A unifying disease model of idiopathic intracranial hypertension: A narrative review

The aim of this study was to synthesize a unifying disease model for idiopathic intracranial hypertension (IIH) based on the current literature.

IIH is a complex neurological condition defined by abnormally elevated intracranial pressure in the absence of an identifiable etiology. Although various causal mechanisms are thought to contribute to the development of IIH pathophysiology, how they interrelate remains poorly understood.

Here, we synthesize emerging evidence indicating that cerebrospinal fluid (CSF) and interstitial fluid (ISF) dyshomeostasis drive IIH pathology and how alterations in neurofluid regulation are associated with transverse sinus stenosis, brain volume, and the cerebral glymphatic system.

We propose a unified disease model where obesity-mediated metabolic dysfunction results in impaired glymphatic clearance with consequential accumulation of brain ISF with resultant increased brain volume. This subsequently results in extramural compression of the dural venous sinuses. Dural venous stenosis causes venous hypertension with further veno-glymphatic congestion and a positive feedback loop on impaired glymphatic drainage, which further perpetuates interstitial fluid stasis and increased brain volume with increased intracranial pressure.

The presented unifying disease model integrates various observations and suspected drivers of the condition into a cohesive framework of IIH pathogenesis that may be used for future investigations and clinical conceptualization.