Abstract

Purpose: Hematoma expansion (HE) following acute intracerebral hemorrhage (ICH) is common and associated with poor outcome. Ongoing clinical trials therefore focus on restricting HE. In order to provide treatment options to the patients at highest risk of HE, we aimed to develop a prediction score for HE. Methods: We performed a prospective cohort study of consecutive primary ICH patients presenting to a single center over a 12-year period, with available baseline and follow-up CTs. HE was assessed using semi-automated software and defined as 6 mL or 33% growth. Our cohort was randomly divided in a 2/3 development and 1/3 validation cohort. Uni- and multivariate logistic regression was performed to assess clinical and neuroimaging covariates for relationship with HE. A prediction model was derived based on regression estimates, and this model was subsequently tested in the validation cohort. Results: 817 ICH patients were included: 544 in the development cohort and 273 in the validation cohort. Overall, HE occurred in 156 patients (19%). In multivariate analysis, warfarin use (OR 2.09 [95%CI 1.24-3.52], p = 0.006), shorter time to CT (≤6 vs. >6 hours; OR 2.14 [95%CI 1.18-3.90], p = 0.013), baseline ICH volume (<30, 30-60, >60 mL; OR 1.90 [95%CI 1.01-3.55], p = 0.045), and the CT angiography spot sign (OR 3.59 [95%CI 1.77-7.29], p = 0.0004) were predictive of HE. The derived prediction score (0-9) showed a linear relation with the probability of HE and mortality (at discharge and 90 days), in both the development and the validation cohorts. The probability of HE in the validation cohort was 0%, 10%, 39%, and 54% for categorized scores 0, 1-3, 4-6, and 7-9, respectively. The c statistics were 0.69 for the development cohort and 0.78 for the validation cohort. Conclusion: Warfarin use, presentation within 6 hours after ICH, larger ICH volumes at baseline, and the CT angiography spot sign are independent predictors of HE and mortality. Based on these findings, we developed a prediction score for HE. Since no therapy has demonstrated benefit in a randomized trial, our results open a path for individualized treatment and trial design in ICH, aimed at patients at highest risk of HE.

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