Multiple Sclerosis (MS) is a chronic neurological condition that impairs motor and sensory functions, particularly gait. Non-invasive neuromodulation techniques aim to enhance functional recovery and motor-cognitive outcomes, though their effectiveness remains debated. This study compared the effects of transcranial direct current stimulation (tDCS) and trans-spinal direct current stimulation (tsDCS), combined with robotic-assisted gait training (RAGT), on motor function and fatigue in people with MS (pwMS). This double-blind, randomized, sham-controlled clinical trial included 35 pwMS, who participated in 12 sessions of 20 min anodal tDCS (n = 11), cathodal tsDCS (n = 12), or sham treatment (n = 12), in addition to RAGT. Primary outcomes were assessed using the Timed 25-foot Walk (T25-FW), Timed Up and Go (TUG), walking speed, and Multiple Sclerosis Walking Scale-12 (MSWS-12). Fatigue was assessed with the Fatigue Severity Scale (FSS) and the Fatigue Impact Scale (FIS). ClinicalTrials number: NCT06121635. Significant improvements in gait speed, T25-FW, MSWS-12, TUG scores, and fatigue (FSS) favored tDCS and tsDCS over sham stimulation. While no differences were found between tDCS and tsDCS, the tsDCS group showed a significant improvement in the FIS physical subscale compared to sham, unlike the tDCS group. tDCS and tsDCS, combined with RAGT, improve walking and reduce fatigue in pwMS, highlighting their potential in motor rehabilitation.

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