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

Abstract

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. 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. 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 (<i>P</i>=0.001) and PDGF (<i>P</i>=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] ×10^-3·min^-1) compared with good clinical outcome (median [interquartile range], 2.0 [1.60-2.42] ×10^-3·min^-1; <i>P</i><0.001). In models adjusted by age, World Federation of Neurosurgical Societies, hypertension, intraparenchymal hematoma, aneurysm size, and time to magnetic resonance imaging, elevated K-trans values remained independently associated with poor outcome (adjusted odds ratio per interquartile range increase, 3.31 [95% CI, 1.485-7.377]; <i>P</i>=0.003). Increased blood-brain barrier permeability correlates with circulating neuroinflammatory mediator levels and is associated with poor clinical recovery at 3 months. These findings support the potential role of white matter permeability alterations as both biomarker and therapeutic target in subarachnoid hemorrhage.