The Glymphatic System in Idiopathic Intracranial Hypertension

Area of Science:

• Neurology
• Physiology
• Pathophysiology

Background:

• Idiopathic intracranial hypertension (IIH) mechanism remains unclear despite hormonal and metabolic insights.
• The glymphatic system, recognized in 2012, has generated hypotheses regarding its role in IIH.
• This review examines glymphatic system anatomy, physiology, and its connection to IIH.

Purpose of the Study:

• To review the current understanding of the glymphatic system's role in idiopathic intracranial hypertension (IIH).
• To analyze hypotheses linking glymphatic transit to IIH pathogenesis.
• To identify gaps in knowledge and suggest future research directions.

Main Methods:

• A comprehensive literature search was performed across major databases (PubMed, Embase, Web of Science, Cochrane Library) on December 10, 2025.
• Snowballing and reverse snowballing techniques were employed to identify relevant studies.
• Two independent reviewers screened and selected 32 relevant publications for this state-of-the-art review.

Main Results:

• Thirty-two studies were included after screening 136 records, with duplicates and irrelevant articles excluded.
• Three main hypotheses emerged: glymphatic dysfunction causing IIH, veno-glymphatic dysfunction causing IIH, and adaptive glymphatic changes.
• Evidence suggests glymphatic transit is altered in IIH but may be secondary and adaptive, not causative.

Conclusions:

• Current hypotheses suggest glymphatic transit is altered in IIH, but evidence increasingly points to secondary changes rather than a primary pathogenic role.
• The dynamic nature of glymphatic transit across the disease course, without clear intracranial pressure correlation, supports a secondary role.
• Future research should be prospective, multimodal, and consider variables like disease duration, venous sinus stenosis, and treatment status.