BACKGROUND AND PURPOSE: Although onset-to-treatment time is associated with early clinical recovery in acute ischemic stroke (AIS) patients treated with intravenous tissue plasminogen activator (tPA), the effect of the timing of tPA-induced recanalization on functional outcomes remains debatable. METHODS: We conducted a multicenter, prospective observational cohort study to determine whether early (within 1-hour from tPA-bolus) complete or partial recanalization assessed during 2-hour real-time transcranial Doppler monitoring is associated with improved outcomes in patients with proximal occlusions. Outcome events included dramatic clinical recovery (DCR) within 2 and 24-hours from tPA-bolus, 3-month mortality, favorable functional outcome (FFO) and functional independence (FI) defined as modified Rankin Scale (mRS) scores of 0-1 and 0-2 respectively. RESULTS: We enrolled 480 AIS patients (mean age 66±15 years, 60% men, baseline National Institutes of Health Stroke Scale score 15). Patients with early recanalization (53%) had significantly (P<0.001) higher rates of DCR at 2-hour (54% vs. 10%) and 24-hour (63% vs. 22%), 3-month FFO (67% vs. 28%) and FI (81% vs. 39%). Three-month mortality rates (6% vs. 17%) and distribution of 3-month mRS scores were significantly lower in the early recanalization group. After adjusting for potential confounders, early recanalization was independently associated with higher odds of 3-month FFO (odds ratio [OR], 6.19; 95% confidence interval [CI], 3.88 to 9.88) and lower likelihood of 3-month mortality (OR, 0.34; 95% CI, 0.17 to 0.67). Onset to treatment time correlated to the elapsed time between tPA-bolus and recanalization (unstandardized linear regression coefficient, 0.13; 95% CI, 0.06 to 0.19). CONCLUSIONS: Earlier tPA treatment after stroke onset is associated with faster tPA-induced recanalization. Earlier onset-to-recanalization time. RESULTS: in improved functional recovery and survival in AIS patients with proximal intracranial occlusions.

2nd Department of Neurology Attikon University Hospital School of Medicine National and Kapodistrian University of Athens Athens Greece

Department of Cerebrovascular Disease 115 The People Hospital Ho Chi Minh Vietnam

Department of Emergency Medicine Clinica Alemana of Santiago University of Desarrollo Santiago Chile

Department of Hygiene Epidemiology and Medical Statistics School of Medicine National and Kapodistrian University of Athens Athens Greece

Department of Neurology and Stroke Center IdiPAZ Health Research Institute La Paz University Hospital Autonomous University of Madrid Madrid Spain

Department of Neurology Sana Hospital Lubeck Lübeck Germany

Department of Neurology University Hospital of Alexandroupolis Democritus University of Thrace Alexandroupolis Greece

Department of Neurology University Hospital Schleswig Holstein Campus Lubeck Lübeck Germany

Department of Neurology University of Alabama at Birmingham Birmingham AL USA

Department of Neurology University of Ioannina School of Medicine Ioannina Greece

Department of Neurology University of Tennessee Health Science Center Memphis TN USA

Department of Neuroscience Hamad General Hospital Doha Qatar

Division of Neurology Department of Medicine University of Alberta Edmonton AB Canada

Division of Neurology National University Hospital Yong Loo Lin School of Medicine National University of Singapore Singapore

Medical Faculty Masaryk University Brno Czech Republic

Neurology Department and International Clinical Research Center St Anne's Hospital Brno Czech Republic

Stroke Unit Department of Neurological Sciences LUNIC Laboratory HUG University Hospital and Medical Faculty of Geneva Geneva Switzerland

Stroke Unit Department of Neurology Brugmann University Hospital Brussels Belgium

Stroke Unit Department of Neurology Vall d'Hebron University Hospital Vall d'Hebron Research Institute Barcelona Spain

Torrecardenas Hospital University of Almeria School of Health Sciences Almeria Spain

Vascular Neurology Program Neurology Service Department of Medicine Clinica Alemana of Santiago University of Desarrollo Santiago Chile

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