Venous hypertension is a rare cause of myelopathy that can be misdiagnosed as myelitis and be worsened by glucocorticosteroids.This study is aims to identify a fluid biomarker with diagnostic value in Venous Hypertensive Myelopathy (VHM).a retrospective diagnostic study PATIENT SAMPLE: The patients diagnosed as having myelopathy between December 2020 and June 2022 were divided into a VHM group (n=71) and an inflammatory myelopathy (IM) group (n=123). A non-inflammatory neurological disorders (NIND) group (n=53) was also acquired as baseline control.The primary outcome was the diagnostic accuracy of the fluid biomarkers in the VHM and IM groups.The albumin, immunoglobulins, oligoclonal bands, neuron-specific enolase, myelin basic protein, and S100β were measured in their cerebrospinal fluid (CSF) and paired serum samples. Potential diagnostic biomarkers were screened through univariate and collinearity analyses. The diagnostic performance of these biomarkers was assessed by plotting the receiver-operating characteristic curves. Additionally, the predictive value of clinical factors and biomarkers for diagnosis was evaluated using multivariable logistic regression analysis.The quantitative and normalized CSF-S100β values were significantly lower in the VHM group (P<.05). Analysis of receiver-operating characteristic curves adjusted for age and sex showed that the normalized CSF-S100β discriminated between VHM and IM (area under the curve (AUC) 0.884, 95% confidence interval [CI] 0.817-0.938). Particularly, it performed well in the AUC for normalized CSF-S100β (AUC 0.9400, 95% CI 0.8621-1.000) when oligoclonal bands and flow-void sign were negative.The normalized CSF-S100β can differentiate between VHM and IM.Copyright © 2024. Published by Elsevier Inc.