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Suresh C. Patel, MD; Steven R. Levine, MD; Barbara C. Tilley, PhD; James C. Grotta, MD; Mei Lu, PhD; Michael Frankel, MD; E. Clarke Haley, Jr, MD; Thomas G. Brott, MD; Joseph P. Broderick, MD; Steven Horowitz, MD; Patrick D. Lyden, MD; Christopher A. Lewandowski, MD; John R. Marler, MD; K. M. A. Welch, MD; for the National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group

JAMA. 2001;286:2830-2838.

Context  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.

Design and Setting  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).

Patients  Of 624 patients enrolled in the trial, baseline CT scans were retrieved and reviewed for 616 (99%).

Main Outcome Measures  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 ( = 0.23; P<.001) and time from stroke onset to baseline CT scan ( = 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.

Author Affiliations: Henry Ford Hospital and Health Science Centers, Detroit, Mich (Drs Patel, Lu, and Lewandowski); Mount Sinai School of Medicine, New York, NY (Dr Levine); Medical University of South Carolina, Charleston (Dr Tilley); University of Texas Medical Center, Houston (Dr Grotta); Emory University School of Medicine, Atlanta, Ga (Dr Frankel); University of Virginia Health System, Charlottesville (Dr Haley); Mayo Clinic, Jacksonville, Fla (Dr Brott); University of Cincinnati, Cincinnati, Ohio (Dr Broderick); University of Missouri, Columbia (Dr Horowitz); University of California Stroke Center, San Diego (Dr Lyden); National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Md (Dr Marler); and University of Kansas Medical School, Kansas City (Dr Welch). A complete list of the National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group members has been published previously (N Engl J Med. 1995;333:1586-1587).

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