Glymphatic system dysfunction in epilepsy: a review of mechanisms and clinical evidence

The glymphatic system is a glial-dependent waste clearance pathway, a perivascular network responsible for the clearance of metabolic waste and neurotoxic proteins through cerebrospinal fluid-interstitial fluid exchange. It may play a critical role in the pathophysiology of various neurological diseases, including epilepsy. Neuroinflammation and blood-brain barrier disruption associated with seizures may impair glymphatic function, while impaired waste clearance may, in turn, facilitate epileptogenesis. Diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) has emerged as a noninvasive imaging marker of glymphatic function. Patients with focal and generalized epilepsy consistently demonstrate reduced DTI-ALPS indices in comparison to healthy controls, with greater impairment associated with older age, longer disease duration, cognitive dysfunction, and drug-resistant epilepsy.