtenburg and Thompson 1996). Mirsky and Jessen (2005) point out that there is no comparable Schwann cell death

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Fig. 4.5  The proximal stump of the median nerve 3 months after rupture of the nerve and of the axillary artery, which was not repaired 8 mm from the tip of the neuroma. Disintegration of axon and of myelin with very scanty evidence of regeneration activity. x 4880.

following nerve transection after the first post natal week. In adult animals Schwann cells survive in the distal stumps for several months although their numbers slowly decrease and they respond less well to extrinsic signals: “although most Schwann cells within the main nerve trunks survive, there is also increased Schwann cell death within the nerve, indicating a partial dependence on axonal signals. Since the cells can be rescued by application of exogenous neuregulin-1, it is likely that the death is caused, at least in part, by loss of contact with axon associated neuregulin as axons degenerate after transection.” These findings provide further evidence about the harmfulness of delay before repair of divided nerves an also offer a possible explanation for the rather poor recovery of muscle function in the neonate (Anand and Birch 2002). The axon. The axon sprouts form clusters which are surrounded by the cytoplasm of one Schwann cell and its basal lamina: “the regenerating units” of Morris et al. (1972a, b). Dyck et al. (2005) say: “sometimes in abortive regeneration many, (as many as 25–20 or more) neurites will be found in a cluster - regenerative nerve fibre clusters.” The sprouts within one regenerating unit represent the regenerative effort of one

Surgical Disorders of the Peripheral Nerves

Fig. 4.6  The proximal stump of the median nerve 3 months after rupture of the nerve and of the axillary artery, which was not repaired 2 cm proximal to the rupture. One surviving myelinated axon embedded within dense collagen. x 3400.

neurone and its axon (Figs. 4.7–4.9). The proximal segments of regenerating axons become ensheathed by Schwann cells. Enlargement of the diameter of the axon is one important signal for myelination. The regenerating sprouts of unmyelinated fibres remain so. The ensheathment of the growing axon is brought about by complex interactions involving the laminin component of the basal lamina and receptors such as the integrins in the plasma membrane of the Schwann cell and also between the adjacent plasma membranes of the axon and the Schwann cell (Mirsky and Jessen 2005). Reorganisation of regenerating nerve fibres by compartmentation. Cajal (1928b) described the process called “compartmentation” by Morris et al. (1972c) in which the proximal stump becomes divided into “mini fascicles,” replacing the original large bundles (Cabaud et  al. 1982). Griffin and Hoffman (1993) described the process by which endoneurial fibroblasts proliferate, migrate, and form a partial basal lamina: “adopting the appearance of perineurial cells; in extreme cases they divide into “mini fascicles”.” We have seen this pattern in many grafts in small mammals and in failed grafts coming to revision in the human. Even after an ideal

Regeneration and Recovery

Fig. 4.7  Regenerating units. Proximal stump of ulnar nerve at 3 weeks after section. (Electronmicroscopic study by Stephen Gshmeissner) Numerous axon sprouts, Schwann cell processes, commencing remyelination with some retrograde degeneration. x 2784.

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Fig. 4.9  Regenerating units. Proximal stump of ulnar nerve at 3 weeks after section. (Electronmicroscopic study by Stephen Gshmeissner) Axonal sprouts adjacent to a Schwann cell nucleus x 3190.

Fig. 4.8  Regenerating units. Proximal stump of ulnar nerve at 3 weeks after section. (Electronmicroscopic study by Stephen Gshmeissner) Axonal sprouts and Schwann cells x 17980.

laboratory repair, immediate suture after clean transection, regenerating nerve fibres burst out from the perineurium at the suture line and form mini fascicles in the epineurium. Perhaps the process of compartmentation into mini fascicles should be seen as an aberrant or incomplete form of regeneration? (Figs. 4.10–4.13). Guidance and selection. In a carefully performed crush by jeweller’s forceps only the axon is interrupted and growth cones elongate along former Schwann tubes, “the cluster of axonal sprouts Schwann cells and macrophages enclosed in a Schwann cell basal lamina tube are the counterpart of what light microscopists call bands of Büngner” (Dyck et al. 2005). Unfortunately this most favorable situation is rarely

Fig. 4.10  Compartmentation or mini fascicle formation in the proximal stump of the common peroneal nerve ruptured 9 weeks previously in an 8 year old boy. Myelinated and unmyelinated axons and their ensheathing Schwann cells are loosely associated with perineurial like fibroblasts. x 3400.

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Surgical Disorders of the Peripheral Nerves

Fig.  4.11  Failure of regeneration through a graft inserted 3 years p­ reviously to bridge a gap in the median nerve. The proximal suture line. Many small bundles (minifascicles) of regenerating myelinated fibres. Scale bar: 100 mm.

Fig. 4.12  The middle of the graft. Increasing fibrosis and loss of neural elements. Scale bar: 100 mm.

encountered in clinical practice. Other mechanisms become important in the control of the exuberant but chaotic regeneration which occurs after nerve repair. Witte and Bradke (2005) describe the guidance of the growth cone: “guidance cues act either by direct contact (e.g., between the axonal growth cone and a repelling environment) or as diffusible factors that are secreted by the target regions. Thus they act as short range or long range cues.” If the “growth cone” encounters non neural tissue, axonal elongation still occurs and may even be followed by myelination. Witzel and Brushart (2003) studied the behaviour of axons traversing a gap. Some projected directly into distal Schwann tubes even though they meandered about in the gap and continued to produce collateral sprouts. Others “arborized,” sampling a number of distal tubes, whilst still others ended in the gap whilst sending out minute sprouts with multiple growth cones. Lundborg (1991) helpfully defines the terms neurotrophic and neurotropic. “A neurotrophic factor (nemron (neurone)

Fig. 4.13  Failure of regeneration through a graft inserted 3 years previously to bridge a gap in the median nerve. Distal segment of graft. Poor regeneration. Scale bar: 100 mm.

and trofh (trophe): nutrition) is a substance influencing survival and growth of nerve cells. A neurotropic factor (nemron (neurone) and tropoV (tropos): way, conduct) is a substance exerting an attraction, at a distance, on growing axons.” He later refined this view (Lundborg 2004a) because neurotrophic factors such as nerve growth factor (NGF) also exert a tropic influence. Trophic and tropic influences are preferable terms. Experiments were undertaken in which axons growing from the proximal stump were “offered” a choice between nerve, tendon and granulation tissue as distal targets. Nerves almost exclusively grew towards nerves (Lundborg et  al. 1986, MacKinnon et  al. 1986a). An even further degree of specificity may lead motor axons to motor endings and sensory axons to sensory endings (Brushart 1988). Brushart and Seiler (1987) studied regeneration in the rat femoral nerve using retrograde labeling techniques and demonstrated that motor axons entering sensory pathways were “pruned” whilst those entering motor pathways were

Regeneration and Recovery

maintained. Redundant axon sprouts atrophy (Bennett et al. 1986, MacKinnon et al. 1986b, Brushart 1993). There are limits to neurotropism: in experimental repairs where the stumps were deliberately malaligned axonal dispersion was determined by fascicular size, not by fascicular identity (Brushart et al. 1995). Hall (2005a) puts it thus: “there is no doubt that, providing the gap length does not exceed 1 cm, adult rat axons and their associated cells behave as though they are responding to “tropic” signals emanating from a distal stump. The extent to which specificity exists at the fascicular or nerve trunk level has been difficult to establish, perhaps because it is only unmasked in particular experimental protocols, and cannot be demonstrated when axons are challenged to enter grafts rather than intact distal stumps.” Clinicians must strive for accurate topographical alignment during repair whether by suture or by graft, and must accept the limitations of neurotropism exerted by a cutaneous nerve graft. Maturation. Initially, there are more axonal sprouts than there were axons in the intact nerve, but only those that establish connections with end organs survive (Sanders and Young 1946, Aitken et al. 1947). This can cause difficulty in estimating recovery by the numbers of myelinated nerve fibres (MNF) crossing a lesion. In a series of experiments, the sciatic nerve of the rat was transected and repaired by immediate (primary) or delayed suture at 2 weeks, or by immediate grafting or delayed grafting. Predegenerate grafts were also tested. (Birch 1989). The nerves were examined 1 year later. Even at this interval the numbers of MNF at the suture line and in the proximal segment of grafts were increased by about one third more than the number in the proximal trunk or in control nerves. The numbers of MNF in the distal trunk were reduced by about 25% in the primary sutures, by 33% in the secondary sutures and primary grafts and by 40% in the delayed and predegenerate grafts. These differences corresponded to such functional measures of outcome as power and weight of the reinnervated muscles. As connections are established and the regenerating nerve matures, the original profusion of Schwann cells gives way to the more orderly arrangement characteristic of the healthy nerve. Sanders and Young (1946) and Vizoso and Young (1948) studied internodal length and fibre diameter in the developing and regenerating nerves of rabbits. In the adult the former relationship between fibre length and internodal length did not reappear: internodal lengths were always shorter in the regenerated than in the healthy nerve. Griffin and Hoffman (1993) suggest that this is because longitudinal growth in regeneration occurs at the growing tip, whereas the internodal length increases by true longitudinal elongation during growth after birth. The production of nerve growth factors in the distal nerve by endoneurial fibroblasts, macrophages, Schwann cells and by muscle and skin provide an environment friendly to regenerating axons. Indeed, Griffin and Hoffman (1993) remark

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“given the environment of the distal stump, it is perhaps surprising that functional restoration is so seldom the consequence of nerve injury in humans.” The perspective of most clinicians is perhaps rather different: they think that the results they obtain are not all that bad considering the natural difficulty encountered by regenerating nerve fibres in reaching their targets. When there is a lesion “in continuity” or when healthy nerve end has been opposed to healthy nerve end, the elongating axon enters the environment most favorable to it: the denervated distal stump. Early and accurate suture of a divided nerve is followed by reconstitution of the trunk which is closest to normal. On two occasions the suture lines of the median and ulnar nerves 12 months after reattachment of the amputated hand were inspected during operations of tenolysis. The perineurium surrounding the bundles had reformed, there was only slight thickening of the epineurium and there was no visible neuroma. One indication about the accuracy of repairs completed within 3 or 4 h of the injury is the temporary restoration of conduction. On several occasions we have evoked the appropriate muscular response by stimulating the nerve trunk proximal to the repair. After even the most careful primary suture of a cleanly divided nerve it seems that there is: (1) a diminution in the number of nerve fibres which have made successful reconnection with their target tissues; (2) reduction in the calibre of those nerve fibres; (3) shortening of the internode and (4) slowing of conduction. These facts should not permit any sense of therapeutic nihilism: the best chance for the restoration of useful function rests on following the fundamental principles in the treatment of wounds by prevention of sepsis, restoration of flow through an injured axial artery, restoration of perfusion of the tissues, stabilisation of any fracture and providing full thickness skin cover over the repair. The nerve itself should be repaired as soon as reasonably possible. Whilst there may be a limit to technique much more needs to be done to improve the organisation of the handling of severe nerve injuries. The neuroma. Neuroma is a common example of the fate of the regenerating axons which are unable to form any connections with original targets. Griffin and Hoffman (1993) describe the behaviour of the growth cones when they enter “trackless regions of connective tissue or other foreign tissue even in this setting, the impulse to growth and extend continues; it may result in a meandering elongation followed by at least partial axonal maturation and myelination, culminating a neuroma near the site of the injury, or fronds of regenerating fibres extending over connective tissue planes.” A neuroma is an expression of the vitality of the neurones producing new axons. After amputations of the lower limb it is common to find neuromas of the main nerves 3  cm or more in length, which contain abundant myelinated nerve fibres rather chaotically organised into mini fascicles. Barnes et  al. (1945) revealed the capacity for robust regeneration many months

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after injury. An ulnar nerve was exposed more than 600 days after it had been divided. It could not be repaired. A piece of the distal stump of the nerve was removed and sutured to the proximal stump after the neuroma had been resected. It was a predegenerate graft. This segment was later removed and examined. The graft was reinnervated throughout but there was no myelination of the fibres. Barnes and his colleagues thought that this lack of myelination was due to endoneurial collagenisation, with consequent narrowing of the Schwann tubes, a suggestion made earlier by Holmes and Young (1942). Another reason is provided by Li et al. (1998) who showed that Schwann cells separated from axons for a long time lose their capacity to support regeneration and remyelination. The only way to avoid inflicting neuromas upon patients during the course of treatment is to avoid cutting nerves. Sometimes neuromas are responsible for severe and debilitating pain particularly so when the nerve is only partially injured. It seems strange that wounding a terminal branch of a cutaneous nerve so often leads to severe pain whilst the planned and deliberate section of that nerve at its origin very rarely does so. (Fig. 4.14) It is usual to find numerous axons, some of them myelinated, in the tissues bridging nerve stumps in the human: so it was in the cases studied by Terenghi et al. (1998). These findings illustrate the difference between regeneration and recovery. The extent of reinnervation of the skin by collateral sprouting after resection of a cutaneous nerve was examined by Healy et al. (1996). Twenty patients were studied in whom upper limb nerves had been used as grafts. The area of donor nerve sensory defect shrank by rather small amounts: 6  mm for light touch, 7  mm for sharp pain, and 11.5 mm for heat pain. There was no change in the area of loss for warming and cooling sense. Healy and his colleagues

Fig.  4.14  NGF immunoreactive fibres in a human painful neuroma, x 40 (Courtesy of Professor Praveen Anand).

Surgical Disorders of the Peripheral Nerves

found that sweating did recover, and caution against using this as an indication of nerve recovery (Figs. 4.15–4.17). The rate of regeneration. The rate of peripheral outgrowth of regenerating fibres is reckoned at about 1 mm a day in the human adult: that is about the rate of slow axoplasmic transport. The rate is substantially faster in children, as indeed it is in young experimental animals. It is almost certainly faster after primary than after secondary repair (Birch and Raji 1991) and is faster proximally than distally. We suggest a rate of 2 mm a day after suture of clean wounds of nerves at clavicular level and in the proximal part of the lower limb. Indeed, we have seen a rate of 3 mm a day after suture, or even after graft of ruptures performed within 24 h of injury, a rate similar to that recorded by Holmes and Young (1942) in their experiments on rabbit nerves. Why not? Such wounds are nearer to the nerve cell than are more distal injuries. Case report. A 24 year old soldier sustained a missile injury to the upper thigh which caused an extensive comminuted fracture of the sub trochanteric region of the femur. The fracture was stabilised and the sciatic defect, which measured more than 5  cm, was grafted 5 days after injury by Wing Commander Ian Sargent and Mr Garth Titley, Birmingham. By 180 days there were strong Tinel signs for both divisions

Fig. 4.15  Useless regeneration. Failure of recovery in a median nerve sutured 3 years previously. Proximal to the suture line. Clusters of myelinated axons extensive endoneurial collagenisation x 4300.

Regeneration and Recovery

Fig. 4.16  Useless regeneration. Failure of recovery in a median nerve sutured 3 years previously distal to the suture line. There was no recovery of function in spite of the presence of regenerating well myelinated axons x 4300.

of the sciatic nerve in the upper third of the leg at a distance of 44 cm from the proximal suture line. Flexion of the heel was powerful and there was early recovery into tibialis anterior suggesting that motor axons had traversed at least 35 cm (2 mm a day) of the length of the limb. The patient had no pain. This example of strong regeneration after urgent repair is by no means unusual, indeed we consider it the rule.

4.2 The Repair of Large Gaps Direct apposition may be impossible because of the fixed retraction of stumps in delayed cases or because so much of the nerve has been destroyed by the injury. Methods of bridging this gap have been extensively studied for more than 100 years. They include: 1. Autogenous grafts of cutaneous nerves 2. Autogenous grafts of main nerves. These may be vascularised as a pedicle or as a free graft 3. Homografts or allografts 4. Non neural material

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Fig. 4.17  Useless regeneration. Failure of recovery in a median nerve sutured 3 years previously. Biopsy of the skin of the index finger. Schwann cell processes and some unmyelinated axons x 18000.

Sanders (1942) recognized the essential role of Schwann cells when he classed operations for the repair of large gaps in the peripheral nerves into two groups: those which provide orientated live Schwann cell columns, down which large numbers of fibres can grow and become mature,........ and those which provide some form of artificial scaffolding down which....... the new fibres and Schwann cells can grow in a regular manner.

The Schwann cells promote, sustain and guide regenerating axons. Regeneration in the peripheral nervous system is possible only because of the interaction between the Schwann cell and the axon (Hall 2005a,Hall 2005b). Some of these methods are now considered. The technical aspects are set out in Chap. 7 and results in Chaps. 8–10. Regeneration through grafts. Tinel (1917) wrote: “when the distance between the segments of the nerve trunk is too great to permit direct suture the only legitimate operation is nerve grafting as recommended by J and A Déjerine and Mouzon.” He further added “nothing but nerve tissue can serve as a conductor for regenerating axis cylinders” and roundly castigated “mischievous” operations such as lateral implantation, transplantation of a motor nerve into a sensory one and isolation of nerve by foreign body. Only the

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interposition of a “muscular- or better still, a fatty-layer” between a nerve and callus or bony projection is permitted. It seems difficult to add to this. Sanders (1942) thought that the earliest adequately studied case of repair by fresh autograft was that performed by Dean in 1896 and reported by Sherren (1906), and he commended the series of Foerster (1929), Bunnell and Boyes (1939) and Joyce (1919) for their thoroughness. Sanders (1942) confirmed and extended observations made by workers in the first decades of the 20th century in concluding that: “autografts remain alive and myelin fragmentation and Schwann multiplication go on in them much as in a normal peripheral stump.” Human cutaneous nerve grafts could be fully reinnervated, presenting an appearance barely distinguishable from normal (Seddon et al. 1942, Gutmann and Sanders 1942, Seddon 1954. The ulnar nerve could be used with success but nerves of larger caliber were much less successful; a grafted segment of the common peroneal nerve simply necrosed (Seddon 1947). These observations stimulated the development of the vascularised ulnar nerve as a pedicle graft (Strange 1947) and a similar method for the common peroneal nerve MacCarty (1951). Millesi (1973) provides further evidence about the ill effects of tension and also about the necessity of accurate topographical disposition of the grafts. It is often said that grafting is the “gold standard” in the repair of nerves with defects but adherence to the gold standard led to severe financial difficulties for more than one nation and a considerable set back in Churchill’s career whilst he was Chancellor of the Exchequer in the 1920s. We have seen a high rate of failure amongst the more than 4,000 grafts of trunk nerves carried out since 1965. We are not alone in recording a success rate for repair of the more severe injuries to nerves which is little better than that set out in the Medical Research Council Special Report Series No. 282 (1954). The chief advantage of grafting is that it overcomes tension, which, as Highet and Sanders (1943) demonstrated, leads to a slow traction injury and ischaemia of the nerve after removing protecting splints. Seddon (1975b) commented that: “suture under tension… is not practiced by any knowledgeable surgeon today” and he referred to the normal elasticity of nerve which is not a negligible factor. Wide retraction of the stumps in closed traction lesion is usual and it is a simple matter to draw the nerves back to their normal position during operation performed within the first 1 or 2 days. It is always easy to be wise after the event but it now seems that suture would have been the better way forward in some of our cases particularly for nerves injured at the elbow, the knee and the wrist. In an earlier study of repair of the median and ulnar nerves at the wrist and forearm (Birch and Raji 1991) there was no detectable difference in the results between the 25 sutures and the 35 grafts. The gap after resection of the neuroma was measured with the elbow extended and the wrist at 20° dorsi flexion. The average gap was 2.5 cm in the sutures and 5.5 cm in the grafts. Trumble (1991) provides sound advice about reasonable methods of diminishing

Surgical Disorders of the Peripheral Nerves

the gap between nerve stumps by careful mobilisation and by positioning of adjacent joints and he emphasizes that the gap is always longer in delayed repairs. Wherever possible the stumps of transected or ruptured nerves should be approximated at the first operation in cases where circumstances prevent primary repair. The shortage of available donor graft means that the sciatic nerve should be sutured wherever possible, even though the patient must endure a hip spica with gradual release for some weeks. Clinicians must never forget that nerve grafts obtain their blood supply from the bed in which they lie. The admonitions of Tinel and Delorme were restated by Seddon (1947): “since the wounds of nerves that call for repair by grafting are usually extensive the need for the replacement of skin scars by healthy tissue arises with corresponding frequency. Nothing less than a full thickness flap or tube pedicle graft will suffice since it is important the graft should lie, so far as is possible, in healthy well vascularised tissue.” Leaving a nerve graft within scarred muscle or underneath split skin graft just will not do. The limitations of conventional grafting. 1. There is only a limited amount of cutaneous nerve available. In an adult with a complete lesion of the brachial plexus it is possible to collect about 180 cm of nerve by using both sural nerves with the cutaneous nerves of sensation from the injured limb. 2. The added defect imposed upon the patient may be too severe. The lateral cutaneous nerve of forearm and the superficial radial nerve provide significant innervation to the skin of the thumb, the thenar eminence and the palm of the hand. We use them only when the parent nerve is irreparably damaged. The supraclavicular nerves provide important sensation from the skin above the clavicle, over the shoulder and the upper part of the chest. The sural nerve innervates the heel and it should not be used for repair of low lesions of the tibial nerve. Pain is a common complication after deliberate wounding of the terminal branches of the nerves of cutaneous sensation and it is advisable always to section the donor nerve proximally, deep to the deep fascia. We agree with Seddon (1975c) in favoring the medial cutaneous nerve of forearm over other cutaneous nerves. 3. The architecture of a cutaneous nerve bears little resemblance to that of a main nerve trunk. The fifth cervical nerve contains between four and eight bundles. The largest of these requires one strand of cutaneous nerve which may contain between 8 and 20 such bundles. Dyck et al. (2005) examined the cross sectional area occupied by myelinated nerve fibres (MNF) in the roots of the spinal nerves, in the spinal nerves and more peripheral nerves. Myelinated fibres accounted for between 46% and 70% of the cross sectional areas of the ventral root of L5; the area fell to between 23.8% and 34.5% in the proximal sural nerve. The area occupied by MNF in the dorsal roots of

Regeneration and Recovery

L5 lay between 35.8% and 50.1%. In equally painstaking studies Dyck et al. (2005) showed that the median diameter of MNF in the ventral root of L5 was 12 mm. It was about 5 mm in the tibial nerve and just under 4 mm in the sural nerve. The median diameters in the fibres of the dorsal root resembled those found in the peripheral nerves. These findings suggest that there are serious defects in cutaneous nerve grafts particularly when they are used for repair of the ventral roots of the brachial plexus or the most proximal parts of the spinal nerves because of the disproportion in the volumes occupied by conducting tissue and the calibre of nerve fibres. Seddon (1975c) had this to say about the possible effects of fibre size: “it might therefore be thought that motor recovery through the cutaneous nerve graft would be appreciably inferior to the sensory recovery. The evidence presented by our series of cases shows that this possible objection has little substance; and Simpson and Young (1945) have shown that large fibres in the proximal stump have no difficulty in inflating rather smaller distal Schwann tubes, and so attaining a diameter sufficient for their effective function.” However Young (1942) recognized the limitations of experimentation on small mammals and in particular, the robust regeneration characteristic of the rat and the rabbit. The problem resurfaces when regenerating axons having traversed the graft reach the distal trunk of the nerve for here, particularly in late or neglected cases, the Schwann tubes are embedded in dense collagen. 4. The recognition that Schwann cells may be specific either to motor or to sensory axons casts a shadow over the use of cutaneous nerves for the repair of main nerves (Hall 2009, Höke et al. 2006). Nichols et al. (2004) and Lago et al. (2007) showed that the regeneration of motor axons is better promoted by a graft of a “motor” nerve whilst the regeneration of sensory axons is better through a graft from a cutaneous nerve. Whilst there is no such thing as a purely motor or sensory nerve within the peripheral nervous system these findings may account for the relative success of vascularized main nerve grafts. We reproduce a section through such a graft showing numerous myelinated and unmyelinated fibres but, perhaps disappointingly, we show sections through a failed vascularised sural nerve graft in which the vascular anastomosis remained patent and yet regeneration failed (Figs. 4.18–4.22). 5. The nerve pedicle operations remain extremely useful in the most severe cases especially so in otherwise irreparable injury of the sciatic nerve. It is strange that these innovative techniques seem to have been forgotten by so many clinicians. 6. The most elaborate method of nerve repair cannot overcome the baleful effect of delay. Allografts. The advantages of the autogenous cable graft are now so well known that we tend to forget that earlier last

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Fig. 4.18  Regeneration through a vascularised ulnar nerve graft (fifth cervical nerve to lateral cord). Although the biceps muscle recovered well, the appearance of the hand led the patient to demand amputation. Note the numerous myelinated and unmyelinated fibres without excess of collagenisation x 2142.

century surgeons obtained what we would now consider remarkably good results with grafts which would now not be used. Thus, Mayo-Robson (1917) reported a good result after repair of a lesion of the median nerve with an allograft of median nerve, and another good result after repair of another lesion of the median nerve with a length of the spinal cord of a rabbit. Barton (2005) has provided us with details of the use of calf’s nerve for repair of a war wound to the right (dominant) median nerve, in 1917. The operation was done at Baschurch Military Hospital (in Shropshire). The patient lived to the age of 90 years and recovery was good enough for him to act as organist to various churches and chapels. The method was thoroughly and extensively reviewed by Sanders (1942), and by Sunderland (1978). Seddon (1975d) pointed out that the immune reaction may be avoided either by reducing the antigenicity of the graft or by suppression of the response in the host: “it must be remembered that repair of a nerve is not a life saving operation.” A number of methods were used including treating the graft with alcohol or with other agents, freeze drying and irradiation. The results were generally very poor but there was the occasional success. The introduction of newer methods of immuno suppression

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Fig.  4.19  Failure of regeneration through a vascularised sural nerve graft used to repair a long defect in the median nerve. At re-exploration two years after operation the vascular anastomosis was found to be patent. (Electronmicroscopic study by Michael Kayser) Just distal to the proximal suture line. Mini fascicles (arrows) of myelinated and unmyelinated nerve fibres x 2108.

allowed MacKinnon (1996) to give a qualified recommendation: “In the carefully selected patient with an otherwise irreparable nerve injury, consideration for nerve transplantation should be given.” Hand transplantation provides one dramatic example of allograft. Schuind et al. (2006) described the first Belgian patient at 37 months after operation, showing very impressive recovery for motor, sensory and sympathetic functions. Larsen et al. (2007) sound a warning note in reporting Epstein Barr virus infection complicating transplantation of a nerve allograft from a living donor.

4.2.1 Other, Non Neural, Material for Grafts: Entubation Surgeons have for many years sought a source of material for graft to supplement or to replace the rather meagre stock provided by dispensable cutaneous nerves.

Surgical Disorders of the Peripheral Nerves

Fig. 4.20  Just distal to the proximal suture line. A mini fascicle (small arrows) of myelinated and unmyelinated nerve fibres lie just outside the perineurium of one of the vascularised strands (large arrows) x 6270.

The freeze thawed muscle graft (FTMG) introduced by Glasby et al. 1986 is a method which has been used extensively in laboratory and clinical studies. Hall (1997) showed that axonal regrowth through short acellular muscle grafts requires a sustained supply of Schwann cells, perineurial cells, and fibroblasts. Schwann cells may migrate from the stumps of the nerve on either side of the acellular graft or which may be “seeded” in that graft (Calder and Green 1996). Thomas et al. (1994) defined a particular role for FTMG in the repair of damaged cutaneous nerves, in the treatment of the painful states arising from such damage. Although in such cases an adequate supply of nerve is available for grafting it seems perverse to inflict a lesion on a cutaneous nerve in a patient suffering from the results of damage to another. A paper of importance appeared from Pereira et al. (2008) who treated the leprotic hand and foot by replacing the damaged segment of the median or tibial nerve with FTMG. Most patients recovered protective sensation; their ulcers healed. Doubtless, a number of amputations were prevented. One

Regeneration and Recovery

Fig.  4.21  The middle part of the graft. Endoneurial fibrosis; myelinated and unmyelinated axons; a suggestion of new perineurium formed from fibroblasts (arrows). x 1770.

intriguing finding was the improvement in the condition of the skin in one third of the contralateral feet. Entubation. In 1997 Lundborg and colleagues (Lundborg et al. 1997) published a significant paper describing a prospective randomized trial comparing silicone entubution and suture of median and ulnar nerves in the forearms of 18 patients. Recovery was studied most thoroughly and no significant difference in outcome between the two groups was noticed. They wrote “in one case, the tube was removed at 11 weeks. Upon opening the tube, it was found that the former empty space was now occupied by newly formed nerve tissue in direct continuity with the proximal and distal ends..... it was not possible to define the exact level of the previous nerve injury.” The proposed advantages following placing of nerve stumps within a silicone tube, so providing a “chamber” separate from the surrounding tissues, include: the local accumulation of neurotrophic factors; the longitudinal orientation of fibrin matrix within the tube; and the possibility for the regenerating axons to be better guided into distal Schwann tubes across the gap. The tube must not be too tight. Silicone entubation may cause constriction and fibrosis of a sutured nerve (Birch 1979).

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Fig.  4.22  Failure of regeneration through a vascularised sural nerve graft used to repair a long defect in the median nerve. At re-exploration 2 years after operation the vascular anastomosis was found to be patent (Electronmicroscopic study by Michael Kayser). The distal portion of the graft. This shows one of the few surviving clusters of neural elements. Several myelinated and unmyelinated axons lie within the perineurium x 4408.

With the exception of some cases using the freeze-thawed muscle graft, it seems that the upper limit of a defect reparable by these methods is 3 cm. Repair of the long gap by means other than autogenous graft remains elusive. De Ruiter et  al. (2009) conclude that there is, as yet, little evidence demonstrating the superiority of empty, hollow biodegradable nerve tubes over suture or autografting and that: “the repair of all sorts of nerve lesions may lead to unnecessary failures and, again, a discontinuation of interest in the concept of the nerve tube. The extensions of the applications, especially in a repair of larger mixed or motor nerves, should be carefully evaluated.” Hall (2005b) defines the ideal conduit which should have: “walls that are biologically bio compatible and resorbable, sufficiently robust to resist collapse, and yet not so rigid that they compress the structures which they surround, and a lumen whose contents…. facilitate orientated and sustained axonal elongation. It goes without saying that it must also be easy to handle and to suture. It also goes without saying that

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such a device does not currently exist.” Some show promise: one such is the bioresorbable glass fibre technique investigated by Bunting et  al. (2005) in nerves of the rat. Axonal regeneration was indistinguishable from that seen in autografts. Hall’s more recent essay (2009) reviews the use of such natural polymers as collagen and various polysaccharides and a wide range of synthetic polymers. One essential requirement of the biodegradable conduit is that the degradation products must not be cytotoxic. Manipulating the behaviour of the growth cone will determine the path of the regrowing axon “since wherever the growth cone goes, the rest of the attached axon must surely follow.” Hall (2009) goes on: “given that axons and Schwann cells comigrate, it is perhaps surprising that little or no attention has thus far been paid to manipulating Schwann cell outgrowth from the nerve stumps.” The work of Caddick et al. (2006) opens the possibility of encouraging the differentiation of mesenchymal stem cells along a Schwann cell lineage. Cells were removed from the marrow of long bones of rates and cultured. Those cells cultured with glial growth factor (GGF) increasingly expressed such Schwann cell markers as S-100, p75, and glial fibrillary acidic protein (GFAP). The cells were then co cultured with neurones from the dorsal root ganglion and those which expressed Schwann cell markers enhanced neurite outgrowth from the sensory neurones to the same level as that produced by Schwann cells. This work represents a potentially important advance because the culture of autologous Schwann cells in the adult human is such a lengthy process. The development of micro-machined sieve electrodes may prove to be extremely important. These are made from silicone (Wallman et  al. 2001) or polyimide (Zhao et  al. 1997, Navarro et al. 1998) and are inserted into conduits to create a neural interface which can be used to control a limb prosthesis. Is it possible that these developments might enable the reconnection of stumps of the spinal nerves within the spinal canal, a concept put forward by Bonney (1977).

4.3 Nerve Transfer Nerve transfer, also known as neurotisation, or nerve crossing, involves the passing of nerve fibres from a healthy nerve to the distal stump of an injured nerve and this principle can be applied in a number of ways. 1. End to side transfer by suture of the distal stump of the injured nerve onto or within the epineurium of the healthy donor. 2. Transection of a healthy donor nerve and transfer onto the distal stump of the injured nerve. 3. Transfer of one or more healthy bundles within an uninjured donor to the recipient. This important technique was studied and used by Oberlin et al. (1994) and it rests on

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the functional segregation and topographical organisation of nerve fibres within the donor nerve trunk so that it is possible to take one bundle from the ulnar nerve to reinnervate the nerve to biceps without inflicting any significant loss of function within the hand. The method has been extended to the transfer of intact bundles from C7 or C8 to the suprascapular nerve or to the avulsed ventral root of an adjacent spinal nerve. 4. Transfer of the proximal stump of a divided nerve onto the distal stump of another divided nerve. 5. Direct muscular neurotisation. Sometimes a nerve is avulsed from the muscle. The musculocutaneous and the circumflex nerves are most commonly affected. Sorbie and Porter (1969) took the nerve to the flexor carpi ulnaris muscle in dogs and implanted it into flexor carpi radialis. Muscle volume was restored and the twitch strength of the reinnervated muscle reached 50% of normal by 40 weeks. Brunelli and Monini (1985) developed a concept of implantation of a working nerve directly into the paralyzed muscle, calling this method “direct muscular neurotization.” Narakas (1988) described considerable experience with the method. The extent of afferent reinnervation of the muscle offers a fruitful field of study. End-to-side repair. Insertion of the stumps of damaged nerves into adjacent undamaged nerves is amongst the earliest of methods tested for bridging large defects. Sanders (1942) pointed out that the operation of “double lateral implantation” could be performed in one of two ways. The prepared stumps might be implanted into longitudinal slits between the bundles of the host nerve; or, some bundles within the host nerve could be cut at two levels and the prepared stumps sutured to these. In the first operation, axons from the implanted central stump might grow down through the epineurium: “an environment which contains no Schwann cells.” Kilvington (1907) investigated the second method, where bundles of the undamaged nerve were sectioned to act as a bridging graft and showed that there was histological evidence of reinnervation of the distal part of the damaged nerve. Ballance and Ballance (1903) used the technique in repair of the facial nerve. Kettle (2003) provides an extensive review and a careful analysis of the method using nerves in the sheep as a model. She demonstrated that end-to-side nerve repair “did support nerve regeneration” but her findings “do not support the view that this technique is associated with a functional outcome.” Carlstedt (2007a) sets out important objections to the technique. The internal environment of an uninjured nerve is not conducive to new axonal growth. It is only after injury to the donor nerve, by opening the perineurium that changes are induced in the Schwann cell phenotype more favorable to axonal growth. Regeneration is now end to end. One carefully studied clinical example comes from Irwin et al. (2006) whose patient sustained severe injuries to both legs. A below knee amputation proved necessary on the

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right side but the undamaged plantar skin of the right foot was used to successfully resurface the left foot in which the plantar skin had been avulsed. The right tibial nerve was transferred to the intact left tibial nerve by an end-to-side method without incision of the epineurium. Quantitative sensory testing (QST) at 9 months revealed that the patient could localize pressure but was not able to feel cotton wool or pinprick over the sole. She could perceive a graded monofilament of 7.5 g on the sole (normal, less than 0.08 g). Vibration sense was present but the threshold was elevated. She could not detect warm or cool sensations but sweating was close to normal. By 16 months there was clear improvement in the thresholds to vibration and light touch. Vibration thresholds now lay within normal limits and the monofilament threshold had improved to 1.66 g. She could not recognize cotton wool and a pin prick was felt as a touch. There was no change in the thermal threshold. She recovered some large sensory fibre function (vibration sense and touch) and autonomic function; there was no evidence of recovery of small sensory fibre function. Nerve transfer. When, as happens with serious injuries of the brachial plexus, nerves are so badly damaged that no repair is possible and no recovery can be expected, the question of “neurotizing” or reinnervating the distal stump with the proximal stump of an intact nerve or nerves is raised. Warren Low, working at St Mary’s Hospital, Paddington with Wilfred Harris, was probably the first to suggest this expedient and to put the suggestion into practice (Harris and Low 1903). The validity of the method was, however, open to question. The matter was raised again by Tuttle (1913), who reported on the use of the spinal accessory nerve as a donor. Transfer of the hypoglossal nerve to the facial nerve became a well recognized remedy for facial paralysis in the early years of the last century (Ballance and Ballance 1903) before it was superceded by grafting (Ballance and Duel 1932, Bunnell and Boyes 1939, Collier 1940). Probably the first recorded success from nerve transfers in the brachial plexus was that of Seddon (1975c), who with Yeoman transferred intercostal nerves into the musculocutaneous nerve. Seddon acknowledged an earlier contribution: “in a case of traumatic tetraplegia extending up to the fifth cervical segment Benassy and Robart (1966) helped the patient very considerably by severing an intact musculocutaneous nerve and uniting it to the neighbouring totally paralysed median.” Tsuyama and Hara (1973) adopted intercostal nerve transfer for patients with complete avulsion injury in 1965 and Nagano et al. (1989) described the results in 179 patients More than 80% of their patients regained functional flexion of the elbow. Kotani et al. (1972) and Allieu (1989) described the use of the distal part of the spinal accessory nerve in re-innervation of the upper limb preserving rami to the upper fibres of trapezius. A great deal of detailed and important work towards the study of potential nerves

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available for transfer is set out in the volumes published by the Groupe d’Étude de la Main which were brought together by Alnot and Narakas (1989, 1996). Nerve transfer has developed as an essential part of the treatment of severe intradural lesions of the brachial plexus, and until the place of intradural re-attachment or repair is established, it is likely to remain so. It is also valuable in some peripheral lesions. Gore (1978) restored powerful wrist extension by transferring a nerve to the medial head of triceps to the radial nerve, 15 months after the injury. Gousheh (2002, personal communication) transfers the nerve to the lateral head of gastrocnemius to the deep division of the common peroneal nerve in severe lesions. The superficial division, which is usually more amenable to repair, can be grafted at the same time. Carlstedt (2007b) recommends the technique “in cases where intra spinal repair of a lumbosacral plexus lesion is impossible, eg. when there is no proximal, ventral root stump to use for reconstruction, it is possible to perform nerve transfers.” One example is described in the important paper from Lang et  al. (2004). The patient, a 5 year old girl, presented with bilateral, asymmetric injuries to the lumbo-sacral plexus. Paralysis of the abductors of the hip on one side was treated by placing a graft between the superior gluteal nerve and two bundles within the femoral nerve. Paralysis of the extensor muscles of the knee on the other side was treated by transfer of intercostal nerves 10 and 11 to the femoral nerve. 18 months later the child was able to walk independently. Brunelli and Brunelli (1999) enabled a paraplegic patient to walk by transfer of the ulnar nerve to the superior gluteal and femoral nerves. The deficit in the hand was remedied by musculo-tendinous transfer. Contra-lateral transfer. A more daring idea comes from Gu and his colleagues in Shanghai. The contra-lateral seventh cervical nerve is used to re-innervate the upper limb after a complete lesion of the brachial plexus. A vascularized ulnar nerve is used as an interposed graft. The first operations were performed in 1986 and Gu and his colleagues described promising results in ten patients with adequate follow up in 1992 (Gu et al. 1992). The method is supported by a considerable amount of experimental work (Chen and Gu 1994). One of us was able to examine some of the patients operated by Professor Gu and his colleagues in Shanghai, and some details of one of these follows. Case report. The patient, a male aged 27, sustained a complete preganglionic lesion of the right brachial plexus in a motor cycle accident on the 18th June 1993. At 3 months accessory to suprascapular and phrenic to muculocutaneous transfers were performed. At four and a half months intercostal nerves were transferred to the thoracodorsal nerve and the contralateral C7 was sutured to the ulnar nerve from the damaged limb. Eight months later the distal stump of this vascularised graft was sutured to the median nerve. The patient was examined 18 months after re-innervation of the

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median nerve. Power in the long digital and wrist flexors was MRC grade 4. There was some activity in abductor pollicis brevis and the patient was able accurately to localize touch to the thumb, the index and middle fingers. This patient had regained true hand function which could have come only from contralateral C7. Those of us examining him were unable to find any significant deficit of power or sensation in the donor limb. Closely scrutinized series have been reported by Waikakul et al. (1999) and Songcharoen et al. (2001). Our own experience of the transfer of contra-lateral spinal nerves is confined to two cases of bilateral and complete lesions of the brachial plexus. All available post ganglionic ruptures were used to reinnervate the less severely damaged upper limb. (Chap. 9). Limitations of nerve transfer: 1. There are far fewer MNF in the donor nerves than in the main trunks. The number of MNF in the spinal accessory nerve at the base of the posterior triangle is about 1,500; that number in C5, usually the smallest of the spinal nerves forming the brachial plexus, is at least 25,000. 2. The deficit imposed on the patient must not be too severe. No nerve of vital function should be used for the sake of regaining a non vital function. Phrenic nerve palsy at birth is life threatening. Some adults experience serious ventilatory impairment following injury to the phrenic nerve complicating lesions of the brachial plexus. Blaauw et al. (2006) condemn transfer of the hypoglossal nerve because of the high morbidity and disturbance of speech. We have seen one adult patient where both hypoglossal nerves were used in whom there was very serious disturbance of speech and swallowing for as long as 6 months after operation.

4.3.1 Recovery of Cutaneous Sensation after Nerve Transfer The infant. The recovery of sensation within the hand in children after repair of the brachial plexus in infancy is remarkably good. Anand and Birch (2002) studied 24 patients with severe birth lesions of the brachial plexus, in 20 of whom the plexus had been repaired. The recovery of sensation was far better than that of skeletal muscle and sympathetic function. Sensation was normal in all dermatomes for at least one modality in 16 examined hands and there was accurate localisation in the dermatomes of avulsed spinal nerves which had been reinnervated by intercostal nerves transferred from remote spinal segments. These findings are described in more detail in Chap. 10: there too are described the results of sensory recovery after nerve transfer in children and young adolescents. The reason for this difference has been sought in the better adaptation of the child’s central receptor mechanisms. The poor recovery of muscle function in these

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children may reflect the greater vulnerability of the immature nervous system to avulsion or proximal axonotomy. The adult. Özkan et al. (2001) treated 20 cases of irreparable lesions of ulnar or median nerves by transfer of the digital nerve from the inner to the outer side of the appropriate digit. Extensive sensory retraining was used in all patients and accurate localisation was restored in 18. Battiston and Blanzetta(1999) reported useful recovery into six of seven cases of high ulnar lesion by transfer of the distal part of the anterior interosseous nerve and the palmar cutaneous branch of the median nerve to the ulnar nerve at the wrist. We have transferred the dorsal branch of the ulnar nerve or the medial cutaneous nerve of forearm to the median nerve with modest success. Whilst transfer of the intercostal nerves to the lateral or medial cords often improves the trophic state of the skin of the hand in adults with severe injuries to the brachial plexus it is usual to find that stimulation of the reinnervated skin is referred to the chest wall. Appropriate referral and accurate localisation has been seen in only nine cases and these were patients with substantial muscle recovery through the transfer. Htut et al. (2006) studied 76 patients with severe injuries to the brachial plexus repaired by conventional graft, nerve transfer or reimplantation. Stimuli were appreciated in the reinnervated skin of the hand in only a few patients. More than one half of patients experienced “wrong way” sensations such as pins and needles in the affected arm or hand while shaving, touching or tapping the ipsilateral cheek or lip. In some patients these sensations were evoked by warming or cooling or by transcutaneous nerve stimulation. Two patients experienced sensations in the affected arm or hand when the ipsilateral leg was stimulated. These referred sensations could be unpleasant, with a painful or gripping quality and in one patient coughing produced a squeezing or gripping feeling at the wrist. This “wrong way” sensation generally occurred within 2 months of the operation, some months before the development of “right way” sensation which followed regeneration from the donor nerve into its new territory. In the “right way” sensation stimulation of the hand evoked feelings in the chest wall, the territory of the donor nerve.

4.3.2 Recovery of the Deep Afferent Pathways after Nerve Transfer The capacity of the child’s central nervous system to adapt to a new peripheral situation is illustrated by the case of a 13 year old boy who suffered avulsion of C5, C6 and C7 in a road traffic accident (Fig. 4.23). It seems likely that there was some reinnervation of the deep afferent pathway from the muscle spindles and the tendon sensory organs so that an appropriate pattern of inhibition and facilitation was restored within the spinal cord.

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Fig. 4.23  A 13 year old boy. Right sided lesion. Avulsion of C5, C6 and C7.Repair at 2 months: accessory to suprascapular transfer, and one bundle of the ulnar nerve to the nerve to biceps and the nerve to the medial head of triceps; the medial cutaneous nerve of the forearm was transferred to the lateral root of the median nerve. Results at 18 months: full range of lateral rotation; abduction to 60°; power of elbow flexion MRC grade 4; and power of elbow extension, MRC Grade 3+. There was a full range of active flexion and extension without obvious cocontraction.

There is considerable adaptation of the central receptor and effector mechanisms in adults after nerve transfer. The association between activity in biceps with clenching of the fist after ulnar to biceps transfer is useful in the early stages of rehabilitation. Independent flexion of the elbow without associated activity in the flexor muscles of the forearm is usual by 24 months after operation. Kanamura et al. (1993) studied 14 patients after intercostal to musculocutaneous nerve transfer. Percussing the biceps tendon induced sensory evoked potentials in four cases and appropriate reflex activity was demonstrated by electromyography. These workers concluded that: “muscle afferent fibres in the intercostal nerves reinnervated mechano-sensors in the biceps, and these evoked both cortical sensory activity and muscle activity which represents the classical stretch reflex” Sai et al. (1996) confirmed these findings in a study of 15 patients. Recovery of the elbow flexion reflex was confirmed by electromyography in nine cases and in five “tapping at various frequencies induced gradual augmentation of the integrated electromyogram of reinnervated biceps,” implying reinnervation of the muscle spindles by 1a and 2 fibres. Mano et al. (1995) demonstrated remapping within the cortical motor cortex by magnetic stimulation in 44 patients. At intervals ranging from 4 to 33 months after the nerve transfer a change from the intercostal area to that of the arm was found, and this was associated with a clear separation between ventilatory effort and that of elbow flexion. Further observations about the changes within the central nervous system following intercostal nerve transfer were made by Malessy et al. (1998) and by Malessy et al. (2003) who used functional magnetic resonance imaging (FMRI) and cortical magnetic stimulation.

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Voluntary elbow flexion became independent of breathing. In those patients who regained a powerful biceps the distribution of cortical activity did not materially differ between the injured and the uninjured arms. Regeneration of end-organs. There is, evidently, a limit to the period during which an end-organ can be denervated and yet recover after reinnervation. All end-organs have been studied: the earliest were perhaps the motor end-plates. Bowden and Gutmann (1944) did an extensive study of the response of the motor end-plates to denervation, finding that after 3 months it became increasingly difficult to identify the organs. Denervation for up to 3 years produced no degeneration nor disruption of the muscle fibres themselves. However, “shrinkage and increase of connective tissue may be too advanced to allow recovery after reinnervation.” After 3 years, disruptive changes occurred in the muscle fibres. Gutmann and Young (1944) investigated the reinnervation of muscle in rabbits and found that when muscles were kept denervated for increasing periods the proportion of old end-plates which became reinnervated was progressively reduced: “Most of the nerve fibres escape and run along between the muscle fibres, ultimately making contact with the sarcoplasm and forming new plates.” They had the opportunity of examining the extensor carpi radialis muscle of a patient whose radial nerve was repaired 5 years earlier after it had been interrupted. There was no recovery of motor power. Examination of a piece of this muscle showed that “although abundant nerve fibres were present they had failed to make connexions with the muchatrophied muscle fibres.” The regeneration of muscle spindles has been extensively studied by, amongst others, Barker et al. (1986), Barker et al. (1990), and Banks (2005). After crush injury (axonotmesis) regeneration and recovery of function is good although there is a reduction in the number of primary endings in the terminal bands coiled around nuclear bag fibres. This is related to the duration of denervation. Regeneration after repair of the nerve is much more variable. A muscle spindle may become reinnervated by afferents normally destined for the tendon organ although Barker et al. (1990) indicated that delaying repair for up to 8 weeks “did not give rise to any significant detrimental effect on such reinnervation.” The behaviour of the Golgi tendon organ has been investigated by Scott (1995, 2005). It appears that the tendon organ is relatively resistant to denervation atrophy: “after crush injury there is usually successful restoration of the 1b afferent ending, although it is reduced in extent” (Scott 2005). The pattern of recovery is worse following nerve repair. Many tendon organs remain uninnervated and the regenerated endings are frequently abnormal in appearance. Scott identified three deleterious factors: (1) the effects of denervation on the afferent axon; (2) the consequences of reinnervation by inappropriate axons, and (3) the effects caused by the reorganisation of the motor units after repair causing

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s­ ignificant alterations in the mechanical input to an individual tendon organ. Changes in the number and distribution of muscle afferent neurons in the dorsal root ganglion of the rat following transection and repair of the sciatic nerve were investigated by Myles et al. (1992). The cell bodies were labeled by injecting horse radish peroxidase into the extensor digitorum longus 300 days after the first operation. The number of labeled cells was diminished, the cell size was reduced and the somatotopic organisation of neurones within the dorsal root ganglion was altered. Michael Glasby and his colleagues investigated recovery in the deep afferent pathway in the new born and 1 year old sheep (Fullerton et al. 2001). In the first experiment the sixth cervical nerve was ruptured and immediately grafted and in the second experiment the ventral root of C6 was avulsed from the spinal cord and immediately repaired by autologous coaxial freeze thawed skeletal muscle graft. The nerves were examined 1 year later, by electrophysiological and morphometric methods. Regeneration of the largest, fastest conducting nerve fibres was defective in both the new born and in the 1 year old sheep. The maximum conduction velocity never reached normal levels and the diameter of the fibres, the axons and the thickness of the myelin sheath were all reduced. These workers found: “a selective failure of regeneration of the largest diameter fibres..... it seems more likely that the failure of recovery of fine movements is due to the fact that the proprioceptive pathway involving 1a, 1b and group 2 fibres on the afferent side and the process of a and g coactivation on the efferent side, is lost.” The changes are not confined to the end-organs of the motor apparatus: the cutaneous sensory receptors similarly undergo a slow degenerative change after denervation. After 3 years they may in fact disappear. Reinnervation tends to reverse these changes, though the longer the period of denervation has been, the less complete will be the regeneration. It is not too surprising that correlation of histological evidence of regeneration of cutaneous nerves with clinical evidence of recovery is often imperfect. Thus, Jabaley et  al. (1976) attempted to correlate sensory function with evidence of cutaneous reinnervation after section and repair of the median nerve. They found that there was no such correlation. Indeed, in one case, after division and repair of the median and ulnar nerves, two point discrimination was seriously defective in the thumb; yet, blindfold identification of objects was regularly correct and the pickup test of Moberg (1958) was performed in 1950s. Histological examination of the skin of the index and little fingers showed only an occasional nerve fibre and a few Meissner corpuscles. In contrast, a woman whose median nerve had been repaired by fascicular suture regained plentiful cutaneous innervation, but was unable to pick up objects because she could not feel them. On the other hand, Dellon and Munger (1983), using the partially denervated finger tips of three patients to correlate observations of sensibility with the presence of reinnervated

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sensory corpuscles as seen by light and electron microscopy, found that in all cases the reinnervated receptors identified were appropriate to provide the neurophysiological basis for the observed results of quality of sensibility.

4.3.3 Complications of Regeneration Recovery of function after repair of nerves is often marred by cocontraction and pain, reflecting imperfect regeneration of both the afferent and the efferent pathways. Cocontraction. The normal movement of joints is brought about by the smoothly coordinated and controlled activity in muscles and precise and delicate regulation by inhibition and facilitation of the motor neurones. Beevor (1904) showed that the sensory motor cortex controls movements rather than individual muscles. The conversion of an antagonist to an agonist is the basis of musculotendinous transfer and it is common to see patients actively extending the knee or the ankle and toes as soon as the post operative splint is removed after hamstring to quadriceps transfer or anterior transfer of tibialis posterior. This control is damaged in lesions in continuity, especially of the brachial plexus; the joints of the shoulder girdle are especially vulnerable. It is possible that some of this is caused by the reinnervation of muscle units in antagonists by the same parent motor neuron but this explanation cannot account for the initial association between ventilatory and elbow flexion effort after intercostal transfer nor for the later separation of these functions. Muscles reinnervated by nerve repair or through a serious lesion in continuity usually fail to convert after muscle transfer irrespective of their power. Perhaps the defective reinnervation of the deep afferent pathways from the muscle spindles and the tendon receptors blinds muscles, which are, after all, sensory as well as effector organs. Cocontraction is common after reimplantation of the avulsed ventral root. Hallin et al. (1999) showed, in experiments on primates, that the motor neurones reinnervating the biceps were both abundant and scattered about in the anterior horn but that: “in double labeling experiments, simultaneous links to both antagonistic and agonistic muscles from the same neurone could not be demonstrated.” Carlstedt (2007c) thinks that: “the structural basis for deficient performance such as synkinesis or cocontraction was not due to the same neurones innervating antagonistic muscles, but rather was the effect of an unspecific reinnervation by inappropriate neurones under inappropriate supraspinal control.” Another possible mechanism is described by Camp and Allen (2008) who reported cocontraction between the trapezius and the swallowing muscles in a 27 year old woman who had sustained a basal skull fracture (Fig. 4.24). There was a severe but incomplete lesion of the spinal accessory nerve at or close to the jugular foramen and involuntary activity in

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Fig. 4.25  A 25 year old man. Penetrating missile wound to the shoulder, the exit wound close to the upper medial border of the scapula damaging the spinal accessory nerve at the level of the spine of the scapula. There was cocontraction between trapezius, levator scapulae and the rhomboid muscles.

Fig. 4.24  Cocontraction between platysma, trapezius, and other neck muscles (Courtesy of Camp and Allen).

sternocleidomastoid and trapezius with swallowing. There was abnormal synchronous activity between fibres within the spinal accessory the glossopharyngeal and vagus nerves. Camp and Allen suggest that there was aberrant reinnervation by motor fibres from the cranial root of the accessory nerve, or by motor fibres from the vagus, or glosso pharyngeal nerves. Other patients have been seen in whom a partial lesion of the peripheral nerve incited abnormal activity in motor fibres within adjacent peripheral nerves (Fig.  4.25). It is possible that disturbance at a spinal or supraspinal level underlies the abnormal muscle patterning seen in some cases of recurrent or habitual dislocation of the glenohumeral joint. Regeneration and Pain. Pain is, of course, a common feature of nerve injury particularly when the agent remains active but nerve regeneration itself may be associated with pain, particularly in adults. Anand (pers comm, 2009) has pointed out that there is a lifelong need for regeneration in the autonomic nerves to the smooth muscle of the skin and viscera and also in the somatic nerves of the skin. In traumatic

neuropathy the event is usually an isolated episode involving one nerve. The neuropathy induced by chemotherapy is cyclical, so that there are repeated sequences of axonopathy followed by regeneration. In diabetic neuropathy pain is usually associated with regeneration and in this disease the process is a lifelong event (Figs. 4.26a–d and 4.27a–d). Many patients experience flitting, deep, cramping pain in muscle, months after repair of the brachial plexus or high lesions of the sciatic nerve and shortly before obvious recovery of muscle function. We consider this a reassuring symptom and often suggest to patients that this is perhaps the only “good” form of neuropathic pain. The mechanism is obscure but the close relation to return of muscle activity suggests some reintegration of the deep afferent pathway. Anand and his colleagues have carried out extensive investigations in human nerve tissue and these provide some understanding about the mechanisms underlying pain associated with regeneration. In one study neurones from the dorsal root ganglion, which had been avulsed from the spinal cord, were cultured with a variety of neurotrophins including nerve growth factor (NGF), glial derived nerve factor (GDNF) and neurotrophin 3 (NT3) (Anand et al. 2006). The neurotrophins induced an increase in cell size and an increase in the proportion of cells exhibiting the receptor TRPV1, characteristic of nociceptor fibres. TRPV1 is the receptor for capsaicin, a potent nociceptor, and is expressed in DRG neurones, in painful neuromas and in the nerves of hypersensitive skin. The increase in this receptor was most marked in the larger cell bodies. Neurotrophin production is increased after nerve injury, indeed it is essential for the survival of the cell body and the regenerating axon. This finding provides one possible explanation for the mechanical sensitivity, at times so severe as to merit the term mechanical allodynia, which so often disturbs sensory recovery (Fig. 4.28). Durrenberger et al. (2004) studied the production of prostanoids, which are potent chemical mediators of inflammation

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Fig. 4.26  A 26 year old woman developed back pain radiating to the left foot and an ankle a sprain whilst training for a run. Over a few weeks she developed allodynia to touch, changes in colour and sweating and an abnormal foot posture. Clinical examination and quantitative sensory testing revealed a mechanical allodynia, elevated cold threshold and reduced heat pain threshold over the affected limb. Below knee amputation was performed. Examples of various nerve markers in the skin of the

calf close to the ankle. (a) Preserved sub-epithelial nerve fibres stained with the marker PGP9.5 (arrowed) x 40. (b) Unusually dense PGP9.5 fibres around blood vessels in the skin (arrowed) x 40. (c) Increased intra-epithelial transient receptor potential TRPV1 (heat receptor) fibres (arrowed) x 40. (d) A few sub-epithelial TRPM8 (cool receptor) fibres, (arrowed) x 40 (Courtesy of Professor Praveen Anand).

associated with nerve injury, in the human and the rat. Prostanoids sensitise nerve terminals. The enzymes responsible for prostanoid production are the cyclooxygenases (Cox-1 and Cox-2). The immunoreactivity for Cox 2 increased in cells resembling macrophages especially in the nerve proximal to the injury. The number of cells labeled for the enzyme reached a peak at between 4 or 6 weeks after injury. Anand et al. (2008) studied cannabinoid receptors in human nerves and neurones cultured from avulsed dorsal root ganglia. The cannabinoid receptor 2 (CB2) inhibits nociception and reduces pain, possibly by inhibiting inflammatory cell action or by inducing the release of the endogenous opiate b endorphine and it does this without inducing effects on the central nervous system which are associated with activation of a cannabinoid

receptor 1 (CB1). It was shown that agonists to CB2 block the action of capsaicin by impeding the activation of inward cation currents and preventing the increase in intracytoplasmic Ca++. Anand and her colleagues concluded that: “CB2 receptor agonists functionally inhibited nociceptive signaling in human primary sensory neurones.” Studies of the sodium channels Nav1.9 and Nav1.8 by Yiangou et  al. (2000) provides some understanding of the phenomenon of the “irritable” healing nerve and of the painful quality sometimes seen with Tinel’s sign. The channel Nav1.8 accumulated at the site of the injury in the proximal part of the nerve. One form of the channel Nav1.9 was not expressed at all in the infant nerves. Whilst much more needs to be done to explain the mechanisms underlying neuropathic pain and also the pain

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Fig. 4.27  Further examples of skin staining with various nerve markers in the patient illustrated in Fig.  4.26. (a) Sub-epithelial TRPM8 (cool and menthol receptor) fibres (arrowed) x 40. (b) PGP9.5 ­(structural marker) staining of injured nerve showing ovoid typical of Wallerian

degeneration. (c) Increased intra-epithelial (arrowed) and sub-epithelial TRPV1 (heat and capcaisin receptor) fibres x 40. (d) Basal keratinocytes (arrow head) and sub-epithelial NGF immunoreactive fibres (arrowed) x 40 (Courtesy of Professor Praveen Anand).

of regeneration these investigations of the cellular and molecular level in human tissue undoubtedly opens important lines of enquiry.

central nervous system. Although as long ago as 1907 Kilvington demonstrated the ability of the axons of the anterior horn cells to regenerate, and Tower (1943) showed the same, the matter was not systematically pursued. The latter indeed stated that the object of her work was “to prove unfounded the prevailing assumption that ventral nerve roots cannot regenerate if avulsed from the spinal cord.” She did just that in experiments on cats. Freeman (1952) used plasma clot suture for intradural transplantation of anterior spinal nerve roots in immature male guinea baboons. He reported functional restoration of a spinal reflex pattern of activity, and drew the conclusion that regeneration had occurred. Ochs and Barnes (1969) showed regeneration of ventral root fibres into dorsal roots in the cat, as shown by axoplasmic flow of radio-labeled leucine. Sanjuanbenito et al. (1976) demonstrated axonal regeneration in the ventral roots of the cat.

4.4 Regeneration after Intradural Injury The intradural, preganglionic lesions of the brachial plexus and to a lesser extent the similar lesions of the lumbosacral plexus have to be discussed separately in the matter of regeneration. It has for some time been clear that repair of such lesions offered the best chance of restoration of function and avoidance of pain, but the formidable technical difficulties of this have for years deterred most aspirants. There was, in addition, the discouraging thought that even if repair could be achieved, success required regeneration in the

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Fig. 4.28  Small to medium sized neuronal cell bodies and nerve fibres from a human dorsal root ganglion 3 weeks after avulsion immunostained with antibody to TRPV1 (heat and capsaicin receptor, black). The cell bodies of large diameter neurones are weakly stained. x 40 (Courtesy of Professor Praveen Anand).

The demonstration of Nathaniel and Nathaniel (1973) that in adult rats the dorsal root fibres could regenerate into the spinal cord after crushing seemed to indicate that the proximal limb of the axon of the sensory cell could make its way into the substantia gelatinosa and posterior funiculi. Bonney and Jamieson (1979) achieved reattachment of dorsal roots in the case of a man with a severe traction lesion of the brachial plexus. That was followed by recovery of proximal muscle function. Then Jamieson and Eames (1980) studied in adult dogs the regeneration of motor and sensory axons after avulsion and reimplantation. They found that, whereas there was significant regeneration of motor axons across the zone of repair, there was no regeneration of sensory axons. It appeared that whereas the motor axons behaved as part of the peripheral nervous system, the central process of the axon of the sensory cell behaved as part of the central system. Regeneration through the ventral root. Carlstedt and his colleagues have taken the matter far forward in extensive experimental studies which confirmed the reinnervation of skeletal muscle after ventral root implantation into the spinal cord. It was not even necessary to re-implant the roots along the anterolateral sulcus; sub-pial implantation near the sulcus was all that was necessary. This far reaching work is outlined by Carlstedt (1991, 2007d). Carlstedt et  al. (1995) reported the results of repair in man, of one root by direct implantation and of another by an intervening graft. There was secure evidence of functional reinnervation (Fig. 4.29). Regeneration through the dorsal root. The difference in behaviour of the nerve fibres within the dorsal and the ventral roots has been extensively studied by Carlstedt and his colleagues. Avulsion of the dorsal root causes proliferation of the asytrocytes which form a glial scar: “the astrocyte

Fig. 4.29  A horse radish peroxidase (HRP) filled motor neurone regenerated into an avulsed and implanted ventral root. (Above) Scale bar 20 mm. (Below). Scale bar 200 mm (Courtesy of Thomas Carlstedt).

barrier, developed as a response to nerve fibre degeneration, is most effective in preventing regeneration” (Carlstedt 1997, Carlstedt 2007d). However regeneration is possible in the immature animal before the establishment of the astrocyte population (Carlstedt 1988). It became clear that regeneration is enhanced if the transitional zone is bypassed by implanting the dorsal root directly into the spinal cord. This is followed by a substantial outgrowth of axons of the dorsal horn neurones to the injured dorsal root. Outgrowth from the secondary sensory neurones in the dorsal horn is further enhanced by excision of the dorsal root ganglion (Carlstedt 1997). Other methods have been used to enhance dorsal root fibre regeneration including glial cell transplants (Kliot et al. 1990), inflicting a preliminary or conditioning lesioning of the nerve before the implantation (Chong et al. 1999), and by transplanting olfactory ensheathing cells (Ramon-Cueto and Nieto-Sampedro 1994). Carlstedt and his colleagues applied olfactory ensheathing cells to reattached dorsal roots: the interposition enabled a “bridging channel” between the Schwann cells and the atrocytes, that is, between the peripheral and the central nervous systems (Li et al. 2004) (Fig. 4.30).

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avulsion of the ventral root. Nor can it, any longer, be a matter of doubt that this regeneration is capable of restoring useful function within the upper limb.

4.5 Recovery of Function after Nerve Repair a rule that a biologist, at any rate, finds useful is to suspect both those who lay down that results must be quantitative, and those who deny that they can be, but particularly to suspect the latter. (Young 1993)

Fig. 4.30  Regeneration through a reimplanted dorsal root. Olfactory ensheathing cells (green) in the proximal part of the dorsal root. Red stained regenerating nerve fibres passing between the root and the spinal cord. Original magnification x 180. Courtesy of Thomas Carlstedt.

Avulsion of the roots has a devastating effect on cells within the dorsal and ventral horns. It seems that the motor neurones can be rescued by reconnection with the periphery. Bergerot et  al. (2004) combined reimplantation with intrathecal delivery of glial derived neurotrophic factor (GDNF), and the intraperitoneal injection of a neuroprotective agent, riluzole. The population of the anterior horn neurones was maintained at 80% of the contra lateral side. Hart et  al. (2004) showed that dorsal horn neurones were protected by repair of the nerve within 24 h combined with the administration of acetyl-l-carbitine (ALCAR) or N-acetylcytseine (NAC). “As work in this field expands, it will be necessary to examine the effect of a solely motor innervation of muscles on their function. Doubtless, the search for sensory reinnervation will have to continue” (Birch and Bonney 1998a). Since that time we have confirmed the existence of myelinated afferent fibres in the ventral root of the human; their role awaits study. It is difficult to explain the level of function that has been seen in some successful cases after reimplantation without some elements of recovery of the muscle afferent pathway. In one case, which was demonstrated at the 7th International Brachial Plexus Meeting in London in 2008 the restoration of the biceps tendon reflex was demonstrated in a man who had undergone reimplantation of the ventral root of C6 six years previously. There can be no doubt that the motor neurones in the anterior horn are capable of regenerating new axons through the scar caused by

In clinical practice, most injuries of nerves short of transection inflict damage of all three grades of severity. The quality of reinnervation and hence of recovery depends first on the extent of damage causing degeneration and in particular loss of continuity of the basal lamina. A nerve fibre recovers completely after conduction block (neurapraxia), so long as the causative factor ceases to operate. Since this recovery does not have to be determined by axonal regrowth, it occurs over minutes, hours, days, weeks or – rarely– months. A nerve fibre will regenerate to its correct target after axonotomy so long as the basal lamina is preserved and the causative factor is removed. But recovery will take as long as it takes for the axon to re-innervate its target. Thus, recovery is the rule after “axonotmesis.” A nerve fibre will only regenerate to its correct target after axonotomy with interruption of the basal lamina if it is correctly directed to its target field or is drawn there by the operation of growth factors and other guiding mechanisms. Thus, in the case of individual nerves when the promptitude and quality of primary treatment is equal, the quality of recovery will depend on (1) the nature of the lesion: (2) the incidence of axonotomy: (3) the incidence of interruption of the basal lamina: (4) the obstacles posed to correct targeting by the complexity of functional representation in the nerve and the consequent liability to axon/target confusion; (5) the distance of the lesion from the target organs. We have already indicated that there are in effect no “purely motor” or “purely sensory” nerves, but the liability to axon/target confusion is plainly greater in a nerve such as the median with an extensive motor and cutaneous sensory distribution than it is in the posterior interosseous nerve, with no cutaneous sensory distribution. It is not doubted that full maturation of the regenerating nerve fibre depends on the establishment of the connection with its end-organ. The quality of recovery after neurotmesis and repair depends chiefly on the number of axons reaching their correct targets and on the later development and myelination of those axons. Factors influencing such re-innervation are: (1) the promptitude of repair; (2) the quality and viability of the opposed nerve ends; (3)The quality and accuracy of fascicular matching; (4) the degree of damage to the nerve ends

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during suture; (5) the length of gap after resection; (6) the number of channels provided by the interposed graft for the regenerating columns; (7)the extent of fibroblastic infiltration of the stumps and of the interposed grafts.

4.5.1 Methods The methods used for measurement of power, of cutaneous sensibility and sympathetic function are set out in the following Chap. 5. We have made only slender progress towards measuremt of recovery in the deep afferent pathways. The documents which have been developed to record progress are illustrated in Chaps. 5 and 10. Recall. Recovery of nerves after suture is a prolonged business. Omer (1998) described recovery of the small muscles of the hand 8 years after nerve repair and he pointed out: “these well documented late returns of neurological function to the intrinsic muscles of the hand are contrary to all results previously reported.” Case report. Primary repair of median and ulnar nerves was performed in a 22 year old staff nurse. Recovery was quite good, but marred by cold sensitivity, so that her result was considered only fair at 3 years after operation. She came to see us 7 years after operation to report a striking improvement during the previous few months. Over-sensitivity had disappeared, the final result for the ulnar nerve was considered excellent – and it was very good for the median. Case report. A 39  year old nursing sister wounded the digital nerves to little and ring fingers. Recovery was marred by cold sensitivity, and overreaction to light touch, until there was quite sudden resolution, over a few weeks, of these difficulties 6 years after operation. Zachary (1954) analyzed the duration of followup in patients with nerves repaired in the five Medical Research Council Nerve Injury Centres. More than 70% of them were seen at 60 months. Most of the failed repairs of the radial nerve were subsequently treated by flexor to extensor muscle transfer and after excluding these the rate of recall at 5 years was close to 80%. It has always been difficult to match this in civilian practice, indeed, clinicians, now, may find it impossible to do so as they find themselves working in an over politicized, management led and target driven health service. We must do what we can. Adequate assessment of outcome after severe injuries to the brachial and lumbosacral plexus in the adult requires at least 5 years of study. In some patients even this is inadequate (Chap. 9). The length of the follow up must be longer still in children with birth lesions of the brachial plexus (BLBP) or in those with severe injuries to the main nerves of the lower limb because of the ever present risk of secondary deformity from muscular imbalance or impaired

Surgical Disorders of the Peripheral Nerves

growth and because of the high incidence of posterior dislocation at the shoulder in BLPP. As it is our follow up is adequate in 1,060 repairs of closed traction lesion of the supraclavicular brachial plexus in the adult, in 1,128 (250 repairs) cases of BLPP and in around 1,800 repairs of main nerves. The results are related in later chapters. Grading of results. The results for nerves as a whole are graded by systems based on those developed by Seddon (1975e) which were drawn from those used in the five Specialist Nerve Injury Units (Zachary 1954). In some nerves muscular function is a good deal more important than recovery of sensation and for the circumflex, musculocutaneous, radial, femoral and common peroneal nerves, little significance is attributed to return of cutaneous sensation except when recovery is complicated by significant pain when the result is considered poor. Recovery of sensation has been given equal importance to muscle function in describing results of repairs of median and ulnar nerves and of the tibial division of the sciatic nerve. One could argue that sensibility is the most important function of the median and tibial nerves. Three grades are used (Birch, Bonney 1998): 1. Good, which means that recovery of function is substantial, that it enables the patient to use the part and to lead a normal life without difficulty and that they are not troubled by pain or over reaction. 2. Fair, implies recovery of function which is useful but which falls far short of normal. The patient is sufficiently aware of the hand or the foot that they do not damage it. Muscle power of MRC grade 2 or 3 restores some balance across a joint and it may be possible to supplement this with the appropriate muscle transfer to enhance, for example, flexion of the elbow or extension of the wrist. 3. Poor, means no or insignificant recovery and this grade is used in all cases with persisting spontaneous neuropathic pain, hypersensitivity or over reaction. The criteria used for grading results in individual nerves are set out in Chap 8. All systems of measurement have their defects and it seems the more closely one looks at the result of a nerve repair the more defects are revealed. Birch and Raji (1991) and Kline and Hudson (1995) introduced an “excellent” result, a result which we have given to a small number of repairs of the median and ulnar nerves nerve in the forearm and to some cases of repair of the spinal accessory nerve. The outcome is set out according to the cause of injury: the “tidy” wound from knife, glass or scalpel; the “untidy” wound from axes, saw, penetrating missile, open fracture or dislocation or burn; and the closed traction lesion. The effects of associated arterial injury are severe: such cases are considered separately in each of the three main groups. This reflects our view that the two factors of overwhelming significance on outcome are first, the violence of the injury and the extent

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of damage to the nerve and adjacent tissues and second, delay before repair. Other factors which are important in prognosis were clearly defined in the Medical Research Council Special Report Series No. 282 (1954), by Seddon (1975c), Sunderland (1978), and Kline and Hudson (1995), Kline and Hudson (2008, 2008) amongst others. We shall examine these.

4.6 Factors in Prognosis Age. Recovery of function after repair of a nerve in a child is, on the whole, better than in the adult, but it is not as good as has sometimes been assumed. This comes as no surprise if we take into consideration the increased vulnerability of the immature nervous system to axonotomy. Some of the most difficult problems in reconstruction follow failure of recovery of either of the divisions of the sciatic nerve in the growing child. The unpredictability and the limitations of outcome after repair of the plexus in birth lesions are related in Chap. 10. The recovery of skeletal muscle and of sympathetic efferent function after injuries to the brachial or lumbosacral plexus in the growing child is generally inferior to that seen following urgent repair in adults. There is often severe shortening of the limb and atrophy of the hand or foot. On the other hand the recovery of cutaneous sensation in the infant or child is often remarkably good. The results after repair of digital nerves provides one example of the difference between the adult and the child (Table 4.1). Goldie et  al. (1992) made a detailed study of 27 adult patients. Thirty nerves were repaired, all but one by primary repair using sutures for we did not have access to fibrin clot glue at that time. The digital artery was repaired if that had been damaged. Examination for sensation was thorough and it was helped by using weighted pins designed for us by Professor Ruth Bowden. The results were surprisingly disappointing, an indication perhaps that the more scrupulously that one examines outcome from a nerve repair the more one will find wrong. Thirty-seven per cent of fingers regained normal two-point discrimination but

only 27% of patients graded their overall result as “excellent” and 40% complained of persistent hyperaesthesia up to 2 years. Goldie and Coates concluded: “following repair of the divided digital nerve, normal sensation will never be regained. Hyperaesthesia may be present for months or years but will ultimately resolve. The final result will take two or three years to achieve.” Fortunately results do seem to be a good deal better in children. It does seem odd that recovery of sensation after a well executed primary repair of the median nerve at the wrist is regularly better than that from repair of digital nerves more distally. It is only fair to add that a number of patients reported striking improvement in sensation, with sudden loss of cold sensitivity and hypersensitivity to touch, some years after repair. There seems a trend towards neglecting nerve injuries in patients of a certain age, a policy for which we find a remarkable absence of supporting evidence. Indeed, the changes in the peripheral nerves with aging (Chap. 2) suggest that the older patient may in fact be more likely to develop severe pain after injury to a nerve. Some striking results have been seen after repair of the brachial plexus in patients aged over 65 years. In several of these the relief of pain and with it the improvement in the patient’s mental well being, were remarkable. It may be administratively convenient to ignore the elderly but they are, after all, still human beings and the risk of losing independence calls for a far more rational and vigorous approach than is often, too often, seen. Level of injury. This is undoubtedly important for the median, ulnar and radial nerves but it seems to be much less important for the sciatic nerve and its divisions. Only rarely is extension of the digits regained after injuries to the brachial plexus, the posterior cord or the radial nerve in the axilla. Urgent repair of lesions of C5 and C6 is often followed by recovery to a level far higher than that seen after repair of combined lesions of the circumflex, the suprascapular and the musculocutaneous nerves. There seems little doubt, however, that repair of the recurrent motor branch of the median nerve at the wrist, of the posterior interosseous nerve and of the deep branch of the ulnar nerve is followed by a return of function which is scarcely ever seen after high repairs of main nerves. On the other hand lesions of the distal

Table 4.1  Recovery of sensation after repair of 129 digital nerves. Grade Adults Repair within 48 h of injury Repair 2 weeks or more after injury Excellent

1

0

Children (aged 1 years or less) Repair at varying intervals after injury 17

18

Good

33

9

8

50

Fair

24

11

2

37

Poor

16

74 17 digital arteries repaired at primary operation. 20 flexor tendons repaired at primary operation.

8

0

24

28

27

129

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branches of such cutaneous nerves as the sural, the medial cutaneous of forearm and the superficial radial nerve have deservedly gained an ill reputation. The nerve. Whilst there is no such thing as a purely “motor” or “sensory” nerve in the peripheral nervous system, it appears that recovery after repair of nerves which have no cutaneous distribution is generally better than after repair of main nerves. The spinal accessory and the nerve to serratus anterior generally recover well after repair. The suprascapular fares better than the circumflex. It is more than 50 years since Zachary established that recovery for the common peroneal nerve is far inferior than for the tibial nerve, an observation which has been repeatedly confirmed. The blood supply to the most proximal segment of the radial nerve and to the common peroneal nerve is rather poor, so that transection of these nerves is likely to enhance ischaemic changes in the distal segment.

4.7 Severity of Injury Useful recovery in function cannot be expected if the fundamental principles of treatment of a wound are neglected. Arteries must be repaired, the tissues of the limb must be perfused, the skeleton must be stabilized and repaired nerves and vessels must be covered by full thickness skin. Michael Glasby and his colleagues used the freeze-thawed muscle graft (FTMG) in a series of experiments which showed that recovery is worsened by delay, by arterial injury, by fractures, by cavitation and by haematoma (Fullerton et al. 1998, Glasby et al. 1997, Glasby et al. (1998).

Surgical Disorders of the Peripheral Nerves

inevitable.” Zachary and Holmes (1946) compared 55 cases of primary sutures of nerves referred to the Peripheral Nerve Injury Centre, at the Wingfield-Morris Hospital, Oxford, during the years 1940–1944 with 36 “early” secondary sutures. The results of secondary suture were distinctly better. The primary repair was resected and the nerve re-sutured in 16 patients. Histological examination of the resected material revealed a number of causes for the failure of the first operation: poor matching of the proximal and distal stumps; coarse suture material lodged between the stumps; separation of the stumps; and dense scar between or within the stumps. Zachary and Holmes concluded that “Formal nerve suture should be undertaken at the earliest moment when it is possible to recognise the extent of damage to the nerve, excise the injured segment, and bring together the mobilised nerve ends without the prospect of undue post operative tension.” These are painful but important findings: the lesson is that the results of operating on peripheral nerves depend to an extent hardly matched in any other branch of surgery on the skill of the surgeon and the quality of the technique. The clinician must always bear in mind that the sooner the distal segment is connected to the cell body and proximal segment the better the result will be. The quality of treatment of the wound at first operation and the timing of repair of the nerves are factors within the control of clinicians. The last 20 years has seen extensive laboratory work which confirms the view, long held by many clinicians, that the central nervous system suffers after interruption of a peripheral nerve. The rapidity and the severity of that response to violent proximal nerve injury is the over arching biological imperative which must guide action.

4.8 Delay References Sherren (1908) examined 50 cases of primary suture performed at the London Hospital. Pain sensibility recovered before touch; tactile localisation continued to improve for more than 2 years. Recovery of power was rather slower. There was no recovery in only one patient, whose wound had become infected. Sherren recommended primary suture “because the prognosis after secondary suture is more unfavourable.” Platt and Bristow (1924) reviewed the late results of nerve injuries treated in the First World War, and noted the “extreme perfection attained after so-called primary suture,” acknowledging that the more severe gunshot wounds of nerves were treated by secondary suture. Platt (1937) wrote “in primary sutures performed under ideal conditions, complete recovery of motor power and recovery of protopathic sensibility at least, is to be expected.....however, in more extensive wounds with widespread bruising and multiple tendon injuries, and in wounds in which infection had already secured a hold, partial or complete failure after primary suture is almost

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141 Brushart TM, Mather V, Sood R, Koschorke G-M (1995) Dispersion of regenerating axons across enclosed neural gaps. J Hand Surg Am 20:557–564 Bunnell S, Boyes JH (1939) Nerve grafts. Am J Surg 44:64–75 Bunting S, Di Silvio L, Deb S, Hall S (2005) Bioresorbable glass fibres facilitate peripheral nerve regeneration. J Hand Surg Br 30: 242–247 Cabaud HE, Rodky G, Nemeth TJ (1982) Progressive ultrastructural changes after peripheral nerve transection and repair. J Hand Surg Am 7:353–365 Caddick J, Kingham PJ, Gardiner NJ, Wyburg M, Terenghi G (2006) Phenotypic and functional characteristics of mesenchymal stem cells differentiated along a Schwann cell lineage. Glia 54:840–849 Cajal SRY (1928a) A regenerative process of the central stump. In: Degeneration and regeneration of the nervous system. Oxford University Press, London, Chapter 7, pp 141–166 (Trans ed: May RM) Cajal SRY (1928b) Late conditions shown by the nerve sprouts of the central stump and of the scar. In: Degeneration and regeneration of the nervous system. Oxford University Press, London, Chapter 9, pp 198–222 (Trans ed: May RM) Cajal SRY (1928c) Experiments dealing with the transplantation of nerves or their products, designed to prove especially an attractive or neurotropic action on nerve sprouts. In: Degeneration and regeneration of the nervous system. Oxford University Press, London, Chapter 15, pp 329–361 (Trans ed: May RM) Calder JS, Green CJ (1996) Nerve-muscle sandwich grafts: the importance of Schwann cells in peripheral nerve regeneration through muscle basal lamina conduits. J Hand Surg Br 20:423–428 Camp SJ, Allen D (2008) Cocontraction of swallowing musculature and trapezius following basal skull fracture. Injury Extra 39:95–97 Carlstedt T (1988) Reinnervation of the mammalian spinal cord after neonatal dorsal root crush. J Neurocytol 17:335–350 Carlstedt T (1991) Experimental studies on surgical treatment of avulsed spinal nerve roots in brachial plexus injury. J Hand Surg Br 16:477–482 Carlstedt T (1997) Nerve fibre regeneration across the peripheral-central transitional zone. J Anat 190:51–56 Carlstedt T (2007a) End to side or termino-lateral neurorrhaphy. In: Central nerve plexus injury. Imperial College Press, London, pp 70–71 Carlstedt T (2007b) Outcome of nerve transfer. In: Central nerve plexus injury. Imperial College Press, London, pp 71–74 Carlstedt T (2007c) Cocontraction. In: Central nerve plexus injury. Imperial College Press, London, pp 144–150 Carlstedt T (2007d) Basic science of experimental root injuries. In: Central nerve plexus injury, Chap 6. Imperial College Press, London, pp 78–111 Carlstedt T, Crane P, Hallin RG, Noren G (1995) Return of function after spinal cord implantation of avulsed spinal nerve roots. Lancet 346:1323–1325 Chen L, Gu YD (1994) An experimental study of contralateral C7 root transfer with vascularised nerve grafting to treat brachial plexus root avulsion. J Hand Surg Br 19:60–66 Chong MS, Woolf CJ, Haque NS, Anderson PM (1999) Axonal regeneration from injured dorsal roots into the spinal cord of adult rats. J Comp Neurol 410:42–54 Collier J (1940) Facial paralysis and its operative treatment. Lancet 1:91 Dellon AL, Munger BL (1983) Correlation of histology and sensibility after nerve repair. J Hand Surg Am 8:871–875 Durrenberger PF, Facer P, Gray RA, Chessell IP, Naylor A, Bountra C, Banati RB, Birch R, Anand P (2004) Cyclooxygenase – 2 (Cox-2) in injured human nerve and a rat model of nerve injury. J Peripher Nerv Syst 9:15–24 Dyck PJ, Thomas PK (2005) Peripheral neuropathy, 4th edn. Elsevier, Philadelphia

142 Dyck PJ, Dyck PJB, Engelstad J (2005) Pathological alterations of nerves. In: Dyck PJ, Thomas PK (eds) Peripheral neuropathy, 4th edn. Elsevier, Philadelphia, pp 733–829 Foerster O (1929) Die therapie der Schussverletzungen der peripheren nerven, resultate der plexus operationen. In: Foerster BO (ed) Handbuch der neurologie von lewandowski, vol 2. Springer, Berlin, pp 1676–1691 Forsmann J (1900) Zur kenntnis des neurotropismus. Ziegler’s Beiträge Zur Pathol Anat 27:407 Freeman LW (1952) Observations on spinal nerve root transplantation in the male guinea baboon. Ann Surg 136:206–210 Fullerton AC, Glasby MA, Lawson GM (1998) Immediate and delayed nerve repair using freeze-thawed muscle autografts in complex nerve injuries. Associated long bone fracture. J Hand Surg Br 23:360–364 Fullerton AC, Myles LM, Lenihan DV, Hems TEJ, Glasb M (2001) Obstetric brachial plexus palsy: a comparison of the degree of recovery after repair of 16 ventral root avulsions in newborn and adult sheep. Br J Plas Surg 54:697–704 Glasby MA, Gschmeissner SE, Huang CL, De Souza BA (1986) Degenerated muscle grafts used for peripheral nerve repair in primates. J Hand Surg Br 11:347–351 Glasby MA, Fullerton AC, Lawson GM (1997) Immediate and delayed nerve repair using freeze-thawed muscle autografts in complex nerve injuries. Cavitation, fibrosis and haematoma. J Hand Surg Br 22:479–485 Glasby MA, Fullerton AC, Lawson GM (1998) Immediate and delayed nerve repair using freeze-thawed muscle autografts in complex nerve injuries Associated arterial injury. J Hand Surg Br 23(3):354–359 Goldie BS, Coates CJ, Birch R (1992) The long term results of digital nerve repair in no man’s land. J Hand Surg Br 12:75–77 Gore RV (1978) A new method of nerve repair: repair of a lesion of the radial nerve with a branch to the triceps muscle. Br J Surg 65: 352–353 Griffin JW, Hoffman PN (1993) Degeneration and regeneration in the peripheral nervous system. In: Dyck PJ, Thomas PK, Lambert EH, Bunge R (eds) Peripheral neuropathy, 3rd edn. WB Saunders, Philadelphia, Chapter 22, pp 361–376 Gu YD, Zhang GM, Chen DS, Yan JG, Cheng XM, Chen L (1992) Seventh cervical nerve root transfer from the contralateral healthy side for treatment of brachial plexus root avulsion. J Hand Surg Br 17:518–521 Gutmann E, Sanders FK (1942) Functional recovery following nerve grafts and other types of nerve bridges. Brain 65:373–408 Gutmann E, Young JZ (1944) The reinnervation of muscle after various periods of atrophy. J Anat 78:15–43 Hall S (1997) Axonal regeneration through acellular muscle grafts. J Anat 190:57–71 Hall S (2005a) Mechanisms of repair after traumatic injury. In: Dyck PJ, Thomas PK (eds) Peripheral neuropathy, 4th edn. Elsevier Saunders, Philadelphia, Chapter 58, pp 1403–1434 Hall S (2005b) The response to injury in the peripheral nervous system. J Bone Joint Surg Br 87:1309–1319 Hall SM (2009) Biomaterials for the repair of peripheral nerves. In: di Silvio L (ed) Cellular response to biomaterials, Chap. 11. Woodhead, Cambridge, pp 252–290 Hallin R, Carlstedt T, Nilsson-Remahl IA, Risling M (1999) Spinal cord implantation of avulsed ventral roots in primates: correlation between restored motor function and morphology. Exp Brain Res 124(3):304–310 Harris W, Low VW (1903) On the importance of accurate muscular analysis in lesions of the brachial plexus and the treatment of Erb’s palsy and infantile paralysis of the upper extremity by cross-union of nerve roots. Br Med J 2:1035–1038 Hart AM, Terenghi G, Kellerth JO, Wiberg M (2004) Sensory neuroprotection, mitochondrial preservation and therapeutic potential of N-acetyl-cysteine after nerve injury. Neuroscience 125:91–101

Surgical Disorders of the Peripheral Nerves Healy C, Lequesne PM, Lynn B (1996) Collateral sprouting of cutaneous nerves in man. Brain 119:2063–2072 Highet WB, Sanders FK (1943) The effects of stretching nerves after suture. Br J Surg 30:355–369 Höke A, Redett R, Hameed H, Jari R, Zhou C, LI ZB, Griffin JW, Brushart TM (2006) Schwann cells express motor and sensory phenotypes that regulate axon regeneration. J Neurosci 26:9646–9655 Holmes W, Young JZ (1942) Nerve regeneration after immediate and delayed suture. J Anat 77:63–96 Htut M, Misra P, Anand P, Birch R, Carlstedt T (2006) Pain phenomena and sensory recovery following brachial plexus avulsion injury and surgical repair. J Hand Surg Br 31:596–605 Irwin MS, Abhilash J, Anand P, Manchahal J (2006) Free innervated sole of foot transfer for contralateral lower limb salvage. Plast Recon Surg 118:93e–97e Jabaley ME, Burns JE, Orcutt BS, Bryant WM (1976) Comparison of histologic and functional recovery after peripheral nerve transection and repair. J Hand Surg 1:119–130 Jamieson A, Eames RA (1980) Reimplantation of avulsed brachial plexus roots: an experimental study in dogs. Int J Microsurg 2:75–80 Joyce JL (1919) Nerve suture. Br J Surg 6:418 Kanamura A, Suzuki S, Sibuya M, Homma I, Sai K, Hara T (1993) Sensory reinnervation of muscle receptor in human. Neuroscience 161:27–29 Graham K (1904) On somepoints in the early development of motor nerve trunks, etc. in lepidosiren. Trans Roy Soc Edin 41:121–128 Kettle S (2003) The use of end to side repair of peripheral nerves for neurotization after loss of nerve tissue in a large tissue model. MD Thesis. University of Edinburgh Kilvington B (1907) An investigation on the regeneration of nerves, with regard to surgical treatment of certain paralysies. Br Med J 1:988–990 Kline DG, Hudson AR (1995) Nerve injuries. WB Saunders, Philadelphia Kline DG, Hudson AR (2008) Nerve injuries, 2nd edn. Saunders Elsevier, Philadelphia (with Kim DH, Midha R, Murovic JA, Spinner RJ) Kliot M, Smith GM, Siegal JD, Silver J (1990) Astrocyte-polymer implants promote regeneration of dorsal root fibres into the mammalian spinal cord. Exp Neurol 109:57–69 Kotani PT, Matsuda H, Suzuki T (1972) Trial surgical procedures of nerve transfers to avulsion injuries of the plexus brachialis. Excerpta Medica International Congress Series Number 291 (1973). Proceedings of the 12th Congress of S.I.C.O.T. Tel Aviv, October 9–12 1972, pp 348–351 Lago N, Ceballos D, Rodriguez FJ, Stieglitz T, Navarro X (2007) Effects of motor and sensory nerve transplants on amount and specificity of sciatic nerve regeneration. J Neurosci Res 85:2800–2812 Lang EM, Borges J, Carlstedt T (2004) Surgical treatment of lumbosacral plexus injuries. J Neurosurg Spine 1:64–71 Larsen M, Habermann TM, Bishop AT, Shin AY, Spinner RJ (2007) Epstein-Barr virus infection as a complication of transplantation of a nerve allograft from a living related donor. J Neurosurg 106: 924–928 Li H, Wigley C, Hall SM (1998) Chronically denervated rat Schwann cells respond to Ggf in vitro. Glia 21:1–14 Li Y, Carlstedt T, Berthold CH, Raisman G (2004) Interaction of transplanted olfactory ensheathing cells and host astrocyte processes provides a bridge for axons to regenerate across dorsal root entry zone. Exp Neurol 188:300–308 Lundborg G (1991) Neurotropism, frozen muscle grafts and other conduits. J Hand Surg Br 16:473–476 Lundborg G (2003) Nerve injury and repair. A challenge to the plastic brain. The Bunge Memorial Lecture. J Peripher Nerv Syst 8:209–226 Lundborg G (2004a) The growth cone. In: Nerve injury and repair, 2nd edn. Elsevier/Churchill Livingstone, Philadelphia, p 13

Regeneration and Recovery Lundborg G, Dahlin LB, Danielsen N, Nachemson AK (1986) Tissue specificity in nerve regeneration. Scand J Plast Reconstr Surg 6:265–281 Lundborg G, Dahlin L, Dohi D, Kanje M, Terad N (1997) A new type of “bioartificial” nerve graft for bridging extended defects in nerves. J Hand Surg Br 22:299–303 MacCarty CS (1951) Two-stage autograft for repair of extensive damage to sciatic nerve. J Neurosurg 8:319 MacKinnon SE (1996) Nerve allotransplantation following severe tibial nerve injury. J Neurosurg 84:671–676 MacKinnon S, Dellon L, O’brian J (1986a) Changes in nerve fibre numbers distal to a nerve repair in the rat sciatic model. Muscle Nerve 14:1116–1122 MacKinnon SE, Dellon AL, Lundborg G, Hudson AR, Hunter D (1986b) A study of neurotropism in a primate model. J Hand Surg Am 11:888–894 Malessy MJ, Thomeer RT, Van Dijk JG (1998) Changing central nervous system control following intercostal nerve transfer. J Neurosurg 89:568–574 Malessy MJ, Bakker D, Dekker AJ, Van Dijk JG, Thomeer RT (2003) Functional magnetic resonance imaging and control over the biceps muscle after intercostal-musculocutaneous nerve transfer. J Neurosurg 98:261–268 Mano Y, Nakamuro T, Tamara R, Takayang T, Kawanishi K, Tamai S, Mayer RF (1995) Central Motor re-organisation after anastamosis of the musculocutaneous and intercostal nerves following clinical root avulsion. Ann Neurol 38:15–20 Mayo-Robson AW (1917) Nerve grafting as a means of restoring function in limbs paralysed by gunshot or other injuries. Br Med J 1:117–118 Medical Research Council Special Report Series No. 282. (1954). Peripheral nerve injuries. Seddon HJ (ed). HSMO London. Millesi H (1973) Microsurgery of peripheral nerves. Hand 5:157–160 Mirsky R, Jessen KR (2005) Molecular signalling in Schwann cell development. In: Dyck PJ, Thomas PK (eds) Peripheral neuropathy, 4th edn. Elsevier Saunders, Philadelphia, Chapter 16, pp 341–376 Moberg E (1958) Objective methods for determining the functional value of sensibility in the hand. J Bone Joint Surg Br 40:454–476 Morris JH, Hudson AH, Weddell G (1972a) A study of degeneration and regeneration in the divided rat sciatic nerve based on electron microscopy ii the development of the “regenerating unit”. Zeitschrift für Zellforschumg 124:103–130 Morris JH, Hudson AH, Weddell G (1972b) Changes in the axons of the proximal stump. Zeitschrift für Zellforschumg 124:131–164 Morris JH, Hudson AH, Weddell G (1972c) Changes in fascicular microtopography. The perineurium and endoneurial fibroblasts. Zeitschrift für Zellforschumg 124:165–203 Mott FW, Halliburton WD (1901) The chemistry of nerve-degeneration. Phil Trans R Soc Lond B 194:437–466 Myles LM, Gilmour JA, Glasby M (1992) Effects of different methods of peripheral nerve repair in the number and distribution of muscle afferent neurons in the rat dorsal root ganglion. J Neurosurg 77:457–462 Nagano A, Tsuyama N, Ochiai N, Hara T (1989) Direct nerve crossing with the intercostal nerve to treat avulsion injuries of the brachial plexus. J Hand Surg Am 14(6):980–985 Narakas AO (1988) Neurotization or nerve transfer in traumatic brachial plexus lesions. In: Tubiana R (ed) The hand III. WB Saunders, Philadelphia, Chapter 62, pp 656–683 Nathaniel EJM, Nathaniel DR (1973) Regeneration of dorsal root fibers into the adult rat spinal cord. Exp Neurol 40:333–350 Navarro X, Calvet S, Rodriguez FJ, Stieglitz T, Blau T, Buti M, Valderrama E, Meyer JU (1998) Stimulation and recording from regenerated peripheral nerves through polyimide sieve electrodes. J Peripher Nerv Syst 3:91–101 Nichols CM, Brenner MJ, Fox IK, Tung TH, Hunter DA, Rickman SR, MacKinnon SE (2004) Effects of motor versus sensory nerve grafts on peripheral nerve regeneration. Exp Neurol 190:347–355

143 Oberlin C, Beal D, Leechavengvongs S, Salon A, Dauge MC, Sarly JJ (1994) Nerve transfers to biceps muscle using part of ulnar nerve for C5-C6 avulsion of the brachial plexus: anatomical study and report of four cases. J Hand Surg Am 19:232–237 Ochs S, Barnes CD (1969) Regeneration of ventral root fibers into dorsal roots shown by axoplasmic flow. Brain Res 15:600–603 Omer GE (1998) Peripheral nerve injuries and gunshot wounds. In: Omer GE, Spinner M, Van Beek AL (eds) Peripheral nerve problems, 2nd edn. WB Saunders, Philadelphia, Chapter 41, pp 398–405 Őzkan T, Őzer K, Gülgőnen A (2001) Restoration of sensibility in irreparable ulnar and median nerve lesions with use of sensory nerve transfer: long-term follow up of 20 cases. J Hand Surg Am 26:44–51 Pereira JH, Palande DD, Narayanakumar TS, Subramian AS, Gschmeissner S, Wilkinson M (2008) Nerve repair of denatured muscle autografts promotes sustained sensory recovery in leprosy. J Bone Joint Surg Br 90:220–224 Platt H (1937) Discussion on injuries to peripheral nerves. Proc R Soc Med Lond 30:863 Platt H, Bristow WR (1924) The remote results of operations for injuries of the peripheral nerves. J Br J Surg 11:535–567 Ramon-Cueto A, Nieto-Sampedro M (1994) Regeneration into the spinal cord of transected dorsal root axons is promoted by ensheathing glial transplants. Exp Neurol 127:232–244 De Ruiter GCW, Spinner RJ, Yaszmenski MJ, Windebank AJ, Malessy MJA (2009) Nerve tubes for peripheral nerve repair. Neurosurg Clin North Am 20:91–106 Sai K, Kanamura A, Sibuya M, Homma I, Hara T (1996) Reconstruction of tonic vibration reflex in the biceps brachii reinnervated by transferred intercostals nerves in patients with brachial plexus injury. Neurosci Lett 206:1–4 Sanders FK (1942) The repair of large gaps in the peripheral nerves. Brain 65:281–337 Sanders FK, Young JZ (1946) The influence of peripheral connections on the diameter of regenerating nerve fibres. J Exper Biol 22:203–212 Sanjuanbenito L, Esteban A, Gonzalez-Martinez E (1976) Regeneration of the spinal ventral roots. Acta Neurochir 34:203–214 Schuind F, Van Holder C, Mouraux D, Robert CH, Meyer A, Saliva P, Vermeylen N, Abramowicz D (2006) The first Belgian hand transplantation – 37 months results. J Hand Surg Br 31:371–376 Scott JJ (1995) The functional recovery of muscle proprioception after peripheral nerve lesions. J Peripher Nerv Syst 1:19–27 Scott JJA (2005) The Golgi tendon organ. In: Dyck PJ, Thomas PK (eds) Peripheral neuropathy (in two volumes), 4th edn. Elsevier Saunders, Philadelphia, Chapter 7, pp 151–161 Seddon HJ (1947) The use of autogenous grafts for the repair of large gaps in peripheral nerves. Br J Surg 35:151–167 Seddon HJ (1954) Nerve grafting. In: Peripheral nerve injuries by the Nerve Injury Committee of the Medical Research Council MRC Special Report Series 282. Hmso, London, pp 402–403 Seddon HJ (1975a) Degeneration and regeneration. In: Surgical disorders of peripheral nerves, Chap. 2, 2nd edn. Churchill Livingstone, Edinburgh, pp 9–31 Seddon HJ (1975b) Repair and tension. In: Surgical disorders of peripheral nerves, 2nd edn. Churchill Livingstone, Edinburgh, pp 298–299 Seddon HJ (1975c) Nerve Grafting and kindred procedures. In: Surgical disorders of peripheral nerves, 2nd edn. Churchill Livingstone, Edinburgh, pp 287–302 Seddon HJ (1975d) Homografts. In: Surgical disorders of peripheral nerves, 2nd edn. Churchill Livingstone, Edinburgh, p 299 Seddon HJ (1975e) Results of repair of the nerves. In: Surgical disorders of peripheral nerves, 2nd edn. Churchill Livingstone, Edinburgh, pp 303–314 Seddon HJ, Young JZ, Holmes W (1942) The histological condition of a nerve autograft in man. Br J Surg 29:378–384 Sherren J (1906) Some points in the surgery of the peripheral nerves. Edin Med J 20:217–231

144 Sherren J (1908) Injuries of nerves and their treatment. James Nisbet, London Simpson SA, Young JZ (1945) Regeneration of fibre diameter after cross-unions of visceral and somatic nerves. J Anat 79:48 Songcharoen P, Wongtrakul S, Mahrisavariya B, Spinner RJ (2001) Hemi-contralateral C7 transfer to median nerve in the treatment of root avulsion brachial plexus injury. J Hand Surg Am 26:1058–1064 Sorbie C, Porter TL (1969) Reinnervation of paralysed muscles by direct motor nerve implantation: an experimental study in a dog. J Bone Joint Surg Br 51:156–164 Strange FGS (1947) An operation for pedicle nerve grafting. Br J Surg 34:423–425 Sunderland S (1978) Nerve and nerve injuries, 2nd edn. Churchill Livingstone, Edinburgh Terenghi G, Calder JS, Birch R, Hall SM (1998) A morphological study of Schwann cells and axonal regeneration in chronically transected human peripheral nerve. J Hand Surg Br 23:583–587 Thomas M, Stirratt A, Birch R, Glasby M (1994) Freeze thawed muscle grafting for painful cutaneous neuromas. J Bone Joint Surg Br 76:474–476 Tinel J (1917) Nerve wounds (Revised and edited by Joll CA). Ballière Tindall and Cox, London Tower SS (1943) Regenerative capacity of ventral roots after avulsion from the spinal cord. Arch Neurol Psychiatry 49:1–12 Trachtenburg JT, Thompson WJ (1996) Schwann cell apoptosis at developing neuromuscular junctions is regulated by glial growth factor. Nature 379:174 Trumble TE (1991) Overcoming defects in peripheral nerves. In: Gelberman RH (ed) Operative nerve repair and reconstruction. JB Lippincott, Philadelphia, Chapter 36, pp 507–524 Tsao JW, George EB, Griffin W (1999) Temperature modulation reveals three distinct stages of Wallerian degeneration. J Neurosci 19: 4718–4726 Tsuyama N, Hara T (1973) Intercostal nerve transfer in the treatment of brachial plexus injury of root-avulsion type. Proceedings of the

Surgical Disorders of the Peripheral Nerves S.I.C.O.T. Tel Aviv Oct. 9–12 1972. Excerpta Medical International Congress Series No. 291: 348–351 Tuttle H (1913) Exposure of the brachial plexus with nerve transplantation. JAMA 61:15–17 Vizoso AD, Young JZ (1948) Internode length and fibre diameter in developing and regenerating nerves. J Anat 82:110–134 Waikakul S, Orapin S, Vanadurongwan V (1999) Clinical results and contralateral C7 root neurotization to the median nerve in brachial plexus injuries with total root avulsions. J Hand Surg Br 24:556–560 Wallman L, Zhang Y, Laurell T, Danielson N (2001) The geometric design of micromachined silicon sieve electrodes influences functional nerve regeneration. Biomaterials 22:1187–1193 Witte H, Bradke F (2005) Guidance of axons to targets in development and in disease. In: Dyck PJ, Thomas PK (eds) Peripheral neuropathy, 4th edn. Elsevier Saunders, Philadelphia, Chapter 21, pp 447–481 Witzel C, Brushart T (2003) Morphology of peripheral axon regeneration. J Peripher Nerv Syst 8:75–76 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 (1993) First evidence of axonal transport. In: DyckPJ TPK, Griffin JW, Low PA, Poduslo JF (eds) Peripheral neuropathy, 3rd edn. WB Saunders, Philadelphia, p 2 Zachary RB (1954) Results of nerve sutures. In: Seddon HJ (ed) Peripheral nerve injuries. Medical Research Council. Special report series No. 282, pp 354–387 Zachary RB, Holmes W (1946) Primary suture of nerves. Surg Gynaecol Obstet 82:632–651 Zhao Q, Drott J, Laurell T, Wallman L, Lundstrom K, Bjursten LM, Lundborg G, Montelius L, Danielson N (1997) Rat sciatic nerve regeneration through a micromachined silicone chip. Biomaterials 18:75–80

5

Clinical Aspects of Nerve Injury

Clinical aspects: acute injury; penetrating missile wounds; symptoms and signs; importance of recognition of differential affection of fibres of different sizes; recognition of level and depth of lesion; significance of Tinel’s sign; examination of sensibility; quantitative sensory testing; the motor pathways; examination of muscles; late signs of nerve injury; records; signs of regeneration; aids to diagnosis. “Few surgeons see their patients from the beginning to the end. One could well wish that there was no evil in this. But there is much of evil, and not least is the fact that the orthopaedic surgeons work has enormously increased” (Keogh 1917).

In the acute injury the object of the clinician must be to recognise the fact of injury as soon as possible after the event, and later to go on to determine the nerve or nerves affected, the level or levels of injury and the extent and depth of the lesion or lesions. That this is not always easy nor always appreciated is apparent to anyone who has been able to study the records of the medical defense organisations. The history is important: high velocity injury, compound fracture and wounding, accidental, criminal, surgical or all three, are likely to mean that there has been a serious lesion. The use of a knife, often enough in the hand of a surgeon, is an indication that a nerve is likely to have been partly or completely severed. Advice from witnesses or emergency paramedical staff is always valuable. Potentially life or limb threatening injuries complicate closed traction lesion of the supraclavicular brachial plexus in at least 20% of cases. Even more patients with injuries to the lumbo-sacral plexus are so threatened. The subclavian artery is ruptured in 10% of complete lesions of the brachial plexus and in as many as 30% of cases of violent traction injury of the infraclavicular portion of the brachial plexus. The incidence of arterial lesion is high after fracture dislocations of the shoulder and elbow, higher still after fracture dislocations of the knee. It is important always to search with diligence for occult injuries to the head, the spine, the chest, the abdomen and pelvis before embarking upon treatment of the nerve lesion, both at the first hospital but also after transfer to another Unit (Fig. 5.1). The site and nature of the wound or wounds must be observed. In closed injuries the presence of swelling and bruising may give some indication of severity (Novak and Baratz 2006). In all cases of limb injury the adequacy of perfusion as judged by the state of the pulses, by colour and by temperature must be observed. Indications of associated

fracture must be sought (Fig. 5.2). In cases of serious injury, special attention has to be given to the patient’s general condition as shown by colour, pulse, blood pressure, respiration and other indicators. We follow Rank et al. (1973) in distinguishing between “tidy” wounds as from a knife and “untidy” wounds, such as those seen in open fracture. Soft tissue damage is worse in the latter; nerves and vessels are often

Fig. 5.1  This motor cyclist struck his shoulder against a traffic bollard. There is bruising and swelling of the left shoulder, neck and upper arm. Total avulsion.

R. Birch, Surgical Disorders of the Peripheral Nerves, DOI: 10.1007/978-1-84882-108-8_5, © Springer-Verlag London Limited 2011

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Fig. 5.2  The Platt lesion. A 64 year old woman avulsed the fibular styloid standing up from a chair. The common peroneal nerve was ruptured.

Fig. 5.3  Bullet wound of divisions of the sciatic nerve in the thigh. The common peroneal nerve (above) was transected and repaired (neurotmesis). The tibial nerve (below, sling) recovered spontaneously (axonotmesis).

subjected to traction. In penetrating missile wounds it is important to distinguish between the shot gun, the hand gun or rifle and the fragment (Fig.  5.3–5.5). The immensely destructive effect of a close range shotgun injury is much more than that of wounds from more distant discharge. This fact was recognised by Stewart (Stewart and Birch 2001) who classed penetrating missile wounds of the brachial plexus into high energy transfer (HET) and massive energy

Fig. 5.4  Close range shot gun blast to the posterior triangle of the neck. There was rupture of the first part of the subclavian artery.

transfer (MET) injuries. Wounds from bomb fragments and shell splinters have some of the characteristics of shotgun injury, though on a larger scale and with a higher velocity. The International Committee of the Red Cross (ICRC) wound classification, described by Coupland (1993), has enhanced the understanding of the treatment of war wounds. Coupland writes “the surgical task presented by any wound

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147

Fig. 5.5  Penetrating missile wound. A military rifle bullet entered in the front of the shoulder, passed through the quadrilateral tunnel, destroying the circumflex nerve and posterior circumflex artery and exited posteriorly destroying the infraspinatus and much of the overlying skin.

depends on the wound severity i.e. the degree of tissue damage, and also the structure (s) that may have been injured. Recognition of this demands a clinical classification of wounds that is based on the features of the wound and not on the weaponry or the presumed velocity of the missile.” The system scores certain features of a wound: the maximum diameter, in centimeter, of the entry (E) and of the exit(X) wounds; the presence and the size of the cavity (C); the presence of a fracture (F) and the extent of comminution of that fracture; injury to a vital structure which may be the dura, the

pleura, the peritoneum, or a major vessel; and the retention of metallic fragments (Tables 5.1 and 5.2). The wounds are graded according to the amount of tissue damage by the E, X, C, and F scores into low energy transfer, high energy transfer and massive wounds, and then typed according to the structures injured. The wound is then placed in 1 of 12 categories by grade and type. We are indebted to Colonel Michael Stewart FRCS and his colleagues in the RAMC, Major K Brown, Major W Eardley FRCS, Major A Ramasamy FRCS, and for their extensive advice about the

Table 5.1  The red cross wound classification (Drawn from Coupland 1993). 1. The Field Wound Score

2. Subsequent Analysis. (A) Extent of Tissue Damage

E

Entry

diameter of entry wound, in centimeter

Grade 1

E + X < 10: CO, F0 or F1

Low energy transfer

X

Exit

diameter of exit wound, in centimeter

Grade 2

E + X < 10: c0 or F2

High energy transfer

C

Cavity

Grade 3

E + X > 10: c0 or F2

Massive energy transfer

F

V

M

Fracture

Vital Structure Metallic body

0

wound cavity too small to take two fingers

1

Wound cavity admits two or more fingers

0

No fracture

1

Simple fracture

2

Comminuted fracture

0

No injury to brain, vessels or viscera

1

Injury to the above

0

No metal fragment seen on radiograph

(B) Type Of Wound According To Structure Injured

ST

F0 and V0

F

F1 or F2 and V0

1

One fragment

V

F0 and V1

2

More than one fragment

VF

F1 or F2 and V1

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Surgical Disorders of the Peripheral Nerves

Table 5.2  The 12 categories of wounds (Drawn from Coupland 1993). Grade I Grade II Grade III ST

Small simple wounds

2ST

3ST

F

1F

2F

3F

V

1V

2V

3V

VF

1VF

2VF

3VF Large wounds threatening life or limb

Fig. 5.6  Military rifle bullet, before debridement (above) and after debridement (below). Type 3F wound: E3, X8, C2, F2. The common peroneal nerve recovered (axonotmesis) (Courtesy of Major K Brown RAMC).

use of the IRCR classification in battle casualties and also for their providing numerous examples. They point out that the classification is somewhat defective in the analysis of severe blast injuries (Figs. 5.6 and 5.7).

5.1 Associated Symptoms and Signs The early symptoms of acute nerve injury are abnormal sensations, alteration or loss of sensibility, weakness, motor paralysis, impairment of function and sometimes pain.

Sometimes the patient is aware of warming and dryness of all or part of an extremity. Abnormal sensations or paraesthesiae, most often “pins and needles,” are usually associated with continuing noxious process. They are of course commonly associated with recovery of a transient conduction block. Their mechanism in that process was ingeniously explored by Merrington and Nathan (1949). Increasing pain and deepening of the nerve lesion signifies continuing noxious process. The patient’s failure to observe warming and anhidrosis is, regrettably, often shared by the examining clinician (Fig. 5.8). Pain, though not always present, is a most important symptom. It may be immediate or delayed; episodic or continuous; of all grades of severity. Its occurrence after injury often means that the noxious process is continuing, as when a nerve is stretched over a bony projection, compressed by a hard object or constricted by, for instance, a suture. It is a regular feature of injury caused by critical ischaemia. Such pain is neurostenalgia. It indicates not only that the noxious process is continuing but also that the lesion of the nerve may be deepening and it is an important indication for operation. Neuropathic pain is never easy to recognise in the injured patient who is probably confused, distressed and in pain. It can be distinguished from the pain of fracture or dislocation by loss of sensation, by painful, spontaneous sensory symptoms, (dysaesthesiae), expressed in the territory of the nerve, and by lancinating or shooting pain radiating into the distribution of that nerve. In some patients neuropathic pain is so severe that it overwhelms the pain from a fracture. Mothers may advise the clinician that the pain is worse than that of child birth. A constant crushing, bursting or burning pain in the otherwise undamaged hand or foot indicates serious and continuing injury to major trunk nerves. Progression of sensory loss with a deep bursting or crushing pain within the muscles of the limb, often accompanied by allodynia indicates impending critical ischaemia until proven otherwise. Two rare and easily recognizable forms of severe pain quite often begin soon after injury: they are (1) the pain associated with intradural damage to nerve roots, particularly in traction lesions of the brachial plexus, and (2) causalgia. These, and related matters are discussed in Chaps. 9 and 12. Examination should enable the clinician to extend the knowledge afforded by the history and the narrative of symptoms to permit accurate diagnosis to be made. All findings should be recorded in such a manner that the record will be intelligible later not only to the examiner but also to others. Unfortunately, the signs of acute nerve injury have to be sought at a time when the patient may be the least able to co-operate in an examination; soon after wounding, when there is likely to be distress and when the general condition may be affected by loss of blood and other injuries. The examination often has to be done in the often unfavorable

Clinical Aspects of Nerve Injury Fig. 5.7  A massive blast injury to the buttock and thigh. E more than 20, X0, C1, F0, V0. The profunda femoris artery was intact, the sciatic nerve recovered (axonotmesis) (Courtesy of Major K Brown RAMC).

Fig. 5.8  Sympathetic paralysis seen within a few days of transection of (left) the median nerve at the elbow and (right) the tibial nerve in the thigh.

149

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Surgical Disorders of the Peripheral Nerves

Figures 5.9–5.32 show the sensory loss after transection, rupture, or avulsion of spinal and peripheral nerves Fig. 5.9   Complete avulsion of C4–T1 in two patients.

surroundings of an accident department. The patient may be a distressed child; an older child, an adolescent or an adult patient who may be affected by drink or drugs or by both. When the lesion has been inflicted by a surgeon or anesthetist, the patient’s response is likely to be distorted by post operative pain, by the effects of recent general anaesthesia or by sedative or analgesic drugs. The patient’s ignorance of medical process and even his or her trust in “the doctor” may lead him or her to think that pain and paralysis after operation is just something to be expected. That faith or even deference may inhibit him or her from voicing a complaint. These are no conditions for a quiet and comprehensive “neurological examination,” yet this is the time when the fact of nerve injury must at least be recognised if the best result is to be obtained from treatment. The examiner should at all times bear in mind that if there is a wound over the line of a main nerve and if there is any suggestion of loss of sensibility or impairment of motor function in the distribution of that nerve, it must be regarded as having been cut until and unless it is proved otherwise. Sensory loss is determined by response to light touch and pin prick and if circumstances permit, the patient outlines the area of sensory loss which is marked by a black skin marker pen. The surrounding zone of incomplete sensory loss can be similarly marked in red, and the limb then photographed (Figs. 5.9–5.32). Selected muscles are examined. The patient lying supine is usually able to demonstrate

Fig. 5.10  Sensory loss in avulsion of C5-T1. C4 innervates the skin of the outer aspect of the shoulder; T2 innervates the skin of the inner aspect of the arm.

Clinical Aspects of Nerve Injury

151

Fig. 5.11  Avulsion of C4, C5, C6, C7.

Fig. 5.13  Avulsion of C5. The area of sensory loss is usually larger than that seen after rupture of the circumflex nerve (see Fig. 5.19).

Fig.  5.12  In this patient with T6 spinal cord lesion and on clinical examination, C5 and C6 lesion, operation showed avulsion of C5, C6 and C7.

activity in serratus anterior by lifting the shoulders away from the couch, by “forward shrugging.” A radiograph of the chest will detect, inter alia, elevation of the hemi diaphragm. It is usually possible to observe the presence of flexion and abduction at the shoulder, flexion and extension of the elbow and wrist and flexion and extension of the fingers. The radial, median and ulnar nerves are tested by asking the patient to form an “O” between the thumb and little finger, to give the “thumbs up,” and to open and close the fingers like a fan. It should be possible, by gentle persuasion, to observe active flexion and abduction at the hip,

extension at the knee, and extension and flexion at the heel and toes. The palmar and plantar skin is scrutinised for changes in colour and in sweating. Although this may be more difficult in pigmented skin such changes are detectable. The standard tendon reflexes are examined. A more detailed examination is possible when the patient’s condition is stable, and when pain has been controlled. Limb dominance, occupation, marital status, underlying disease or continuing medication are recorded if this has not already been done. Neuropathic pain is by now somewhat easier to recognise, for this is less responsive to analgesics than is pain from skeletal injury.

5.2 Recognition of the Level and the Depth of Injury In the absence of wounding clinicians should be able to arrive at an accurate diagnosis of the level and depth of a lesion by clinical examination. A sound grasp of the level of the branches of the trunk nerves and of the contribution to those nerves coming from individual spinal nerves is a prerequisite. “Aids to Examination of the Peripheral Nervous System,” originally produced by the Medical Research Council and now in its

152

Surgical Disorders of the Peripheral Nerves

Fig. 5.14  Rupture of C5 and C6. Sensory loss does not extend to the thumb and the index finger.

Fig. 5.16  The area of sensory abnormality after section of the lateral cord in the axilla. As in Fig.  5.15, there was no complete loss of sensation. Fig. 5.15  Transection of C8 and T1. The area of sensory disturbance extends into the arm (medial cutaneous nerve of arm).

fourth edition under the direction of Michael O’Brian (2000), is essential reading. This slim volume should be in the possession of all doctors engaged in injury work. It easily fits into a pocket, but now that white coats have been abolished perhaps nurses and therapists who, of course, continue to wear their uniforms, might be invited to carry the volume.

To take one example, the level of injury to the posterior cord and the radial nerve can be determined by examining teres major (inferior subscapular nerve), latissimus dorsi (thoraco dorsal nerve), and deltoid (circumflex nerve). The nerves to the long head of triceps leave the main trunk proximal to the spiral groove. Those innervating the medial head of triceps pass away from the radial nerve at the entrance to and in the first part of the spiral groove whereas those innervating the lateral head of the muscle leave the main nerve

Clinical Aspects of Nerve Injury

still more distally. Paradoxically, the contribution from the spinal nerves is in reverse order: the medial head is usually innervated by the eighth cervical nerve, the long head by the seventh cervical nerve and the lateral head by the sixth cervical nerve. The nerve to brachioradialis consistently passes away from the trunk about three finger breadths above the lateral epicondyle; the nerve to extensor carpi radialis longus

Fig. 5.17  Rupture of the posterior divisions of the trunks of the brachial plexus deep to the clavicle.

Fig. 5.18  Rupture of the medial cord in the axilla. Loss of sensation was confined to the forearm and hand. There is sympathetic paralysis in the ulnar three fingers.

153

comes off about a centimeter more distally. One nerve to extensor carpi radialis brevis leaves the main nerve about 1 cm above the lateral epicondyle and another at the level of the branching into superficial radial and posterior interosseous nerves. Lesions of the sciatic nerve are often, incorrectly, placed at the knee, to the common peroneal nerve. These errors are prevented by examining gluteus medius, gluteus maximus and biceps femoris. Some of the most serious mistakes in the diagnosis and treatment of patients with injured nerves are made because the examiner fails accurately to assess the depth of injury, failing to distinguish between degenerative and non-degenerative injury and to estimate the extent in the nerve of each type of lesion. Some atavistic urge seems to cause clinicians to play down the severity of nerve injury. Perhaps beneath this urge there is a feeling that if there is a serious injury, much hard and possibly unrewarding work is going to be required. The tendency is of course particularly marked in cases of closed injury and of injury during operation. Too often the mantra “Neuropraxia” is pronounced: too often the soothing words “just some bruising of the nerve” are uttered. The diagnosis of the depth of the injury depends on the history and signs and on the simplest electrical examination. Serious injuries are likely to cause serious lesions of nerves. Severance of a nerve with a cutaneous sensory component will lead to well-defined loss of sensibility and to complete motor, sudomotor and vasomotor paralysis in the distribution of the nerve. Simple conduction block is likely to produce a patchy loss of sensibility and a patchy motor loss.

154

Surgical Disorders of the Peripheral Nerves

Fig. 5.20  Rupture of circumflex and musculocutaneous nerves. Fig. 5.19  Rupture of the circumflex nerve.

Further, it is likely to bear more heavily on the large axons than on the small ones: vibration sense and sensibility to light touch are likely to be impaired, whereas pain sensibility may be unaffected. If the axons are damaged (degenerative lesion), stimulation of the nerve below the level of the lesion 6 days after injury will not elicit a motor response. (Landau 1953, Gilliatt and Taylor 1959). If the axons are intact (conduction block) stimulation will evoke a motor response. It will, equally, be possible to stimulate and record from the nerve below the level of the lesion. This simple but rarely used test can permit the early recognition of the depth of the lesion. A firm diagnosis of neurapraxia should never be made unless 1 week after the injury stimulation of the nerve below the level of the lesion produces a motor response.

5.3 Signs The early signs of nerve injury are alteration or loss of sensibility, weakness or paralysis of muscles; vasomotor and sudomotor paralysis in the distribution of the affected nerve or nerves, and abnormal sensitivity over the nerve at the point of injury. For the reasons given, testing of sensibility is often difficult soon after wounding, or when nerve injury is associated with fracture of a long bone. In addition, it may even be

that for a few hours there is conduction across a clean transection without retraction of nerve ends (Smith and Mott 1986). The actions of some muscles can be simulated by the actions of others, so that the fact of paralysis can be missed in the early stages after nerve injury. However, one almost infallible sign is always present in the first 48 h after deep injury of a nerve with a cutaneous sensory component: because of the affection of small as well as of large fibres, the skin in the distribution of the affected nerve is warm and dry. (Bonney 1983, Birch 1986) In the small child, there may be an abnormal posture of the denervated digits (Fig. 5.33). Canale et al. (2000) describe a sign for anterior interosseous palsy in children. When the child is asked to bend the index finger they do it with the other hand. Other early signs which indicate a deep injury to a nerve include changes in texture of the skin rather like “goose pimples” development of a skin rash, and hypersensitivity surrounding the area of anaesthesia. Another good test for nerve injury in small infants is the “immersion test”: the injured hand or foot is placed, for a few minutes, in warm water. The skin of the denervated digits fails to wrinkle. When there is no breach of the skin and the injury of the nerve is caused by pressure or distortion, there is usually differential affection of fibres. Szabo et  al. (1984), working with volunteer human subjects on the effects of an acute rise of pressure on the median nerve in the carpal tunnel, plainly showed that vibratory thresholds were the earliest measure of a decrease in nerve function. The largest fibres were the most susceptible to pressure. The use of vibratory, or

Clinical Aspects of Nerve Injury

155

Fig. 5.21  Sensory loss in two cases of rupture of the musculocutaneous nerve. Both patients were able to supinate the forearm fully; the power of elbow flexion was around 30%.

Fig. 5.22  Two examples of high lesion of the radial nerve. Right: there is early recovery into the wrist extensors after repair.

pressure stimuli as a non-invasive diagnostic test may, as the authors suggest, have a significant role in clinical work and in research. The smaller ones are spared, so that there is rarely any sudomotor or vasomotor paralysis, and delayed pain sensibility is preserved. We have however seen cases in which pressure paralysis was deep enough to affect the autonomic fibres. In one young girl whose attempt at suicide with narcotic drugs led to prolonged pressure on the tibial and

common peroneal nerves, there was prolonged vasomotor and sudomotor paralysis of the foot. In the case of intraneural hemorrhage or injection the situation is different: small fibres are early affected, sometimes, as with injection of local anaesthetic, before the large fibres. When the injected fluid is itself noxious there is early affection of all sizes of fibre. Peripheral ischaemia is usually signalled by pain, but in cases in which the vascular injury is

156

Surgical Disorders of the Peripheral Nerves

Fig. 5.25  Section of the median and the palmar cutaneous nerve at wrist. Fig. 5.23  Transection of median, ulnar, medial cutaneous nerve of forearm, and brachial artery in the arm of a 14 year old boy. Note the extent of skin innervation provided by the superficial radial and lateral cutaneous nerves of forearm. The intact radial nerve permits a sort of grasp.

associated with fracture, the significance of that pain may not be recognised. Ischaemia affects first the large fibres: discriminative sensibility and vibration sense are first affected (MacKinnon and Dellon 1988) It is not easy to test these modalities when ischaemia is developing because of damage to a main vessel associated with a fracture of a long bone, but if action is not taken until superficial sensibility is lost, it will come too late.

5.4 Tinel’s Sign

Fig.  5.24  High median nerve injury: no active flexion of the index finger and thumb.

Tinel (1915, 1917) was probably the first to draw attention to the indication of the “growing point” of the regenerating axons signalled by the production of paraesthesiae by tapping over the course of the nerve. Buck-Gramcko and Lubahn (1993) remind us that Tinel made the observation at about the same time that Hoffman working on the other side of the Western Front, made a similar discovery (Hoffman 1915a, b). Properly, the sign should be called the “Hoffman-Tinel sign.” Tapping the skin over the course of a recovering nerve reveals the presence of regenerating axons by the production of paraesthesiae in the sensory distribution of the nerve. Rothwell’s translation of Tinel (1917) says: “When compression or percussion is lightly applied to the injured nerve trunk, we often find, in the cutaneous region of the nerve, a creeping sensation usually compared by the patient to that caused by

Clinical Aspects of Nerve Injury

157

Fig. 5.26  A typical area of loss of sensibility after division of the median nerve at the wrist, sparing the palmar cutaneous branch.

Fig. 5.27  The area of sensory loss and “clawing” of little and ring fingers after division of ulnar nerve in the forearm.

electricity.... The “formication sign” is thus of supreme importance since it enables us to see whether the nerve is interrupted, or in the course of regeneration; whether a nerve suture has succeeded or failed, or whether regeneration is rapid and satisfactory, or reduced to a few insignificant fibres. All clinicians will recognise this sign. The element of unreliability is introduced by the fact that some of those regenerating axons are not on their way to any target. However, these

points can be stated: (1) a strongly positive Tinel sign over a lesion soon after injury indicates rupture of axons or severance of the nerve; (2) in favorable degenerative lesions (axonotmesis) or after repair which is going to be successful, the centrifugally moving Tinel sign is persistently stronger than that at the suture line; (3) after repair which is going to fail, the Tinel sign at the suture line remains stronger than that at the growing point; (4) failure of distal progression of

158

Surgical Disorders of the Peripheral Nerves

Fig. 5.28  The area of loss of sensibility in two cases of injury to the femoral nerve at, or proximal to the groin crease.

Fig.  5.29  Cutaneous distribution of the sacral plexus. Left showing area of sensory loss after closed fracture/dislocation of sacro-iliac joint. Right showing area of loss of sensibility after open fracture/dislocation of the pelvis. The muscles of the buttock are wasted.

Fig.  5.30  The area of sensory loss after transection of sciatic nerve in the thigh is confined to the leg and foot.

Clinical Aspects of Nerve Injury

159

Fig. 5.33  Infant’s hand 24 h after section of the palmar nerves to the index finger and thumb. Note that the anaesthetic digits are held out from the others. There was no tendon injury.

Fig. 5.31  Area of sensory loss after high division of common peroneal nerve. Note the pressure sore caused by a conventional ankle-foot orthosis.

conduction block for, at least, a significant number of axons within the nerve. It is important always to remember Tinel’s own advice that a positive sign should not be confused with the “hypersensitivity seen in some cases of neuralgia” (Tinel 1917). The Tinel-like sign elicited by percussion over schwannoma or over nerves in the early stages of entrapment neuropathy, such as the ulnar nerve at the elbow or the median nerve at the wrist, does not indicate that axons have been ruptured, rather that nerve fibres have become sensitised because of focal demyelination and changes in the expression of voltage gated ion channels at the level of lesion.

5.5 Eliciting the Tinel Sign in Closed Lesions

Fig. 5.32  Area of sensory loss after interruption of the deep division of the common peroneal nerve. Left, showing the leg of a 29 year old man in whom severe “compartment syndrome” was overlooked after intramedullary nailing of closed fracture of tibial shaft. The anterior compartment was infarcted and it was excised. Right, showing the area of sensory loss after transection of the deep division of the common peroneal nerve by a knife.

the Tinel sign in a closed lesion indicates rupture or other injury not susceptible of recovery by natural process; (5) a positive Tinel sign means the lesion is degenerative, not a

The examiner’s finger percusses along the course of the nerve from distal to proximal starting well below the presumed level of lesion. The patient is asked to say when the advancing finger elicits a wave or a surge of pins and needles or abnormal sensations, which may be painful, into the distribution of the nerve which must be clearly indicated by the examiner. A positive Tinel sign indicates that axons are ruptured at that level. The sign can be regularly elicited on the day of injury in a conscious patient. The level of the sign should be measured from a fixed point and the distance entered into the records. In the upper limb, we use the tip of the coracoid, the medial or lateral epicondyle and the styloid process of the radius and in the lower limb, the tip of the greater trochanter, the tip of the styloid process of the fibula and the lower points of the medial and the lateral malleoli, whichever is appropriate. At times the examination is painful and patients need to be warned about that. Percussion over the swollen posterior triangle of the neck in cases of multiple

160

Surgical Disorders of the Peripheral Nerves

Fig. 5.34  Static and progressing Tinel’s signs. A 43 year old woman sustained a complete and very painful, lesion of the common peroneal nerve from the kick of a horse. There was a strong, painful, Tinel sign at the level of lesion at the time of exploration 10 weeks after injury. The nerve was deeply compressed by scar from which it was removed. Her pain was abolished. The rate of progress of the Tinel sign for the superficial and the deep divisions of the nerve was about 2 mm a day. There was complete recovery.

avulsion usually elicits painful sensory phenomena which do not radiate into the dermatomes of the injured nerves. A strongly positive Tinel sign indicates to the clinician the level of lesion, and also the depth of lesion. Axons are ruptured where the percussing finger evokes radiation of sensations into the distribution of the nerve under examination. Subsequent examinations may provide evidence that the lesion is regenerating by demonstrating centrifugal progression of the sign which becomes progressively stronger at the distal rather than at the proximal level of sign (Fig. 5.34). Kato (Kato and Birch 2006) examined the evolution of Tinel’s sign in 137 nerves injured by closed fracture or dislocation. Recovery was good in 69 of the 86 nerves where the Tinel sign progressed. or where no Tinel sign was present. A static Tinel sign was one of the indications for operation in 43 of 51 nerves. Thirty-two were repaired and the other 19, which were embedded in callus or caught within a fracture or joint, could not have recovered spontaneously. Table 5.3 shows the

value of a static or advancing Tinel sign in predicting recovery in degenerative lesions after closed injury to the common peroneal, the radial and tibial nerves. An advancing sign proved misleading in 18 nerves. In most of these the distal muscles had been damaged by ischaemia so that the regenerating axons arrived at target organs which were irredeemably fibrosed. One case, of a radial nerve damaged by closed fracture of the humeral shaft was initially seen by one of us (RB) who predicted recovery because the Tinel sign was advancing. Marco Sinisi noted that there was discrepancy between the advancing sign and the failure of recovery of brachio radialis and when he exposed the nerve he found that about three quarters of it was embedded in the fracture; the surviving portion was destined for the superficial radial nerve. Tinel’s sign is particularly valuable in the diagnosis of post ganglionic rupture of the spinal nerves of the brachial plexus (Landi and Copeland 1979). If percussion in the posterior triangle induces radiation as far as the elbow then rupture of C5 is likely; rupture of C6 is anticipated when radiation extends to the lateral forearm and thumb and when radiation extends to the whole hand, especially to the dorsum, then rupture of C7 is expected. Table 5.4 summarises the role of Tinel’s sign in the early diagnosis of rupture of the spinal nerves in 100 consecutive cases of closed traction lesions of the supraclavicular brachial plexus. Most patients were examined within 14 days of injury: a positive sign was found in nine cases of lesion to C5 and C6 yet these nerves were found avulsed. Irradiation into the territory of the supraclavicular nerve (C4) was sometimes wrongly ascribed to a rupture of C5 and irradiation from percussion over a rupture of C5 sometimes extends to the forearm suggesting rupture of C6. Nineteen spinal nerves were found to be ruptured even though no Tinel sign was detected. These stumps were concealed by torn muscle or haematoma, and the level of rupture was close to the foramen. Absence of the sign over a peripheral nerve which is not working, suggests conduction block. The absence of the sign in closed traction lesion of the supraclavicular brachial plexus indicates one of two things: that the nerve has been avulsed or the lesion is conduction block. The distinction between these two is usually straight forward.

Table  5.3  Tinel’s sign as a guide to prognosis in 339 consecutive cases of degenerative lesions in closed injuries to the common peroneal (171 cases), the radial (139 cases) and the tibial (29 cases) nerves examined 2000–2007. Tinel Sign – Progressing Tinel Sign – Static Spontaneous Misleading – no, or poor, Spontaneous recovery Rupture or other lesion not suscepRecovery spontaneous recovery tible to recovery by natural process Common peroneal nerve with divisions

84

12

0

75

Radial nerve

103

5

0

31

Tibial nerve

16

1

0

12

TOTAL

203

18

0

118

Clinical Aspects of Nerve Injury

161

Table 5.4  Tinel’s sign in closed traction lesions of the brachial plexus in 100 adult patients examined and operated 2004–2005. Tinel sign absent Spinal Tinel sign present (358 nerves). Findings nerves (142 nerves). Findings at operation at operation Intact

Rupture

Avulsion Intact

Rupture Avulsion

C5

1

58

4

0

10

27

C6

0

41

5

10

6

38

C7

0

24

0

40

2

34

C8

0

4

0

45

0

51

T1

0

TOTAL 1

4

1

52

1

42

131

10

147

19

192

5.6 Tinel’s Sign and Recovery Henderson (1948) made serial observations on Tinel’s sign in 400 cases of nerve injury in his fellow prisoners of war. Henderson thought that the behaviour of the sign provided certain indications of satisfactory, or unsatisfactory, spontaneous regeneration by 4 months after the injury so that “a strongly positive sign at the level of the lesion, which gradually diminished as the sensitivity of the distal part of the nerve increased, progress peripherally, and faded centrally, was a certain indication that satisfactory spontaneous regeneration was in progressed. Poor recovery, attributed to great axonal confusion at the site of injury, was observed in cases where the sciatic lesion remained sensitive and a positive sign developed in the most proximal muscles within the distribution of the damaged nerve.” The situation is much more straightforward for the clinician examining main nerves damaged by closed fractures or dislocations in civilian practice and it is usually possible to distinguish between axonotmesis and neurotmesis by between 4 and 6 weeks from the day of the injury in closed lesions of the radial, median, ulnar, common peroneal and tibial nerves. Ruth Bowden found that clinically detectable recovery was evident by 64 days in 14 cases of axonotmesis of the radial nerve (Bowden and Scholl 1954). An advancing Tinel sign may be found when only a few nerve fibres are regenerating as in cases where trunk nerves are entrapped within a fracture or joint. Useful function will not return if the target organs are damaged by fracture or sepsis or, above all, by ischaemia. An advancing Tinel sign should be treated with caution in lesions of the common peroneal nerve, where some degree of post ischaemic fibrosis of the anterior compartment is found in about one-fifth of cases. Centrifugal progress of the sign is often unreliable in predicting recovery of lesions of the sciatic nerve incurred during arthroplasty of the hip. Most of these are mixed lesions, some nerve fibres are intact, others sustain conduction block whilst many more have sustained degenerative lesions which may or may not

be naturally favorable. Tinel’s sign can be detected over such “motor” nerves, as the posterior interosseous, but it is more difficult to elicit the sign over deep seated nerves such as the circumflex, the eighth cervical or first thoracic nerves. The sign advances more rapidly in degenerative lesions of naturally favorable prognosis (axonotmesis) than it does after repair of a nerve. A rate of progression of about 2 mm a day is usual. Tinel’s sign progresses more rapidly after repair of proximal lesions, particularly so when the repair is done urgently. Progression at the rate of 3 mm a day is by no means unusual after urgent repair of the supraclavicular brachial plexus in the segment from the neck to the upper arm. Thereafter, progress slows. Similar rates of advance are seen after urgent repairs of the sciatic nerve wounded in the buttock. These rates are close to those recorded by Bowden and Scholl (1954). Bowden and Scholl offered a caveat: “the choice of time for exploration of an injured nerve cannot be based on estimates of rates of recovery alone; in each individual case, all clinical factors must be taken into consideration. Where there is any reasonable doubt about the state of the nerve or the integrity of a suture line, operation should not be delayed since in experienced hands exploration is without harmful effect.” The distance between the sign and a suitable fixed bony point is recorded in the case notes at every examination. The rate of progress of the sign in a healing nerve matches that of the slow anterograde axonal transport system.

5.7 Examination of Sensibility Highet proposed a system for the examination of sensibility and muscle power in a memorandum submitted to the Nerve Injuries Committee of the Medical Research Council in 1941 and this, with some modifications, was adopted by that Committee. The Medical Research Council (MRC) method of recording sensibility offers a reasonable method for recording and measuring progress. As is the case with all such schemes it has obvious disadvantages, but no comprehensive method has yet been devised that does not have the overwhelming disadvantage of extreme complication (Table 5.5). So far as possible, sensation to light touch and pin prick, vibration sense and position sense should be tested, and the area of skin affected should be recorded. The timing of the response to pin prick and the ability to localise to the area of stimulation should if possible be noted. Anhidrosis is easily perceptible; vasomotor paralysis is shown by warming of the skin and, in the finger tips, by capillary pulsation. The examiner should use the pulp skin of his or her fingers, not back of the hand, which is, of course, less densely innervated. Our methods: The modalities routinely tested are light touch, temperature, position sense, pain, two point discrimination,

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Table 5.5  Sensory recovery. The original grading by Highet (1941) Stage 0

Absence of sensibility in the autonomous zone of the nerve

Stage 1

Recovery of deep cutaneous pain sensibility within the autonomous zone

Stage 2

Return of some degree of superficial pain and tactile sensibility within the autonomous zone

Stage 3

Return of superficial pain and tactile sensibility throughout the autonomous zone with the disappearance of over-response

Stage 4

Return of sensibility as in Stage 3 with the addition that there is recovery of two-point discrimination within the autonomous zone

The Medical Research Council System by Seddon (1954) S0

Absence of sensibility in the autonomous area

S1

Recovery of deep cutaneous pain sensibility within the Autonomous area of the nerve

S2

Return of some degree of superficial cutaneous pain and tactile sensibility within the Autonomous area of the nerve

S3

Return of some degree of superficial cutaneous pain and tactile sensibility within the Autonomous area with disappearance of any previous over-reaction

S3+

Return of sensibility as in Stage 3 with the addition that there is some recovery of two-point discrimination within the Autonomous area

S4

Complete recovery

localisation and pressure. The stereognosis test has been used since 1975 (Wynn Parry and Salter 1976). Light touch: A wisp of cotton wool is moved lightly across the area under test. Temperature: Metal tubes are used: one contains cold water, the other, warm at about 35°C. These are applied alternately to the area under test. Position sense: All nearby joints, other than the one being tested, must be stabilised. The patient is first shown the direction in which the joint is being moved. Then, with eyes closed, he or she is asked to indicate the direction in which the joint is being moved. Pin prick: A bluntened pin is lightly applied to the skin and the patient is asked to say whether it feels sharp or blunt. Two point discrimination: This is done with the blunted points of a compass or the ends of a paper clip or with a special device. The patient is first instructed: “I shall touch your finger now with one point; now with two. If you feel one, say “one”; if you feel two, say “two”; if you are in doubt, say “one.”” Then, with closed eyes, the patient attempts distinction between one and two points. Two point discrimination is valuable because it indicates the degree of reinnervation of slowly adapting receptors. Of course, Highet (1941) used the test in his system of sensory grading. It is subject to limitations. The patient easily gets confused; it is difficult or impossible to ensure that the same

pressure is used throughout the test. Brand (1985) showed that even skilled clinicians used, during the test, pressures varying from 4 to 40 g/unit area. Such variability leads, of course, to error when results of different observers are compared. Bell and Burford (1982) using transducers and oscilloscopes, found that the difference between the pressure applied to one point and that applied to two easily exceeded the resolution threshold for normal sensitivity. They concluded that two point discrimination had poor validity. Refinements of the method were introduced by von Greulich (1976) and by MacKinnon and Dellon (1985). These were based on the use of as ring with circumferential prongs set at varying intervals. Useful instruments had, of course, been developed previously by Mannerfeldt. Dellon (1978) introduced the concept of moving two-point discrimination. The patient is asked to move his or her finger across a number of ridges separated by varying intervals. He or she then identifies the shortest interval appreciated, which is invariably less than that recorded by the static test. We think that this ingenious method is, to a certain extent, artificial since normal sensibility requires handling of an object between thumb and finger – a process that excites a far greater range of sensory receptors. However, Novak and MacKinnon (1999) found that a high degree of inter observer reliability between moving two point discrimination, static two point discrimination, and Semmes Weinstein filament tests. Localisation: We use the chart devised by Wynn Parry and Salter (1976) in which the hand is divided into different numbered areas. The blindfolded patient is asked to point to the area being touched, and this is recorded on the card. Thus, if a touch on the tip of the index finger is felt as a touch on the base, the number of the former area is recorded on the latter area on the chart. The localisation and texture and shape recognition charts were brought to the Peripheral Nerve Injury Unit by Christopher Wynn Parry when he joined the staff at the Royal National Orthopaedic Hospital as Director of Rehabilitation in 1975 (Figs. 5.35 and 5.36). Pressure: The padded blunt end of a pencil is used to indent the skin only lightly. We also use Von Frey hairs and the weighted pins (5 and 10 g) developed by Ruth Bowden. Recognition of textures and shapes: Riddoch (1940) asked patients to recognise different coins by touch. Porter (1966) asked patients to recognise steel type letters, in dimension 1.0 by 0.8  cm. The letters must be identical in reverse and H, O, U, V, Y are used. The “pick up” test (Moberg 1958) is, of course, a measurement of function as well as of sensibility. So is the assessment of ability to recognise objects, the importance of which we believe was first recognised by Wynn Parry and Salter (1976) and used at RAF Chessington and then subsequently in the PNI Unit at the Royal National Orthopaedic Hospital(Wynn Parry 1981). The blindfolded patient is presented with a series of objects of differing shape, texture and surface character, and asked to distinguish them. The number correctly identified and the

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Fig. 5.35  Chart recording improvement of the measurement of ability to recognise and to localise at intervals after repair of median nerve at wrist.

Fig. 5.36  Another example of recovery of recognition and localisation after repair of median nerve.

time taken are recorded. Later, common textures and small and large objects in daily use are presented for recognition. Rosen and Jerosch-Herold (2000), Jerosch-Herold (2000, 2005) thought that the shape and texture identification test may provide a better record of regeneration than those for two point discrimination.

5.8 Quantitative Sensory Testing Dyck et  al. (2005) classified methods of measurement of different modalities of sensation into three groups. Semi quantitative sensory tests include the usual techniques which are useful in traumatic neuropathy where there is a

164

normal limb available for control. Quantitative sensory testing (QST) is the use of stimuli which are more precisely quantitative and more rigorously tested but the environment is not controlled. In laboratory QST all aspects of the examination are predetermined, standardised and controlled. Our experience is drawn from the work of Praveen Anand who has examined many hundreds of patients at our joint clinics over the last 20 years, first at the London Hospital and later at Imperial College, London (Anand et  al. 1994, 1996) These investigations confirm the presence and the extent of axonopathy which cannot be detected by standard neurophysiological investigation. Focal, or generalised, neuropathy has been demonstrated in patients wrongly labelled as “complex regional pain syndrome Type 1” (CRPS Type 1) or even as malingerers. Our findings in some patients diagnosed with “CRPS Type 1” provide support for the critique from Oaklander et al. (2006). The differential susceptibility to the lesion between different groups of nerve fibres have been confirmed. The rates of recovery of different populations of nerve fibres have been analyzed in many cases of favorable, degenerative lesion (axonotmesis) and after repair. Profound differences between the infant and the adult have been revealed after repair of lesions of the brachial plexus (Anand and Birch 2002, Htut et  al. 2006). The general assumption that the smallest fibres regenerate more rapidly has been called into question and we have shown that reinnervation of the skin lags far behind reinnervation of skeletal muscle after repair of the brachial plexus in the adult. The methods used are now outlined. Thermal threshold: A thermal threshold testing system (Somedic, Stockholm, Sweden) with a rate of rise in temperature of 1°C/s, is used. The small thermode (15 × 25 mm) is placed at the appropriate site, and the base line temperature is set at a neutral point between 30°C and 32°C. Thermal threshold is determined for cool and warm sensation by four separate consecutive tests for reach modality. The mean difference from base line temperature is recorded as threshold. The patient indicates their recognition of the stimulus by pressing a button. No significant difference has been seen by using either verbal or manual indication of change. “Abnormal” (more than two SD above the mean) values in children are: warm sensation greater than 3.8, cool sensation greater than 2.3; for adults aged between 20 and 30 years, abnormal values are: warm sensation greater than 3.9 and cool sensation greater than 2.6 (Fig. 5.37). Light touch: Thresholds are determined using Semmes Weinstein hairs which are made by A. Ainsworth, University College, London, UK. The number of the hair reliably detected (three or more out of five trials) with the lowest force is recorded and values are then transferred into respective gram values. A threshold to light touch greater than that elicited by the number three filament (0.0479g) is abnormal (Fig. 5.38).

Surgical Disorders of the Peripheral Nerves

Fig. 5.37  Testing of warm and cool thermal thresholds (Courtesy of Dr. Peter Misra).

Fig. 5.38  Monofilament perception to assess punctate touch (Courtesy of Dr. Peter Misra).

Vibration sense: The threshold is measured with a biothesiometer (Biomedical Instrument Company, Newbury, Ohio, USA) placed at the distal interphalangeal joint of a

Clinical Aspects of Nerve Injury

Fig. 5.39  Measurement of vibration perception thresholds (Courtesy of Dr. Peter Misra).

digit or over bony prominence in more proximal joints. Three ascending and three descending trials are carried out and values averaged. In children, an abnormal value is more than 8 V; in adults, it is more than 10 V (Fig. 5.39). These are subjective tests, they depend on the patient’s own perception of stimulus. Other methods are used to measure function in the post ganglionic sympathetic efferent fibres and the histamine induced flare response mediated by the axon reflex. Sweating: This is measured in the palm of the hand using an evaporimeter (Servomed, Stockholm, Sweden) in grams per square meter per hour. The instrument has two sensors which measure the relative humidity in an open cylinder at different distances from the skin surface and signals derived from these transducers are computed to provide first, the partial pressure of the water saturation gradient and then the evaporation rate. A value less than 50% of the contralateral hand is considered abnormal (Fig. 5.40). The Histamine induced flare response: The flare induced by the intradermal injection of 0.03 ml of histamine 1 mg/ml is measured by laser Doppler fluxmetry (Fig. 5.41). We have investigated conduction in smaller nerve fibres and in the motor pathways by techniques which supplement classical neurophysiological investigative methods. Contact heat evoked potential stimulator (CHEPS) enables studies of conduction within small sensory fibres (Ad and C fibres). The CHEPS machine (Medoc Ltd., Ramat Yishai, Israel) rapidly stimulates cutaneous small nerve fibres, and resulting evoked potentials can be recorded from the scalp. The machine can be put into a MR scanner so that functional MR images are available. Patients with symptoms of sensory neuropathy have been studied using CHEPS, and the findings compared to other objective measures of small nerve fibres such as the histamine-induced skin flare response and intra-epidermal fibres counts (IEF). CHEPS has been compared with the results of quantitative sensory testing (QST)

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Fig. 5.40  Quantitative sweat testing (Courtesy of Dr. Peter Misra).

Fig.  5.41  Histamine induced flair assessment using laser Doppler scanning (Courtesy of Dr. Peter Misra).

(Atherton et al. 2007). Amplitudes of Ad evoked potentials (mV) following face, arm or leg stimulation were reduced in such patients. The reduced leg skin flare responses correlated

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the level of brachial plexus or spinal cord injury, and in the analysis of the variable susceptibility of different populations of nerve fibres (Figs. 5.42 and 5.43). Conduction in somatic efferent pathways: Transcranial magnetic stimulation (TMS) or transcranial electromagnetic evoked potentials (TCEMEP) is a technique in which the motor cortex is stimulated by a brief electromagnetic stimulus delivered through a hand held magnetic stimulating circular coil. We use single pulse TMS with the Magstim®200 Monophasic stimulator (Novametrix Medical Systems Ltd., Whitland, UK) to assess motor pathways (see Htut et al. 2007). A high power 90 mm coil is placed over the head at the area over the motor cortex or over the dorsal skin of the neck. The evoked motor response can be detected by electrodes placed over the relevant upper limb muscles and the motor action potentials recorded on an EMG machine. Facilitation is used whenever possible; the patient is asked to attempt to contract the muscle from which the recording is made, as this can improve the amplitude of the recorded motor response. Responses from the injured and the contra-lateral (intact) limb can be compared (Fig. 5.44).

with leg Ad amplitudes. In leg skin biopsies, IEF counts were reduced and these also correlated with Ad amplitudes. CHEPS appears to be a sensitive measure, with abnormalities observed in some symptomatic patients who did not have significant IEF loss and/or QST abnormalities. CHEPS thus provides a clinically practical, non-invasive and objective measure and it has proved to be a useful tool for the diagnosis of sensory small fibre neuropathy, in the assessment of

5.9 Examination of Muscles 5.9.1 Some Pitfalls

Fig. 5.42  Contact heat evoked potential studies. The skin is stimulated by a thermode (in this case placed over the forearm) and the evoked potentials are recorded and averaged using an electroencephalographic (EEG) system with appropriate electro-placements and filtering (Courtesy of Professor Praveen Anand and Dr. Peter Misra).

Trick movements. Accuracy of assessment may be impaired by failure to recognise substitution of the action of paralyzed

Cz [uV]

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Fig. 5.43  Findings from contact heat evoked potential stimulation. The evoked potentials recorded from electrodes placed on the scalp.

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Clinical Aspects of Nerve Injury

Fig. 5.44  Magnetic stimulation of, in this case, the brain demonstrates central and peripheral motor integrity and conduction times. Stimulation can also be applied to the neck so that the motor cortex and the motor roots are magnetically stimulated and recordings are made from limb muscles (Courtesy of Dr. Peter Misra).

muscle by the “trick” movement. Such movements are, of course, useful for the patient in providing function when the primary movers are permanently paralyzed. They may be produced by direct substitution, by an accessory insertion, by the “tenodesis effect” or by rebound. It is important for the examiner to palpate the belly of the muscle under examination and at the same time, to palpate the tendon of that muscle. Direct substitution: Most patients with paralysis of the deltoid muscle can, when the spinati and the rotator cuff are preserved, abduct the limb at the gleno-humeral joint. Even the clavicular part of pectoralis major and the long head of triceps can affect abduction when the humerus is rotated laterally by the action of the infraspinatus. When the biceps brachii and the brachialis muscles are paralyzed, the action of the brachioradialis alone often suffices to flex the elbow to, at least, power MRC Grade 4. Of course, the power of gravity suffices to extend the elbow in the absence of triceps. We have seen how a kind of opposition of the thumb can be produced by action of the flexor brevis and abductor longus when the thenar muscles supplied by the median nerve are paralyzed. Strong extension of the fingers can give an impression of an abducting action in the interossei, whilst strong flexion can give the appearance of an adducting action. The interosseous muscles extend the proximal interphalangeal joints whilst the metacarpophalangeal joints are flexed. Unfortunately, there is no substitute for the abductors of the hip. Lesions of the gluteal nerve leave the patient with serious defects in stability of the pelvis and in their gait. Accessory insertion: The abductor and flexor brevis pollicis have insertions to the extensor expansion, so that abduction of the thumb extends the interphalangeal joint, even when the extensor muscles are paralyzed.

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“Tenodesis” action: When the long flexors of the fingers are paralyzed, extension of the wrist produces in them sufficient tension to cause flexion of the interphalangeal joints. It is this action that is exploited in the tenodesis of paralyzed finger flexors to give a grip when the wrist is extended. Rebound: When the antagonist to a paralyzed muscle contracts strongly and relaxes quickly it may appear as a contraction of paralyzed muscles. In paralysis of the common peroneal nerve, the patient can mimic active extension of the toes or active extension at the ankle by strong contraction and sudden relaxation of the flexors. Anatomical variations: Some of these have been described in Chap. 1. T1 provides functional extension of the digits in at least 10% of patients. Powerful extension of the digits is seen in more than one-third of patients in whom C5, C6 and C7 have been ruptured or avulsed. The ulnar nerve frequently sends a branch to the distal medial head of triceps, the radial nerve consistently innervates part of the brachialis and there are commonly variations in the innervation of the small muscles of the hand. Measurement of muscle power: No system for recording of motor power has really superseded that proposed in 1941 by Highet (1954) to the Nerve Injuries Committee of the Medical Research Council (Table 5.6). The scale is non linear. Sharrard (1953) estimated that a lower limb muscle graded as MRC 4, possessed about 40% of normal strength and that a grade 3 muscle was about 15% as strong as normal. Trumble et al. (1995) made objective measurements of muscle power by the use of force transducers; they used the results to “quantitate” the MRC Grades. Thus, they reckon Table 5.6  Motor recovery. The original grading proposed by Highet (1941) Stage 0

No contraction

Stage 1

Return of perceptible contraction in proximal muscles

Stage 2

Return of perceptible contraction in both proximal and distal muscles

Stage 3

Return of function in both proximal and distal muscles to such an extent that all important muscles are of sufficient power to act against resistance

Stage 4

Return of function as in Stage 3 with the addition that all synergic and isolated movements are possible

Stage 5

Complete recovery

The Medical Research Council System by Seddon (1954) M0

No contraction

M1

Return of perceptible contraction in the proximal muscles

M2

Return of perceptible contraction in both proximal and distal muscles

M3

Return of perceptible contraction in both proximal and distal muscles of such degree that all important muscles are sufficiently powerful to act against resistance

M4

Return of function as in Stage 3 with the addition that all synergic and independent movements are possible

M5

Complete recovery

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that Grade M3 represented 17–42% of the function of the healthy muscle, and that Grade M4 represented 66–79%. The use of this technique is, unfortunately, too time consuming for use in most clinical work. Mills (1997) studied the first dorsal interosseous muscle in cases of amyotrophic lateral sclerosis. He found a linear relationship between the degree of wasting and the amplitude of the compound motor action potential (CMAP). That relation was exponential between the MRC Grade and the CMAP: “in effect, a reduction of one point on the scale is associated with, on average, halving of the CMAP amplitude.” Kaufmann (2005) comments:“the proportion of maximum strength required to overcome gravity is markedly different between muscle groups. Therefore manual muscle testing has limited value, particularly in the lower extremity.” Muscles work at about 25% of normal strength during walking, which is more or less equivalent to an MRC Grade of 3+ (Perry et al. 1986). The considerable reserve permits more strenuous activity and provides endurance. The assessment of motor function is extended by methods used to determine the stamina of muscles. The simplest method is to record with a stamina gauge or spring balance the length of time during which the subject can maintain contraction as a standard percentage of his or her maximal strength. Or, repeated contractions are made at maximal strength and the number that can be made before amplitude falls to 50% of the original, is recorded. A standard dynamometer or a sphygmomanometer with an aneroid or mercury gauge may be used. It is preferable to use a size of bulb to fit the size of the hand.

5.9.2 Our Methods We use the instruments devised by Mannerfeldt and made by HC Ulrich (Ulm) (Birch 1989; Birch and Raji 1991, Dunnet et al. 1995). The power of pinch grip is reduced by about one-third in low median palsy, and by nearly three quarters in low ulnar palsy. Power grip is reduced by about one-half in high ulnar palsy and it is as low as 20% in radial palsy, such is the importance of extension of the wrist (Fig. 5.45). A myometer (model D60107MK1. Penny and Giles Transducers, Christchurch, Hampshire) is used for the examination of more proximal muscles. For the shoulder and arm, the patient is seated comfortably with their back erect against the upright of a chair, both upper limbs are held in the same position. The examiner applies force against the arm using the appropriate cup. The amount of force required to overcome the patient’s resistance is noted and recorded as a percentage of the opposite limb. For hip flexion, the patient lies supine, on their side for abduction and for extension prone. Power of extension of the knee is best

Surgical Disorders of the Peripheral Nerves

measured with the patient sitting with the legs over the side of the couch (Fig. 5.46). Although many patients with isolated paralysis of deltoid show a complete range of active movement at the shoulder, the power of forward flexion and abduction is reduced to about 40% of the uninjured side. The power of extension of the shoulder, measured at 90° of abduction, is reduced to as little as 5%. The power of abduction after a “good” result of repair of the circumflex nerve reaches about 60% of the uninjured side. The power of elbow flexion after musculocutaneous palsy is reduced to between 20 and 40% of the uninjured side. It approaches 60–80% of normal after successful repair of the nerve. The power of dorsiflexion of the ankle after “good” results of repair of the common peroneal nerve is around 50% of normal, that of extension of the knee after successful repair of the femoral nerve, about 60% of normal. Although these figures fall short of normal, they are, of course, far superior to the power restored by muscle transfers.

5.9.3 Clinical Examination It is with the large proximal muscles, about the shoulder girdle and about the hip, that serious mistakes are most common. Delay before diagnosis of nerve injury is, in many cases, quite alarming despite the reliability of precise but elementary clinical examination. Thoraco scapular, thoraco humeral, and scapulo humeral muscles. Narakas (1993) described a simple clinical measure, the inferior scapulo-humeral angle (ISHA), which is very helpful in the analysis of injuries to the nerves to these muscles. The inferior scapulo-humeral angle is subtended by the long axis of the humerus and the lateral border of the scapula. The tip of that angle is centred over the glenohumeral joint. It is measured at rest and then with the arm in full active elevation. It measures the range of elevation at the glenohumeral joint (Fig. 5.47). Narakas acknowledged that Inman et  al. (1944) had earlier arrived at this concept. Narakas(1993) measured the inferior SHA in 170 patients with nerve injuries affecting the shoulder girdle, and also in patients with rupture of the rotator cuff. The active inferior SHA was reduced to 30° or less in patients with isolated rupture of the rotator cuff, in cases of suprascapular nerve palsy, or in combined lesions of these nerves with or without concomitant rupture of the cuff. The angle was substantially reduced in lesions of the spinal accessory nerve; it was least reduced in cases of serratus anterior palsy. We have used the method of Narakas since 1993. Its role in the analysis of shoulder deformities in more than 1,500 cases of birth lesion of the brachial plexus is described in Chap. 10. It has been applied in over 800 adult cases of nerve lesions affecting the thoraco-scapular girdle. This simple investigation measures the respective contributions to elevation provided by the

Clinical Aspects of Nerve Injury

169

Fig. 5.45  Measurement of grip and pinch. Top left measuring of pinch grip between thumb and index finger, top right showing the “median power grip” with use of thumb; bottom left showing “ulnar power grip” with thumb excluded; bottom right another method for measuring grip strength.

thoraco-scapular and the gleno-humeral joints. Stiffness of the joints is detected by measuring the passive range which, in the normal limb, lies between 170 and 180°. This simple investigation should be more widely used. Combined lesions of the accessory nerve and the nerve to serratus anterior are, fortunately, rare, for these are crippling and painful (Fig. 5.48). The trapezius muscle is tested by asking the patient to elevate the limb or to press forward against resistance. The lower fibres can be tested by asking the patient to put a hand

behind the back and press it against the trunk. The rhomboids are tested by pressing in the opposite direction (Fig. 5.49). The action of the levator scapulae muscle is best felt at the beginning of abduction of the shoulder from a resting position of 30° of abduction. In her study of iatrogenous lesions of the spinal accessory nerves, Camp (2010) found that the diagnosis was made by the responsible surgeon in only three cases and the average delay before diagnosis was no less than 18 months (Fig. 5.50). This delay is inexplicable. Most patients experienced

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Fig. 5.46  Measuring power of muscles at the shoulder. The patient is seated.

Fig. 5.47  The active inferior scapula-humeral angle (ISHA) in a normal shoulder lies between 150° and 170°.

immediate severe pain and demonstrated remarkable loss of function. The posture of the scapula is characteristic. It drops downwards, and away from the spine. The average ISHA, in Camp’s cases, was about 50°. The “winging” is often wrongly attributed to paralysis of serratus anterior muscle (Fig. 5.51). The nerve to serratus anterior is a frequent victim of the attentions of surgeons and transection is associated with pain

and loss of function only slightly less than that seen after accessory palsy. The usual way to test the serratus anterior muscle is to ask the patient to press against the wall with both hands. Weakness is shown by winging of the scapula on the affected side. The method is, unfortunately, inapplicable just when it is most needed: in paralysis of the upper limb from a complete lesion of the brachial plexus. The examiner

Clinical Aspects of Nerve Injury

171

Fig. 5.48  Two examples of combined palsy of the spinal accessory and the nerve to serratus anterior.

Fig. 5.49  The lower border of trapezius, 1, is demonstrated by forcing the left hand against the spine and the rhomboids, 2, are shown by pressing the right hand away from the spine against resistance. “T” towards, trapezius; “R” rearwards, rhomboids.

supports the paralyzed upper limb with one arm; the index finger and thumb of the examiner’s other hand grip below a pole of the scapula; the patient is asked to push forwards. Protraction of the scapula shows that serratus anterior is not paralyzed (Fig. 5.52). The nerve is particularly susceptible to involvement in neuralgic amyotrophy. The ISHA was, on average, 130° in 45 patients with lesions of the nerve. The scapula is elevated and approaches the spine (Fig. 5.53). The circumflex and suprascapular nerves – the rotator cuff. Inman et  al. (1944) studied the joints of the shoulder girdle by inserting pins into the skin of volunteers and recording movement, by radiographs and by measurement of

current action potentials, from the muscles. They observed: “it should be clearly recognized that the standard text book teaching on these motions is entirely incorrect. These state that gleno humeral motion occurs up to a right angle and that thereafter further elevation is brought about by rotation of the scapula. Roentgenography and examination of the living proved beyond any doubt that scapula and humeral motion are simultaneously continuous” (Fig. 5.54). Recognition of rupture of the circumflex nerve can be very difficult. One reason for this is the widely held (and erroneous) view that the deltoid muscle is the abductor of the gleno humeral joint (Figs. 5.55–5.57). Wynn Parry (1981) examined 145 patients with paralysis confined to the deltoid muscle. He found that the range of abduction was full, or nearly so, and described a system of training compensatory movements which enabled most of his patients to return to full military duties: “it must be stressed that these movements providing full abduction and elevation are not trick actions in the sense usually associated with this word; all the muscles involved normally help to abduct the shoulder. The scapulo-humeral rhythm is quite normal and in the later stages of re-education the patient does not even need to rotate the humerus externally to initiate the movement.” Seddon (1975) was a little more cautious: “this perfect abductor action of the supraspinatus is rare; it is more usual to find abduction to about 155°, with the arm a little in front of the coronal plane of the body.” Curiously, the loss of abduction caused by lesions of the suprascapular nerve and/or of rupture of the rotator cuff is frequently and wrongly attributed to a lesion of the circumflex nerve (Figs. 5.58–5.60). In 63 cases we found that the active ISHA was diminished by about 20° in uncomplicated ruptures of the circumflex when there was no stiffness of the shoulder. The

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Fig. 5.50  Right spinal accessory palsy. The scapula drops down and away from the spine. The active ISHA is 30°.

Fig. 5.51  Left spinal accessory palsy. Scapular winging, without prominence of the lower fibres of the trapezius, in a case where there is some early recovery into the upper fibres after repair of the spinal accessory nerve. At rest, the scapula is displaced downwards and away from the spine.

Clinical Aspects of Nerve Injury

Fig.  5.52  A method of examining serratus anterior. The examiner grasps the lower pole of the scapular between finger and thumb and the patient is asked to thrust the upper limb forwards. The examiner will be unable to block protraction of the scapula if serratus anterior is normal.

angle is reduced to less than 30° in most cases of suprascapular palsy or in complete ruptures of the rotator cuff (78 cases). Perhaps the most reliable sign of circumflex palsy is weakness of extension. The power of extension at the shoulder abducted to 90° is as little as 5–10% of normal when the deltoid is

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paralyzed. The diagnosis of rupture of the circumflex nerve is only easy when it is too late to do anything about it, that is, when the atrophy of the muscle is all too plain. It is a very hard matter for the clinician treating a patient with fracture/dislocation of the shoulder to examine function in the muscles. The area of loss of sensation is inconsistent and some patients will describe sensation of the skin over the muscle as abnormal rather than absent. It is probably helpful for the treating clinician to bear the possibility of nerve injury in mind and to plan for examination of the muscles about the shoulder at 1 week after urgent treatment by which time sensory loss and paralysis can be readily detected. Examination of the adductors and medial rotators of the shoulder is usually straight forward. The subscapularis, the most powerful of the muscles comprising the rotator cuff, is more difficult to test. Placing the hand behind the back is a complex movement and requires integrity of the thoracoscapular muscles. It is usually impaired in patients with lesions of the spinal accessory, the nerve to serratus anterior or dorsal scapular nerves. Isolated paralysis of the subscapularis is rare. If the tendon is ruptured many patients are still able to maintain a full range of medial rotation although power is reduced in the last 20° or 30° (Figs. 5.61–5.63).

Fig. 5.53  Scapular winging in nerve to serratus anterior lesion. This is easily distinguishable from the winging provoked by accessory palsy by the position of the scapula which is drawn upwards and towards the spine by the unopposed action of trapezius, levator scapulae, and rhomboids.

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Fig. 5.54  The deltoid. The anterior, middle, 1, and posterior, 2, components of the muscle should be observed and palpated during resisted abduction and extension.

All three heads of triceps should be examined for this provides information about which spinal nerves have been injured and offers an indication of the level of injury of the radial nerve (Fig. 5.64). Ruptures of the musculocutaneous nerve are frequently missed at first examination because brachioradialis is such a powerful flexor and also because the radial nerve often innervates the lateral portion of brachialis (Figs. 5.65 and 5.66). The power of supination and pronation of the forearm should be tested from the neutral position: it is important to remember that both biceps and supinator contribute to supination, and that the long flexor muscles of the forearm can often give useful pronation when the pronator teres muscle is paralyzed or weak. Paralysis of the extensor and flexor muscles of the wrist may be masked by the extensor and flexor muscles to the digits. Extensor pollicis longus is capable of extending the wrist, abductor pollicis longus can mimic this action if the wrist is partially pronated. It is important to palpate both the muscle and the tendon under examination (Fig. 5.67). The long flexors of the fingers: The flexor superficialis, usually innervated by the median nerve, acts on the proximal interphalangeal joints of the medial four digits. Its action on individual fingers is best tested by holding three of the digits almost straight and asking the patient to flex the free finger. Because the tendons of the superficialis are largely independent of each other and those of profundus are not, the former muscle will act to flex the proximal interphalangeal joint (Fig. 5.68).

Surgical Disorders of the Peripheral Nerves

The medial half of the flexor digitorum profundus (FDP) is usually innervated by the ulnar nerve; the lateral part, by the median nerve. With the exception of that to the index finger, the tendons are closely associated with each other, and independent movement is, in most cases, hardly possible. The test for the integrity of the profundus requires the subject to flex the distal interphalangeal joint of one finger with the proximal joints of that finger and all joints of the other fingers stabilised. One quick way to test the FDP simultaneously is to ask the patient to curl the fingers into the palm with the metacarpophalangeal joints extended. The examiner’s finger cannot extend the distal interphalangeal joint if the muscle is normal. The division of the supply of the intrinsic muscles of the hand between the median and ulnar nerves varies from subject to subject (Rowntree 1949). The most common arrangement is for the ulnar nerve to supply all muscles with the exception of the first lumbrical, the abductor brevis and opponens pollicis, and part of the flexor brevis pollicis. Most of the intrinsic muscles act on the metacarpo-phalangeal joints to flex, adduct and abduct. The particular action of the thenar muscles is to oppose the thumb to the little finger, and the muscle particularly responsible for rotating the metacarpal bone during that movement is the opponens. When the median nerve has been cut the opposing action of the thenar muscles can be mimicked by the combined action of an ulnar-innervated flexor brevis and the abductor longus muscle. Comparison with the intact side will usually show that this combined action does not reproduce the rotational action of the opponens. Similarly, the abducting action of the abductor brevis can in the absence of median nerve function be imitated by the action of the abductor longus muscle. These points are important in the early stages when there is no wasting to guide the examiner (Figs. 5.69 and 5.70). The action of the thumb in pinching against the forefinger is modified and weakened by the loss of the stabilising action of the flexor brevis pollicis on the first metacarpophalangeal joint. Without that action, pinch has to be mediated by the action of the flexor longus pollicis on the interphalangeal joint. The power of the ulnarinnervated muscles of the hand is best tested by examining the power of abduction and adduction of the fingers. The ease with which a sheet of paper may be pulled from between two adducted fingers gives some indication of this power.

5.9.4 The Lower Limb There is no great difficulty in testing the muscles connecting the pelvis to the femur in the healthy subject, but things are

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Fig. 5.55  Elevation of the upper limb in full medial rotation by the supraspinatus in the absence of deltoid in four cases of proven rupture of the circumflex nerve. Bottom left and right: note the activity in the clavicular head of pectoralis major.

different when this has to be done soon after replacement arthroplasty. Our observations suggest that in this situation there is also quite often a certain reluctance to look. In one case, a “drop foot” was observed soon after arthroplasty, but it was not until a year later that another examiner found paralysis of most of the muscles of the buttock. Superior gluteal palsy is crippling, yet delay in diagnosis is common. Much can be learnt from watching the patient walk. The integrity of the smaller glutei is tested with the patient standing; that of

the rotators of the hip with the patient seated, and that of the gluteus maximus with the patient prone (Fig.  5.71). It was common experience at times when poliomyelitis was common to see children and young adults walking quite well even though their quadriceps muscles were paralyzed (Fig. 5.72). Of course, they did this by a form of adaptation, a trick movement, in which the tensor fascia lata was responsible for stabilisation of the knee. In many cases there was the added factor of a hyperextension deformity of the knee. It is, however,

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Fig. 5.56  The movement of the scapula in another case of rupture of the right circumflex nerve. The active ISHA on the side of the injury(bottom right) is reduced by 20° showing that 20° of the range of elevation is provided by extra movement at the thoraco-scapular joint.

Fig. 5.57  Combined injuries to the suprascapular and circumflex nerves. Left: showing the range of elevation in a patient with irreparable injury to the right suprascapular nerve but with a good result after repair of the circumflex nerve. Right: showing the elevation in another patient in whom repair of the left suprascapular nerve was successful but whose circumflex nerve injury was irreparable.

Clinical Aspects of Nerve Injury

Fig. 5.58  The infraspinatus, 1, is examined by resisting lateral rotation with the warm against the side.

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the diagnosis was recognised only after the patients fell and damaged themselves. A lesion of the femoral nerve high enough to paralyze both hip flexors and extensor muscles of the knee is crippling. Examination of the power of flexion of the hip is best done with the patient lying supine. The power of extension of the knee is best measured with the patient sitting and the examiner should attempt to assess bulk and power in the three superficial components of the muscle, the vastus medialis, the rectus femoris, and the vastus lateralis. The flexors of the knee are best examined with the patient prone: it is usually possible to distinguish the action of the biceps femoris from that of the medial hamstrings. It is necessary, in testing the power of the flexors of the ankle, to make sure that the action is in fact effected by the soleus and gastrocnemius: the tibialis posterior and the flexors of the toes can produce ankle flexion, though they cannot sustain the patient’s weight. Both tibialis muscles effect inversion of the foot; the anterior muscle is the principal extensor of the ankle. It is not always easy to measure the strength in the evertor muscles of the ankle, (peroneus longus and brevis). It may be easier to detect early recovery with the patient lying on their side and the foot held plantigrade. The muscle belly and the tendon are observed and palpated (Fig. 5.73). We know of no really satisfactory way of testing the integrity of the intrinsic muscles of the foot. Some individuals can use these muscles independently of each other, most cannot (Fig. 5.74).

5.9.5 Late Signs of Nerve Injury

Fig. 5.59  Initiation of abduction, with opening of the active ISHA was the first sign of recovery into supraspinatus after repair of the suprascapular nerve. The lesion of the circumflex nerve was irreparable.

quite wrong to assume that an adult with a deep femoral nerve lesion could walk comfortably and without risk. In six of our cases of femoral palsies incurred during total hip arthroplasty,

Two weeks after a complete degenerative lesion, the area of loss of sensibility is well defined; the beginning of wasting indicates the extent of the motor affection. Anhidrosis is still present, but with the degeneration of peripheral fibres the warm isothermia of the skin gives way to poikilothermia and later to cold isothermia (Figs. 5.75 and 5.76). As time goes by, the changes of disuse appear: thinning of the skin; even ulceration from accidental injury; loss of substance in the tips of the digits; loss of skin markings; constant coldness and cyanosis; stiffness of joints; contractures; unmistakable wasting. Nails become brittle and discoloured and are prone to infection. Hair growth is disturbed, hairs are often coarse (Figs. 5.77–5.79). These changes occur rapidly in the ischaemic limb. At a late stage in partial denervation or with incomplete recovery after a deep lesion there may be muscle spasms and spontaneous fasciculation. Prolonged denervation of a growing limb leads to defective growth: this is of course well seen after birth injury of the brachial plexus. Lewis and Pickering (1936) thought that the changes in denervated limbs were simply the result of disuse rather than that of the loss of a “trophic” function of the nerves. However, it is a fact that in cases of greatly prolonged conduction block, the changes are always far less than they are in

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Fig. 5.60  Rupture of rotator cuff with lesions of the suprascapular and circumflex nerves from fracture/dislocation of the shoulder. Above showing the range of elevation at the right shoulder in 74 year old ex-paratrooper in whom there was clear evidence of recovery for both of the nerves. Below: this shipwright held onto a cable to rescue a man from the Thames. The weight of the man and the force of the current was such that he felt the muscles tearing in his right shoulder, then he felt the head of the humerus pulling out from the socket and then his arm went dead. Mr. Sait (Dartford) confirmed rupture of the rotator cuff by MR scan. Electromyography (Dr. Cordivari, Queen Square) showed that the suprascapular nerve was intact and that there was, at 8 weeks, reinnervation of the posterior deltoid. A Tinel sign was detectable at the posterior aspect of the shoulder. A subsequent repair of the rotator cuff, performed by Mr. Sait, was successful.

Fig. 5.61  The clavicular head, 1, of pectoralis major is best examined by resisting adduction and medial rotation with the arm elevated.

Fig. 5.62  The sternal head, 1, of pectoralis major is tested with the arm in adduction.

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Fig. 5.65  Brachio radialis is a powerful flexor of the elbow. The biceps muscle and its tendon should be observed and palpated. 1. Biceps brachii, 2. Biciptal aponeurosis, 3. Medial head of triceps, 4. Brachioradialis, 5. Biceps tendon.

Fig. 5.63  Teres major, 2, and latissimus dorsi, 3, are tested by resisting adduction. The muscles are seen and palpated. The posterior deltoid, 1, is seen.

Fig. 5.64  The lateral, 1, long, 2, and medial, 3, heads of triceps are examined by observing and palpating the muscle.

degenerative lesions. We have seen that in degenerative lesions profound changes take place in both motor and sensory end-organs. The distal axon normally maintains a dense population of end-organs in skin and sweat glands and in the muscular component of arterioles. It is hard to resist the conclusion that the changes of “disuse” are at least in part due to the loss of distal axons and of their end-organs, and to the effects of that loss on superficial tissues. An extreme form of severe trophic changes in long standing “conversion paralysis” is described in Chap. 14.

Fig. 5.66  Elbow flexion. 1. Brachioradialis, 2. Brachialis, 3. Biceps, 4. Bicipital aponeurosis.

By the time the changes of degeneration are present, the patient is a better candidate for the examination halls than for restorative treatment. The object of the clinician must be to make the diagnosis before the signs of peripheral degeneration have appeared; before the best time for intervention has passed. Unfortunately, the peripheral neurologist is still likely to be presented with cases in which delay in diagnosis has permitted the development of these signs. The last are at this stage well marked; their absence in association with

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Fig. 5.67  Activity in extensor carpi radialis brevis, 1, and longus, 2, is noted by observing and palpating the muscle bellies and their tendons.

Fig. 5.69  Below: the first dorsal interosseous, 1, and adductor pollicis, 2, muscles (ulnar nerve) are examined by thumb to index pinch grip. Above: abductor pollicis brevis, 3, (median nerve) is tested by resisting abduction of the thumb at right angles to the palm of the hand.

Fig. 5.68  Flexor digitorum superficialis is examined by immobilising the other digits.

persistent partial motor and sensory paralysis almost certainly means that the lesion was partly or wholly a conduction block.

5.9.6 Signs of Reinnervation The detection of initial and continuing reinnervation is often very important in aiding a decision about intervention. After

such a procedure, it is important as an indicator of success or failure, and consequently as a guide to a second intervention. In cases in which long spatial and temporal distances separate a lesion from the nerve’s target, the Tinel sign is useful but can mislead, especially when the target tissues have been damaged by ischaemia or sepsis. After a degenerative lesion, recovery proceeds centrifugally, so that the first sign of reinnervation is voluntary contracture in the muscle most proximally innervated. Sensibility too recovers centrifugally. As Head et  al. (1905) observed, its quality improves over successive months, doubtless with re-­myelination of the larger axons Recovery of sensibility may be preceded by recovery of sweating; indeed, sweating may be restored without any later recovery of sensibility; light touch sensibility may return in the absence of nociception and sweating In non degenerative lesions, recovery is not necessarily nor even generally centrifugal: distal muscles may well recover before proximal ones; loss or alteration of sensibility may anyway be patchy; vasomotor and sudomotor paralysis is rare. Because the lesion depends so much on demyelination, and in particular on demyelination of large fibres, a dissociated loss of position sense and vibration sense may be a good indicator of its type.

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Fig. 5.71  Above: the power of the abductors of the hip is tested with the patient in a lateral position, resisting abduction on the lower limb. Below: gluteus maximus is tested with the patient prone resisting extension at the hip.

Fig. 5.70  The small muscles of the hand in lesions of the ulnar nerve. Above: “Froment’s sign” is positive in the patient’s left hand. Below: clawing is corrected by passive flexion at the metacarpophalangeal joints.

Very often, in recovery after both degenerative and nondegenerative injuries, the patient experiences radiated pain and paraesthesiae and asks the clinician whether these feelings indicate progressive recovery. We have seen that Merrington and Nathan (1949) explored the nature and origin of paraesthesiae after conduction block: certainly, such feelings indicate recovery in that condition. They do not necessarily, nor even often, have that significance in the case of degenerative lesions. Features of imperfect recovery: Imperfect recovery, common in the adult after repair of a degenerative lesion, is apparent to the patient through: (1) Weakness and sometimes wasting; (2) alteration of sensibility;(3) dysfunction; (4) (sometimes) pain; (5) (sometimes) sensitivity over the site of the lesion; (6) exaggerated reaction of the affected part to external cold; (7) stiffness and even deformity of the joints of the affected part. The exaggerated reaction to cold requires some further comment; all other aspects are treated elsewhere. Cold affects healthy nerves: it affects even more severely those in which the number of functioning axons is

reduced, So, conditions of cold which would not seriously affect healthy nerves are liable badly to affect damaged nerves in which regeneration has been imperfect. Both motor and sensory function are affected. The cold affects not only nerve function; it affects too the skin and deep tissues of the affected limb, which is quick to cool and slow to warm. Sensitivity to cold may prevent return to work in the cold room of a butcher or fishmonger, or to outdoor work with machinery, even when recovery after repair of a median nerve at the wrist has been otherwise good. The response to cold stimulus was analyzed, in normal hands, by Davis and Pope (2002). Aching pain was experienced at temperatures of 15°C or less and prickling sensations were induced by even colder stimuli. Cold related symptoms after injury to peripheral nerves seem to be an exaggeration of this response. Irwin et  al. (1997) noted immediate onset of symptoms in one-third of their patients. Symptoms had developed within 3 months in the remaining two-thirds. The problem was worse after untidy injuries and after injury to the axial artery. Kay (1985) “found no relationship between arterial inflow and cold intolerance” but there was a tendency for the symptoms to be worse with poorer nerve function. Vasospasm may contribute to the problem (Backman et al. 1993). An unpleasant sensation of intense coldness was associated with blanching or discolouration of

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injured fingers in more than 70% of the patients described by Lithell et al. (1997). Malenfant et al. (1998) studied cold intolerance in patients with burns and demonstrated changes in sensation in normal skin in the contra lateral uninjured limb.

Surgical Disorders of the Peripheral Nerves

5.10 Records Recovery after severe injuries to nerves is prolonged, and persisting pain and loss of function interfere with rehabilitation. We have developed a number of systems which record the

Fig.  5.74  The small muscles of the foot, 1. The patient is asked to “make a fist” with their toes.

Fig. 5.72  Extension of the knee. The muscle bellies of vastus medialis, rectus femoris, and vastus lateralis can be seen and felt. Note the action of the tensor fascia lata which can, in some patients, extend the knee against gravity. Note the fascia lata, 1, the vastus lateralis, 2, the rectus femoris, 3, and vastus medialis, 4.

Fig. 5.73  Eversion at the ankle. The muscle bellies of peroneus brevis, 1, and longus, 2, and their respective tendons are observed and palpated.

Fig. 5.75  Late changes after nerve injury. Severe wasting of the hand with contractures, 1 year after stab wound to the lower part of the brachial plexus.

Clinical Aspects of Nerve Injury Fig. 5.76  Late changes after nerve injury. Left: there is sympathetic paralysis and unnoted burns after high lesion of the median nerve. Right: wasting and ulceration of the skin of middle finger and accidental injury to index finger after median nerve injury. The patient was working as a stone mason.

Fig. 5.77  Post ischaemic contracture in the hand. A 63 year old man lay in a coma for 18 h. There was compression of the axillary neurovascular bundle. The range of extension (left) and of flexion (right) is shown 1 year later.

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Fig. 5.78  Post ischaemic fibrosis. The lateral geniculate artery was lacerated during arthroscopic meniscectomy. The false aneurysm which ensued remained undetected for 4 days in spite of his intense causalgia. The position of the leg, ankle and foot 3 years after injury.

progress after nerve injury, associated injuries and their consequences, and after “reconstruction” operations. Information is collected about the effects on daily life, on work or training or study. The evolution of pain, its response to treatment or to recovery is recorded. The progress for the nerve is recorded

Fig. 5.79  Late skin changes after nerve injury. Left: a skin rash in the distribution of C5, 6 months after rupture. Right: skin rash in the distribution of the common peroneal nerve 1 year after rupture at the knee.

Surgical Disorders of the Peripheral Nerves

sequentially for motor, sensory, and sympathetic function and a final grade is offered for the whole nerve. Suitably modified forms are used for injuries to the shoulder girdle and gleno-humeral joint, for injuries in the lower limb and for penetrating missile wounds (Fig. 5.80). Other forms are used for traumatic lesions of the brachial plexus (Fig. 5.81a and b). The documents used for birth lesions of the brachial plexus are illustrated in Chap. 10. These records are placed in the case notes at the patient’s first attendance, and remain there until treatment is completed. Information is transferred from the form onto appropriate data bases throughout treatment. These computerised systems certainly ease analysis but never replace the hand written entry made at every visit. All systems fail to a greater or lesser extent in (1) failing adequately to record the stamina of muscles; (2) failing adequately to record function of the sensory end-organs in muscles, tendons and particular capsules and ligaments and (3) failing adequately to record co-contraction. Co-contraction is particularly common after injuries to the brachial plexus in adults and in infants. Special apparatus is indeed available for testing stamina of muscles, in particular those of the hand. The amount of time involved is, however, too great to permit the routine use of these methods. Evidently, tests such as Moberg’s “pick-up” test to some extent examine deep as well as superficial sensibility, but there is no good measure of the extent of re-innervation of muscle spindles. The examination of tendon reflexes is, evidently, a coarse method of testing the function of the Golgi organs and muscle spindles, but more precise methods are lacking. We do not know how much the function of a muscle recovered after nerve repair is impaired by defect of input from it. It is probable that impairment of the

Clinical Aspects of Nerve Injury

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Fig. 5.80  The document used for recording data in patients with compound nerve injury.

deep afferent pathway is one factor underlying co-contraction; such impairment is certainly a major cause of the regular failure of muscle transfers using reinnervated muscles.

5.11 Aids to Diagnosis Electrophysiological examination: We owe much to our colleagues, Dr. Nicholas Murray, Dr. Shelagh Smith, and Dr. Peter Misra, Dr. Carla Cordivari and their colleagues at the National Hospital for Nervous Diseases with whom joint electrodiagnostic clinics have been held for more than

20 years. More than 1,000 patients have been seen at these clinics, which provide prompt and valuable information about diagnosis and prognosis. This collaborative approach is also useful in teaching and in training. The cases are presented by the surgeon who offers a diagnosis of the level and of the depth of lesion and of the likely prognosis. That diagnosis is then confirmed, expanded or refuted by studies of sensory and motor conduction and by electromyography of selected muscles. More than 2,000 other patients have been seen by our colleagues at the National Hospital whose work represents a contribution in the analysis of injuries of profound importance.

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Electrophysiological examination (Wynn Parry 1953, Smith 1996, 1998, 1999) is certainly the foremost aid to diagnosis, though in the acute stage the process is often hampered by pain and by local conditions. It must be done properly and results must expertly be interpreted. It is no substitute for clinical observation; it must not be used as device for deferring decision and delaying action. It can help in diagnosis of

Fig. 5.81  The document used for collecting data about patients with injuries to the brachial plexus.

Surgical Disorders of the Peripheral Nerves

the site and depth of a lesion and in the recognition and measurement of recovery. The extension of the process to the detection and measurement of potentials evoked from the cortex provides valuable evidence in the case of suspected avulsion of the roots of the brachial plexus. Perhaps the simplest, yet often neglected, technique of electrophysiological examination is that of stimulating the nerve below the level of

Clinical Aspects of Nerve Injury

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Fig. 5.81  (continued)

the lesion and observing the motor response. If, 3 days after injury, stimulation below the level of the lesion produces a normal response in the muscles supplied by the nerve, the odds are that the lesion is a conduction block. If there is no motor response or if the response is much subdued, then the lesion is degenerative. The introduction of electrophysiological process during operation has brought massive advantages, in particular in (1) determining neural continuity across a lesion in continuity;

(2) determining the site of a conduction block; (3) determining which part of a nerve has suffered axonal interruption; (4) determining whether an apparently intact component of the brachial plexus has intact central connections. We are profoundly glad that the whole matter is considered at length in the next Chapter by an expert in the field. Magnetic resonance imaging: Whilst magnetic resonance neurography is uniquely informative in the diagnosis and accurate measurement of the extent of tumors in or near

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nerves, in the more difficult entrapment syndromes, and in closed traction injuries of the brachial and lumbo-sacral plexus, the full potential of the method in the diagnosis of closed injuries to peripheral nerves has yet to be fully exploited. Ultrasonography seems more promising High resolution ultrasonography: Dr. Susan Krone (2005) (Maidstone) read an exceptional paper at the Royal National Orthopaedic Hospital in 2005 in which she outlined the application of this method for the display of major nerves and of their constituent bundles during regional anaesthesia. She pointed out that this investigation could prove valuable in the first days after closed injury before fracture haematoma is transformed into scar. Krone further suggested that the method might have a place in the examination of the neonatal brachial plexus in cases of birth lesion at a time when ossification of the cervical spine is limited. Martinoli et al. (1996) provided an important review: When examined with high-frequency probes, peripheral nerves show a peculiar arrangement of their internal structures. Using 15 MHz transducers the nerve appears to be composed of multiple hypo-echoic parallel discontinuous linear areas separated by hyper-echoic bands. The hypo-echoic areas are arranged in series and appear well defined and elongated according to the longitudinal axis of the nerve. On transverse sections, the hypoechoic areas become rounded and are embedded in a homogenous hyper-echoic background. Side by side comparison between ultrasound scans and respective histologic slides demonstrated that the hypo-echoic areas coincide with fascicles of neuronal fibres, whereas the hyper-echoic background correlates with the epineurium and passes into the spaces between the individual fascicles of nerve substance.

These workers go on to point out that the arrangement of fascicles is related to the ultrasound frequency employed. 15 MHz transducers are optimal but tissue penetration of these is poor so that their use is limited to the examination of nerves running within 2 cm from the skin surface. Deeper nerves can be examined using lower frequency probes but the fascicular pattern is less well defined with such transducers. The arrangement of bundles can be detected using a frequency as low as 7.5 MHz. Chan (2003), and Perlas and his colleagues (Perlas et al. 2003) show that the brachial plexus, in the posterior triangle of the neck, can be closely examined using high resolution ultrasonography. The potential for diagnosing nerve transection by ultrasound was examined by Cartwright et al. (2007), from the Wake Forest school of Medicine in 2007. The median, ulnar and radial nerves were transected in the arms of fresh cadavers and sham skin incisions were performed throughout the arm. The nerves were then scanned by an ultrasonographer who was unaware of the sites of transection. High resolution ultrasound was able to identify transected nerves with 89% sensitivity and 95% specificity. These workers conclude that: “this proof of concept study shows that ultrasound can accurately identify a nerve transection, which should lead to further ultrasound studies in patients with traumatic peripheral nerve injuries.” Two such studies are

Surgical Disorders of the Peripheral Nerves

provided by Cokluk and Aydin (2007 a, b) of the Department of Neurosurgery in Samsun, Turkey, who published two important papers in 2007. In all, 58 patients were examined The nerves investigated in the upper limb included the brachial plexus (4 cases) the ulnar nerve (9 cases) the radial nerve (6 cases) the median nerve (17 cases). In the lower limb, the femoral nerve(5 cases) and the sciatic nerve (17 cases) were examined. The examination was performed using a Tosbee ultrasound (Toshiba Inc., Tokyo) with a 5–7.5  MHz linear probe. The patients with injuries in the upper limb were placed supine. Ultrasound gel was plastered on the probe surface and the skin to enhance visualisation of peripheral nerves and the musculo-skeletal structures. The examination commenced about 10  cm proximal to the suspected region and continued 10  cm distally. Bone, muscles, tendons, vascular structures, and peripheral nerves were identified and distinguished. “Continuity, architecture, shape, calibration and integrity of the involved nerve and peripheral tissues were examined in the perpendicular and transverse planes.” The femoral nerve was examined with the patient supine, the sciatic nerve was examined with the patient placed prone. Sixteen of these patients were examined within 3 days of injury. In most cases the diagnosis made by ultrasound was matched with the findings at subsequent operation. The investigation proved reliable in identifying the nerve, in localising the level of injury and in the recognition of the nature of that injury. Toros et al. (2009) provide further valuable information about the technique. It seems likely that ultrasonography, in skilled hands, has enormous potential in the early detection of ruptures or other serious injuries to nerves. A number of orthopaedic and fracture surgeons are already well versed in the technique and we hope that the very real difficulty of recognition of rupture of the nerve trunk in a closed fracture will be overcome by the widespread use of this method by interested clinicians.

References Anand P, Birch R (2002) Restoration of sensory function and lack of long-term chronic pain syndromes after brachial plexus injury in human neonates. Brain 125:113–122 Anand P, Warner G, Parrett A, Terenghi G, Kopelman P, Ghatei MA, Bloom SR, Sinicropi D, Williams-Chestnut RE (1994) Nerve growth factor related small fibre dysfunction in human diabetic neuropathy. Ann Neurol 36:284A Anand P, Terenghi G, Warner G, Kopelman P, Sinicropi DV, WilliamsChestnut RE (1996) The role of nerve growth factor in human diabetic neuropathy. Nat Med 2:703–707 Atherton DD, Facer P, Roberts KM, Misra VP, Chizh BA, Bountra C, Anand P (2007) Use of the novel contact heat evoked potential stimulator (CHEPS) for the assessment of small fibre neuropathy: correlations with skin flare responses and intra-epidermal nerve fibre counts. BMC Neurol 7:21

Clinical Aspects of Nerve Injury Backman C, Nystr m A, Balkman A, Bjerle P (1993) Arterial spasticity and cold intolerance after digital replantation. J Hand Surg Br 18:551–555 Bell J, Burford W (1982) The force time relationship of clinically used sensory testing instruments. Presented at the American Society for Surgery of the Hand, 37th Annual Meeting, New Orleans Birch R (1986) Lesions of peripheral nerves: the present situation. J Bone Joint Surg Br 68:2–8 Birch R (1989) The repair of peripheral nerves: experimental and clinical observations. Thesis for the degree of Master of Surgery, University of Cambridge Birch R, Raji ARM (1991) Repair of median and ulnar nerves. J Bone Joint Surg Br 73:154–157 Bonney G (1983) Peripheral nerve lesions. In: Harris NH (ed) Clinical orthopaedics, Wright, Bristol, pp 726 Bowden REM, Scholl DA (1954) Rates of regeneration. In: Seddon HJ (ed) Peripheral nerve injuries, vol 282, Medical Research Council Special Report Series. HMSO, London, pp 16–24 Brand PW (1985) Clinical mechanics of the hand. Mosby, St. Louis, pp 61–191 Buck-Gramcko D, Lubahn JD (1993) The Hoffman-Tinel sign. J Hand Surg Br 18:800–805 Camp SJ (2010) Lesions of the spinal accessory nerve. J Bone Joint Surg (in print) Canale ST, Beaty JH, Warner WC, Sharp RS (2000) Passive flexion sign: a simple tool for diagnosis of anterior interosseous nerve injury in children. J Bone Joint Surg 82:1354–1355 Cartwright MS, Chloros GD, Walker FO, Wiesler ER, Campbell WW (2007) Diagnostic ultrasound for nerve transection. Muscle Nerve 35(6):796–799 Chan V (2003) Applying ultrasound imaging to Interscalene brachial plexus block. Reg Anesth Pain Med 28:340–343 Cokluk C, Aydin K (2007a) Ultrasound examination in the surgical treatment for upper extremity peripheral nerve injuries: part I. Turk Neurosurg 17(4):277–282 Cokluk C, Aydin K (2007b) Ultrasound examination in the surgical treatment for upper extremity peripheral nerve injuries: part II. Turk Neurosurg 17(3):197–201 Coupland RM (1993) War wounds of limbs. Butterworth Heinemann, Oxford, London Davis KD, Pope GE (2002) Noxious cold evokes multiple sensations with distinct time cause. Pain 98:179–185 Dellon AL (1978) The moving two-point discrimination test: clinical evaluation of the quickly-adapting fibre receptor system. J Hand Surg 3:474–481 Dunnet W, Housden P, Birch R (1995) Results of flexor to extensor tendon transfer. J Hand Surg Br 20(1):26–28 Dyck PJ, O’Brien PC, Johnson DM, Klein CJ, Dyck PJB (2005) Quantitative sensory testing. In: Dyck PJ, Thomas PK (eds) Peripheral neuropathy, 4th edn. Elsevier, Philadelphia Gilliatt RW, Taylor JC (1959) Electrical changes following section of the facial nerve. Proc R Soc Med 52:1080–1083 Head H, Rivers WHR, Sherren J (1905) The afferent nervous system from a new aspect. Brain 28:99–116 Henderson WR (1948) Clinical assessment of peripheral nerve injuries. Tinel’s test. Lancet 2:801–806 Highet WB (1941) Memorandum to the nerve injuries committee of the Medical Research Council and published in the Special Report Series No. 282 1954. HMSO, London Highet WB (1954) Quoted by Zachary RB. In: Seddon HJ (ed) Peripheral nerve injuries Medical Research Council Special Report Series No 282. HMSO, London, p 355 Hoffman P (1915a) Über eine Methode, den Erfolg einer Nervennant zu beurteilen. Med Klin 11:359–360 Hoffman P (1915b) Weiterres über das Verhalten frisch regenerierter Nerven über die Methode, den Erfolg einer Nervennaht Frühzeitig zu beurteilen. Med Klin 11:856–858

189 Htut M, Misra P, Anand P, Birch R, Carlstedt T (2006) Pain phenomena and sensory recovery following brachial plexus avulsion injury and surgical repair. J Hand Surg Br 31:596–605 Htut M, Misra VP, Anand P, Brich R, Carlstedt T (2007) Motor recovery and the breathing arm after brachial plexus surgical repair including re-implantation of avulsed spinal nerves into the spinal cord. J Hand Surg 32E:170–178 Inman VT, Saunders JB, Abbott LC (1944) Observation on the function of the shoulder joint. J Bone Joint Surg 26:1–31 Irwin MS, Gilbert SEA, Terenghi G, Smith RW, Green CJ (1997) Cold intolerance following peripheral nerve injury. Br J Hand Surg 22:308–316 Jerosch-Herold C (2000) Should sensory function after median nerve injury and repair be quantified using two point discrimination as a critical measure? J Plast Reconstr Surg 34:339–343 Jerosch-Herold C (2005) Assessment of sensibility after nerve injury and repair: a systematic review of evidence for validity, reliability and responsiveness of tests. J Hand Surg Br 30:252–264 Kato N, Birch R (2006) Peripheral nerve palsies associated with closed fractures and dislocations. Injury 37:507–512 Kaufmann KR (2005) Quantitative muscle strength assessment. In: Dyck PJ, Thomas PK (eds) Peripheral neuropathy, 4th edn. Elsevier, Philadelphia, pp 1095–1102 Kay S (1985) Venous occlusion plethysmography in patients with cold related symptoms after digital salvage procedures. J Hand Surg Br 10:151–154 Keogh Sir Alred (1917) Introduction to: notes on military orthopaedics (Author. Robert Jones), Cassell, London Krone S (2005) Ultrasound guided regional anaesthesia. Invited paper to advanced orthopaedic anaesthesia and critical care. Royal National Orthopaedic Hospital, Stanmore, Middlesex, 16 September 2005 Landau WM (1953) The duration of neuromuscular function after nerve section. Neurosurgery 10:64–68 Landi A, Copeland S (1979) Value of the tinel sign in brachial plexus lesions. Ann R Coll Surg Engl 61:470–471 Lewis T, Pickering GW (1936) Circulatory changes in the fingers in some diseases of the nervous system, with special reference to the digital atrophy of peripheral nerve lesions. Clin Sci 2:149–183 Lithell M, Backman C, Nystr m Å (1997) Pattern recognition in posttraumatic cold intolerance. J Hand Surg 22:783–787 MacKinnon SE, Dellon AL (1985) Two point discrimination tester. J Hand Surg Am 10:906–907 MacKinnon SE, Dellon AL (1988) Ischaemia of nerve: loss of vibration sensibility. In: Surgery of the peripheral nerve. Thieme Medical Publishers/Georg Thieme Verlag, Stuttgart, New York, p 57 Malenfant A, Forget R, Amsel R, Papillon J, Frigon J-Y, Choinière M (1998) Tactile thermal and pain sensibility in burned patients with and without chronic pain and paraesthesia problems. Pain 77: 241–251 Martinoli C, Serafini G, Bianchi S, Bertoletto M, Gandolfo N, Derchi LE (1996) Ultrasonography of peripheral nerves. J Peripher Nerv Syst 1:169–178 Merrington WR, Nathan PW (1949) A study of post-ischaemic paraesthesiae. J Neurol Neurosurg Psychiatry 12:1–18 Mills K (1997) Wasting, weakness and the MRC scale in the first dorsal interosseous muscle. J Neurol Neurosurg Psychiatry 62:541–542 Moberg E (1958) Objective methods for determining the functional value of sensibility in the hand. J Bone Joint Surg Br 40:454–476 Narakas AO (1993) Paralytic disorders of the shoulder girdle. In: Tubiana R (ed) The hand, vol. 4. Saunders, Philadelphia, pp 112–125, Chapter 9 Novak VP, Baratz ME (2006) Antero-medial ecchymosis about the elbow in an adult with a distal humerus fracture. J Hand Surg Am 31:860–862 Novak CB, MacKinnon SE (1999) Letter to editor. J Hand Surg Am 24: 869–870

190 O’Brian M (ed) (2000) Aids to the examination of the peripheral nervous system, 4th edn. Elsevier, London Oaklander AL, Rismiller JG, Gelman LB, Zheng L, Chang Y, Gott R (2006) Evidence of focal small-fibre axonal degeneration in complex regional pain syndrome-1 (reflex sympathetic dystrophy). Pain 120:235–243 Perlas A, Chan V, Simons M (2003) Brachial plexus examination and localization using ultrasound and electrical stimulation. Anaes­ thesiology 99:429–435 Perry J, Ireland ML, Gronley J, Hoffer MM (1986) Predictive value of manual muscle testing and gait analysis in normal ankles by dynamic electromyography. Foot Ankle Int 6:254 Porter RW (1966) New test for finger sensation. BMJ 2:927 Rank BK, Wakefield AR, Hueston JT (1973) Surgery of repair as applied to hand injuries, 4th edn. Churchill Livingstone, Edinburgh Riddoch G (1940) The coin test. In: Surgical disorders of the peripheral nerves (Attributed: Seddon HJ 1975), Churchill Livingstone, Edinburgh, p 53 Rosén B, Jerosch-Herold C (2000) Comparing the responsiveness over time of two tactile gnosis test: two-point discrimination and the STI test. J Hand Surg 5:114–119 Rowntree T (1949) Anomalous innervation of the hand muscles. J Bone Joint Surg Br 31:505–510 Seddon HJ (1975) Surgical disorders of the peripheral nerves, 2nd edn. Churchill Livingstone, Edinburgh, London, New York, p 177 Seddon HJ (ed) (1954) Peripheral nerve injuries. Medical Research Council Special Report Series No 282. HMSO, London Sharrard WJW (1953) Correlations between the changes in the spinal cord and muscular paralysis in poliomyelitis. Proc R Soc Lon 40:346 Smith SJM (1996) The role of neurophysiological investigation in traumatic brachial plexus injuries in adults and children. J Hand Surg Br 21:145–148

Surgical Disorders of the Peripheral Nerves Smith SJM (1998) Electrodiagnosis. In: Birch R, Bonney G, Wynn Parry C (eds) Surgical disorders of the peripheral nerves, 1st edn. Churchill Livingstone, Edinburgh, London, pp 467–490, Chapter 19 Smith SJM (1999) Neurophysiological interpretation after nerve injury in the upper limb. Curr Orthopaed 13:27–32 Smith PJ, Mott G (1986) Sensory threshold and conductance testing in nerve injuries. J Hand Surg Br 11:157–162 Stewart M, Birch R (2001) Penetrating missile injuries. J Bone Joint Surg Br 83:517–524 Szabo RM, Gelberman RH, Williamson RV, Dellon AL, Yavu NC, Dimick NP (1984) Vibratory sensory testing in acute peripheral nerve compression. J Hand Surg Am 9:104–109 Tinel J (1915) Le signe du “fourmillement” dans les lésions des nerfs periphériques. Presse Méd 47:388–399 Tinel J (1917) Nerve wounds. Ballière Tindall & Cox, London. Authorised translation by Rothwell F, revised and edited by Joll CA Toros J, Karabay N, Őzaksar K, Sugun TS, Kayalar M, Bal E (2009) Evaluation of peripheral nerves of the upper limb of the upper limb with ultrasonography. J Bone Joint Surg Br 91:762–766 Trumble TE, Kahn U, Vanderhooft E, Bach AW (1995) A technique to quantitate motor recovery following nerve grafting. J Hand Surg Am 20:367–372 von Greulich M (1976) Der zweipunkte-Stern. Handchirurgie 8:97–99 Wynn Parry CB (1953) Electrical methods in diagnosis and prognosis of peripheral nerve injuries. Brain 76:229–265 Wynn Parry CB, Salter RM (1976) Sensory re-education after median nerve lesions. Br J Hand Surg 8:250–257 Wynn Parry CB (1981) Rehabilitation of the hand, 4th edn. Butterworth, London

6

Clinical Neurophysiology in Peripheral Nerve Injuries Shelagh Smith and Ravi Knight

Development of clinical neurophysiology as a diagnostic aid, applications and purpose of clinical neurophysiology, electrodiagnostic techniques and new methodologies, limitations and caveats, safety issues.

6.1 Introduction The Clinical Neurophysiologist participates in clinical evaluation of patients with known or suspected injury to a peripheral nerve, plexus or spinal root, and the information gained from neurophysiological evaluation often contributes directly to therapeutic decision making in such patients. Conduction along sensory and motor nerve axons is essentially an electrical process, and electrophysiological methods are a premier investigation for acquired disorders of peripheral nerves. Clinical neurophysiology alone does not always provide complete diagnostic information; nerve conduction studies and electromyography should be viewed as diagnostic aids, which extend the clinical examination and support other investigative tools, as outlined in Chap. 5. Electrodiagnostic techniques verify or exclude the clinical suspicion of a neuropathological process, and can offer a precise definition of the site, type and degree of a neural lesion, or reveal abnormalities that were clinically uncertain, silent or unsuspected. Electrodiagnostic study in neural injury is principally aimed at: • • • •

Localisation of the lesion Determination of pathophysiology Establishing severity Identification of reinnervation

The action potential in the peripheral nervous system was first described in the nineteenth century by Du Bois-Reymond and Bernstein (Seyffarth 2006; Pearce 2001) and is the fundamental unit of neural activity at the cellular level. The earliest application of electrophysiology in the study of human peripheral nerve disease was the demonstration that conduction velocity is slowed in injured regenerating nerve (Hodes et al. 1948). Considerable advances occurred during the 1940s and 1950s. Simpson reported delayed conduction in the median nerve in carpal tunnel syndrome (Simpson 1956), and Dawson in London developed an averaging technique for sensory nerve

recording using superimposed photographic traces of potentials (Dawson and Scott 1949). Further work with Dawson’s averaging method was carried out by Gilliatt and Sears at the Institute of Neurology in London, who applied it to the clinical study of nerve lesions (Gilliatt and Sears 1958), and P.K. Thomas, who described abnormalities of nerve conduction in ulnar neuropathies at the elbow and in the hand. An important contribution to the understanding of the basis of nerve conduction abnormalities was the experimental work on diphtheritic neuropathy by Lambert’s group at the Mayo Clinic, which identified segmental demyelination as the cause of slow nerve conduction velocity (Kaeser and Lambert 1962). Investigation of electrical properties of muscle fibres, notably by Lord Adrian and colleagues in Cambridge during the 1920s (Adrian 1925), and later by Buchthal in Sweden, led to the introduction of electromyography into clinical practice. Buchthal’s group went on to describe the characteristics of normal motor unit potentials, and the abnormalities seen on EMG in a wide range of myopathic and neurogenic disorders in man (Buchthal et al. 1957). Following these pioneering developments, a range of techniques for clinical study of peripheral and proximal nerves has been introduced and the pathophysiological basis of nerve conduction abnormalities clarified through correlation with morphological changes seen on nerve biopsy. The diagnostic role of electrophysiological investigation is further extended through introduction of methods for evaluation of previously inaccessible parts of the nervous system, including central motor and sensory pathways, and small myelinated and unmyelinated nerve fibres.

6.2 Electrodiagnostic Techniques In the clinical setting, summated responses from supramaximal stimulation of a sensory nerve (sensory nerve action potential) and motor nerve (compound muscle action potential) are

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respectively recorded over the cutaneous course of the sensory nerve, and from the belly of the muscle, using surface electrodes applied to the skin. Needle electromyography (EMG) records electrical activity from within muscle, and describes the integrity of the motor unit – which comprises a single alpha-motor neurone and all of the muscle fibres it innervates. Action potentials of single motor and sensory nerve fibres are summated to produce compound responses or potentials. These have a triphasic character, and parameters such as amplitude, duration, latencies and conduction velocities are determined efficiently by computer software integral to modern neurophysiological equipment. Normative data are available for a range of nerves and muscles, and enable quantification of any deviation from the norm. Conventional or standard nerve conduction studies assess function and conduction in large fast conducting nerve fibres – principally the A beta nerve fibres that mediate fine touch, with velocities in the range of 40–60  m/s. Slower conducting small myelinated A-delta and unmyelinated B fibres, mediating pain and temperature sensation, with typical conduction velocities of 3–10  m/s, cannot be assessed with standard nerve conduction tests. Evaluation of small fibre function requires specialised techniques previously accessible in a few neuroscience centres, but now more widely available (detailed application of these techniques in clinical practice is further discussed in Chap. 5). Somatosensory evoked potentials are of especial value in establishing presence of a pre-ganglionic lesion, proximal to the sensory or dorsal root ganglion, through measurement of the passage of near-field potentials resulting from stimulation of a mixed nerve or dermatome, at the level of the lumbar or cervical spine, and further cranially at the somatosensory cortex. They may indicate the presence of clinically unsuspected disease, or a second level injury in the central nervous system. Case Report: A 37 year old man had sustained multiple shrapnel injuries including one penetrating the neck anteriorly, with a fragment still lodged in the spinal canal. He developed proximal weakness in the right upper limb and paraesthesia in a C5 and C6 distribution; he also complained of numbness in the left leg. The right brachial plexus was explored approximately 1 week after injury. The plexus was considered intact by direct visual inspection; the subclavian vein was repaired. The patient was referred for neurophysiological investigation because of persisting sensory symptoms and arm weakness. The nerves studied were bilateral median, ulnar and radial sensory; right median motor, right ulnar motor, bilateral musculocutaneous and axillary motor. Extensive EMG sampling was undertaken in the deltoid, infraspinatus, biceps, triceps, brachoradialis and first DIO muscles of the right arm, and in mid and lower cervical paraspinal muscles bilaterally. Lower limb SSEPs were performed with tibial nerve stimulation to evaluate sensory symptoms in the left leg. The abnormal findings were a relatively small median sensory potential from the right thumb (12  uV compared

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with 35  uV in the left arm), and evidence of denervation (large or polyphasic MUPs, reduced recruitment) in right deltoid, infraspinatus and biceps. Fibrillations were present in infraspinatus > biceps. Cervical paraspinal muscles were normal. Cortical SSEPs from the left tibial nerve were poorly formed compared with the right leg; latency was normal but amplitude was reduced. Responses from the cervical cord were normal. Neurophysiological interpretation: evidence of a partial proximal lesion of the right brachial plexus affecting the upper trunk. The SSEP findings are suggestive of an axonal lesion in somatosensory pathways between the upper cervical spine and primary sensory cortex.

6.2.1 Glossary of Electrodiagnostic Procedures Compound sensory action potential (SNAP): is recorded following synchronous stimulation of a sensory nerve, or the sensory fibres within a mixed nerve. Stimulation and recording along the course of the sensory nerve are undertaken using electrodes placed on the skin surface. Needle electrodes may be used if the nerve is relatively inaccessible or deep to the skin surface (e.g., lateral femoral cutaneous nerve). SNAP amplitudes are small, in the order of microvolts; averaging of 10–20 responses is required to optimise signal to noise ratio (Fig. 6.1). SNAP onset and peak latencies are measured as the time interval to the initial deflection, and the next positive or negative deflection. Conduction velocity is calculated by dividing latency by the distance from the stimulating cathode (Fig. 6.2). Mixed nerve action potential (NAP): is obtained by percutaneous stimulation over nerve trunk, which contains sensory as well as motor fibres, such as the median nerve from

Fig.  6.1  Median sensory action potential recording (orthodromic): stimulation of digit 2, skin recording electrodes placed over median nerve at wrist.

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Fig. 6.2  Median sensory action potential: A2 response from digit 2, A3 response from palmar stimulation (recorded on Nicolet Viking™ EMG system). Markers are set to onset and peak latency; amplitude measures are shown in far right column of numerical data.

the palm, or ulnar nerve action potential recorded from ulnar groove; evoked responses recorded over the skin surface. Amplitude of the NAP is similar to that of SNAPs. Compound muscle action potential (CMAP): is the summated response from the synchronous stimulation of motor nerve fibres evoked by per-cutaneous stimulation over the trunk of a motor nerve. The CMAP response is recorded through skin or needle electrodes placed near to the motor point of a muscle or muscle belly, with a reference electrode placed over an inactive site such as the bony point of muscle insertion (Figs. 6.3 and 6.4). CMAP responses typically have amplitude of several millivolts: they are much larger than SNAP or NAP potentials, and averaging of summated responses is generally not required. CMAP amplitude is influenced by the size, duration, and temporal dispersion of single muscle fibre action potentials, and number of functional motor units within the muscle. Amplitude measurements are made to negative peak, or peak to peak; distal latency is the time interval between stimulation of the nerve and the onset of the response. Motor conduction velocity or speed or propagation of action potential along the nerve is calculated as conduction time/conduction distance (Fig. 6.5).

Fig. 6.3  Median nerve motor study: CMAP recorded with electrodes placed over the APB muscle, with stimulation of the median nerve at the wrist above the carpal tunnel.

H reflex (after Hoffman) : a late CMAP response of consistent latency obtained by anterograde stimulation of alphamotor neurones, which activates Ia fibres innervating muscle

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Fig.  6.4  Tibial nerve motor study: CMAP recorded with electrodes placed over the adductor hallucis muscle, with stimulation of the tibial nerve trunk at the medial malleolus.

spindles forming the afferent arc of this monosynaptic reflex. H reflexes are most readily obtained from the gastrocnemiussoleus muscles; the responses are analogous to the ankle jerk, and may be useful in suspected S1 radiculopathy. F response (from foot, where first obtained): is a late CMAP response of varying latency, produced by non-synaptic, retrograde activation of the anterior horn cell by electrical stimulation of the motor nerve. Activation of different motor units, and collision of action potentials accounts for

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the variability of latency. F responses are a useful measure of conduction in proximal parts of motor nerves, which may be inaccessible to direct stimulation. Central motor conduction time (CMCT): measures the latency of the cortical motor evoked potential (MEP) to a muscle, from which is subtracted the peripheral conduction time from the anterior horn cell to the muscle. The former is usually determined by transcranial magnetic stimulation over the scalp, the latter estimated from F response latency (Figs. 6.6 and 6.7). CMCT is a particularly useful test of the gross integrity of the corticospinal or pyramidal pathway to a muscle. Tests of neuromuscular transmission: include repetitive stimulation at low (3 Hz) and high (20–50 Hz) frequencies, to assess muscle fibre fatiguability, and single fibre EMG (SFEMG). In repetitive nerve stimulation, a decrement of CMAP amplitude and area of >10% is found in disordered post-synaptic transmission, as in acquired and congenital myasthenia gravis. Disorders of neuromuscular transmission cause increased temporal variability in the firing patterns of individual muscle fibres within the same motor unit (“jitter”). This is measured using specialised single fibre EMG needles to record pairs of potentials; SFEMG is a more sensitive (95–98%) test of disordered neuromuscular transmission than repetitive stimulation (Fig. 6.8). Electrotonus: is a generic term for nerve excitability studies, which provide information about the membrane properties of the axon at the site of stimulation. In contrast to

Fig. 6.5  Normal compound muscle action potential recorded from APB. Arrow marks distal motor latency; amplitudes of the distal (wrist) and proximal (elbow) responses are measured from baseline to negative peak.

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axon reflex loop, evoking a sweat response that can be quantified (QSART). This thermoregulatory sweat test is reliable and reproducible. 3. Thermal thresholds – a psychophysical test measuring threshold for perception of temperature sensation, useful in the interrogation of small myelinated A delta (cold threshold) and unmyelinated C (heat threshold) fibre function, with the method of limits used as the most common algorithm (Fig. 6.9).

Fig. 6.6  One of the authors (RK) demonstrating transcutaneous magnetic brain stimulation to measure central motor conduction time in a normal volunteer.

conventional nerve conduction techniques, electronus determines change in membrane potential caused by activation and deactivation of electrogenic ion pumps and channels (Kiernan et al. 2000, 2001a; Nodera and Kaji 2006). Nerve excitability studies are being used to delineate patterns and mechanisms of axonal injury, although there is to date very limited application in traumatic nerve injury. Quantitative sensory testing: small nerve fibre function can be assessed using 1. Sympathetic skin response – a galvanic response of the eccrine sweat glands to electrical (sometimes other sudden noxious) stimulation, and a useful screen of integrity of the sudomotor cholinergic system. The SSR is evoked by passing a current between two points on the skin, measuring electrical skin resistance between these points. 2. Sudomotor axon reflex – post-ganglionic sudomotor cholinergic axon terminals are antidromically stimulated with iontophoresed acetylcholine. This produces orthodromic release of acetyl choline at the nerve endings through an

Sensory evoked potentials (SSEPs) – external (electrical) stimulation of a peripheral nerve trunk in upper or lower limbs evokes responses in peripheral nerve pathways and the central nervous system. Short latency somatosensory evoked potentials (SSEPs) refer to that part of the waveform that occurs within 25 ms (N20) of median nerve stimulation, and within 40–50 ms of tibial nerve stimulation (P40). The best waveform is identified with multiple scalp recordings. Bilateral stimulation, and recording over multiple sites (peripheral nerve, plexus, spinal cord, somatosensory cortex) provides internal control and helps localise the anatomical level of the lesion (Fig. 6.10). Cutaneous stimulation in various dermatomal areas produces dermatomal SEPs (DSEPs). Sensory evoked potentials are used in evaluation of spinal cord disorders and radiculopathies, and in assessment of central sensory pathways. They are not disease specific, but reduction in amplitude generally indicates axonal loss, and prolonged latencies suggest demyelinating pathology, which may be subclinical. Electromyography (EMG): the recording and analysis of spontaneous, insertional and volitional electrical activity of muscle, usually by insertion of a concentric needle electrode. (The term “EMG” is often used colloquially to refer to electrodiagnostic studies that incorporate nerve conduction, with or without electromyography and other investigative techniques. This is misleading and should be avoided. Nerve conduction studies and electromyography, whilst inter-related, are distinct procedures).

• Insertional activity: describes electrical activity generated during needle electrode insertion. • Spontaneous activity following nerve injury leading to denervation typically includes fibrillation potentials and positive sharp waves (spontaneously generated action potentials of individual muscle fibres), fasciculations (spontaneous discharges of individual motor units), and complex repetitive discharges (polyphasic action potentials of uniform morphology and frequency [5–100 Hz], with abrupt onset and offset). EMG records motor unit action potentials (MUPs), generated from single discrete motor units, these being the anatomic and functional unit of an anterior horn cell and its connections (axons, neuromuscular junction) to the level of the muscle fibres. In EMG, MUPs represent the compound

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Fig. 6.7  Motor evoked potentials in abductor digiti minimi in the right hand, transcranial magnetic stimulation applied to scalp overlying the left motor cortex. Sequential cortical evoked responses are displayed; central motor conduction time is calculated using shortest latency responses (A5 & A6).

Fig. 6.8  Compound muscle action potential (CMAPs) evoked by repetitive stimulation at 3 Hz. In this normal subject, there is no significant drop in amplitude or change in area of the evoked potentials in the eight sequential responses.

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Fig. 6.9  thermal thresholds measured in foot of subject with Fabry’s disease (Morgan et al. 1990) in which there is preferential involvement of A-delta fibres, causing elevation of threshold to cooling.

firing characteristics or recruitment and interference pattern. Recruitment refers to the successive activation of motor units following volitional muscle contraction, and interference pattern, the electrical activity recorded during maximal contraction of the muscle (Fig. 6.11). Quantitative EMG (QEMG): uses descriptive as well as automated quantitative methods such as turns/amplitude analysis, frequency analysis to describe morphology and firing characteristics of MUPs. Surface EMG: this records grouped MUPs from muscles using surface electrodes applied to the skin surface, and is useful for multi-level muscle recording in neurogenic disorders to detect fasciculations, and in the study of neurological disorders such as tremor and dystonia (movement disorders in which there is sustained focal, segmental or generalised muscle contraction or tone).

6.2.2 Intra-operative Neurophysiological Procedures

Fig. 6.10  SSEP recording, median nerve stimulation at wrist, evoked response in plexus (N9), spinal cord (N13) and sensory cortex (N20).

action potentials of muscle fibres within the recording territory of the needle electrode, and are described in terms of their duration, amplitude, number of phases, and by the

Electrophysiological monitoring is used in a wide range of surgical procedures to assist the surgeon and maximise functional return for the patient. Techniques have been developed to guide dissection, identify the region of injury, monitor function in sensory and motor nerves and pathways, and protect against iatrogenic injury. A medico-legal role is secondary to these clinical purposes. Monitoring techniques must have the fundamental ability to provide rapid and reliable information about function, at an early and reversible stage

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Fig. 6.11  Normal MUPs recorded from concentric EMG needle placed in deltoid. Upper trace shows full recruitment pattern of motor units of varying size and firing rates.

of potential neural injury. Choice of technique is determined by surgical procedure and neural structures at risk; careful planning between clinical neurophysiologist, surgeon and anaesthetist is required ahead of surgery to select the most appropriate monitoring procedure, enable correct positioning of electrodes used for recording and stimulation, and optimise anaesthesia. Inhalation anaesthetics abolish or markedly attenuate SSEPs, and full neuromuscular blockade will prevent acquisition of EMG; for monitoring of motor nerve or root function using free running or stimulated EMG, partial neuromuscular blockade (up to 75%) (Holland 1998) or short acting neuromuscular blocking agents are required. Free running and stimulated EMG: is used to monitor function in muscles innervated by specific motor nerves or motor roots considered to be at risk during surgery; needle EMG electrodes are placed into the belly of muscles to record motor unit activity evoked by neural stimulation, or to record abnormal high frequency EMG activity (neurotonic discharges) which appear when blunt trauma is applied to motor nerves (Beatty et  al. 1995). For stimulated EMG, bipolar neural stimulation is preferable, as this minimises current

spread to closely lying or adjacent nerves – particularly problematic in plexus surgery. Current spread may also occur through liquid pools in the surgical field; in this situation, hook electrodes can be used to lift the nerve clear for stimulation. EMG signals cannot be recorded during diathermy, because of high frequency artefact. Nerve action potentials: are recorded direct from a nerve to assess continuity across the site of a nerve injury or lesion. In the setting of a post-ganglionic nerve injury, the presence of a nerve action potential indicates at least several thousand intact or regenerating axons, and correlates with functional recovery (Kline and Happel 1993), potentially obviating the need for nerve graft or repair. Somatosensory, dermatomal and root evoked potentials: are used to assess afferent pathways from peripheral nerve or dermatome through plexus and dorsal columns of the spinal cord to somatosensory cortex. Intra-operative SSEPs are the most commonly used modality in spinal surgery to reduce iatrogenic neurological injury, but give limited or no information about individual roots and motor pathways. Recording electrodes may be placed epidurally, on the surface of the

Clinical Neurophysiology in Peripheral Nerve Injuries

cervical cord, or over the cortex. Predictors of post-operative deficit are a 50% reduction in SSEP amplitude; the operation should stop if this occurs, and resume only when there is recovery of the potential. Evidence that SSEP monitoring may protect against spinal cord injury is drawn principally from retrospective reviews of outcome, with and without monitoring; there are no randomised controlled trials of efficacy – such trials now viewed as being unethical. Motor evoked potentials (MEPs): are increasingly used to assess efferent motor pathways and function in corticospinal tracts during spinal surgery and neurosurgery (Sutter et  al. 2007). Current methodology includes ‘D’ wave monitoring and direct recording of EMG in individual muscles. The ‘D’ wave recorded epidurally, represents descending asynaptic volleys in the fast conducting neurones in the corticospinal tract, evoked by single pulse transcranial stimulation. Direct EMG/MUP recording requires multi-pulse stimulation, with multiple motor tracts being involved in generation of responses. Long term motor deficit has been reported to occur post-operatively when there is >50% reduction in the cord D wave in combination with bilateral loss of muscle EMG (Deletis and Sala 2007), whereas motor function was only transiently impaired following surgery in those cases showing unilateral or bilateral loss of muscle EMG, but an unchanged or lesser reduction (90° for stimulation. Knowledge of normal anatomical variants or anomalous innervation is essential (Sonck et al. 1991), and some anomalies are relatively common. The Martin–Gruber anastomosis between the median and ulnar nerves in the forearm is estimated to occur in about 20% of the population. In this anastomosis, median nerve fibres leave the main nerve trunk or the anterior interosseus branch in the forearm, cross over to the ulnar nerve and terminate in intrinsic hand muscles normally supplied by the ulnar nerve. This manifests electrophysiologically as a median evoked CMAP at the wrist being larger than that evoked by stimulation at the wrist – a reversal of the usual pattern of CMAP amplitude – and/or anomalous morphology of the CMAP. A Martin-Gruber anastomosis can present diagnostic difficulties in carpal tunnel syndrome, because some median fibres will be spared from compression at the wrist, and the anatomical variant may also affect electrodiagnosis of ulnar neuropathies at the elbow, where a severe lesion may appear less so because of anomalous innervation of intrinsic hand muscles by the crossed median nerve fibres. Other anomalous innervations include the “all median” and “all ulnar” hands, variations in sensory innervation on the dorsal side of the hand, and the accessory deep peroneal nerve, a branch of the deep peroneal nerve which runs around the lateral malleolus to innervate part of the extensor digitorum muscles in the foot.

Surgical Disorders of the Peripheral Nerves

Errors can be led by the examiner, who may fail to test enough nerves for identification of a more diffuse problem such as a generalised neuropathy underlying an apparently focal entrapment, or who may omit stimulation of nerves in proximal sites for detection of high level conduction block, or who applies the wrong procedure for the clinical problem, such as standard nerve conduction studies in a patient whose clinical symptoms suggest a small fibre neuropathic process. In EMG examination of muscles, several sites must be sampled, since the recording area of a concentric needle is quite small, with the potential to miss a focal area of denervation, reinnervation or myopathic change. Reinnervation proceeds along time as well as space, and assessment of its rate and degree will require serial EMG recordings. Whilst needle EMG may confirm reinnervation, clinical return of movement across the joint may not occur as the number of reinnervated muscle fibres may not be sufficient. Unlike certain other laboratory tests which have absolute meaning if abnormal, clinical neurophysiological data must always be placed in clinical context, and numerical results should not be over-interpreted. For example, sub-clinical slowing of median nerve conduction across the wrist does not equate in itself to carpal tunnel syndrome. Over simplification of findings must be avoided: some patients will have multiple diagnoses, such as a co-existing neuropathy in a patient with obvious primary muscle disease. Crucially, the test strategy should be based on the patient’s symptoms and signs, rather than adhering to fixed protocols of investigation. An important consideration when using serial nerve conduction studies to evaluate progression of a neuropathy, or recovery of a focal nerve lesion, is inter- and intra-examiner variability. Intra-examiner consistency of results is high, whereas amplitudes of SNAPs and CMAPs can vary quite considerably when tests are performed by different examiners (Bleasel and Tuck 1991). Hence, longitudinal nerve conduction studies are best undertaken by the same examiner. Most will be gained from clinical neurophysiological testing if the questions posed by the referring clinician are specific, explicit and answerable. Referrals should be considered in terms of (1) what knowledge will be gained about the patient from the investigation (2) how and whether the result may alter management (3) the degree of urgency of the request. The latter has some practical importance in the UK where clinical neurophysiology is a relatively scarce resource. Regular collaboration and communication between clinicians and clinical neurophysiologists is highly advantageous; the joint peripheral nerve trauma clinics run between the Royal National Orthopaedic Hospitals and the Clinical Neurophysiology department at the National Hospital, Queen Square, since the mid 1980s are a testament to the clinical value of such interaction. The report of the investigation should contain numerical data for all nerves and muscles included in the test, a

Clinical Neurophysiology in Peripheral Nerve Injuries

summary of the findings, and a clinical interpretation. Styles vary according to local laboratory practice, and to some extent, automated report generating systems embedded in modern neurophysiology recording equipment.

6.4 Safety Aspects Nerve conduction studies and needle EMG are generally well tolerated, although patients will experience some discomfort from transcutaneous nerve stimulation and EMG needle insertion. Test procedures are relatively safe, being largely non-invasive (American Association of Electro­ diagnostic Medicine Professional Practice Committee 1999), but there are some risks associated with procedures (Al Shekhlee et  al. 2003). EMG can be hazardous in patients with coagulation disorders or who are taking anti-coagulants, such as warfarin, that prolong prothrombin or partial thromboplastin time. Patients on intensive care often have a higher risk of clotting disorders, or may be on high dose heparin; a clotting screen is prudent before EMG investigation is performed. Needle EMG is safe in patients on low dose aspirin. Peritonitis is a potential complication of needle examination of intercostal and abdominal muscles, and pneumothorax is a risk of needle insertion into intercostal, serratus anterior, suprapinatus and paraspinal muscles. Nerve injury may occur on needle EMG examination of gluteal muscles (sciatic), flexor pollicis longus (superficial radial), pronator quadratus (ulnar) and pronator teres (median). These hazards can be avoided by appropriate positioning of the patient and careful EMG technique. There is a small risk that the electrical field generated by nerve stimulation may alter function of implanted cardiac pacemakers and cardioverter/defibrillator devices, and cardiological advice should be obtained before proceeding. Electrodes must be placed at least 15  cm from the device; stimulus duration should be less than 0.2 ms, and repetition rate no more than 1 Hz. Repetitive nerve stimulation techniques, including those for evaluation of recovery cycles and nerve excitability should not be performed in patient with pacemakers in situ. Appropriate infection control measures are used to minimise risk of transmission of diseases such as Hepatitis B and C, HIV and transmissible spongiform encephalopathies. Infection risk is increased when performing EMG in intrinsic foot muscles in patients with peripheral vascular disease, or in limbs of patients who have undergone extensive lymph node dissection, such as in breast cancer surgery (Al Shekhlee et al. 2003), and should only be performed in such cases if the clinical value of diagnostic information obtained from EMG outweighs infection hazard.

201

6.5 Pathophysiological Correlates Neurophysiological correlates of morphological and functional changes following different types of neural injury, distinction between neurapraxia, axonotmesis, neurotmesis, time course of neurophysiological changes after injury, neurophysiological markers of regeneration and reinnervation

The pathophysiological response of large fibre peripheral nerves to a wide range of injurious processes and pathologies is limited either to loss of axons or demyelination, or a combination of these two processes. The repertoire of response in small diameter unmyelinated nerve fibres is even more restricted – these will either survive or show axon loss (Table 6.1). The principal electrophysiological markers of demyelination are reduction in conduction velocity and occurrence of conduction block. Axonal loss manifests electrophysiologically as attenuation of amplitude of evoked sensory or motor response, with relatively little change in conduction velocity, unless axonal degeneration is of severe degree. Up to 30% reduction in conduction velocity may be seen in less extensive axonal atrophy, due probably to axonal shrinkage or secondary demyelination (Baba et al. 1982). Needle EMG has particular value in assessing the degree and duration of motor nerve axonal loss. Fibrillation potentials and other markers of acute denervation appear first in proximal muscles; the timing of their appearance is dependant on the distance between the site of the nerve lesion and muscle, and is also influenced to some extent by age (see later section on birth lesions of the brachial plexus). There may be an interval of up to 10–40 days before fibrillations appear, limiting the value of early EMG in assessment of axonal damage after nerve trauma, and quantification of fibrillations does not give Table 6.1  electrophysiological consequences of demyelination. Electrophysiological change Pathophysiological basis Slowing of conduction

Caused by delays in regeneration of action potentials at the nodes of Ranvier, or by a transformation of saltatory to linear conduction in a demyelinated segment (Bostock and Sears 1976)

Conduction block

Failure of transmission of action potentials

Decrement in CMAP

Impaired transmission of trains of action potentials manifest as decrement of the CMAP to repetitive stimulation at high frequencies, as a result of greater internal longitudinal resistance and unavailability of current for impulse propagation in the demyelinated segment (Davis 1972). CMAP compound muscle action potential.

202

a direct measure of the degree of axonal loss. As the motor unit undergoes remodelling during denervation and reinnervation, motor unit potentials undergo morphological change from highly polyphasic, complex unstable units seen in the earlier stages to more stable, large units of longer duration that signal axonal reinnervation and re-growth.

6.5.1 Types of Nerve Lesion: the Electrophysiological Consequences In severe focal nerve injury which results in axonal damage or death, conduction failure or block occurs at the site of injury. Distal to this, axons undergo a process of Wallerian degeneration but continue to conduct impulses until axonal degeneration is sufficiently advanced to cause conduction failure. With lesser degrees of neural injury, myelinated nerve fibres may undergo focal demyelination, resulting in either conduction slowing or conduction block. Conduction slowing per se does not produce clinical symptoms, whereas the clinical effects of conduction block are similar to those of axon loss, resulting in weakness or sensory deficit. Demyelinating conduction block may co-exist with axonal degeneration, and the CMAP can aid distinction of focal demyelination causing conduction block from axonal degeneration – a near normal CMAP at 7 days after injury in a clinically weak muscle indicates that significant axonal loss or denervation has not occurred. Both conduction block and conduction failure affect amplitudes of evoked responses from motor and sensory nerves. However, in conduction block, amplitudes are affected when stimulating above or at the site of block, but not below the lesion, whereas conduction failure affects amplitudes when stimulating at any point along the nerve length, distal or proximal to the lesion. The optimal timing for neurophysiological assessment of degree and type of lesion after the initial injury is usually between days 8 and 10, but the length of the distal stump is important in determining the time course of pathophysiological change, with short distal stumps showing the earliest onset of SNAP or CMAP abnormality. In general terms, the CMAP response declines by day 3–5 after nerve injury, and is absent by day 7–9 (Chaudhry and Cornblath 1992). Changes in the sensory response tend to lag behind CMAP diminution by 2–3 days. Immediately after nerve transection, no changes are evident at the level of the neuromuscular junction and the sarcolemmal membrane. Depending upon the length of the distal stump, there is failure of neuromuscular transmission 8–20  h after nerve section (Miledi and Slater 1970). Other length dependent changes of note are a reduction in resting membrane potential and increased sensitivity to acetyl choline (denervation hypersensitivity). The latter occurs as a result of a proliferation of acetyl choline receptors at sites

Surgical Disorders of the Peripheral Nerves

other than the endplate. In motor nerves, abnormal spontaneous activity (fibrillations, sharp waves) occurs 1–4 weeks after the injury, according to distance between the site of neural injury and the motor units in the target muscle. Fibrillation potentials appear when there is spontaneous and asynchronous depolarisation of the muscle membrane. At the ultrastructual level, fibrillations are initiated at the endplates as result of increased sodium conductance, and propagate along the muscle fibre (Smith and Thesleff 1976). The intensity of fibrillation activity approximates to the severity of axonal damage, and the size of the potentials and frequency of firing diminish over time (Fig. 6.12). Nerve lesions due to compression, which are characterised by neurapraxia or axonotmesis, result in focal slowing of conduction as a consequence of localised narrowing, with nodal and paranodal demyelination. Distal to the point of compression, axonal narrowing may produce slowing along the length of the nerve. The earliest electrophysiological abnormality in compressive neuropathies producing conduction block is a significant reduction of the amplitude of the CMAP proximal to the site of the compression. If Wallerian degeneration occurs, there is disruption of axonal conduction to the muscle fibre, which then fires spontaneously, manifesting electrophysiologically as fibrillations and positive sharp waves. Compressive neuropathies can be primarily Schwann cell mediated, rather than a mild form of Wallerian degeneration. Animal studies have shown early Schwann cell apoptosis and proliferation following nerve compression, with down-regulation of myelin

25

20

15

10

5

0

1

2

3

4

5

6

7

8

9

10

Number of days after nerve injury CMAP amplitude (mV) SNAP amplitude (microvolts) Fibrillations (frequency)

Fig. 6.12  Temporal sequence of electrophysiological changes after nerve injury.

Clinical Neurophysiology in Peripheral Nerve Injuries

203

proteins, myelin associated glycoprotein in particular. Axonal integrity is generally unimpaired, allowing for local de-and remyelination, as well as axonal sprouting. Seddon in his classic review (Seddon 1943), recounts the historical classification of nerve injuries into (1) complete anatomical division, (2) a lesion in continuity, and (3) transient block. He credits Prof Henry Cohen with creation of the now standard terms of neurotmesis, where there is loss of anatomical and functional continuity, although the epineurium may be intact, axonotmesis, in which complete peripheral (Wallerian) degeneration occurs but recovery takes place because of the preservation of axon sheaths and the internal architecture, and neurapraxia, where invariably complete recovery of function occurs without peripheral degeneration. Sunderland extended classification of neural injury by emphasising histological changes that occur in a nerve trunk in his categorisation of five different types or degrees of nerve injury (Sunderland 1990). The relationship between these classification systems, and the electrophysiological changes that may be seen in different types of nerve injury, are summarised in (Table 6.2). Neurapraxia: blunt trauma or stretch produces neurapraxia, which is characterised pathologically by focal demyelination. Loss of the myelin sheath impairs the transmission of impulses by changing the biophysical properties of the paranodal and internodal membranes (Bostock and Sears 1976). There is an increase in membrane capacitance and a reduction in the transverse resistance in paranodal and internodal regions, with a resultant deficiency in the current available to depolarise the next node of Ranvier. Demyelination of the paranodal segment in particular markedly influences membrane capacitance, with exposure of the potassium channels leading to persistent hyperpolarisation. In addition, the Na+/K+ ATPase electrogenic pump further drives the membrane towards the

K+ equilibrium potential, which in turn reduces the safety factor for transmission of the action potential (Sears and Bostock 1981). Conduction block thus ensues, characterised clinically by acute weakness in the affected limb, and motor nerve conduction studies typically demonstrate a significant drop in amplitude across the demyelinated nerve segment. Early experimental work confirmed the earliest involvement of large myelinated fibres (Aguayo et al. 1971), with the most superficial fibres being most severely affected. In an animal model of traumatic conduction block in the baboon (Papio papio), in which neurapraxia was induced by pneumatic pressure, the spatial extent or length of the compressive lesion correlated directly with the severity and duration of conduction block (Ochoa et al. 1971). Since axons remain intact in a neurapraxic lesion, function is restored by focal remyelination within days to weeks. Nerve dysfunction may be even more shortlived in transient conduction block following deforming mechanical injury such as compression and traction. The contribution of vascular or ischaemic injury to conduction block was raised by Denny-Brown and others (Denny Brown and Brenner 1944), with subsequent researchers concluding that both biomechanical and vascular factors were responsible. However histological evidence from the work of Gilliatt and associates (Gilliatt 1981), in particular the finding of nodal intussusception, reinforces the role of mechanical deformation as the principal mechanism in the pathogenesis of conduction block in compressive nerve lesions. Neurophysiologically, the neurapraxic lesion manifests with a small/absent CMAP stimulating at and above the site of the lesion, whereas nerve stimulation below the lesion evokes a normal response. Focal slowing of conduction may be demonstrable across the lesion. There are similar changes in the evoked responses of sensory nerves, but demonstration of conduction block in sensory nerves is more difficult, since

Table 6.2  Nerve injury classification and their electrophysiological correlates. Classsification Seddon Sunderland Pathology

Electrophysiological Correlate

Neurapraxia

Grade 1

Myelin injury or ischaemia

Conduction block, with or without conduction slowing

Axonotmesis

Grade 2

Axon loss

Fibrillations

Stromal derangement

Mild diminution to complete absence of SNAP and CMAP responses, in proportion to degree of axonal loss

Endoneurium, perineurium and epineurium intact

± varing degrees of conduction block and slowing associated with myelin injury

Grade 3

Endoneurium disrupted

Fibrillations

Grade 4

Perineurium disrupted

Grade 5

Epineurium disrupted

Nerve distal to lesion shows normal conduction

Absent SNAP and CMAP responses Fibrillations Absent SNAP and CMAP responses Neurotmesis

Fibrillations

Absent SNAPs and CMAPs CV conduction velocity, SNAP sensory nerve action potential, CMAP compound muscle action potential.

204

there is a normal drop in SNAP amplitude when the distance between recording and stimulation sites is 25  cm or more. Fibrillations and other evidence of denervation do not occur in neurapraxic injury. However, since these changes may not appear for up to 2 weeks, neurapraxic lesions cannot be conclusively distinguished from axonal degenerative lesions in the first few days after injury. The term neurapraxia, which typically guarantees rapid and complete recovery, is best reserved for those situations where electrodiagnosis has conclusively shown that demyelinating conduction block is solely responsible for the neural lesion. Axonotmesis: In axonal injuries that do not involve the supporting perineurium, the perineurial sheath provides a channel for axonal regeneration from the cell body, facilitating recovery. Although axonal function is disrupted immediately after the injury, the disconnected distal segment survives for the next 4–7 days. As Wallerian degeneration proceeds centrifugally, the distal segment becomes progressively inexcitable. Axonotmesis and neurotmesis show similar electrophysiological features in the first few days after nerve injury. Initially, the CMAP is small or absent proximal to the lesion, and normal below the site of injury, prior to Wallerian degeneration. In the second week after injury, axonotmetic lesions show progressive reduction in CMAP and SNAP amplitude distal to the site of injury, and fibrillations may appear, depending on distance between site of injury and muscle. Regeneration occurs from the intact nerve cell body, at an average rate of 1 mm/day. The extent to which recovery is possible depends on the degree of internal disorganisation within the nerve, and the distance between the lesion site and the end organs. Neurotmesis In neurotmesis, the nerve is severed or axonal disorganisation is so severe that axonal regrowth is impossible. Axons in the nerve segment below the site of injury remain viable, and therefore excitable, for a few days. If in the second week of injury, stimulation of the distal segment evokes no response, the term neurotmesis can be applied. However, even up to 2 weeks after injury, axonotmesis or lesser degrees of axonal damage cannot be reliably distinguished from neurotmesis using electrophysiologic testing. Neurotmesis is established with certainty only by direct observation of the nerve, but will be suspected in open wounds where significant axonal loss is likely to have occurred through penetrating injury. Since electrodiagnostic testing cannot reliably distinguish neurotmesis and lesser degrees of axonal injury in the first few days after nerve injury, early surgical exploration is recommended if there is suspicion that the nerve is transected or fully sectioned. However early (day 2–3) EMG examination is advocated in the context of iatrogenous nerve injury, since demonstration of even a few volitional motor unit action potentials is evidence for neural continuity although this may not be clinically apparent (Aminoff 2004). Demonstration of conduction across the site of the nerve injury using direct nerve stimulation is also valuable in this situation.

Surgical Disorders of the Peripheral Nerves

6.5.1.1 Special Types of Neural Injury Cold thermal nerve injury: significant nerve injury is found at temperatures below 10°C. Action potentials are preserved between 5°C and 15°C (Paintal 1965). Depending upon the degree of cooling and the duration of exposure, the continuum of pathology includes mild reversible conduction block at the milder end, and axonal swelling and Wallerian degeneration at the severe extremity. The epineurium and perineurium are relatively resistant to injury and are therefore preserved (Denny-Brown et al. 1945). Electrophysiologically, there is an increase in the nerve action potential amplitude and duration (area under the curve) initially, with significant reduction of amplitude and area beginning at 16°C. The temperature is independent of nerve diameter, but lower in unmyelinated nerve fibres (Franz and Iggo 1968). There is also a reduction in conduction velocity, likely related to altered function at the sodium channels (Kiernan et al. 2001b), although experimental studies on rat sciatic nerve suggest that passive properties of the axon may contribute to the reduction in conduction velocity seen at low temperatures (Stecker and Baylor 2009). In the clinical situation, trench foot caused by non-freezing cold, is a typical example of cold induced nerve injury. Although the literature is scarce, case reports suggest damage to myelinated and unmyelinated nerve fibres, with ischaemia and reperfusion contributing to the injury (Irwin et al. 1997). Electrical neural injury: these represent 3–6% of admissions to burns units (Sances et al. 1979). The mechanism of injury is somewhat contentious, although generated heat is generally regarded as being the principal causative agent (Lee and Astumian 1996). Electroporation, a transient opening of ion channels in the cell membrane and ion fluxes leading to cell death, is sometimes invoked as a mechanism in tissue injury (Jellinek 1960). A direct correlation between the strength of current and duration of exposure, with a critical level of irreversible injury (30 mA/3 mm nerve diameter/5 s shock) was noted in experimental studies (Alexander 1941), but scarring and concomitant vascular injury significantly influence the severity and ultimate outcome of neural injury. Nerve injuries may be caused by direct heat (contact burn), and range in severity from reversible conduction block to severe axonal loss. Typically, isolated or multiple mononeuropathies in the vicinity of the electrical discharge occur acutely in about a third of electrical injuries (Duncan 2001) although delayed motor neuronopathies, suggesting involvement of the anterior spinal cord have been described (Ratnayake et  al. 1996; Fu et al. 2008), and may relate to ischaemia of the anterior spinal artery (Ko et al. 2004). Radiation injury to nerves: ionising radiation as a cause of extrinsic nerve damage has been recognised for several decades. The pattern of the response is independent of the type of ionising radiation, and shows an initial period of enhanced activity, reflected in increased conduction velocity

Clinical Neurophysiology in Peripheral Nerve Injuries

and spike amplitude, and reduction in threshold, likely caused by a physico-chemical change in the nerve membrane itself. There is then progressive decline of activity, with the greatest vulnerability seen in small diameter sensory fibres. The total dose of irradiation, rather than the frequency, determines the severity of damage, which may range from myelin fragmentation to Wallerian degeneration (Love 1983). Secondary neural damage is caused by fibrotic and ischaemic change. The most common clinical situation is iatropathic, with brachial and lumbosacral plexus lesions following radiotherapy for adenocarcinomas of the breast, ovary, and lymphomas accounting for most cases. Rare mononeuropathies of the sciatic and femoral nerve have been described (Gikas et al. 2008). Radiation induced brachial plexopathy is more common in younger patients and in those receiving concomitant chemotherapy, and is directly correlated with fraction size, with >2 Gy doses producing more extensive and severe lesions (Olsen et al. 1993). Sensory disturbance is universal. Electromyography is useful in differentiating neoplastic from radiation plexopathy, as myokymias and fasciculations are characteristic of the latter (Lederman and Wilbourn 1984).

6.5.2 Regeneration and Reinnervation Rates of axon regeneration appear to be similar in all somatic nerve fibres (Sunderland 1991). The rate of maturation correlates inversely with nerve thickness, and is influenced by local factors such as level, duration and severity of the lesion, as well as systemic factors such as age and temperature. Nerve repair occurs by two processes – axonal sprouting, with new growth of axons making functional contact with end organs or muscle fibres, and axonal regeneration along the nerve fibres. Histologically, nodal sprouting from the nodes of Ranvier, as well as terminal sprouting from intact nerve terminals, can be identified (Edds 1949). Nodal sprouting is principally determined by the distance between the node and the endplate zone, through the vacant perineurial sheath (Hoffman 1950; Slack and Williams 1981). Factors influencing nodal sprouting include age, type of injury (crush versus complete section), and type of muscle fibre (fast versus slow twitch). When nerve injury is complete, recovery can only take place through axonal regeneration, and reliable electrophysiological monitoring of motor nerve axonal growth is difficult until neuromuscular junctions begin to be reestablished. Reinnervation is heralded by reduction in the amount of fibrillations and other spontaneous activity in a muscle, but this is not easily quantified. The earliest definite electrophysiological evidence of reinnervation is recruitment of a few small unstable MUPs on volitional effort, or evoked by stimulation of the motor nerve distal to the site of injury (nascent units) (Table 6.3).

205 Table  6.3  Electromyography (EMG) findings in denervation and reinnervation. Denervation

Reinnervation

Spontaneous activity – fibrillations, positive sharp waves in acute denervation; fasciculations and complex repetitive discharges in chronic denervation Early

Normal MUPs with increased duration because of late potentials or satellite fibres incorporated through collateral sprouting

On-going

Moderate amplitude polyphasic MUPs of long duration, unstable firing due to variable conduction along unmyelinated sprouts and low safety margin of neuromuscular transmission

Late

Large amplitude increased duration MUPs with stable transmission

MUP motor unit potential.

Immature nerves are typically relatively inexcitable and require higher levels of stimulus intensity to evoke a response. Regenerating nerves also show slower conduction speeds, before remyelination is complete, which manifests as slow velocity and increased distal motor latencies. As maturation and regeneration proceeds, the number of MUPs and size of evoked CMAP increases. On needle EMG, MUPs show increased duration reflecting the enlarged motor unit, and increased polyphasia reflecting reinnervation and increased temporal dispersion of the individual muscle fibre potentials. Recruitment is reduced, and MUP firing rates increase disproportionately in relation to the number of motor units activated. Evidence of recovery of sensory nerves is usually found around the same time as the small unstable MUPs begin to be detected. Regenerating sensory potentials are initially low amplitude and often show dispersion. Recordable nerve action potential responses indicate the presence of at least several thousand moderate-diameter regenerating fibres, and this number of fibres correlates with clinical recovery of injured nerves in experimental animal models (Kline and DeJonge 1968). Whilst clinical tests such as an advancing Hoffman-Tinel sign provide useful indication of recovery in sensory nerves, quantitative sensory tests can help to establish the degree and type of small fibre involvement, although agreement between the two methods may not be evident (Leffler and Hansson 2008). In partial nerve injury, recovery incorporates regeneration of severely affected axons, and reinnervation through collateral sprouting from nerve fibres spared by the injury. Collateral reinnervation usually precedes axonal regeneration, and results in motor units that have increased amplitude, fibre density, territory and duration. The degree of motor axon regeneration may be quantifiable through measures such as automated analysis of MUP shape and firing

206

rates (Dorfman et al. 1989), estimation of motor unit number (McMomas et al. 1971) and estimation of axon number by approximation of conduction velocity (Dorfman 1984). Electrophysiological evaluation can play only a very limited role in the early stages of neural regeneration, before sensory or muscle end organs are reinnervated – although this is arguably the stage at which assessment of potential for recovery would be most valuable for the clinician. Even the detection of a few motor units in previously paralyzed muscles does not necessarily imply that recovery will be complete enough to result in return of useful clinical function.

6.6 Clinical Applications Neurophysiological findings in focal nerve lesions of the upper and lower limbs, plexopathies, radiculopathies, diffuse or multilevel disorders; clinical applications and uses of specific electrodiagnostic techniques

6.6.1 Upper Limb Neuropathies 6.6.1.1 Median Nerve Median neuropathy at the wrist Carpal tunnel syndrome, with a corrected average annual incidence of 60–120/100,000 is probably the commonest surgical referral to the neurophysiology department. Dysfunction of the median nerve is caused by increased pressure between the flexor retinaculum and the floor of the carpal tunnel. Clinical symptomatology includes weakness in the hand, and sensory disturbance that may involve the forearm and upper arm, as well as the hand, with nocturnal and positional provocation of sensory symptoms as well recognised features. There is a bimodal distribution of frequency with a peak at 50–59 years, and another at 75–84 years. Aetiology is multifactorial, with factors such as age, sex, body mass index (BMI) and pregnancy, as well as diseases such as diabetes and rheumatoid arthritis contributing to the disorder (Bland 2005; Becker et al. 2002). Some controversy surrounds the aetio-pathogenesis of the nerve damage, with both deranged myelination and ischaemic axonal injury invoked as primary mechanisms (Kiernan et al. 1999). Correlation of clinical severity with degree of neurophysiological abnormality has been validated in several studies. Bland, using one of the largest databases of 8,501 patients with carpal tunnel syndrome, has demonstrated a strong linear correlation of clinical with neurophysiological severity using a 7 point scoring system of electro physiological abnormality (Bland 2000) (Table 6.4).

Surgical Disorders of the Peripheral Nerves Table 6.4  Neurophysiological grading of median nerve compression in carpal tunnel syndrome, Canterbury system (Adapted from Bland 2000). Grade Degree of Neurophysiological abnormality severity 0

Nil

Nil

1

Very mild CTS

Abnormality detected only in two sensitive tests (e.g., inching, palm-wrist median/ulnar comparison, ring finger “double peak”)

2

Mild CTS

Orthodromic sensory conduction velocity from index finger to wrist 50%

Unfavourable rupture

Neurotmesis

Reduced/8 mm. Significant cold sensitivity and hypersensitivity

Fair. M3, S3

No sensation or severe cold sensitivity and hypersensitivity

Bad M0,1, S0, 1 or 2

Table 8.17  Results of 108 repairs in 95 adult patients: tidy wounds (1977–1985). Grade Nerve Primary repair Delayed repair Graft 35 48 nerves 25 nerves nerves Median

3

0

0

Ulnar

5

0

0

Median

16

5

4

Ulnar

15

2

7

Fair: 39 nerves

Median

7

8

8

Ulnar

2

5

9

Poor: 10 nerves

Median

0

2

2

3

5

Excellent: 8 nerves Good: 49 nerves

Ulnar 0 Drawn from Birch and Raji (1991).

Equivalent on Seddon’s grading

Watson-Jones (1930) analysed more than 100 nerve lesions from amongst 5,000 consecutive patients seen in the Liverpool Fracture Service over the course of 2 years. The nature of injury to the ulnar nerve from fracture of the medial epicondyle, to the common peroneal nerve from fracture of the fibula and the vulnerability of the median nerve distal to

Table  8.18  Repair of 264 median and ulnar nerves in tidy wounds injured between the distal wrist crease and elbow in adults aged between 16 and 65 years (1979–2004). Repair type (number of cases). Outcome Primary Delayed Graft Total repair repair Excellent

13

2

2

17

Good

52

15

34

101

Fair

25

30

52

107

Poor

2

16

21

39

92 63 109 This includes the cases in Tables 8.15 and 8.17.

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pronator quadratus is clearly described. Platt and Watson Jones were strongly in favour of exploration of nerves injured by fractures. Siegel and Gelberman (1991) review the subject thoroughly, finding 85% of nerve palsies recovering spontaneously from closed fractures and 65–70% doing so after open fractures. However ninety per cent of those nerves which went on to recovery had done so by 4 months. These cannot have been wholly degenerative lesions. Siegel and

Compound Nerve Injury

Gelberman set out their indications for intervention which include (1) the fracture needs internal fixation; (2) there is associated vascular injury (3) wound exploration of an open fracture is necessary and (4) a fracture or dislocation is irreducible. We might add to this two more: (5) the lesion deepens while it is under observation, and (6) the lesion occurred during operation for internal fixation. The association between displaced fragments of bone and serious nerve lesions is relevant too. Goldie and Powell (1991) described a case where the median nerve was transfixed by a fragment of the distal radius. They intervened urgently, on the basis of a near complete nerve lesion and radiological evidence of a skeletal cause. Recovery was good. In Omer’s prospective study (Omer 1974) 83% of nerve palsies from closed upper limb fractures recovered; no less than 90% of these had done so by 3 months. If there was no recovery by 7 months then there would be none. Seddon’s own figures (Seddon 1975b) are interesting: 146 from 212 of cases of nerves injured in fractures or dislocations of the upper limb spontaneously recovered to near normal levels but less than one half of his 57 cases of nerve palsies after skeletal injury in the lower limb did so. One third of his own series of radial nerves so injured did not recover but of course these were referred cases. Seddon (1975b) related the information provided by Böhler from the fracture services of Salzburg and Vienna. There were 57 cases of radial palsy in 765 closed fractures of the humeral shaft, an incidence of 7.4%. Spontaneous recovery occurred in 47, so the incidence of unfavourable radial lesions in this series is less than 2%.

8.6.1 The Nerve and the Pattern of Fracture Lambert’s (2005) further opinion on the subject of radial nerve palsy associated with fractures of the shaft of the humerus offers clinicians insights which extend well beyond his theme. Unfortunately this article is available only on the electronic version of the journal. Lambert identifies three important features. First is ‘anatomical fixity’: ‘nerves are injured more readily at or near zones of relative fixity of the nerve within the surrounding tissue. Thus, peri-articular fractures and dislocations are associated with the higher risk of nerve and vascular injuries. Nerves are relatively fixed by the muscular branches entering muscle, the shorter the branch to the muscle, the greater fixity the nerve has relative to the mobile tissues around it.’ The length of the radial nerve trunk between the relatively fixed point of the nerves to the lateral head of triceps and the next fixed point where the nerve pierces the lateral intermuscular septum lies between 10 and 15 cm: ‘injury of some degree is certain if the nerve is stretched between 1.5 and 2.0 cm in the longitudinal axis of the humerus’. Next comes the fracture pattern: ‘short

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oblique, transverse, segmental, and open fractures, in which the intermuscular septum is torn (indicative of the energy of the injury), and the fracture inherently unstable, are associated with a higher incidence of radial palsy than long spiral fractures in which the intermuscular septum may not be torn’. The third element discussed is the blood supply to the nerve. The radial nerve may become relatively ischaemic because of compression by the intermuscular septum: ‘a similar picture occurs in lesions close to the intermuscular septum where direct injury is a result of compression of the nerve trunk and indirect injury through hypoperfusion both contribute to the syndrome of neurostenalgia, the burning painful paraesthesiae associated with sensory motor nerve palsy of variable depth: decompression of the nerve may dramatically relieve the pain’. Lambert concludes that the outlook for a radial nerve injury is far better if exploration and repair are performed within 4 weeks of transection or rupture: ‘perineural fibrosis, intraneural ischaemic fibrosis, and hypoperfusion in the surrounding ischaemic penumbra of the zone of the injury all contribute to the difficulty of exploration and successful nerve repair in the late presentation’. These observations are general to the field of nerves injured by fractures or dislocations. We agree with his final comment: ‘meta-analyses can be useful, but should not supplant clinical observation and decisions based on the logical analysis of fractures type and nerve function in the individual patient, aided by electrophysiological investigation where necessary. Knowledge of, and therefore comfort with, the surgical exposure of a radial nerve is clearly important: lack of either might actually be the most important factor in the decision to treat the nerve expectantly.’ The view that injured nerves can be neglected for 3 months seems to be growing, presumably to ‘see what happens’. Such a policy is baleful, indeed it is deplorable. Each patient should be considered as an individual and not subjected to the rote of an algorithm. In most cases clinical examination will answer the following questions: 1. Is this lesion to the nerve complete or incomplete? 2. Is the lesion one of conduction block or is it one of Wallerian degeneration? Repeated examination during the ensuing 4–6 weeks will usually distinguish between those nerve palsies which are showing signs of recovery from those which are not. We have seen, over the last 10 years, several hundreds of patients in whom the injury was of such a nature that rupture of a nerve could and should have been anticipated. We have seen far too many patients who have lost their means of earning a living or of maintaining their independence because of neglect of the first principles of treatment of the consequences of radial or common peroneal palsies. Matters are not helped by the rise of subspecialisation. The case now described is but one of many.

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Case Report: A 71 year old woman fell in the street sustaining a displaced fracture at the neck of the humerus. The distal fragment was displaced medially and clearly impinged upon the neurovascular axis. She developed pain, which worsened and over the next eight days she experienced a deepening palsy of the median, musculocutaneous, the radial and ulnar nerves. No action was taken because the ‘shoulder surgeon’ was on leave. Delayed hemi arthroplasty was followed by gradual improvement in her pain over the course of the next 6 months but this did not disappear and recovery for the ulnar nerve in particular was poor. We think that this patient’s age had something to do with her neglect, for had she not been a particularly articulate person it is possible that no active treatment would have been offered. Clinicians should not forget that neurophysiological investigations may confirm, or modify, a clinical diagnosis and it has to be said that the service provided by some electrodiagnostic departments to fracture services is poor. We have seen far too many patients who have waited for months before the investigation was done and we have seen patients who, on their own initiative, paid for the investigation to be done privately rather than wait for months. It is fortunate for them that they were not excommunicated from the National Health Service because of their ‘queue jumping’. Case Report: A 78 year old woman fell at home dislocating her elbow. This was promptly reduced in a nearby Accident and Emergency Department but she experienced intense pain and developed a complete median palsy. A letter was written to her family practitioner by the first surgeon five days later which said: ‘I expect she is going to have problems with pain control … she may well consult you regarding this aspect of her care’. Her family practitioner sought a second opinion which was provided 6 weeks after the injury. The second surgeon asked for urgent neurophysiological investigation. These were not performed for 4 weeks and did no more than confirm the clinical diagnosis that the median nerve, entrapped within the elbow joint, was by now destroyed. We follow the following principles in the approach to nerves injured by skeletal injury: 1. Clinical examination usually permits the distinction between lesions of conduction block from deeper, degenerative lesions. 2. A diagnosis of neurapraxia should not be made in the presence of significant neuropathic pain. This suggests that the noxious agent is still at work upon the nerve. 3. Deepening of the lesion whilst under observation indicates bleeding until proven otherwise. 4. The diagnosis of neurapraxia cannot be regarded as secure until the persistence of conduction in the distal segment of the nerve is demonstrated after about eight days from the injury.

Surgical Disorders of the Peripheral Nerves

5. An advancing Tinel’s sign distinguishes the degenerative lesion of favourable prognosis (axonotmesis) from the unfavourable lesion (neurotmesis) in the main nerves of the limb and in particular, the median, the ulnar, the radial, and the common peroneal and tibial nerves. This investigation should enable the clinician to come to a view about the likelihood of recovery at no later than 6 weeks from the injury. Unfortunately, the circumflex nerve cannot be examined by this method because is so deeply seated. 6. Lesions of the sciatic, the tibial and the common peroneal nerves are usually associated with high energy injuries. The likelihood of recovery in the untreated case is generally bad. These three nerves should always be exposed during operation upon the fracture or dislocation (Fig. 8.40). 7. If a surgeon elects to convert a closed fracture to an open one by whatever technique, then the lesion of the nerve should be exposed. The nerve, indeed the nerve with the adjacent artery, may be in the fracture or in the joint. Both will certainly be displaced from their normal position (Fig 8.41). 8. Whilst the presence of nerve palsy is not necessarily an indication for operation the presence of a complete lesion of the main nerve adds to the argument for open treatment of the fracture.

Fig. 8.40  ‘Closed’ intramedullary nailing of fractured shaft of femur. The sciatic nerve was exposed 5 months later. It was in the fracture.

Compound Nerve Injury

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Understanding of their rôle, and of the consequences following lesions has been increased by such studies as those provided by Comtet, Hertzberg and Alnaasan (1993); by Narakas (1993), and by Coene (1985). Pain is usual after injuries to the accessory nerve and the nerve to serratus anterior. Now is as good a time as any to dispel a commonly held misconception that the two peripheral nerves without a cutaneous sensory component are purely ‘ motor’ nerves. This is quite wrong. Both contain large numbers of myelinated and non myelinated afferent fibres. Biopsies of the suprascapular nerve weeks after proven preganglionic injury to the fifth and sixth cervical nerves showed that over 30% of the larger myelinated fibres survived, those presumably responsible for proprioception with cells in the dorsal root ganglion. Lesions of the spinal accessory nerve, and of the nerve to serratus anterior are caused only rarely by skeletal injury, but the effect upon the shoulder girdle function is so severe that it seems appropriate to discuss them here. ‘Winging’ of the scapula is usual after injury to either nerve and should not be ascribed to paralysis of the serratus anterior. The distinction between the two is easy. In accessory palsy the active inferior scapulo-humeral angle is narrowed, usually to about 30° and the scapula drops downwards and away from the mid line (see Fig. 5.61). In paralysis of serratus anterior the scapula is drawn upwards and towards the mid line. The active ISHA is greater than the range of active abduction, a finding which is characteristic for the nerve to serratus anterior and unlike all other nerve palsies involving the shoulder girdle.

8.6.2.1 The Spinal Accessory Nerve

Fig. 8.41  ‘Closed’ intramedullary nailing of fracture of long bone. The tibial nerve and the posterior tibial artery were in the fracture. The muscles of the deep flexor compartment were fibrosed causing severe clawing of the toes.

8.6.2 The Shoulder Girdle and Gleno-Humeral Joints Bonnel (1989) estimated that one quarter of the nerves of the brachial plexus pass to this complex of joints which permits an extraordinarily wide range of movement for the upper limb. This places the nerves at risk as the spinal nerves passing to the brachial plexus are the weakest link in the suspensory chain. One cranial and three peripheral nerves are of particular significance: the spinal accessory (11th cranial), the nerve to serratus anterior, and the suprascapular and circumflex nerves.

This nerve is vulnerable to the attention of surgeons with inadequate knowledge of topographical anatomy and it is too often divided during lymph node biopsy. Williams et  al. (1996) described the unmistakable syndrome of: pain, drooping of the shoulder, and restricted abduction of the shoulder, in 43 iatrogenous cases. The scapula drops downwards and away from the midline (Chapter 5). Camp (2010) has kindly provided her findings from 89 more iatrogenous cases. The surgeon responsible made the diagnosis only rarely. Most of the lesions were recognised by orthopaedic surgeons, some by neurologists and ten were made by solicitors seeking treatment for their clients. The delay before repair of the nerves was, on average, fully 18 months. Repair of the nerve was generally successful, often strikingly so. Most patients experienced early relief of pain and in most there was considerable improvement in function. Pain relief and improvement in function was regained by repair so late as four years after the injury (Fig. 8.42). The spinal accessory nerve appears to be less vulnerable to the harmful effects of delay before repair

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Surgical Disorders of the Peripheral Nerves

supraclavicular brachial plexus, where the fifth, sixth and seventh cervical nerves are avulsed from the spinal cord. The position of the scapula is characteristic. It is drawn upwards, and towards the spine by the unopposed action of trapezius and the levator scapulae muscles. Abduction is restricted, usually to less than 90°, but the inferior scapulo-humeral angle widens as the weight of the upper limb thrusts the scapula towards the mid line. Repair of this nerve, either by suture, graft or by transfer of the deep divisions of intercostal nerves, is attended with a higher success rate than that seen after repair of any other peripheral nerve. This is fortunate because muscle transfers for the paralysed serratus anterior muscle are unreliable and provide only limited function.

8.6.3 The Clavicle

Fig. 8.42  The left spinal accessory nerve was repaired 4 years after injury. Function at 14 months. Table  8.19  Repair by graft of 98 iatrogenous lesions of the spinal accessory nerve. Grade Function Pain Excellent

Normal

None

8

Good

Abduction ³150°

Occasional – no analgesics

58

Fair

Improved, but abduction