Clinical and diagnostic features

Children with DMD almost always have delayed motor milestones and about one-third of patients will also have learning difficulties leading to global developmental delay. The child often walks after 18 months of age, and when he does begin to walk he may be clumsy, and rarely acquires the ability to run or jump. If there is no family history the diagnosis may not be suspected until muscle weakness is obvious, usually by 5 years of age.

Progressive hip and knee extensor weakness causes difficulty in getting up from the floor resulting in a typical Gowers’ manouevre, whereby the child must give some assistance to hip and knee extension by pushing off from the thigh with the hand or forearm. With increasing weakness, the child climbs up his legs using both arms. An abnormal ‘waddling’ gait occurs because of early weakness of the hip abductors resulting in an inability to maintain a level pelvis when lifting one leg off the ground. The child inclines the trunk towards the stance leg to bring the centre of gravity of the body over that leg, and as he moves forward this action is continually repeated and accounts for the Trendelenburg sign. This is accompanied by widening of the base of support for increased stability, which contributes to the evolution of hip abduction contractures (iliotibial band tightness).

By 7–8 years of age, contractures of heel cords and ilio-tibial bands lead to toe walking. Without corticosteroid treatment ambulation is always lost by the 13^th birthday and the mean age for loss of ambulation is 9.5 years (Emery & Muntoni, 2003). Prolonged sitting caused by wheelchair dependence leads to the rapid development of flexion contractures of the elbows, hips and knees.

In the early ambulatory phase of DMD, an equinus foot posture is precipitated by relative weakness of the ankle dorsiflexors compared with the better preserved plantar-flexors. Gait analysis has shown that a dynamic equinus is a necessary biomechanical adaptation to maintain knee stability in the presence of gross quadriceps muscle weakness. Forceful action of the ankle plantarflexors provides a torque which opposes knee flexion (Khodadadeh et al., 1986). Thus, contracture of the Achilles tendon, which eventually accompanies disease progression, is secondary to dynamic equinus.

Muscle involvement is bilateral and symmetrical and the proximal muscles are more affected than the distal groups. As the condition progresses the tendon reflexes become depressed and are eventually lost. In the ambulatory stage, the pelvic girdle is slightly more affected than the shoulder girdle. There is more severe weakness in the extensor groups than in the flexors, although this differential muscle involvement becomes less clear as the disease progresses, so that ultimately such patterns of weakness are no longer obvious. Finally, contractures become fixed and a progressive scoliosis develops. Scoliosis exacerbates existing respiratory muscle weakness, and in severe cases may render the child bed-bound if it is not managed with spinal fusion.

Muscle imbalance (caused by the specific pattern of developing weakness) and postural malalignment (resulting from compensatory adjustments to maintain standing equilibrium) are factors precipitating the eventual development of contractures about weight-bearing joints. These are relatively mild while the child remains ambulant but progress rapidly once there is dependence on a wheelchair. These postures combine lumbar lordosis, hip flexion and abduction, and ankle equinus. The first alteration of body alignment in DMD is a lumbar lordosis due to early weakness of the hip extensors, so that active stabilization of the hip joint is compromised. In order to maintain the line of force behind the hip joint and prevent collapse into hip flexion, there is an initial posterior alignment of the upper trunk resulting in a compensatory lumbar lordosis. As weakness progresses this is accompanied by an exaggerated anterior tilt of the pelvis which predisposes to contractures of the hip flexors. By 18 years of age cardiomyopathy and respiratory insufficiency are the norm.

Thus, DMD is a severe life-limiting disease characterized by muscle weakness, contracture, deformity and progressive disability. However, ‘incurable’ is not synonymous with ‘untreatable’. A variety of therapeutic and surgical measures are available that can help to minimize deformity, prolong independent ambulation and maximize functional capabilities. There is evidence that improved management strategies are resulting in increased survival rates (Eagle et al., 2002; Eagle et al., 2007). Corticosteroid treatment results in an increase in muscle strength followed by a slowing down of the dystrophic process (Manzur et al., 2008a). Most boys will die from respiratory or cardiac failure, but the introduction of nocturnal nasal ventilation has improved survival figures, such that the average life expectancy is now 25 years or more with non-invasive ventilation, compared with 19 years without this treatment (Eagle et al., 2002). The principles of successful management are based on an understanding of the natural evolution of patterns of weakness, contracture and deformity, so that intervention can be staged appropriately.

Pathology

Weakness in DMD results from the gradual loss of functional muscle fibres which are replaced by fat and connective tissue due to a lack of dystrophin, a protein encoded by the Xp21 gene, is the primary biochemical defect (Muntoni et al., 2003). Dystrophin is integral within a complex of proteins which stabilizes the integrity of the sarcolemmal membrane, particularly during the stress associated with repeated cycles of contraction and relaxation. Absence of dystrophin in the skeletal and cardiac muscle results in a reduction in permeability of the muscle cell membrane, so allowing excessive quantities of calcium to accumulate within the muscle fibre leading to myofibrillar over-contracture, breakdown of myofibrils and various metabolic disturbances that culminate in muscle fibre degeneration. Dystrophin isoforms are also expressed in Schwann and Purkinge cells found in the brain which is the reason for the high incidence of learning difficulty.

Diagnosis

Diagnosis is suspected by finding a raised serum creatine kinase usually in the region of 50–100 times the normal level. A muscle biopsy is necessary to confirm the diagnosis together with DNA analysis. Muscle biopsy can be undertaken as a percutaneous technique using a biopsy needle or as an open procedure, depending on the practice of the investigating unit. Muscle histology demonstrates dystrophic features which include: an increased variation of fibre size, evidence of necrosis with phagocytosis, an increase in central nuclei, hypercontracted eosinophillic hyaline fibres, and an increase in fat and connective tissue (Figure 10.1). Histochemical staining using antibodies to N, C and rod domain epitopes of dystrophin usually show complete absence of the protein, except for occasional revertent fibres (these are fibres which label normally with antibodies to dystrophin; their origin is not understood).

Figure 10.1 Biopsies of normal (A, C) and dystrophic muscle (B, D–F). Note the abnormal histology of the dystrophic muscle (B) with a wide variation in fibre size, fibrous tissue surrounding the fibres and nuclei within the fibres. An antibody to dystrophin has been used to label the muscle in panels (C–F). Note the normal intense sarcolemmal localization on all fibres in (C), the reduced patchy labelling of dystrophin in a case of Becker muscular dystrophy (BMD) in panel (D), and the absence of dystrophin in a case of Duchenne muscular dystrophy (DMD) in (E). One revertent fibre with apparently normal dystrophin is shown in (F).

(Courtesy of Professor Caroline Sewry.)

Weak or uneven labeling of dystrophin may be seen in BMD and intermediate phenotypes and thus can guide on prognosis. In manifesting carriers, dystrophin immunolabelling demonstrates a mosaic appearance with positive and negative fibres. Immunolabelling with other antibodies in both DMD and BMD shows a reduction of membrane proteins associated with dystrophin, and over expression of utrophin, a protein similar in structure to dystrophin.

DNA testing from a blood sample will demonstrate a frame-shift deletion within the dystrophin gene in approximately 60% of DMD patients, the rest will result from duplications and nonsense mutations (Mastaglia & Laing, 1996). Confirmation of the diagnosis by DNA testing allows carrier detection and prenatal diagnosis in the affected boy’s mother and female relatives. In some cases DNA analysis is the only test required to confirm the diagnosis of DMD. In BMD the reading frame of the gene is preserved (in-frame). Exceptions to the frame-shift rule occur with some deletions and thus a muscle biopsy is recommended to confirm the diagnosis.

General management

Informing parents that their child has DMD causes extreme distress and should only be undertaken by the most senior member of the team, in an appropriate environment, with a support worker present who can maintain contact with the family once they have left the hospital. The information given to the parents must be factual and honest, but delivered with sensitivity and empathy.

The long-term care of the child will require a specialist multidisciplinary team (MDT) liaising closely with community medical, educational and social agencies. As soon as the diagnosis is confirmed the child should have a MDT developmental assessment to screen for learning difficulty so that plans can be made for appropriate educational support. Social services will be required to become involved to ensure the family receives the correct State financial entitlements and will be paramount in arranging home adaptations, which are usually necessary by the time the child is 7 or 8 years of age, when the child has difficulty climbing stairs.

From an early age, tightness and subsequently contractures of the tendo-achilles (TA) develop. Daily passive stretching of the TA and provision of night splints are recommended as soon as any tightening is demonstrated. Later on, when significant pelvic girdle weakness is manifest by a waddling gait, the ilio-tibial bands and hip flexors may start to tighten. Care must be taken to ensure assessment at each outpatient visit with advice to undertake stretching exercises. The priority of physical management is to prolong ambulation for as long as possible, since once ambulation is lost scoliosis and joint contractures develop rapidly. At the point of loss of ambulation, light weight knee-ankle-foot orthoses (KAFOs) can be used to prolong walking (Figure 10.2). This usually involves a minor surgical procedure to percutaneously release any lower limb contractures, usually the TAs, together with an intensive rehabilitation programme. Where there are only moderate contractures of the TAs, serial casting may be an alternative to surgery to allow fitting of the KAFOs (Main et al., 2007). The parents and child must be both strongly motivated and well supported for this form of rehabilitation to be successful.

Figure 10.2 Boy with Duchenne muscular dystrophy. (A) At the point of loss of independent walking. (B) Following percutaneous Achilles tenotomies and rehabilitation in light-weight ischial weight-bearing knee–ankle–foot orthoses (KAFOs).

In recent years, there is growing evidence that treatment with corticosteroids (prednisolone or deflazacort) will stabilize muscle function for some time, therefore delaying the loss of ambulation by up to 2 years (Manzur et al., 2008a). Careful monitoring for side-effects is essential, especially weight gain, which may potentially have a negative effect on function. The potential benefit of longer-term steroid treatment has yet to be evaluated, but some open studies suggest preserved respiratory and cardiac function (Manzur et al., 2008a). Premature loss of ambulation can follow lower limb fractures or ligament strains unless active management, such as internal fixation, is instigated to promote early mobility. Immobilizing any joint beyond the initial painful phase should be actively discouraged.

Once independent ambulation is lost, regular use of a standing frame is recommended to maintain good posture and reduce contracture development. Rigid ankle foot orthoses (AFOs) are recommended for daytime use to maintain a good foot position. Likewise it is essential to ensure that the wheelchair provides good back and neck support (Pope, 2002) and, ideally, the controls of an electric wheel chair should be centrally placed. Swimming and hydrotherapy are particularly useful and enjoyed by the boys who find they can move more easily in the water.

A rapidly progressive scoliosis requiring surgical stabilization will develop in up to 95% of boys. There is, however, a reduced incidence and severity of scoliosis in glucocorticosteroid-treated boys (Biggar et al., 2006) which is likely to be due to prolongation of walking and increase in trunk muscle strength. Posterior spinal fusion is highly successful in correcting the deformity, and in improving posture and the quality of life for both patient and carer (Mehdian et al., 1989). The timing of operation is crucial since a decline in vital capacity occurs at the same time as the development of scoliosis. To avoid undue anaesthetic risks the procedure must be undertaken when the vital capacity is greater than 30% of predicted height (Manzur et al., 2008b). Thus surgical correction is usually recommended when the degree of spinal curvature is still relatively mild.

Management of restricted participation

Restricted participation has replaced the term ‘handicap’ in the revised International Classification of Functioning, Disability and Health by the World Health Organization (WHO ICF, 2001; see Ch. 11) and its management must take into account psychosocial issues, mobility and education. Providing an electric wheelchair is essential to providing a degree of independence, but this requires appropriate home adaptations including: widened doors and indoor/outdoor wheelchair access. A hoist is required for lifting in and out of the wheelchair, and the child will require a ground floor bedroom and bathroom with shower and adapted toilet. An electric bed enables the child to alter his position and saves the parents many sleepless nights. An adapted motor vehicle is required for transport to enable the child to drive his own wheelchair in and out of the vehicle.

The revolution in computer technology and its application to assistive devices has transformed the lives of many disabled people, e.g. the POSSUM system (Patient Operator Selector Mechanisms) enables the child to open and close doors, windows, curtains and turn on and off lights, etc. Access to the internet allows friendships to develop and provides a source of information and various services. Electronic games enable the boys to play competitively alongside their able-bodied companions and probably have a major effect on building self-esteem and reducing boredom.

Respiratory problems

With advancing age, respiratory impairment becomes inevitable and, if not recognized early, is an important cause of unpleasant symptoms or death. Characteristically there is a restrictive defect, with a reduction in total lung capacity caused by a combination of diaphragmatic and intercostal muscle weakness. Chest wall stiffness, recurrent aspiration and an inability to cough effectively compound the respiratory insufficiency leading to an increased frequency of chest infections (Smith et al., 1991). The forced vital capacity is a reliable measure of respiratory function, provided the boy is able to undertake a good technique (in some boys with learning difficulty this may be a problem) (Griggs et al., 1981). The forced vital capacity, when corrected for height, plateaus and then falls progressively on average between 12 and 14 years of age. Once the vital capacity falls below 1 L, in a boy who has reached skeletal maturity, the average life expectancy without treatment is 3 years (Phillips et al., 2001).

Sleep-related respiratory abnormalities play a major role in ventilatory failure, resulting in symptoms of hypercapnia which include: early-morning headache, nausea and sweating, daytime somnolence and a loss of respiratory drive (resulting in rapid deterioration into coma if a high concentration of oxygen is administered). Chronic nocturnal hypoxaemia leads to cor pulmonale (right heart failure), the ECG may show evidence of pulmonary hypertension and right heart strain (Carroll et al., 1991). Once the vital capacity falls below 40% sleep studies should be undertaken at regular intervals to monitor for nocturnal hypoventilation. Treatment by non-invasive nasal ventilation is effective in alleviating symptoms and prolongs survival (Eagle et al., 2002; Jeppesen et al., 2003; Simonds, 2000). There is recent evidence that the cumulative effect of both spinal surgery and nocturnal ventilation further improves survival (Eagle et al., 2007).

Cardiac problems

Post-mortem studies show that all boys with DMD have evidence of cardiomyopathy by 18 years of age. In practice, however, symptomatic cardiomyopathy is less common than might be expected. It has been assumed the sedentary lifestyle of these boys contributes to the lack of symptoms (Hunsaker et al., 1982). Abnormalities of the electrocardiogram are evident from an early age and will be present in all boys by 18 years of age (Nigro et al., 1990); the most common abnormality is a resting tachycardia, which is almost universal. Cardiac arrhythmias occur and may be a cause of early sudden death. When congestive cardiac failure does occur the progression is rapid and relentless. Monitoring with cardiac echo is recommended once ambulation is lost. Early treatment with ACE (angiotensin-converting enzyme) inhibitors has been shown to be beneficial, although the results need to be confirmed (Duboc et al., 2007).

The final illness

Close monitoring and liaison with the general practitioner and palliative care services are paramount. Children’s Respite Hospices play a vital role in supporting families and boys during this difficult time. Patient support groups, such as The Muscular Dystrophy Campaign, frequently fund care workers to support families (see Appendix ‘Associations and Support Groups’).

Clinical and diagnostic features

BMD has a wide spectrum of severity; at the severest end ambulation may be lost by 16 years of age compared with the mildest form which presents with non-progressive cramps and myoglobinuria (Gospe et al., 1989). Distribution of weakness is similar to DMD, but progression of the disease is much slower and contractures are often less severe than in DMD. As with DMD, muscle hypertrophy, especially of the calves, occurs. Up to 40% of patients will lose ambulation, and prolonging ambulation with long-leg calipers is more difficult than in DMD because of adult height.

In some patients, as with DMD, an unexpected malignant hyperthermia reaction following general anaesthesia may be the first manifestation of the disease. Cardiomyopathy is common and more likely to be symptomatic than in DMD. ECG and echocardiogram abnormalities may be evident in up to 50% of cases (Steare et al., 1992) and many patients have successfully undergone cardiac transplantation (Quinlivan & Dubowitz, 1992).

Because the life expectancy is much better than for DMD, genetic implications are more important for the patient who will not father affected sons, but will pass the faulty gene to all daughters who will be carriers for the disorder. The diagnosis is confirmed by finding a deletion, duplication or missense mutation in the dystrophin gene and/or abnormal dystrophin staining on a muscle biopsy.

General management

The management of BMD involves prevention of contractures and prolonging ambulation as with DMD. An active approach to management using low-intensity aerobic exercise has been shown to safely improve fitness and strength in individuals with mild BMD (Sveen et al., 2008). Home adaptations are essential in promoting independence and the patient may require support to continue working in an adapted environment. For those patients who are wheelchair dependent, regular standing, and preventing excessive weight gain and constipation are important. Prevention of respiratory infections by vaccination against influenza and pneumococcus, together with prompt antibiotic treatment of infection are important. Monitoring of respiratory function and overnight oximetry for sleep hypoxaemia are necessary. Symptoms of chronic ventilatory failure should be managed with non-invasive ventilation as for the DMD group. Regular cardiac monitoring with yearly ECGs and cardiac ECHOs every 2 or 3 years is necessary. Early intervention with ACE inhibitors for ventricular dysfunction may be helpful, but as yet has to be fully evaluated. If cardiac symptoms fail to respond to medical treatment, assessment for cardiac transplantation is warranted (Quinlivan & Dubowitz, 1992).

Clinical and diagnostic features

The main feature of the nuclear envelope muscular dystrophies is the predominance of joint contractures and muscle weakness occurring in a scapulo-peroneal distribution. Contractures predominantly affect the neck and spine, elbows and tendo-achilles. Disturbances of cardiac conduction are universal by the second or third decades, and may result in sudden death unless detected and cardiac pacing instituted bb0025(Bialer et al., 1991). Thus, regular ECG and 24-hour ECG monitoring are essential. Muscle weakness is slowly progressive, however many patients retain some ambulation throughout adult life.

General management

Management of contractures involves passive stretching exercises and night splints, as discussed below. Provided the diagnosis is made sufficiently early, the insertion of a cardiac pacemaker may be life-saving. In the case of ADEDMD a defibrillator pace-maker is recommended.

The associated weakness is usually mild. However, due to rigidity of the spine throughout its length, the patient is unable to compensate for any hip extensor weakness with a lumbar lordosis, as is commonly seen in many of the other neuromuscular diseases. Instead, the patient maintains the centre of mass with increasing equinus at the ankles, leading to secondary contracture of the Achilles tendon. If these contractures become severe, they may in themselves jeopardize mobility and require percutaneous surgical correction. Management should be aimed at controlling the progression of deformity by appropriate strengthening, passive stretching and splinting techniques (see Ch. 12 & 14).

General management

As with other disabling neuromuscular diseases, patients with LGMD need help and support to adapt their environment to suit their needs. A self-raising chair or pneumatic cushion can be invaluable in assisting rising to standing. Adaptations to the patient’s home may be required to ensure appropriate bathroom facilities, hoists or stair lifts. Adaptations to the patient’s vehicle may also be required to maintain independence. Weight gain can be a major problem for some individuals, especially when they are confined to a wheelchair, and may compromise respiration. Encouraging exercise is important for general health and well being; swimming is an excellent example which also helps maintain strength. Low-intensity aerobic training has been show to improve exercise performance in patients with LGMD type 21 (Sveen et al., 2007). Many patients appreciate the benefit of regular passive stretching exercises and the opportunity to stand using either a tilt table or standing frame. Prevention of chest infections with pneumococcal vaccination and yearly flu vaccines is important for any patient with evidence of respiratory muscle weakness.

Clinical and diagnostic features

Reduced fetal movements during pregnancy suggest that signs are already present before birth, such infants are frequently born with arthrogryposis. Features in early infancy consist of muscle weakness and generalized hypotonia, ‘floppiness’, poor suck and respiratory difficulty (Kobayashi et al., 1996). In childhood, motor milestones are delayed, with severe and early contractures and often joint deformities. Weakness is greater in the pelvic girdle and upper leg muscles than in the shoulder girdle and upper arm muscles. On the whole, with the exception of Fukuyama congenital muscular dystrophy (FCMD), these conditions are relatively slowly progressive and functional ability can initially improve over time. Contractures at birth are common, and may restrict function to a greater degree than weakness if not controlled. It is particularly important to be vigilant for the insidious development of contractures and to treat them promptly.

Other features of the disease are hip dislocation, pes cavus and kyphoscoliosis. The motor development is slow, leading to late sitting, standing and walking, which is achieved in some but not all. Intelligence is normal in merosin deficient CMD and Ullrich CMD, but will be reduced in the muscle eye brain forms of CMD, where there are structural brain abnormalities, such as polymicrogyria and cerebellar cysts. Serum CK activity is usually very high in the early stages. In this group of patients vision should be assessed to exclude myopia and cataracts. In the Ullrich form of CMD intelligence and vision are normal, but there may be skin changes such as keloid scars or follicular hyperplasia.

General management

Attention to feeding and breathing is important in the neonatal period. Some patients will require percutaneous endoscopic gastrostomy (PEG) feeding due to bulbar involvement. Later on, useful mobility should be maintained for as long as possible. Regular exercise should be encouraged and obesity avoided. Regular gentle stretching is required to avoid or control contractures (see below). Nocturnal hypoventilation may develop at any time but is most common in the second decade and responds well to nocturnal non-invasive ventilation.

General management

Studies of specific treatment for FSH are limited. Patients often develop a marked lumbar lordosis and low back pain due to pelvic girdle weakness, so that strengthening the pelvic musculature plus passive stretching exercises to minimize hip flexion contractures may be helpful. A recent study of mildy affected patients with FSH showed that low-intensity aerobic training over a 12-week period improved exercise performance (Olsen et al., 2005). Ankle–foot orthoses (AFOs) can be provided to control for foot drop, but may not be tolerated unless the ankle achieves plantigrade and quadriceps strength is at least antigravity (Eagle et al., 2001).

Thoracoscapular fusion can be effective in the long term for patients with scapular winging, provided the deltoid muscle remains functional (Rhee & Ha, 2006). More recently scapulothoracic fixation (scapulopexy) using wires to reposition the scapula over the ribs, without arthrodesis, has been shown to be successful (Gianinni et al., 2007). Both techniques result in improved range of movement and appearance of the shoulder and this is most beneficial for patients whose occupation specifically requires the ability to sustain flexion and abduction.

General management

Education, monitoring and avoidance of complications remain the cornerstone in the management of patients with myotonic dystrophy. Cardiac arrhythmias are the most serious complication and permanent cardiac pacing may sometimes be required. A 12-lead electrocardiogram (ECG) should be undertaken annually and 24-hour ECG monitoring is necessary once there is evidence of conduction abnormalities, such as prolongation of the PR interval.

Speech and language therapy input may help with the bulbar symptoms. Foot drop can be improved by the use of AFOs. Sleep studies should be contemplated if there is a change in the pattern of daytime somnolence. Anaesthesia and surgery require special attention because of the general anaesthesia risk. In addition to the risks already mentioned, patients may slip into respiratory failure in the postoperative period and are at risk of aspiration pneumonia as a consequence of their abnormal bulbar function. All patients should be advised to carry an alert card outlining the anaesthetic risks. Several drugs, such as phenytoin, can be used to relieve the myotonia, although in practice the side-effects often outweigh any benefit.

Measurement of muscle strength

Strength assessment provides information for the planning and monitoring of intervention as well as diagnostic information.

Measurement of joint range

The development of joint contractures should be monitored carefully and joint ROM can be measured using a goniometer. However, caution must be taken with this method as it shows variable inter-rater reliability and measurements should be made by the same assessor where possible (Pandya et al., 1985).

Measurement of functional performance

The quantification of muscle strength has proved to be of value in the assessment and management of many muscle diseases, but it can be seen that this is a measure of impairment and is incomplete without concomitant measures of disability and ultimately the handicap to the patient. Measures of functional performance range from simple tests such as the ability to rise from the floor to more detailed measures of motor ability including gait analysis (D’Angelo et al., 2005; Khodadadeh et al., 1986; Sutherland et al., 1981). These measurements are susceptible to the effects of impairments other than strength, but it is important in terms of patient management to determine whether a change in disability can properly be attributed to a change in the strength of the muscles measured.

There may be disparities between strength and disability in muscle for a variety of reasons. These include: a failure to assess the relevant muscle groups that cause disability; a failure to note progressing severe weakness in an important group, perhaps because of the averaging of many groups; or the intrusion of other factors, such as the development of compensatory biomechanical manoeuvres or a gain in weight or height. It is of paramount importance that the measure of physical performance is both valid and reliable, and these factors need to be recognized.

Motor ability tests

Classically the most commonly used measures of motor ability have been those developed for DMD by Vignos et al. (1963), Brooke et al. (1981) and the Hammersmith Motor Ability Scale (HMAS) (Scott et al., 1982). The Vignos scale was originally designed as a functional classification and its sensitivity as an objective measure of function is doubtful. The HMAS has been widely used in clinical practice, although there is little published information about its reliability and validity. This scale has recently been modified, is now known as the ‘North Star Ambulatory Assessment’ and been shown to have excellent inter-observer reliability (Mazzone et al., 2009). Its 17 motor activities are biased towards activities involving the lower limbs, making it suitable for assessment of ambulant patients (Table 10.3). The patient sequentially performs a succession of movements that are scored on a 3-point scale which can be completed in 15 minutes. A functional test, the EK scale, for non-ambulant patients with DMD has been shown to be reliable by Steffensen et al. (2002).

Table 10.3 North Star Amulatory Assessment

Scores: 2 – ‘Normal’: achieves goal without assistance; 1 – Modified method but achieves goal independent of physical assistance from another; 0 – Unable to achieve independently. R, right leg; L, left leg

(Reprinted from Mazzone ES, Messina S, Vasco G et al. Reliability of the North Star Ambulatory Assessment in a multicentric setting. Neuromuscular Disorders, 2009; 19:458-461, with permission from Elsevier.)

Timed tests

Timed performance tests are commonly used as supplementary measures of physical performance as a means of reflecting progressive weakness (Brooke et al., 1981). A timed walk over a fixed distance or time, such as the 10 m test or the 6 minute walk test, can reliably detect changes over time (Mazzone et al., 2009). The 10 m walk test can predict loss of ambulation (McDonald et al., 1995). Timing the Gowers’ manoeuvre is a useful measure of changing function and supine lying is a more reproducible starting position than is sitting.

Lung function

Spirometry forms part of the regular assessment to monitor changes in lung function. Inspiratory and expiratory mouth pressures can also be measured to assess the strength of the respiratory muscles. Details of lung function tests can be found elsewhere; see Chapter 15 and also Griggs et al. (1981) and Hough (1991).

Maintenance of muscle strength

There are very few controlled studies on the effect of exercise in neuromuscular disease and many are not disease specific. The results of mild to moderate resistance exercise programmes in muscular dystrophies have shown limited increases in strength, with no negative effect on muscle function (Ansved, 2003). Greatest effects occur in patients with mild to moderate weakness and in the more slowly progressive conditions, whilst patients with severely weak muscles do not generally benefit from strengthening programmes. It appears in normal subjects that a prerequisite for successful strength training is a high content of type II fibres (Jones et al., 1989). The relative deficiency of type II fibres in DMD (Dubowitz, 1985) may contribute to the poor force-generating capacity of dystrophic muscle and could also be a limiting factor in the eventual benefit of a strengthening programme.

Consistent reductions in maximal or peak oxygen uptake, pulmonary ventilation, work capacity and endurance have been reported in both rapidly and slowly progressive neuromuscular disorders (Kilmer, 2002). Short-term studies in disease-specific patients (Olsen et al., 2005; Sveen et al., 2007; Sveen et al., 2008) indicate low to moderate intensity aerobic exercise is well tolerated with functional improvements in aerobic capacity.

Eccentric muscle training is increasingly being used in the training of athletes to facilitate the development of muscle power, i.e. the rate of force generation. However, eccentric exercise can cause appreciable morphological damage to muscle fibres (Newham et al., 1986) and damage of this nature is commonly seen in the muscles of patients with myopathic diseases. Whilst normal muscle recovers from this damage, eccentric exercise would seem best avoided in muscle disease in favour of more traditional concentric protocols.

Edwards et al. (1987) documented important differences in the rate of progression of various muscle groups and highlighted a particularly rapid loss of force in the hip and knee extensors. Insufficiency of these muscle groups has been shown to be the key deficit in functional decline and gait deterioration in DMD (Sutherland et al., 1981). Whilst maximizing muscle strength to achieve optimal or improved functional ability is a primary objective of treatment, the effect of specific muscle strengthening programmes on function in neuromuscular disorders awaits objective evaluation. To devise a strengthening programme, the required functional gain should be considered and appropriate muscle groups targetted.

It is well accepted that in normal individuals physical exercise increases muscle strength, whilst inactivity causes de-conditioning, and there is also widespread observation amongst clinicians that severe restriction of activity causes rapid weakening of muscle in dystrophic conditions and should be avoided. It is therefore important that the duration of enforced immobilization during any acute illness, and after surgery, should be kept to a minimum so that the patient’s return to mobility is not compromised by muscle atrophy. Exercise and strength training in patients with neuromuscular disorders is discussed in Chapter 18.

Weakness occurs when a muscle is held in a shortened position due to joint deformity, and also when it is contracting over a reduced range (Gossman et al., 1982). The establishment of compensatory postures, long before the development of fixed contracture, means that the muscle is biomechanically disadvantaged earlier than is obvious, since it is continually contracting over a shortened range. This could be a major factor in further progression of the disease as optimal function of the muscle is prevented. Joint positioning during strengthening may therefore be important but research in these patients is still required.

Electrical stimulation of normal muscle can improve strength and fatiguability but evidence that the technique is safe, as well as beneficial, in muscle disorders has yet to be produced (see Chapter 12).

Retarding contracture progression

The management of contractures is one of the major contributions of physiotherapy in neuromuscular disease. The aim is not only to retard the progression of contracture, but also and more importantly to promote or prolong independent ambulation and functional ability. Impairment of mobility caused by contractures compromises the strength of the muscles working across the involved joint or joints. The force-generating ability of a muscle is influenced by the length at which it contracts (Jones & Round, 1990) and thus the strength of a muscle held in a shortened position is reduced. In the presence of profound weakness, the maintenance of full joint range of motion is essential for optimal muscle function.

A sustained programme of night splinting and passive stretching in the early stages of DMD can retard the development of lower limb contractures. Two studies have specifically evaluated the effect of passive stretching and the use of orthoses on the development of contractures. Both concluded that the combination of passive stretching and night splints are more effective than passive stretching alone at delaying contractures and prolonging independent ambulation (Hyde et al., 2000; Scott et al., 1981).

Whilst independently ambulant, the provision of AFOs for control of Achilles tendon contracture should be confined to night use only. Gait analysis has shown that an equinus position of the foot is used as a compensatory manouevre to increase knee stability during walking. Khodadadeh et al. (1986) observed that boys with DMD necessarily adopt a dynamic equinus during gait in order to maintain a knee-extending moment in the presence of gross quadriceps weakness. AFOs intended to correct the foot position by reducing the equinus during walking will have biomechanical effects which will de-stabilize the knee. If there is significant quadriceps weakness the knee will buckle. Thus AFOs used in this way reduce the available compensatory manoeuvres and result in premature loss of ambulation.

Maintenance of activities

A positive management strategy is to introduce a variety of aids to sustain a broad range of normal activities for as long as possible, as outlined above. In children, KAFOs are used to minimize contractures and sustain upright standing posture and prolong walking. Later, a standing frame allows the patients to stand for several hours a day with a view to delaying spinal curvature and contractures of hips, knees and ankles. Lastly, a wheelchair can be introduced as a means to improve mobility and independence. Adults should be encouraged to perform exercise to reduce contractures and thus be able to enjoy physical leisure activities.

Management of scoliosis

Scoliosis is a serious complication of DMD and intermediate SMA. Whilst scoliosis is also associated with other neuromuscular disorders, it is rapidly progressive in these two conditions unless it is treated.

In DMD, a progressive scoliosis almost always develops once the child loses the ability to walk. The period of most rapid deterioration corresponds most closely with the adolescent growth spurt between the ages of 12 and 15 years (McDonald et al., 1995). Progressive scoliosis is also a threat in the adolescent years of patients with type 3 SMA, but due to the profound weakness that is present from early infancy in patients with type 2 SMA it may become a problem at a much earlier age.

The curve often develops in a paralytic long C pattern in the thoraco-lumbar areas and is associated with increasing pelvic obliquity. It further compromises respiratory capacity, which is already restricted by involvement of the respiratory muscles (Kurz et al., 1983). An increasing scoliosis also leads to difficulty in sitting and maintaining head control, and can cause discomfort and pressure areas. Patients will often need to use their elbows for support in maintaining an upright position, so preventing them from using the arms for other functions such as feeding. Untreated, the scoliosis may cause patients to become bedridden.

One of the major benefits of treatment aimed at maintaining an upright posture is that it will help to delay the progression of scoliosis. Once the patient is dependent on a wheelchair, the main means of managing scoliosis are conservative, using a spinal orthosis, or by spinal fusion. The spine should be monitored carefully where scoliosis is a likely complication of the disease, in conjunction with the respiratory capacity using simple spirometry. Once a curve is clinically apparent, any progression is most accurately measured from radiographs using Cobb’s angle. Prompt provision of a spinal orthosis is advisable, to be worn during the day whilst the patient is upright and should be corrective rather than supportive. It is recognized that spinal bracing is not the definitive treatment in curves that are known to be rapidly progressive, but it is important in slowing the rate of progression of the curvature (Seeger et al., 1990) and can be used effectively for skeletally immature patients in whom spinal fusion is not yet indicated.

Posterior spinal fusion is used widely in the management of progressive scoliosis in neuromuscular disease and provides rigid fixation without the need for post-operative immobilization or orthoses. It is effective in achieving maximum curve correction and minimizing respiratory complications. Early surgery is the treatment of choice while respiratory and cardiac function is adequate to undergo the procedure safely. In DMD vital capacity increases with age and growth in the early years, reaches a plateau, and then declines in the early teens. There is therefore a window of opportunity when surgery can be performed safely and this is usually when the curve is 20–40° (Cobb angle) and forced vital capacity is above 30% (Manzur et al., 2008b). Spinal fusion is associated with slowing of the rate of respiratory decline postoperatively, as well as enhanced comfort and seating (Velasco et al., 2007). It has recently been reported that patients with low vital capacity can safely undergo spinal surgery provided it is undertaken in a specialist centre (Gill et al., 2006; Marsh et al., 2003).

In the immediate postoperative period, respiratory therapy to aid removal of secretions will be necessary in patients with a poor cough (see Ch. 15). It is possible for a lumbar lordosis and dorsal kyphosis to be moulded into the rods (Galasko et al., 1992), which helps prevent loss of head control in sitting when weakness of the neck and trunk musculature is likely to be advanced. However, seating requirements will need to be reassessed postoperatively, for example, due to significant upper limb weakness the child is likely to utilize upper trunk flexion to help get his or her mouth down to his or her hands for feeding purposes. Following surgery the height of wheelchair arm supports or table height will need to be adjusted to compensate for a fused spine.

Management of respiratory complications

Chest infections are a serious complication to vulnerable patients with respiratory muscle weakness and a poor cough. Longstanding weakness may lead to more serious secondary problems including widespread microatelectasis with reduced lung compliance, a ventilation perfusion imbalance, and nocturnal hypoxaemia (Smith et al., 1991).

Chest infections should be treated promptly with physiotherapy, postural drainage, antibiotics and, when appropriate, assisted ventilation (see Ch. 15). Spinal orthoses that control scoliosis may reduce respiratory capacity and should be temporarily removed if causing distress or interfering with treatment. The aim of treatment is to help clear the lungs of secretions effectively in the shortest possible time without causing fatigue. Thoracic expansion exercises will allow increased airflow through small airways and the loosening of secretions, while forced expiration techniques, the use of intermittent positive pressure breathing (IPPB) and assisted coughing will aid removal of secretions (Webber, 1988). Diaphragmatic weakness may limit the use of supine or tipped positions for postural drainage. Parents of children prone to recurrent chest infections can become competent at administering chest physiotherapy but will require support that is readily accessible if children become distressed.

Inspiratory muscle training has been reported by some to improve respiratory force and endurance (Martin et al., 1986; Wanke et al., 1994), an effect which may be dose dependent (Topin et al., 2002), whereas others report no significant effects (Rodillo et al., 1989; Stern et al., 1989). Overall training is best started in the early stages of DMD where there is only moderate impairment of lung function. This approach does not appear to be used regularly in clinical practice and has probably been superceded by the successful use of nocturnal ventilation at a later stage.

Respiratory failure may be precipitated by chest infection or it may occur as a result of increasing nocturnal hypoventilation and hypoxia. The onset is often insidious but symptoms include morning drowsiness, headache or confusion and nighttime restlessness, and can be confirmed by sleep study. Life expectancy is less than 1 year once diurnal hypercapnia develops. Symptoms, quality of life and survival can be improved by non-invasive nasal ventilation (Eagle et al., 2002; Simonds, 2000).