Upper Motor Neuron and Spasticity

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Upper Motor Neurone Syndrome and Spasticity Second Edition



Upper Motor Neurone Syndrome and Spasticity Clinical Management and Neurophysiology Second Edition Edited by Michael P. Barnes Professor of Neurological Rehabilitation Walkergate Park International Centre for Neurorehabilitation and Neuropsychiatry Newcastle upon Tyne, UK Garth R. Johnson Professor of Rehabilitation Engineering Centre for Rehabilitation and Engineering Studies (CREST) School of Mechanical and Systems Engineering Newcastle University Newcastle upon Tyne, UK

CAMBRIDGE UNIVERSITY PRESS Cambridge, New York, Melbourne, Madrid, Cape Town, Singapore, São Paulo Cambridge University Press The Edinburgh Building, Cambridge CB2 8RU, UK Published in the United States of America by Cambridge University Press, New York www.cambridge.org Information on this title: www.cambridge.org/9780521689786 © Cambridge University Press 2008 This publication is in copyright. Subject to statutory exception and to the provision of relevant collective licensing agreements, no reproduction of any part may take place without the written permission of Cambridge University Press. First published in print format 2008 ISBN-13 978-0-511-39699-1 eBook (NetLibrary) ISBN-13 978-0-521-68978-6 paperback Cambridge University Press has no responsibility for the persistence or accuracy of urls for external or third-party internet websites referred to in this publication, and does not guarantee that any content on such websites is, or will remain, accurate or appropriate.

Contents List of Contributors page vii Preface to the second edition ix 1 An overview of the clinical management 1 12 Management of spasticity in children 214 of spasticity Rachael Hutchinson and H. Kerr Graham 241 Michael P. Barnes Index 2 Neurophysiology of spasticity 9 Geoff Sheean 3 The measurement of spasticity 64 Garth R. Johnson and Anand D. Pandyan 4 Physiotherapy management of 79 spasticity Roslyn N. Boyd and Louise Ada 5 Seating and positioning 99 Craig A. Kirkwood and Geoff I. Bardsley 6 Orthoses, splints and casts 113 Paul T. Charlton and Duncan W. N. Ferguson 7 Pharmacological management of 131 spasticity Anthony B. Ward and Sajida Javaid 8 Chemical neurolysis in the 150 management of muscle spasticity A. Magid O. Bakheit 9 Spasticity and botulinum toxin 165 Michael P. Barnes and Elizabeth C. Davis 10 Intrathecal baclofen for the control of 181 spinal and supraspinal spasticity David N. Rushton 11 Surgical management of spasticity 193 Patrick Mertens and Marc Sindou v



Contributors Louise Ada Paul T. Charlton Associate Professor Senior Orthotist Discipline of Physiotherapy J. C. Peacock & Son University of Sydney Newcastle upon Tyne, UK Sydney, Australia Elizabeth C. Davis A. Magid O. Bakheit Consultant in Rehabilitation Medicine Professor of Neurological Rehabilitation Walkergate Park International Centre for Department of Rehabilitation Medicine Mount Gould Hospital Neurorehabilitation and Neuropsychiatry Plymouth, UK Newcastle upon Tyne, UK Geoff I. Bardsley Duncan W. N. Ferguson Senior Rehabilitation Engineer Senior Orthotist Wheelchair & Seating Service J. C. Peacock & Son Tayside Rehabilitation Engineering Services Newcastle upon Tyne, UK Ninewells Hospital Dundee, UK H. Kerr Graham Professor of Orthopaedic Surgery Michael P. Barnes Royal Children’s Hospital Professor of Neurological Rehabilitation Melbourne, Australia Walkergate Park International Centre for Rachael Hutchinson Neurorehabilitation and Neuropsychiatry Consultant Paediatric Orthopaedic Surgeon Newcastle upon Tyne, UK Norfolk and Norwich University Hospital NHS Trust Norfolk, UK Roslyn N. Boyd Associate Professor Sajida Javaid Scientific Director Specialist Registrar in Rehabilitation Medicine Queensland Cerebral Palsy and Rehabilitation North Staffordshire Rehabilitation Centre University Hospital of North Staffordshire Research Centre Stoke-on-Trent, UK Department of Paediatrics and Child Health University of Queensland Brisbane, Australia vii

viii Contributors Garth R. Johnson David N. Rushton Professor of Rehabilitation Engineering Consultant in Neurological Rehabilitation Centre for Rehabilitation and Engineering Studies Frank Cooksey Rehabilitation Unit Kings College Hospital (CREST) London, UK School of Mechanical and Systems Engineering Newcastle University Geoff Sheean Newcastle upon Tyne, UK Professor Department of Neurosciences Craig A. Kirkwood University of California – San Diego Medical Senior Rehabilitation Engineer Wheelchair & Seating Service Centre Tayside Rehabilitation Engineering Services San Diego, California, USA Ninewells Hospital Dundee, UK Marc Sindou Professor of Neurosurgery Patrick Mertens Hoˆpital Neurologique et Neuro-Chirurgical Pierre Professor of Neurosurgery Hoˆpital Neurologique et Neuro-Chirurgical Pierre Wertheimer Lyon, France Wertheimer Lyon, France Anthony B. Ward Consultant in Rehabilitation Medicine Anand D. Pandyan North Staffordshire Rehabilitation School of Health & Rehabilitation/Institute for Life Centre Course Studies University Hospital of North Staffordshire Keele University Stoke-on-Trent, UK Staffordshire, UK

Preface to the second edition The first edition of this textbook provided a prac- tical guide and source of references for physicians, surgeons, therapists, orthotists, engineers and other health professionals who are involved in the man- agement of the disabled person with spasticity. The second edition follows the same format. We have updated the chapters and provided new references and described new techniques. We hope we have covered all aspects of management from physiothe- rapy, seating and positioning and orthoses to the use of drugs, intrathecal techniques and surgery. We have also stressed the importance of adequate mea- surement techniques and, indeed, Chapter 3 has been completely rewritten by Garth R. Johnson and Arnand D. Pandyan. We hope that clinicians will con- tinue to find this book helpful and a useful source of reference in their own practise and that it will con- tinue to provide a solid base for a greater understand- ing of the management of spasticity. ix



1 An overview of the clinical management of spasticity Michael P. Barnes Spasticity can cause significant problems with activ- narrowly defined spasticity itself. The UMN syn- ity and participation in people with a variety of neu- drome can occur following any lesion affecting some rological disorders. It can represent a major chal- or all of the descending motor pathways. The clini- lenge to the rehabilitation team. However, modern cal features of the UMN syndrome can be divided approaches to management, making the best use of into two broad groups – negative phenomena and new drugs and new techniques, can produce signif- positive phenomena (Table 1.1). icant benefits for the disabled person. The details of these techniques are outlined in later chapters and Negative phenomena of the UMN syndrome each chapter has a thorough reference list. The pur- pose of this initial chapter is to provide a general The negative features of the UMN syndrome are overview of spasticity management, and it attempts characterized by a reduction in motor activity. Obvi- to put the later chapters into a coherent context. ously this can cause weakness, loss of dexterity and easy fatiguability. It is often these features that are Definitions of spasticity and the upper actually associated with more disability than the pos- motor neurone syndrome itive features. Regrettably the negative phenomena are also much less easy to alleviate by any rehabili- Spasticity has been given a fairly strict and nar- tation strategy. row physiologically based definition, which is now widely accepted (Lance, 1980): Positive phenomena of the UMN syndrome Spasticity is motor disorder characterised by a veloc- These features can also be disabling but neverthe- ity dependent increase in tonic stretch reflexes (muscle less are somewhat more amenable to active inter- tone) with exaggerated tendon jerks, resulting from hyper- vention. At the physiological level there are increased excitability of the stretch reflex, as one component of the tendon reflexes, often with reflex spread. There is upper motor neurone syndrome. usually a positive Babinski sign and clonus may be elicited. These may be important diagnostic signs for This definition emphasizes the fact that spasticity is the physician but are of little relevance with regard only one of the many different features of the upper to the disability. The exception is sometimes the motor neurone (UMN) syndrome. The UMN syn- presence of troublesome clonus. This can be trig- drome is a somewhat vague but nevertheless useful gered during normal walking, such as when stepping concept. Many of the features of the UMN syndrome off a kerb, or can occasionally occur with no obvi- are actually more responsible for disability, and con- ous trigger, such as in bed. In these circumstances sequent problems of participation, than the more clonus can sometimes be a significant disability and 1

2 Michael P. Barnes Table 1.1. Features of the upper motor neurone improvement in the function of the arm, as other syndrome features of the UMN syndrome, particularly muscle weakness, may have a part to play. Negative Positive Soft tissue changes and contractures r Muscle weakness r Increased tendon reflexes with r Loss of dexterity radiation Restriction of the range of movement is not always r Fatiguability simply due to increase of tone and spasticity in r Clonus the relevant muscles. The surrounding soft tissues, including tendons, ligaments and the joints them- r Positive Babinski sign selves, can develop changes resulting in decreased r Spasticity compliance. It is likely that such contractures and r Extensor spasms changes in the soft tissues arise from the muscle r Flexor spasms being maintained in a shortened position. It is pos- r Mass reflex sible, but not absolutely proven, that maintaining a r Dyssynergic patterns of joint through a full range of movement may prevent the longer-term development of soft tissue contrac- cocontraction during movement tures. The frequency of the stretch, either actively r Associated reactions and other or passively, that is required to prevent contractures is unknown. However, it is important to emphasize dyssynergic and stereotypical good posture and seating such that the muscles, as spastic dystonias far as possible, are maintained at full stretch for at least some of every day. The recommendation is that occasionally needs treatment in its own right. The muscles be put through a full stretch for 2 hours other positive features of the UMN syndrome cause in every 24 hours (Medical Disability Society, 1988). more obvious disability. However, more research is needed in this field to determine the degree and frequency of stretch with Spasticity more certainty. A characteristic feature of spasticity is that the hyper- Thus, hypertonia often has both a neural com- tonia is dependent upon the velocity of the muscle ponent (secondary to the spasticity) and a biome- stretch – in other words, greater resistance is felt with chanical component (secondary to the soft tissue faster stretches (this results in the clinical sign of a changes). Obviously biomechanical hypertonia is ‘spastic catch’). Thus, spasticity resists muscle not velocity dependent and restricts movements stretch and lengthening. This has two significant even at slow velocities. Furthermore, biomechanical consequences. First, the muscle has a tendency to hypertonia will not respond to antispastic agents; the remain in a shortened position for prolonged peri- only treatment possibilities relate to physiotherapy, ods, which in turn may result in soft tissue changes stretching, good positioning, splinting and casting. and eventually contractures (Goldspink & Williams, Ultimately surgery may be needed to relieve advanc- 1990). The second consequence is that attempted ing and disabling soft tissue contracture. In practical movements are obviously restricted. If, for exam- terms there is often a mixture of neural and biome- ple, the individual attempts to extend the elbow by chanical hypertonia, and it is very difficult clinically activation of the triceps, this will stretch the biceps, to determine the relative contribution of each of the which in turn will induce an increase in resistance components. Thus, active intervention for spastic- and indeed may prevent full extension of the elbow. ity (e.g. by antispastic medication or local treatment However, it is worth emphasizing that the situa- such as phenol block or botulinum toxin injection) tion is usually more complex. In the above example, relief of the spasticity in the biceps may not lead to

An overview of the clinical management of spasticity 3 is worth undertaking simply to be sure of alleviat- Occasionally a spasm can be useful from a functional ing at least the neural component of the hypertonia. point of view. Placing pressure on the base of the foot There is often a gratifying response even in limbs that in order to stand can sometimes produce a strong appear to have fixed contractures. extensor spasm of the leg, effectively turning it into a rigid splint, which, in turn, aids walking. Occasion- In advanced spasticity, it is often the soft tissue ally individuals can make positive use of self-induced changes that contribute most to the disability and are spasms, such as for putting on trousers. This empha- resistant to treatment. Increasing deformity of the sizes the importance of detailed discussion with the limbs will clearly lead to rapidly decreasing function disabled person and his or her carer before assuming and often result in problems with regard to hygiene, that the spasm will need treatment. Finally, extensor positioning, transferring and feeding and make the and flexor spasms can be extremely painful; even if individual more prone to pressure sores (O’Dwyer not causing undue functional disturbance, they can et al., 1996). need treatment in an attempt to relieve the associ- ated acute pain. Flexor and extensor spasms Spastic dystonia and associated reactions Severe muscle spasms are often found in UMN syn- drome. These can be in either a flexor pattern or an Most of the previously described positive phenom- extensor pattern. ena of the UMN syndrome can occur at rest. Another range of problems can occur on movement. For The commonest pattern of flexor spasm is flexion example, there is the classic hemiplegic posture, of the hip, knee and ankle. The spasms can some- commonly occurring in stroke, that often occurs times occur spontaneously or, more commonly, when the individual tries to walk. This posture con- in response to stimulation, are often mild. Sim- sists of a flexed, adducted, internally rotated arm ple movement of the legs or adjusting position in with pronated forearm and flexed wrist and fin- a chair can be enough to induce the spasm. The gers. The leg is extended, internally rotated and spasms themselves can be painful and are some- adducted, and the ankle is plantar flexed and times so frequent and severe that a permanent state inverted, often with toe flexion. Other patterns of flexion is produced. If spasms worsen suddenly, occurring on movement are sometimes called spas- it is worth looking for aggravating factors such as tic dystonias (Denny-Brown, 1966). This is a term pressure sores, bladder infections, irritation from a that probably ought to be avoided, given the poten- catheter or even such apparently mild stimulants tial confusion with extrapyramidal disease. such as an ill-fitting orthosis or a tight-fitting catheter leg bag. Occasionally constipation or bladder reten- Other problems that occur on movement or tion can also produce a flexor spasm, which can then attempted movement involve co-contraction of the be associated with a reflex emptying (mass reflex) of agonist and antagonists. Simultaneous contraction the bowel or bladder. of agonist and antagonist muscles is a normal motor phenomenon and is required for the smooth move- Similar problems can occur with extensor spasms, ment of the limb. However, in the UMN syndrome, which are commonest in the leg and involve exten- agonist and antagonist muscles may co-contract sion of the hip and knee with plantar flexion and inappropriately and thus disrupt normal smooth usually inversion of the ankle. Once again, such limb movement (Fellows et al., 1994). Sometimes spasms can be triggered by a variety of stimuli and involuntarily activation of muscles remote from the sometimes can be so severe as to produce a perma- muscles involved in a particular task also contract. nent extensor position. Extensor spasms are proba- For example, if the individual attempts to move an bly more common than flexor spasms in incomplete arm, then a leg may extend or flex. Conversely the spinal cord lesions and cerebral lesions, but there is no clear association with any particular pathology.

4 Michael P. Barnes arm can flex when attempting to walk (Dickstein maintaining a suitable seating posture. Spasticity et al., 1996). These ‘associated reactions’ (Walshe, may make it difficult to self-propel a wheelchair. 1923) can interfere with walking by unbalancing Extensor spasms may constantly thrust the individ- the individual or, for example, making it impossi- ual forward while sitting in the chair, giving rise to ble to do any task with the arms while standing. an increased risk of shear forces that can cause pres- Various other patterns of dyssynergic and stereo- sure sores. Seating will often require a considerable typical contractions have been described, such as range of bracing, supports and adjustments in order extensor thrust (Dimitrijevic et al., 1981). However, to allow the person to maintain a useful and com- the labelling of these problems is less helpful than a fortable position. prolonged period of observation and discussion with the disabled person, the family and the person’s car- Loss of dexterity ers. Simple bedside testing is usually inadequate to determine an overall treatment strategy. The pattern In the arm, the UMN syndrome can cause further dif- of spasticity and the functional consequences dur- ficulties with, for example, feeding, writing, personal ing attempted movement as well as at rest all need care and self-catheterization. Mobility in bed may careful assessment, often over prolonged periods of be hampered and loss of dexterity in the arm may time. Reports from a well-educated disabled person make it difficult to self-ambulate in a wheelchair. All who can describe the problems in different circum- these problems can slowly lead to decreased inde- stances are of far more value than a single examina- pendence and a consequent increased reliance on a tion in the outpatient clinic. third party. Clinical consequences Bulbar and trunk problems The above description of the different patterns of the Although most of the functional consequences of UMN syndrome make it clear that there is a poten- spasticity occur in the arm or leg, it is worth remem- tially wide range of functional problems. In order bering that truncal spasticity can cause problems to draw the discussion together, the major conse- with seating and maintaining an upright posture – quences can be annotated as follow. necessary for feeding and communication. Bulbar problems can give rise to difficulty swallowing, with Mobility consequent risk of aspiration or pneumonia. Further problems can arise with communication, secondary Probably the most common consequence of the not only to inappropriate posture but also to spastic UMN syndrome is difficulty walking. The gait can be forms of dysarthria. clumsy and uncoordinated, and falling can become a common event. Eventually walking may become Pain impossible owing to a combination of soft tissue con- tractures, flexor or extensor spasms and unhelpful It is not widely recognized that spasticity and the associated reactions. It is also worth bearing in mind other forms of UMN syndrome can be extremely that individuals with UMN syndrome may often painful. This is particularly the case with flexor have a whole variety of other neurological problems, and extensor spasms, and sometimes treatment is such as cerebellar ataxia or proprioceptive distur- needed simply for analgesia rather than improve- bance, which further compounds the problem. Even ment of function. Abnormal postures can also give if the individual cannot walk, the UMN syndrome rise to an increased risk of musculoskeletal prob- can cause further problems with regard to difficulty lems and osteoarthritic change in the joints. Any peripheral stimuli from problems such as ingrowing

An overview of the clinical management of spasticity 5 toenails or small pressure sores can, in turn, exacer- explanation. This also implies that there should be bate the spasticity, and a vicious circle of increased an appropriate method of measuring outcome, so pain and increased spasticity can ensue. that one knows when the aim is fulfilled. Chapter 3 discusses the topic of measurement in spasticity. Carers and nursing problems Outcomes clearly need to be geared to the aim of treatment. For example, if the aim of the treatment Spasticity is one of the unusual conditions that can is to improve hand function, a simple, reproducible sometimes require treatment of the disabled per- and valid test of hand function will be required. If son for the sake of the carer. Individuals, particularly the outcome is a reduction of pain, perhaps use of with advanced spasticity, can be extremely difficult a visual analogue scale will be helpful. The use of to move and nurse. Transfers from bed to toilet or a global disability or activities of daily living (ADL) bed to wheelchair can be laborious. Hygiene can be scale is usually inappropriate, as subtle treatment a problem with, for example, marked adductor spas- effects may be masked. ticity, causing problems with perineal hygiene and catheter care. Flexion of the fingers can cause partic- It is important, particularly in people needing ular difficulties with hygiene in the palm of the hand. long-term treatment, that the aims and purposes of Thus, aggressive treatment of spasticity can some- treatment be reviewed regularly and new goals set or times be a factor in reducing carer stress, which in old goals adjusted. This is particularly the case with turn can make the difference between the individual the use of long-term antispastic medication when remaining at home or moving into an institution. the side effects of treatment may at some point out- weigh its benefits (see Chapter 7). An approach to management Self-management The previous section indicated the complexity and functional consequences of spasticity. The following Education of the disabled person and his or her chapters in the book outline the detail of the dif- family is vital, as in all rehabilitation management. ferent approaches to the management, but this sec- Spasticity and the UMN syndrome involve complex tion attempts to provide an overview of the process phenomena. The individual needs to be aware of (Fig. 1.1). some of the factors that may aggravate the prob- lem, such as inappropriate positioning, tight-fitting Aims of treatment shoes, or even heavy bedclothes. A detailed appraisal of the pattern of spasticity may enable the individ- The first question to ask is whether treatment is ual to relieve many of the functional problems. Both needed at all. The previous section has shown that the clinician and the individual should be aware of occasionally a spastic pattern can be functionally potential aggravating factors, such as the worsening useful, such as an aid to walking or dressing. Spas- effect on spasticity of bladder infection or constipa- ticity in the UMN syndrome may be abnormal from tion. a neurophysiological point of view, but this does not mean that treatment is always required. The aims of The physiotherapist and the orthotist treatment will always need careful annotation and discussion with the individual. The commoner aims The early involvement of an experienced physio- are to improve a specific function, reduce pain, ease therapist is invaluable. There are many potential the task of caring or prevent long-term problems, interventions, ranging from simple passive range-of- such as soft tissue contractures. The specific aims motion exercises to more complex antispastic phys- of a particular treatment strategy always need clear iotherapy approaches (see Chapters 4 and 5). The physiotherapist can also administer symptomatic

6 Michael P. Barnes Spasticity and UMN syndrome present? Does it interfere with function, care or cause pain? No Yes Might treatment be needed Identify goals to reduce the risk of longer- Is the individual educated term complications? about spasticity? No Yes No Yes • No treatment needed Initiate self-awareness Are there treatable • Monitor programme aggravating factors? No Yes Involve physiotherapist (± orthotist) Remove for posturing/seating/splinting/ orthosis/exercise programme etc. Is spasticity still a problem? Is spasticity still a problem? Yes No Consider oral Monitor Yes No medication Monitor Is spasticity still a problem? (medication insufficient or not tolerated) Yes Consider focal techniques (phenol blocks/botulinum/ intrathecal baclofen) Is spasticity still a problem? Yes Consider surgery Figure 1.1. Flowchart outlining the approach to the overall management of spasticity.

An overview of the clinical management of spasticity 7 treatment such as heat and advice on the use of Chapter 9). The latter, in particular, is a remarkably hydrotherapy as well as the prescription of splints safe and useful technique, but once again it is impor- and casts. At this point the input of an orthotist is tant to emphasize that it is not often used in isola- essential, as many situations are helped by the judi- tion but rather as part of an overall treatment pack- cious application of a suitable orthotic device (see age. For example, the use of botulinum can facilitate Chapter 6). Much can be achieved by these nonin- positioning in physiotherapy or ease the fitting of an vasive techniques before resorting to medication or orthosis. Fortunately, the effect of botulinum toxin invasive focal treatments. is reversible over a period of 2 to 3 months, which enables reappraisal and reassessment on a regular Oral medication basis. Phenol nerve blocks are equally efficacious but more difficult to administer, and there is the risk Chapter 7 outlines the various pharmacological of a permanent effect. However, phenol is very sig- possibilities of antispastic medication. Medication nificantly cheaper than botulinum toxin and thus is should rarely be used in isolation but usually is just more relevant and practical in developing countries. part of a whole treatment strategy. Medication can provide a useful background effect, which makes, Intrathecal and surgical techniques for example, the fitting of an orthosis or positioning in a chair easier and more comfortable. Occasion- Occasionally spasticity is very resistant to interven- ally, particularly in mild spasticity, the use of anti- tion and further invasive techniques need to be con- spastic medication can be sufficient in isolation to sidered. Intrathecal baclofen (see Chapter 10) is now reduce a functional problem, such as troublesome a well-recognized and relatively safe procedure. In clonus. The problem with medication is that it is some centres, it is used in preference to other focal often associated with side effects. These particularly techniques, such as botulinum toxin. The technique focus around increased weakness and fatigueability. is generally safe, although it can occasionally be asso- Spasticity is often a focal problem, and medication ciated with unwanted complications such as pump will clearly give a systemic effect. Thus, muscles that failure, infection or movement of the catheter tip. are not troublesome can be inappropriately weak- ened and the overall functional effect can be made Finally, there is the possibility of surgical interven- worse. tion (see Chapter 11). There are some surgical tech- niques, such as rhizotomy, that relieve spasticity in Medication may reduce some of the positive their own right, but surgery is now often reserved for effects of the UMN syndrome but at the same time the unwanted complications of spasticity, particu- make some of the negative effects worse. The pur- larly soft tissue contracture. If soft tissue contracture poses and goals of medication need to be care- is advanced and disabling, there is often no option fully annotated and the use of medication constantly but to resort to surgical release and repositioning of reviewed. the limb. However, it is probably true that if spasticity is treated appropriately and actively at the outset, it Focal techniques is only the very rare individual who will need surgery. The need for intervention in spasticity is often con- Overall, we hope that this book gives a practical centrated on one or a few muscle groups. Thus, a and straightforward account of the various treatment focal approach is often more appropriate than the approaches to spasticity as well as emphasizing the systemic effect induced by oral medication. In recent importance of setting clear goals with clear outcome years increasing value has been placed on focal tech- measures. We trust the book makes it clear that spas- niques such as phenol and alcohol nerve blocks ticity is a highly variable and dynamic phenomenon. (see Chapter 8) and the use of botulinum toxin (see Treatment needs careful planning, careful monitor- ing and above all the input and involvement not only

8 Michael P. Barnes of the physician, physiotherapist and orthotist but torque development at the elbow in spastic hemiparesis. also of the person with the spasticity and his or her Electroenceph Clin Neurophysiol, 93: 106–12. carer. Goldspink, G. & Williams, P. E. (1990). Muscle fibre and con- nective tissue changes associated with use and disuse. In: REFERENCES Ada, A. & Canning, C. (eds), Foundations for Practice. Top- ics in Neurological Physiotherapy. Heinemann, London, Denny-Brown, D. (1966). The Cerebral Control of Movement. pp. 197–218. Liverpool: Liverpool University Press, pp. 170–84. Lance, J. W. (1980). Symposium synopsis. In: Feldman, R. G., Young, R. R. & Koella, W. P. (eds), Spasticity: Disorder Dickstein, R., Heffes, Y. & Abulaffio, N. (1996). Electromyo- of Motor Control. Year Book Medical Publishers, Chicago, graphic and positional changes in the elbows of spastic pp. 485–94. hemiparetic patients during walking. Electroenceph Clin Medical Disability Society. (1988). The Management of Trau- Neurophysiol, 101: 491–6. matic Brain Injury. Development Trust for the Young Dis- abled, London. Dimitrijevic, M. R., Faganel, J., Sherwood, A. M. & McKay, O’Dwyer, N. J., Ada, L. & Neilson, P. D. (1996). Spasticity and W. B. (1981). Activation of paralysed leg flexors and exten- muscle contracture following stroke. Brain, 119: 1737–49. sors during gait in patients after stroke. Scand J Rehab Walshe, F. M. R. (1923). On certain tonic or postural reflexes Med, 13: 109–15. in hemiplegia with special reference to the so-called ‘asso- ciated movements’. Brain, 46: 1–37. Fellows, S. J., Klaus, C., Ross, H. F. & Thilmann, A. F. (1994). Agonists and antagonist EMG activation during isometric

2 Neurophysiology of spasticity Geoff Sheean Introduction the flexors, that appears to increase with the speed of the testing movements. They also recall a clasp- The pathophysiology of spasticity is a complex sub- knife phenomenon at the knee, tendon hyperreflexia ject and one frequently avoided by clinicians. Some with crossed adductor reflexes, ankle clonus, exten- of the difficulties relate to the definition of spastic- sor plantar responses, a tendency for flexor spasms ity and popular misconceptions regarding the role and, on occasion, extensor spasms. Or perhaps they of the pyramidal tracts. On a more basic level, the picture the stroke patient with a hemiplegic posture, lack of a very good animal model has been a prob- similar hypertonia in the upper limbs but more in lem for physiologists. Nonetheless, a clear concept the flexors, a tendency for extension of the whole leg of the underlying neurophysiology will give the clin- when bearing weight and increasing flexion of the ician better understanding of their patients’ clinical arm as several steps are taken. features and provide a valuable basis upon which to make management decisions. Lance’s definition has been criticized for being too narrow by describing spasticity only as a form of Definition hypertonia (Young, 1994). However, Lance’s defini- tion points out that this form of hypertonia is simply Some of the difficulty that clinicians experience one component of the upper motor neurone (UMN) with understanding the pathophysiology of spastic- syndrome (Table 1.1, p. 2). The clinician tends to pic- ity is due to the definition of this condition. Most ture the whole UMN syndrome and regard all the textbooks launch the discussion with a definition ‘positive’ features of the syndrome as ‘spasticity’. For offered by Lance (1980) and generally accepted by example, increasing flexor spasms is often recorded physiologists: as worsening spasticity. Because these positive fea- tures do tend to occur together, the clinician often Spasticity is a motor disorder characterized by a velocity- uses the presence of these other signs (tendon hyper- dependent increase in tonic stretch reflexes (‘muscle tone’) reflexia, extensor plantar responses, etc.) to conclude with exaggerated tendon jerks, resulting from hyperex- that a patient’s hypertonia is spasticity rather than citability of the stretch reflex, as one component of the upper rigidity or dystonia. motor neurone syndrome. However, these positive features do not always It may be difficult for clinicians to correlate this def- occur together, and other factors may contribute to inition with a typical patient. They may see instead a patient’s hypertonia. Furthermore, the pathophys- a patient with multiple sclerosis who has increased iology of the positive features of the UMN syndrome muscle tone in the legs, more in the extensors than is not uniform, as explained subsequently, and their response to drug treatment may also be different. Thus, there is merit in treating each of the positive 9

10 Geoff Sheean features of the UMN syndrome as separate but over- Human observations were usually afforded by dis- lapping entities and in particular to restrict the defi- ease or trauma and occasionally by stimulation. One nition of spasticity to a type of hypertonia, as Lance of the difficulties with the animal studies, especially has done. with cats, was in translating the findings to humans. Monkey and chimpanzee experiments are thought to Chapter overviews have greater relevance. The studies chiefly focused on which areas of the CNS, when damaged, would Because this is a chapter on spasticity, the ‘negative’ produce motor disturbances and which other areas, features of the UMN syndrome, such as weakness when ablated or stimulated, would enhance or ame- and loss of dexterity, are not discussed. The major- liorate the signs. Lesion studies, both clinical and ity of the ‘positive’ features of the UMN syndrome experimental, may also be difficult to interpret, given are due to exaggerated spinal reflexes. These reflexes that the lesions may not be confined to the target are under supraspinal control but are also influ- area; histological confirmation has not always been enced by other segmental inputs. The spinal mecha- available. nisms or circuitry effecting these spinal reflexes may be studied electrophysiologically. This discussion One early model was the decerebrate cat devel- of the neurophysiology of spasticity begins, then, oped by Sherrington. A lesion between the supe- with the descending motor pathways comprising the rior and inferior colliculi resulted in an immediate upper motor neurones, which, when disrupted, pro- increase in extensor (antigravity) tone. For several duce the UMN syndrome. Following that, the spinal reasons, this model is not especially satisfactory as reflexes responsible for the clinical manifestations a model of human spasticity (Pierrot-Deseilligny & are explained. This section includes the nonreflex Mazieres, 1985; Burke, 1988). or biomechanical factors that are of clinical impor- tance. The final section deals with the spinal mech- This vast body of work was reviewed by Denny- anisms that may underlie the exaggerated spinal Brown (1966) and integrated with his findings. It reflexes. has been excellently summarized more recently by Brown (1994). Descending pathways: upper motor neurones Fibres of the pyramidal fibres arise from both pre- central (60%) and postcentral (40%) cortical areas. Spasticity and the other features, positive and neg- Those controlling motor function within the spinal ative, of the UMN syndrome (as listed in Table 1.1) cord arise from the precentral frontal cortex, the arise from disruption of certain descending path- majority from the primary motor cortex (Brodmann ways involved in motor control. These pathways area 4, 40%) and premotor cortex (area 6, 20%). Post- control proprioceptive, cutaneous and nocicep- central areas (primary somatosensory cortex, areas tive spinal reflexes, which become hyperactive and 3, 1, 2, and parietal cortex, areas 5 and 7) contribute account for the majority of the positive features of the remainder but these are more concerned with the UMN syndrome. modulating sensory function (Rothwell, 1994). At a cortical level, isolated lesions in monkeys and apes of Extensive work was done, mostly on animals, in the the primary motor cortex (area 4) uncommonly pro- latter part of the last century and the early years of duce spasticity. Rather, tone and tendon reflexes are this century to discover the critical cortical areas and more often reduced. It seems that lesions must also motor tracts. These experiments involved making involve the premotor cortex (area 6) to produce spas- lesions or electrically stimulating areas of the cen- ticity. Such lesions made bilaterally in monkeys are tral nervous system (CNS) and observing the results. associated with greater spasticity, indicating a bilat- eral contribution to tone control. Subcortical lesions at points where the motor fibres from both areas of the cortex have converged (e.g. internal capsule) are

Neurophysiology of spasticity 11 more likely to cause spasticity. Even here, though, syndrome is a misnomer, it is so ingrained in clini- some slight separation of the primary motor cortex cal terminology that to attempt to remove it appears (posterior limb) and premotor cortex (genu) fibres pedantic. allows for lesions with and without spasticity (Fries et al., 1993). Brainstem areas controlling spinal reflexes Although both cortical areas 4 and 6 must be The following discussion is readily agreed to be affected to produce spasticity and both contribute somewhat simplistic but is conceptually correct. to the pyramidal tracts, isolated lesions of the pyra- From the brainstem arise two balanced systems for midal tracts in the medullary pyramids (and in the control of spinal reflexes, one inhibitory and the spinal cord) do not produce spasticity. Hence, there other excitatory (Fig. 2.1). These are anatomically are nonpyramidal UMN motor fibres arising in the separate and also differ with respect to suprabulbar cortex, chiefly in the premotor cortex (area 6), that (cortical) control. travel near the pyramidal fibres which must also be involved for the production of spasticity. It is debat- Inhibitory system able whether these other motor pathways should be called extra-pyramidal or parapyramidal. Denny- The parapyramidal fibres arising from the premotor Brown (1966) preferred the former but I favour the cortex are cortico-reticular and facilitate an impor- latter, as does Burke (1988), to emphasize their close tant inhibitory area in the medulla, just dorsal to the anatomical location to the pyramidal fibres and to pyramids, known as the ventromedial reticular for- avoid confusion with the extrapyramidal fibres from mation (Brown, 1994). Electrical stimulation of this the basal ganglia that produce rigidity. This close area inhibits the patella reflex of intact cats. In decer- association of pyramidal and parapyramidal fibres ebrate cats, the previously rigid legs become flaccid continues in the spinal cord where lesions confined (Magoun & Rhines, 1947) and muscle tone is reduced to the lateral corticospinal tract (pyramidal fibres) in cats that have been made spastic with chronic produce results similar to those of the primary motor cerebral lesions (cited in Magoun & Rhines, 1947). In cortex and medullary pyramids, without spasticity. the early spastic stage of experimental poliomyelitis More extensive lesions of the lateral funiculus add in monkeys, the most severe damage was found in spasticity and tendon hyperreflexia. this region (Bodian, 1946). Stimulation of this region in intact cats also inhibits the tonic vibration reflex Given these findings, just what are the conse- (discussed further on). Flexor reflex afferents are quences of a pure pyramidal lesion? In primates, also inhibited (Whitlock, 1990) (see below). That this there is only a loss of digital dexterity (Phillips & inhibitory centre is under cortical control was veri- Porter, 1977) and, in humans, mild hand and foot fied by the finding of potentiation of some of these weakness, mild tendon hyperreflexia, normal tone effects by stimulation of the premotor cortex or inter- and an extensor plantar response (Bucy et al., 1964; nal capsule (Andrews et al., 1973a,b). There may also van Gijn, 1978). Although there are reports that sug- be some cerebellar input (Lindsley et al., 1949). The gest that spasticity might arise from ‘pure’ lesions, descending output of this area is the dorsal reticu- such as strokes, of the pyramidal tracts (Souza et al., lospinal tract located in the dorsolateral funiculus 1988, abstract in English), there is always the concern (Engberg et al., 1968). that these lesions might really have affected adja- cent parapyramidal fibres to some degree. Thus, the Excitatory system bulk of the UMN syndrome, both positive and neg- ative features, is not really due to interruption of the Higher in the brainstem is a diffuse and extensive pyramidal tracts, save perhaps for the extensor plan- area that appears to facilitate spinal stretch reflexes. tar response, but of the parapyramidal fibres (Burke, 1988). Although this implies that the term ‘pyramidal’

12 Geoff Sheean Cortex Pre-motor Supplementary motor area A Internal capsule Ventromedial Bulbopontine Vestibular reticular formation tegmentum nucleus B Inhibitory Excitatory Dorsal reticulospinal tract Lateral corticospinal tract Medial reticulospinal tract Vestibulospinal tract C + ()+ () Segmental interneuronal network Figure 2.1. A schematic representation of the major descending systems exerting inhibitory and excitatory supraspinal control over spinal reflex activity. The anatomical relations and the differences with respect to cortical control between the two systems mean that anatomical location of the upper motor neurone lesion plays a large role in the determination of the resulting clinical pattern. (A) Lesion affecting the corticospinal fibres and the cortico-reticular fibres facilitating the main inhibitory system, the dorsal reticulospinal tract. (B) An incomplete spinal cord lesion affecting the corticospinal fibres and the dorsal reticulspinal tract. (C) Complete spinal cord lesion affecting the corticospinal fibres, dorsal reticulospinal fibres and the excitatory pathways. (+) indicates an excitatory or facilitatory pathway; (−) an inhibitory pathway. The excitatory pathways have inhibitory effects on flexor reflexes. (From Sheean, 1998a.) Stimulation studies suggest that its origin is in the 1990), stimulation of the motor cortex and internal sub- and hypothalamus (basal diencephalon), with capsule does not change the facilitatory effects of efferent connections passing through and receiv- this region (Andrews et al., 1973a,b). Thus, this exci- ing contributions from the central grey and tegmen- tatory area seems under less cortical control than tum of the midbrain, pontine tegmentum and bul- its inhibitory counterpart. Its descending output is bar (medullary) reticular formation (separate from through the medial reticulospinal tracts in the ven- the inhibitory area above). Stimulation of this area in tromedial cord (Brown, 1994). intact monkeys enhances the patella reflex (Magoun & Rhines, 1947) and increases reflexes and extensor The lateral vestibular nucleus is another region tone and produces clonus in the chronic cerebral facilitating extensor tone, situated in the medulla spastic cat mentioned above (see ‘Inhibitory system’ close to the junction with the pons. Stimulation pro- on p. 11) (Magoun & Rhines, 1947). Lesions through duces disynaptic excitation of extensor motoneu- the bulbopontine tegmentum alleviate spasticity rones (Rothwell, 1994). Its output is via the lateral (Schreiner et al., 1949). Although input is said to vestibulospinal tract, located in the ventromedial come from the somatosensory cortex and possi- cord near the medial reticulospinal tract. Although bly the supplementary motor area (SMA) (Whitlock, long recognized as important in decerebrate rigidity, it appears less important in spasticity. An isolated

Neurophysiology of spasticity 13 lesion here has little effect on spasticity in cats flexor spasms. Degeneration of the locus coeruleus is (Schreiner et al., 1949) but enhances the antispastic also seen in Parkinson’s disease and Shy-Drager syn- effect of bulbopontine tegmentum lesions. Similarly, drome and neither have spasticity as a sign. Further- lesions of the vestibulospinal tracts performed to more, the putative mechanism of tizanidine in spas- reduce spasticity had only a transient effect (Bucy, ticity is such that would be mimicked by increased 1938). coerulospinal activity. However, the coerulospinal tract appears to provide excitatory drive to alpha Although both areas are considered excitatory and motoneurones (Fung & Barnes, 1986) and inhibit facilitate spinal stretch reflexes, they also inhibit Renshaw cell recurrent inhibition (Fung et al., 1988), flexor reflex afferents (Liddell et al., 1932; Whitlock, effects, which would be expected to increase stretch 1990), which mediate flexor spasms (see below). reflexes. The lateral vestibulospinal tract also inhibits flexor motoneurones (Rothwell, 1994). Descending motor pathways in the spinal cord As indicated above, the principal descending motor Other motor pathways descending from tracts within the spinal cord in the production of the brainstem spasticity is the inhibitory dorsal reticulospinal tract (DRT) and the excitatory median reticulospinal tract Rubrospinal tract (MRT) and vestibulospinal tract (VST) (Fig. 2.1). As Despite its undoubted role in normal motor control already discussed, isolated lesions of the lateral cor- in the cat, there is some doubt about the impor- ticospinal (pyramidal) tract in monkeys do not pro- tance and even existence of a rubrospinal tract in duce spasticity but rather hypotonia, hyporeflexia man (Nathan & Smith, 1955). In cats, this tract is well and loss of cutaneous reflexes. Extending the lesion developed and runs close to the pyramidal fibres in to involve more of the lateral funiculus (and hence the spinal cord. It facilitates flexor and inhibits exten- the dorsal reticulospinal tract) results in spastic- sor motoneurones (Rothwell, 1994) via interneu- ity and tendon hyperreflexia (Brown, 1994). Sim- rones. In contrast, in man, very few cells are present ilar lesions in man of the dorsal half of the lat- in the area of the red nucleus that gives rise to this eral funiculus produced similar results (Putnam, tract. However, the rubro-olivary connections are 1940). Curiously though, bilateral lesions of the inter- better developed in man than in the cat (Rothwell, mediate portion of the lateral column resulted in 1994). tendon hyperreflexia, ankle clonus and Babinski signs immediately, but rarely spasticity. Brown (1994) Coerulospinal tract points out, however, that there was no histological The clinical benefits of drugs such as clonidine confirmation of the extent of these lesions. In the (Nance et al., 1989) and tizanidine (Emre et al., cat, dorsolateral spinal lesions including the DRT 1994) and of therapeutic stimulation of the locus produce spasticity and extensor plantar responses coeruleus have refocused attention on the nora- (Babinski sign) but not clonus or flexor spasms (Tay- drenergic coerulospinal system. The locus coeruleus lor et al., 1997). Furthermore, these positive UMN resides in the dorsolateral pontine tegmentum and features appeared rapidly. These results support the gives rise to the coerulospinal tract. Coerulospinal idea that the DRT is critical in the production of spas- fibres terminate in the cervical and lumbar regions ticity in man and also show that lesions in the region and appear to facilitate presynaptic inhibition of can result in restricted forms of the UMN syndrome, flexor reflex afferents (Whitlock, 1990). As tizani- especially the dissociation of tendon hyperreflexia dine reduces spasticity as well as flexor spasms, it and spasticity. must also modulate spinal stretch reflexes. How- ever, there is no evidence that the coerulospinal Concerning lesions of the excitatory pathways tracts play a role in the production of spasticity or made in attempt to reduce spasticity, cordotomies

14 Geoff Sheean of the anterior portions of the ventral columns medulla (cortex, corona radiata, internal capsule) or to interrupt the vestibulospinal tracts were only of the DRT in the spinal cord. Theoretically, isolated transiently successful in reducing spasticity in the lesions of the inhibitory medullary reticular forma- legs (Bucy, 1938). These lesions were said to spare tion could do the same but as Brown (1994) points the deeper sulcal regions where the medial reticu- out, strokes in this area tend to be fatal. It is attractive lospinal tract resides. After more extensive cordo- to presume that spasticity develops in this situation tomies were performed, which included these tracts, simply due to the effects of the excitatory system, and following a period of flaccidity, spasticity was which is now unbalanced by the loss of the inhibitory markedly reduced but tendon hyperreflexia, clonus system but the situation is not so simple (see p. 15, and adductor spasms persisted. These findings rein- ‘Mechanism of the change in excitability of the spinal force the more dominant role that the MRT plays reflexes’). and the relatively less important role of the VST and once again illustrates that the positive feature of the Clinicopathological correlation UMN syndrome may occur independently. Further- more, these findings in man tend to support the ideas The clinical picture of the UMN syndrome seems to on the pathophysiology of spasticity developed from depend less upon the etiology of the lesion and more animals. upon its location in the neuraxis. It has been long rec- ognized that the UMN syndrome following cerebral In summary, cortical lesions producing spastic- lesions is somewhat different to that of spinal lesions. ity must involve both the primary motor and pre- Similarly, there are differences between partial or motor cortices. Such lesions affect both pyramidal incomplete spinal lesions and complete lesions. and parapyramidal cortico-reticular reticular fibres, With cerebral lesions, spasticity tends to be less which run adjacent to each other in the corona radi- severe and more often involve the extensors with ata and internal capsule. Conceptually, there is a sys- a posture of lower limb extension. Flexor spasms tem of balanced control of spinal reflexes that arises are rare and the clasp-knife phenomenon is uncom- within the brainstem. There is an inhibitory area in mon. Clonus tends also to be less severe. In contrast, the medullary reticular formation that largely sup- spinal lesions can have very severe spasticity, more presses spinal reflex activity. This region receives cor- often in flexors with a dominant posture of lower tical facilitation from the motor cortex (mainly pre- limb flexion (paraplegia in flexion); prominent flexor motor) via cortico-reticular fibres, which comprises spasms, clasp-knife phenomenon is more common, the suprabulbar portion of the inhibitory system. The as is clonus. output of this medullary inhibitory centre is the dor- sal reticulospinal tract, which runs in the dorsolateral The pathophysiological substrate for these differ- funiculus, adjacent to the lateral corticospinal (pyra- ences may reside in three factors. The existence of midal) tract. Two other areas comprise the excita- cortico-reticular drive to the inhibitory brainstem tory system that facilitates spinal stretch reflexes and centre, the anatomical separateness of the inhibitory extensor tone. The main one arises diffusely through- and excitatory tracts in the spinal cord and the out the brainstem and descends as the medial retic- fact that both the excitatory and inhibitory systems ulospinal tract. The other is the lateral vestibular inhibit flexor reflex afferents, which are responsible nucleus, giving rise to the vestibulospinal tract. Both for flexor spasms. are located in the ventromedial cord, well away from the lateral corticospinal tract and the inhibitory dor- A suprabulbar lesion, say, in the internal capsule, sal reticulospinal tracts. would deprive the inhibitory brainstem centre of its cortical facilitation. This inhibitory centre could, Thus, spasticity arises when the parapyramidal however, continue to contribute some inhibition of fibres of the inhibitory system are interrupted either spinal stretch reflexes and flexor reflex afferents. With of the cortico-reticular fibres above the level of the a partial reduction in inhibitory drive, the excitatory

Neurophysiology of spasticity 15 system would still dominate, facilitating extensors hypersensitivity following ‘denervation’ (Brown, while also inhibiting flexor reflex afferents. Hence, 1994) and unmasking of previously silent synapses the whole syndrome would be milder in form and (Borsook et al., 1998). The idea of collateral sprout- more extensor in type with few flexor spasms. ing as the basis of spasticity was first proposed by McCouch more than 40 years ago (McCouch et al., The chief clinical difference between complete 1958), but later reports that the CNS was capable of and incomplete spinal cord lesions is that incom- sprouting were disputed (Noth, 1991). Subsequently, plete lesions more often show a dominant exten- better evidence appeared that axon terminals in the sor tone and posture with more extensor spasms mammalian spinal cord could sprout and form new than flexor spasms, as opposed to the complete synapses (Hulseboch & Coggeshall, 1981; Krenz & spinal lesion, which is strongly flexor (Barolat & Weaver, 1998). Burke (1988) believes that new Maiman, 1987). An incomplete cord lesion might synapses may simply act to reinforce existing spinal affect the lateral columns (including the inhibitory circuits rather than create entirely new circuits, a DRT) and spare the ventral columns (along with quantitative rather than a qualitative change. Thus, the excitatory system). Thus, the incomplete cord the positive features of the UMN syndrome involve lesion would abolish all inhibition of spinal stretch two main mechanisms (1) disruption of descending reflexes and leave the excitatory system unopposed control of spinal pathways and (2) structural and/or to drive extensor tone but still inhibit flexor reflex functional reorganization at the spinal level (Pierrot- afferents (‘paraplegia in extension’). With complete Deseilligny & Mazieres, 1985). spinal cord lesions, all supraspinal control is lost, and both stretch reflexes and flexor reflex afferents are In some patients, hyperactive reflexes appear completely disinhibited; a strong flexor pattern fol- remarkably quickly, lending some credence to the lows (‘paraplegia in flexion’). idea of a ‘release’ effect. In support of this, CNS plas- ticity has been seen within 24 hours of human limb Mechanism of the change in excitability of the amputation (Borsook et al., 1998); such rapidity sug- spinal reflexes gests the unmasking of silent connections, rather than the formation of new ones. In addition, elec- The above outline of a balanced system of supraseg- trical stimulation of skin overlying the spastic biceps mental inhibitory and excitatory influences on spinal can produce longer-lasting reductions in spasticity, segmental reflexes could imply that the increased indicating a therapeutically useful short-term plas- excitability of spinal reflexes is simply a matter of ticity (Dewald et al., 1996). release or disinihibition. However, following acute UMN lesions there is frequently a variable period The mechanism of reduced spinal reflexes in of reduced spinal reflex activity (‘shock’) and it is spinal shock deserves some discussion in this con- only following resolution of this that hyperactive text. Vibratory inhibition is increased in spinal shock, reflexes appear. This raises the possibility that some suggesting presynaptic mechanisms (Calancie et al., structural and/or functional reorganization within 1993). However, it the acute spinal rat, polysynap- the CNS (‘plasticity’) is responsible. The human CNS tic excitatory postsynaptic potentials (pEPSPs) are has been shown to be quite capable of such plas- markedly prolonged (Li et al., 2004), which argues ticity involving both motor and sensory pathways against increased presynaptic inhibition. It has been following limb amputation (e.g. Chen et al., 1998 & proposed that plasticity may play a role, involving Elbert et al., 1994) and brain injury (Nirkko et al., down-regulation of receptors (Bach-y-Rita & Illis, 1997). For the somatosensory pathways, reorganiza- 1993). Recovery from spinal shock could involve up- tion occurs at cortical, brainstem and spinal levels regulation of receptors, making them more sensitive (Florence & Kaas, 1995). Possible contributory pro- to neurotransmitters (Bach-y-Rita & Illis, 1993). The cesses include collateral sprouting of axons, receptor supersensitivity to monoamines of spinal interneu- rones involved in extensor reflexes in chronic spinal

16 Geoff Sheean rats compared with the acute preparation is an exam- Table 2.1. Classification of positive features of upper ple of this (Ito et al., 1997). Nonsynaptic transmis- motor neurone syndrome by pathophysiological sion could also play a role in spinal shock and its mechanism recovery (Bach-y-Rita & Illis, 1993). Finally, postsy- naptic mechanisms may be involved. In the spinal A. Afferent – disinhibited spinal reflexes shock phase of rats with cord lesions, the motorneu- 1. Proprioceptive (stretch) reflexes rone becomes poorly excitable, especially in exten- Spasticity (tonic) sor motoneurones, as a result of reduced persistent Tendon hyperreflexia and clonus (phasic) inward currents (see ‘Alpha motoneurone excitabil- Clasp-knife reaction ity’ on p. 47, and Heckman et al., 2005, for a review). Positive support reaction? 2. Cutaneous and nociceptive reflexes There may be some additional therapeutic (a) Flexor withdrawal reflexes relevance to understanding the underlying cellu- Flexor spasms lar processes behind the hyperreflexia of the UMN Clasp-knife reaction (with tonic stretch reflex) syndrome (Noth, 1991). If collateral sprouting is Babinski sign responsible, it may be possible to inhibit this process (b) Extensor reflexes (Schwab, 1990). Extensor spasms Positive support reaction Spinal segmental reflexes B. Efferent – tonic supraspinal drive? Hyperexcitability of spinal reflexes forms the basis Spastic dystonia? of most of the ‘positive’ clinical signs of the UMN Associated reactions/synkinesia? syndrome, which have in common excessive mus- Cocontraction? cle activity. These spinal reflexes may be divided into two groups, proprioceptive reflexes and noci- testing of muscle tone, are referred to as tonic stretch ceptive/cutaneous reflexes (Table 2.1). Propriocep- reflexes. The positive support reaction may be in part tive reflexes include stretch reflexes (tonic and due to stretch of muscle proprioceptors in the foot phasic) and the positive supporting reaction. Noci- (Bobath, 1990). ceptive/cutaneous reflexes include flexor and exten- sor reflexes (including the complex Babinski sign). Phasic stretch reflexes The clasp-knife phenomenon combines features of both groups, at least in the lower limbs. The clinical signs arising from hyperexcitability of phasic stretch reflexes include deep tendon hyper- Proprioceptive reflexes reflexia, irradiation of tendon reflexes and clonus. The traditional view is that percussion of the tendon Proprioception is the sensory information about causes a brief muscle stretch, a synchronous dis- movement and position of bodily parts and is medi- charge of the muscle spindles and an incoming syn- ated in the limbs by muscle spindles. Stretch of chronized volley of Ia afferent activity that monosy- muscle spindles causes a discharge of their sen- naptically excites alpha motoneurones. However, sory afferents that synapse directly with and excite Burke (1988) points out that the situation is more the motoneurones in the spinal cord innervating complex. The following summarizes his explanation. the stretched muscle. This stretch reflex arc is the In addition to muscle stretch, the percussion of a ten- basis of the deep tendon reflex, referred to as a pha- don causes a wave of vibration through the limb that sic stretch reflex because the duration of stretch is also capable of stimulating muscle spindles in the is very brief. Reflex muscle contractions evoked by muscle percussed, as well as others in the limb. This longer stretches of the muscle, such as during clinical is the basis of tendon reflex ‘irradiation’, discussed later. Spindle activity from these other muscles could

Neurophysiology of spasticity 17 contribute to the tendon reflex. Furthermore, per- the frequency of spontaneous ankle clonus in spas- cussion also stimulates mechanoreceptors in the tic patients could vary from 2.5 to 5.7 Hz. It was skin and other muscles. The discharge from the mus- also possible to inhibit clonus with strong loads. cle spindles evoked by percussion is far from syn- Load-dependent spontaneous clonus could also be chronous and spindles may fire repetitively. Finally, induced in normal subjects (after prolonged sinu- the reflex is unlikely to be solely monosynaptic. The soidal joint movements) at similar frequencies. This rise time observed in the excitability of the soleus is no surprise as a great many normal people have motoneurones following Achilles tendon percussion experienced ankle clonus at some stage in their lives is around 10 ms, which is ample time for oligo or under certain conditions. The conclusion drawn by polysynaptic pathways to be involved. These do exist Rack et al. (1984) was that clonus is a manifestation for the Ia afferents and could include those from the of increased gain of the normal stretch reflex and that percussed muscle as well as from other muscles in central mechanisms are less dominant in determin- the limb excited by the percussion. Cutaneous and ing the frequency of clonus. other mechanoreceptor afferents also have polysy- naptic connections. H reflexes are commonly used The mechanism underlying clonus is similar to to examine the phasic stretch reflex pathways in the that of tendon hyperreflexia, increased excitability UMN syndrome and considered equivalent to the of the phasic stretch reflex. A rapid dorsiflexion of tendon reflex. This is not the case for many of these the ankle by an examiner produces a brisk stretch of same reasons (see p. 38, ‘Electrophysiological studies the gastrocnemius-soleus. A reflex contraction in the of spinal reflexes in spasticity’). gastrocnemius-soleus is elicited, plantar flexing the ankle. This relieves the stretch, abolishing the stim- In the UMN syndrome, percussion of one tendon ulus to the stretch reflex and so the muscle relaxes. often produces similar brief reflex contractions of If this relaxation is sufficiently rapid while the exam- other muscles in the limb, a phenomenon known iner maintains a dorsiflexing force, another stretch as reflex irradiation. This is not due to the opening reflex will be elicited and the ankle again plantar up of synaptic connections between various mus- flexes. Thus, a rhythmic, pattern of contraction and cles in the limb (Burke, 1988) but to a simpler mech- relaxation is set up that will often continue for as long anism. As mentioned, tendon percussion sets up a as the dorsiflexion force is maintained, referred to as wave of vibration through the limb that is capable sustained clonus. However, unsustained clonus can of exciting spindles in other muscles (Lance & De also occur in UMN lesions. Burke (1988) comments Gail, 1965; Burke et al., 1983). If the stretch reflexes of that the much of the eliciting and maintaining of those muscles are also hyperexcitable, phasic stretch clonus lies in the skilled technique of the examiner reflexes will be evoked. and, as Rack et al. (1984) noted, it was possible to suppress clonus with stronger loads. Clonus is a rhythmic, often self-sustaining con- traction evoked by rapid muscle stretch, best seen Tonic stretch reflexes in the UMN syndrome at the ankle, provoked by a brisk, passive dorsiflexion. It tends to accompany Muscle tone is tested clinically by passive movement marked tendon hyperreflexia and responds similarly of a joint with the muscles relaxed and refers to the to factors that reduce hyperreflexia (Whitlock, 1990). resistance to this movement felt by the examiner. The The rhythmicity suggested a central oscillatory gen- hallmark of the UMN syndrome is a form of hyper- erator, an idea supported by the inability to modify tonia, called spasticity. It had been observed clini- the frequency by external factors (Walsh, 1976; Dim- cally that slow movements would often not reveal itrijevic et al., 1980). However, Rack and colleagues hypertonia but faster movements would and that found that the frequency of the ankle clonus did vary thereafter this resistance increased with the speed of with the imposed load, as had also been found at the passive movements. Electromyographically such other joints countering the central oscillator notion resistance correlated with reflex contraction of the (Rack et al., 1984). By changing the mechanical load,

18 Geoff Sheean (a) (b) 50 μV 50 μV 300°/s 100 ms 300°/s 100 ms 240°/s 240°/s 175°/s 175°/s 117°/s 117°/s 80°/s 80°/s 10° (c) (d) 25 600 Mean biceps EMG level (mV) End of late biceps EMG (ms) 20 500 15 400 300 10 200 5 100 0 0 0 50 100 150 200 250 300 0 100 200 300 400 500 600 Displacement velocity (°/s) End of displacement (ms) Figure 2.2. Surface electromyography (EMG) recordings of the biceps during passive displacements of the elbow of various angular velocities. (a) Normal subjects. No EMG activity (stretch reflex) is elicited until very fast displacements are made (175◦/s and faster). The reflex responses then are brief and terminate before the movement is complete (angular displacement represented below). (b) Spastic subjects show stretch reflexes, even at low angular velocities, which continue for the duration of the movement. (c) The magnitude of the EMG response increases linearly with the speed of the movement. (From Thilmann et al., 1991a.) stretched muscle, which opposes the stretch (Her- second. The latency of the reflex was 61 to 107 ms, man, 1970). These contractions of stretched muscle some of which probably includes the time it takes for are referred to as tonic stretch reflexes to distinguish the mechanical displacement of the elbow to stretch them from the brief stretches that elicit phasic stretch the muscle and excite the spindles (Rothwell, 1994). reflexes. Tonic stretch reflexes have also been studied The reflex contraction was brief and was not main- during active muscle contraction, in part to deter- tained throughout the stretching movement and is mine the role that hyperexcitability of such reflexes probably a phasic stretch reflex, analogous to the ten- might play in the impairment of movement in the don reflex (Rothwell, 1994). UMN syndrome (see following). This was an important finding because it indicated In an elegant experiment, Thilmann and col- that at the velocities of movement usually used to leagues (1991) found stretch reflexes in the relaxed test tone in normal, relaxed muscle (much slower biceps in only half their normal subjects (Fig. 2.2) than 200 degrees per second), there is no stretch and then only with very fast movements; the thresh- reflex. Thus, tonic stretch reflexes do not contribute old was an angular velocity of around 200 degrees per to muscle tone, which therefore must come from the

Neurophysiology of spasticity 19 viscoelastic properties of the muscle. This is dis- decreased threshold, both spastic patients and con- cussed in more detail further on. trols showed similar stretch reflex gains during active elbow flexion, a state assumed to eliminate thresh- The situation was found to be quite different old differences (Powers et al., 1989). This and sim- in hemiparetic spastic (stroke) patients (Thilmann ilar measures of the stretch reflex during voluntary et al., 1991a) in whom stretch reflexes could be contraction are not valid assessments of spasticity, elicited with relatively slow movements – as slow as however, which, by definition, requires the muscle to 35 degrees per second. Reflex activity usually began be at rest. Finally, arguments over the relative differ- at a relatively constant latency, at the end of the 61- to ences in stretch reflex gain between relaxed normal 107-ms window found in normal subjects. However, and spastic muscles may really be pointless given it continued throughout the stretching movement that such a reflex is not even present in normal sub- and usually stopped just before the end of the dis- jects. As Thilmann et al. (1991a) point out, ‘a quali- placement. No EMG activity was seen when the tatively new reflex is present in the spastic subjects’. stretch was held at the end of the displacing move- ment. That is, there was no static stretch reflex. Irrespective of whether the basic alteration is Thus, in this study, as in others (Rushworth, 1960; increased gain or decreased threshold, the common Burke et al., 1970; Herman, 1970; Ashby & Burke, finding is that spasticity is due to hyperactive tonic 1971; Burke et al., 1972), spasticity was found to be stretch reflexes that are velocity sensitive. There is an exclusively dynamic tonic stretch reflex. Other still a threshold velocity of displacement, however, as researchers have found otherwise (Powers et al., a slow movements will not elicit a reflex. Thilmann 1989) (see ‘Static tonic reflexes,’ below). Some vari- et al. (1991a) found this could be as low as 35 degrees ation between patients was seen with faster rates per second in the biceps, while a higher threshold of of displacement producing shorter latency activity 100 degrees per second has been found in the quadri- within the 61- to 107-ms ‘normal’ window in some ceps (Burke et al., 1970). The long latency of these and very slow velocities having much longer laten- reflexes, even accounting for delays due to mechan- cies (up to 400 ms) in others. The amount of reflex ical factors, suggests a polysynaptic pathway. There muscle contraction showed a positive linear corre- is good evidence that Ia afferents from primary mus- lation with the velocity of stretch, thus confirming cle spindles are linked by oligo- and polysynaptic that spasticity is velocity dependent (Burke et al., pathways to their homonymous alpha motoneurons 1970; Ashby & Burke, 1971; Burke et al., 1972; Powers (Burke, 1988; Mailis & Ashby, 1990) and these remain et al., 1989). Hemiparetic patients without spasticity the most likely mediator of tonic stretch reflexes. behaved similarly to the normal subjects. Group II afferents also have polysynaptic connec- tions and may contribute to muscle stretch reflexes The fact that a tonic stretch reflex is not present in (see ‘Group II polysynaptic excitatory pathways’). normal subjects raises the question of whether it is an entirely new reflex arising after a UMN lesion or an Tonic stretch reflexes (TSRs) are not only velocity increase in excitability of an existing, dormant one. If dependent but also length dependent. In the lower it is the latter, is the mechanism a decrease in thresh- limb, the TSR is less sensitive at longer lengths in old or an increase in gain? The case for each has been the ankle plantarflexors (Meinders, 1996) and in the argued (Powers et al., 1988, 1989; Thilmann et al., quadriceps (Burke et al., 1970). In apparent contra- 1991a) and it has even been suggested that stretch diction, some researchers (He, 1998; Fleuren et al., reflex gain in spastic ankles is at the high end of the 2006) have found increased spasticity in the knee normal range (Rack et al., 1984). The absence of the extensors when the rectus femoris was stretched. The reflex in normal subjects, even at rates as high as 500 explanation for this difference may be that the spas- degrees per second (Ashby & Burke, 1971), would ticity was compared between the sitting and supine suggest an implausibly high threshold (Thilmann positions. Although going from sitting to supine does et al., 1991a). Against increased gain and in favor of a lengthen the rectus femoris, it also stretches the

20 Geoff Sheean (a) (a) V.R. intact they observed in the supine position compared with Tension sitting rather than shortening. There are also poten- tial vestibulospinal and other supraspinal influences Secondary concerned with postural control influences that vary Primary with posture to consider (He, 1998). In the upper limb, the effect of length on TSR sensitivity is the (b) V.R opposite. In finger flexors, tonic stretch reflexes are Tension increased in the shorter position and reduced in the lengthened position (Li et al., 2006). This study Secondary of stroke patients confirmed that spasticity is both velocity and length dependent, but it also found an Primary interaction between the two. Velocity dependence 100 Hz was greater at longer lengths and length depen- dence was greater with faster stretches. These obser- (b) Primary vations underline the need to consider not only 160 velocity of stretch but also body position and mus- Dynamic index (impulses s–1) cle length when measuring spasticity, especially in 100 research. 50 Clinical experience has shown that repeated Secondary stretching tends to reduce tone, although usually only for a short time, measured in hours. While some 0 of this reduction is biomechanical (Nuyens et al., 0 20 40 60 2002), reduced tonic stretch reflexes measured elec- Velocity (mm s–1) tromyographically have been observed in the knee extensors (Nuyens et al., 2002) and elbow flexors Figure 2.3. Velocity sensitivity of primary muscle spindle (Schmit et al., 2000), although with high variabil- endings and relative insensitivity of secondary spindle ity (Schmit et al., 2000). The explanation may be endings. (a) Spindle afferent discharges with and without thixotropic changes in spindle sensitivity of habi- fusimotor drive (V. R. = ventral root). Note the dynamic uation of central reflex pathways. These findings sensitivity of the primary spindle endings during the not only support the role of physical treatments course of the stretch. Note also that both spindle endings in spasticity but indicate that spasticity measure- continue to discharge in the hold phase of the stretch, ment needs to take into consideration the number particularly the secondary spindle endings, indicating that of stretches used to evaluate spasticity, as well as both are sensitive to length changes as well as velocity. (b) the factors of length, velocity and position already Graphic representation of the velocity sensitivity of each mentioned. spindle ending, expressed as the dynamic index. (From Matthews, 1972.) The velocity dependence of tonic stretch reflexes has been attributed to the fact that primary mus- iliopsoas muscle, which, as mentioned below (see cle spindles are velocity sensitive in animal models ‘Extensor reflexes and spasms’), tends to induce (Herman, 1970; Dietrichson, 1971, 1973; Rothwell, extensor reflexes in the quadriceps. This may also 1994) (Fig. 2.3). In cats, fusimotor drive increases explain the reduction in hamstring spasticity that the velocity sensitivity but fusimotor drive is not increased in human spasticity (Burke, 1983). This explanation has been challenged by results that show the velocity sensitivity of spasticity is quite weak and nonlinear (Powers et al., 1989). An alterna- tive explanation relies upon the dependence of the

Neurophysiology of spasticity 21 motoneurone firing threshold upon the rate of The mechanism of the decline in stretch-reflex change of the depolarizing current (Powers et al., activity that gives rise to the apparently sudden 1989). Houk and colleagues (1981) studied firing release may be due to two factors. The first is the of primary (Ia) and secondary (group II) spin- velocity sensitivity of the stretch reflex. The resis- dle afferents from the soleus of decerebrate cats. tance produced by the stretch reflex slows the move- They discovered that firing of both afferent fibre ment, which reduces the stimulus responsible for types are length and velocity dependent, with an it to below threshold, the reflex contraction stops interaction between the two that mirrors the find- and the resistance declines. Burke (1988) believes ings in human spastic subjects of Li et al. (2006) that this is all that is required for the clasp-knife mentioned earlier: velocity dependence was greater phenomenon in the biceps brachii but this reason- at longer lengths and length dependence was ing does not explain why the continuing movement greater with faster stretches. Recently, the length after the ‘release’ does not once again evoke a stretch or positional dependence of primary muscle spin- reflex. The clasp-knife phenomenon is seen better in dles in the wrist and finger extensors of nor- the quadriceps where the second factor also applies mal humans has been confirmed (Cordo et al., (Burke, 1988). Here, as well as in the ankle plantar 2001). flexors (Meinders et al., 1996), the tonic stretch reflex seems not only velocity dependent but also length The clasp-knife phenomenon dependent, being less sensitive at longer lengths (Fig. 2.4). Thus, there is not only declining velocity dur- This well-known clinical sign has as its basis a hyper- ing the movement but also increasing length. A crit- excitable tonic stretch reflex. A fast passive move- ical point is reached where these two factors com- ment of a joint in a relaxed limb, usually knee flexion bine to reduce the effective stimulus to the stretch or elbow extension, encounters a gradual buildup of reflex, which suddenly ceases. Continuing move- resistance that opposes the movement momentar- ment does not again evoke a stretch reflex because ily before apparently suddenly melting away, allow- the reflex is relatively insensitive at this longer length. ing continuing stretch with relative ease (Fig. 2.4). While the resistance seems to suddenly melt away, The rapid buildup of resistance is spasticity, through the mechanism is really gradually declining stimu- the mechanisms already discussed. The apparently lus (velocity) and stretch-reflex sensitivity (length). sudden decline in the stretch reflex was initially The length-dependent sensitivity of the stretch reflex attributed to the sudden appearance of inhibition appears to be due to length-dependent inhibition of from the Golgi tendon organs (via Ib afferents), as the stretch reflex by a group of sensory fibres known a means to protect the muscle from dangerously as flexor reflex afferents (FRAs), which are discussed high tension. It had been thought that these organs in more detail further on. In contrast to the quadri- fire only at high muscle tension. However, it was ceps, stretch reflexes in the hamstrings are more sen- later discovered that Golgi tendon organs actually sitive at longer lengths (Fig. 2.4; Burke & Lance, 1973). have quite low tension thresholds (Houk & Henne- man, 1966; cited in Rothwell, 1994). Furthermore, the Static tonic stretch reflexes inhibition of the stretch reflex extends well beyond the reduction in tension; Golgi tendon organs cease As mentioned earlier, the stretch reflexes underly- firing once the tension is relieved (Rothwell, 1994; ing spasticity have been regarded as dynamic, that Fig. 2.5). Finally, there is evidence of reduced Ib is, present only when the joint is moving. Thilmann inhibitory activity in some cases of spasticity (see ‘Ib and colleagues (1991a) found that the stretch reflex Non-reciprocal inhibition’). It is unlikely then that usually declined towards the end of the movement Ib inhibitory activity from the Golgi tendon organs as the velocity declined and if the muscle was held in plays much of a role in the clasp-knife phenomenon stretch at this point, there was no EMG activity. Thus, (Rothwell, 1994). it has been considered that there is no appreciable

22 Geoff Sheean (a) Sec. Velocity Knee e. position f. Tension 5 kg E.M.G. (b) (c) Velocity 300 degrees/ Angle second e 0° Integrated f 90° EMG EMG 0.5 0.2 mV Time mV Seconds Figure 2.4. (a) The clasp-knife phenomenon at the knee. The subject is supine and the knee is passively flexed while surface electromyography (EMG) is recorded from the quadriceps and force exerted by the examiner’s hand at the ankle (reflecting muscle tension). Passive flexion elicits a tonic stretch reflex, associated with rapid build-up of tension (resistance). This abrupted declines (clasp-knife phenomenon), coincident with the cessation of the tonic stretch reflex. (b) and (c) Length-dependent sensitivity of the tonic stretch reflex in the quadriceps (b) and the hamstrings (c). Muscle stretches are performed at increasing length of the muscle. In the quadriceps (b), the maximum reflex is elicited in the first step, with declining responses with increasing muscle length. The opposite is seen in the hamstrings (c), where a tonic stretch reflex is not elicited until the muscle is at nearly full stretch. (From Burke & Lance, 1973.) static component to the tonic stretch reflex of spas- the clasp-knife phenomenon mentioned earlier. The ticity. situation may be truly different at the ankle, where static stretch reflexes have not been seen (Herman, However, several researchers have observed clear 1970; Berardelli et al., 1983; Hufschmidt & Mauritz, reflex activity in the maintained phase of a ramp- 1985). and-hold stretch of elbow flexors (Fig. 2.6) (Denny- Brown, 1966; Powers et al., 1989; Sheean, 1998a). The mechanism of static tonic stretch reflexes pre- They suggested several methodological reasons why sumably involves receptors that are chiefly sensi- such reflex activity might have been missed in previ- tive to muscle length and less to velocity. The pri- ous studies (Powers et al., 1989). One obvious rea- mary muscle spindles (with Ia afferents) are sen- son for its absence in the quadriceps might be sitive to both but mainly to velocity (Rothwell, length-dependent inhibition responsible in part for 1994). The secondary muscle spindles, via the slower

Neurophysiology of spasticity 23 Window 1 Window 2 Window 3 1.1 BRD EMG BB EMG Torque Angle (Nm) (rad) 0.1 20 –5 165 (uv) 0 245 (uv) Figure 2.5. Demonstrating the sensitivity of Golgi tendon 0 2.5 organs to small tensions. Two recordings from stimulation – 0.5 0.0 0.5 1.0 1.5 2.0 of motor axons to the soleus muscle of a cat. The upper trace of each recording represents the force in the tendon, Figure 2.6. Static tonic stretch reflexes in the spastic and the lower trace the tendon organ Ib afferent discharge. biceps brachii (BB) and brachioradialis (BRD). Passive The lower recording shows a vigorous discharge of the extension of the elbow (1 radian stretch at 1 radian/sec) tendon organ, despite the weak contraction. The upper elicits a tonic stretch reflex during the ramp portion of the recording, from a stronger contraction, shows an initial stretch (dynamic tonic stretch reflex). The rectified surface discharge of Golgi tendon organ afferents, with EMG activity continues, especially in brachioradialis, subsequent cessation due to unloading of the receptor by during the ramp phase of the stretch after the movement contraction of neighbouring motor units. (From Houk & has stopped (static tonic stretch reflex). (From Powers Henneman, 1967.) et al., 1989.) conducting group II afferents, maintain an increased suggest a reduced effect of group II afferents. The firing level over baseline for as long as the muscle discovery that group II afferents in the soleus of the is held stretched and would be suitable candidates. decerebrate cat are both length and velocity depen- Some evidence from comparative therapeutic and dent (Houk et al., 1981) supports not only a role electrophysiological studies of baclofen and tizani- for these afferents in the static tonic stretch reflex dine in spinal cats suggests a role of group II afferents but in the dynamic tonic stretch reflex (spasticity) in spasticity (Skoog, 1996). Both agents are equally as well. effective at reducing spasticity. Baclofen strongly depressed group I potentials but had inconsistent Burke suggests that EMG activity continuing effects on group II potentials. In contrast, tizani- beyond the end of a movement must be due to dine strongly depressed the amplitude of monosy- some other stimulus, such as cutaneous stimula- naptic field potentials in the spinal cord caused by tion (Burke, 1988). Therefore, this EMG activity in group II afferents with little effect on group I poten- the hold phase may not be a reflex due to mus- tials. Additionally, L-dopa, which depresses trans- cle stretch reflex. One possibility is a flexor reflex, mission from group II but not group I afferents, mediated by flexor reflex afferents (see following reduces spasticity, tendon hyperreflexia and clonus discussion). in humans with spinal cord injuries (Eriksson et al., 1996). However, the depressed long-latency stretch Tonic stretch reflexes during muscle activation reflexes of the upper limb in the UMN syndrome It is commonly held by clinicians that spastic- ity interferes with muscle function, a belief that

24 Geoff Sheean often leads to vigorous and unhelpful attempts supraspinal control (Fung & Barbeau, 1994), could to reduce tone. Spasticity, however, is defined by contribute to the gait disorder in spasticity (Boor- its presence in relaxed, not activated muscle. Set- man et al., 1992), by failure of the appropriate pattern ting aside semantics, the question is really, could of reflex suppression. In support of this idea, defec- hyperexcitable stretch reflexes impair function? If tive stretch reflex modulation in spastic subjects with the tonic stretch reflex gain of activated spas- multiple sclerosis has been reported (Sinkjaer et al., tic muscles were truly not increased, it would 1996) and hyperactive soleus stretch reflexes during be hard to argue in favour of this. The situa- active dorsiflexion were found that impaired move- tion is further complicated by secondary soft tis- ment (Corcos et al., 1986). Soleus (Yang & Whelan, sue changes that can increase tone, independent 1993; Stein, 1995) and quadriceps (Dietz et al., 1990) of stretch reflexes (see ‘Nonreflex contributions to H reflexes are also normally modulated during gait hypertonia’). and cycling (Boorman et al., 1992) and impaired soleus H reflex modulation has also been found in In contrast with relaxed muscles, tonic stretch spastic patients (Yang et al., 1991a; Boorman et al., reflexes can be elicited in normal subjects while the 1992; Sinkjaer et al., 1995). There was, however, a muscle is voluntarily activated. Under these con- poor correlation between impaired soleus H-reflex ditions, the tonic stretch reflex responses in elbow modulation and the degree of walking difficulty in flexors between normal and spastic subjects are not spastic patients with spinal cord lesions (Yang et al., significantly different (Lee et al., 1987; Powers et al., 1991a). 1989; Burne et al., 2005). This has been taken to indi- cate that the hyperexcitable tonic stretch reflex of However, Ada et al. (1998) found that although spasticity is due to decreased threshold (see above) abnormal tonic stretch reflexes were present at as, once threshold differences had been eliminated rest in the gastrocnemius of spastic subjects (post- by voluntary activation, the stretch reflex gain was stroke), the action tonic stretch reflexes present dur- similar in the two groups. However, Nielsen (1972) ing simulated gait were no different to those of had found that the stretch reflex gain of voluntarily controls. They concluded that spasticity would not activated spastic biceps muscles was fixed at a high contribute to walking difficulties after stroke. Other level compared with normal subjects, in whom gain researchers agree (Sinkjaer et al., 1993) and add that was strongly dependent upon the degree of voluntary nonreflex (soft tissue) hypertonia is more impor- activation. Given this, and the fact that the experi- tant in impairing ankle movement during walk- mental paradigm is difficult to control (Noth, 1991), it ing (Dietz et al., 1981; Dietz & Berger, 1983; Huf- is possible that differences in activated tonic stretch schmidt & Mauritz, 1985). The issue is clearly an reflex gain between the two groups might have been important one. Attempts to reduce spasticity in missed. order to improve function, especially gait, may be futile. A variation on this theme is the modulation of stretch reflexes during more complex movements The physiological mechanisms underlying such as gait. Short-latency stretch reflexes of soleus in stretch reflex hyperexcitability normal subjects show substantial phase-dependent modulation during walking, probably through Ia For a long time, the analogy was drawn between presynaptic inhibition (Dietz et al., 1990) (see ‘Ia the stretch reflex hyperexcitability of the decere- Presynaptic inhibition’ on p. 40). That as much as brate cat and that of human spasticity. In the decere- 30% to 60% of the soleus EMG activity during the brate cat, stretch reflexes are hyperexcitable because stance phase of walking is due to stretch reflexes of increased fusimotor drive (via gamma motoneu- (Yang et al., 1991b) demonstrates their importance in rones) to the muscle spindles making them more normal gait. It has been argued that this impairment sensitive to stretch. Consequently, Ia afferent activity of stretch reflex modulation, because of disrupted

Neurophysiology of spasticity 25 is proportionately increased. A similar mechanism become stiff and less compliant, resisting passive was assumed to be operating in human spasticity, stretch and manifesting as increased tone. The pas- but by the early 1980s it had become evident that sive range of motion might still remain normal if fusimotor activity was not increased. The evidence there is no fixed shortening or contracture. As we for this conclusion was eloquently summarized and saw earlier, normal subjects do not exhibit stretch discussed by Burke (1983). Thus, if excessive pro- reflexes at normal rates of passive limb movement. prioceptive afferent input was not the explanation, Thus, it is the viscoelastic properties of the soft tis- what could explain the enhanced reflex responses sues alone that produce normal muscle tone. In to normal afferent input? Could it be that the alpha other words, normal muscle tone is entirely biome- motoneurones themselves are hyperexcitable, ready chanical, with no neural contribution (Burke, 1988). to overreact in response to the normal and appropri- Thus, there can be no real ‘hypotonia’ due to neu- ate afferent input? Or, given that the reflex circuits rological disease (van der Meche & van Gijn, 1986; activated by the clinical stimuli (e.g. tendon tap, pas- Burke, 1988). In the UMN syndrome, both neural and sive stretch) are complex, involving interneurones biomechanical factors may contribute to increased that are under strong supraspinal control, is it possi- muscle tone. ble that either the gain of these circuits is increased or the threshold lowered? This is an important concept, mainly because the treatment approaches to each type of hyper- The latter is the prevailing view, although it is dif- tonia are different. Increased neural tone might ficult to investigate the possibility of hyperexcitable respond to antispasticity medications or injections alpha motoneurones without using spinal reflexes, of botulinum toxin or phenol, whereas biomechani- as discussed further on (see p. 47, ‘Alpha motoneu- cal tone would not. Increased biomechanical tone is rone excitability’). Thus, the basis of stretch reflex best treated by physical measures, for example, pas- hyperexcitability, which underlies the clinical signs sive stretching, splinting and serial casting. of enhanced tendon reflexes and reflex irradiation, clonus and spasticity, is abnormal processing of pro- The important role that soft tissue changes play prioceptive information within the spinal cord. A in muscle tone and posture has been highlighted by similar mechanism operates in the exaggerated noci- Dietz and colleagues (1981) and confirmed by oth- ceptive and cutaneous reflexes, also an important ers (Hufschmidt & Mauritz, 1985; Thilmann et al., component of the UMN syndrome. As has been men- 1991b; Sinkjaer et al., 1993, 1996; Sinkjaer & Mag- tioned, there has been some argument as to whether nussen, 1994; Nielsen & Sinkjaer, 1996; Becher et al., this abnormal processing arises from an increased 1998). Plantar flexion of the ankle during gait is a gain or from a reduced threshold. common sequela of the UMN syndrome. It was gen- erally assumed that this was produced by a combi- Nonreflex contributions to hypertonia: nation of overactivity of the plantar flexors (referred biomechanical factors to as spasticity) and underactivity of the ankle dorsi- flexors. The latter would occur because of weakness Contractures are a well known and feared complica- from the UMN lesion and possibly reciprocal inhi- tion of the UMN syndrome, reducing the range of bition of these muscles by the presumed overactive motion of a joint. There has been a recent inves- plantarflexors. However, they found that despite the tigation of the relationship between the stretch plantar-flexed ankle, the plantarflexors were actu- reflex hyperexcitability of spasticity and contractures ally underactive rather than overactive and that there (O’Dwyer et al., 1996), discussed later. However, con- was excessive activity in the dorsiflexors, presumably tractures are not the only soft tissue changes to occur in an attempt to correct the posture (Fig. 2.7). The in the UMN syndrome. Muscles and tendons may purpose of the research had been to investigate the suggestion that ‘spasticity’ played a role in the gait disturbance of the UMN syndrome, but it found, at

26 Geoff Sheean 500 1000 1500 2000 ms Arbitrary units500 10001500 ms Gastrocn. m Arbitrary unitsGastroc. m Ant. tibial m 2 Ant. tibial m 2 Ankle joint 1 Ankle joint 1 Goniometer Goniometer Knee joint 0 Knee joint 0 105° 90° 90° 80° 75° 70° 180° 150° 180° 120° 160° 140° Figure 2.7. Electromyographic (EMG) activity (rectified and averaged) during walking of tibialis anterior (ant. tibial m) and gastrocnemius (gastrocn. m) of a normal subject (left side) and a spastic patient (right side). Verticle lines indicate lift-off and touch-down of the foot on the treadmill. Note that in the spastic subject, the foot remains plantarflexed during the swing phase, in the absence of significant EMG activity in gastrocnemius and despite greater than normal EMG activity in tibialis anterior. This indicates that the plantarflexed posture is not due to weakness of tibialis anterior, or to excessive contraction of gastrocnemius, either from stretch or co-contraction. Biomechanical factors in the triceps surae must be causing the resistance to ankle dorsiflexion. (From Dietz et al., 1981.) least at the ankle, that soft tissue changes were more The conditions predisposing to reduced soft tis- important. sue compliance are probably the same as that of contracture formation, that is, prolonged immobi- Similar experiments have been performed in the lization of muscles and tendons at short length. This upper limb, correlating EMG activity of the elbow situation may arise because of spasticity (e.g. elbow flexors, as a measure of stretch reflex hyperexcitabil- flexors resisting straightening), spasms or poor posi- ity (spasticity), and resistance to passive move- tioning of weak muscles. Thus, neural hypertonia ment, measured as torque (Lee et al., 1987; Dietz (spasticity) could result in secondary biomechanical et al., 1991; Ibrahim et al., 1993; O’Dwyer et al., hypertonia (Fig. 2.8). Such soft tissue changes can 1996). Higher-than-normal torque/EMG ratios indi- occur quite rapidly, as early as 2 months after stroke cate a significant soft tissue contribution to muscle (O’Dwyer et al., 1996; Malouin et al., 1997). The stiff- hypertonia. ness could reside in either the passive connective tissue of the muscles, tendons and joints (reviewed In clinical practice, it can be difficult to distinguish in Herbert, 1988; Sinkjaer & Magnussen, 1994) or in between neural and biomechanical hypertonia. the muscle fibres themselves, where histochemical Velocity-dependent hypertonia and the clasp-knife changes resembling denervation have been found phenomenon would suggest a neural cause. Hyper- (Dietz et al., 1986). Muscles immobilized at short tonia with slow stretches would suggest reduced soft length develop altered length–tension relationships tissue compliance (Malouin et al., 1997). The distinc- that make them shorter and stiffer (Fig. 2.9) (see tion often can be made with electromyography or, Herbert, 1988, or Foran et al., 2005, for a review). The less practically, by examination under anesthesia. In number of sarcomeres is also reduced in proportion many cases, both components are present (Sinkjaer et al., 1996; Malouin et al., 1997).

Neurophysiology of spasticity 27 UMN lesion Abnormal muscular Weakness contraction Dynamic Static Immobilization at • Spasticity short muscle length • Spasms • Spastic dystonia • Co-contraction Biochemical changes • Clonus Hypertonia • Reduced compliance • Associated reactions + • Contracture • Flexor withdrawal Reduced ROM Abnormal postures Impaired function Figure 2.8. A model of the interaction between neural and biomechanical components of hypertonia in the upper motorneurone syndrome. Tension BA of the UMN syndrome can rapidly result in reduced soft tissue compliance and muscle shortening. For- Muscle length tunately these changes are reversible if the muscle Figure 2.9. The effects of prolonged immobilization on is lengthened, but timing is important; prolonged muscle length and stiffness. Curve A is from a normal immobilization at short length can result in perma- mouse soleus and curve B is from a soleus muscle nent shortening, or contractures. immobilized in a shortened position for 3 weeks. The length of the muscle is naturally shorter but the It has been assumed that stretch hyperreflexia, length–tension curve is steeper indicating that it is also spasticity, could result in prolonged muscle shorten- stiffer. (From Herbert, 1988, and adapted from Williams & ing, eventually leading to contracture. This assump- Goldspink, 1978.) tion has provided an additional reason for treating spasticity in order to avoid this outcome (Brown, to the reduced length, possibly in order to maintain 1994). However, the relationship between spastic- optimal myofilament overlap. Chronic active mus- ity and contracture has been challenged (O’Dwyer cle shortening – that is, actively contracting mus- et al., 1996). Contractures develop from prolonged cles – appears to accelerate the loss of sarcomeres. muscle shortening, irrespective of whether there is Thus, spasticity and the flexor and extensor spasms active muscle contraction or not (O’Dwyer & Ada, 1996), and result in a reduced range of joint motion. They are frequently accompanied by increased mus- cle stiffness and therefore clinical hypertonia, which may also contribute to a reduced range of motion (O’Dwyer & Ada, 1996). However, fixed muscle short- ening (i.e. contracture) can occur without hyperto- nia; there is a reduced range of joint motion but the tone within the available range of motion is normal. In a study of stroke patients, contracture

28 Geoff Sheean without spasticity was more common than with found to have the effect of ipsilateral excitation of spasticity in elbow flexors (O’Dwyer et al., 1996). flexor and inhibition of extensor muscles (Roth- These authors proposed that the muscle shorten- well, 1994). The result is a ‘triple flexion’ response ing produced by contracture may actually aggra- of ankle dorsiflexion, knee flexion and hip flexion. vate spasticity by shortening intrafusal as well as Sensory afferents that evoke this flexion reflex are extrafusal fibres, thus activating them earlier in functionally defined as FRAs. These include affer- the stretch than usual. An additional hypothesis ents from secondary muscle spindles (group II), that this shortening might also make the spindles nonencapsulated muscle (group II, III and IV), joint more sensitive to stretch (Vandervoot et al., 1992) mechanoreceptors and the skin (Fig. 2.10). Stimu- can be discounted for the same reasons as the lation of FRAs exerts a weaker, opposite effect on increased fusimotor drive theory of spasticity (Burke, the contralateral limb, with inhibition of flexors and 1983). excitation of extensors, resulting in limb extension (the crossed extensor reflex). One purpose of such One possible contribution to stiffness of the a reflex would be to withdraw the limb from the muscle fibres in spasticity is increased thixotropy. stimulus (flexion) while supporting the animal on Thixotropy is a form of resistance to muscle stretch the other extended limb. FRAs have actions other due to intrinsic stiffness of the muscle fibres result- than that described and may also be involved in ing from cross-linking of actin and myosin filaments the ‘stepping generator’ through their ipsilateral and is dependent upon the history of the move- flexion/contralateral extension action (Rothwell, ment (Walsh, 1992). Thixotropic stiffness has been 1994). reportedly increased in spasticity (Carey, 1990) but others have found it to be normal (Brown et al., FRA reflexes are polysynaptic and generally poly- 1987). Thixotropy also affects intrafusal fibres (pri- segmental, the latter suggesting involvement of the mary muscle spindles), altering their sensitivity to propriospinal pathways. The word ‘flexor’ implies stretch (e.g. Hagbarth et al., 1985), but this has yet to that this is their only action but FRAs have access be studied in spasticity. to alternative pathways with differing effects, includ- ing extensor facilitation and flexor inhibition (Burke, Nociceptive/cutaneous reflexes 1988). FRAs are under strong supraspinal control, both excitatory and inhibitory. The flexor reflex is Included in this category are the clinical phenomena facilitated in the spinal cat but suppressed in the of flexor spasms, extensor spasms and the extensor midcollicular (decerebrate) cat (Rothwell, 1994). The plantar response (Babinski sign). These are extero- supraspinal control presumably determines which ceptive reflexes, defined as those mediated by non- of the available pathways are activated by the FRAs proprioceptive afferents from skin, subcutaneous according to the particular task (Burke, 1988). The and other tissues that subserve the sensory modali- DRT is generally accepted to inhibit FRAs (Whitlock, ties of touch, pressure, temperature and pain. The 1990). However, flexor spasms were not produced clasp-knife phenomenon is also discussed again by dorsolateral spinal lesions in cats involving the here briefly. DRT (Taylor et al., 1997). In another study though, a similar lesion enhanced spinal transmission from Flexor withdrawal reflexes and flexor spasms group II and III afferents (Cavallari & Pettersson, 1989). Inhibition also comes from the medial retic- Flexor reflex afferents ulospinal and vestibulospinal tracts (Brown, 1994). The effects of L-dopa and tizanidine indicate that the In the cat, electrical stimulation of a group of sen- FRA activity is strongly suppressed by dopaminer- sory afferents arising from a variety of sources were gic (Schomburg & Steffens, 1998) and noradrenergic (Delwaide & Pennisi, 1994) pathways, respectively.

Neurophysiology of spasticity 29 (a) (b) Figure 2.10. (a) Illustrating the multimodal (skin, muscle, joint) nature of the group II, III and IV fibres that comprise the flexor reflex afferents (FRAs) and some of their central connections. (b) FRAs converge on a polysynaptic spinal network that excites flexor and inhibits extensor motorneurones. The interneurones involved are inhibited by the dorsal reticulospinal tract (DRT) that arises in the pontomedullary reticular formation. Thus, afferent stimuli, both nociceptive and non-nociceptive, from a wide variety of sources, can excite FRAs and produce a flexor withdrawal reflex. In spasticity, these are exaggerated and manifest as flexor spasms. [(a) From Benecke et al., 1987; (b) from Burke, 1988.]

30 Geoff Sheean The corticospinal and rubrospinal tracts facilitate therefore similar to that in the cat. The latency of FRAs (Burke, 1988). Evidence from animal stud- these electrically evoked reflexes suggests they are ies suggests that serotonergic pathways facilitate mediated by group II afferents, which conduct at flexor reflexes (Maj et al., 1985). Supraspinal centres around 40 m/s, and not the very slowly conduct- receive input from the FRAs via ascending tracts, ing C fibres that conduct pain sensation (Rothwell, including the spinocerebellar pathways. Such input 1994). Others have suggested the group III afferents keeps them apprised of the state of the spinal are responsible (Roby-Brami & Bussel, 1993). In the interneuronal networks and no doubt helps in their UMN syndrome, the early component disappears decision as to which of the FRA actions to facili- (Shahani & Young, 1980) while the late component is tate. The quality of the peripheral stimulus may be preserved but desynchronized (Meinck et al., 1985). important, too. Gentle pressure on the cat hindfoot produces an extension response (plantar flexion) Meinck and colleagues investigate this reflex in whereas a noxious pinprick evokes a flexion resp- detail (Meinck et al., 1985) (Fig. 2.11). Tibialis ante- onse (dorsiflexion) (Rothwell, 1994). When facili- rior had the lowest threshold of all the physio- tated in the spinal cat, less than noxious stimuli can logical leg flexors. Tonic activation of the muscles elicit a flexion withdrawal response. FRAs are sup- shortened the latency of both the early and late pressed by opiates (Schomburg & Steffens, 1998). For components and eliminated the threshold differ- a detailed review of flexor reflexes, see Sandrini et al. ences. This suggested supraspinal modulation of (2005). the reflex. Changing stimulus characteristics could also enhance the reflex. In the UMN syndrome, they Flexor withdrawal reflexes found an impaired early component, a net increase in reflex activity, desynchronization, an abnormal Electrophysiologically, the flexor withdrawal reflex sensitivity to facilitation, and irradiation to muscles in the cat has two components (Rothwell, 1994). The not normally involved. Similar findings were found short-latency component has a central delay of only a irrespective of the site of the UMN lesion, spinal few milliseconds, while the delay for the long-latency cord, brainstem or cerebrum. On the other hand, component is 30 to 50 ms. The short-latency compo- Shahani and Young (1980) observed electrophysio- nent appears to inhibit the later one. logical differences in the flexor withdrawal reflexes following spinal cord transection and cerebral hemi- Flexor withdrawal reflexes can be demonstrated sphere lesions. in man by noxious stimulation of the foot. A 10- to 20-ms train of electrical stimuli delivered to the sole Flexor reflexes in spastic subjects can also be at low intensity produces a short-latency response in elicited by ankle movement (Schmidt et al., 2002) tibialis anterior at around 50 to 60 ms. At higher stim- and knee extension (Wu et al., 2006). In animals ulus intensities, a later, stronger response appears (Harris & Clarke, 2003) and in humans (Anderson at around 110 to 140 ms. It is this late component et al., 2004) with spinal cord lesions, the receptive that dorsiflexes the foot and produces the withdrawal field of the flexor reflex enlarges, indicating some (Shahani & Young, 1971). The earlier response acts degree of descending control over the reflex receptive as a priming movement. At higher stimulus intensi- fields. In humans, this expansion occurred into areas ties, the latency of both components decreases (with that would normally produce ankle plantar flexion larger reductions in the later component) and the when stimulated (Anderson et al., 2004). amplitude and duration of the responses increases (Shahani & Cros, 1990). The latency of the late Flexor spasms response would allow time for a cortical component, but the reflex persists in total spinal cord transection, In the UMN syndrome, patients may suffer from indicating its spinal origin. The situation in man is spasms of the legs that resemble those of the flexor withdrawal reflex. These flexor spasms may

Neurophysiology of spasticity 31 occur in response to a variety of sensory stimuli or 1.8 ×T apparently spontaneously. Common stimuli include nociceptive (bed sores) and nonnociceptive cuta- 1.5 ×T neous stimuli, visceral stimuli such as bladder or bowel distension or bladder irritation (cysti- 1.4 ×T 100 μV tis, in-dwelling catheters). Apparently spontaneous 1.3 ×T spasms are probably due to occult stimuli (Whitlock, 1990). It is likely that flexor spasms represent disin- 0 300 0 300 hibited and distorted flexor withdrawal reflexes. Dif- ms ms ferences in the occurrence of flexor spasms in par- tial spinal, complete spinal and cerebral lesions have Figure 2.11. Tibialis anterior flexor withdrawal reflexes been discussed earlier. elicited in a spastic subject by medial plantar nerve stimulation. The hemiplegic side is shown on the left and Flexor spasms are clearly separate from spasticity, the normal side on the right. As stimulus intensity is as defined at the beginning of this chapter. However, increased (expressed as a multiple of motor threshold, T), they often accompany spasticity, especially in spinal the amplitude of the reflex on both sides increases. The cord lesions, and can be painful and debilitating. hemiplegic side shows an absence of the early phase until higher stimulus intensities and a prolonged late phase. The extensor plantar response Furthermore, the latency of the response from the hemiplegic side is highly dependent upon stimulus The extensor plantar response, or Babinski sign, is intensity, whereas the normal side is not. (From Meinck discussed here following flexor spasms as it is really et al., 1985.) best considered a disinhibited flexion withdrawal reflex. Toe extension or dorsiflexion is regarded phys- However, stimulation of the nearby base of the toes iologically as flexion. In the spinal cat, the flexion and pad of the hallux normally produces the oppo- withdrawal reflex includes dorsiflexion of the hallux site response of toe dorsiflexion. Cutaneous fields in addition to the foot. Stroking the sole of an infant’s often overlap and the examiner could stray more foot also produces this response until the age of 1. towards this latter area. The normal plantar response Thereafter, this response is modified, so that the toes would then be the product of two opposing reflexes, and ankle plantar flex while knee flexion and hip flex- with the plantar-flexor reflex tending to dominate. ion are unchanged. This response still withdraws the However, should there be, in addition, contraction stimulated part from the stimulus (sole) by arching of the pretibial muscles (a frequent occurrence in the foot while maintaining contact with the ground anticipation of an unpleasant stroking of the sole), through the toes. Such a modification is seen as an sufficient reciprocal inhibition could be produced adaptation to the upright walking posture (Rothwell, to suppress the plantar-flexor muscles, leaving the 1994). In the upper motor neurone syndrome, the dorsiflexor response unopposed and so the great toe full flexion reflex returns with dorsiflexion of all the dorsiflexes. The reflex response also depends upon toes and the ankle. This is the only sign of the UMN the stimulus. Nonnociceptive sural nerve stimula- syndrome that is unequivocally linked to the pyra- tion produces great toe plantar flexion, but nocicep- midal tracts (Burke, 1988; Nathan, 1994; van Gijn, tive stimulation produces the full flexor withdrawal 1996). reflex, including dorsiflexion of the great toe. However, Burke (1988) points out that the situa- tion is actually quite complex. The plantar response is usually evoked by a stroke along the lateral bor- der of the sole and over the ball of the foot, pro- ducing the normal response of toe plantar flexion.

32 Geoff Sheean Voorhoeve, 1962). Somewhat paradoxically, the extensor plantar response is a firm sign of pyramidal tract injury, which would be expected to reduce FRA activity, not enhance it (Burke, 1988). The explana- tion lies in the complexity of the FRA circuits alluded to earlier, in which there may exist alternative path- ways with opposing actions. The action of the pyra- midal tracts on FRAs from the plantar surface is facil- itation of a reflex of toe plantar flexion (physiological extension). Loss of this facilitation in a pyramidal lesion allows the alternative reflex pathway of great toe dorsiflexion to act unopposed. Despite being an exaggerated flexion reflex, the Babinski sign is not always associated with increases in other flexor reflex activity (van Gijn, 1978). Figure 2.12. Extensor reflexes in the normal lower limb. Extensor reflexes and spasms Recordings from gluteus maximus performing a mild background contraction in response to noxious stimuli In similar way to flexion withdrawal reflexes, non- presented to the skin on different parts of the ventral and nociceptive cutaneous stimulation in cats (Hag- dorsal leg. Immediate strong contraction was produced by barth, 1952) and man (Hagbarth, 1960; Kugelberg, stimulation over the gluteal region, whereas most other 1962) can evoke extension responses in the stimu- areas produced a brief period of inhibition. (From lated limbs. Like flexion withdrawal reflexes, exten- Hagbarth, 1960.) sion reflexes are protective, serving to move the area stimulated away from the stimulus. Whether a stim- Thus, the direction of great toe movement when ulus evokes a flexion or extension response is in the plantar response is tested may depend upon the part dependent upon the location of the stimulus. exact placement of the stimulus and its intensity and Extension responses in man may be evoked from upon the degree of pretibial activation. Burke (1988) cutaneous stimulation of such areas as the groin, would view as definitely pathological an extensor buttock and posterior leg (Fig. 2.12). The ‘crossed plantar response from a nonnociceptive stimulus extension’ component of a contralateral flexion with- given to the midportion of the sole and would be sus- drawal reflex is a form of extension reflex (see above). picious of such a response to a nociceptive stimulus, As already mentioned, flexion and extension reflexes particularly if accompanied by the typical ‘triple flex- are built into the spinal ‘stepping generator’ subserv- ion’ response described earlier. Medical students are ing locomotion. frequently under the misconception that the plantar stimulus should be painful. Furthermore, many neu- Pathologically, extension responses occur in rologists examine with the patient sitting on the side response to proprioceptive input from the hip: iliop- of the bed, with the legs suspended. This can lead to soas stretch (hip extension) induces hip flexion with a slight activation of pretibial muscles against gravity knee extension and ankle plantarflexion in patients and a false-positive response. with spinal cord injury (Kuhn, 1950; Little, 1989; Schmidt & Benz, 2002). This matches clinical obser- An extensor plantar response is a flexion with- vation that going from the sitting to the supine posi- drawal response mediated by FRAs, which are tion is a potent stimulator of extensor spasms (Kuhn, facilitated by the pyramidal tracts (Lundberg & 1950). The positive support reaction, to be described,

Neurophysiology of spasticity 33 is another extensor reflex and may be both proprio- Lt BB ceptive and exteroceptive in nature. Lt TB Following complete spinal cord transection, patients often experience both flexor and exten- Lt FS sor spasms, which is understandable, as both reflex pathways would be completely disinhibited by the Rt FS loss of supraspinal control. Patients may, after several months, settle into a state of predominant extensor Lt Flex A spasms (Hagbarth, 1960; Kugelberg, 1962), but para- plegia in flexion is also common. Perhaps the domi- Figure 2.13. Associated reactions studied in the upper nant posture is a matter of the net effect of the many limb. A patient with a left hemiplegia exhibited progressive afferent (exteroceptive and proprioceptive) inputs at left elbow during gait with each successive step (time the time. A bed sore on the heel or a urinary infec- along the x-axis; total sweep about 54 seconds). Surface tion could transform paraplegia in extension into electromyography (EMG) was recorded from the left (Lt) paraplegia in flexion. For reasons outlined earlier, biceps (BB) and triceps (TB) brachii. Traces labelled left partial spinal cord lesions tend to have fewer flexor (Lt) and right (Rt) FS represent successive footsteps. spasms and take on a more dominant extensor tone Flexion angle (Flex A) of the left elbow is shown in the (Barolat & Maiman, 1987). bottom trace. Note increasing elbow flexion but a stable level of biceps EMG activity, indicating biomechanical Thus, both flexor and extensor spasms appear factors in the elbow flexion. (From Dickstein et al., 1996.) to be exaggerated manifestations of existing spinal reflexes (Burke, 1988) that exist for stance and loco- of motor effort (e.g. the effort of walking) and the motion. Often they are inappropriate and unwanted, degree of hypertonia in the limb showing the asso- but extensor spasms and an extensor posture ciated reaction. Thus, physiotherapists have used could also be viewed as functionally advantageous the associated reaction as a gauge of the patient’s by providing a rigid supporting limb for stance spasticity and overall motor function, and it has and gait. even been treated directly (Bobath, 1990). The phe- nomenon of associated reaction was first reported Other UMN phenomena by Walshe in 1923 and has been described variously as ‘released postural reactions deprived of volun- Associated reactions tary control’ (Walshe, 1923), ‘synkinesia’ (Bourbon- nais, 1995) and ‘stereotypic flexor synergy’ (Bobath, In the UMN syndrome, physical activity in one part 1990). of the body may be accompanied by unnecessary involuntary activity in another. A typical example Dickstein and colleagues (1996) have investigated would be the progressive elbow flexion seen in a the associated reaction of elbow flexion in hemi- patient with hemiparetic stroke during walking and paretic subjects during walking. They found a rapid is a familiar component of the ‘hemiplegic posture’. increase in elbow flexion during the first four steps Associated reactions can also occur with involun- and a gradual increase thereafter (Fig. 2.13). Con- tary activity such as coughing, sneezing and yawn- firming previous notions, the degree of elbow flex- ing. Generally the part showing the associated reac- ion correlated with the Ashworth score (Ashworth, tion, the elbow flexors in the example given, are also 1964) of elbow flexor tone. However, there was a poor affected by the UMN syndrome and usually display some degree of spasticity. The extent of the associ- ated reaction seems to depend upon both the degree

34 Geoff Sheean correlation between the EMG activity of the elbow sive co-contraction is a normal feature, associated flexors and the degree of elbow flexion. They con- with heteronymous, monosynaptic Ia projections cluded that nonreflex soft tissue changes played an from biceps to triceps and to regional synergists important role in this associated reaction. and antagonists (O’Sullivan et al., 1998). Normally these connections become restricted to primary Clearly though, there is also a neural component synergists in the 4 years of life (O’Sullivan et al., involving motoneurone activity. The mechanism of 1998). this is uncertain, but it is thought to be multifac- torial (Dewald & Rymer, 1993). Dewald and Rymer Controlled co-contraction thereafter is an impor- (1993) concluded that enhanced flexion withdrawal tant feature of normal motor function providing reflexes probably do not play the primary role but postural stability or fixation of a body part – for that disturbed descending supraspinal commands example, to stabilize the wrist when hitting a ten- may be involved. Their hypothesis is that unaf- nis ball. In these situations it is considered appro- fected bulbospinal motor pathways with more dif- priate and functional and a manifestation of normal fuse, polysegmental motoneurone connections may reciprocal innervation. Normal co-contraction is ini- assume the role of the damaged UMN tracts in trans- tiated and modulated as the movement demands. mission of descending voluntary commands. These Co-contraction is dysfunctional when it is inappro- older bulbospinal pathways are less focussed than priate or excessive and impairs agonist function, also the pyramidal tracts. They have substantial connec- making the agonist appear weaker than it is. Dys- tions to motoneurones of the axial and proximal functional or pathological co-contraction is a com- limb musculature, which could result in the syner- mon feature of dystonia and has been demonstrated gic patterns observed. Propriospinal pathways could more in cerebral palsy (Crenna, 1998) than in adult also be involved. Compatible with the pattern of brain injury (O’Sullivan et al., 1998). Furthermore, tone in the hemiparetic UMN syndrome, descending the contribution of pathological co-contraction in motor drive may favour flexors rather than extensors adult spasticity to impaired movement is contro- through increased excitability of flexor motoneu- versial (Conrad et al., 1985), with both protagonists rones and the interneurones of the flexor reflex path- (Yanagisawa & Tanaka, 1978; Corcos et al., 1986; ways. El-Abd, 1993) and antagonists (Mizrahi & Angel, 1979; Dietz et al., 1981; Dietz & Berger, 1983; Fel- A further contributing factor could be vestibu- lows et al., 1994; Davies et al., 1996). This is partic- lospinal reflexes. Assumption of the upright pos- ularly so for movements of the ankle, where some ture, as in walking, enhances excitability of ‘antigrav- researchers believe that biomechanical factors may ity’ motoneurones. Disinhibition of this pathway be more important (Dietz, 1981; Dietz & Berger, 1983; could generate sufficient descending motor drive to Becher et al., 1998). These results have been chal- produce elbow flexion (and leg extension). Such a lenged (Conrad et al., 1985). The question of the mechanism could contribute to the so-called hemi- existence and importance of co-contraction has plegic posture, a form of spastic dystonia (Burke, therapeutic relevance; inappropriate antagonist 1988) (see ‘Spastic dystonia’ on p. 35). Alternatively, it contraction could be reduced focally by botulinum could simply contribute to an increased excitability toxin injections (Sheean, 1998b) or phenol nerve of the elbow flexor motoneurones, such that non- blocks or by other antispasticity agents such as focussed descending voluntary commands would baclofen (Latash & Penn, 1996). favour these flexors. The pathophysiological substrate of co- Spastic co-contraction contraction in dystonia is impairment of Ia reciprocal inhibition (Berardelli et al., 1998) in the Co-contraction refers to the simultaneous con- spinal cord. Normally, agonist Ia activity exerts an traction of both agonist and antagonist muscles. inhibitory effect on the antagonist motoneurones In normal postnatal motor development, exten- via an interneurone (see Fig. 2.19, p. 42). This activity

Neurophysiology of spasticity 35 is influenced by supraspinal inputs (co-contraction tion occurring simultaneously with or before con- is activated and deactivated at a cortical level traction of the agonist (Fig. 2.14) during a non- (Humphrey & Reed, 1983) and by other segmental isometric contraction. Finally, there are examples afferents (Delwaide & Olivier, 1987). Abnormalities where the antagonist co-contraction overwhelms the of Ia reciprocal inhibition have been reported in agonist, producing the movement opposite of that spasticity and could contribute to co-contraction intended (Fig. 2.15). A common clinical scenario (Crone, 1994; Okuma et al., 1996). Impaired spinal is the patient with spastic finger flexors and weak Ia reciprocal inhibition in dystonia probably arises extensors whose fingers flex more when he or she is from disordered supraspinal modulation and a sim- trying to extend them. ilar mechanism in spasticity is probable. In spastic cerebral palsy the heteronymous Ia connections of Despite this, there is some indication that hyperac- infancy mentioned earlier are persistent, but this tive stretch reflexes in an antagonist could interfere is not the case in adult hemiparesis due to stroke with movement. This is discussed further on, under (O’Sullivan et al., 1998). Some evidence suggests ‘The spastic movement disorder’. that impaired Ib reciprocal inhibition could con- tribute to co-contraction in the lower limb [see ‘Ib Intact Ia reciprocal inhibition in the UMN syn- Nonreciprocal (autogenic) inhibition’ on p. 43]. Fur- drome may also cause problems. The ankle plan- ther discussion of reciprocal inhibition is presented tar flexors are frequently overactive and can inhibit below. the ankle dorsiflexors through preserved (Yanagi- sawa et al., 1976) or even increased (Ashby & Wiens, Co-contraction should be differentiated from a 1989) Ia reciprocal inhibition, contributing to their hyperactive stretch reflex in the antagonist mus- apparent weakness and foot drop. Furthermore, local cle that is elicited by the lengthening produced by anaesthetic injections into the triceps surae to block the agonist action. For example, active elbow exten- afferent fibres led to increased strength of the ankle sion by triceps will lengthen the biceps and may dorsiflexors (Yanagisawa & Tanaka, 1978). Dietz and elicit a stretch response. This will appear as simul- colleagues (1981) have challenged this whole con- taneous contraction of both muscles but is funda- cept, however, finding minimal plantar-flexor EMG mentally different to co-contraction produced by activity and excessive activation of ankle dorsiflex- simultaneous motor drive to both muscles, a ‘diffu- ors during walking, despite a plantar-flexed posture sion of descending commands’ (Fellows et al., 1994). and hypertonia at the ankle. They concluded that soft Both situations could arise from similar pathophys- tissue changes were responsible, rather than neural iological mechanisms, however – that is, defects of causes. Ia reciprocal inhibition (Delwaide & Olivier, 1987). The distinction could be made by isometric con- Spastic dystonia traction of triceps that does not stretch biceps; the presence of biceps activity would indicate true Dystonia is a condition characterized by ‘sustained co-contraction. One difficulty in interpreting iso- muscle contractions, frequently causing twisting and metric studies is the normal occurrence of co- repetitive movements, or abnormal postures’ (Fahn contraction in isometric movements (Flanders & et al., 1987). This definition usually refers to condi- Cordo, 1987). Thus, in one study (Fellows et al., tions arising from basal ganglia disorders. Patients 1994), there was no greater co-contraction of elbow suffering an UMN syndrome frequently adopt an flexors and extensors during isometric contrac- abnormal posture, well known to most clinicians as tions in hemiparetic patients compared with normal the ‘hemiplegic’ or ‘decorticate’ posture. The hemi- controls. plegic posture involves flexion of the elbow, wrist and fingers with adduction of the shoulder and pronation Another indication that co-contraction is not a of the forearm. The leg is extended at the hip and stretch reflex in an antagonist induced by agonist knee, plantar flexed and inverted at the ankle, with contraction is the appearance of antagonist contrac- adduction of the hip. This may be loosely described

36 Geoff Sheean :CP 53, Cerebral aP ls:y Reahcing Foraw rd twi h Left Uper miL b Calirb ation: 250 μv; 25 ° 80.00 se.c Bicesp (40x) Braahci lsi 4( 0x) rB ac-Rh ad 4( 0x) lE ob lf–w ex up (1x) Lat Triec ps (40x) Med Treci ps 4( 0x) 0.80 se.c Figure 2.14. Co-contraction of elbow flexors and extensors during attempted extension. Note that EMG activity in the brachioradialis begins at the same time as the triceps, before any stretching of the elbow flexors has taken place indicating that this form of co-contraction is not a stretch reflex. (From Mayer & Herman, 2004.) Up Relax 0.2 Torque (V) 0 −0.2 0.5 Tibialis anterior 0 (V) −0.5 0.5 Triceps surae 0 (V) −0.5 85 90 95 s Figure 2.15. An attempt at isometric ankle dorsiflexion increases EMG activity in the ankle plantarflexors causing plantarflexion (downward torque). After a few seconds the ankle dorsiflexors are activated but are unable to overcome the ankle plantarflexors. The resting position was seated, with the hip flexed at 30 degrees and the ankle fixed at 90 degrees. The knee was fully straight, placing stretch on the gastrocnemius muscle, which probably accounts for the small amount of EMG activity in the triceps surae at rest. This shows a clear example of a misdirected descending command from dorsiflexors to plantarflexors – no stretch or other afferent input could account for this. (From Gracies, 2005.)

Neurophysiology of spasticity 37 0.0250 Extensors (V) 0.0150 0.0250 Flexors (V) 0.0150 150 deg 1.5 100 deg 50 deg 0 deg Elbow 10 20 30 40 50 60 Angle (V) S 0.5 0 Figure 2.16. Spastic dystonia is sensitive to stretch. The figure shows the rectified EMG tracings of a hemiplegic patient. Initially, the elbow is highly flexed by the elbow flexor contraction. Stepwise extension by ramp and hold stretches were applied every 15 seconds at a rate of 10 degrees per second. Note that the EMG activity gradually decreases with each stretch. (From Gracies, 2005.) as ‘dystonia’, but the term is confusing when (see ‘Tonic stretch reflexes’ on p. 17). Spastic dystonia used in the context of the UMN lesion and may arise from continuous supraspinal drive from spasticity. areas disinhibited by the UMN lesion to the spinal motoneurones. In addition to stretch, spastic dys- Although frequently accompanied by spasticity, tonia is altered by postural changes (Denny-Brown, the hemiplegic posture of spastic dystonia is fun- 1966), presumably through vestibular mechanisms damentally different. Spasticity is velocity depen- (Burke, 1988). The phenomenon of associated reac- dent and mediated by hyperactive proprioceptive tions (see above) indicates that the hemiplegic pos- stretch reflexes. The continuous muscle contrac- ture is also subject to other influences. tion maintaining spastic dystonia is present without limb movement. Furthermore, it is not dependent Another finding in patients with UMN syndrome upon afferent input from the limb, as it persists after is delayed relaxation after voluntary contraction dorsal root section (Denny-Brown, 1966). Although caused by continued firing of motor units. Some con- spastic dystonia is not dependent upon afferent sider this a form of spastic dystonia (Gracies, 2005). input from the limb, it is affected by the degree As discussed below, motoneuronal hyperexcitability, of stretch placed on the muscle (Denny-Brown, plateau potentials and repetitive firing could under- 1966). For example, prolonged stretching can reduce liethis(see‘Alpha motoneurone excitability’on p. 47). spastic dystonia (Fig. 2.16), as every physiothera- pist knows. The sensitivity of spasticity to stretch Thus, unlike most of the other positive features of is well known and has already been described, the UMN syndrome, the motor drive behind spas- including its diminuation with repeated stretching tic dystonia is not a spinal reflex; it is efferent medi- ated rather than afferent mediated. This distinction

38 Geoff Sheean has important therapeutic implications. Spastic dys- Electrophysiological studies of spinal tonia would not be expected to respond well to reflexes in spasticity traditional antispastic therapies such as diazepam and baclofen, which suppress spinal reflex activ- It is well established that spinal phasic and tonic ity, or to dorsal rhizotomy, as Denny-Brown (1966) stretch, flexor withdrawal and other reflexes are found. If plateau potentials are involved tizanidine hyperexcitable in the UMN syndrome following might be effective, however (see ‘Alpha motoneurone interruption of the descending UMN pathways. excitability’). Spastic dystonia should still respond However, the actual spinal circuitry responsible for to treatments that modify motor nerve or muscle the production of these effects is less well estab- activity, such as dantrolene, botulinum toxin, phenol lished. A number of the spinal reflex mechanisms injections and peripheral nerve section. It should be involved in motor control, already mentioned, have noted that some sustained abnormal postures in the been studied electrophysiologically in an attempt UMN are reflex mediated, such as the continuous leg to understand the basis of the hyperexcitable pro- flexion of ‘paraplegia in flexion’ following total spinal prioceptive reflexes and other phenomena of the cord section (already discussed). Soft tissue and joint UMN syndrome (Table 2.2). Most attention has been pathology may also contribute to sustained abnor- given to inhibitory mechanisms, with the expec- mal postures. tation of finding decreased inhibition. However, excitatory mechanisms and the level of excitabil- Positive support reaction ity of alpha motoneurones have also been exam- ined. Flexor withdrawal reflexes, the basis of flexor This term is more commonly used by physiothera- spasms in the UMN syndrome, have already been pists than physicians to describe a pattern of plantar discussed. flexion and inversion of the ankle of a patient with an UMN syndrome upon attempted weight bear- Spinal inhibitory mechanisms ing (Bobath, 1990). Others have termed this phe- nomenon the tonic ambulatory foot response (Man- The four main spinal inhibitory activities that have fredi et al., 1975). There may be extension of the knee, been studied are Ia presynaptic inhibition, Ia recipro- producing a pattern of extensor thrust of the lower cal inhibition, Ib nonreciprocal inhibition and Ren- limb (Schomberg, 1990). A positive support reaction shaw cell inhibition. Most techniques are based upon can be extremely debilitating and prevent standing modulation of H reflexes, which are discussed briefly. and walking. It is presumed to be a reflex involving a proprioceptive stimulus elicited by stretch of the H reflexes intrinsic foot muscles and an exteroceptive stimu- lus elicited by contact of the foot with the ground These were first discovered in the triceps surae by (Bobath, 1990). A similar physiological spinal exten- Hoffman in 1926, hence the name H reflex. Low- sor reflex exists in infants (Rothwell, 1994) and is nor- intensity electrical stimulation of the tibial nerve in mally suppressed. Analogous to the Babinski sign, the popliteal fossa elicits a reflex contraction of tri- this reflex is presumably disinhibited by the UMN ceps surae without direct activation of the motor lesion. axons in the nerve (Fig. 2.17). By selecting appro- priate stimulus parameters, the Ia afferents could The supraspinal control of this reflex in humans be stimulated selectively. The latency of the reflex is not known. However, a positive support reaction is around 30 ms. For a long time the H reflex was appeared in the cat following a lesion of the dorso- incorrectly thought to be equivalent to the tendon lateral funiculus containing the (inhibitory) reticu- reflex (T reflex), except that the spindle is bypassed. lospinal pathways, accompanied by spasticity (Tay- It had considered that comparison of H- and lor et al., 1997).