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.