ObjectiveTo evaluate the association between the cerebrovascular reactivity to carbon dioxide (CO₂-CVR) and the deep white matter hyperintensity (WMH) burden in patients with migraine.MethodsA total of 86 nonelderly patients with episodic migraine without vascular risk factors and 35 headache-free controls underwent 3T MRI. Deep WMHs were quantified with a segmentation method developed for nonelderly migraineurs. The interictal CO₂-CVR was measured with transcranial Doppler with the breath-holding method. The mean breath-holding index of the bilateral middle cerebral arteries (MCA-BHI) was square root transformed and analyzed with univariate and multivariate logistic regression models to determine its association with the highest tertiles of deep WMH burden (number and volume).ResultsA low MCA-BHI was independently associated with the highest tertile of deep WMH number in patients with migraine (adjusted odds ratio [OR] 0.02, 95% confidence interval [CI] 0.0007–0.63, p = 0.026). In controls, the MCA-BHI was not associated with deep WMH number. Interaction analysis revealed that migraine modified the effect of MCA-BHI on deep WMH number (p for interaction = 0.029). The MCA-BHI was not associated with increased deep WMH volume in both patients and controls. Age was independently associated with deep WMH volume in patients (adjusted OR 1.07, 95% CI 1.004–1.15, p = 0.037).ConclusionsIn this study, we found a migraine-specific association between a reduced CVR to apnea and increased number of deep WMHs in healthy, nonelderly patients with migraine. A dysfunctional vascular response to apnea may predispose migraineurs to an increased risk of WMHs.