Neuromuscular Notes: Exercise and Rehabilitation Medicine in Neuromuscular Disease

Neuromuscular disorders present a unique and challenging situation for physicians, therapists, and other health care personnel in many ways. Compared with exercise and rehabilitation approaches for individuals with central nervous system disorders, another layer of complexity exists for exercise and rehabilitation methods in neuromuscular diseases, because many symptoms can be exacerbated or triggered by physical activity. Because of substantial heterogeneity among neuromuscular disorders, no single exercise or rehabilitation program will be appropriate for all individuals. Many of these disorders are complex and require a multidisciplinary team, including many members (eg, physical therapists, occupational therapists, speech therapists, orthotists, prosthetists, physicians), to ensure delivery of a safe, effective, and sustainable program.

Motor Neuron Disease

Exercise can be challenging for individuals with motor neuron disease (MND) but is necessary to provide these individuals with the best possible function and quality of life. An explosion of data regarding exercise in MND has emerged in the past decade, challenging old assumptions and making awareness of the current data a priority for the neuromuscular specialist.

There are insufficient data to draw definite conclusions for the benefit of exercise in MND as a whole, but severe adverse effects are rarely reported. The current evidence, although limited, suggests a benefit for exercise that does not produce fatigue, dyspnea, or delayed-onset muscle soreness.

Amyotrophic Lateral Sclerosis

Overtaxing stressed motor neurons with exercise is a particular concern in the setting of relentless, progressive disease, such as amyotrophic lateral sclerosis (ALS). A 2013 Cochrane review¹ concluded that there was weak evidence for the benefit of exercise and no evidence of harm in those with ALS, noting the strength of the data was poor and that more studies were needed. Additional studies have emerged since then, and a recent meta-analysis concluded that exercise can lead to long-term functional gains without adverse effects, but no improvements in quality of life.² Although more data would be helpful, the current cost–benefit ratio of prescribing exercise for individuals with ALS appears to be positive.

Spinal Muscular Atrophy

A 2019 Cochrane review³ reported that 1 small, randomized controlled trial (RCT) of 6 months’ duration using combined aerobic and resistance training in individuals with spinal muscular atrophy (SMA) did not show any definite benefit in strength, functional measures, or quality of life. No adverse events were seen in either group. However, this topic will be worth revisiting given the emergence of recently introduced highly effective disease-modifying treatments for SMA.

Spinal Bulbar Muscular Atrophy/Kennedy Disease

There are little high-quality data on the effect of exercise in individuals with spinal bulbar muscular atrophy (Kennedy disease). A recent Cochrane review could draw no conclusions about benefits or drawbacks of physical activity interventions in those with this condition.⁴ A single individual in 1 trial experienced a significant increase in creatine kinase levels and subjective inability to perform activities of daily living.⁵

Postpolio Syndrome

Exercise is an important consideration for individuals with postpolio syndrome (PPS). Despite theoretical concerns about overtaxing already stressed motor neurons, reviews of studies performed to date have shown no worsening of symptoms, decline in motor unit number estimation measures, creatine kinase elevations, or signs of worsening on histopathology.⁶ European Federation of Neurological Societies guidelines from 2006⁷ indicate level B evidence that training in warm climates and nonswimming water exercises are particularly useful (ie, for improving fatigue, pain, and cardiovascular conditioning), but a Cochrane review including more recent trials⁸ concluded that there was very low-quality evidence of benefit. Despite this, it is reasonable to prescribe the aforementioned types of exercise for individuals with PPS due to the low overall risk of these exercises.

Inherited and Acquired Neuropathies

Neuropathy affects many individuals worldwide—approximately 193 million, or 2.4% of the global population⁹—and is associated with pain, numbness, and weakness. Various pharmacologic treatments are available, but exercise has gained prominence as a nonpharmacologic approach for the management of neuropathy. A recent meta-analysis of exercise for all forms of peripheral neuropathy indicated that exercise is beneficial for people with diabetic peripheral neuropathy and chemotherapy-induced peripheral neuropathy, 2 of the most common forms of peripheral neuropathy.¹⁰ Endurance training and sensorimotor training have proven to be beneficial for people with diabetic peripheral neuropathy, resulting in improvements seen in balance, Berg Balance Scale score, Timed-Up-and-Go-Test score, nerve conduction velocity of the peroneal and sural nerves, and HbA1c levels. Moderate- to vigorous-intensity exercise (at 40% to 70% of heart rate reserve) 3 to 6 times per week for 8 to 12 weeks was recommended for this population.

For individuals with chemotherapy-induced peripheral neuropathy, exercise, particularly sensorimotor training, resulted in improved static balance, quality of life, and neuropathy-induced symptoms. In most studies, the term sensorimotor training was used as a broad term for balance exercises, such as maintaining postural control on an unstable surface or in an unstable position. The effects in this group were measurable in as little as 4 weeks with interventions conducted twice per week.

For many other types of neuropathy, it is difficult to make evidence-based recommendations about exercise because of a lack of high-quality evidence. A recent systematic review of 6 RCTs looked at the effects of exercise on neuropathy for people with Charcot-Marie-Tooth (CMT) disease.¹¹ CMT is a disorder with heterogeneous genetic causes. In the systematic review, the data revealed that exercise improved strength in children with CMT. Evidence regarding the effect of exercise in adults with CMT and on other aspects of health (ie, aerobic capacity, quality of life, overall function) was of low quality. More data are needed to guide definitive recommendations.

With regard to hereditary neuropathy with liability to pressure palsies, there is less substantial evidence. However, there have been several cases of individuals with hereditary neuropathy with liability to pressure palsies experiencing their first exacerbation within the context of exercise. Most of these data derive from soldiers completing military exercises.^12,13 Based on these studies, it would be prudent for individuals with these disorders to avoid activities that would place compressive force on vulnerable nerves.

Overall, sensorimotor training has great potential for treatment of most neuropathies; combined with endurance training, it is the best treatment option for neuropathies. Variability exists concerning the specific interventions used among studies, however. When prescribing exercise, it is imperative to determine the appropriate dosage, frequency, and modality. Further research in this area is needed to define these parameters more specifically.

Myopathic and Neuromuscular Junction Disorders

In the case of metabolic myopathies and disorders such as myasthenia gravis (MG), exercise is often the activity that precipitates or exacerbates symptoms. Indeed, exercise intolerance is a hallmark of these disorders. Individuals often require activity and exercise modifications to help manage long-term symptoms and to prevent acute exacerbations. For example, individuals with McArdle disease often present with symptoms related to high-intensity exercise; as such, substituting shorter bouts of exercise of low to moderate intensity spaced out over the week can be helpful.^14,15 For other disorders—like fatty acid oxidation defects—progressive exercise training in a fed state is medically indicated to prevent adverse effects or exacerbation of the condition. Furthermore, such individuals with fatty acid oxidation defects should avoid fasting and exercise during illness.¹⁶

In the case of MG, exercise should be performed only in cases of mild or controlled disease.¹⁷ There is a benefit of moderate-intensity exercise (ie, a total of 150 minutes of moderate-intensity exercise over the course of a week) in improving endurance and quality of life, as well as modest muscle strengthening, in individuals with mild or controlled disease.¹⁸

There appears to be support in the literature for recommending that low- to moderate-intensity exercise is beneficial for range of motion, contracture prevention, and quality of life in numerous disorders, including myotonic dystrophy type I, dystrophinopathies, and facioscapulohumeral muscular dystrophy.^19-24 For all these disorders, screening for common comorbid—and often disease-related—cardiac and respiratory dysfunction is indicated before individualized exercise routines are prescribed. Proper prescription and fitting of orthoses (Table)—particularly ankle foot orthoses—can improve balance and walking in neuromuscular disorders to make low-intensity ambulation safe and tolerable.²⁵

Conclusions

There is insufficient evidence to support a standard regimen of exercise for individuals with neuromuscular disorders. Low- to moderate-intensity exercise benefits physical conditioning, maintenance of joint range of motion, and quality of life for many individuals. High-intensity exercise may be detrimental and is not routinely recommended. Exercise recommendations must be individualized, with consideration given to the disease type and severity of the individual’s condition. Proper prescription of lower limb orthoses that address deficits and lifestyle can help promote safe and tolerable ambulation. Further studies on the effects of exercise in individuals with neuromuscular disorders are needed because the evidence reflects heterogeneous interventions and exercises for various disorders.