This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (138)  • Contact me when this article is cited  Related Content  • Related article  • Similar articles in JAMA  Topic Collections  • Neurology  • Cerebrovascular Disease  • Stroke  • Alert me on articles by topic  Social Bookmarking   What's this?

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).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati     What's this?

RELATED ARTICLE

December 12, 2001
JAMA. 2001;286(22):2883-2884.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

ABC/2 for rapid clinical estimate of infarct, perfusion, and mismatch volumes
Sims et al.
Neurology 2009;72:2104-2110.
ABSTRACT | FULL TEXT  

Acute Stroke Triage to Intravenous Thrombolysis and Other Therapies with Advanced CT or MR Imaging: Pro MR Imaging
Kohrmann and Schellinger
Radiology 2009;251:627-633.
FULL TEXT  

The HAT Score: A simple grading scale for predicting hemorrhage after thrombolysis
Lou et al.
Neurology 2008;71:1417-1423.
ABSTRACT | FULL TEXT  

Symptomatic intracerebral hemorrhage and recanalization after IV rt-PA: A multicenter study
Saqqur et al.
Neurology 2008;71:1304-1312.
ABSTRACT | FULL TEXT  

Intracerebral haemorrhage after thrombolysis for acute ischaemic stroke: an update
Derex and Nighoghossian
J. Neurol. Neurosurg. Psychiatry 2008;79:1093-1099.
ABSTRACT | FULL TEXT  

Thrombolysis for acute ischaemic stroke: a new challenge for emergency medicine
Kendall
Emerg. Med. J. 2008;25:471-475.
ABSTRACT | FULL TEXT  

Haemorrhagic transformation in acute ischaemic stroke following thrombolysis therapy: classification, pathogenesis and risk factors
Thanvi et al.
Postgrad. Med. J. 2008;84:361-367.
ABSTRACT | FULL TEXT  

Antithrombotic and Thrombolytic Therapy for Ischemic Stroke: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition)
Albers et al.
Chest 2008;133:630S-669S.
ABSTRACT | FULL TEXT  

Alberta Stroke Program Early CT Scoring of CT Perfusion in Early Stroke Visualization and Assessment
Aviv et al.
Am. J. Neuroradiol. 2007;28:1975-1980.
ABSTRACT | FULL TEXT  

Intravenous Alteplase for Stroke: Beyond the Guidelines and in Particular Clinical Situations
De Keyser et al.
Stroke 2007;38:2612-2618.
ABSTRACT | FULL TEXT  

Can the Ischemic Penumbra Be Identified on Noncontrast CT of Acute Stroke?
Muir et al.
Stroke 2007;38:2485-2490.
ABSTRACT | FULL TEXT  

Acute Ischemic Stroke
van der Worp and van Gijn
NEJM 2007;357:572-579.
FULL TEXT  

Intravenous thrombolysis in acute ischaemic stroke: from trial exclusion criteria to clinical contraindications. An international Delphi study
Dirks et al.
J. Neurol. Neurosurg. Psychiatry 2007;78:685-689.
ABSTRACT | FULL TEXT  

CT-NIHSS Mismatch Does Not Correlate With MRI Diffusion-Perfusion Mismatch
Messe et al.
Stroke 2007;38:2079-2084.
ABSTRACT | FULL TEXT  

Guidelines for the Early Management of Adults With Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists.
Adams et al.
Circulation 2007;115:e478-e534.
ABSTRACT | FULL TEXT  

Guidelines for the Early Management of Adults With Ischemic Stroke: A Guideline From the American Heart Association/ American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: The American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists
Adams et al.
Stroke 2007;38:1655-1711.
ABSTRACT | FULL TEXT  

Identification of the penumbra and infarct core on hyperacute noncontrast and perfusion CT
Parsons et al.
Neurology 2007;68:730-736.
ABSTRACT | FULL TEXT  

Intracranial Hemorrhage Associated With Revascularization Therapies
Khatri et al.
Stroke 2007;38:431-440.
ABSTRACT | FULL TEXT  

African American women have poor long-term survival following ischemic stroke.
Qureshi et al.
Neurology 2006;67:1623-1629.
ABSTRACT | FULL TEXT  

Reversed Discrepancy between CT and Diffusion-Weighted MR Imaging in Acute Ischemic Stroke.
Kim et al.
Am. J. Neuroradiol. 2006;27:1990-1995.
ABSTRACT | FULL TEXT  

Association of Serial Biochemical Markers With Acute Ischemic Stroke: The National Institute of Neurological Disorders and Stroke Recombinant Tissue Plasminogen Activator Stroke Study
Jauch et al.
Stroke 2006;37:2508-2513.
ABSTRACT | FULL TEXT  

How well does ASPECTS predict the outcome of acute stroke treated with IV tPA?
Weir et al.
Neurology 2006;67:516-518.
ABSTRACT | FULL TEXT  

Hemostatic Activation and Outcome After Recombinant Tissue Plasminogen Activator Therapy for Acute Ischemic Stroke
Tanne et al.
Stroke 2006;37:1798-1804.
ABSTRACT | FULL TEXT  

Is IV tissue plasminogen activator beneficial in patients with hyperdense artery sign?
Qureshi et al.
Neurology 2006;66:1171-1174.
ABSTRACT | FULL TEXT  

Extent of Early Ischemic Changes on Computed Tomography (CT) Before Thrombolysis: Prognostic Value of the Alberta Stroke Program Early CT Score in ECASS II
Dzialowski et al.
Stroke 2006;37:973-978.
ABSTRACT | FULL TEXT  

Presence of Early Ischemic Changes on Computed Tomography Depends on Severity and the Duration of Hypoperfusion: A Single Photon Emission-Computed Tomographic Study
Hirano et al.
Stroke 2005;36:2601-2608.
ABSTRACT | FULL TEXT  

Importance of Early Ischemic Computed Tomography Changes Using ASPECTS in NINDS rtPA Stroke Study
Demchuk et al.
Stroke 2005;36:2110-2115.
ABSTRACT | FULL TEXT  

CT Sign of Brain Swelling without Concomitant Parenchymal Hypoattenuation: Comparison with Diffusion- and Perfusion-weighted MR Imaging
Na et al.
Radiology 2005;235:992-948.
ABSTRACT | FULL TEXT  

Prediction of Hemorrhagic Transformation in Acute Ischemic Stroke: Role of Diffusion-Weighted Imaging and Early Parenchymal Enhancement
Kim et al.
Am. J. Neuroradiol. 2005;26:1050-1055.
ABSTRACT | FULL TEXT  

Early Signs of Brain Infarction at CT: Observer Reliability and Outcome after Thrombolytic Treatment--Systematic Review
Wardlaw and Mielke
Radiology 2005;235:444-453.
ABSTRACT | FULL TEXT  

ASPECTS on CTA Source Images Versus Unenhanced CT: Added Value in Predicting Final Infarct Extent and Clinical Outcome
Coutts et al.
Stroke 2004;35:2472-2476.
ABSTRACT | FULL TEXT  

Multiparametric Iterative Self-Organizing MR Imaging Data Analysis Technique for Assessment of Tissue Viability in Acute Cerebral Ischemia
Mitsias et al.
Am. J. Neuroradiol. 2004;25:1499-1508.
ABSTRACT | FULL TEXT  

Hourly Blood Pressure Monitoring After Intravenous Tissue Plasminogen Activator for Ischemic Stroke: Does Everyone Need It?
Aiyagari et al.
Stroke 2004;35:2326-2330.
ABSTRACT | FULL TEXT  

Antithrombotic and Thrombolytic Therapy for Ischemic Stroke: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy
Albers et al.
Chest 2004;126:483S-512S.
ABSTRACT | FULL TEXT  

Are There Time-Dependent Differences in Diffusion and Perfusion Within the First 6 Hours After Stroke Onset?
Fiehler et al.
Stroke 2004;35:2099-2104.
ABSTRACT | FULL TEXT  

Predictors of Hyperacute Clinical Worsening in Ischemic Stroke Patients Receiving Thrombolytic Therapy
Leigh et al.
Stroke 2004;35:1903-1907.
ABSTRACT | FULL TEXT  

Diagnosis of stroke on neuroimaging
Wardlaw and Farrall
BMJ 2004;328:655-656.
FULL TEXT  

Case 5-2004 - A 57-Year-Old Man with Slurred Speech and Left Hemiparesis
Carter et al.
NEJM 2004;350:707-716.
FULL TEXT  

Ischemic Stunning of the Brain: Early Recanalization Without Immediate Clinical Improvement in Acute Ischemic Stroke
Alexandrov et al.
Stroke 2004;35:449-452.
ABSTRACT | FULL TEXT  

Early Ischemic Signs Should Not Be Used as Exclusion Criteria in Thrombolysis Trials * Response
Hamann et al.
Stroke 2004;35 :e3-e4.
FULL TEXT  

NIHSS/EIC Mismatch Explains the >1/3 MCA Conundrum * Response * Response
Grotta et al.
Stroke 2003;34 :e148-e149.
FULL TEXT  

Selection of Acute Ischemic Stroke Patients for Intra-Arterial Thrombolysis With Pro-Urokinase by Using ASPECTS
Hill et al.
Stroke 2003;34:1925-1931.
ABSTRACT | FULL TEXT  

Community-Based Thrombolytic Therapy of Acute Ischemic Stroke in Helsinki
Lindsberg et al.
Stroke 2003;34:1443-1449.
ABSTRACT | FULL TEXT  

May 13 Highlights
Neurology 2003;60:1403-1405.
FULL TEXT  

Sensitivity and Interrater Agreement of CT and Diffusion-Weighted MR Imaging in Hyperacute Stroke
Saur et al.
Am. J. Neuroradiol. 2003;24:878-885.
ABSTRACT | FULL TEXT  

Factors Influencing Outcome and Treatment Effect in PROACT II
Wechsler et al.
Stroke 2003;34:1224-1229.
ABSTRACT | FULL TEXT  

Visible infarction on computed tomography is an independent predictor of poor functional outcome after stroke, and not of haemorrhagic transformation
Wardlaw et al.
J. Neurol. Neurosurg. Psychiatry 2003;74:452-458.
ABSTRACT | FULL TEXT  

Guidelines for the Early Management of Patients With Ischemic Stroke: A Scientific Statement From the Stroke Council of the American Stroke Association
Adams et al.
Stroke 2003;34:1056-1083.
FULL TEXT  

Early Major Ischemic Changes on Computed Tomography Should Preclude Use of Tissue Plasminogen Activator
von Kummer
Stroke 2003;34:820-821.
FULL TEXT  

Early Major Ischemic Changes on Computed Tomography Should Not Preclude Use of Tissue Plasminogen Activator
Lyden
Stroke 2003;34:821-822.
FULL TEXT  

Stroke Neuroimaging
Warach
Stroke 2003;34:345-347.
FULL TEXT  

Imaging-Based Decision Making in Thrombolytic Therapy for Ischemic Stroke: Present Status
Schellinger et al.
Stroke 2003;34:575-583.
ABSTRACT | FULL TEXT  

Cerebral Blood Flow Predicts Lesion Growth in Acute Stroke Patients
Fiehler et al.
Stroke 2002;33:2421-2425.
ABSTRACT | FULL TEXT  

Treatment of Acute Ischemic Stroke: Part I: Recanalization Strategies
Broderick and Hacke
Circulation 2002;106:1563-1569.
FULL TEXT  

Baseline Blood Pressure but Not Early Computed Tomography Changes Predicts Major Hemorrhage After Streptokinase in Acute Ischemic Stroke
Gilligan et al.
Stroke 2002;33:2236-2242.
ABSTRACT | FULL TEXT  

Correlation of Apparent Diffusion Coefficient and Computed Tomography Density in Acute Ischemic Stroke
Kucinski et al.
Stroke 2002;33:1786-1791.
ABSTRACT | FULL TEXT  

Thrombolytic Treatment of Acute Ischemic Stroke
Meschia et al.
Mayo Clin Proc. 2002;77:542-551.
ABSTRACT  

Early Ischemic Changes on Computed Tomography in Patients With Acute Stroke
Fiorelli et al.
JAMA 2002;287:2361-2362.
FULL TEXT