Proof of Concept: Endogenous Antiangiogenic Factors Predict the Occurrence of Symptomatic Vasospasm Post Subarachnoid Hemorrhage

Abstract

The pathogenesis of vasospasm (VS) post aneurysmal subarachnoid hemorrhage (SAH) is multifactorial and not completely understood. The authors hypothesize that circulating antiangiogenic factors play an important role in brain injury post SAH and that elevated levels predict the occurrence of symptomatic vasospasm. In this study the authors measured the serum and cerebrospinal fluid (CSF) levels of soluble endoglin (sEng) and soluble fms-like tyrosine kinase 1 (sFlt1) in controls and SAH patients within 48h of the bleed. Patients were prospectively followed and subcategorized into those with (sVS) and without symptomatic vasospasm (no-sVS). Compared to healthy controls, SAH patients had higher CSF levels of sEng (0.037 vs. 0.251ng/ml; P=0.02) and sFlt1 (0.068 vs. 0.679ng/ml; P=0.001). In the subgroup analysis, sVS patients had higher CSF levels of sEng and sFlt1 than no-sVS patients (sEng: 0.380 vs. 0.159ng/ml, P=0.02; sFlt1: 1.277 vs. 0.343ng/ml, P=0.01). The serum levels of sEng and sFlt1 were not statistically different among the different groups. Based on these results the authors conclude that elevated CSF levels of sFlt1 and sEng herald the occurrence of symptomatic VS post SAH.