title: Ultra-early intravenous stroke thrombolysis: do all patients benefit similarly?
abstract: OBJECTIVE
  We previously reported increased benefit and reduced mortality after ultra-early stroke thrombolysis in a single center. We now explored in a large multicenter cohort whether extra benefit of treatment within 90 minutes from symptom onset is uniform across predefined stroke severity subgroups, as compared with later thrombolysis.
  
  
  METHODS
  Prospectively collected data of consecutive ischemic stroke patients who received i.v. thrombolysis in 10 European stroke centers were merged. Logistic regression tested association between treatment delays, as well as excellent 3-month outcome (modified Rankin scale, 0-1), and mortality. The association was tested separately in tertiles of baseline National Institutes of Health Stroke Scale.
  
  
  RESULTS
  In the whole cohort (n=6856), shorter onset-to-treatment time as a continuous variable was significantly associated with excellent outcome (P<0.001). Every fifth patient had onset-to-treatment time≤90 minutes, and these patients had lower frequency of intracranial hemorrhage. After adjusting for age, sex, admission glucose level, and year of treatment, onset-to-treatment time≤90 minutes was associated with excellent outcome in patients with National Institutes of Health Stroke Scale 7 to 12 (odds ratio, 1.37; 95% confidence interval, 1.11-1.70; P=0.004), but not in patients with baseline National Institutes of Health Stroke Scale>12 (odds ratio, 1.00; 95% confidence interval, 0.76-1.32; P=0.99) and baseline National Institutes of Health Stroke Scale 0 to 6 (odds ratio, 1.04; 95% confidence interval, 0.78-1.39; P=0.80). In the latter, however, an independent association (odds ratio, 1.51; 95% confidence interval, 1.14-2.01; P<0.01) was found when considering modified Rankin scale 0 as outcome (to overcome the possible ceiling effect from spontaneous better prognosis of patients with mild symptoms). Ultra-early treatment was not associated with mortality.
  
  
  CONCLUSIONS
  I.v. thrombolysis within 90 minutes is, compared with later thrombolysis, strongly and independently associated with excellent outcome in patients with moderate and mild stroke severity.
authors: From the Departments of Neurology and Stroke Units, Helsinki University Central Hospital, Helsinki, Finland (D.S., T.T.); Department of Neurology, University of Heidelberg, Heidelberg, Germany (P.R., W.H.); Department of Neurology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland (P.M., A.E.); Department of Neurology, Universitätsklinikum Erlangen, Erlangen, Germany (L.B., M.K.); Department of Neurology, Tampere University Hospital, Tampere, Finland (J.O., H.N.); Department of Neurology, University Lille Nord de France (K.M., D.L.); Department of Neurology and Stroke Units, University Hospital Basel, Basel, Switzerland (D.J.S., H.G., S.E.); Department of Neurology, University of Bern, Bern, Switzerland (S.J., B.W., H.P.M.); Department of Neurology, Hospital Clínic Institut d'Investigacions Biomediques August Pi i Sunyer, Barcelona, Spain (V.O., A.C.); and Department of Neurology, Kantonsspital St. Gallen, St. Gallen, Switzerland (B.W.).
authors: Daniel
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authors: Strbian
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authors: Ringleb
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authors: Lorenz
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authors: Breuer
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authors: DJ
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authors: Leys
authors: Heikki
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authors: Numminen
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authors: M
authors: Köhrmann
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authors: Hacke
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authors: Tatlisumak
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000401:mortality* / Q000628:therapy*; D002543:Cerebral Hemorrhage / Q000401:mortality / Q000628:therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020521:Stroke / Q000401:mortality* / Q000628:therapy*; D015912:Thrombolytic Therapy; D013997:Time Factors
keywords: emergencies; ischemic stroke; onset to needle time; outcome; thrombolysis