No Changes in Functional Connectivity After Dimethyl Fumarate Treatment in Multiple Sclerosis

Introduction: Despite the increased availability of disease-modifying therapies (DMTs) for treating relapsing-remitting multiple sclerosis (RR-MS), only a few studies have evaluated DMT-associated brain functional changes. Methods: We investigated whether significant resting-state functional connectivity (FC) changes occurred in RR-MS patients after 6 and 12 months of dimethyl fumarate (DMF) treatment using both a seed-based and data-driven approach. Results: Thirty patients were followed up after 6 months of therapy, and 27 of them reached a 12-month follow-up. Three patients at baseline and only one after 12 months showed gadolinium-enhancing lesions. We did not find any significant FC changes after therapy at either time point. After 12 months of DMF, we observed relatively modest brain volume loss and a significant improvement in Paced Auditory Serial Addition Test 3 s and 25-Foot Walk Test scores. Conclusion: The absence of FC changes could be due to the low degree of baseline inflammation in our patients, though we cannot exclude that more time may be required to observe such changes. No FC changes may reflect a beneficial effect of DMF therapy, as supported by conventional MRI findings and clinical improvement.