title: Lack of clinical significance of early ischemic changes on computed tomography in acute stroke.
abstract: BACKGROUND
  The prevalence and clinical significance of early ischemic changes (EICs) on baseline computed tomography (CT) scan of the head obtained within 3 hours of ischemic stroke are not established.
  
  
  OBJECTIVE
  To determine the frequency and significance of EIC on baseline head CT scans in the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA (recombinant tissue plasminogen activator) Stroke Trial.
  
  
  METHODS
  The original study, a randomized controlled trial, took place from January 1991 through October 1994 at 43 sites, during which CT images were obtained within 3 hours of symptom onset and prior to the initiation of rt-PA or placebo. For the current analysis, detailed reevaluation was undertaken after October 1994 of all baseline head CT scans with clinical data available pretreatment (blinded to treatment arm).
  
  
  METHODS
  Of 624 patients enrolled in the trial, baseline CT scans were retrieved and reviewed for 616 (99%).
  
  
  METHODS
  Frequency of EICs on baseline CT scans; association of EIC with other baseline variables; effect of EICs on deterioration at 24 hours (>/=4 points increase from the baseline National Institutes of Health Stroke Scale [NIHSS] score); clinical outcome (measured by 4 clinical scales) at 3 months, CT lesion volume at 3 months, death at 90 days; and symptomatic intracranial hemorrhage (ICH) within 36 hours of treatment.
  
  
  RESULTS
  The prevalence of EIC on baseline CT in the combined rt-PA and placebo groups was 31% (n = 194). The EIC was significantly associated with baseline NIHSS score (rho = 0.23; P<.001) and time from stroke onset to baseline CT scan (rho = 0.11; P =.007). After adjusting for baseline variables, there was no EIC x treatment interaction detected for any clinical outcome, including deterioration at 24 hours, 4 clinical scales, lesion volume, and death at 90 days (P>/=.25), implying that EIC is unlikely to affect response to rt-PA treatment. After adjusting for NIHSS score (an independent predictor of ICH), no EIC association with symptomatic ICH at 36 hours was detected in the group treated with rt-PA (P>/=.22).
  
  
  CONCLUSIONS
  Our analysis suggests that EICs are prevalent within 3 hours of stroke onset and correlate with stroke severity. However, EICs are not independently associated with increased risk of adverse outcome after rt-PA treatment. Patients treated with rt-PA did better whether or not they had EICs, suggesting that EICs on CT scan are not critical to the decision to treat otherwise eligible patients with rt-PA within 3 hours of stroke onset.
authors.affiliation: Division of Neuroradiology, Henry Ford Hospital and Health Science Centers, 2799 W Grand Blvd, K-3, Detroit, MI 48202-2689, USA. spatel@rad.hfh.edu
authors.forename: S C
authors.initials: SC
authors.lastname: Patel
authors.forename: S R
authors.initials: SR
authors.lastname: Levine
authors.forename: B C
authors.initials: BC
authors.lastname: Tilley
authors.forename: J C
authors.initials: JC
authors.lastname: Grotta
authors.forename: M
authors.initials: M
authors.lastname: Lu
authors.forename: M
authors.initials: M
authors.lastname: Frankel
authors.forename: E C
authors.initials: EC
authors.lastname: Haley
authors.forename: T G
authors.initials: TG
authors.lastname: Brott
authors.forename: J P
authors.initials: JP
authors.lastname: Broderick
authors.forename: S
authors.initials: S
authors.lastname: Horowitz
authors.forename: P D
authors.initials: PD
authors.lastname: Lyden
authors.forename: C A
authors.initials: CA
authors.lastname: Lewandowski
authors.forename: J R
authors.initials: JR
authors.lastname: Marler
authors.forename: K M
authors.initials: KM
authors.lastname: Welch
mesh_terms: D000368:Aged; D002545:Brain Ischemia / Q000000981:diagnostic imaging*; D006801:Humans; D020300:Intracranial Hemorrhages / Q000000981:diagnostic imaging; D016015:Logistic Models; D008875:Middle Aged; D010960:Plasminogen Activators / Q000627:therapeutic use*; D016012:Poisson Distribution; D011994:Recombinant Proteins; D012306:Risk; D012720:Severity of Illness Index; D020521:Stroke / Q000000981:diagnostic imaging* / Q000188:drug therapy* / Q000503:physiopathology; D016019:Survival Analysis; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D011994:Recombinant Proteins; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator