Neuromuscular diseases are a broad group of disorders that affect the motor unit. Recent advances in genetics and molecular biology have greatly furthered understanding of these diseases. Unfortunately, this has not greatly modified treatment strategies. This article addresses some common features of these diseases, and some less commonly addressed issues.
The motor unit is the site of pathology for the neuromuscular diseases. This structure includes the anterior horn cell, its axon (including its myelin sheath), the neuromuscular junction, and the skeletal muscle fibers it innervates. Numerous mechanisms may account for the pathology in the motor unit, including heritable genetic defects and new mutations (eg, spinal muscular atrophies, dystrophinopathies), strong environmental–genome interactions (eg, acute idiopathic demyelinating polyradiculoneuropathy, hereditary pressure palsy), and environmental causes (eg, tick paralysis, polio). In the past few decades, advances in molecular biology and genetics have brought incredible insight into the underlying mechanisms in many of these conditions. This new knowledge, however, has led to a confusingly large number of subtypes of many disorders. For example, the hereditary motor and sensory neuropathies as previously defined by phenotypic appearance had only several subtypes, whereas several types of just hereditary motor and sensory neuropathy type I are now known based on the genetic and molecular pathophysiology.
Because of the wide variety of pathophysiologic mechanisms of the various neuromuscular diseases, each has its own specific medical and rehabilitation needs. The authors believe that several general rehabilitation principles have applications for the broad category of disease processes. This article discusses some of the more important issues.
Diagnosis
Medical history and physical examination remain the mainstay in diagnosing neuromuscular diseases. Because these disorders frequently present with classic findings, many clues can be obtained from talking to and examining patients and their families. In the past, electrodiagnostic studies were commonly used as an extension of the physical examination to further qualify disorders. Nerve conduction velocities were important for differentiating disorders of myelin and neurons, whereas needle electromyography would highlight denervation and various myopathic features. Despite what is frequently taught to budding electromyographers (ie, electromyography and nerve conduction studies are mildly uncomfortable), these studies can be demanding on patients, especially children, depending on the extent of study needed. Muscle and nerve biopsies were often still necessary after electrodiagnostic evaluation to further define the disorder.
With the advent of genetic testing, many disorders can now be detected with just a single venipuncture. Although this is still uncomfortable, it is significantly less painful than multiple electrical stimulations and intramuscular electrical recordings. Numerous tests are available for many heritable neuropathies and myopathies, including mitochondrial disorders. Currently, genetic testing is expensive and cannot be used as a screening tool. Therefore, clinicians must conduct a more thorough history and physical examination (and sometimes nerve conduction velocity or electromyography studies) and narrow the differential diagnosis before ordering these diagnostic tests. Tables 1, 2, and 3 list the more common inheritance patterns of some common disorders.
| Muscular dystrophy | Inheritance pattern |
|---|---|
| Congenital | AR |
| Duchenne | XR |
| Becker | XR |
| Emery-Dreifuss | XR, AD, AR |
| Facioscapulohumeral | AD |
| Oculopharyngeal | AD |
| Limb-girdle | AD, AR |
| Hereditary motor and sensory neuropathy subtype | Inheritance pattern |
|---|---|
| CMT1 | Most are AD, some X-linked |
| CMT2 | Most are AD, some X-linked |
| CMT3 | AD, AR |
| CMT4 | AR |
| Site | Prevalence |
|---|---|
| Low back | 70% |
| Knees | 53% |
| Ankles | 50% |
| Toes | 46% |
| Feet | 44% |
Conversely, inflammatory myopathies and neuropathies are usually not heritable or defined by a genetic abnormality. Diagnosis still relies on clinical history, physical examination findings, elevation of serum muscle enzymes, electrodiagnostic evaluation, and biopsy of muscle tissue.
Deconditioning
Restoring function is the key principal of rehabilitation medicine. Perhaps most important in rehabilitating neuromuscular disorders is to prevent or delay complications and functional losses initially. Clinicians must educate patients and encourage a lifestyle that emphasizes activities that promote maintenance of function, which will decrease the risk or delay the onset of complications and functional losses.
Among preventable complications that can markedly affect functioning is the process of deconditioning . Deconditioning occurs when a person drops from a certain level of physical activity to a lower level, causing the body to adapt to the lesser demands. Near-complete inactivity (most commonly bedrest) has the most dramatic effects. The process of deconditioning has been extensively studied in healthy subjects (especially relating to space travel), showing a vast array of physiologic changes that occur even with short periods of decreased activity. These changes are directly related to the changes in levels of activity and can negatively impact function .
Short periods of complete bedrest for a typical person will have some effects on function, but these are often minimal and recovery can occur rapidly. The opposite is true in more rapidly progressive neuromuscular diseases. Short periods of forced bedrest can have devastating effects, dramatically affecting function and possibly prognosis. For example, a boy who has Duchenne muscular dystrophy (MS) who is confined to a few days of bedrest for an acute illness can prematurely lose the ability to walk and become wheelchair-dependent, which may lead to the start of multiple musculoskeletal changes (eg, multiple contractures, scoliosis, increased pulmonary restrictive disease) and markedly change the nature of the disease/functional state. If hospitalization or surgery is necessary, these patients should become mobilized as early as possible . Physical and occupational therapists should be consulted early to help maintain activity.
Deconditioning
Restoring function is the key principal of rehabilitation medicine. Perhaps most important in rehabilitating neuromuscular disorders is to prevent or delay complications and functional losses initially. Clinicians must educate patients and encourage a lifestyle that emphasizes activities that promote maintenance of function, which will decrease the risk or delay the onset of complications and functional losses.
Among preventable complications that can markedly affect functioning is the process of deconditioning . Deconditioning occurs when a person drops from a certain level of physical activity to a lower level, causing the body to adapt to the lesser demands. Near-complete inactivity (most commonly bedrest) has the most dramatic effects. The process of deconditioning has been extensively studied in healthy subjects (especially relating to space travel), showing a vast array of physiologic changes that occur even with short periods of decreased activity. These changes are directly related to the changes in levels of activity and can negatively impact function .
Short periods of complete bedrest for a typical person will have some effects on function, but these are often minimal and recovery can occur rapidly. The opposite is true in more rapidly progressive neuromuscular diseases. Short periods of forced bedrest can have devastating effects, dramatically affecting function and possibly prognosis. For example, a boy who has Duchenne muscular dystrophy (MS) who is confined to a few days of bedrest for an acute illness can prematurely lose the ability to walk and become wheelchair-dependent, which may lead to the start of multiple musculoskeletal changes (eg, multiple contractures, scoliosis, increased pulmonary restrictive disease) and markedly change the nature of the disease/functional state. If hospitalization or surgery is necessary, these patients should become mobilized as early as possible . Physical and occupational therapists should be consulted early to help maintain activity.
Maintenance of muscular strength and endurance
Perhaps the most common complaints with neuromuscular diseases are weakness and fatigue. Weakness is the inability to generate sufficient contractile force or tension in a muscle (ie, a lack of strength or force), whereas fatigue is the inability to maintain tension or a decrease in force-generating capacity with repeated contraction (ie, lack of endurance) . Weakness and fatigue can be caused by a deficiency in any component in the motor system (eg, muscle, neuromuscular junction, lower motor neuron, upper motor neuron, other cortical structures). Weakness and fatigue (or poor strength and endurance) are closely related. Maintaining or improving strength and endurance is a main goal in managing neuromuscular disorders.
Maintaining strength and endurance requires the routine contraction of the muscle against resistance. In the healthy person, this is typically accomplished through daily activities. Increased stress on the muscle causes physiologic changes to the motor system that increase strength and endurance. Reports have shown that contractions as small as 20% of maximal voluntary contraction are all that is necessary to prevent disuse atrophy.
Strength and endurance training are systematic approaches to increasing strength and endurance through regular exercise. Progressive resistance training is the most widely accepted form of strength training. With regular training, strength has been shown to markedly increase . Jones and Rutheford showed that even a limited program (10 repetitions of 60%–90% maximum load per day) could have significant effects on strength (0.5%–1.0% increase per day over a training period of several weeks). After a 12-week program, force was increased by 25% per unit area. When training, the most dramatic increases in strength are noted in the first several weeks, followed by continued increases but at a slower rate. These initial gains are believed to be from neurologic changes (eg, more efficient recruitment) , whereas the later gains are caused by muscular hypertrophy and biochemical changes . Although force is known to be directly proportional to cross-sectional area of a muscle, the study by Jones and Rutheford showed marked increases in strength with little change in cross-sectional area. Table 4 summarizes adaptations to deconditioning and training.
| System | Deconditioning | Strength training | Aerobic training |
|---|---|---|---|
| Muscular |
|
|
|
| Skeletal |
| Increased bone density | Increased bone density (if weight-bearing activity) |
| Cardiovascular |
|
|
|
| Neurologic | Less efficient motor recruitment |
| Decreased sympathetic activity |
| Endocrine |
|
|
|
Overwork injury
In 1958, Bennett and Knowlton raised the concern of overwork in diseases with partial innervations. They defined overworking a muscle “by continued voluntary activity to overuse a muscle to a point where long-lasting impairment of that muscle results.” Clinical experience was cited and five cases were discussed (four postpolio and one cervical spinal cord injury). They summarized the five key risks for overwork injury as when (1) repeated demands on a muscle equal or exceed the maximum strength and endurance, (2) maximum work output of the muscle does not challenge the muscle circulation, (3) the individual is conditioned to tolerate a high disparity between innervation effort and extent of response, (4) initial innervation effort is so great that incremental increases are below the least detectable difference, and (5) motivation for performance is so great as to negate the sensation of tiredness.
Therefore, overwork is clearly a risk of intense exercise in healthy individuals and those who have neuromuscular disease. Rhabdomyolysis is seen on occasion after intense athletic activities, and would fit the criteria of overwork.
Johnson and Braddom also discussed overwork weakness; they described more weakness in the dominant extremities in three generations of a family that had facioscapulohumeral MS. The sole exception was one member who used his nondominant arm more routinely at work. They concluded that this asymmetrical weakness was caused by overwork and that “strengthening and endurance exercises may be contraindicated.” Based on the sometimes asymmetric nature of facioscapulohumeral MS, the validity of these conclusions has been questioned . When relating this finding to Bennett and Knowlton’s report, routine use of a dominant extremity does not fit their definition of overwork; daily submaximal use of the dominant extremity in routine activities of daily living does not amount to the effort needed to cause overwork weakness.
These two articles have been routinely cited as evidence of overwork weakness contraindicating muscular strength and endurance training in neuromuscular diseases. However, several problems are associated with this thinking. First, only two neuromuscular diseases (postpolio and facioscapulohumeral MS) were evaluated. One cannot necessarily generalize all neuromuscular diseases from these two specific diseases. Each disease must be evaluated based on its pathophysiologic mechanisms and then risk assessed appropriately (eg, one would suspect a higher risk for muscle damage in a myopathy versus neuropathy). Second, according to Bennett and Knowlton, overwork weakness results from intense activity, but low-intensity training programs can increase muscular strength and endurance, and presumably function. Also, neither report was a prospective, controlled study. Numerous prospective studies report improved or maintained muscular strength and endurance in various neuromuscular diseases .
Like any effective therapy, strength training has associated risks. Numerous studies have clearly shown that strength training can cause muscle damage in normal neuromuscular systems, especially eccentric contractions . Although studies have shown strength gains in various neuromuscular diseases, they have been short-term and do not necessarily show the impact on final outcome . Numerous studies report exercise-induced injury in neuromuscular diseases . Taylor and colleagues’ report in mdx mice is especially concerning. Clearly, studies must be performed in specific disorders to better define the benefits and risks in each disease.
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