Harriott, Andrea M.

White matter hyperintensities (WMHs) are common MRI findings and established markers of cerebral small-vessel disease associated with stroke, cognitive decline, and vascular risk factors. Several studies have suggested that individuals with migraine, particularly migraine with aura (MA), may have an increased burden of WMHs compared with individuals without migraine. Early population-based studies and meta-analyses reported a higher prevalence of WMHs in migraine, whereas more recent large neuroimaging cohorts have reported conflicting findings or no association. Differences in study design, migraine ascertainment, MRI acquisition parameters, WMH quantification methods, and adjustment for vascular risk factors complicate interpretation of the existing literature. An updated systematic review focusing on methodologically comparable population-based cohorts is therefore warranted. The primary objective of this systematic review and meta-analysis is to determine whether adults with migraine have a higher prevalence or burden of WMHs on MRI than non-migraine controls. Secondary objectives include evaluating associations according to migraine subtype (MA vs. migraine without aura and episodic vs. chronic migraine), sex, WMH location, age, and MRI acquisition or WMH quantification methods, as well as examining longitudinal WMH progression where available. We will include population-based cross-sectional or longitudinal cohort studies of adults undergoing brain MRI with sequences suitable for WMH detection. Migraine exposure may be defined using International Classification of Headache Disorders criteria, structured interviews, validated questionnaires, physician diagnosis, or ICD codes. Controls must originate from the same source population. Searches will be conducted in PubMed/MEDLINE, EMBASE, Web of Science, and Scopus. Study selection, data extraction, and risk-of-bias assessment will be performed independently by two reviewers using Covidence, and risk of bias will be evaluated using the ROBINS-E tool. Because WMH burden is reported using heterogeneous metrics across studies, the primary synthesis will use a precision-weighted direction-of-effect approach, in which each study contributes the direction of the association, weighted by statistical precision. Where sufficiently comparable outcomes are available, random-effects meta-analysis will be performed. Sensitivity analyses will explore the influence of diagnostic criteria, MRI field strength, and confounder adjustment. This review will provide an updated and methodologically rigorous synthesis of the evidence on the association between migraine and WMHs.

Abstract Objective The objective was to determine if migraine is independently associated with a greater odds of spontaneous coronary artery dissection (SCAD) in a case–control study. Background There is growing evidence that migraine is associated with SCAD, a non‐atherosclerotic, non‐traumatic cause of myocardial infarction. However, few studies have examined the independent association between migraine and SCAD. Methods A total of 1295 SCAD cases and 1291 (1:1) age, sex, and race/ethnicity matched controls presenting to the Boston, Massachusetts area, using the International Classification of Diseases ninth revision and 10th revision codes from our Research Patient Data Registry, were identified between the years 1990 and 2022. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated. For mediation, total effects, natural direct, and indirect effects were estimated using causal inference. Receiver operating characteristic (ROC) curves and area under the curve (AUC) was used to determine predictive power. Statistical significance was defined as p < 0.05. Results Adjusting for age, sex, and race/ethnicity, the data demonstrated an almost two‐fold increased odds of SCAD in patients with migraine (aOR 1.96, 95% CI 1.48–2.6; p < 0.001). There was no effect of aura phenotype on this association. Fibromuscular dysplasia (FMD) was found only in patients with SCAD ( n = 133). After accounting for vascular risk factors, there was no longer an independent association between migraine and SCAD (aOR 0.90, 95% CI 0.63–1.29; p = 0.568). Using a model that adjusted for only demographic variables produced a ROC curve with the lowest predictive power (AUC 0.55) for SCAD, while the vascular risk factor‐adjusted model had a higher predictive power (AUC 0.83). Hypertension appeared to mediate some of the effect of migraine on SCAD (proportion of effect mediated 0.70). FMD was highly associated with an increased risk of SCAD. There remained no independent association between SCAD and migraine when FMD was included in the model. Conclusions The migraine–SCAD association can be partially attributed to the connection between migraine and vascular comorbidities including hypertension and FMD.