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.

Background and Purpose: Multiple sclerosis (MS) presents significant challenges due to its inflammatory and degenerative nature, often manifesting in debilitating symptoms such as gait disturbances. Non-invasive stimulation techniques, such as trans-spinal direct current stimulation (tsDCS), offer promising avenues for enhancing functional recovery, but evidence on tsDCS effectiveness in neurological disorders remains sparse. This study aimed to investigate the effects of cathodal tsDCS on gait function and fatigue in people with MS (pwMS) compared to sham tsDCS. Methods: Twenty-two pwMS received 6 sessions of 20-minute cathodal tsDCS (n = 11) or sham tsDCS (n = 11) in addition to a physiotherapy program. The primary outcomes were the Timed 25-Foot Walk (T25-FW), Timed Up and Go test (TUG), gait speed, and the Multiple Sclerosis Walking Scale-12 (MSWS-12) evaluated before and after treatment. The secondary outcome was fatigue, measured with the Fatigue Severity Scale (FSS) and Fatigue Impact Scale (FIS). Results: Intergroup comparisons showed a significant improvement in the cathodal tsDCS group compared to the sham tsDCS group. Specifically, there was a greater reduction in pre-post values for T25-FW (Median: −4.43; Range: −12.1 to −1.0), MSWS-12 (−16.70; −31.7 to −5.0), TUG (−6.03; −20.8 to −0.7), FSS (−0.30; −2.2 to 0.1), and FIS-Physical (−4.00; −13.0 to 0.0). Additionally, walking speed increased significantly (0.15; 0.02 to 0.24) in the cathodal tsDCS group. Moreover, all gait-related outcomes and FSS showed large effect sizes ( r > 0.5), indicating a strong intervention effect. Discussion and Conclusions: Incorporating cathodal tsDCS into a physiotherapy program improved walking function and fatigue in pwMS. Although replication is warranted, these results hold promise for clinical applications, highlighting tsDCS as a potential tool for enhancing motor function and reducing fatigue in pwMS. Video Abstract available: for more insights from the authors (see Supplemental Digital Content available at http://links.lww.com/JNPT/A542).