Effect of Intravenous Thrombolysis on MRI Parameters and Functional Outcome in Acute Stroke <6 Hours

Background and Purpose— The goals of this study were to examine MRI baseline characteristics of patients with acute ischemic stroke (AIS) and to study the influence of intravenous tissue plasminogen activator (tPA) on MR parameters and functional outcome using a multicenter approach. Methods— In this open-label, nonrandomized study of AIS patients with suspected anterior circulation stroke, subjects received a multiparametric stroke MRI protocol (diffusion- and perfusion-weighted imaging and MR angiography) within 6 hours after symptom onset and on follow-up. Patients were treated either with tPA (thrombolysis group) or conservatively (no thrombolysis group). Functional outcome was assessed on day 90 (modified Rankin Score; mRS). Results— We enrolled 139 AIS patients (no thrombolysis group, n=63; thrombolysis group, n=76). Patients treated with tPA were more severely affected (National Institutes of Health Stroke Scale score, 10 versus 13;P =0.002). Recanalization rates were higher in the thrombolysis group (Thrombolysis in Myocardial Infarction criteria 1 through 3 on day 1; 66.2% versus 32.7%;P <0.001). Proximal vessel occlusions resulted in larger infarct volumes and worse outcome (P =0.02). Thrombolysis was associated with a better outcome regardless of the time point of tPA treatment (≤3 hours or 3 to 6 hours) (univariate analysis: mRS ≤2, P =0.017; mRS ≤1, P =0.023). Age (P =0.003), thrombolytic therapy at 0 to 6 hours (P =0.01), recanalization (P =0.016), lesion volume on day 7 (P =0.001), and initial National Institutes of Health Stroke Scale score (P =0.001) affected functional outcome (mRS on day 90) positively (multivariate analysis). The time point of tPA therapy affected the recanalization rate (P =0.024) but not final infarct volume. Conclusions— In this pilot study, tPA therapy had a beneficial effect on vessel recanalization and functional outcome. Multiparametric MRI delineates tissue at risk of infarction in AIS patients, which may be helpful for the selection of patients for tPA therapy. tPA therapy appeared safe and effective beyond a 3-hour time window. This study delivers the rationale for a randomized, MR-based tPA trial.

[1]  R. Bloch,et al.  Interobserver agreement for the assessment of handicap in stroke patients. , 1988, Stroke.

[2]  E. Tournier-Lasserve.  CACNA1A mutations , 1999, Neurology.

[3]  P. Toutouzas,et al.  Percutaneous implantation of autologous vein graft stent for treatment of coronary artery disease , 1995, The Lancet.

[4]  A. Demchuk,et al.  Why are stroke patients excluded from TPA therapy? , 2001, Neurology.

[5]  J. Röther.  CT and MRI in the diagnosis of acute stroke and their role in thrombolysis. , 2001, Thrombosis research.

[6]  A. Furlan,et al.  Use of tissue-type plasminogen activator for acute ischemic stroke: the Cleveland area experience. , 2000, JAMA.

[7]  R. Higashida,et al.  Intra-arterial Prourokinase for Acute Ischemic Stroke: The PROACT II Study: A Randomized Controlled Trial , 1999 .

[8]  A. Fox,et al.  Evaluation of early computed tomographic findings in acute ischemic stroke. , 1999, Stroke.

[9]  W. Hacke,et al.  Thrombolysis in acute ischemic stroke: controlled trials and clinical experience. , 1999, Neurology.

[10]  Randomised controlled trial of streptokinase, aspirin, and combination of both in treatment of acute ischaemic stroke. Multicentre Acute Stroke Trial--Italy (MAST-I) Group. , 1995, Lancet.

[11]  A. Alexandrov,et al.  High rate of complete recanalization and dramatic clinical recovery during tPA infusion when continuously monitored with 2-MHz transcranial doppler monitoring. , 2000, Stroke.

[12]  A. Alexandrov,et al.  Clinical recovery from acute ischemic stroke after early reperfusion of the brain with intravenous thrombolysis. , 1999, The New England journal of medicine.

[13]  M. Moseley,et al.  Intra-arterial rtPA treatment of stroke assessed by diffusion- and perfusion-weighted MRI. , 1999, Stroke.

[14]  A. Alexandrov,et al.  Timing of recanalization after tissue plasminogen activator therapy determined by transcranial doppler correlates with clinical recovery from ischemic stroke. , 2000, Stroke.

[15]  G. Albers,et al.  Expanding the window for thrombolytic therapy in acute stroke. The potential role of acute MRI for patient selection. , 1999, Stroke.

[16]  G. Hankey,et al.  Streptokinase for acute ischemic stroke with relationship to time of administration: Australian Streptokinase (ASK) Trial Study Group. , 1996, Journal of the American Medical Association (JAMA).

[17]  M. Kaste,et al.  Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS) , 1995, JAMA.

[18]  Gary Duckwiler,et al.  Thrombolytic reversal of acute human cerebral ischemic injury shown by diffusion/perfusion magnetic resonance imaging , 2000, Annals of neurology.

[19]  D Schneider,et al.  Reperfusion and metabolic recovery of brain tissue and clinical outcome after ischemic stroke and thrombolytic therapy. , 2000, Stroke.

[20]  L. Munari,et al.  RANDOMIZED CONTROLLED TRIAL OF STREPTOKINASE, ASPIRIN, AND COMBINATION OF BOTH IN TREATMENT OF ACUTE ISCHEMIC STROKE , 1995 .

[21]  C. Weiller,et al.  Severe ADC Decreases Do Not Predict Irreversible Tissue Damage In Humans , 2002, Stroke.

[22]  T. Brott,et al.  Improved Reliability of the NIH Stroke Scale Using Video Training , 1994, Stroke.

[23]  M. Cowan,et al.  American Heart Association. , 2018, P & T : a peer-reviewed journal for formulary management.

[24]  J Fiehler,et al.  Apparent Diffusion Coefficient Decreases and Magnetic Resonance Imaging Perfusion Parameters are Associated in Ischemic Tissue of Acute Stroke Patients , 2001, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[25]  W Hacke,et al.  Feasibility and practicality of MR imaging of stroke in the management of hyperacute cerebral ischemia. , 2000, AJNR. American journal of neuroradiology.

[26]  Joseph P. Broderick,et al.  Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group. , 1995 .

[27]  M. Kaste,et al.  Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II) , 1998, The Lancet.

[28]  U. Grzyska,et al.  The predictive value of early CT and angiography for fatal hemispheric swelling in acute stroke. , 1998, AJNR. American journal of neuroradiology.

[29]  M E Moseley,et al.  Evaluation of early reperfusion and IV tPA therapy using diffusion- and perfusion-weighted MRI , 1999, Neurology.

[30]  H. S. Mueller,et al.  The Thrombolysis in Myocardial Infarction (TIMI) trial. Phase I findings. , 1985, The New England journal of medicine.

[31]  W. Hacke,et al.  Early recanalisation in acute ischaemic stroke saves tissue at risk defined by MRI , 1999, The Lancet.

[32]  G. Albers,et al.  Intravenous tissue-type plasminogen activator for treatment of acute stroke: the Standard Treatment with Alteplase to Reverse Stroke (STARS) study. , 2000, JAMA.

[33]  Y. Samson,et al.  Prediction of Malignant Middle Cerebral Artery Infarction by Diffusion-Weighted Imaging , 2000, Stroke.

[34]  A. Alexandrov,et al.  Thrombolysis in Brain Ischemia (TIBI) Transcranial Doppler Flow Grades Predict Clinical Severity, Early Recovery, and Mortality in Patients Treated With Intravenous Tissue Plasminogen Activator , 2001, Stroke.

[35]  W. Hacke,et al.  Monitoring intravenous recombinant tissue plasminogen activator thrombolysis for acute ischemic stroke with diffusion and perfusion MRI. , 2000, Stroke.

[36]  P Trouillas,et al.  Randomised double-blind placebo-controlled trial of thrombolytic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators. , 1998, Lancet.

[37]  Nirds,et al.  Tissue plasminogen activator for acute ischemic stroke. The National Institute of Neurological Disorders and Stroke rt-PA Stroke Study Group , 1995 .

[38]  W Hacke,et al.  Stroke magnetic resonance imaging within 6 hours after onset of hyperacute cerebral ischemia , 2001, Annals of neurology.

[39]  R Bakshi,et al.  Diffusion-weighted MRI as an evolving standard of care in acute stroke , 2000, Neurology.

[40]  G. Albers,et al.  Recombinant tissue-type plasminogen activator (Alteplase) for ischemic stroke 3 to 5 hours after symptom onset. The ATLANTIS Study: a randomized controlled trial. Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke. , 1999, JAMA.

[41]  J. Wardlaw,et al.  Systematic Review of Diffusion and Perfusion Imaging in Acute Ischemic Stroke , 2000, Stroke.

[42]  R. O’Connor,et al.  Thrombolytic therapy for acute ischemic stroke: why the majority of patients remain ineligible for treatment. , 1999, Annals of emergency medicine.

[43]  C. Weiller,et al.  Type and extent of hemispheric brain infarctions and clinical outcome in early and delayed middle cerebral artery recanalization , 1992, Neurology.

[44]  D. Blacker.  High Rate of Complete Recanalization and Dramatic Clinical Recovery During tPA Infusion When Continuously Monitored With 2-MHz Transcranial Doppler Monitoring , 2000 .

[45]  Rao Ak,et al.  Thrombolysis in myocardial Infarction (TIMI) trial–phase I , 1990 .