Signs of Cortical Inflammation in Migraine Measured with Quantitative Magnetic Resonance Imaging: A Registry for Migraine (REFORM) Study

Objective The involvement of cortical inflammation in migraine, particularly migraine with aura, has been a subject of considerable interest, but has proved challenging to demonstrate. We aimed to detect and characterize signs of cortical inflammation in adults with migraine using a novel, multimodal magnetic resonance imaging (MRI) technique. Methods We used T2 mapping to measure water content/cellularity, T1 mapping to measure tissue microstructure integrity, and apparent diffusion coefficient (ADC) mapping to measure intra‐ or extracellular edema. We compared these values between participants with migraine (with and without aura) and healthy controls using general linear models adjusted for age and sex. Result Two hundred ninety‐six adult participants with migraine and 155 age‐ and sex‐matched healthy controls provided eligible imaging data. Among the participants with migraine, 103 had migraine with aura, 180 chronic migraine, and 88 were ictal during the scan. Participants with migraine had higher quantitative T2 (qT2) in the left occipital cortex than healthy controls ( p < 0.0001). In migraine with aura, the higher qT2 was more widespread and located bilaterally in the occipital cortices, compared with controls (left, p < 0.0001; right p = 0.004). Post‐hoc analysis revealed overlapping ADC elevations in migraine with aura compared with controls ( p = 0.0069). Interpretation Quantitative MRI changes compatible with cortical inflammation were detected in participants with migraine, and appeared driven by the subgroup with aura. Higher occipital qT2 in migraine with aura might represent either extracellular edema or accumulation of inflammatory microglia or astrocytes. These results support the importance of cortical inflammation in migraine pathophysiology, particularly in migraine with aura. ANN NEUROL 2025