Cerebrovascular reactivity and deep white matter hyperintensities in migraine: A prospective CO₂ targeting study

Several studies suggested the association of migraine with deep white matter hyperintensities (WMHs). We aimed to explore the cerebrovascular reactivity (CVR), deep WMH burden, and their association in patients with migraine using a state-of-the-art methodology. A total of 31 patients with migraine without aura and 31 age/sex-matched controls underwent 3T MRI with prospective end-tidal carbon dioxide (CO₂) targeting. We quantified deep WMH clusters using an automated segmentation tool and measured voxel-wise CVR by changes in blood oxygen level-dependent signal fitted to subjects' end-tidal CO₂. The association of migraine and CVR with the presence of WMH in each voxel and interaction of migraine and CVR on WMH were analysed. Patients had a higher number of deep WMHs than controls (p = 0.015). Migraine and reduced CVR were associated with increased probability of having WMHs in each voxel (adjusted OR 30.78 [95% CI 1.89-500.53], p = 0.016 and adjusted OR 0.30 [0.29-0.32], p < 0.001, respectively). Migraine had an effect modification on CVR on deep WMHs (p for interaction <0.001): i.e. the association between CVR and WMH was greater in patients than in controls. We suggest that the migraine-WMH association can be explained by the effect modification on the CVR.