Molecular Signatures of Vascular Injury Are Associated With Early Growth of Intracerebral Hemorrhage

Abstract

Background and Purpose— To investigate whether molecular markers of inflammation and endothelial injury are associated with early growth of intracerebral hemorrhage (ICH). Methods— In a multicenter prospective study, we determined concentrations of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-9 (MMP-9), and cellular fibronectin (c-Fn) in blood samples obtained on admission from 183 patients with primary hemispheric ICH of <12 hours’ duration. Patients had a neurological evaluation and a computed tomography (CT) scan performed at baseline and at 48±6 hours. Early growth of the ICH was defined as a volume increase >33% between the 2 CT examinations for ICH with a baseline volume <20 mL and >10% for ICH ≥20 mL. Clinical, radiological, and biochemical predictive factors of ICH enlargement were analyzed by logistic regression analysis. Results— Fifty-four (29.5%) patients showed a relevant early growth of ICH. High leukocyte count and fibrinogen levels, low platelet count, and intraventricular bleeding were associated with early ICH growth in bivariate analyses. Plasma concentrations of IL-6 (median [quartiles]: 19.6 [13.6; 29.9] versus 15.9 [11.5; 19.8] pg/mL), TNF-α (13.5 [8.4; 30.5] versus 8.7 [4.7; 13.5] pg/mL), MMP-9 (153.3 [117.7; 204.7] versus 70.6 [47.8; 103.8] ng/mL), and c-Fn (8.8 [6.2; 12.5] versus 2.8 [1.6; 4.2] μg/mL) were significantly higher in patients with early growth of ICH (all P <0.001). C-Fn levels >6 μg/mL (OR, 92; 95%CI, 22 to 381; P <0.0001) and IL-6>24 pg/mL (OR, 16; 95%CI, 2.3 to 119; P =0.005) were independently associated with ICH enlargement in the logistic regression analysis. Conclusions— Molecular signatures of vascular injury and inflammatory markers in the early acute phase of ICH are associated with subsequent enlargement of the hematoma.