Glymphatic Dysfunction in High-Frequency Episodic Migraine: Evidence From DTI-ALPS and Exploratory White Matter Analysis.

OBJECTIVE: To explore glymphatic function and white matter microstructural alterations in high-frequency episodic migraine (HFEM). METHODS: This study included 31 healthy controls (HCs), 44 patients with low-frequency episodic migraine (LFEM), and 27 with HFEM. Glymphatic function was indirectly assessed using diffusion tensor image analysis along the perivascular space (DTI-ALPS), while white matter integrity was examined using tract-based spatial statistics (TBSS). RESULTS: The ALPS index was higher in LFEM than HFEM. In the combined migraine cohort, it was negatively associated with attack frequency, showed a trend toward a negative association with the Migraine Disability Assessment Scale (MIDAS) score, and was positively associated with the visual analogue scale (VAS) score. Exploratory mediation analysis indicated that attack frequency showed a significant statistical mediating role in the association between the ALPS index and MIDAS score. No significant between-group differences in white matter FA survived correction for multiple comparisons in the TBSS analysis. CONCLUSIONS: The ALPS index showed a frequency-related pattern, with relatively higher values in LFEM and lower values in HFEM, suggesting differences in glymphatic function across attack-frequency stages of episodic migraine. Attack frequency showed a significant statistical mediating role in the association between glymphatic function and migraine-related disability. The exploratory TBSS analysis did not identify significant white matter FA differences after correction for multiple comparisons.