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STUDY FINDS ENDURANCE TRAINING BENEFITS SOME LIMB-GIRDLE MUSCULAR DYSTROPHY PATIENTS

ARTICLE IN BRIEF

✓ Investigators reported that moderate-intensity endurance training is a safe method to increase exercise performance and daily function in patients with LGMD21.

Patients with limb-girdle muscular dystrophy type 2I (LGMD21) may safely benefit from a regimen of low to moderate endurance training, according to a new study in the Jan. 2 Neurology (2007;68:59–61). A team of Danish investigators studied nine patients who used a stationary exercise bicycle for three months, and reported that they had significantly improved physical performance and work capacity without muscle problems.

But experts not involved with the study cautioned that the trial findings, while interesting, involved too few patients to be applicable to all patients with LGMD21.

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Patients with LGMD21 usually lead a sedentary lifestyle, but a new study suggests that exercise in a controlled setting may be safe and effective.

The patients participated in five 30-minute exercise sessions per week, at 65 percent of their maximum oxygen capacity. Creatine kinase (CK) levels, a biomarker of muscle damage, did not rise significantly during the study period, nor did their condition worsen during the training, according to the senior study author John Vissing, MD, PhD, professor of neurology at the National University Hospital in Copenhagen.

STUDY PROTOCOLS

Investigators compared fitness levels in six men and three women with LGMD2I with nine healthy age- and sex-matched controls. Patients averaged 48 years in age. One patient had macroglossia, seven had calf hypertrophy, and three had asymptomatic dilated cardiomyopathy. Mean vital capacity was 3.9 liters.

After an initial supervised training period, patients exercised at home on a stationary bicycle ergometer. Sessions increased in number over the first four weeks, reaching five sessions per week for the last eight weeks.

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Dr. John Vissing: “We studied just one level of exercise intensity, using one type of exercise; endurance-aerobic training. It still needs to be investigated whether strength training at different intensities and aerobic training at higher intensities also improve muscle function in muscular dystrophies.”

“We found that 12 weeks of low-intensity aerobic training is an effective and safe way to increase physical fitness in these patients,” Dr. Vissing said in a telephone interview.

Training improved maximal oxygen uptake by 21 percent and workload capacity by 27 percent, which was similar to improvements observed in healthy controls. There were no signs of muscle damage as monitored by CK levels and occurrence of necrotic, apoptotic, or regenerative fibers. This suggests such training may have longer benefits, Dr. Vissing said, but he added that further studies are needed to confirm the findings.

“We saw the same effect of training in all patients, and these results appear to be prolonged,” Dr. Vissing told Neurology Today. “Some patients have been training for almost one year now. They don't get a lot better than after the three months of training, but the benefit is maintained.”

Most LDMD2I patients reported improved physical endurance, leg muscle strength, and walking distance, with no worsening of symptoms or adverse events. While improved oxygen capacity was used as an objective measure of improved fitness, the patients also reported having more energy, endurance, and stability when they walked.

IMPORTANCE OF AEROBIC TRAINING

“We had previously found that aerobic training, as used in the present study, is beneficial for other muscular dystrophies, such as myotonic dystrophy, mitochondrial myopathy, and facioscapulohumeral dystrophy, in which the molecular defects do not involve structural proteins in muscle,” Dr. Vissing said. “For decades, it was thought that patients with muscular dystrophies related to structural protein defects are more vulnerable to muscle damage by the act of contraction. This notion stems from old, preliminary studies on patients with Duchenne dystrophy, in which strength training evoked increased serum CK levels.”

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Dr. Glen Lopate: “Its hard to extrapolate this kind of data to the general muscular dystrophy population, and because they already have damage due to their disease there is the potential for much greater muscle damage with exercise. We dont even know if mild exercise helps, and there could be long-term consequences from more intense aerobic training.”

In LGMD2I, alpha-dystroglycan is defective because of impaired glycosylation of the protein. This protein is embedded in the muscle cell membrane, and is thought to play an important role in stabilizing the link between the contractile apparatus and the extracellular matrix. The present study provides proof-of-concept that training may be safe and beneficial despite defects involving structural proteins of muscle.

Physicians should recommend endurance training for patients with LGMD21 only in a controlled setting, and they should be carefully instructed about the frequency, intensity, and duration of the exercise, Dr. Vissing advised. “Training has to be performed at a reasonable level of intensity, which is found by monitoring heart rate – this is critical,” he said.

Are further studies warranted given the small number of patients in this trial? “I would say more studies are not necessary before recommending patients to start a mild endurance training program, although we do need more research in the field overall, and the long-term effects needs to be explored more,” he said.

“We studied just one level of exercise intensity, using one type of exercise: endurance-aerobic training. It still needs to be investigated whether strength training at different intensities and aerobic training at higher intensities also improve muscle function in muscular dystrophies,” he said.

“However, the evidence favoring training of patients with muscular dystrophies clearly suggests that past recommendations of leading a sedentary life and avoiding physical exertion in muscular dystrophies should be abandoned.”

A CAUTIONARY NOTE

While the findings appear to be encouraging, they must be viewed with caution given the size of the study group, said Neurology Today associate editor-in-chief Steven Ringel, MD, professor of neurology and director of the neuromuscular division at the University of Colorado Health Science Center in Denver.

“These patients had a milder form of muscular dystrophy and received some mild benefit, but the larger picture, especially with treating other more advanced and aggressive dystrophies, has shown that exercise appears to have only a modest benefit, so nothing has really changed,” he told Neurology Today in a telephone interview. “This is a small study, so it's difficult to generalize results to a larger patient population.”

Nonetheless, he agreed that the paper demonstrates “proof of concept” and helps quantify the effects of exercise in a small subgroup of patients with muscular dystrophy.

“But from a practical standpoint for clinicians, I don't believe the findings are very helpful,” he said. For most patients, there is a small therapeutic window in which exercise may help, he explained, but this window is only open for a short period of time – especially with more aggressive forms of the disease.

“In my practice, and in my opinion, stretching is the most important exercise for these patients, followed by aerobics,” Dr. Ringel said. “I don't put much emphasis on weight training though, because they don't need strength, they need mobility, and patients with muscular dystrophy are at much higher risk of overexertion injury.”

“I don't want to be a naysayer, but these patients have to be extremely careful – they need to go very slow,” he continued. “My concern is that patients will hear about this study and start exercising on their own, especially men, and suffer overexertion injuries. In my experience, men always try to overdo it and get into trouble. Unlike women, who tend to be more cautious, men tend to exercise past their physical limitations, trying to exercise away their disease.”

BENEFITS VS. RISK

Dr. Vissing and the Copenhagen Muscle Research Center are one of the few groups that have looked at aerobic exercise protocols in muscular dystrophy patients, and they have reported similar benefits in two other types of the disease, noted Glen Lopate, MD, associate professor of neurology at Washington University School of Medicine in St. Louis, MO.

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Dr. Steven P. Ringel: “In my practice, and in my opinion, stretching is the most important exercise for these patients, followed by aerobics. I dont put much emphasis on weight training though, because they dont need strength, they need mobility, and patients with muscular dystrophy are at much higher risk of overexertion injury.”

“They reached the same conclusion in the past – in the short term there were no obvious deleterious effects from endurance training. But I don't think it's clear whether there are any real benefits,” he told Neurology Today in a telephone interview.

“It's hard to extrapolate this kind of data to the general muscular dystrophy population, and because they already have damage due to their disease there is the potential for much greater muscle damage with exercise. We don't even know if mild exercise helps, and there could be long-term consequences from more intense aerobic training,” he commented.

“I don't recommend exercise for my patients with muscular dystrophy,” he continued. “They're not going to get stronger even if their aerobic capacity increases. We just don't have enough data yet for me to recommend that they go out and ride a stationary bicycle five times a week.”

LGMD: A CLINICALLY HETEROGENEOUS GROUP OF MUSCULAR DYSTROPHIES

Limb-girdle muscular dystrophy (LGMD) comprises a genetically and clinically heterogeneous group of childhood and adult onset muscular dystrophies distinct from the X-linked dystrophinopathies. Patients show weakness and wasting of limb musculature with more proximal involvement than distal. Onset and severity of symptoms vary widely and are, to some extent, dependent upon the molecular etiology of the disease.

Phenotypes for ten of the fifteen known LGMD genes are autosomal recessive. LGMD type 2I is a mild allelic variant of congenital muscular dystrophy caused by deficiency of fukutin-related protein.

REFERENCE

• Sveen M-L, Jeppesen TD, Vissing J, et al. Endurance training: An effective and safe treatment for patients with LGMD21. Neurology 2007;68:59–61.