Idiopathic intracranial hypertension: a step change in understanding the disease mechanisms

The understanding of idiopathic intracranial hypertension (IIH) has evolved over the past few years. Previously, IIH was considered a disease exclusively affecting the neuro-ophthalmic axis, characterized by raised intracranial pressure, headache and papilloedema, and resulting in the risk of severe and permanent visual loss and life-changing disabling headaches. Recent advances have begun to redefine IIH as a probable metabolic disease involving a range of systemic manifestations. More than 95% of individuals affected by the disease are women of reproductive age with obesity. The incidence is rapidly rising and parallels the escalating worldwide obesity rates. Contemporary insights identify associations with insulin resistance, type 2 diabetes and a twofold increased risk of cardiovascular disease in excess of that driven by obesity alone. Adipose distribution in people with IIH, like that in other metabolic diseases, is preferentially centripetal and is associated with changes in intracranial pressure. Evidence now demonstrates adipose tissue dysfunction in people with IIH, involving transcriptional and metabolic priming for lipogenesis and weight gain. Hormonal perturbations are also observed, including a unique phenotype of androgen excess that promotes cerebrospinal fluid secretion. Knowledge of these additional disease features is driving research into novel therapeutic targets and altering the approach to multidisciplinary care. The incidence of idiopathic intracranial hypertension is rapidly rising in line with global obesity rates. This Review summarizes evidence suggesting that the condition is not idiopathic but is instead related to systemic metabolic and hormonal perturbations and should thus be considered a metabolic disease. Key points Idiopathic intracranial hypertension (IIH) is emerging as a probable metabolic disease encompassing a range of systemic manifestations. Key disease features of IIH are broadening to include impaired fertility, gestational diabetes, pre-eclampsia, increased risk of cardiometabolic complications and reversible cognitive dysfunction. Comorbid associated conditions include polycystic ovarian syndrome, obstructive sleep apnoea, anxiety and depression. A positive relationship between headache and intracranial pressure has been observed, and specific signalling pathways have been speculated to be mechanistic drivers of IIH headaches. Weight loss is established as the only disease-modifying therapy, with bariatric sur