Background: Concomitant acute ischemic lesions are detected in 0-39% of patients with spontaneous intracerebral hemorrhage (ICH). Etiology and impact on functional outcomes are poorly understood nor is it known if intraventricular recombinant tissue plasminogen activator (rtPA) impacts incidence.
Methods: Prospective analysis of incidence and etiology of ischemic lesions in all 500 patients enrolled in the CLEAR III trial, a multicenter, double-blind, randomized study comparing EVD + intraventricular rtPA vs. EVD + placebo for treatment of obstructive intraventricular hemorrhage (IVH) and ICH volume <30cc. Two independent stroke neurologists (WZ and LR) evaluated clinical ischemic events reported during acute hospitalization.
Results: Ischemic strokes occurred in 19/500 (3.8%) at median [iqr] 10[5,19] days after ICH onset. Mean age was 57.3±10.5 years. Median NIHSS was 18[12.5-37]. ICH locations were basal ganglia (15/19), frontal lobe (1); 3/19 had primary IVH. All strokes but one were distant from the ICH (7 contralateral, 6 bilateral, 3 ipsilateral,1 infratentorial). Compared to patients without strokes, patients with strokes had similar ICH (8.1[12.5] vs. 7.7[10.9]cc) and IVH volumes (23.2[30.1] vs. 24.6[25.3]cc), non-significantly higher admission systolic (201 vs. 193mmHg) and diastolic (111 vs. 107mmHg) blood pressure (BP), and larger decrease in SBP from admission to randomization (54.5 vs. 48mmHg, p=0.13). Mortality was significantly higher in patients with strokes at 30 (26.3% vs. 8.5%, p=0.008) and at 180 days (33.3% vs. 13.7%, p=0.02). Mortality was significantly associated with ischemic stroke after adjustment for ICH and IVH volumes, age and Glasgow Coma Scale (p=0.03 for both day 30 and 180). There were no significant differences in comorbidities between the two groups.
Conclusions: Incidence of ischemic strokes in the CLEAR III trial was low but significantly associated with increased early and late mortality. Mass effect and stroke risk factors did not appear to contribute. Acute phase BP reduction may be a predisposing factor. These results permit future correlation of ischemic complications with treatment rendered (thrombolysis versus placebo), with upcoming unblinding of the trial.