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

Abstract

Background: 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. Methods: In this prospective age- and sex-matched controlled study, 30 migraine patients receiving either anti-CGRP mAbs (fremanezumab) (n = 15) or oral preventive medications (n = 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. Results: 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 (p = 0.026) and left rostral middle frontal cortex (p = 0.007). These cortical changes correlated with treatment response to anti-CGRP mAbs (β = -0.429, 95% CI [-0.777, -0.081], p = 0.016 in the right caudal anterior cingulate; β = -0.224, 95% CI [-0.390, -0.057], p = 0.008 in the left rostral middle frontal cortex). Conclusions: 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.

Keywords: anti-calcitonin gene-related peptide monoclonal antibody; cortical thickness; migraine; prospective study; treatment.

Figure 1

Flow diagram of the study.

Figure 2

Cortical thickness changes in anti-CGRP responders versus non-responders. (A) The right caudal anterior cingulate cortex showing significant cortical thinning in responders compared to non-responders (B) The left rostral middle frontal cortex showing significant reduction in cortical thickness in responders. Brain surfaces are displayed with anatomical labels and group differences in cortical thickness are visualized.