Transcutaneous electrical nerve stimulation improves walking in fatigued persons with multiple sclerosis: a randomized controlled trial

BACKGROUND: Walking difficulties and fatigue severely limit daily life in persons with multiple sclerosis (pwMS). Sensory stimulation, such as transcutaneous electrical nerve stimulation (TENS), might offer a non-pharmacological strategy to enhance motor function through sensorimotor interactions in the central nervous system. OBJECTIVE: This randomized, double-blinded, sham-controlled, parallel-group superiority trial investigated the effects of TENS applied to the knee extensors, with and without concurrent exercise, on walking and fatigue in pwMS. METHODS: PwMS (n = 80) with fatigue (FSS>4 or MFIS>38) and walking difficulties (MSWS-12>30) were randomized to one of four groups: TENS only (TENS; n = 21), TENS+exercises (COMBINATION; n = 20), sham stimulation (SHAM; n = 20) or sham+exercises (EXERCISE; n = 19) using a computer-generated stratified randomization. Each group performed twelve 10-min sessions over 4 weeks. Participants and outcome assessors were blinded to the stimulation type. Primary outcomes were walking performance (6-minute walk test, 6-MWT), fatigue (FSS, MFIS), and self-reported walking limitations (MSWS-12). Secondary outcomes were knee extensor strength and force steadiness and the 30-second chair-stand test (30-CST). Outcomes were assessed at baseline, immediately post-intervention, and at 2-week follow-up. RESULTS: Intention-to-treat linear mixed-effect models showed a significant time*group interaction for the 6-MWT (p < .05). Relative to SHAM, within-group comparisons indicated significant improvements in the TENS group only (+35 m [95% CI: 23.1-46.5] post-intervention; +35 m [95% CI: 22.4-48.4] at follow-up). Clinically meaningful improvements (>21.6 m) in walking distance were achieved by 74% of the TENS group compared to 44%, 40% and 28% in the COMBINATION, SHAM and EXERCISE group. FSS, MFIS, MSWS-12 and secondary outcomes improved across all groups, with no between-group differences. No important harms were notified. CONCLUSIONS: TENS during rest, but not during exercise, improved walking performance in pwMS more than SHAM, but not subjective outcomes such as fatigue or perceived walking limitations. Future studies should investigate underlying neurophysiological mechanisms to optimize therapeutic outcomes. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05321927).