Mobility and balance rehabilitation in multiple sclerosis: A systematic review and dose-response meta-analysis

•The results of our review provide Level I evidence on the effects of balance intervention to improve mobility and balance in PwMS. Interventions satisfying task-oriented principles appear to be the best for improving mobility and balance rehabilitation.•High dosage of rehabilitation interventions lasting more than 40 min should be specifically delivered to improve balance impairments.•New taxonomy of rehabilitation interventions, high-quality experimental studies with large samples, and long follow-ups are needed to identify patients’ clinical features clusters and develop balance and gait treatment recommendations for clinicians. To assess the benefits of neurological rehabilitation and the dose-response relationship for the treatment of mobility and balance in multiple sclerosis. We included studies investigating the effects of neurological rehabilitation on mobility and balance with the following eligibility criteria for inclusion: Population, People with Multiple Sclerosis (PwMS); Intervention, method of rehabilitation interventions; Comparison, experimental (specific balance intervention) vs control (no intervention/no specific balance intervention); Outcome, balance clinical scales; Study Design, randomised controlled trials. We conducted a random effects dose-response meta-analysis to assess linear trend estimations and a one stage linear mixed effects meta-regression for estimating dose-response curves. We retrieved 196 studies from a list of 5020 for full text review and 71 studies (n subjects=3306) were included. One study was a cross-over and 70 studies were randomized controlled trials and the mean sample size per study was 46.5 ± 28.6 (mean±SD) with a mean age of 48.3 ± 7.8years, disease duration of 11.6 ± 6.1years, and EDSS of 4.4 ± 1.4points. Twenty-nine studies (40.8%) had the balance outcome as the primary outcome, while 42 studies (59.1%) had balance as secondary outcome or did not specify primary and secondary outcomes. Thirty-three trials (46.5%) had no active intervention as comparator and 38 trials (53.5%) had an active control group. Individual level data from 20 studies (n subjects=1016) were analyzed showing a medium pooled effect size for balance interventions (SMD=0.41; 95% CIs 0.22 to 0.59). Moreover, we analyzed 14 studies (n subjects=696) having balance as primary outcome and BBS as primary endpoint yielding a mean difference of 3.58 points (95% CIs 1.79 to 5.38, p