Glymphatic System Dysfunction in Epilepsy: Clinical and Translational Perspectives

Area of Science:

• Neuroscience
• Neurology
• Biomedical Engineering

Background:

• Epilepsy traditionally viewed as neuronal hyperexcitability.
• Emerging evidence links seizures to broader brain homeostasis disturbances (metabolic, inflammatory, vascular, sleep).
• Brain-wide clearance mechanisms, like the glymphatic system, are understudied in epilepsy.

Purpose of the Study:

• Review current knowledge of glymphatic system anatomy and physiology.
• Synthesize evidence of glymphatic dysfunction in epilepsy.
• Discuss clinical implications and therapeutic potential of glymphatic modulation.

Main Methods:

• Literature review focusing on glymphatic system function and dysfunction.
• Synthesis of neuroimaging advances related to glymphatic transport.
• Analysis of emerging evidence linking glymphatic impairment to epilepsy syndromes.

Main Results:

• Glymphatic system dysfunction is implicated across various epilepsy syndromes.
• Impaired waste clearance correlates with disease burden, cognitive decline, and treatment outcomes.
• Sleep-wake state significantly modulates glymphatic transport, relevant to epilepsy.

Conclusions:

• Glymphatic system dysfunction is a system-level abnormality in epilepsy.
• This offers a framework integrating metabolic, vascular, and sleep aspects of epilepsy.
• Modulating glymphatic function presents potential therapeutic strategies for epilepsy.