Stroke thrombolysis

Lindsberg PJ, Mattie HP. Therapy of basilar artery occlusion a systematic analysis comparing intra-arterial and intravenous thrombolysis. Stroke 2006 37 922-928. 

Greer DM, Koroshetz WJ, Cullen S, Gonzalez RG, Lev MH. Magnetic resonance imaging improves detection of intracerebral hemorrhage over computed tomography after intra-arterial thrombolysis. Stroke 2004 35 491 95. 

Nakano S, Iseda T, Yoneyama T, Kawano H, Wakisaka S. Direct percutaneous transluminal angioplasty for acute middle cerebral artery trunk occlusion an alternative option to intra-arterial thrombolysis. Stroke 2002 33 2872-2876. 

Abou-Chebl A, Bajzer CT, Krieger DW, Furlan AJ, Yadav JS. Multimodal therapy for the treatment of severe ischemic stroke combining GPEh/IIIa antagonists and angioplasty after failure of thrombolysis. Stroke 2005 36 2286-2288. 

Bousser MG. Cerebral venous thrombosis nothing, heparin, or local thrombolysis Stroke 1999 30 481 83. 

Butcher K, Parsons M, Baird T, Barber A, Donnan G, Desmond P, Tress B, Davis S (2003) Perfusion thresholds in acute stroke thrombolysis. Stroke 34 2159-2164... 

Lindsberg PJ, Mattie HP (2006). Therapy of basilar artery occlusion a systematic analysis comparing intra-arterial and intravenous thrombolysis. Stroke 37 922-928 Lindsberg PJ, Soinne L, Tatlisumak T et al. (2004). Long-term outcome after intravenous thrombolysis of basilar artery occlusion. Journal of the American Medical Association 292 1862-1866... 

Hjort, N., et al., MRI detection of early blood-brain barrier disruption parenchymal enhancement predicts focal hemorrhagic transformation after thrombolysis. Stroke, 2008. 39(3) p. 1025-8. 

KidweU, C.S., et al.. Predictors of hemorrhagic transformation in patients receiving intra-arterial thrombolysis. Stroke, 2002. 33(3) p. 717-24. 

The second hypothesis, that patients should be selected for thrombolysis depending on whether or not they exhibit a diffusion-perfusion mismatch, may have enormous implications for stroke therapy in the near future, and is one of the most actively investigated and debated subjects in neuroimaging. 

However, several important studies have shown that intravenous thrombolysis may be beneficial more than 3 hours after stroke onset, provided that only patients with a significant diffusion-perfusion mismatch are treated. In one such smdy, Ribo et al. found that patients with a significant diffusion-perfusion mismatch could be treated safely and effectively in the 3-6-hour time period. In phase II of the desmo-teplase in acute stroke (DIAS) trial, patients with diffusion-perfusion mismatch were treated with desmoteplase up to 9 hours after stroke onset, and showed better outcomes than patients given placebo, with only a minimal incidence of symptomatic hemorrhage. Similar success was achieved in the same time window by the dose escalation study of desmoteplase in acute ischemic stroke (DEDAS). ... 

These studies raise the possibility that, one day, imaging-based treatment protocols may allow for intravenous thrombolysis in patients well outside of the now-accepted 3-hour window, provided they demonstrate substantial diffusion-perfusion mismatch. Such protocols could allow for treatment of a vastly larger number of patients than are currently treated. It has been estimated that only 1-7% of acute stroke patients currently receive thrombolytic medication, and that, in up to 95% of cases, they are ineligible because they present outside of the 3-hour time window. As many as 80% of patients who present 6 hours after stroke onset may demonstrate a significant diffusion-perfusion mismatch. "... 

Dzialowski I, Hill MD, Coutts SB, Demchuk AM, Kent DM, Wunderlich O, von Kummer R. Extent of early ischemic changes on computed tomography (CT) before thrombolysis prognostic value of the Alberta Stroke Program Early CT Score in ECASS II. Stroke 2006 37 973-978. 

Hacke W, Albers G, Al-Rawi Y, Bogousslavsky J, Davalos A, Eliasziw M, Fischer M, Furlan A, Kaste M, Lees KR, Soehngen M, Warach S, Group DS. The Desmoteplase in Acute Ischemic Stroke Trial (DIAS) a phase II MRI-based 9-hour window acute stroke thrombolysis trial with intravenous desmoteplase. Stroke 2005 36 66-73. 

Parsons MW, Barber PA, Chalk J, Darby DG, Rose S, Desmond PM, Gerraty RP, Tress BM, Wright PM, Donnan GA, Davis SM. Diffusion- and perfusion-weighted MRI response to thrombolysis in stroke. Ann Neurol 2002 51 28-37. 

Lev MH, Segal AZ, Farkas J, Hossain ST, Putman C, Hunter GJ, Budzik R, Harris GJ, Buonanno FS, Ezzeddine MA, Chang Y, Koroshetz WJ, Gonzalez RG, Schwamm LH. Utility of perfusion-weighted CT imaging in acute middle cerebral artery stroke treated with intra-arterial thrombolysis prediction of final infarct volume and clinical outcome. Stroke 2001 32 2021-2028. 

Hacke W, Kaste M, Fieschi C, Toni D, Lesaffre E, von Kummer R, Boy sen G, Bluhmki E, Hoxter G, Mahagne MH. Intravenous thrombolysis with recombinant tissue plasminogen activator for acute hemispheric stroke. The European Cooperative Acute Stroke Study (ECASS). JAMA 1995 274 1017-1025. 

Clark WM, Wissman S, Albers GW, Jhamandas JH, Madden KP, Hamilton S. 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. JAMA 1999 282 2019-2026 [see comment]. 

Cho A-H, Lee DH, Kim JS, Choong GC, Kwon SU, Suh DC, Choi J, Chun S-B, Kim SJ, Kang D-W. MRI-Based thrombolysis in acute stroke patients with unclear onset time is safe and feasible Stroke 2006 37 634 (abstract, American Stroke Association International Stroke Conference 2006). 

Stroke is the leading cause of major long-term disability in adults and the third leading cause of death in the United States. On average, a new stroke occurs every 45 seconds. Thrombolytic therapy with intravenous recombinant tissue-plasminogen activator (IV rt-PA) is the most effective treatment for acute ischemic stroke. In this chapter, we review the rationale for thrombolysis in acute ischemic stroke, clinical evidence supporting the use of thrombolytics, and the application of thrombolysis in practice. 

TABLE 3.1 Large Randomized Controlled Trials of Intravenous Thrombolysis for Acute Ischemic Stroke. 

The current use of IV rt-PA for acute stroke thrombolysis is based on the NINDS rt-PA study, a two-part randomized, double blind, placebo-controlled trial. " This trial was preceded by two open-label, dose-escalation safety studies that suggested that treatment within 180 minutes of stroke onset, and rt-PA dosages no higher than 0.95 mg/kg, was safe and effective. ... 

Three large randomized trials, the European Cooperative Acute Stroke Study (ECASS) parts I and II, and the Alteplase Thrombolysis for Acute Noninterven-tional Therapy in Ischemic Stroke (ATLANTIS), have investigated the efficacy of IV rt-PA in acute stroke beyond the 3-hour window. All three studies showed high rates of sICH complicating rt-PA treatment, and no overall efficacy of rt-PA. 

A combined analysis of the ATLANTIS, ECASS-11, and NINDS rt-PA study data found that females had a greater benefit from rt-PA than males (p = 0.04), despite similar initial stroke severity and rates of slCH." This finding may not be relevant to the clinical, FDA-approved use of rt-PA, because most of the analyzed subjects from ATLANTIS and ECASS-11 were randomized greater than 3 hours after stroke onset. Therefore, sex should not be a criterion for patient selection for thrombolysis. 

The authors concluded that campaigns to educate patients to seek treatment sooner should be major components of system-wide interventions to increase the rate of thrombolysis for acute ischemic stroke. There is some evidence that public education may help to increase the rate of rt-PA utilization by encouraging earlier presentation when stroke symptoms occur. ... 

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