Tsivgoulis, GeorgiosSaqqur, MaherSharma, Vijay K.Brunser, AlejandroEggers, JürgenMikulik, RobertKatsanos, Aristeidis H.Sergentanis, Theodore N.Vadikolias, KonstantinosPerren, FabienneRubiera, MartaShahripour, Reza BavarsadNguyen, Huy ThangMartínez-Sánchez, PatriciaSafouris, ApostolosHeliopoulos, IoannisShuaib, AshfaqDerksen, CarolVoumvourakis, KonstantinosPsaltopoulou, TheodoraAlexandrov, Anne W.Alexandrov, Andrei V.CLOTBUST-PRO investigators2021-08-062021-08-062020Journal of Stroke, 2020, vol.22(1):130-140https://doi.org/10.5853/jos.2019.01648http://hdl.handle.net/11447/4248Background 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 (jos-2019-01648P<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.enThrombolysisStrokeReperfusionOutcomesArticle