title: Defining clinically relevant cerebral hemorrhage after thrombolytic therapy for stroke: analysis of the National Institute of Neurological Disorders and Stroke tissue-type plasminogen activator trials.
abstract: OBJECTIVE
  Several definitions have been proposed to distinguish clinically relevant from incidental cerebral hemorrhagic transformation after thrombolytic therapy for acute ischemic stroke. We investigated which definition best identifies cerebral hemorrhages that alter long-term functional outcome in the National Institute of Neurological Disorders and Stroke (NINDS) tissue-type plasminogen activator (tPA) trials.
  
  
  METHODS
  We analyzed 4 candidate hemorrhage definitions for which the NINDS tPA trials public data set had relevant data. For each, we identified tPA-treated patients having that hemorrhage type and compared their actual functional outcomes at 90 days with their predicted outcomes had they not received tPA and not had the hemorrhage. Projected outcomes without tPA were based on a 17-variable prognostic model derived from the NINDS tPA trials placebo group.
  
  
  RESULTS
  Among the 312 patients treated with intravenous tPA, 33 (10.6%) experienced any radiological intracerebral hemorrhage <36 hours of treatment, 16 (5.1%) a radiological parenchymal hematoma, 20 (6.4%) a NINDS tPA trials-defined symptomatic intracerebral hemorrhage, 12 (3.8%) an European-Australian Cooperative Acute Stroke Study 2 (ECASS2)-defined symptomatic intracerebral hemorrhage, and 6 (1.9%) a modified version of the Safe Implementation of Thrombolysis in Stroke Monitoring Study (mSITS-MOST)-defined symptomatic intracerebral hemorrhage. The ECASS2 and mSITS-MOST definitions identified the largest hemorrhage-related change in 90-day modified Rankin Scale scores (2.26-0.32=1.94, P=0.0001; 2.81-0.63=2.18, P=0.0002, respectively). These definitions also distinguished the largest hemorrhage-related change in 90-day mortality (64.7%-7.6%=57.1%; P=0.0004 for ECASS2; 68.4%-19.5%=48.9%; P=0.0152 for mSITS-MOST).
  
  
  CONCLUSIONS
  The ECASS2 and mSITS-MOST symptomatic intracerebral hemorrhage definitions, which combine radiological features and occurrence of substantial early neurological deterioration, best identify tPA hemorrhages that alter final patient outcome.
authors.affiliation: From the Divison of Neurology (N.M.R., J.L.S.) and Department of Mathematics (J.A.G.), David Geffen School of Medicine at UCLA; Departments of Neurology and Emergency Medicine and Stroke Center, State University of New York Health Science, Brooklyn (S.R.L.); and Department of Neurology, Kings County Hospital Center, Brooklyn, NY (S.R.L.). nealrao@mednet.ucla.edu.
authors.forename: Neal M
authors.initials: NM
authors.lastname: Rao
authors.affiliation: From the Divison of Neurology (N.M.R., J.L.S.) and Department of Mathematics (J.A.G.), David Geffen School of Medicine at UCLA; Departments of Neurology and Emergency Medicine and Stroke Center, State University of New York Health Science, Brooklyn (S.R.L.); and Department of Neurology, Kings County Hospital Center, Brooklyn, NY (S.R.L.).
authors.forename: Steven R
authors.initials: SR
authors.lastname: Levine
authors.affiliation: From the Divison of Neurology (N.M.R., J.L.S.) and Department of Mathematics (J.A.G.), David Geffen School of Medicine at UCLA; Departments of Neurology and Emergency Medicine and Stroke Center, State University of New York Health Science, Brooklyn (S.R.L.); and Department of Neurology, Kings County Hospital Center, Brooklyn, NY (S.R.L.).
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Gornbein
authors.affiliation: From the Divison of Neurology (N.M.R., J.L.S.) and Department of Mathematics (J.A.G.), David Geffen School of Medicine at UCLA; Departments of Neurology and Emergency Medicine and Stroke Center, State University of New York Health Science, Brooklyn (S.R.L.); and Department of Neurology, Kings County Hospital Center, Brooklyn, NY (S.R.L.).
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Saver
mesh_terms: D002543:Cerebral Hemorrhage / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000628:therapy*; D002986:Clinical Trials as Topic; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D055825:National Institute of Neurological Disorders and Stroke (U.S.); D011379:Prognosis; D011859:Radiography; D020521:Stroke / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000628:therapy*; D015912:Thrombolytic Therapy / Q000379:methods* / Q000592:standards*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome; D014481:United States
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator
keywords: brain ischemia; cerebrovascular disorders; hemorrhage; stroke; thrombolysis
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