Association between headache laterality in migraine and hemispheric distribution of white matter hyperintensities on MRI

Objective The goal of this study was to clarify whether headache laterality in patients with migraine with "typically" left- or right-sided headache during attacks is associated with the distribution of hemispheric white matter hyperintensities on brain MRI. Background Cerebral white matter hyperintensities (WMHs) are hyperintense lesions visible on brain MRI believed to result from microvascular disease. WMHs occur four times more commonly in patients with migraine, though the cause and relevance of this association are currently unclear. Methods This is a cross-sectional study in which the MRI of patients with migraine with typically left- or right-sided headache during attacks was evaluated. All WMHs were identified, and their location documented by reviewers blinded to headache laterality. We used Chi-square, Wilcoxon rank-sum, and Poisson regression to compare the characteristics of the two groups and multiple regression models to estimate the association of headache laterality with hemispheric WMH distribution while controlling for potential confounders. Results Of 5,627 patients with migraine screened, 340 had typically left- or right-sided headache during attacks. Of these, 159 patients had an eligible brain MRI for review. Patients with left-sided headache were more likely to have hypertension (30.8% vs. 14.5%; p = 0.020) but less likely to smoke cigarettes (34.1% vs. 50.7%; p = 0.036) compared to patients with right-sided headache. Left-sided headache was associated with a higher burden of WMHs overall (9.8 vs. 6.2; p < 0.001), as well as in the left brain (5.1 vs. 3.3; p < 0.001) and right brain (4.7 vs. 3.0; p < 0.001) independently, and a higher periventricular Fazekas score (0.9 vs. 0.7; p = 0.033), compared to patients with right-sided headache. Headache laterality remained significantly associated with hemispheric WMH distribution after adjusting for age, hypertension, diabetes, and cigarette smoking. Conclusion Patients with typically left-sided headache during migraine attacks have a higher burden of WMHs, both on the left and right sides of the brain, and higher periventricular Fazekas score, than patients with typically right-sided headache during attacks.