The heterogeneity of glymphatic-related MRI alterations in migraine: a cross-sectional multimodal study

Glymphatic dysfunction has been implicated in migraine. However, a comprehensive assessment using noninvasive multimodal magnetic resonance imaging (MRI) to elucidate its potential pathophysiological role is still lacking. A total of 123 participants were enrolled, including 38 patients with episodic migraine (EM), 46 patients with chronic migraine (CM), and 39 healthy controls (HCs). Glymphatic-related MRI measures, including diffusion tensor imaging along the perivascular space (DTI-ALPS) index, choroid plexus volume (CPV), and coupling between blood oxygen level-dependent signals and cerebrospinal fluid signals (BOLD-CSF coupling), were compared across the groups. Regional analyses were performed by hemisphere for DTI-ALPS and CPV metrics, and by network level for BOLD-CSF coupling. Partial correlations and multivariable linear regression were used to assess associations among glymphatic-related MRI measures and with clinical scales. Using general linear models adjusted for age, sex, years of education, and relevant covariates, the left, right, and mean DTI-ALPS index were significantly lower in both EM and CM patients than in HCs after Bonferroni correction for post hoc pairwise comparisons (PBon < 0.01 and PBon < 0.001). CM patients also showed weaker global BOLD-CSF coupling than HCs (PBon < 0.05). At the network level, CM patients showed weaker BOLD-CSF coupling in the dorsal attention network than HCs, but this difference did not survive false discovery rate (FDR) correction. CPV metrics did not differ significantly across groups. Partial correlation analyses revealed negative correlations between the DTI-ALPS index and CPV metrics in CM patients (PFDR < 0.01 and PFDR < 0.001). Negative associations between Headache Impact Test-6 (HIT-6) scores and CPV metrics were observed in EM patients, but these findings did not survive correction for multiple comparisons. Altered DTI-ALPS index and BOLD-CSF coupling with relatively preserved CPV in migraine highlight the need for a multidimensional MRI framework to characterize glymphatic-related alterations.