Idiopathic Intracranial Hypertension, Basic Concepts and Emerging Molecular, Genetic, and Immunological Therapies

Idiopathic intracranial hypertension (IIH) is a chronic disorder characterized by elevated intracranial pressure (ICP) without an identifiable intracranial mass lesion or abnormal cerebrospinal fluid (CSF) composition. Traditionally viewed as a disorder of impaired CSF absorption or venous outflow obstruction, IIH predominantly affects women of reproductive age with obesity and remains a major cause of preventable visual loss. Emerging evidence, however, suggests that IIH is driven by a broader biologic framework involving dysregulated CSF secretion, metabolic and endocrine dysfunction, immune activation, and genetic susceptibility.

This narrative review synthesizes recent advances in the molecular and cellular pathophysiology of IIH and examines emerging mechanism-based therapeutic strategies. Particular emphasis is placed on choroid plexus biology and hormonally regulated CSF hypersecretion mediated through glucocorticoid metabolism via 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) and androgen signaling pathways that modulate Na⁺/K⁺-ATPase activity. Distinct metabolic features of IIH, including visceral adiposity, insulin resistance, and adipose tissue inflammation, are integrated with evidence of systemic and central immune dysregulation. Recent genetic and biobank-based studies further support IIH-specific biological risk extending beyond obesity alone and implicate pathways involved in steroid metabolism, ion transport, vascular biology, and glymphatic regulation. We additionally review translational and clinical evidence supporting targeted therapies, including glucagon-like peptide-1 (GLP-1) receptor agonists and 11β-HSD1 inhibitors, which demonstrate ICP-lowering effects that may occur partially independent of weight loss.

Accumulating mechanistic evidence supports a paradigm shift in IIH from a diagnosis of exclusion toward a biologically defined neuroendocrine disorder characterized by dysregulated CSF secretion, endocrine and metabolic dysfunction, inflammation, and impaired glymphatic regulation. Advances in molecular biology and translational therapeutics are enabling the development of targeted, disease-modifying therapies and may facilitate future precision medicine approaches for IIH management.