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      Outcome after systemic thrombolysis is predicted by age and stroke severity: an open label experience with recombinant tissue plasminogen activator and tirofiban

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          Abstract

          Stroke patients can recover upon intravenous thrombolysis but remain impaired in lacking recanalization. We sought to investigate the clinical effect of systemic thrombolysis with an intravenous bolus of 20 mg recombinant tissue plasminogen activator (rtPA) and an infusion of body-weight adjusted tirofiban for 48 hours in acute stroke. This prospective, open label study, included 192 patients (68±13 years, 50% males) treated between 1 January 2005 and 31 December 2007. The neurological deficit was assessed with the National Institutes of Health stroke scale (NIHSS). Follow-up was performed using a telephone interview of modified Rankin Scale (mRS) and Barthel index. The site of cerebral artery occlusion was determined by computed tomography or magnetic resonance angiography. Data were analyzed by descriptive statistics and multiple regression analyses. Eighty-one percent of the patients had an infarct in the middle cerebral artery (MCA) territory and were severely affected with a median NIHSS of 10. During treatment on the Stroke Unit the patients improved (P<0.0001) except for patients who deceased due to malignant infarction (n=10) or cerebral haemorrhage (n=6); 18 percent deceased within 100 days which was predicted by older age (76 + 10 years, P<0.05) and more severe affection on admission (P<0.0001). Also, these patients more frequently had atrial fibrillation (P<0.03) than the surviving patients. The surviving patients had more frequently distal MCA occlusions and improved further (P<0.0001). At follow-up 48% of the patients had a mRS of 0 and 1. Similarly to intravenous thrombolysis with body-weight adjusted rtPA, poor prognosis was predicted by higher age, more severe neurological deficit at stroke admission, and a proximal MCA occlusion. Half of the surviving patients improved to no or minimal impairment.

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          Magnetic resonance imaging profiles predict clinical response to early reperfusion: the diffusion and perfusion imaging evaluation for understanding stroke evolution (DEFUSE) study.

          To determine whether prespecified baseline magnetic resonance imaging (MRI) profiles can identify stroke patients who have a robust clinical response after early reperfusion when treated 3 to 6 hours after symptom onset. We conducted a prospective, multicenter study of 74 consecutive stroke patients admitted to academic stroke centers in North America and Europe. An MRI scan was obtained immediately before and 3 to 6 hours after treatment with intravenous tissue plasminogen activator 3 to 6 hours after symptom onset. Baseline MRI profiles were used to categorize patients into subgroups, and clinical responses were compared based on whether early reperfusion was achieved. Early reperfusion was associated with significantly increased odds of achieving a favorable clinical response in patients with a perfusion/diffusion mismatch (odds ratio, 5.4; p = 0.039) and an even more favorable response in patients with the Target Mismatch profile (odds ratio, 8.7; p = 0.011). Patients with the No Mismatch profile did not appear to benefit from early reperfusion. Early reperfusion was associated with fatal intracranial hemorrhage in patients with the Malignant profile. For stroke patients treated 3 to 6 hours after onset, baseline MRI findings can identify subgroups that are likely to benefit from reperfusion therapies and can potentially identify subgroups that are unlikely to benefit or may be harmed.
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            Effects of alteplase beyond 3 h after stroke in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET): a placebo-controlled randomised trial.

            Whether intravenous tissue plasminogen activator (alteplase) is effective beyond 3 h after onset of acute ischaemic stroke is unclear. We aimed to test whether alteplase given 3-6 h after stroke onset promotes reperfusion and attenuates infarct growth in patients who have a mismatch in perfusion-weighted MRI (PWI) and diffusion-weighted MRI (DWI). We prospectively and randomly assigned 101 patients to receive alteplase or placebo 3-6 h after onset of ischaemic stroke. PWI and DWI were done before and 3-5 days after therapy, with T2-weighted MRI at around day 90. The primary endpoint was infarct growth between baseline DWI and the day 90 T2 lesion in mismatch patients. Major secondary endpoints were reperfusion, good neurological outcome, and good functional outcome. Patients, caregivers, and investigators were unaware of treatment allocations. Primary analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00238537. We randomly assigned 52 patients to alteplase and 49 patients to placebo. Mean age was 71.6 years, and median score on the National Institutes of Health stroke scale was 13. 85 of 99 (86%) patients had mismatch of PWI and DWI. The geometric mean infarct growth (exponential of the mean log of relative growth) was 1.24 with alteplase and 1.78 with placebo (ratio 0.69, 95% CI 0.38-1.28; Student's t test p=0.239); the median relative infarct growth was 1.18 with alteplase and 1.79 with placebo (ratio 0.66, 0.36-0.92; Wilcoxon's test p=0.054). Reperfusion was more common with alteplase than with placebo and was associated with less infarct growth (p=0.001), better neurological outcome (p<0.0001), and better functional outcome (p=0.010) than was no reperfusion. Alteplase was non-significantly associated with lower infarct growth and significantly associated with increased reperfusion in patients who had mismatch. Because reperfusion was associated with improved clinical outcomes, phase III trials beyond 3 h after treatment are warranted.
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              Impact of collateral flow on tissue fate in acute ischaemic stroke.

              Collaterals may sustain penumbra prior to recanalisation yet the influence of baseline collateral flow on infarct growth following endovascular therapy remains unknown. Consecutive patients underwent serial diffusion and perfusion MRI before and after endovascular therapy for acute cerebral ischaemia. We assessed the relationship between MRI diffusion and perfusion lesion indices, angiographic collateral grade and infarct growth. Tmax perfusion lesion maps were generated and diffusion-perfusion mismatch regions were divided into Tmax >or=4 s (severe delay) and Tmax >or=2 but <4 s (mild delay). Among 44 patients, collateral grade was poor in 7 (15.9%), intermediate in 20 (45.5%) and good in 17 (38.6%) patients. Although diffusion-perfusion mismatch volume was not different depending on the collateral grade, patients with good collaterals had larger areas of milder perfusion delay than those with poor collaterals (p = 0.005). Among 32 patients who underwent day 3-5 post-treatment MRIs, the degree of pretreatment collateral circulation (r = -0.476, p = 0.006) and volume of diffusion-perfusion mismatch (r = 0.371, p = 0.037) were correlated with infarct growth. Greatest infarct growth occurred in patients with both non-recanalisation and poor collaterals. Multiple regression analysis revealed that pretreatment collateral grade was independently associated with infarct growth. Our data suggest that angiographic collateral grade and penumbral volume interactively shape tissue fate in patients undergoing endovascular recanalisation therapy. These angiographic and MRI parameters provide complementary information about residual blood flow that may help guide treatment decision making in acute cerebral ischaemia.
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                Author and article information

                Journal
                Neurol Int
                NI
                NI
                Neurology International
                PAGEPress Publications (Pavia, Italy )
                2035-8385
                2035-8377
                06 September 2012
                14 June 2012
                : 4
                : 2
                : e9
                Affiliations
                [1 ]Department of Neurology, University Hospital Düsseldorf,
                [2 ]Biomedical Research Centre, Heinrich-Heine-University Düsseldorf, Germany;
                [3 ]Florey Neuroscience Institutes, Melbourne, Australia;
                [4 ]Department of Neurology, Mediclin Fachklinik Rhein Ruhr, Essen, Germany
                Author notes
                Correspondence: Rüdiger J. Seitz, Department of Neurology, University Hospital Düsseldorf Moorenstrasse 5, 40225 Düsseldorf, Germany. Tel. +49.211.8118974 - Fax: +49.211.8118485. E-mail: seitz@ 123456neurologie.uni-duesseldorf.de

                Funding: the study was supported by the Competence Net Stroke of the BMBF.

                Conflict of interests: the authors report no potential conflict of interests.

                Article
                ni.2012.e9
                10.4081/ni.2012.e9
                3490474
                23139853
                38384cd5-b1d5-48b6-8534-41f9cd7fa31c
                ©Copyright R.J. Seitz et al., 2012

                This work is licensed under a Creative Commons Attribution NonCommercial 3.0 License (CC BY-NC 3.0).

                Licensee PAGEPress, Italy

                History
                : 28 September 2011
                : 11 June 2012
                : 30 July 2012
                Categories
                Article

                Neurology
                tirofiban,stroke,impairment.,brain infarct,thrombolysis
                Neurology
                tirofiban, stroke, impairment., brain infarct, thrombolysis

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