Efficacy of transcranial direct current stimulation on motor and cognitive functions in patients with multiple...

Multiple Sclerosis (MS) is a chronic neurological disorder affecting 2.8 million individuals worldwide, characterized by motor dysfunction and cognitive impairment that remain poorly addressed by pharmacological interventions alone. Transcranial Direct Current Stimulation (tDCS) has emerged as a promising non-invasive neuromodulation technique for symptom management in MS patients.

This systematic review and meta-analysis aimed to evaluate the efficacy of tDCS in improving motor and cognitive functions in patients with MS, and to assess its safety profile.

A comprehensive literature search was conducted across PubMed, Scopus, EMBASE, Wiley Online Library, and Google Scholar databases. Studies were selected based on PICOS criteria, including randomized controlled trials and quasi-experimental studies involving adults (≥ 18 years) with all types of MS receiving tDCS interventions. Methodological quality was assessed using RoB 2.0 and ROBINS-I. Meta-analyses were performed using RevMan 5.4.1 with random-effects models for outcomes with substantial heterogeneity and fixed-effects models where I² = 0%. Additionally, the protocol was prospectively registered with the Open Science Framework.

Twenty-two studies published between 2015 and 2025 were included in this review. Meta-analysis revealed that tDCS significantly improved information processing speed (SDMT: MD = 7.71, 95% CI: 1.60-13.82, p = 0.01) and functional mobility (TUG: MD = -1.03 s, 95% CI: -2.08-0.02, p = 0.05). While individual studies showed improvements in gait speed and balance, pooled analyses for these outcomes did not reach statistical significance (gait speed: MD = 0.16 m/s, 95% CI: -0.07-0.38, p = 0.18; Berg Balance Scale: MD = 1.18, 95% CI: -2.03-4.39, p = 0.47). Qualitative analysis revealed consistent improvements in manual dexterity, working memory, executive function, and complex attention. Additionally, no serious adverse events were reported across studies; mild and transient side effects (e.g., tingling, itching) were noted, and completion rates were high (98% in studies that reported them).

This systematic review provides preliminary evidence supporting tDCS as a potentially beneficial adjunctive intervention for MS patients, particularly for cognitive processing speed enhancement based on two small studies. While individual studies reported motor improvements, pooled meta-analyses for gait speed and balance failed to demonstrate statistical significance, indicating insufficient evidence for definitive motor benefits despite positive signals in individual trials. The substantial limitation of small study numbers per meta-analysis (2-6 studies), combined with limited MS subtype-specific data in most studies, significantly constrains confidence in these findings and limits assessment of external validity across different MS populations. Larger, standardized, multi-center randomized controlled trials with adequate subgroup representation and extended follow-up periods are essential to establish clinical significance and treatment durability.