Idiopathic intracranial hypertension (IIH) with venous sinus stenosis (VSS) may lead to a vicious cycle of elevated intracranial pressure (ICP) and subsequent brain damage. This study aimed to characterize metabolic alterations and identify potential biomarkers in IIH with VSS compared to individuals with normalized ICP after stent treatment. Patients with trans-stenotic pressure gradient (TSPG) ⩾8 mmHg were defined as the new-onset IIH group (NIG), while those with TSPG <8 mmHg after stenting formed the post-stent follow-up group (PFG). After propensity score matching, 19 participants were included in each group. Metabolomic profiling was conducted using cerebrospinal fluid (CSF), femoral vein plasma, and jugular bulb plasma. Compared with PFG, NIG exhibited elevated purine metabolites in CSF, including hypoxanthine (AUC = 0.801) and inosine (AUC = 0.783), both correlated with TSPG. Femoral vein plasma showed reduced citric acid and cis-aconitic acid levels in NIG, with PS (P-20:0/22:6) and LPC 20:4 identified as potential biomarkers (AUCs = 0.823 and 0.787, respectively). Jugular bulb plasma further revealed brain-derived disturbances in the citrate cycle, arachidonic acid metabolism, and unsaturated fatty acid metabolism. These findings highlight characteristic metabolic disorders in IIH with VSS and suggest predictive markers for elevated TSPG.
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