Measuring the effects of exercise in neuromuscular disorders: a systematic review and meta-analyses [version 1; peer review: 2 approved]

Abstract

Background: The benefit and safety of exercise training for patients with neuromuscular disorders (NMDs) has long been a contentious topic. This is, in part, due to recognised challenges associated with rare diseases including small and heterogenous patient populations. We performed a systematic review and meta-analyses to evaluate the effectiveness and safety of interventional exercise and establish minimal clinically important differences (MCID) in outcomes to facilitate clinical interpretation. Methods: We searched six databases from inception to Mar 2018. Aerobic, strength, and combined (aerobic and strength) intervention were eligible. Meta-analyses compared outcomes at baseline with those after at least six weeks (before-after exercise within individuals). A further meta-analysis compared outcomes before-after exercise between groups (exercise training versus usual care). Disease heterogeneity was explored using a random effect model. This study was registered (PROSPERO, CRD42018102183). An interactive database was developed to facilitate full interrogations of data. Results: We identified 130 articles describing 1,805 participants with 35 different forms of NMD. Of these studies, 76 were suitable for meta-analyses. Within group and between group meta-analyses detected an increase in peak aerobic capacity (p=0·04), and peak power (p=0·01). Six-minute walk test (p=0·04), sit-to-stand (STS) (repetitions) (p=0·03), STS (seconds) (p=0·04), rise from supine (p=0·008), SF-36 (p=0·0003), fatigue severity (p=<0·0001), citrate synthase (p=0·0002), central nuclei (p=0·04), type 1 (p=0·002) and type II muscle fibre area (p=0·003), were only able to detect change within group meta-analyses. Substantial I2 statistic heterogeneity was revealed for STS (seconds) (I²=58·5%; p=0·04) and citrate synthase (I²=70·90%; p=0·002), otherwise heterogeneity for all outcomes was low. No study-related serious adverse events were reported nor significant increases in creatine kinase. Conclusions: Exercise training in patients with NMDs appears to cause no harm across a range of outcomes. With the emergence of new therapeutic strategies, defining MCID is vital in informing future clinical trial design.