title: Acute Ischemic Stroke with Very Early Clinical Improvement: A National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator Stroke Trials Exploratory Analysis.
abstract: BACKGROUND
  A high proportion of patients excluded from recombinant tissue plasminogen activator (rt-PA) treatment because of rapid improvement occurring before treatment decision had incomplete recovery. The National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Trials dataset allows for systematic analyses of very early postrandomization improvement (VEPRIM) in stroke severity as a National Institutes of Health Stroke Scale (NIHSS) score was available for all subjects enrolled in the study at baseline (NIHSSB) and at 2 hours after randomization (NIHSS2H). We explored various definitions of VEPRIM to characterize predictive values for clinical outcomes.
  
  
  METHODS
  Post hoc analyses of the NINDS rt-PA Stroke Trials were conducted. VEPRIM was defined as the difference between the NIHSSB and the NIHSS2H scores using 3 approaches: raw, percent, and normalized change. We assessed the association between VEPRIM and 3-month favorable outcome (mRS score of 0-1), symptomatic intracerebral hemorrhage (sICH), and death.
  
  
  RESULTS
  In the 624 subjects, every VEPRIM definition was independently associated with an increased probability of favorable outcome: for each unit of change within the VEPRIM definitions, there were 2%-24% (all P < .05) relative increased probability of favorable outcome, 2%-15% (all P < .05) decreased likelihood of death, and 2%-13% (all P < .05) decreased likelihood of sICH. Adjusting for NIHSSB and prestroke mRS scores, there was a significant rt-PA treatment effect for improvement seen for all 3 VEPRIM definitions.
  
  
  CONCLUSIONS
  VEPRIM predicted favorable outcomes independent of definition and treatment arm. Patients with VEPRIM by any definition, while doing better than patients without VEPRIM, also derived increased clinical benefit when treated with rt-PA compared to placebo. Even with VEPRIM, a substantial percentage of patients had unfavorable outcomes.
authors.affiliation: Downstate Medical Center, The State University of New York, Brooklyn, New York. Electronic address: clotilde.balucani@downstate.edu.
authors.forename: Clotilde
authors.initials: C
authors.lastname: Balucani
authors.affiliation: Downstate Medical Center, The State University of New York, Brooklyn, New York; Departments of Neurology and Emergency Medicine, Kings County Medical Center, Brooklyn, New York.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Levine
authors.affiliation: Department of Pediatrics, University of Cincinnati, Cincinnati Children's Hospital, Cincinnati, Ohio.
authors.forename: Jane C
authors.initials: JC
authors.lastname: Khoury
authors.affiliation: Department of Neurology, University of Cincinnati Medical Center, Cincinnati, Ohio.
authors.forename: Pooja
authors.initials: P
authors.lastname: Khatri
authors.affiliation: Department of Neurology, University of California Los Angeles, Los Angeles, California.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Saver
authors.affiliation: Department of Neurology, University of Cincinnati Medical Center, Cincinnati, Ohio.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Broderick
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D055825:National Institute of Neurological Disorders and Stroke (U.S.) / Q000592:standards; D017063:Outcome Assessment, Health Care / Q000379:methods* / Q000592:standards*; D012720:Severity of Illness Index; D020521:Stroke / Q000188:drug therapy*; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D016896:Treatment Outcome; D014481:United States
chemical_list: D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator
keywords: Acute stroke; minor stroke; rapidly improving stroke symptoms; stroke outcomes; tPA; thrombolysis