Physical exercise training might improve muscle and cardiorespiratory function in spinal muscular atrophy (SMA). Optimization of aerobic capacity or other resources in residual muscle tissue through exercise may counteract the muscle deterioration that occurs secondary to motor neuron loss and inactivity in SMA. There is currently no evidence synthesis available on physical exercise training in people with SMA type 3. To assess the effects of physical exercise training on functional performance in people with SMA type 3, and to identify any adverse effects. On 8 May 2018, we searched the Cochrane Neuromuscular Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase, CINAHL, AMED, and LILACS. On 25 April 2018 we searched NHSEED, DARE, and ClinicalTrials.gov and WHO ICTRP for ongoing trials. We included randomized controlled trials (RCTs) or quasi-RCTs lasting at least 12 weeks that compared physical exercise training (strength training, aerobic exercise training, or both) to placebo, standard or usual care, or another type of non-physical intervention for SMA type 3. Participants were adults and children from the age of five years with a diagnosis of SMA type 3 (Kugelberg-Welander syndrome), confirmed by genetic analysis. We used standard Cochrane methodological procedures. We included one RCT that studied the effects of a six-month, home-based, combined muscle strength and recumbent cycle ergometry training program versus usual care in 14 ambulatory people with SMA. The age range of the participants was between 10 years and 48 years. The study was evaluator-blinded, but personnel and participants could not be blinded to the intervention, which placed the results at a high risk of bias. Participants performed strength training as prescribed, but 50% of the participants did not achieve the intended aerobic exercise training regimen. The trial used change in walking distance on the six-minute walk test as a measure of function; a minimal detectable change is 24.0 m. The change from baseline to six months' follow-up in the training group (9.4 m) was not detectably different from the change in the usual care group (-0.14 m) (mean difference (MD) 9.54 m, 95% confidence interval (CI) -83.04 to 102.12; N = 12). Cardiopulmonary exercise capacity, assessed by the change from baseline to six months' follow-up in peak oxygen uptake (VO2max) was similar in the training group (-0.12 mL/kg/min) and the usual care group (-1.34 mL/kg/min) (MD 1.22 mL/kg/min, 95% CI -2.16 to 4.6; N = 12). A clinically meaningful increase in VO2max is 3.5 mL/kg/min.The trial assessed function on the Hammersmith Functional Motor Scale - Expanded (HFMSE), which has a range of possible scores from 0 to 66, with an increase of 3 or more points indicating clinically meaningful improvement. The HFMSE score in the training group increased by 2 points from baseline to six months' follow-up, with no change in the usual care group (MD 2.00, 95% CI -2.06 to 6.06; N = 12). The training group showed a slight improvement in muscle strength, expressed as the manual muscle testing (MMT) total score, which ranges from 28 (weakest) to 280 (strongest). The change from baseline in MMT total score was 6.8 in the training group compared to -5.14 in the usual care group (MD 11.94, 95% CI -3.44 to 27.32; N = 12).The trial stated that training had no statistically significant effects on fatigue and quality of life. The certainty of evidence for all outcomes was very low because of study limitations and imprecision. The study did not assess the effects of physical exercise training on physical activity levels. No study-related serious adverse events or adverse events leading to withdrawal occurred, but we cannot draw wider conclusions from this very low-certainty evidence. It is uncertain whether combined strength and aerobic exercise training is beneficial or harmful in people with SMA type 3, as the quality of evidence is very low. We need well-designed and adequately powered studies using protocols that meet international standards for the development of training interventions, in order to improve our understanding of the exercise response in people with SMA type 3 and eventually develop exercise guidelines for this condition.
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