Impaired meningeal lymphatic drainage correlates with headache intensity in episodic migraine
Xiao Ren, Han Wang, Yi He, Chengsi Wu, Kaixiao Chen, Fuqing Zhou, Zhihua Xiao, Yi Liu, Yonggang Wang, Daojun Hong
Abstract
BACKGROUND: Migraine pathophysiology involves trigeminovascular activation and neuroinflammation, with neuropeptides such as calcitonin gene-related peptide (CGRP) playing a key role. Growing evidence implicates glymphatic system dysfunction, particularly meningeal lymphatic vessel (mLV) mediated cerebrospinal fluid (CSF) and waste clearance, as a potential contributor. However, multi-level imaging assessments glymphatic system in episodic migraine (EM) remain limited. METHODS: We prospectively enrolled 38 EM patients and 22 age- and sex- comparable healthy controls (HCs). Glymphatic function was systematically evaluated using 3T MRI. Dynamic contrast-enhanced MRI (DCE-MRI) was used to quantify mLV drainage kinetics including Wash-in rate, Time-to-Peak (TTP), Initial Area Under Curve (IAUC) and Ktrans along the superior sagittal sinus (mLV-SSS) and sigmoid sinus (mLV-SS). Diffusion tensor imaging along perivascular spaces (DTI-ALPS) index was used to assess parenchymal interstitial fluid dynamics. Structural MRI was used to rate enlarged perivascular spaces (EPVS) in centrum semiovale (CSO), basal ganglia (BG), and midbrain (MB). Finally, the correlations among clinical characteristics and neuroimaging data were analyzed. RESULTS: Compared to HCs, EM patients showed impaired meningeal lymphatic drainage on DCE-MRI, with reduced wash-in rate, prolonged TTP, and lower IAUC and Ktrans in both mLV-SSS and mLV-SS. Within the EM cohort, these kinetic abnormalities were associated with higher headache intensity on the visual analogue scale (VAS). Although overall DTI-ALPS index did not differ between groups. but high-grade EPVS in the centrum semiovale was more prevalent in EM, with no between-group differences in the basal ganglia or midbrain. CONCLUSION: We demonstrate in vivo impairment of meningeal lymphatic drainage in EM, linked to headache intensity. While DTI-ALPS index in parenchymal glymphatic flow was not altered, the increased burden of centrum semiovale EPVS provide complementary evidence for glymphatic system involvement. These findings support glymphatic involvement and highlight mLVs as a potential therapeutic target in early stage of migraine.