title: Strokes with minor symptoms: an exploratory analysis of the National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator trials.
abstract: OBJECTIVE
  The pivotal National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator trials excluded patients with ischemic stroke with specific minor presentations or rapidly improving symptoms. The recombinant tissue plasminogen activator product label notes that its use for minor neurological deficit or rapidly improving stroke symptoms has not been evaluated. As a result, patients with low National Institutes of Health Stroke Scale scores are not commonly treated in clinical practice. We sought to further characterize the patients with minor stroke who were included in the National Institute of Neurological Disorders and Stroke trials.
  
  
  METHODS
  Minor strokes were defined as National Institutes of Health Stroke Scale score ≤ 5 at baseline for this retrospective analysis, because this subgroup is most commonly excluded from treatment in clinical practice and trials. Clinical stroke syndromes were defined based on prespecified National Institutes of Health Stroke Scale item score clusters. Clinical outcomes were reviewed generally and within these cluster subgroups.
  
  
  RESULTS
  Only 58 cases had National Institutes of Health Stroke Scale scores of 0 to 5 in the National Institute of Neurological Disorders and Stroke trials (42 recombinant tissue plasminogen activator and 16 placebo), and 2971 patients were excluded from the trials due to "rapidly improving" or "minor symptoms" as the primary reason. No patients were enrolled with isolated motor symptoms, isolated facial droop, isolated ataxia, dysarthria, isolated sensory symptoms, or with only symptoms/signs not captured by the National Institutes of Health Stroke Scale score (ie, National Institutes of Health Stroke Scale=0). There were ≤ 3 patients with each of the other isolated deficits enrolled in the trial.
  
  
  CONCLUSIONS
  The National Institute of Neurological Disorders and Stroke trials excluded a substantial number of strokes with minor presentations, those that were included were small in number, and conclusions about outcomes based on specific syndromes cannot be drawn. Further prospective, systematic study of this subgroup is needed.
authors.affiliation: Department of Neurology, University of Cincinnati, Cincinnati, OH 45267-0525, USA. pooja.khatri@uc.edu
authors.forename: Pooja
authors.initials: P
authors.lastname: Khatri
authors.forename: Dawn O
authors.initials: DO
authors.lastname: Kleindorfer
authors.forename: Sharon D
authors.initials: SD
authors.lastname: Yeatts
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Saver
authors.forename: Steven R
authors.initials: SR
authors.lastname: Levine
authors.forename: Patrick D
authors.initials: PD
authors.lastname: Lyden
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Moomaw
authors.forename: Yuko Y
authors.initials: YY
authors.lastname: Palesch
authors.forename: Edward C
authors.initials: EC
authors.lastname: Jauch
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Broderick
mesh_terms: D000368:Aged; D003072:Cognition Disorders / Q000517:prevention & control; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D055825:National Institute of Neurological Disorders and Stroke (U.S.); D011994:Recombinant Proteins / Q000627:therapeutic use*; D012189:Retrospective Studies; 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: D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator
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