Transcranial Direct Current Stimulation May Benefit Patients With MS

Maggie L. Shaw

With most current therapies for patients with multiple sclerosis (MS) targeting disease progression, a recent review evaluated transcranial direct current stimulation’s ability to improve certain disease symptoms.

With most current therapies for patients with multiple sclerosis (MS) targeting disease progression, a recent review evaluated the ability of transcranial direct current stimulation (tDCS) to improve 4 disease symptoms: cognitive impairment, mood disturbance, pain, and fatigue.

The results of the review and meta-analysis, published in Frontiers in Neurology, demonstrate that although patients receiving tDCS showed symptom improvement in the 4 areas, cognition and fatigue results were affected by the specific assessment method used.

“Specifically in patients with MS, studies suggest that tDCS could serve as a promising tool to improve cognition, neuropathic pain, mood, and fatigue,” the authors stated. “However, the methodological discrepancies across these trials have yielded conflicting results and therefore a lack of consensus.”

Their goal with their review was to drill down to clearer guidelines on tDCS, and their final analysis encompassed 17 articles written in English—published between January 1990 and May 2020 on PubMed, Medline, and Web of Science—and 383 study participants, 66% of whom had relapsing-remitting MS. Four articles each evaluated cognition and mood, 3 assessed pain, 2 investigated mood status, and 14 assessed fatigue.

For cognition, whereas a strong effect size of 1.15 (95% CI, 0.20-2.10; P = .01) was seen with the Symbol Digit Modalities Test (SDMT), it was much weaker for the Attention Network Test (ANT), at –0.49 (95% CI, −0.97 to −0.02; P = .04). In addition, there was no heterogeneity among the ANT studies (Q = 3.42; I2 = 41.55; P = .18). Publication bias was deemed absent.

When the effect of tDCS on mood was evaluated, a strong effect was again seen, of 0.92 (95% CI, –0.03 to 1.88; P = .05), and heterogeneity was seen across the studies (Q = 12.08; I2 = 75.17; P = .007). Publication bias was not seen, according to rank correlation (tau = 0.33; P = .49)

The measure of pain had a moderate mean effect size, at 0.59 (95% CI, 0.08-1.10; P = .02), and neither heterogeneity (Q = 3.49; I2 = 42.82; P = .02) nor publication bias (tau = 0.00; P = 1.00) were found.

A mean effect size of 0.60 (95% CI, 0.31-0.89; P < .001) was seen for fatigue, along with heterogeneity (Q = 38.45; I2 = 55.79; P = .002) across the 14 articles and publication bias (tau = 0.39; P = .02) by rank correlation. However, because there was such a variety in the effect sizes within these articles, the authors performed subgroup analyses based on the stimulation intensity (low: < 2 mA vs high: > 2 mA) and outcomes measures (Fatigue Severity Scale [FSS] vs Modified Fatigue Impact Scale [MFIS] vs other outcomes for fatigue) they applied.

Mean effect size ranged from 0.60 (95% CI, 0.25-0.95; P = .001) in studies with a low-intensity (< 2 mA) tDCS to 0.62 (95% CI, 0.05-1.19; P =.03) in studies with a high-intensity tDCS. And for the outcomes measures, the mean effect size ranged from 0.31 (95% CI, 0.03-0.60; P = .03) for MFIS to 0.53 (95% CI, 0.23-0.82; P < .001) for other fatigue outcomes to 1.14 (95% CI, 0.68-1.60; P < .001) for FSS.

The authors note that their findings only suggest potential benefits of tDCS regarding cognition, mood disturbance, pain, and fatigue associated with MS, and that ongoing investigation into tDCS is important, especially regarding its longer-term risks and benefits and because individual response can vary.

“This meta-analysis suggests preliminary evidence of favorable effects of tDCS on cognition, mood disturbance, pain, and fatigue in MS,” they conclude. “Further well-designed studies are necessary to determine the neural plasticity changes induced by tDCS, optimize stimulation protocol and identify the subgroups of patients who would benefit most.”


Hsu WY, Cheng CH, Zanto TP, Gazzaley A, Bove RM. Effects of transcranial direct current stimulation on cognition, mood, pain, and fatigue in multiple sclerosis: a systematic review and meta-analysis. Front Neurol. Published online March 8, 2021. doi:10.3389/fneur.2021.626113