@article{3121295,
    title = "Thrombolysis for acute ischemic stroke in the unwitnessed or extended therapeutic time window",
    author = "Tsivgoulis, G. and Katsanos, A.H. and Malhotra, K. and Sarraj, A. and Barreto, A.D. and Köhrmann, M. and Krogias, C. and Ahmed, N. and Caso, V. and Schellinger, P.D. and Alexandrov, A.V. and Tsivgoulis, G.",
    journal = "Functional Neurology",
    year = "2020",
    volume = "94",
    number = "12",
    pages = "e1241-e1248",
    publisher = "Lippincott Williams and Wilkins",
    doi = "10.1212/WNL.0000000000008904",
    keywords = "alteplase;  fibrinolytic agent;  tissue plasminogen activator, adult;  aged;  all cause mortality;  Article;  blood clot lysis;  brain hemorrhage;  brain ischemia;  controlled study;  disease course;  female;  Functional Independence Measure;  human;  major clinical study;  male;  mortality risk;  neuroimaging;  priority journal;  randomized controlled trial;  Rankin scale;  recanalization;  treatment outcome;  brain ischemia;  cerebrovascular accident;  diagnostic imaging;  fibrinolytic therapy;  intravenous drug administration;  meta analysis;  procedures;  time to treatment, Administration, Intravenous;  Brain Ischemia;  Fibrinolytic Agents;  Humans;  Neuroimaging;  Stroke;  Thrombolytic Therapy;  Time-to-Treatment;  Tissue Plasminogen Activator;  Treatment Outcome",
    abstract = "ObjectiveTo assess the utility of IV thrombolysis (IVT) treatment in patients with acute ischemic stroke (AIS) with unclear symptom onset time or outside the 4.5-hour time window selected by advanced neuroimaging.MethodsWe performed random-effects meta-Analyses on the unadjusted and adjusted for potential confounders associations of IVT (alteplase 0.9 mg/kg) with the following outcomes: 3-month favorable functional outcome (FFO; modified Rankin Scale [mRS] scores 0-1), 3-month functional independence (FI; mRS scores 0-2), 3-month mortality, 3-month functional improvement (assessed with ordinal analysis on the mRS scores), symptomatic intracranial hemorrhage (sICH), and complete recanalization (CR).ResultsWe identified 4 eligible randomized clinical trials (859 total patients). In unadjusted analyses, IVT was associated with a higher likelihood of 3-month FFO (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.12-1.96), FI (OR 1.42, 95% CI 1.07-1.90), sICH (OR 5.28, 95% CI 1.35-20.68), and CR (OR 3.29, 95% CI 1.90-5.69), with no significant difference in the odds of all-cause mortality risk at 3 months (OR 1.75, 95% CI 0.93-3.29). In the adjusted analyses, IVT was also associated with higher odds of 3-month FFO (adjusted OR [ORadj] 1.62, 95% CI 1.20-2.20), functional improvement (ORadj 1.42, 95% CI 1.11-1.81), and sICH (ORadj 6.22, 95% CI 1.37-28.26). There was no association between IVT and FI (ORadj 1.61, 95% CI 0.94-2.75) or all-cause mortality (ORadj 1.75, 95% CI 0.93-3.29) at 3 months. No evidence of heterogeneity was evident in any of the analyses (I2 = 0).ConclusionIVT in patients with AIS with unknown symptom onset time or elapsed time from symptom onset >4.5 hours selected with advanced neuroimaging results in a higher likelihood of CR and functional improvement at 3 months despite the increased risk of sICH. © American Academy of Neurology."
}