Role of the glymphatic system in idiopathic intracranial hypertension

Abstract

This review discusses the potential significance of glymphatic system dysfunction in the pathophysiology of idiopathic intracranial hypertension (IIH). IIH is a clinical syndrome characterised by signs and symptoms which arise from raised intracranial pressure (ICP), in the absence of a clear primary cause of intracranial hypertension. The underlying pathophysiological mechanisms driving IIH remain unclear and raised cerebrospinal fluid (CSF) secretion, reduced fluid drainage, and elevated cerebral venous sinus pressure do not fully explain the condition's aetiology. There is a growing literature which implicates the glymphatic system, a mechanism by which fluid moves into the brain parenchyma via peri-arterial channels and out via perivenous spaces and brain lymphatics, in IIH pathogenesis. We propose that aquaporin-4 (AQP4) changes, neurogliovascular unit disruption, a pro-inflammatory CSF profile and impaired glymphatic outflow are the main mechanisms driving glymphatic dysfunction in IIH. However, it remains unclear which of these mechanisms are primary causes and which are secondary effects. Further studies using CSF tracers, electron microscopy, and immunohistochemistry are needed to better evaluate the cellular and molecular pathology associated with IIH at different timepoints in the disease course, which will help elucidate the mechanistic role of the glymphatic system in the condition's pathogenesis.

Keywords: Aquaporin-4; Cerebrospinal fluid dynamics; Glymphatic system; Idiopathic intracranial hypertension; Neurogliovascular unit.