Non-invasive brain stimulation on clinical symptoms in multiple sclerosis patients: A systematic review and meta-analysis.

ABSTRACT

BACKGROUND: Non-invasive brain stimulation (NIBS) has demonstrated mixed effects on the clinical symptoms of multiple sclerosis. This systematic review and meta-analysis aimed to evaluate the effects of NIBS techniques on the most common symptoms of MS. METHODS: A literature search was performed until October 2022 which included randomized controlled trials and quasi-experimental studies that used sham-controlled NIBS in patients with MS. We calculated the Hedge's effect sizes of each domain of interest and their 95% confidence intervals (95% CIs) and performed random effects meta-analyses. RESULTS: A total of 49 studies were included in the systematic review (944 participants). Forty-four eligible studies were included for quantitative analysis, of which 33 applied transcranial direct current stimulation (tDCS), 9 transcranial magnetic stimulation (TMS), and 2 transcranial random noise stimulation (tRNS). We found a significant decrease in fatigue (ES  - 0.86, 95% CI  - 1.22 to - 0.51, p < 0.0001), pain (ES - 1.91, 95% CI, - 3.64 to - 0.19, p=  0.03) and psychiatric symptoms (ES - 1.44, 95% CI - 2.56 to - 0.32, p = 0.01) in favor of tDCS compared with the sham. On the other hand, there was no strong evidence showing tDCS effectiveness on motor performance and cognition (ES - 0.03, 95% CI - 0.35 to 0.28, p = 0.83 and ES 0.71, 95% CI, - 0.09 to 1.52, p = 0.08, respectively). Regarding TMS, we found a significant decrease in fatigue (ES - 0.45, 95% CI - 0.84 to -0.07, p = 0.02) and spasticity levels (ES - 1.11, 95% CI - 1.48 to - 0.75, p < 0.00001) compared to the sham. However, there was no strong evidence of the effectiveness of TMS on motor performance (ES - 0.39, 95% CI - 0.95 to 0.16, p = 0.16). Finally, there was no significant evidence showing the effectiveness of tRNS on fatigue levels (ES - 0.28, 95% CI - 1.02 to 0.47, p = 0.46) and cognitive improvement (ES - 0.04, 95% CI - 0.6, 0.52, p = 0.88) compared with the sham. CONCLUSIONS: Overall, most studies have investigated the effects of tDCS on MS symptoms, particularly fatigue. The symptom that most benefited from NIBS was fatigue, while the least to benefit was motor performance. In addition, we found that disability score was associated with fatigue improvement. Thus, these findings support the idea that NIBS could have some promising effects on specific MS symptoms. It is also important to underscore that studies are very heterogeneous regarding the parameters of stimulation, and this may also have influenced the effects on some specific behavioral domains.