Cerebrospinal Fluid Total Iron and Fe2+ Strongly Associated with The Incidence of Hydrocephalus in Intracerebral Hemorrhage Patients with Intraventricular Extension

Abstract

Background Hydrocephalus (HCP) is a known complication of spontaneous intracerebral hemorrhage (ICH) extension into the ventricles (IVH) and is associated with poorer patient outcomes. The mechanisms in HCP development are not yet clear. Biomarkers in CSF could predict the risk of shunt-dependent hydrocephalus, to improve clinical outcomes in these patients, and could be more reliable than CT-scan evaluation. Aim This study aimed to test the reliability of measuring Fe²⁺, Fe³⁺, total iron concentration, and high mobility group box 1 (HMGB1) protein levels as CSF biomarkers to predict the risk of shunt-dependent hydrocephalus in ICH + IVH patients. We compared marker reliability with CT-scan mGraeb score to predict hydrocephalus. Methods All adult ICH + IVH patients with hydrocephalus admitted to Siloam Hospitals Lippo Village between March 2021 until December 2023 were included in this cohort study. The patient's clinical and radiological characteristics were retrieved, and CSF samples were obtained during EVD placement. Statistical analyses were performed to reveal potential clinical, radiological, and biomarker values as predictors of shunt-dependent hydrocephalus in ICH + IVH patients. Results Thirty-six ICH + IVH + HCP patients, including 16 females (44.4%) and 20 males (55.6%) were included in this study, with mean age of 60.75 years. Seventeen patients (47.2%) were diagnosed with shunt-dependent hydrocephalus. Logistic regression analyses revealed that increased total Fe (p = 0.048) and Fe2+ (0.045) were significantly associated with the incidence of shunt-dependent hydrocephalus. Receiver operating curves (ROC) revealed that the AUCs from total iron (0.716), Fe2+ (0.758), Fe3+ (0.651), and HMGB1 (0.722) are higher than the AUC of mGraeb score (0.528). Conclusion Based on the results from logistic regression analyses and constructed ROCs, CSF total iron and Fe²⁺ are reliable prognosticators of shunt-dependent hydrocephalus in ICH + IVH + HCP patients. These biomarkers are more sensitive and specific in predicting hydrocephalus compared to mGraeb score.