The Glymphatic System in Idiopathic Intracranial Hypertension

Despite advances in clarifying hormonal and metabolic factors relevant to the pathophysiology of idiopathic intracranial hypertension (IIH), its mechanism remains incompletely defined. Recognition of the glymphatic system in 2012 fostered several hypotheses regarding roles it might play in IIH. This State-of-the-Art Review describes the glymphatic system's anatomy and physiology, factors relevant both to the glymphatic system and IIH, methods of obtaining experimental evidence, and how the existing evidence has tested and shaped hypotheses relating glymphatic transit and IIH.

A literature search was conducted on December 10, 2025, to identify publications related to the glymphatic system in IIH, using PubMed, Embase, Web of Science, and the Cochrane Library. Snowballing and reverse snowballing were used to identify additional references relevant to explicitly stated links between the glymphatic system and IIH. References were screened using Covidence by 2 independent reviewers.

One hundred thirty-six records were identified; 60 were duplicate, 27 were excluded in screening due to lack of applicability. Among the 49 retrieved, 17 were excluded due to incorrect patient population (8), reviews without critique, expert opinion, or new hypotheses (8), or language (1). Thirty-two were included in this review.

Three categories of hypothesis relating to glymphatic transit in IIH were identified in the literature: (1) glymphatic dysfunction causes IIH, (2) veno-glymphatic dysfunction causes IIH, and (3) glymphatic function is altered but adaptive in IIH with clinical decompensation when its fluid transit capacity is overwhelmed. While glymphatic transit seems not to be normal in IIH, recent evidence suggesting dynamic transit across the disease course without clear correlation with intracranial pressure favors a novel hypothesis: that glymphatic changes may be secondary to IIH without playing a central role in its pathogenesis. Further prospective and ideally multimodal work is required, taking into account an increasing number of potentially relevant variables which may influence glymphatic transit in IIH, including disease duration, venous sinus stenosis, and treatment status.