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      Clinical and Magnetic Resonance Imaging Predictors of Very Early Neurological Response to Intravenous Thrombolysis in Patients With Middle Cerebral Artery Occlusion

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          Abstract

          Background

          The early identification of patients who are unlikely to respond to intravenous recombinant tissue plasminogen activator (IV‐tPA) could help select candidates for additional intra‐arterial therapy or add‐on antithrombotic drugs during the acute stage of stroke. Given that very early neurological improvement (VENI) is a reliable surrogate of early recanalization, we assessed the clinical and magnetic resonance imaging predictors of lack of VENI.

          Methods and Results

          We reviewed consecutive ischemic stroke patients with middle cerebral artery occlusion and treated within 4.5 hours by IV‐tPA between 2003 and 2012 in our center, where magnetic resonance imaging is systematically implemented as first‐line diagnostic workup. Lack of VENI was defined as a <40% decrease in baseline National Institutes of Health Stroke Scale (NIHSS) score 1 hour after start of IV‐tPA. Poor outcome was defined as a 3‐month modified Rankin scale ≥2. Associations between lack of VENI and potential determinants were assessed in logistic regression models. In all, 186 patients were included (median baseline NIHSS score, 16; median onset to treatment time, 155 minutes). One hundred forty‐three patients (77%) had no VENI. The variables significantly associated with lack of VENI in multivariable analysis were baseline NIHSS (OR, 1.08; 95% CI, 1.01 to 1.16 per 1‐point increase; P=0.03), onset to treatment time >120 minutes (OR, 2.94; 95% CI, 1.31 to 6.63; P=0.009) and diffusion weighted imaging—Alberta Stroke Programme Early CT Score ≤5 (OR, 3.60; 95% CI, 1.14 to 11.35; P=0.03). Patients without VENI were more likely to have a modified Rankin Scale ≥2 than those without VENI (68% versus 24%; OR, 5.01; 95% CI, 2.12 to 11.82) and less likely to have recanalization after 24 hours (OR, 0.41; 95% CI, 0.19 to 0.88).

          Conclusions

          Lack of VENI provides an early estimate of 3‐month outcome and recanalization after IV‐tPA. Baseline NIHSS, onset to treatment time, and diffusion weighted imaging—Alberta Stroke Programme Early CT Score could help to predict lack of VENI and, in turn, might help early selection of candidates for complementary reperfusion strategies.

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          Most cited references20

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          Improving modified Rankin Scale assessment with a simplified questionnaire.

          The modified Rankin Scale (mRS) is a popular primary stroke outcome measure, but its usefulness is limited by suboptimal reliability (inter-rater agreement). We developed and tested the reliability of a simplified mRS questionnaire (smRSq) in 50 patients after stroke seen in outpatient clinics. Randomly chosen paired raters administered the smRSq within 20 minutes of each other and the ratings were blinded until the end of this study. Agreement among the raters was 78%, the kappa statistic was 0.72 (95% CI, 0.58-0.86), and the weighted kappa(w) statistic taking into account the extent of disagreement was 0.82 (95% CI, 0.72-0.92). The average time to administer the smRSq was 1.67 minutes. The smRSq appears to have very good reliability that is similar to that of a structured interview mRS and is considerably less time-consuming.
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            Imaging of the brain in acute ischaemic stroke: comparison of computed tomography and magnetic resonance diffusion-weighted imaging.

            Controversy exists about the optimal imaging technique in acute stroke. It was hypothesised that CT is comparable with DWI, when both are read systematically using quantitative scoring. Ischaemic stroke patients who had CT within six hours and DWI within seven hours of onset were included. Five readers used a quantitative scoring system (ASPECTS) to read the baseline (b) and follow up CT and DWI. Use of MRI in acute stroke was also assessed in patients treated with tissue plasminogen activator (tPA) by prospectively recording reasons for exclusion. Patients were followed clinically at three months. bDWI and bCT were available for 100 consecutive patients (admission median NIHSS = 9). The mean bDWI and bCT ASPECTS were positively related (p<0.001). The level of interrater agreement ranged from good to excellent across all modalities and time periods. Bland-Altman plots showed more variability between bCT and bDWI than at 24 hours. The difference between bCT and bDWI was < or =2 ASPECTS points. Of bCT scans with ASPECTS 8-10, 81% had DWI ASPECTS 8-10. Patients with bCT ASPECTS of 8-10 were 1.9 times more likely to have a favourable outcome at 90 days than those with a score of 0-7 (95% CI 1.1 to 3.1, p = 0.002). The relative likelihood of favourable outcome with a bDWI ASPECTS 8-10 was 1.4 (95% CI 1.0 to 1.9, p = 0.10). Of patients receiving tPA 45% had contraindications to urgent MRI. The differences between CT and DWI in visualising early infarction are small when using ASPECTS. CT is faster and more accessible than MRI, and therefore is the better neuroimaging modality for the treatment of acute stroke.
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              Comparison of intravenous alteplase with a combined intravenous-endovascular approach in patients with stroke and confirmed arterial occlusion (RECANALISE study): a prospective cohort study.

              The efficacy of intravenous (IV) alteplase is restricted by the speed of recanalisation and the site of the occlusion. The aim of this study was to ascertain the effect of a combined IV-endovascular approach (intra-arterial alteplase and, if required, additional thrombectomy) in patients with stroke due to arterial occlusion. We compared recanalisation rates, neurological improvement at 24 h, and functional outcome at 3 months between two periods (February, 2002, to March, 2007, vs April, 2007, to October, 2008) in patients in a prospective registry who were treated with different regimens of alteplase within 3 h of symptom onset. Patients with confirmed occlusion who were treated before April, 2007, were treated with IV alteplase; after April, 2007, patients were treated with a systematic IV-endovascular approach. Analysis was by intention to treat. 46 (87%) of 53 patients treated with the IV-endovascular approach achieved recanalisation versus 56 (52%) of 107 patients in the IV group (adjusted relative risk [RR] 1.49, 95% CI 1.21-1.84; p=0.0002). Early neurological improvement (NIHSS score of 0 or 1 or an improvement of 4 points or more at 24 h) occurred in 32 (60%) patients in the IV-endovascular group and 42 (39%) patients in the IV group (adjusted RR 1.36, 0.97-1.91; p=0.07). Favourable outcome (mRS of 0-2 at 90 days) occurred in 30 (57%) patients in the IV-endovascular group and 47 (44%) patients in the IV group (adjusted RR 1.16, 0.85-1.58; p=0.35). The mortality rate at 90 days was 17% in both groups, and symptomatic intracranial haemorrhage was reported in five (9%) patients in the IV-endovascular group and in 12 (11%) patients in the IV group. Better clinical outcome was associated with recanalisation in both groups and with time to recanalisation in the IV-endovascular group. An IV-endovascular approach is associated with higher recanalisation rates than is IV alteplase in patients with stroke and confirmed arterial occlusion. In patients treated with an IV-endovascular approach, a shorter time from symptom onset to recanalisation is associated with better clinical outcomes.
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                Author and article information

                Journal
                J Am Heart Assoc
                J Am Heart Assoc
                ahaoa
                jah3
                Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
                Blackwell Publishing Ltd
                2047-9980
                December 2013
                19 December 2013
                : 2
                : 6
                : e000511
                Affiliations
                [1 ]Université Paris Descartes Sorbonne Paris Cité, INSERM UMR S894, Hôpital Sainte‐Anne, Paris, France (G.T., M.T., D.C., O.N., V.D., J.C.B., C.O., E.T.)
                [2 ]Université de Caen Basse Normandie, INSERM U919, GIP Cycéron, CHU Côte de Nacre, Caen, France (M.A., E.T.)
                Author notes
                Correspondence to: Emmanuel Touzé, MD, PhD, Université Caen Basse Normandie, CHU Côte de Nacre, Service de Neurologie, Caen, France. E‐mail: touze-e@ 123456chu-caen.fr

                Drs Apoil and Turc contributed equally.

                Article
                jah3382
                10.1161/JAHA.113.000511
                3886747
                24308937
                bb768507-c8f9-4933-85ca-11127f3785e1
                © 2013 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 05 September 2013
                : 11 January 2013
                Categories
                Original Research
                Cardiovascular Surgery

                Cardiovascular Medicine
                acute stroke,thrombolysis,outcome
                Cardiovascular Medicine
                acute stroke, thrombolysis, outcome

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