Abstract
Background/Objectives: 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). Methods: 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. Results: 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. Conclusions: tDCS and tsDCS, combined with RAGT, improve walking and reduce fatigue in pwMS, highlighting their potential in motor rehabilitation.