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      Reperfusion-Related Intracerebral Hemorrhage

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      Frontiers of Neurology and Neuroscience
      S. Karger AG

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          Abstract

          The efficacy of intravenous thrombolysis (IVT) for acute ischemic stroke patients has been well established worldwide, with endovascular therapy performed in patients who have failed or are ineligible for IVT and who have major vessel occlusion. The most feared complication of acute stroke reperfusion therapy is intracerebral hemorrhage (ICH), as these patients have a poor clinical outcome and high mortality. The fundamental mechanisms responsible for reperfusion-related ICH include increased permeability and disruption of the blood-brain barrier. Recombinant tissue plasminogen activator may exacerbate the blood-brain barrier disruption through its pharmacological action during IVT. Furthermore, interactions between the device and the vessel walls and contrast intoxication may also be related to ICH, which includes the occurrence of subarachnoid hemorrhage after endovascular therapy. Numerous factors have been reported to be associated with or to be able to predict ICH, and several scoring systems have been developed for predicting symptomatic ICH (sICH) after IVT. However, a scoring system with enough power to detect an unacceptably high risk of sICH or to provide information on when to withdraw IVT has yet to be definitively established. In current clinical practice, acute stroke patients without contraindications for IVT who have been identified by conventional computed tomography scans normally undergo IVT, irrespective of any clinical predictors of ICH after IVT. Strategies that have been suggested for preventing reperfusion-related ICH in high-risk patients include intensive blood pressure control, tight glycemic control, and the avoidance of early aggressive antithrombotic therapy. If sICH, and especially massive parenchymal hematoma, does occur, hematoma expansion needs to be prevented through the use of tight blood pressure control and other methods. Although evidence of efficacy has yet to be established, surgical removal is performed not only for the purpose of saving lives but also for improving the functional outcome. In order to develop therapeutic strategies for reperfusion-related ICH that will lead to an improved stroke prognosis, further studies are warranted.

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          Most cited references20

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          Time to treatment with intravenous tissue plasminogen activator and outcome from acute ischemic stroke.

          Randomized clinical trials suggest the benefit of intravenous tissue-type plasminogen activator (tPA) in acute ischemic stroke is time dependent. However, modest sample sizes have limited characterization of the extent to which onset to treatment (OTT) time influences outcome; and the generalizability of findings to clinical practice is uncertain. To evaluate the degree to which OTT time is associated with outcome among patients with acute ischemic stroke treated with intraveneous tPA. Data were analyzed from 58,353 patients with acute ischemic stroke treated with tPA within 4.5 hours of symptom onset in 1395 hospitals participating in the Get With The Guidelines-Stroke Program, April 2003 to March 2012. Relationship between OTT time and in-hospital mortality, symptomatic intracranial hemorrhage, ambulatory status at discharge, and discharge destination. Among the 58,353 tPA-treated patients, median age was 72 years, 50.3% were women, median OTT time was 144 minutes (interquartile range, 115-170), 9.3% (5404) had OTT time of 0 to 90 minutes, 77.2% (45,029) had OTT time of 91 to 180 minutes, and 13.6% (7920) had OTT time of 181 to 270 minutes. Median pretreatment National Institutes of Health Stroke Scale documented in 87.7% of patients was 11 (interquartile range, 6-17). Patient factors most strongly associated with shorter OTT included greater stroke severity (odds ratio [OR], 2.8; 95% CI, 2.5-3.1 per 5-point increase), arrival by ambulance (OR, 5.9; 95% CI, 4.5-7.3), and arrival during regular hours (OR, 4.6; 95% CI, 3.8-5.4). Overall, there were 5142 (8.8%) in-hospital deaths, 2873 (4.9%) patients had intracranial hemorrhage, 19,491 (33.4%) patients achieved independent ambulation at hospital discharge, and 22,541 (38.6%) patients were discharged to home. Faster OTT, in 15-minute increments, was associated with reduced in-hospital mortality (OR, 0.96; 95% CI, 0.95-0.98; P < .001), reduced symptomatic intracranial hemorrhage (OR, 0.96; 95% CI, 0.95-0.98; P < .001), increased achievement of independent ambulation at discharge (OR, 1.04; 95% CI, 1.03-1.05; P < .001), and increased discharge to home (OR, 1.03; 95% CI, 1.02-1.04; P < .001). In a registry representing US clinical practice, earlier thrombolytic treatment was associated with reduced mortality and symptomatic intracranial hemorrhage, and higher rates of independent ambulation at discharge and discharge to home following acute ischemic stroke. These findings support intensive efforts to accelerate hospital presentation and thrombolytic treatment in patients with stroke.
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            Blood-brain barrier, reperfusion injury, and hemorrhagic transformation in acute ischemic stroke.

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              Risk factors for intracranial hemorrhage in acute ischemic stroke patients treated with recombinant tissue plasminogen activator: a systematic review and meta-analysis of 55 studies.

              Recombinant tissue plasminogen activator (rtPA) is an effective treatment for acute ischemic stroke but is associated with an increased risk of intracranial hemorrhage (ICH). We sought to identify the risk factors for ICH with a systematic review of the published literature. We searched for studies of rtPA-treated stroke patients that reported an association between a variable measured before rtPA infusion and clinically important ICH (parenchymal ICH or ICH associated with clinical deterioration). We calculated associations between baseline variables and ICH with random-effect meta-analyses. We identified 55 studies that measured 43 baseline variables in 65 264 acute ischemic stroke patients. Post-rtPA ICH was associated with higher age (odds ratio, 1.03 per year; 95% confidence interval, 1.01-1.04), higher stroke severity (odds ratio, 1.08 per National Institutes of Health Stroke Scale point; 95% confidence interval, 1.06-1.11), and higher glucose (odds ratio, 1.10 per mmol/L; 95% confidence interval, 1.05-1.14). There was approximately a doubling of the odds of ICH with the presence of atrial fibrillation, congestive heart failure, renal impairment, previous antiplatelet agents, leukoaraiosis, and a visible acute cerebral ischemic lesion on pretreatment brain imaging. Little of the variation in the sizes of the associations among different studies was explained by the source of the cohort, definition of ICH, or degree of adjustment for confounding variables. Individual baseline variables were modestly associated with post-rtPA ICH. Prediction of post-rtPA ICH therefore is likely to be difficult if based on single clinical or imaging factors alone. These observational data do not provide a reliable method for the individualization of treatment according to predicted ICH risk.
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                Author and article information

                Journal
                FNN
                Frontiers Neurology Neuroscience
                10.1159/issn.0300-5186
                Frontiers of Neurology and Neuroscience
                Frontiers Neurology Neuroscience
                S. Karger AG (Basel, Switzerland karger@ 123456karger.com http://www.karger.com )
                978-3-318-05596-2
                978-3-318-05597-9
                1660-4431
                1662-2804
                November 2015
                12 November 2015
                : 37
                : New Insights in Intracerebral Hemorrhage
                : 62-77
                Affiliations
                Department of Cerebrovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan
                Article
                FNN2016037062 Toyoda K, Anderson CS, Mayer SA (eds): New Insights in Intracerebral Hemorrhage. Front Neurol Neurosci. Basel, Karger, 2016, vol 37, pp 62-77
                10.1159/000437114
                26587772
                e15ac5ea-a399-4bcf-884a-d6809f9b4b0e
                © 2016 S. Karger AG, Basel

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                History
                Page count
                Figures: 2, Tables: 2, References: 64, Pages: 16
                Categories
                Chapter

                Medicine,General social science
                Medicine, General social science

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