Stroke, Vol 23, 632-640, Copyright © 1992 by American Heart Association
TG Brott, EC Haley Jr, DE Levy, W Barsan, J Broderick, GL Sheppard, J Spilker, GL Kongable, S Massey and R Reed
BACKGROUND AND PURPOSE: Thrombolytic agents hold theoretical promise as
therapy for cerebral infarction. This study was designed to evaluate the
safety of tissue plasminogen activator, to accomplish urgent patient
treatment, and to estimate potential efficacy of tissue plasminogen
activator. METHODS: Following neurological evaluation and computed
tomography of the brain, patients with acute ischemic stroke were evaluated
and treated with intravenous tissue plasminogen activator under an
open-label, dose-escalation design within 90 minutes from symptom onset.
End points examined included symptomatic and asymptomatic intracranial
hematoma, systemic hemorrhage, and neurological outcome at 2 hours, 24
hours, and 3 months. RESULTS: Seventy-four patients were treated within 90
minutes of symptom onset over seven dose tiers of tissue plasminogen
activator, ranging from 0.35 mg/kg to 1.08 mg/kg. Intracranial hematoma
with associated neurological deterioration occurred in three patients and
was related to increasing doses of tissue plasminogen activator (p =
0.045). Intracranial hematoma did not occur in any of the 58 patients
treated with less than or equal to 0.85 mg/kg. Major neurological
improvement occurred in 22 patients (30%) at 2 hours from the initiation of
tissue plasminogen activator and in a total of 34 patients (46%) at 24
hours, but major neurological improvement was not related to increasing
doses of tissue plasminogen activator or to stroke type. CONCLUSIONS:
Patients with acute stroke can be evaluated and treated within 90 minutes.
Tissue plasminogen activator for acute ischemic infarction is not without
risk, but the potential for clinical benefit justifies a randomized
clinical trial. To date, differences in hemorrhagic risk or neurological
benefit of tissue plasminogen activator for particular ischemic stroke
types are not apparent.
ARTICLES
Urgent therapy for stroke. Part I. Pilot study of tissue plasminogen activator administered within 90 minutes
Department of Neurology, University of Cincinnati, Ohio.
This article has been cited by other articles:
 |
|
 |
|
  B R Thanvi, S Treadwell, and T Robinson Haemorrhagic transformation in acute ischaemic stroke following thrombolysis therapy: classification, pathogenesis and risk factors Postgrad. Med. J., July 1, 2008; 84(993): 361 - 367. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.J. Dickinson Intracerebral haemorrhage revisited QJM, November 1, 2007; 100(11): 715 - 719. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Pagola, M. Ribo, J. Alvarez-Sabin, M. Lange, M. Rubiera, and C. A. Molina Timing of Recanalization After Microbubble-Enhanced Intravenous Thrombolysis in Basilar Artery Occlusion Stroke, November 1, 2007; 38(11): 2931 - 2934. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Fiehler, G. W. Albers, J.-M. Boulanger, L. Derex, A. Gass, N. Hjort, J. S. Kim, D. S. Liebeskind, T. Neumann-Haefelin, S. Pedraza, et al. Bleeding Risk Analysis in Stroke Imaging Before ThromboLysis (BRASIL): Pooled Analysis of T2*-Weighted Magnetic Resonance Imaging Data From 570 Patients Stroke, October 1, 2007; 38(10): 2738 - 2744. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kunte, S. Schmidt, M. Eliasziw, G. J. del Zoppo, J. M. Simard, F. Masuhr, M. Weih, and U. Dirnagl Sulfonylureas Improve Outcome in Patients With Type 2 Diabetes and Acute Ischemic Stroke Stroke, September 1, 2007; 38(9): 2526 - 2530. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.W. Kerber, I. Wanke, J. Bernard Jr., H.H. Woo, M.W. Liu, and P.K. Nelson Rapid Intracranial Clot Removal with a New Device: The Alligator Retriever AJNR Am. J. Neuroradiol., May 1, 2007; 28(5): 860 - 863. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Sattin, S. E. Olson, L. Liu, R. Raman, and P. D. Lyden An Expedited Code Stroke Protocol Is Feasible and Safe Stroke, December 1, 2006; 37(12): 2935 - 2939. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. Tomsick 2006: A Stroke Odyssey AJNR Am. J. Neuroradiol., November 1, 2006; 27(10): 2019 - 2021. [Full Text] [PDF]
|
|
|
|
|
|
T. Yamaguchi, E. Mori, K. Minematsu, J. Nakagawara, K. Hashi, I. Saito, Y. Shinohara, and for the Japan Alteplase Clinical Trial (J-ACT) Gro Alteplase at 0.6 mg/kg for Acute Ischemic Stroke Within 3 Hours of Onset: Japan Alteplase Clinical Trial (J-ACT) * Supplemental Appendix 2 Stroke, July 1, 2006; 37(7): 1810 - 1815. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R.M. Sugg, E.A. Noser, H.M. Shaltoni, N.R. Gonzales, M.S. Campbell, R. Weir, E.D. Cacayorin, and J.C. Grotta Intra-arterial reteplase compared to urokinase for thrombolytic recanalization in acute ischemic stroke. AJNR Am. J. Neuroradiol., April 1, 2006; 27(4): 769 - 773. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ribo, J. Alvarez-Sabin, J. Montaner, F. Romero, P. Delgado, M. Rubiera, R. Delgado-Mederos, and C. A. Molina Temporal Profile of Recanalization After Intravenous Tissue Plasminogen Activator: Selecting Patients for Rescue Reperfusion Techniques Stroke, April 1, 2006; 37(4): 1000 - 1004. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Yong, H.-C. Diener, M. Kaste, and J. Mau Characteristics of Blood Pressure Profiles as Predictors of Long-Term Outcome After Acute Ischemic Stroke Stroke, December 1, 2005; 36(12): 2619 - 2625. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ribo, C. Molina, J. Montaner, M. Rubiera, R. Delgado-Mederos, J. F. Arenillas, M. Quintana, and J. Alvarez-Sabin Acute Hyperglycemia State Is Associated With Lower tPA-Induced Recanalization Rates in Stroke Patients Stroke, August 1, 2005; 36(8): 1705 - 1709. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Khatri, J. P. Broderick, A. M. Pancioli, E. C. Haley Jr, K. C. Johnston, P. D. Lyden, T. M. Hemmen, and For the TNK in Stroke Investigators Risk of Thrombolysis-Associated Intracerebral Hemorrhage: The Need to Compare Apples With Apples * Response: Stroke, June 1, 2005; 36(6): 1109 - 1110. [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Hill, A. M. Buchan, and for The Canadian Alteplase for Stroke Effectivenes Thrombolysis for acute ischemic stroke: results of the Canadian Alteplase for Stroke Effectiveness Study Can. Med. Assoc. J., May 10, 2005; 172(10): 1307 - 1312. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ribo, C. A. Molina, A. Rovira, M. Quintana, P. Delgado, J. Montaner, E. Grive, J. F. Arenillas, and J. Alvarez-Sabin Safety and Efficacy of Intravenous Tissue Plasminogen Activator Stroke Treatment in the 3- to 6-Hour Window Using Multimodal Transcranial Doppler/MRI Selection Protocol Stroke, March 1, 2005; 36(3): 602 - 606. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Ingall, W. M. O'Fallon, K. Asplund, L. R. Goldfrank, V. S. Hertzberg, T. A. Louis, and T. J. H. Christianson Findings From the Reanalysis of the NINDS Tissue Plasminogen Activator for Acute Ischemic Stroke Treatment Trial Stroke, October 1, 2004; 35(10): 2418 - 2424. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ribo, J. Montaner, C. A. Molina, J. F. Arenillas, E. Santamarina, M. Quintana, and J. Alvarez-Sabin Admission Fibrinolytic Profile Is Associated With Symptomatic Hemorrhagic Transformation in Stroke Patients Treated With Tissue Plasminogen Activator Stroke, September 1, 2004; 35(9): 2123 - 2127. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Montaner, I. Fernandez-Cadenas, C. A. Molina, J. Monasterio, J. F. Arenillas, M. Ribo, M. Quintana, P. Chacon, A. L. Andreu, and J. Alvarez-Sabin Safety Profile of Tissue Plasminogen Activator Treatment Among Stroke Patients Carrying a Common Polymorphism (C-1562T) in the Promoter Region of the Matrix Metalloproteinase-9 Gene Stroke, December 1, 2003; 34(12): 2851 - 2855. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. Seitz, M. Hamzavi, U. Junghans, P. A. Ringleb, C. Schranz, and M. Siebler Thrombolysis With Recombinant Tissue Plasminogen Activator and Tirofiban in Stroke: Preliminary Observations Stroke, August 1, 2003; 34(8): 1932 - 1935. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Montaner, C. A. Molina, J. Monasterio, S. Abilleira, J. F. Arenillas, M. Ribo, M. Quintana;, and J. Alvarez-Sabin Matrix Metalloproteinase-9 Pretreatment Level Predicts Intracranial Hemorrhagic Complications After Thrombolysis in Human Stroke Circulation, February 4, 2003; 107(4): 598 - 603. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Castellanos, R. Leira, J. Serena, J. M. Pumar, I. Lizasoain, J. Castillo, A. Davalos, and G. F. Hamann Plasma Metalloproteinase-9 Concentration Predicts Hemorrhagic Transformation in Acute Ischemic Stroke * Editorial Comment Stroke, January 1, 2003; 34(1): 40 - 46. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A.K. Gilligan, R. Markus, S. Read, V. Srikanth, T. Hirano, G. Fitt, M. Arends, B.R. Chambers, S.M. Davis, and G.A. Donnan Baseline Blood Pressure but Not Early Computed Tomography Changes Predicts Major Hemorrhage After Streptokinase in Acute Ischemic Stroke Stroke, September 1, 2002; 33(9): 2236 - 2242. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Montaner, J. Alvarez-Sabin, C. Molina, A. Angles, S. Abilleira, J. Arenillas, M. A. Gonzalez, and J. Monasterio Matrix Metalloproteinase Expression After Human Cardioembolic Stroke: Temporal Profile and Relation to Neurological Impairment Stroke, August 1, 2001; 32(8): 1759 - 1766. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Berger, M. Fiorelli, T. Steiner, W.-R. Schabitz, L. Bozzao, E. Bluhmki, W. Hacke, and R. von Kummer Hemorrhagic Transformation of Ischemic Brain Tissue : Asymptomatic or Symptomatic? Stroke, June 1, 2001; 32(6): 1330 - 1335. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Tejima, Y. Katayama, Y. Suzuki, T. Kano, and E. H. Lo Hemorrhagic Transformation After Fibrinolysis With Tissue Plasminogen Activator : Evaluation of Role of Hypertension With Rat Thromboembolic Stroke Model Stroke, June 1, 2001; 32(6): 1336 - 1340. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Grotta, K. M. A. Welch, S. C. Fagan, M. Lu, M. R. Frankel, T. Brott, S. R. Levine, P. D. Lyden, and P. D. Lyden Clinical Deterioration Following Improvement in the NINDS rt-PA Stroke Trial Stroke, March 1, 2001; 32(3): 661 - 668. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A C Pereira, P J Martin, and E A Warburton Thrombolysis in acute ischaemic stroke Postgrad. Med. J., March 1, 2001; 77(905): 166 - 171. [Full Text]
|
|
|
|
|
|
V. Keris, S. Rudnicka, V. Vorona, G. Enina, B. Tilgale, and J. Fricbergs Combined Intraarterial/Intravenous Thrombolysis for Acute Ischemic Stroke AJNR Am. J. Neuroradiol., February 1, 2001; 22(2): 352 - 358. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Roth, L. Lovell, R. L. Harvey, A. W. Heinemann, P. Semik, and S. Diaz Incidence of and Risk Factors for Medical Complications During Stroke Rehabilitation Stroke, February 1, 2001; 32(2): 523 - 529. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Marler, B. C. Tilley, M. Lu, T. G. Brott, P. C. Lyden, J. C. Grotta, J. P. Broderick, S. R. Levine, M. P. Frankel, S. H. Horowitz, et al. Early stroke treatment associated with better outcome: The NINDS rt-PA Stroke Study Neurology, December 12, 2000; 55(11): 1649 - 1655. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Broderick, M. Lu, R. Kothari, S. R. Levine, P. D. Lyden, E. C. Haley, T. G. Brott, J. Grotta, B. C. Tilley, J. R. Marler, et al. Finding the Most Powerful Measures of the Effectiveness of Tissue Plasminogen Activator in the NINDS tPA Stroke Trial Stroke, October 1, 2000; 31(10): 2335 - 2341. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Mohr Thrombolytic Therapy for Ischemic Stroke: From Clinical Trials to Clinical Practice JAMA, March 1, 2000; 283(9): 1189 - 1191. [Full Text] [PDF]
|
|
|
|
|
|
P. Trouillas, L. Derex, N. Nighoghossian, J. Honnorat, W. Li, P. Neuschwander, G. Riche, J. C. Getenet, Y. Berthezene, F. Turjman, et al. rtPA intravenous thrombolysis in anterior choroidal artery territory stroke Neurology, February 8, 2000; 54(3): 666 - 666. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Lewandowski, M. Frankel, T. A. Tomsick, J. Broderick, J. Frey, W. Clark, S. Starkman, J. Grotta, J. Spilker, J. Khoury, et al. Combined Intravenous and Intra-Arterial r-TPA Versus Intra-Arterial Therapy of Acute Ischemic Stroke : Emergency Management of Stroke (EMS) Bridging Trial Stroke, December 1, 1999; 30(12): 2598 - 2605. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Yanamoto, I. Nagata, I. Nakahara, N. Tohnai, Z. Zhang, H. Kikuchi, and C. Iadecola Combination of Intraischemic and Postischemic Hypothermia Provides Potent and Persistent Neuroprotection Against Temporary Focal Ischemia in Rats • Editorial Comment Stroke, December 1, 1999; 30(12): 2720 - 2726. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fiorelli, S. Bastianello, R. von Kummer, G. J. del Zoppo, V. Larrue, E. Lesaffre, A. P. Ringleb, S. Lorenzano, C. Manelfe, and L. Bozzao Hemorrhagic Transformation Within 36 Hours of a Cerebral Infarct : Relationships With Early Clinical Deterioration and 3-Month Outcome in the European Cooperative Acute Stroke Study I (ECASS I) Cohort Stroke, November 1, 1999; 30(11): 2280 - 2284. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. I. Suarez, J. L. Sunshine, R. Tarr, O. Zaidat, W. R. Selman, C. Kernich, and D. M. D. Landis Predictors of Clinical Improvement, Angiographic Recanalization, and Intracranial Hemorrhage After Intra-Arterial Thrombolysis for Acute Ischemic Stroke Stroke, October 1, 1999; 30(10): 2094 - 2100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Zivin Thrombolytic stroke therapy: Past, present, and future Neurology, July 1, 1999; 53(1): 14 - 14. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-M. Lai, P. W. Duncan, and J. Keighley Prediction of Functional Outcome After Stroke : Comparison of the Orpington Prognostic Scale and the NIH Stroke Scale Stroke, September 1, 1998; 29(9): 1838 - 1842. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Brott, M. Lu, R. Kothari, S. C. Fagan, M. Frankel, J. C. Grotta, J. Broderick, T. Kwiatkowski, C. Lewandowski, E. C. Haley Jr, et al. Hypertension and Its Treatment in the NINDS rt-PA Stroke Trial Stroke, August 1, 1998; 29(8): 1504 - 1509. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Grond, C. Stenzel, S. Schmulling, J. Rudolf, M. Neveling, A. Lechleuthner, S. Schneweis, and W.-D. Heiss Early Intravenous Thrombolysis for Acute Ischemic Stroke in a Community-Based Approach Stroke, August 1, 1998; 29(8): 1544 - 1549. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Slyter Ethical Challenges in Stroke Research Stroke, August 1, 1998; 29(8): 1725 - 1729. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Wildermuth, M. Knauth, T. Brandt, R. Winter, K. Sartor, and W. Hacke Role of CT Angiography in Patient Selection for Thrombolytic Therapy in Acute Hemispheric Stroke Stroke, May 1, 1998; 29(5): 935 - 938. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Pancioli, J. Broderick, R. Kothari, T. Brott, A. Tuchfarber, R. Miller, J. Khoury, and E. Jauch Public Perception of Stroke Warning Signs and Knowledge of Potential Risk Factors JAMA, April 22, 1998; 279(16): 1288 - 1292. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. D. Firlik, A. M. Kaufmann, L. R. Wechsler, K. S. Firlik, M. B. Fukui, and H. Yonas Quantitative Cerebral Blood Flow Determinations in Acute Ischemic Stroke : Relationship to Computed Tomography and Angiography Stroke, November 1, 1997; 28(11): 2208 - 2213. [Abstract] [Full Text]
|
|
|
|
|
|
T. F. Choudhri, B. L. Hoh, R. A. Solomon, E. S. Connolly Jr, and D. J. Pinsky Use of a Spectrophotometric Hemoglobin Assay to Objectively Quantify Intracerebral Hemorrhage in Mice Stroke, November 1, 1997; 28(11): 2296 - 2302. [Abstract] [Full Text]
|
|
|
|
 |
|
 L. R. Caplan, J. P. Mohr, J. P. Kistler, W. Koroshetz, J. Grotta, L. R. Caplan, J. P. Mohr, J. P. Kistler, W. Koroshetz, and J. Grotta Should Thrombolytic Therapy Be the First-Line Treatment for Acute Ischemic Stroke? N. Engl. J. Med., October 30, 1997; 337(18): 1309 - 1313. [Full Text]
|
|
|
|
|
|
A Systems Approach to Immediate Evaluation and Management of Hyperacute Stroke : Experience at Eight Centers and Implications for Community Practice and Patient Care Stroke, August 1, 1997; 28(8): 1530 - 1540. [Abstract] [Full Text]
|
|
|
|
|
|
C. Motto, E. Aritzu, E. Boccardi, C. De Grandi, A. Piana, and L. Candelise Reliability of Hemorrhagic Transformation Diagnosis in Acute Ischemic Stroke Stroke, February 1, 1997; 28(2): 302 - 306. [Abstract] [Full Text]
|
|
|
|
|
|
B. C. Tilley, J. Marler, N. L. Geller, M. Lu, J. Legler, T. Brott, P. Lyden, and J. Grotta Use of a Global Test for Multiple Outcomes in Stroke Trials With Application to the National Institute of Neurological Disorders and Stroke t-PA Stroke Trial Stroke, November 1, 1996; 27(11): 2136 - 2142. [Abstract] [Full Text]
|
|
|
|
|
|
H. P. Adams, T. G. Brott, A. J. Furlan, C. R. Gomez, J. Grotta, C. M. Helgason, T. Kwiatkowski, P. D. Lyden, J. R. Marler, J. Torner, et al. Guidelines for Thrombolytic Therapy for Acute Stroke: A Supplement to the Guidelines for the Management of Patients With Acute Ischemic Stroke: A Statement for Healthcare Professionals From a Special Writing Group of the Stroke Council, American Heart Association Circulation, September 1, 1996; 94(5): 1167 - 1174. [Full Text]
|
|
|
|
|
|
J. Rother, F. Guckel, W. Neff, A. Schwartz, and M. Hennerici Assessment of Regional Cerebral Blood Volume in Acute Human Stroke by Use of Single-Slice Dynamic Susceptibility Contrast-Enhanced Magnetic Resonance Imaging Stroke, June 1, 1996; 27(6): 1088 - 1093. [Abstract] [Full Text]
|
|
|
|
|
|
P. Trouillas, N. Nighoghossian, J.-C. Getenet, G. Riche, P. Neuschwander, J.-C. Froment, F. Turjman, J.-X. Jin, D. Malicier, G. Fournier, et al. Open Trial of Intravenous Tissue Plasminogen Activator in Acute Carotid Territory Stroke : Correlations of Outcome With Clinical and Radiological Data Stroke, May 1, 1996; 27(5): 882 - 890. [Abstract] [Full Text]
|
|
|
|
|
|
The National Institute of Neurological Disorders a Tissue Plasminogen Activator for Acute Ischemic Stroke N. Engl. J. Med., December 14, 1995; 333(24): 1581 - 1588. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. F. Hamann, Y. Okada, R. Fitridge, and G. J. del Zoppo Microvascular Basal Lamina Antigens Disappear During Cerebral Ischemia and Reperfusion Stroke, November 1, 1995; 26(11): 2120 - 2126. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. L. Frey, K. A. Greene, M. H. Khayata, B. L. Dean, J. A. Hodak, and R. F. Spetzler Intrathrombus Administration of Tissue Plasminogen Activator in Acute Cerebrovascular Occlusion Angiology, August 1, 1995; 46(8): 649 - 656. [Abstract] [PDF]
|
|
|
|
|
|
G. R. Thomas, H. Thibodeaux, C. J. Errett, M. M. Bednar, C. E. Gross, and W. F. Bennett Intravenous Aspirin Causes a Paradoxical Attenuation of Cerebrovascular Thrombolysis Stroke, June 1, 1995; 26(6): 1039 - 1046. [Abstract] [Full Text]
|
|
|
|