J Neuro Rehab 1997;11:69-80
©1997 Demos Vermande

Used with permission    EDITOR NOTE THIS STUDY IS FROM 1997 about 22 years ago. Make sure to verify any information that you use from this study

From the Department of Rehabilitation Medicine
University of Washington, School of Medicine. Seattle, Washington.

Address correspondence and reprint requests to:
Gregory T. Carter. M.D., 500 S.E Washington, Chehalis, WA 98531

Supported by Research and Training Center Grant H133B30026 from the National Institute on Disability and Rehabilitation Research.

The goals of rehabilitation in patients with neuromuscular disease (NMD) are to maximize and prolong independent function and locomotion, inhibit physical deformity, and provide access to full integration into society. Management is best carried out by a multidisciplinary team consisting of physicians, nurses, therapists, social and vocational counselors, and psychologists, among others. Treatment is goal-oriented, using various modalities. Stretching, range of motion, timely surgical correction of spinal deformities and contractures, and bracing may improve or prolong ambulation as well as enhance functional use of the extremities. Moderate resistance (submaximal) weight lifting and aerobic exercise may improve strength and cardiovascular performance in slowly progressive NMDs. For patients with advanced restrictive lung disease, positive pressure ventilation may improve breathing and comfort. Cardiac complications in some NMDs can be severe and may require monitoring. Nutritional, psychological, and vocational considerations should also be part of the management of NMD. Major advances in biomedical and computer engineering continue to provide more functional equipment, allowing better strategies for improvement of quality of life. Key Words: Neuromuscular disease-Rehabilitation-Disability-Muscular dystrophy-Myopathy.

Introduction

Although currently incurable, neuromuscular diseases (NMDs) are not untreatable. The goals of rehabilitation in patients with NMDs are to maximize functional capacities, prolong or maintain independent function and locomotion, inhibit or prevent physical deformity, and provide access to full integration into society with good quality of life. The comprehensive management of the varied clinical problems associated with NMDs is an arduous task. For this reason, the multidisciplinary approach is much more effective and takes advantage of the expertise of many clinicians rather than placing the burden on one.

Management is best carried out by a team consisting of doctors, physical, occupational, and speech therapists, social workers, vocational counselors, and psychologists, among others. Treatment is goal-oriented, using various modalities. Impairment and disability should be thoroughly assessed based on the World Health Organization criteria as applied to neuromuscular diseases (Table 1). Impairment is evaluated by measurements of strength, range of motion, spine deformity, cardiac and pulmonary function, and intellectual capacity. Disability is evaluated by measures of mobility and upper extremity function, cardiopulmonary adaptations, cardiac and pulmonary complications, and psychosocial adjustment.

Table 1. Disability in neuromuscular diseases. World Health Organization (WHO) definitions of impairment, disability, and disadvantage, based on organ systems
Organ	Impairment (usually progressive)	Disability	Disadvantage (handicap)
Skeletal muscle	Strength and endurance	Motor performance Mobility	Quality of life Educational opportunities
		Upper extremity function	Employment opportunities
		Fatigue	Dependency and disadvantage
Bone & joint	Joint Contractures Spine Deformity	Function Pain and deformity
Lungs	Pulmonary function	Restrictive Lung Disease (RLD) Fatigue
Heart	Cardiomyopathy Conduction defects	Cardiopulmonary adaptations Fatigue
CNS	Intellectual capacity	learning ability Psychosocial adjustment

Ideally, due to the significant mobility problems associated with most NMDs, all key clinic personnel should be available at each visit. Tertiary care medical centers in larger urban areas can usually provide this type of service. This may be an independent clinic or a clinic funded by one or more of the consumer driven organizations sponsoring research and clinical care for people with NMDs, including the Muscular Dystrophy Association (MDA). Governmental agencies that support research in NMDs include the National Institute on Disability and Rehabilitation Research (NIDRR), which is a division of the Department of Education, as well as the National Institutes of Health (NIH).

An accurate confirmation of the diagnosis is critical and involves thorough clinical evaluation electrodiagnostic studies, and often a muscle or nerve biopsy. For many of the diseases, DNA analysis of leukocytes or other cellular components obtained through a blood draw is commercially available and contributes greatly to the accuracy of the diagnosis.

Once the diagnosis is confirmed, the patient and family should be thoroughly educated about the expected outcome and what problems may be encountered. The physician should then assess the goals of patient and family and orchestrate a palliative and rehabilitative program that matches those goals. Enrollment in an experimental protocol should be encouraged and facilitated; this not only furthers science but also provides some hope for the patient.

Overview of the Major Neuromuscular Diseases

Duchenne and Becker Muscular Dystrophy

Both Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD are inherited X-linked recessive diseases affecting primarily skeletal muscle and myocardium. Dystrophin, a large cytoskeletal protein in the subsarcolemmal lattice, which stabilizes the plasma membrane during muscle contractions, is absent in DMD and of abnormal molecular weight and/or reduced amounts in BMD (1). This results in an unstable muscle cell membrane and impaired intracellular homeostasis, causing muscle fibers to continually deteriorate and regenerate until the capacity for repair is no longer sufficient and the muscle fibers undergo irreversible degradation with replacement by fat and connective tissue (1,2). The abnormal gene for DMD and BMD is on the short arm of the X chromosome at position Xp21 (1,2).

DMD is the most common neuromuscular disease of childhood, with prevalence rates ranging from 19 to 95 per million and an estimated overall prevalence of 63 per million (3). This progressive myopathy is universally fatal, with death usually occurring from respiratory or cardiac complications. BMD has a lower incidence than DMD, with prevalence rates for BMD ranging from 12 to 27 per million and a recently estimated overall prevalence of 24 per million (2,3). BMD shows a similar pattern of muscle weakness to DMD but with later onset and much slower rate of progression (4).

Myotonic Muscular Dystrophy

Myotonic muscular dystrophy (MMD), an autosomal dominant multisystem hereditary muscular dystrophy with an incidence of 1 in 8,000, is characterized clinically by progressive, predominantly distal muscle weakness and myotonia. Associated findings include frontal baldness, gonadal atrophy, cataracts, and cardiac dysrhythmias (3,5). Two types are recognized: noncongenital (NC-MMD) and congenital (C-MMD). In MMD a DNA sequence within the gene on chromosome 19q 13.3, is repeated many times, leading to an enlarged, unstable area of the chromosome. Called a triplet repeat mutation, the flawed gene grows by sudden leaps when transmitted from generation to generation, causing the disease to occur at a younger age and in a more severe form (5,6). C-MMD patients have been shown to have substantially more repeats than those found in NC-MMD patients. The repeated DNA sequences known as CTG (trinucleotide cytosine, thymine guanidine) are linked to the production of a protein (myotonin-protein kinase) that has important functions in smooth and skeletal muscle, eye, hair, and brain, and decreased levels of messenger RNA and protein expression (5,6).

Facioscapulohumeral Dystrophy

Facioscapulohumeral dystrophy (FSHD) is a slowly progressive myopathy with autosomal dominant inheritance and prominent involvement of facial musculature. Prevalence is difficult to ascertain due to undiagnosed mild cases but has been estimated at 10-20 per million (3). The abnormal gene is known to be near the end of chromosome 4, although exact DNA testing for diagnostic purposes is not yet available except possibly in cases in which a detailed genetic analysis of a family exists (7). FSHD can be quite heterogeneous in its clinical presentation and course, which leads to questions regarding genetic homogeneity (7). Sporadic forms may be referred to as FSH syndrome (FSHS).

Limb-Girdle Syndrome

Limb-girdle syndrome (LGS), a heterogeneous group of myopathies that share some clinical features, has been classified into five types: autosomal recessive muscular dystrophy of childhood (ARMDC), autosomal dominant late-onset (ADLO), pelvifemoral (PF:), scapulohumeral (SH), and myopathy limited to quadriceps (8,9). In any of these, expression may be in either sex, with primary involvement of the shoulder and/or pelvic girdle muscles and a variable rate of progression. LGS is no longer considered a distinct nosological entity and is thought to be a wide variety of muscle disorders predominantly affecting the limb girdle muscles. Genetic studies have identified one form linked to chromosome 15q, another form to chromosome 2p, and two more severe forms to 13ql2 and 17ql2-q21 (8,9). Defects at the chromosome 13q locus and 17q locus result in a specific abnormality in the transmembrane dystrophin associated glycoprotein. and patients with this defect may clinically resemble severe BMD despite the normal expression of dystrophin (10).

Late-onset limb girdle muscular dystrophy with autosomal dominant inheritance has been linked to chromosome 5 but may also be present in childhood and referred to as Bethlem myopathy (8). Pelvifemoral LGS is so heterogeneous that its existence as a discrete disorder remains controversial. Due to substantial heterogeneity, prevalence rates for these syndromes have not been reported.

The Charcot-Marie-Tooth Syndromes

Also known as hereditary motor and sensory neuropathy (HMSN), Charcot-Marie-Tooth (CMT) syndromes are among the most common hereditary neuromuscular diseases, with prevalence ranging from 14 to 282 per million (3 ). There are at least eight forms of HMSN. Types I, II, and III represent the Charcot-Marie-Tooth syndrome. HMSN I (hypertrophic nerve), the most common HMSN, is characterized by markedly reduced conduction velocities in peripheral motor and sensory nerves. HMSN II (neuronal form) exhibits predominant axonal loss, while conduction velocities remain relatively normal. HMSN II is usually a less severe disease than HMSN I, although clinically it may not be easily distinguished from type I. HMSN III is a congenital hypomyelinating neuropathy, with symptoms beginning in infancy (11).

There are several notable subtypes. HMSN type 1a has a DNA duplication at the 17p11.2 locus for the peripheral myelin protein 22 (PMP22) gene. Point mutations in the PMP22 gene have recently been identified in some HMSN 1a patients who did not exhibit the duplication (11,12). The defect in HMSN type 1b is located on chromosome 1 with another myelin protein defect (12,13). Five families have been reported with autosomal dominant HMSN 1b mapping to chromosome 1q21-23 (13). Additionally, autosomal dominant HMSN 1c, which does not map to chromosome 1 or 17, has been reported (13,14).

Spinal Muscular Atrophy

There are at least three forms of spinal muscular atrophy (SMA), all of which involve selective destruction of anterior horn cells (15). These disorders are inherited, autosomal recessive traits. SMA I, also known as Werdnig-Hoffman disease (WHD) or acute, infantile-onset SMA, is a severe disorder that results in death before the age of two years. SMA II, also referred to as early-onset, intermediate SMA, or chronic Werdnig-Hoffman disease, is less severe, with signs and symptoms becoming apparent in the first 6 to 18 months of life. SMA III, also known as Kugelberg-Welander disease (KWD), is a chronic, later onset disorder, associated with significantly less morbidity. Signs and symptoms of SMA III become apparent between ages 5 and 15 years (15). Genetic studies indicate that all types of SMA may be caused by different defects occurring in genes located on the long arm of chromosome 5q13.1, including the survival motor neuron gene and the neuronal apoptosis inhibiting protein (NAIP) gene (15,16).

Prevalence rates for types II and III range from as high as 40 per million among children to around 12 per million in the general population (3).

Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS), like SMA, is a motor neuron disorder (MND). ALS rapidly destroys upper and lower motor neurons, causing spasticity and diffuse muscular atrophy and weakness. Most ALS cases are acquired and occur sporadically. Approximately 1% of ALS cases result from a familial trait due to a specific gene defect on chromosome 21q12.1, leading to an abnormality in the production of the antioxidant enzyme Cu/Zn superoxide dismutase (SOD1) (17). Current popular theories regarding the etiology of sporadic ALS include excessive glutamate activity in the brain and spinal cord due to defective cellular transport mechanisms and/or possible deficiencies in various neurotrophic growth factors (17,18).

ALS most commonly strikes people between 40 and 60 years of age, with a mean age of onset of 58 yrs. (19,20,21). The overall prevalence rate in the worldwide population is between 5 and 7 per 100,000. making it one of the most common neuromuscular diseases worldwide (3,20.21) Overall, he median 50% survival rate is 2.5 yrs. (19,20,21).

Spectrum of Clinical Problems and Treatment Paradigms

Weakness and the Role of Exercise

Skeletal muscle weakness is the ultimate cause of the majority of clinical problems in NMDs. There have been several well-controlled studies looking at the effect of exercise as a means to gain strength in NMDs (22,23,24,25). In slowly progressive NMDs, a 12-week moderate resistance (30% of maximum isometric force) exercise program resulted in strength gains ranging from 4% to 20% without any notable deleterious effects (23). In the same population, a 12-week high resistance (training at the maximum weight a subject could lift 12 times) exercise program showed no further added beneficial effect compared to the moderate resistance program, and there was evidence of overwork weakness in some subjects (24). In a comparative study, CMT patients appeared to benefit significantly from a strengthening program whereas MMD patients showed neither beneficial nor detrimental effects (25). It is likely that the most effective exercise regimens for neuropathies and myopathies will be different, although further studies are needed to confirm this. Due to the active, ongoing muscle degeneration in the rapidly progressive disorders DMD and ALS, the risk for overwork weakness is great and exercise should be prescribed cautiously with a common sense approach.

Dystrophin deficient muscle is very susceptible to exercise-induced muscle injury (26). Using voluntary running protocols, we studied the effect of exercise on skeletal muscle from both normal and mdx mice, a genetically homologous murine model of DMD (27,28,29). In contrast to normal mice, mdx mice show considerable avoidance behavior for exercise. which may be an intuitive survival strategy. After exercise on a mouse wheel ad libitum, the extensor digitorum longus (EDL) and soleus muscles of adult mdx mice became significantly weaker and showed histochemical signs of further damage (figure 1) compared to control mdx muscles (27).

Figure 1. Photomicrograph of quadriceps muscle from adult mdx mouse 3 days following running exercise and subsequent tail vein injection of 10,000 molecular weight fluorescent dextran. There is significant intracellular staining in several fibers (center), indicating membrane damage. Central nuclei, present in regenerating fibers, are shown by focal intense areas of fluorescence.

All patients with NMDs should be advised not to exercise to exhaustion due to the risk of muscle damage and dysfunction. Patients participating in an exercise program should be cautioned of the warning signs of overwork weakness, which include feeling weaker rather than stronger within 30 minutes post exercise or excessive muscle soreness 24-48 hours following exercise. Other warning signs include severe muscle cramping, heaviness in the extremities, and prolonged shortness of breath.

Nonetheless, early intervention with gentle, low impact aerobic exercise like walking, swimming, and stationary bicycling will improve cardiovascular performance and increase muscle efficiency and thus help fight fatigue. Fatigue in NMDs is multifactorial and is due in part to impaired muscular activation, generalized deconditioning, and diminished cardiopulmonary performance from immobility (30,31). Aerobic exercise not only improves physical functioning but also is beneficial in fighting depression, maintaining ideal body weight, and improving pain tolerance.

Exercise may induce muscle cramping in NMD, presumably due to sarcolemmal instability (27,29). Exercise may also cause symptomatic muscle spasms related to spasticity in ALS (30). Baclofen acts to facilitate motor neuron inhibition at the spinal levels and is a good initial agent to use. The benzodiazepines and other centrally acting muscle relaxants may induce somnolence and respiratory suppression. Dantrolene, by impairing excitation-contraction coupling, is effective at reducing muscle tone but also causes generalized muscle weakness and should not be used. Membrane stabilizing agents like tocainamide, mexilitine, and phenytoin may also be helpful, particularly in the myotonic disorders. Amitriptyline, although reportedly effective in relieving myotonia in human MMD, does not have any effect on normal or myotonic mouse skeletal muscle (32). Slow (30 second sustained), static muscle stretching may also be helpful.

Although still considered the clinical standard, manual muscle testing for assessment of strength in NMD has been shown to be unreliable (33,34,35,36). A hand-held myometer or MicroFET® type of strength measuring device is far more reproducible and as easy to use in a clinical setting (33,34). Quantitative methods, including isokinetic measurements, are reliable yet require more sophisticated equipment and usually cannot be done in the clinic (33,36). NMDs may present with fairly asymmetrical patterns of weakness. The notable exception is CMT, where marked asymmetry in strength should raise the possibility of a concomitant focal entrapment neuropathy or other diagnosis (37).

Limb Contractures and Scoliosis: The Role of Stretching, Bracing, and Surgery

Although there is some variability in reported incidence, significant joint contractures and scoliosis develop in a large percentage of DMD and SMA II patients (2,15,18). Joint contracture and scoliosis may occur but are not usually major clinical problems in the other NMDs (18). All NMD patients should have an examination of the spine and major joints at each clinic visit.

Figure 2. Profound shoulder girdle muscular atrophy and subluxation in an adult with facioscapulohumeral dystrophy.

The occurrence of contractures appears to be directly related to prolonged static positioning of the limb, and these contractures often develop soon after wheel-chair reliance (38,39). Several studies have shown that wheelchair reliance and lack of lower extremity weight bearing contribute to the rapid acceleration of contractures (2,38). Upper extremity contractures may occur in ambulatory patients with focal, proximal atrophy, particularly at the shoulder girdle (Figure 2). This may be worsened by subluxation. Slings may be helpful to support the joint but do not prevent contracture formation or subluxation. Gentle static stretching and splinting may slow the progression contractures but this has not been well studied. Although orthopedic contracture release allows a patient to be braced and may prolong ambulation, it appears that weakness is the major factor that inhibits ambulation, not joint contracture per se. In a randommed tral, Manzur and colleagues showed no benefit to early surgical treatment of contractures in DMD (40). Studies indicate that weakness is the major cause of loss of ambulation in DMD, not contracture formation (2,38). Wheelchair reliance and scoliosis were both found to be age-related phenomena but not necessarily linked causally. Several investigators note no relationship between age of wheelchair reliance and subsequent progression of scoliosis (2,38). Lord and colleagues reported a 3.5 year difference between wheelchair dependency and scoliosis in DMD (41). The causal relationship between loss of ambulatory status and scoliosis is doubtful given the substantial time interval between the two variables in most subjects. Further, a significant percentage of DMD and some SMA patients develop scoliosis before they become wheelchair-dependent (2,15). It is more likely that both wheelchair reliance and scoliosis are related to other factors (e.g., age, adolescent growth spurt, increasing weakness of trunk musculature, or other unidentified factors) and thus represent coincidental signs of disease progression.

DMD patients develop scoliosis most commonly between the ages of 13 and 15 years, corresponding closely with the adolescent growth spurt (2). While there is evidence on computerized tomography for asymmetric involvement of the erector spinae in DMD, it is extremely difficult to clinically detect asymmetric paraspinous muscle strength (42). Studies of trunk flexor or extensor strength in NMD patients with or without scoliosis showed no significant difference in MMT, although this method is not capable of measuring asymmetric strength (2,42,43). Several studies confirm that primary or single thoracolumbar curves are more common than lumbar curves (44,45,46,47). Spinal bracing has not been shown to be effective in preventing progression of scoliosis in NMD (48,49). Patients with DMD and SMA should be followed closely with serial radiographs and have appropriate and timely spinal instrumentation and fusion, which should be done before the primary curve becomes greater than 25° and vital capacity (VC) has not gone below 50% of predicted (50,51,52). Although progressive neuromuscular scoliosis does create significant positioning and musculoskeletal problems, it has not been shown to directly affect pulmonary function (53,54,55). Complications increase substantially if the patient already has compromised breathing. If surgery is done in curves that have progressed much beyond 40°, the likelihood of successful correction and fusion is diminished (2,52,53,54,55).

Bracing to Prolong or Maintain Ambulation

The purpose of bracing at any level is to improve function and stability. The use of long leg bracing prolongs ambulation time and has been advocated in DMD partly on the presumption that this will delay scoliosis (2,48,51,52). Several studies have suggested that the ability to continue ambulation with long leg braces for several years may also be indicative of a slower disease progression rate with relatively less weakness of trunk musculature present at a given age (2,30). Any association between prolonged ambulation with long leg bracing and delayed or decreased scoliosis in DMD may not be directly causal. Due to weakness in both proximal (hip and knee extension) and distal (ankle plantar and dorsiflexion) muscle groups in DMD, a long leg brace or knee-ankle foot orthosis (KAFO) is generally needed (2,18,30).

Most CMT patients require short leg braces or ankle-foot orthoses (AFOs). These should be custom-made of a lightweight polymer such as polypropylene or carbon filer resin and should fit intimately to provide good stability and prevent pressure sores. The older, traditional double metal upright AFOs built-in to the shoe may be too heavy and can actually hinder ambulation. If there is severe distal muscle weakness and ankle instability, the braces should be high profile, coming around the ankle in front of the malleoli. A pes cavus foot with a hammertoe deformity can be accommodated with a built-up arch and metatarsal bar. Patients with CMT are at high risk for neuropathic arthritis (Charcot joint) and skin ulcers. Their skin and weight-bearing joints should be closely examined at every clinic visit.

Patients with other NMDs may also benefit from bracing, depending on the distribution of weakness, gait problems, and joint instability created by the weakness. In making the decision to brace, the clinician should also consider the added weight of the brace and whether or not the patient is willing to use a brace. If there are questions about whether or not a brace would help, the patient should be tried in an off-the-shelf model first, along with careful assessment by the clinician. Most patients require a short course of physical therapy after the braces are made to help them use the braces effectively.

Restrictive Lung Disease

Restrictive lung disease (RLD) is common in most NMDs due to weakness of the diaphragm, chest wall, and abdominal musculature (2,15,18,56). RLD can become quite severe in DMD, SMA, MMD, and ALS. Patients should be educated early in the disease process so informed decisions can be made farther down the line (18,56,57,58,59). Routine pulmonary function tests (PFTs), including forced vital capacity (FVC) and maximal inspiratory and expiratory pressures (MIP/MEP), should be monitored closely. The MIP reflects diaphragmatic strength and the ability to ventilate. The MEP reflects chest wall and abdominal muscle strength and the ability to cough and clear secretions.

Ultimately, most patients with severe RLD develop hypoventilation, which leads to elevated CO2 levels (18,56,58,59,60). Measuring only O2 saturation levels with pulse oximetry may be inadequate. End tidal CO2 levels or arterial blood gases (ABGs) should be measured periodically, depending on the clinical condition of the patient. A thorough review of systems will help define any problems. Patients who are hypoventilating often become hypercapnic at night and complain of a morning headache, restlessness or nightmares, and poor quality sleep. This may cause daytime somnolence. Insufficient respiration with hypoxia may occur later, especially if the lung is damaged by chronic aspiration.

Options for noninvasive interventions include a chest cuirass or porta-lung, which mechanically inflates the lung by creating negative chest wall pressure, similar to the iron lungs commonly used during the polio out-breaks. Although effective, these devices are cumbersome and may be poorly tolerated (18,56,57,60). Intermittent positive pressure ventilation (IPPV) by mouth avoids the need for tracheostomy and maintains reasonable quality of life. Bimodal positive airway pressure (BiPAP) is the best initial form. This can be done in the home and should be considered the preferred modality of assisted ventilation in NMDs (57). It generally takes some work with a respiratory therapist to get a good face or lip seal on the mask or nasal/oral orthotic interface. Patients may benefit initially from using assisted ventilation mainly at night. If better airway access becomes absolutely necessary and the informed patient desires more aggressive care, a tracheostomy may be done.

There have been numerous case reports of respiratory failure in people with CMT, the etiology of which has remained elusive. Electrodiagnostic and pathologic studies on the phrenic nerve in CMT confirm that it is involved in the disease (61,62). In one study phrenic nerve latency was abnormally prolonged in 96% of the CMT subjects, but significant PFT abnormalities and clinical symptoms were uncommon and did not correlate with phrenic nerve latencies (61). Although phrenic nerve latencies are markedly prolonged in CMT, they are not useful in predicting respiratory dysfunction.

Bulbar palsy and dysphagia may occur in ALS and some rare forms of SMA (15,18,30). Early signs of dysphagia include changes in voice patterns (voice becoming hoarse) and persistent coughing after swallowing liquids, which can indicate micro-aspiration. A speech therapist should be consulted early on for clinical swallowing evaluations, and recommendations on dietary modification. Thickening liquids and preparing food that forms a bolus easily will help. A modified barium swallow (MBS) is helpful in accurately determining the presence of aspiration as well as in defining which food textures the patient can safely swallow (63).

A percutaneous endoscopic gastrostomy (PEG) cube may be needed for nutrition. If necessary, a laryngeal diversion (laryngotracheal separation) procedure has several distinct advantages over tracheostomy (64). In this procedure, the trachea is surgically separated and a cutaneous tracheostoma is formed with the distal segment. The proximal trachea is either oversewn or sewn side-on-end into the esophagus. This procedure completely eliminates the possibility of aspiration and requires much less deep suctioning than tracheostomy. The tracheostoma does not require any hardware (such as a tracheostomy tube), and the patient may still take some food for pleasure without risk of aspirating. The primary disadvantage is complete loss of phonation since air no longer flows through the vocal cords, so it is only recommended when there is severe dysarthria accompanying the dysphagia and the patient’s speech is unintelligible. While preserving the ability to phonate, a tracheostomy actually increases aspiration risk, requires significantly more care, and provides no better airway access (64).

Cardiac Complications

Significant cardiac involvement occurs in DMD, BMD, MMD, and some cases of the ARMDC subtype of LGS (2,4,5,8). There is a high (60%-80%) occurrence of cardiac involvement in DMD and BMD subjects across all ages (2,4,65,66). Electrocardiogram (ECG) and echocardiographic abnormalities in DMD and BMD are not generally associated with a high incidence of early clinical heart disease in the pre-adolescent years. Dystrophin has been localized to the membrane surface of cardiac Purkinje fibers, and defective dystrophin expression likely contributes to the cardiac conduction disturbances seen in DMD and BMD (67).

In spite of significant ECG and echocardiographic abnormalities, only about 30% of DMD patients have clinical cardiovascular complications (2,65.66). Myocardial impairment remains clinically silent until late in the course of the disease, possibly due to the absence of exertional dyspnea secondary to lack of physical activity. Pulmonary hypertension has also been implicated in the cardiorespiratory insufficiency of DMD. Death has been attributed to congestive heart failure in as many as 40% of patients with DMD by some investigators (65.66).

The pattern of occasional life-threatening cardiac involvement in BMD may be more rapid than the progression of skeletal myopathy (4,18,65). The cardiac compromise may be disproportionately severe relative to the degree of restrictive lung disease in some BMD subjects. The evidence for significant myocardial involvement in BMD is sufficient to warrant screening of all these pa-tients at regular intervals using ECG and echocardiography. Close follow-up is needed for those with myocardial involvement. The slowly progressive nature of this dystrophic myopathy, which is compatible with many years of functional mobility and longevity, makes these patients suitable candidates for cardiac transplantation if end-stage cardiac failure occurs. Successful cardiac transplantation has been increasingly reported in BMD subjects with cardiac failure who are otherwise still quite physically functional (4).

Electrocardiographic abnormalities have been extensively reported in myotonic muscular dystrophy (5). Approximately 33% of NC-MMD subjects had first degree AV block, 17% had left axis deviation, and 5% had left bundle branch block and, rarely, complete heart block requiring pacemaker placement. Although few subjects show clinical signs and symptoms of cardiomyopathy, sudden death does occur in relatively young NC-MMD subjects and bundle of His conduction delays have been reported (5). Any MMD subject with dyspnea, chest pain, or cardiac symptoms should receive thorough cardiac evaluation including bundle of His studies.

Cardiac involvement has only recently been recognized in LGS patients (8). As in BMD, the cardiac manifestations in LGS may predate the clinical evidence of skeletal myopathy (8,68). Approximately 22% of ARMDC patients demonstrate left ventricular hypertrophy on ECG. Left ventricular hypokinesis with a compensatory resting tachycardia, as seen in DMD, is not a common finding in ARMDC and intervention is rarely warranted (2,8,68).

Nutritional Management

In more severe NMDs there is an increasing tendency toward obesity around or after loss of independent ambulation. Obesity is common in NMDs, particularly DMD where a 54% prevalence has been reported (2,69). In prior studies obesity was unrelated to strength decline. age of wheelchair reliance, functional grade status, timed motor performance, pulmonary function, likelihood of ECG abnormalities, or age at death (2). Weight control has its primary rationale in ease of care, particularly ease of transfers and skin care.

Malnutrition may be a significant problem in advanced stages of DMD, ALS, and SMA. Nutritional compromise becomes particularly problematic if there is severe RLD with increased work of breathing, which may also influence caloric intake. Self-feeding often becomes impossible during this period. DMD patients may develop signs and symptoms of upper gastrointestinal dysfunction, making feeding more difficult (70). Nutritional counseling with energy intake and energy allowance estimations should be done for all NMD patients with severe RLD (FVC < 50% predicted). Placement of a PEG tube may facilitate nutrition even if the patient can swallow because it allows for rapid and easy delivery of large amounts of calories and fluids. Patients should be reassured that they will still be able to eat food orally for enjoyment.

Psychosocial and Vocational Considerations

The majority of people with NMDs show intellectual levels within the normal range. However, approximately 30-50% of DMD and MMD patients will manifest mild clinical impairment (2,4,5,7, 8,11,15,71). Nonetheless, a large percentage of NMD patients exhibit elevated scores for hypochondriasis, depression, and hysteria on the Minnesota Multiphasic Personality Inventory (MMPI) test (2,4,5,7,8,11,15). In one study these indicators of emotional pathology were associated with unemployment, whereas loss of ambulation and arm function were not. Overall, employment rates are substantially lower for people with NMDs than for the able-bodied (18). Despite this, a higher level of education correlated with higher employment rate and improved self-esteem in this group (18). This implies that altered personality profiles in people with NMDs substantially impact social integration and employment rates, and, indeed, may be as important as physical abilities with respect to this. Education appears to be very important with respect to employability and self-esteem and should be emphasized in people with NMDs.

Patients should be referred to a support group. Support groups are often a great resource, not only for psychological support but also for problem solving and recycling of equipment such as hospital beds.

Reactive clinical depression may occur in advanced DMD and ALS. Good family, social, and religious support systems are helpful. Antidepressant medication may provide assistance with mood elevation, appetite stimulation, and sleep. Antidepressants with significant anticholinergic activity may help dry oral secretions in ALS and minimize drooling. Referral to a psychiatrist or clinical psychologist may be required. Depression in the spouse or significant other, family, or friends should not be overlooked and group/family counseling may be helpful.

Equipment

There are a number of additional useful equipment items that can substantially improve quality of life, including a hand-held shower, bath tub bench, grab bars, raised toilet seat, hospital bed, commode chair, ADL aids (sock aid, grabbers, etc.), and wheelchair ramp. Wheelchairs should be properly fitted (generally by an occupational therapist) and must have adequate lumbar support and good cushioning to avoid pressure ulcers. Simply giving the patient a prescription for a wheelchair often results in the patient’s getting a standard manual chair that does not fit properly. Although expensive, an electric wheelchair can be justified on the basis that it will help prolong independent mobility and thus markedly improve quality of life.

A good pressure-relieving mattress (air or dense foam) should be used on the bed at home, along with foam wedges to facilitate proper positioning. This helps prevent pressure ulcers and contractures. Wheeled walkers or quad (four point) canes may also help, depending on the pattern of weakness. Frequently severe weakness in the neck flexors and extensors cause a “floppy head” associated with severe neck pain and tightness. This may be helped by a hard cervical (Philadelphia type) or Freeman collar. Communicative aids including an alphabet, word board, or speech synthesizer help with dysarthria in ALS. An occupational therapist can help define which, if any, of these devices will be useful to the patient.

Areas of Future Research

Major advances in the understanding of the molecular basis of many NMDs has greatly enhanced diagnostic accuracy and may provide the basis for therapeutic intervention. There are many promising strategies developing for gene insertion and DNA repair, which are already impacting prenatal diagnostic capabilities and may someday lead to the ability to reverse or even cure some NMDs (72).

There have also been major pharmacologic advances. Riluzole is a neuroprotective agent that appears to inhibit glutaminergic neurotransmission in the spinal cord (73). It is the first agent approved by the Food and Drug Administration (FDA) for use in ALS. Although it has only a modest beneficial effective at improving life expectancy in ALS, it is nonetheless a major advance-ment (73). Various neurotrophic growth factors also appear promising, some of which are now being tried via intraventricular delivery systems (74).

Although not FDA-approved for this use, prednisone, at 1 mg/kg/day, given to DMD boys between ages 4 to 8 years old, has been shown to prolong time of ambulation and should at least be considered for use in this disease, although major side effects include weight gain, osteoporosis, and mood lability (75). Important advances in the use of reliable functional assessment tools have made it easier to judge the effectiveness of experimental interventions. The Timed Motor Performance assessment (Table 2) developed by Brooke and co-workers is one good example of a simple measurement scale that can be used at routine clinic visits (76).

Major advances have been made in the fields of biomedical engineering and computer science, providing patients with NMDs refined, more functional equipment and allowing better strategies for improvement of quality of life. As progress continues to change our management of NMD, it also changes the expectations of patients. Many patients with severe NMD may now live through child-bearing years, possibly bearing children, and expecting to enjoy a high quality of life (77). A comprehensive approach to management of the NMD patient can often fulfill these expectations.

Table 2. Timed motor performance tasks. Time to perform is measured in seconds with a stopwatch. Failure is considered inability to complete the task by a time limit of 120 seconds.

• Standing from lying supine.
• Climbing 4 standard stairs (beginning and ending standing with arms at sides).
• Running or walking 30 feet (as fast as is compatible with safety).
• Standing from sitting on chair (chair height should allow feet to touch floor).
• Propelling a wheelchair 30 feet.
• Putting on a T-shirt (sitting in chair – see instructions).
• Cutting a 3″ x 3″ premarked square from a piece of paper with safety scissors (lines do not need to be followed precisely).

Glossary of Acronyms

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