Inflammation in Idiopathic Intracranial Hypertension: An Immunometabolic Mechanistic Framework and Clinical Implications.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a multifactorial disorder characterized by sustained intracranial pressure (ICP) elevation in the absence of identifiable causes, predominantly affecting obese women of reproductive age. Although the pathophysiology of IIH remains incompletely understood, accumulating evidence indicates that inflammation is closely intertwined with metabolic, vascular, and cerebrospinal fluid (CSF) disturbances.

METHODS: We performed a structured literature search of PubMed, EMBASE, Web of Science, and the Cochrane Library for studies relevant to the pathophysiology of IIH, with a particular focus on inflammatory mechanisms, molecular signatures, and clinical correlates.

RESULTS: The reviewed evidence indicates that inflammatory activation within the choroid plexus and cerebral endothelium is associated with enhanced activity of sodium-potassium adenosine triphosphatase (Na+/K+-ATPase), Na+-K+-2Cl- cotransporter (NKCC1), and aquaporin-1 (AQP1), impaired barrier integrity, and increased CSF secretion. In parallel, inflammatory fibrosis of arachnoid villi and dysfunction of glymphatic-lymphatic outflow pathways may impede CSF reabsorption, further contributing to ICP elevation. At the systemic level, obesity-associated adipokines, proinflammatory cytokines, and endocrine dysregulation-particularly involving glucocorticoid and sex-steroid signaling-appear to amplify neuroinflammatory cascades linked to altered CSF homeostasis. Clinically, patients with IIH exhibit elevated inflammatory biomarkers (C-reactive protein, neuron-specific enolase, neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios), intrathecal immunoglobulin G (IgG) synthesis, and increased neurofilament light chain levels, consistent with combined immune activation and neuroaxonal stress. Common comorbidities such as anemia, obstructive sleep apnea, and thrombophilia may further exacerbate inflammatory and hypoxic burden. Collectively, these findings support a conceptual shift from IIH as a purely mechanical disorder toward an immunometabolic disease of CSF regulation.

CONCLUSIONS: In this review, we integrate mechanistic, clinical, and molecular evidence linking inflammation to IIH pathophysiology, and discuss how inflammatory biomarkers, metabolic modulators, and targeted anti-inflammatory strategies could inform future diagnostic, prognostic, and therapeutic frameworks. A more precise understanding of these immunometabolic pathways may help redefine IIH as a biologically stratified and therapeutically tractable disorder.