Cortical Thickness Changes in Migraine Patients Treated with Anti-Calcitonin Gene-Related Peptide Monoclonal Antibodies: A Prospective Age- and Sex-Matched Controlled Study

<b>Background:</b> Migraine is associated with structural brain abnormalities, including cortical thickness changes. Anti-calcitonin gene-related peptide monoclonal antibodies (anti-CGRP mAbs) are a novel therapy for migraine prevention, but their effects on cortical structures are poorly understood. <b>Methods:</b> In this prospective age- and sex-matched controlled study, 30 migraine patients receiving either anti-CGRP mAbs (fremanezumab) (<i>n</i> = 15) or oral preventive medications (<i>n</i> = 15) underwent 3T MRI scans before and after treatment. Treatment response was defined as a ≥50% reduction in monthly headache days after 3 months. Cortical thickness was analyzed across 46 cortical regions, comparing patients treated with anti-CGRP mAbs to those receiving oral preventive treatment, as well as responders to non-responders within the anti-CGRP group. <b>Results:</b> Cortical thickness changes did not differ significantly between the anti-CGRP and oral treatment groups. However, among patients receiving anti-CGRP mAbs, responders showed significant decreases in cortical thickness compared to non-responders, particularly in the right caudal anterior cingulate (<i>p</i> = 0.026) and left rostral middle frontal cortex (<i>p</i> = 0.007). These cortical changes correlated with treatment response to anti-CGRP mAbs (β = -0.429, 95% CI [-0.777, -0.081], <i>p</i> = 0.016 in the right caudal anterior cingulate; β = -0.224, 95% CI [-0.390, -0.057], <i>p</i> = 0.008 in the left rostral middle frontal cortex). <b>Conclusions:</b> This exploratory study, based on a small sample size, suggests that cortical thickness changes may be associated with treatment response to anti-CGRP mAbs rather than with CGRP mAb treatment itself. Further studies with larger cohorts are needed to confirm these findings.