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Objective: To compare the effects of anodal trans-cranial direct current stimulation (a-tDCS) over primary motor and dorsolateral prefrontal cortices on Fatigue Severity Scale and its lasting effect on fatigue reduction and improvement in quality of life in patients with multiple sclerosis. Design: A randomized, double-blinded, sham-controlled parallel clinical trial study. Setting: Neurological physiotherapy clinics. Subjects: Thirty-nine participants were randomly assigned to three groups: dorsolateral prefrontal cortex a-tDCS, primary motor a-tDCS (experimental groups) and sham a-tDCS. Finally, 36 participants completed the whole study ( n = 12 in each group). Interventions: Participants in the experimental groups received six-session a-tDCS (1.5 mA, 20 minutes) during two weeks (three sessions per week). The sham group received six sessions of 20-minute sham stimulation. Main measures: The Fatigue Severity Scale and quality of life were assessed before, immediately and four weeks after the intervention. Results: Findings indicated a significant reduction in the Fatigue Severity Scale and a significant increase in the quality of life in both experimental groups, immediately after the intervention ( P < 0.001), while Fatigue Severity Scale and quality of life changes were not significant in the sham a-tDCS group ( P > 0.05). In addition, improvement of the variables remained four weeks after the intervention in dorsolateral prefrontal cortex a-tDCS (mean differences (95% confidence interval): 0.03 (−0.63 to 0.68) as compared to primary motor (−0.62 (−0.11 to −1.14) and sham a-tDCS groups (−0.47 (−1.37 to 0.43)). Conclusion: Both primary motor and dorsolateral prefrontal cortex a-tDCS as compared to sham intervention can immediately improve fatigue and quality of life. However, the effects last up to four weeks only by the dorsolateral prefrontal cortex a-tDCS.

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III.