The emerging role of the meningeal lymphatic and glymphatic systems in migraine pathophysiology: a systematic review

Migraine is a common, debilitating neurological disorder of unclear pathophysiology. Recent evidence has implicated impaired meningeal lymphatic function and its interaction with the glymphatic system in the development of neuroinflammation and pain sensitization. This systematic review aimed to summarize existing evidence on the role of the meningeal lymphatic and glymphatic systems in migraine pathophysiology. Following the PRISMA 2020 recommendations, we searched PubMed, Web of Science, and Scopus from inception to December 15, 2025. Inclusion criteria comprised human or animal studies examining meningeal lymphatic or glymphatic function in migraine or validated migraine animal models. SYRCLE’s risk of bias tool for animal studies and the Joanna Briggs Institute (JBI) critical appraisal tools were used for quality assessment. The search yielded a total number of 457 records, out of which 10 articles fulfilled the eligibility criteria. These comprised six imaging studies conducted on human populations and four preclinical studies performed on animal models. Studies using dynamic contrast-enhanced (DCE)-MRI have shown changes in lymphatic enhancement characteristics in both episodic and chronic migraines. Diffusion tensor imaging along perivascular spaces (DTI-ALPS) yielded heterogeneous findings, with abnormalities more consistently observed in chronic and high-frequency migraine. Preclinical models demonstrated that cortical spreading depression, nitroglycerin exposure, and familial hemiplegic migraine mutations impaired glymphatic influx and reduced cerebrospinal fluid efflux through meningeal lymphatic vessels. Initial research has shown that altered lymphatic and glymphatic systems may be related to migraine. Nonetheless, there is no existing literature on whether these conditions can be considered causative agents for migraines. There is a need for longitudinal imaging studies in a larger population. PROSPERO ID: CRD420251266296.