Evolving evidence in adult idiopathic intracranial hypertension: pathophysiology and management

Abstract

Idiopathic intracranial hypertension (IIH) is a rare but important disease associated with significant morbidity. There is an expected rise in prevalence in line with the escalating global burden of obesity. Modern revisions in the terminology and diagnostic criteria for IIH help guide clinicians in investigations and researchers in standardising recruitment criteria for clinical trials. The pathophysiology of IIH is incompletely characterised; suggested underpinning mechanisms include the role of cerebrospinal fluid regulation as well as metabolic and endocrinological perspectives. Recent treatment trials are providing insights into the management but debate still surrounds key areas in treatment. This review will provide an up-to-date discussion on the potential pathogenic mechanisms and management of IIH.

Keywords: BENIGN INTRACRAN HYP; CSF DYNAMICS; HEADACHE; NEUROOPHTHALMOLOGY.

Figure 1

Schematic diagram of the possible pathophysiological mechanisms in idiopathic intracranial hypertension (IIH). Cerebrospinal fluid (CSF) is produced mainly by the choroid plexus epithelial cells, with a small amount being secreted by ependymal cells that line the ventricular system. Classically, CSF was thought to drain predominantly through the subarachnoid space through arachnoid granulations into the superior sagittal sinus. Evidence also suggests CSF drains through the cribriform plate along cranial nerves into the nasal lymphatics (yellow). The most recent hypothesis proposes bulk flow of fluid along perivascular routes (glymphatic pathway) which is cleared from the brain into the subarachnoid CSF, bloodstream or cervical lymphatics. Supporting this concept is the recent discovery of lymphatic vessels (yellow) in the dura that drain into the deep cervical lymph nodes.

Figure 2

(A) MRI T1-weighted sagittal imaging demonstrating an empty sella (the pituitary gland has been flattened against the wall of the sella). (B) MRI T2-weighted axial image demonstrating flattening of the posterior globes at the insertion of the optic nerves, protrusion of the optic nerve head into the vitreous and increased fluid in the optic nerve sheath complex bilaterally. (C) MRI T2-weighted axial image demonstrating tortuosity (kinking) of the intraorbital optic nerve on the left with fluid in the associated optic nerve sheath complex. (D) MR venography (posterior view) demonstrating a longitudinal extensive left transverse sinus stenosis (extraluminal appearance).

Figure 3

Comprises three patients (A–C). All have a composite of colour fundus photograph on left hand side. Spectral domain (SD) optical coherence tomography (OCT) cross-section image through the optic nerve head, above. The extent on the retinal nerve fibre layer is depicted between the fine red (internal limiting membrane (ILM)) and green lines in this grey scale image. SD-OCT retinal nerve fiber layer (RNFL) thickness line graph showing RNFL thickness values, below. The fine black line depicting the patient's data, and the block colours (green, yellow, red) showing the normative data. Humphrey visual field 24-2 grey scale image on right. VFI, visual field indicator; MD, mean deviation; PSD, pattern SD. Patient A, a newly diagnosed patient with IIH, showing Frisen grade 3, there is obscuration of more than one major vessel leaving the disc, there is a circumferential halo and elevation of all borders. Paton's lines (curvilinear chorioretinal folds adjacent to the temporal (left hand side) of the optic disc margin) are evident. Patient B, a newly diagnosed patient with IIH with Frisen grade 2 there is no major vessel obscured. Circumferential halo and elevation of the nasal border only. Patient C, a treated patient with IIH who has resolved papilloedema (Frisen grade 0). There is reduction in the RNFL thickness which is due to resolution of swelling, but also axonal loss. There is a centrocecal visual field defect.