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Time Course of Tissue Plasminogen Activator–Induced Recanalization in Acute Cardioembolic Stroke: A Case-Control Study

Background and Purpose— The relationship between arterial recanalization, infarct size, and outcome in patients treated with intravenous thrombolytics remains unclear. Therefore, we aimed to determine the time course of recombinant tissue plasminogen activator (rtPA)-induced recanalization in patients with cardioembolic stroke treated <3 hours from symptom onset and to investigate the relationship between arterial recanalization, infarct volume, and outcome. Methods— We prospectively studied 72 patients with an acute cardioembolic stroke in the middle cerebral artery territory: 24 treated with rtPA at <3 hours and 48 matched controls. Serial transcranial Doppler examinations were performed on admission and at 6,12, 24, and 48 hours. Infarct volume was measured by use of CT at day 5 to 7. Modified Rankin Scale score was used to assess outcome at 3 months. Results— Rate of 6-hour recanalization was higher (P <0.001) in the rtPA group (66%) than in the control group (15%). Five (20.8%) rtPA patients and 15 (31.2%) controls recanalized between 6 and 12 hours, and 2 (8.3%) patients and 12 (25%) controls between 12 and 48 hours, respectively. At 48 hours, 75% of rtPA patients and 27% of controls had improved (P <0.001). Infarct volume was 50.2±40.3 cm3 in rtPA patients and 124.8±81.6 cm3 in controls (P <0.001). Moreover, infarct volume was associated strongly (P <0.001) with duration of middle cerebral artery occlusion. At 3 months, 14 (58%) rtPA patients and 11 (23%) controls (P =0.037) became functionally independent (modified Rankin Scale score ≤2). A close relationship (P =0.002) existed between modified Rankin Scale score at 3 months and time to reperfusion. In addition, clinical outcome was associated strongly (P =0.001) with degree of 6-hour recanalization. Logistic regression analysis identified National Institutes of Health Stroke Scale score <17 (odds ratio 12.1, 95% confidence interval 2.8 to 68, P =0.001) and early recanalization (odds ratio 23.4, 95% confidence interval 5.4 to 96, P =0.001) as independent predictors of functional independence at 3 months. Conclusions— Intravenous rtPA is associated with early recanalization, which leads to lower infarct size and better clinical outcome. Early recanalization is a powerful independent predictor of functional independence at 3 months.