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      Functional Outcome of Hemorrhagic Transformation after Thrombolysis for Ischemic Stroke: A Prospective Study

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          Abstract

          Background/Aims: Hemorrhagic transformation (HT) is usually taken into account when symptomatic, but the role of asymptomatic HT is not well known. The aim of our study was to evaluate the link between HT after thrombolysis for ischemic stroke and functional outcome at 3 months, with particular emphasis on asymptomatic HT. Methods: Our study was performed prospectively between June 2012 and June 2013 in the Stroke Unit of the University Hospital Center of Tours (France). All patients treated with intravenous thrombolysis were consecutively included. HT was classified on susceptibility-weighted imaging (SWI) with 3-tesla MRI at 7 ± 3 days after treatment. We evaluated functional outcome at 3 months using the modified Rankin Scale (mRS). Dependency was defined as an mRS score of ≥3. Results: After 1 year, 128 patients had received thrombolytic therapy for ischemic stroke, of whom 90 patients underwent both 3-tesla MRI and SWI at day 7. Fifty-two had HT, including 8 symptomatic cases. At 3 months, 68% of those patients were dependent compared to 31% of patients without HT [OR 4.6 (1.9-11.4), p = 0.001]. In asymptomatic HT, the rate was 62% [OR 3.5 (1.4-8.9), p = 0.007], but did not reach significance after adjustment for stroke severity. Discussion: Our study found no statistically significant effect of HT on outcome after adjustment for initial stroke severity. However, the innocuousness of HT is not certain, and only few studies have already highlighted the increased risk of dependency. Using 3-tesla MRI with SWI allows us to increase the detection rate of small hemorrhage. Conclusion: HT after thrombolysis is very frequent on SWI, but the initial stroke severity is an important predictor to assess the role of HT for patient outcome.

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          Most cited references7

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          Predicting the risk of symptomatic intracerebral hemorrhage in ischemic stroke treated with intravenous alteplase: safe Implementation of Treatments in Stroke (SITS) symptomatic intracerebral hemorrhage risk score.

          Symptomatic intracerebral hemorrhage (SICH) is a serious complication in patients with acute ischemic stroke treated with intravenous thrombolysis. We aimed to develop a clinical score that can easily be applied to predict the risk of SICH. We analyzed data from 31 627 patients treated with intravenous alteplase enrolled in the Safe Implementation of Treatments in Stroke (SITS) International Stroke Thrombolysis Register. The outcome measure was SICH per the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST) definition: a Type 2 parenchymal hemorrhage with deterioration in National Institutes of Health Stroke Scale score of ≥ 4 points or death. Univariate risk factors associated with the outcome were entered into a logistic regression model after stratification of continuous variables. Adjusted ORs for the independent risk factors were converted into points, which were summated to produce a risk score. We identified 9 independent risk factors for SICH: baseline National Institutes of Health Stroke Scale, serum glucose, systolic blood pressure, age, body weight, stroke onset to treatment time, aspirin or combined aspirin and clopidogrel, and history of hypertension. The overall rate of SICH was 1.8%. The risk score ranged from 0 to 12 points and showed a >70-fold graded increase in the rate of SICH for patients with a score ≥ 10 points (14.3%) compared with a score of 0 point (0.2%). The prognostic discriminating capability by C statistic was 0.70. The SITS SICH risk score predicts large cerebral parenchymal hemorrhages associated with severe clinical deterioration. The score could aid clinicians to identify patients at high as well as low risk of SICH after intravenous alteplase.
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            Defining clinically relevant cerebral hemorrhage after thrombolytic therapy for stroke: analysis of the National Institute of Neurological Disorders and Stroke tissue-type plasminogen activator trials.

            Several definitions have been proposed to distinguish clinically relevant from incidental cerebral hemorrhagic transformation after thrombolytic therapy for acute ischemic stroke. We investigated which definition best identifies cerebral hemorrhages that alter long-term functional outcome in the National Institute of Neurological Disorders and Stroke (NINDS) tissue-type plasminogen activator (tPA) trials.
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              Is asymptomatic hemorrhagic transformation really innocuous?

              Asymptomatic hemorrhagic transformation (HT) is not associated with immediate deterioration of patients with acute ischemic stroke. However, it is unclear whether it is clinically innocuous with respect to long-term outcome. The aim of this study was to determine the impact of asymptomatic HT on 3-month outcome. A consecutive series of 1,618 patients, hospitalized between January 2004 and August 2007 for ischemic stroke within 7 days from symptom onset were identified in a prospective stroke registry database. Those who had no evidence of acute cerebral ischemia on diffusion-weighted MRI, who did not undergo T2-weighted gradient echo MRI, whose modified Rankin Scale (mRS) score at 3 months after stroke onset was not available, or who had symptomatic HT were excluded. The odds ratio (OR) of asymptomatic HT was calculated for the full distribution of mRS score and adjusted for variables with p < 0.25 with respect to their associations with asymptomatic HT or functional outcome. Of 1,412 patients eligible for the study, 100 (7.1%) had asymptomatic HT. Patients who experienced asymptomatic HT were more likely to have cardioembolic stroke, to receive thrombolytic therapy, to receive anticoagulation with heparin, and to have a higher initial NIH Stroke Scale score. The crude and adjusted ORs of asymptomatic HT for an increment of mRS score at 3 months were 2.94 (95% confidence interval 2.05-4.24) and 1.90 (1.27-2.82), respectively. Our study shows that the odds of a worse outcome are increased by a factor of 2 in patients with asymptomatic HT compared with those without HT after acute ischemic stroke.
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                Author and article information

                Journal
                CEE
                CEE
                Cerebrovasc Dis Extra
                10.1159/issn.1664-5456
                Cerebrovascular Diseases Extra
                S. Karger AG
                1664-5456
                2015
                September – December 2015
                09 October 2015
                : 5
                : 3
                : 103-106
                Affiliations
                Stroke Unit, University Hospital Center of Tours, Tours, France
                Author notes
                *Dr. Mariam Annan, CHU de Tours, Service de Neurologie et Neurophysiologie Clinique, 2 boulevard Tonnellé, FR-37000 Tours (France), E-Mail m.annan@univ-tours.fr
                Article
                440737 PMC4662290 Cerebrovasc Dis Extra 2015;5:103-106
                10.1159/000440737
                PMC4662290
                26648965
                94ac52fb-1724-4edd-ac99-93aa54a9451f
                © 2015 The Author(s) Published by S. Karger AG, Basel

                This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 09 July 2015
                : 14 August 2015
                Page count
                Tables: 1, References: 7, Pages: 4
                Categories
                ESC Award 2015

                Geriatric medicine,Neurology,Cardiovascular Medicine,Neurosciences,Clinical Psychology & Psychiatry,Public health
                Thrombolysis,Hemorrhagic transformation,Functional outcome,Ischemic stroke

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