Blood-Brain Barrier Disruption Predicts Poor Outcome in Subarachnoid Hemorrhage: A Dynamic Contrast-Enhanced MRI Study

Abstract

BACKGROUND: Spontaneous aneurysmal subarachnoid hemorrhage induces early blood-brain barrier permeability dysfunction, although its clinical relevance and underlying mechanisms remain poorly understood. We aimed to evaluate the association between blood-brain barrier disruption, quantified with dynamic contrast-enhanced magnetic resonance imaging at the end of the early brain injury period, circulating neuroinflammatory mediators, and long-term clinical outcomes. METHODS: We analyzed a prospective cohort of subarachnoid hemorrhage patients who underwent dynamic contrast-enhanced magnetic resonance imaging at a median (interquartile range) of 4 (2-6) days after clinical onset. Permeability maps were used to obtain K-trans values as a measure of increased blood-brain barrier permeability in the whole brain, gray matter, and white matter. Circulating neuroinflammatory molecules, including IL (interleukin) 8 and PDGF (platelet-derived growth factor), were measured using Multiplex-ELISA in blood samples collected concurrently with magnetic resonance imaging acquisition. Poor clinical outcome was defined as a modified Rankin Scale score of >2 at 90 days. Associations between K-trans values, neuroinflammatory mediators, and clinical outcomes were assessed using univariate and multivariate regression models. RESULTS: From 153 patients initially screened, 96 were finally included (63% females; median age, 55 years; 43% premorbid hypertension; 32% World Federation of Neurosurgical Societies grade 4-5; 31% poor outcome). In adjusted linear regression analyses, higher K-trans values were significantly associated with increased IL-8 (P=0.001) and PDGF (P=0.018) levels. In univariate analysis, K-trans values in white matter were significantly higher in patients with poor clinical outcome (median [interquartile range], 2.5 [2.07-6.09] x10(-3)min(-1)) compared with good clinical outcome (median [interquartile range], 2.0 [1.60-2.42] x10(-3)min(-1); P