ALS Outcomes Similar With Either Intensive or Usual Exercise Regimens


Study results suggest that no difference in outcomes of function, survival, fatigue, or quality of life are seen between those undergoing intensive or standard exercise regimens.

Dr Jessica Mandrioli

Jessica Mandrioli, MD, from the Department of Neurosciences at Azienda Ospedaliero Universitaria di Modena, in Italy

Jessica Mandrioli, MD

Patients with amyotrophic lateral sclerosis (ALS) who undergo high-frequency physical exercise may not experience better functional outcomes, motor and respiratory function, survival, fatigue, or quality of life compared with those who utilize a standard exercise regimen, according to new study results.1

Those undergoing an intensive exercise regimen (n = 32), defined as 45-minute sessions 5 times per week, reported a total score of 27.25 (standard deviation [SD], 9.20) at 24 months compared with a score of 29.00 (SD, 13.89) for those undergoing usual exercise regimen (n = 33), defined as 45-minute sessions twice per week (P = .737), on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-r).

Likewise, the results for the intensive and usual groups, respectively, were similar at 3 months (34.87 [8.49] vs. 36.39 [8.01]; P = .485), 6 months (33.08 [SD, 9.76] vs. 33.08 [SD, 9.42]; P = .999), 9 months (32.23 [SD, 9.15] vs. 31.52 [SD, 9.73]; P = .804), 12 months (30.16 [SD, 9.78] vs. 28.94 [SD, 10.87]; P = .723), and 18 months (26.35 [SD, 10.79] vs. 30.64 [SD, 9.53]; P = .293)

“Our study demonstrated that there are no major changes in ALS disease progression, as well as in survival and respiratory function, induced by high‐frequency motor exercise training of ALS patients,” wrote co-author Jessica Mandrioli, MD, from the department of neurosciences at Azienda Ospedaliero Universitaria di Modena, in Italy, and colleagues. “The role of exercise in ALS has been intensely debated in these years, when epidemiological studies shed different light toward physical activity as an exogenous risk factor for the development of the disease.”

Mandrioli et al noted that irrespective of exercise’s contribution to ALS-related degeneration, some studies have shown that patients’ exercise tolerance is impacted by the level of impairment on the oxygen transport-utilization chain of the skeletal muscles. “Previous reports have attributed the lowered oxygen consumption to deconditioning,” they wrote.

Respiratory function was serially assessed by forced vital capacity percentage (FVC%), with the 24-month measurements reported as 64.33 (SD, 32.28) for the intensive group and 65.56 (SD, 44.27) for the usual group (P = .942). At 6 months, the respective measurements were 66.24 (SD, 44.96) and 77.91 (SD, 31.82; P = .308), and at 12 months they were 80.88 (SD, 41.41) and 74.47 (SD, 35.27; P =.647). All told, no significant difference was consistently observed between the 2 arms at different time points during the follow‐up period.

In terms of quality of life, the investigators found that at 2 years, reported scores on the Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) were 74.64 (SD, 42.18) for the intensive group and 99.00 (SD, 48.75) for the usual group (P = .358). As was the case with respiratory function, no significant differences were observed between groups. With respect to the Fatigue Severity Scale measurements, scores were actually increased in the intensive group during the last 12 months of follow‐up.

This study was intended to be reflective of standard physical rehabilitation programs, which often advise a mixture of exercises over one modality, in the context of the advised frequency of exercise. While no benefit or harm was observed in the intensive regimen arm, the investigators concluded that this does provide reassurance about the possible risks of repeated exercise in patients with ALS.

“On the other hand, since the relevance of physical therapy is often questioned by patients and in particular at which degree they should insist in doing exercise at local physical therapy centers, we provide evidence that twice‐a‐week programs are not inferior to five times/week programs to maintain a good functional reserve,” Mandrioli and colleagues noted.

The study authors reported several limitations, one of which was the loss of information during follow‐up due of the high number of dropouts because of death or tracheostomy, explained by the long-term nature of the follow-up. Nevertheless, the authors noted that length is also a strength of the study, as, to their knowledge, previous investigations on exercise in ALS had a maximum follow‐up of only 6 months. Other limitations to consider were the selection of exercises that may not be considered optimal and the treatment duration as a 10‐week regimen (although followed by continuation by the patient and caregiver at home) may be not sufficient to determine a true effect of exercise.

“Our study showed that twice‐a‐week sessions composed of a mixture of exercises may have the same beneficial effect on the patient that high‐frequency physical exercise programs, but further studies are warranted to overcome our study limitations,” Mandrioli and colleagues concluded.


1. Zucchi E, Vinceti M, Malagoli C, et al. High‐frequency motor rehabilitation in amyotrophic lateral sclerosis: a randomized clinical trial. Ann Clin Tansl Neur. Published online March 18, 2019. Accessed March 20, 2019.

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