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Background: White matter injury (WMI) is observed after experimental intracerebral hemorrhage (ICH). Supporting clinical data are sparse. We assessed the presence, extent, and progression of WMI in ICH patients.Methods: Retrospective review of data from consecutive 65 patients with spontaneous supratentorial ICH who had baseline brain MRI within 7 days of ICH onset and repeat MRI afterwards (median 83 days). We used Fazekas scale (FZS) to grade the severity of WMI. Clinical and imaging characteristics of patients with and without WMI progression were compared by uni- and multi-variate logistic regression analyses.Results: For the entire cohort, the mean total FZS score increased from 2.9±1.6 on baseline to 3.3±1.6 on repeat MRI (p=0.00; Z=-4.38). The progression of WMI was noted both ipsi- and contra-lateral to the ICH; the mean score increased from 2.9±1.6 to 3.1±1.5 (p=.00; Z=-3.56) in the contralateral hemisphere and 2.8±1.6.to 3.1±1.6 (p=.00; Z=-4.49) in the ipsilateral hemisphere. Similar results were noted when subjects were stratified based on ICH location; lobar (n =51) and deep (n =14). The severity of WMI was greater in lobar than deep ICH [3.2±1.5 vs. 2.1±1.4 on initial MRI (p=0.03), and 3.5±1.5 vs. 2.6±1.6 on repeat scan (p=0.06)]. However, the extent of WMI progression did not differ by ICH location. Seventeen patients with lobar and 6 with deep ICH (35.4%) showed evidence of WMI progression. The characteristics of patients with and without WMI progression were comparable. The time interval from baseline to repeat MRI did not differ between the groups (p=0.68). Only, baseline ICH volume [p=0.049; OR 1.038; 95%CI=1.00-1.08] and presence of intraventricular hemorrhage [p=0.004; OR 5.69; 95%CI=1.64-19.78] emerged as predictors of WMI progression. Patients with WMI progression had worse 3-month outcome, defined as mRS >2, (34.8% vs. 11.9%; p<0.05 on uni- and multivariate analyses).Conclusions: WMI progresses over time in ICH patients, and is associated with worse outcome. This novel finding could represent a potential therapeutic target. Future prospective larger studies are needed to confirm our findings.