Toward Brain-Computer Interface motor rehabilitation for people with Multiple Sclerosis

Background Multiple Sclerosis (MS) is a chronic neurodegenerative disease in which the immune system attacks the myelin sheaths around nerves. People with MS (pwMS) often experience pain, fatigue, cognitive dysfunction, and reduced mobility. Today, MS is incurable, and treatments can at best slow the progression of the disease and manage symptoms. We conducted a preliminary, single-arm study using a motor-imagery brain–computer interface (MI-BCI) with functional electrical stimulation (FES) and virtual reality avatar targeting gait in pwMS. Methods Twenty-six pwMS were enrolled; 24 completed 30 BCI sessions. Outcomes were assessed at Baseline, immediately post-treatment (Post1, week 13) and during follow-up (Post2, week 17; Post3, week 37). Change from baseline was analyzed using mixed models for repeated measures (with log-ratio models for skewed measures) and multiplicity control. This uncontrolled study is hypothesis-generating. Results Patients treated with the BCI-based intervention obtained significant improvements that were largely maintained to 6 months after the therapy. The walking endurance, assessed by the 6-minute walking test (6MWT), increased by 37.3 m (95% CI 21.50–53.10) after the treatment ( p < 0.001), exceeding the minimal clinically important difference (MCID). This improvement in the walking endurance was maintained during the following 6 months after the intervention. Mobility/speed improved: TUG and T25FW times decreased by −15.5% and −16.4% after the last BCI session (both p < 0.001), with benefits persisting after 6 months. Spasticity (MAS) declined by about 1 point, and patient-reported outcomes improved statistically and clinically (MSIS-29 10.18 points, MFIS 7.29 points). Pairwise post-visit contrasts were not significant, consistent with maintenance. Exploratory models found no consistent MS-subtype effect on 6MWT change and suggested larger gains with higher baseline EDSS. Two discontinuations were due to participant availability, not concerns with fatigue or safety. Conclusion In this preliminary, single-arm study, a MI-BCI + FES system was associated with statistically significant, clinically meaningful gains in gait endurance, mobility/speed, spasticity, and patient-reported outcomes, sustained up to 6 months after the intervention.