Report on the Muscular Dystrophy Campaign workshop: Exercise in neuromuscular diseases Newcastle, January 2002

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1 Neuromuscular Disorders 12 (2002) Workshop report Report on the Muscular Dystrophy Campaign workshop: Exercise in neuromuscular diseases Newcastle, January 2002 Michelle Eagle Newcastle Muscle Centre, Institute of Genetics, International Centre for Life, Newcastle NE1 3BZ, UK Accepted 28 May Representatives from around the UK gathered in Newcastle to review the evidence for the way exercise and orthotics are used in the management of neuromuscular diseases. Participants included physiotherapists, an orthotist, family care officers, a rehabilitation doctor, a scientist with experience in animal models of muscular dystrophy, and patient representatives with facioscapulohumeral muscular dystrophy (FSH) and Duchenne muscular dystrophy (DMD). The aims of the workshop were 1. To define current practice in the prescription of exercise in neuromuscular conditions. 2. To appraise and evaluate the evidence for the use of the following: (a) Active/resisted exercises. (b) Passive or stretching exercises including orthoses. (c) Respiratory muscle training. 3. To suggest guidelines for exercise and orthosis prescription where this could be based on evidence or a consensus of expert opinion. These broad aims were specifically targeted at the management of DMD and Becker muscular dystrophy, FSH muscular dystrophy, myotonic dystrophy, spinal muscular atrophy (SMA) Types II and III, and the more diverse groups of congenital muscular dystrophies, myopathies and limb girdle muscular dystrophies. 1. Current practice Only in a few limited areas is there a published evidence base for the type, duration and frequency or mode of delivery of exercise or physical therapy in the neuromuscular disorders. The group agreed that the main aims of physiotherapy are to (a) Maintain or improve muscle strength by exercise. (b) Maximise functional ability by exercise and the use of orthoses. (c) Minimise the development of contractures by stretching and splinting. The methods by which these aims are implemented vary both in the components of the individual exercises and the programmes within which these exercises are contained. On the whole though, exercise programmes tend to be linked with activities of daily living. The role of strengthening exercises is controversial particularly in DMD. Maintenance of symmetry was thought by workshop participants to be an important goal and therapeutic options include splinting or stretching the contracted muscle and/or strengthening opposing muscle groups. All participants agreed that care must be taken not to overwhelm the family with too many exercises particularly as recent evidence suggests that too many exercises can adversely affect compliance [1]. Even within the UK, therapy provision varies according to available resources. Hydrotherapy is often the preferred treatment for children with neuromuscular disorders but there is very little objective published evidence of the benefits. In small children, hydrotherapy is usually enjoyable but older children and adults may prefer land-based therapy because of difficult access to pools, becoming cold easily and embarrassment. In adults, access to therapy in general is varied and often very limited. Many patients at best have blocks of therapy on a yearly basis; others have no access at all except in acute situations or for chest physiotherapy when required. The majority of therapists have little experience with inherited adult neuromus /02/$ - see front matter q 2002 Elsevier Science B.V. All rights reserved. PII: S (02)

2 976 M. Eagle / Neuromuscular Disorders 12 (2002) cular conditions and are unable to offer advice based on evidence or experience. The use of orthoses is variable with no guidelines available to therapists or orthotists. 2. Exercise in DMD There has been concern that overactivity may induce muscle damage. Some of the widely held views on this are based on evidence from studies with the mdx mouse. Care must be taken in extrapolating from exercise studies in mdx mice to predicting effects in DMD patients because not only is muscle size, the forces experienced and the stance of the mouse very different from humans but also the natural history of muscular dystrophy is very different in the mdx mouse compared to DMD patients. A number of different studies compare the performance of mdx to normal mouse muscles in response to electrical stimulation or to various forms of exercise in the intact animal. Some studies appear contradictory but many of the differences are methodological relating to the use of different equipment, different periods of exercise, different ages of mice and the examination of different muscles. The function of dystrophin and the mechanism by which its absence causes muscle pathology is not fully understood but it is possible that increased mechanical stresses that are placed on the muscle particularly during eccentric exercise may accelerate the disease process [2]. There is evidence that indicates eccentric activity in the mdx mouse leads to increased muscle damage although one study reported that this was no different from controls [3 5]. Preventing muscle contraction by denervation eliminated muscle fibre necrosis in young mdx mice [6] and extensor digitorum longus muscle overload by synergist ablation led to strength deficits in mdx compared to strength increases in normal mice [7]. Repeated treadmill exercise reduced strength in the mdx mouse [8,9] and caused increased muscle lesions [10] but appeared to enhance contractile strength in the mdx diaphragm [11,12]. Endurance exercise appears to be beneficial in terms of strength and decreased fatigue [13 17]. Mouse studies suggest that eccentric exercise should be avoided, as dystrophic muscle is very prone to damage under these conditions. Long-term endurance exercise appears to do little harm and may provide benefit. Studies in dystrophic mdx mice show that eccentric exercise (e.g. downhill running) leads to increased muscle damage whereas voluntary wheel running or swimming does no harm and may improve strength and fatigue resistance. Although as we have said care should be taken in extrapolating to humans this may direct research to be cautious regarding eccentric activities such as going downstairs and to investigate exercises such as swimming. In patients with DMD there were very few randomised or controlled trials and patient populations were often heterogeneous [18 40]. The value of different modes of strengthening exercises is unclear as comparisons between studies are difficult to draw. For example de Lateur and Giaconi [41] reported improvement in strength following sub-maximal exercise whereas Scott et al. [39] reported no detrimental effect or improvement when comparing active versus resisted exercise but did not measure function. Vignos and Watkins [38] reported increased strength in the first few months of an exercise regime but this was not maintained over longer term. Improvements in function were not seen in patients with DMD but were in patients with limb girdle or FSH muscular dystrophy. The timing of the intervention may impact on the effectiveness of the response as strengthening exercises may be more effective if introduced when muscle weakness is not severe [24]. Low frequency electrical stimulation may improve quadriceps strength in young boys with DMD although no functional improvement was noted [42]. Stimulation at high frequencies, however, may be deleterious [43]. In ambulant patients with DMD highly repetitive, low intensity aerobic training (swimming or running) causes biochemical adaptations in slow twitch (type I) muscle fibres. In high intensity low repetitive anaerobic exercise (strengthening) there is a shift to adaptation in fast twitch (type 2) fibres. Therefore, the type of training may be significant in evaluating the effectiveness in particular diseases according to specific fibre type deficiency [44]. There is no evidence in humans that increased activity or resisted exercise caused physical deterioration [39,45]. Evidence for exercise in non-ambulant patients with DMD is scarce. Two studies showed very little or no improvement in strength in children who were unable to walk [46,47]. However, the benefits of activity and the social and psychological aspects of participation were recognised by workshop participants as very important although not researched. Studies on the effect of exercise in human patients are difficult to reproduce, have variable patient populations and are generally observational and uncontrolled. No clearly defined exercise protocols can be drawn from research evidence. There is some evidence to suggest physiological improvement in muscle as a result of exercise but there is little evidence to suggest functional improvement as a result of training programmes. There is no evidence on the role of stretching or mobilising exercises in the non-ambulant patient or on the psychological benefits of participation in activity. There is a great deal of further research to be done on the role of various types of exercise and on the timing of the intervention. Stringent controls are required to assess the effect of exercise because the process of normal muscle maturation and degeneration occur alongside each other in addition to the usual reasons for including controls in trials [41]. 3. Recommendations for exercise in DMD See also recommendations for orthotics provision. It

3 M. Eagle / Neuromuscular Disorders 12 (2002) must be emphasised that these recommendations are based on current expert opinion only and that research is needed to improve the evidence base in all the areas suggested Ambulant children 1. Daily stretches to the gastrocnemius soleus complex, hip flexors and iliotibial band. 2. Encourage voluntary active exercise such as swimming or hydrotherapy and cycling (may be motor assisted). 3. Symmetry to be promoted in posture, exercises and activities. 4. Eccentric activities such as running downhill and excessive walking downstairs to be avoided Non-ambulant children 1. Mobilising passive or active assisted exercises to maintain and promote symmetry and comfort. These may be land based programmes or in water if preferred. Wheelchair/seating prescription, respiratory and spinal management have not been discussed in this workshop but they are clearly important issues that need consideration in the holistic management of the young person. 4. SMA, congenital muscular dystrophy, myopathy and FSH muscular dystrophy of childhood These are relatively rare conditions, so few therapists have significant experience other than those in specialist centres. The role of exercise, stretching and orthoses is not well established in the literature for the congenital muscular dystrophies, FSH or SMA. There is some evidence that knee-ankle-foot-orthoses (KAFOs) can promote walking or standing in children with SMA type II and congenital muscular dystrophy [48]. Hydrotherapy is the treatment of choice by many therapists but the only available evidence is uncontrolled and observational [49,50]. These studies showed no evidence that exercise improves spinal posture, contractures or overall function in SMA II. Therapists base their treatment protocols on regular assessment and review rather than on evidence. 5. Recommendations for FSH, congenital muscular dystrophy and SMA Precise diagnosis should be obtained where possible so that the predicted complications or features of the disease can be addressed and assessed. Until there is research evidence for treatment protocols the following recommendations are made. In addition to the following see recommendations for prescription of orthoses. 1. A full assessment prior to prescribing a treatment regime must be carried out and include measurement of respiratory function, strength, range of movement and function. 2. Muscle groups that are thought to be prone to contractures should be targeted for stretching exercises and if there is antigravity power in the opposing muscle group, low resistance exercises may be considered. 3. Activity programmes to include advice on swimming or hydrotherapy, cycling and riding where appropriate. 6. Orthoses and contracture development in neuromuscular disorders Most neuromuscular research into exercise or orthoses comes from DMD or animal studies and there is almost nothing to be found on adult neuromuscular disorders or congenital myopathies or dystrophies. This is an area that needs to be redressed since contractures are a primary problem in some neuromuscular disorders. 6. Contracture development Recognised patterns of weakness in the neuromuscular disorders result in muscle imbalance and lead to postural compensations to maintain standing equilibrium. These factors are thought to precipitate changes in muscle length and the development of contractures particularly about weight-bearing joints. The ability of a muscle to generate force is influenced by the length at which it contracts so that a muscle which is already weakened by a pathological process, may be further compromised if it is held in a shortened position [51]. In the presence of muscle weakness, joint range of motion and the length of the muscle/tendon complex may be relevant for optimal muscle function but published data about the relationship between contractures and muscle power are sparse. The assessment tools for measurement of contactures are limited and there are no standard measuring techniques. The same assessor should make repeated measurements where possible [52]. Manual muscle testing is often used for grading muscle strength but is probably an insufficiently sensitive outcome measure to evaluate change [53]. Static prolonged posture such as holding computer game controls for many hours in a day or sitting in a particular posture is anecdotally thought to favour development of contractures but again is not substantiated by sound research evidence [54]. Most therapists would advise frequent change of posture and passive or active assisted movement of joints that are held in one position. Elbow contractures are rare in ambulant DMD and usually develop after years sitting with flexed elbows in a wheelchair suggesting that they are due to

4 978 M. Eagle / Neuromuscular Disorders 12 (2002) posture, but additional factors such as differential progression of muscle weakness may be involved. In other conditions contractures appear not to be positional and are specific characteristics of the disease [55]. A number of theories, based on clinical observation, have been advanced to explain the characteristic hyperlordotic and equinus gait of the patient with DMD. The most plausible theory relates these changes to substitution patterns for hip extensor and quadriceps weakness. With the advent of gait analysis technology a biomechanical analysis of the dynamic motion and forces about joints is possible. A small number of gait analysis studies have been undertaken in DMD and have shown that quadriceps insufficiency is the key functional deficit in gait deterioration, and an equinus gait is a necessary compensation to keep the forces about proximal joints within the limits controllable by weak muscles [56,57]. This supports the view that the primary problem at least in DMD is muscle weakness and that contractures develop secondary to this weakness. However, this is not widely appreciated by some clinicians who perceive contractures as a primary feature of the disease. This can lead to inappropriate management recommendations such as surgical release of equinus or the prescription of ankle-foot-orthoses (AFOs) for the ambulant child while the child is independently ambulant, resulting in knee instability or collapse, and premature loss of ambulation. 7. AFOs Orthoses, principally AFOs supplied as night splints, are used in neuromuscular disorders to control the development of reduced range of movement at the ankle joint by applying a prolonged passive stretch to the gastrocnemius soleus complex. It has been demonstrated in animal studies that if healthy muscle is immobilised in a shortened position, sarcomeres will be lost, and conversely, a muscle immobilised in a lengthened position will add on sarcomeres. Similarly in dystrophic mice a muscle immobilised in a lengthened position is capable of adding on sarcomeres but this is at a slower rate [58]. A stretch of 30 min daily has been shown to prevent the loss of sarcomeres and prevent much of the muscle atrophy associated with immobilisation in the shortened position [59]. No equivalent information is available in the human subject. Two studies specifically evaluate the effect of orthoses on the development of contractures. Both concluded that the use of passive stretching and night splints were more effective than passive stretching alone at both delaying contracture development and prolonging independent ambulation [60,61]. Since gastrocnemius is a two-joint muscle, which crosses both the ankle and the knee, an effective stretch will be provided if both the foot is held at plantargrade or maximum dorsiflexion and the knee is held in extension. This type of night splint is not routinely supplied since anecdotally it is not well tolerated, interfering with sleep. Theoretically, an AFO crossing only the ankle joint could possibly increase knee contractures since the child may flex the knee to escape a stretch at the ankle. No information is available relating to this but clinical experience suggests this is not a major problem. 8. KAFOs KAFOs were first described in 1962 to extend the independent walking ability of 15 boys with DMD [62]. Since then the use of lightweight materials in the construction of orthoses has led to the increasingly widespread use of cosmetically acceptable KAFOs. When combined with a programme of surgical release of contractures and intensive rehabilitation it is possible to prolong ambulation when independent walking ceases. A structured review of 35 studies reported a median prolongation of independent walking for 24 months [63]. It was impossible to extract information on the effect of prolonged ambulation on contracture development due to missing data or because the progression of contractures was expressed differently in the selected articles. A comprehensive attempt to specifically evaluate the long-term outcome of such a programme on lower limb contractures retrospectively studied 144 DMD boys over 40 years evaluating the effect of physiotherapy and orthopaedic treatment on contractures of the lower extremities and on the duration of the ability to walk [64]. The nature and length of the study clearly implies the conclusions should be viewed cautiously. They report contractures were best controlled when patients were managed with a combination of daily passive stretching exercises, prescribed periods of standing and walking, tenotomy of the achilles tendon, posterior tibial transfer, and application of KAFOs. Five to seven years after the operation and bracing, control of contractures was still good, especially for the patients who had posterior tibial tendon transfer. The programme enabled patients who had been managed with bracing to walk until a mean age of 13.6 years. In another retrospective study walking in KAFOs beyond the age of 13 years was the most important factor in delaying the progression of scoliosis [65]. Expert opinion at this workshop suggests that the best time for the introduction of KAFOs is when walking is almost impossible so that their use provides an improvement in functional ability. Therapists at the workshop were in agreement that poorly fitting KAFOs compromise a successful outcome and strongly recommended using orthotists with specific experience in neuromuscular disorders to measure and supply these orthoses. 9. Standing frames/swivel walkers Information from questionnaires on orthotic prescription patterns in The Netherlands indicate that AFOs and standing frames are primarily the type of orthoses prescribed for the

5 M. Eagle / Neuromuscular Disorders 12 (2002) purpose of contracture prevention or reduction in DMD [66]. The numbers, however, are small with a total of 53 DMD boys being cared for by 25 physicians across the country. Swivel walkers modified for children with DMD may have a role in the prevention of contractures [67] but no comprehensive study has been undertaken on the effect of either standing frames or swivel walkers on lower limb contractures in neuromuscular disorders. 10. Conclusions and recommendations 1. Night-time AFOs in addition to stretching daily are recommended for ambulant children with DMD to maintain the length of the gastrocnemius soleus complex. There is no evidence on when to supply night splints but it is recommended that this be when there is loss of dorsiflexion. 2. AFOs are not recommended for ambulant children with DMD as this compromises their ability to walk by preventing characteristic equinus gait. In ambulant children with other neuromuscular disorders careful assessment is essential to ensure that walking is not compromised. 3. Clinical experience suggests that daytime AFOs should be supplied once ambulation is lost to prevent painful contractures and foot deformity. If tenotomies are performed in the non-ambulant child AFOs should be worn during the day. 4. KAFOs can be used to prolong ambulation for approximately 2 years in DMD. They can also help delay the onset of lower limb contractures and weaker evidence suggests that prolonging ambulation beyond 13 years may delay the onset of scoliosis. They should be supplied at the time of loss of ambulation by an orthotist with experience in neuromuscular disorders. 5. In SMA II KAFOs may be used to promote ambulation and there is limited evidence to suggest delayed onset scoliosis and contractures. 6. The benefit of a standing posture in the non-ambulant child to control contractures is logical but not evidenced. Standing frames or swivel walkers may be used in children with neuromuscular disorders. 11. Exercise in adults with muscular dystrophy The evidence is sparse, frequently anecdotal and particularly in FSH the role of exercise is complicated by anecdotal reports that overuse or overwork may induce weakness, however, no controlled studies into overwork weakness have been conducted and the importance of characteristic asymmetry is often overlooked [68]. The results of years of high resistance training in well observed if poorly controlled patients directly refute the overwork theory [24]. The evidence presented by Brouwer et al. [69] is compelling in that it confirms right-handed patients are weaker on the right whereas right-handed controls are stronger on the right. There were too few left-handed patients and controls to allow statistical analysis on lefthandedness. The relationship between overwork and weakness was difficult to prove as asymptomatic patients showed the same pattern of asymmetry as symptomatic patients and there was no relationship between age, sex, and duration of symptoms and severity of muscle weakness. Anecdotal evidence from the authors experience suggested exercise or overload might have led to greater weakness. They have no experience of patients improving strength with exercise and conclude that there is a genetic predisposition of specific muscles to become more or less affected and that the link between handedness and weakness is suggestive of mechanical factors. There is no explanation for the asymmetry seen in facial muscles where there is no preferential use of left or right side. A study that looked at the relationship between phenotype and genotype in monozygotic twins with FSH concluded that asymmetry of involvement was independent of handedness as demonstrated by a pair of twins that were both right handed but who had reverse asymmetry [70]. Clinically fatigue and/or pain may be seen in patients with FSH which may be associated with overwork but it is not known if this is also associated with increased weakness nor whether it differs from other neuromuscular disorders [71]. Motor learning is an interesting phenomenon that does not support or reject the overwork weakness theory. In a randomised and controlled crossover study, patients with FSH were found to change the pattern of muscle activity following repetition of a standardized task [72]. This suggested that practice may improve the efficiency of the muscle but there was no evidence of the longevity of the improved response or whether there was any functional improvement noted by patients. A few studies have looked at the effect of strengthening exercises in adults with neuromuscular disorders and shown increased strength and endurance but all were small studies with heterogeneous populations of patients showing considerable inter-subject variability [24,37,38,73 76]. One relatively consistent finding suggests that patients with a variety of neuromuscular disorders who are still quite strong are more likely to improve strength and or endurance than patients who are severely weak [24]. In myotonic dystrophy there is better evidence to suggest that patients can benefit from muscle strengthening programmes and aerobic training [37,77]. However, due to other manifestations of the disease such as cardiac problems, reduced respiratory volume, short attention span, memory loss, visual spatial problems, and particularly poor motivation leading to poor compliance with treatment programmes the beneficial effect may be limited. Foot drop can be a particular problem in myotonic dystro-

6 980 M. Eagle / Neuromuscular Disorders 12 (2002) phy and although there are no published data workshop participants reported anecdotal evidence to suggest AFOs may be beneficial. A small pilot study of the use of AFOs in adults with FSH and foot drop reported that improvements in gait were likely if plantargrade could be achieved passively at the ankle joint and if quadriceps strength was above antigravity [78]. It has been suggested that inspiratory breath holding techniques are avoided in myotonic dystrophy although there is no published evidence of harm, as these techniques have an effect on sinus heart rhythm [79]. At least 30 min exercise five times per week of moderate intensity have been recommended to minimise mortality in normal subjects [80]. How this relates to patients with muscle disease is not clear but the general effects of exercise such as improvement in psychological well-being are thought to be at least as important in patients with muscle disease. 12. Recommendations 1. An accurate diagnosis should be made so that the possible complications and manifestations of the disease can be considered in devising a physical treatment plan and assessment programme. 2. The possibility of overuse fatigue, pain or weakness should be considered especially in FSH muscular dystrophy but there is no reliable evidence to suggest that exercise is contraindicated. 3. Active low resistance exercise may be prescribed to improve strength and endurance in relatively well maintained muscles (stronger than grade 3 MRC scale). 4. Where possible active exercise on a regular basis to promote general physical health to be encouraged. 5. Patients with myotonic dystrophy may be given an active resisted exercise regime but may need additional support and motivation. 6. Avoid inspiratory breath holding techniques in myotonic dystrophy. 7. AFOs may be used in ambulant patients with foot drop but not effective if plantar grade cannot be achieved at the ankle joint and/or there is significant quadriceps weakness. 13. Respiratory muscle training Inspiratory muscle (IM) weakness is defined as a condition in which the capacity of the breathing muscles to generate force is impaired. This is measured by assessing the maximal pressure during a maximal voluntary static inspiratory contraction. Rest reverses inspiratory fatigue. Normally, little force is required to achieve normal lung volumes. To reduce total lung capacity (TLC), IM force is usually reduced to less than 50% of predicted value. A 50% reduction in IM force resulted in only a 6% reduction in TLC in patients with amytrophic lateral sclerosis (ALS) [81]. The vital capacity (VC) is the difference between TLC and residual volume. Residual volume may be increased due to weakness of the expiratory muscles. So patients with inspiratory and expiratory muscle weakness have a more profound reduction in VC. Increased compliance due to stiffening of the costo-vertebral joints may result in micro-atelectasis leading to a focus for infection. In dogs micro-atelectasis can be reversed by deep inspiration or incentive spirometry [82]. McCool and Tzelepis [83] reviewed the evidence for respiratory muscle training in eight papers with a total of 75 patients with neuromuscular disorders and hypothesised that by strengthening the IMs respiratory failure may be delayed or reversed and ineffective coughing may be improved by strengthening expiratory muscles. They concluded that both force and endurance could be improved without side effects. However, severely affected patients were unlikely to benefit, possibly because they were already working at their maximum capacity. Patients with bestpreserved VC were more likely to improve. It has proven difficult to evaluate and compare existing studies of respiratory muscle training. The period of training varies from 3 weeks to several years. The range of patients varies in disease severity and in diagnosis even within groups and furthermore the methods used to test respiratory muscle strength are variable [84 89]. The evidence for respiratory muscle training is contradictory and leaves more questions than answers. In patients where fatigue contributes to exercise limitation (as opposed to patients whose exercise tolerance is reduced by limb muscle strength or cardiovascular fitness), respiratory muscle training may be more effective. Possibly patients with slowly progressive disease are more likely to benefit than those with rapidly progressive disease. Critically, however, is the likelihood of non-compliance. Rewards of computer games are unlikely to provide enough incentive to comply when the evidence is weak and the results are not likely to have an immediate impact [89,90]. There is little evidence to suggest that improvements are clinically relevant. Gross and Meiner [91] suggest fewer chest infections but mostly functional improvement is not documented. The benefits of training may or may not be maintained once training stops and the effects of respiratory muscle training may be real, or due to a learning effect [85,86,92]. 14. Conclusions 1. Endurance is more likely to improve than strength but there is no strong evidence of functional improvement. 2. Patients with well preserved VC and slowly progressive disease are more likely to improve than patients with rapidly progressive disease and already compromised respiratory muscles.

7 M. Eagle / Neuromuscular Disorders 12 (2002) There may be a learned component. 4. Effects are likely to last for only a short time after training stops. 15. Recommendations The current evidence for respiratory muscle training is insufficient to advocate an exercise regime. It is possible that a short-term respiratory training programme may be of benefit prior to surgery but this would need to be researched. 16. Where do we go from here? There is some evidence to suggest that exercise can improve muscle strength. However, it is not clear what the frequency, duration and type of exercise should be. Further evidence suggests muscles that are relatively strong are more likely to improve with exercise than muscles that are already very weak. It is also possible that the effect of exercise may be different in diseases where the primary defect lies in the structural proteins of the muscle membrane as opposed to diseases where non-structural proteins are involved as in some of the recently recognised limb girdle muscular dystrophies [93]. The advances in diagnostic techniques give us a new opportunity to understand the effect of exercise in a clearly defined patient population. The effect of disuse atrophy on normal muscle is understood but how disuse affects diseased muscle is unclear. Much of this uncertainty can be addressed by a meticulous approach to study design and rigorous assessment procedures. At the heart of therapeutic intervention is the desire to improve functional ability and quality of life but very few attempts have been made to objectively assess the effects of strength training on the rate of disease progression and functional ability. There is reasonable clinical evidence for the use of some orthoses, for example KAFOs and night splints in DMD but there remains much uncertainty about the timing of interventions and in some neuromuscular diseases the role of orthoses has not been investigated at all. There has still been no specific work to quantify and examine the relationship between the degree and distribution of muscle weakness, development of postural compensations and progression of contractures. This is not only required in the more common DMD but also other conditions such as the heterogeneous group of congenital muscular dystrophies and myopathies, some of which are particularly prone to contracture development and rigidity of the spine. A better understanding of the mechanism of contracture development is important in providing a sound scientific basis for treatment rationales. The scientific strength of many of the studies examined in this workshop was poor and further research is needed to clarify issues raised in these studies some of which were conducted many years ago. The range of research methodology now available is more stringent, better defined and diagnostic criteria are sufficiently advanced to enable precise classification of diseases. Some therapy regimes have slipped into standard practise without evidence and there may be ethical dilemmas in withdrawing or changing existing therapeutic practise. It may be that methods other than randomised controlled trials be employed but where there is no evidence, comparative studies of two or more different therapeutic regimes should not be unethical. Producing reliable evidence will require a long-term effort. First we need to establish which assessment tools already in existence can be used and develop new ones if necessary. The natural history and the progression of muscle weakness and contractures still must be established in some areas. Development of assessment tools may be a necessary prerequisite to evaluating physical therapeutic interventions. We do not have an infrastructure or funding in place that would enable us to conduct the multicentre trials necessary to achieve the numbers required for reliable and valid results but this is where we must direct our efforts now. Acknowledgements This workshop was made possible by the financial support of the Muscular Dystrophy Campaign (UK). Appendix A. Workshop participants Julie Cassell, FCO, Queens Medical Centre Nottingham. Zoe Cave, Physiotherapist, Frederick Holmes School, Hull. Joy Donaldson, Senior Physiotherapist, Frederick Holmes School, Hull. Helen Dowden, Senior Physiotherapist, Ralph Thoresby High School, Leeds. Michelle Eagle, Physiotherapy Research Practitioner in NMD, Newcastle Muscle Centre, Newcastle. Jane Freebody, Senior Physiotherapist, Department of Clinical Neurology, Oxford. Pamela Foley, Senior Physiotherapist, Ireland. Stephen Gordon, FSH patient representative. Kath Houghton, FCO, Newcastle Muscle Centre Newcastle. Gordon McLurg, DMD patient representative. Marion Mclurgh, DMD representative. Norvil Mclurgh, DMD representative. Marion Main, Superintendent Physiotherapist, Hammersmith Hospital, London. Lindsey Pallant, Senior Physiotherapist, Leeds General Infirmary Leeds. Colin Peacock, Peacocks Medical Group Limited Newcastle upon Tyne.

8 982 M. Eagle / Neuromuscular Disorders 12 (2002) Dr Margaret Phillips, University of Nottingham Rehabilitation Research Unit, Derby. Jennie Sheehan, Clinical Specialist in NMD Guy s Hospital London. Nicky Thompson, Clinical Specialist in Gait Analysis, Nuffield Orthopaedic Centre Oxford. Dr Dominic J. Wells, Reader in Transgenic Biology Gene Targeting Unit, Imperial College, London. References [1] Chappell F, Williams B. Rates and reasons for non-adherance to home physiotherapy in paediatrics. Physiotherapy 2002;88(3): [2] Petrof BJ. The molecular basis of activity-induced muscle injury in Duchenne muscular dystrophy. Mol Cell Biochem 1998;179(1-2): [3] Weller B, Karparti G, Carpenter S. Dystrophin deficient mdx muscle fibres are preferentially vulnerable to necrosis induced by experimental lengthening contractions. J Neurol Sci 1990;100(1-2):9 13. [4] Mokhtarian A, Lefaucheur JP, Even PC, Sebille A. Effects of treadmill exercise and high fat feeding on muscle degeneration in mdx mice at the time of weaning. Clin Sci (Lond) 1992;89(4): [5] Saco P, Jones DA, Dick JR, Verbova G. Contractile properties and susceptibility to exercise induced damage of normal and mdx mouse tibialis anterior muscle. Clin Sci (Lond) 1992;89(4): [6] Karpati G, Carpenter S, Prescott S. Small-caliber skeletal muscle fibers do not suffer necrosis in mdx mouse dystrophy. Muscle Nerve 1988;11(8): [7] Dick J, Verbova G. Progressive deterioration of muscles in mdx mice induced by overload. Clin Sci (Lond) 1993;84(2): [8] Hudecki MS, Pollina C. Strength and endurance in the therapeutic evaluation of prednisolone treated mdx mice. Res Commun Chem Pathol Pharmacol 1993;79(1): [9] Granchelli JA, Pollina C, Hudecki MS. Pre-clinical screening of drugs using the mdx mouse. Neuromuscul Disord 2000;10(4-5): [10] Zeman RJ, Peng H, Danon MJ, Etlinger JD. 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