Objective: This study aims to investigate the pathogenic mechanisms of IESS, utilizing metabolomics and proteomics analyses to uncover potential biomarkers for the disease, thereby providing new insights for diagnostic and therapeutic strategies. Methods: Cerebrospinal fluid samples from 6 IESS patients and 6 control subjects with benign intracranial hypertension were collected and analyzed using metabolomics and proteomics techniques. Significant differential metabolites and proteins were identified and correlated to determine key proteins associated with specific metabolites. The study then expanded the sample size to 10 per group and validated the identified proteins through ELISA analysis.