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

Objective: To assess the benefits of neurological rehabilitation and the dose-response relationship for the treat-ment of mobility and balance in multiple sclerosis. Methods: 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. Results: 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<0.0001). Finally, we performed meta regression of the 20 studies showing an association between better outcome, log of intensity defined as minutes per session (B=1.26; SEB=0.51; p = 0.02) and task-oriented intervention (B=0.38; SEB=0.17; p = 0.05). Conclusion: Our analyses provide level 1 evidence on the effect of balance intervention to improve mobility. Furthermore, according to principles of neurological rehabilitation, high intensity and task-specific interventions are associated with better treatment outcomes.