Stroke intravenous

Muir KW, Lees KR, Ford I, Davis S. Magnesium for acute stroke (intravenous magnesium efficacy in stroke trial) randomised controlled trial. Lancet 2004 363 439 45. 

Sasaki O, Shigekazu T, Koike T, Koizumi T, Tanaka R. Fibrinolytic therapy for acute embolic stroke intravenous, intracarotid, and intra-arterial local approaches. Neurosurgery 1995 36 246-253. 

FIGURE 2.6 Dynamic susceptibility contrast imaging. Axial images of the brain are acquired repeatedly, in this case every 1.5 seconds. As a bolus of intravenously injected contrast material enters the brain, first arteries, then brain parenchyma, and finally veins demonstrate a transient loss of signal intensity. In this acute stroke patient, hypoperfusion of the left middle cerebral artery territory results in delayed arrival of the contrast bolus and prolonged stasis of contrast within the tissue. 

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. "... 

CTP is a relatively recent development in acute stroke imaging that is already in routine clinical use in many centers. CTP and MRP are similar in that both techniques are based on rapid serial image acquisition during intravenous injection of a bolus of contrast material. In both techniques, measurements of density over time (for CTP) or signal intensity over time (for MRP) are converted to contrast agent-versus-time curves, and these are processed in similar ways to yield the same perfusion measurements (most often CBV, CBF, and MTT). Example CTP images are shown in Figure 2.12. 

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. 

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. 

Ribo M, Molina CA, Rovira A, Quintana M, Delgado P, Montaner J, Grive E, Arenillas JE, Alvarez-Sabin J. 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 2005 36 602-606. 

Anonymous. Intracerebral hemorrhage after intravenous t-PA therapy for ischemic stroke. The NBSfDS t-PA Stroke Study Group. Stroke 1997 28 2109-2118. 

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. 

Intravenous rt-PA More Than 3 Hours Beyond Stroke Onset... 

E, Davis S, Donnan G, Schneider D, Diez-Tejedor E, Trouillas R Randomised double-blind placebo-controlled trial of thrombol3ffic therapy with intravenous alteplase in acute ischaemic stroke (ECASS II). Second European-Australasian Acute Stroke Study Investigators. Lancet. 1998 352 1245-1251. 

Tanne D, Gorman MJ, Bates VE, Kasner SE, Scott P, Verro P, Binder JR, Dayno JM, Schultz LR, Levine SR. Intravenous tissue plasminogen activator for acute ischemic stroke in patients aged 80 years and older The tPA stroke survey experience. Stroke. 2000 31 370-375. 

Tanne D, Kasner SE, Demchuk AM, Koren-Morag N, Hanson S, Grond M, Levine SR. Markers of increased risk of intracerebral hemorrhage after intravenous recombinant tissue plasminogen activator therapy for acute ischemic stroke in clinical practice The Multicenter rt-PA Stroke Survey. Circulation. 2002 105 1679-1685. 

Sherman DG, Atkinson RR Chippendale T, Levin KA, Ng K, Futrell N, Hsu CY, Levy DE. Intravenous ancrod fortreatment of acute ischemic stroke The STAT study A randomized controlled trial. Stroke Treatment with Ancrod Trial. JAMA. 2000 283 2395-2403. 

Kent DM, Selker HP, Ruthazer R, Bluhmki E, Hacke W. The Stroke-Thrombol3dic Predictive Instrument. A predictive instrument for intravenous thrombolysis in acute ischemic stroke. Stroke. 2006 37 2957-2962. 

Albers GW, Bates VE, Clark WM, Bell R, Verro P, Hamilton SA. Intravenous tissue-type plasminogen activator for treatment of acute stroke The Standard Treatment with Alteplase to Reverse stroke (STARS) study. JAMA. 2000 283 1145-1150. 

Chiu D, Krieger D, Villar-Cordova C, Kasner SE, Morgenstem LB, Bratina PL, Yatsu FM, Grotta JC. Intravenous tissue plasminogen activator for acute ischemic stroke Feasibility, safety, and efficacy in the first year of clinical practice. Stroke. 1998 29 18-22. 

Wang DZ, Rose JA, Honings DS, Garwacki DJ, Milbrandt JC. Treating acute stroke patients with intravenous tPA. The OSF stroke network experience. Stroke. 2000 31 77-81. 

Grotta JC, Burgin WS, El-MitwaUi A, Long M, Campbell M, Morgenstem LB, Malkoff M, Alexandrov AV. Intravenous tissue-type plasminogen activator therapy for ischemic stroke Houston experience 1996 to 2000. Arch Neurol. 2001 58 2009-2013. 

Smith EE, Abdullah AR, Petkovska I, Rosenthal E, Koroshetz WJ, Schwamm LH. Poor outcomes in patients who do not receive intravenous tissue plasminogen activator because of mild or improving ischemic stroke. Stroke. 2005 36 2497-2499. 

Katzan IL, Hammer MD, Hixson ED, Purlan AJ, Abou-Chebl A, Nadzam DM. Utilization of intravenous tissue plasminogen activator for acute ischemic stroke. Arch Neurol. 2004 61 346-350. 

Wiese KM, Talkad A, Mathews M, Wang D. Intravenous recombinant tissue plasminogen activator in a pregnant woman with cardioembolic stroke. Stroke. 2006 37 2168-2169. 

Shuayto MI, Lopez JI, Greiner R Administration of intravenous tissue plasminogen activatorin apediatric patient with acute ischemic stroke. JChildNeurol. 2006 21 604—606. 

IMS Study Investigators. Combined intravenous and intra-arterial recanalization for acute ischemic stroke the Interventional Management of Stroke study. Stroke. 2004 35 904-911. 

Microplasmin is a truncated form of plasmin that is more resistant to the effects of antiplasmin. In a rabbit stroke model, intravenous microplasmin infusion resulted in a high rate of clot lysis without increasing the rate of ICH. In addition, there was significant improvement in the behavioral rating scores, suggesting a neu-roprotective effect. The ongoing MITI-IV trial is a 40-patient multicenter, double-blind, placebo-controlled trial using three different intravenous doses of microplas-min to treat acute ischemic stroke (NIHSS >6 and <22) within 12 hours of symptom onset. 

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