RNA in blood is altered prior to hemorrhagic transformation in ischemic stroke.
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ABSTRACT:
SUBMITTER: Jickling GC
PROVIDER: S-EPMC3752310 | biostudies-literature | 2013 Aug
REPOSITORIES: biostudies-literature
Publications
RNA in blood is altered prior to hemorrhagic transformation in ischemic stroke.
Jickling Glen C GC Ander Bradley P BP Stamova Boryana B Zhan Xinhua X Liu Dazhi D Rothstein Lena L Verro Piero P Khoury Jane J Jauch Edward C EC Pancioli Arthur M AM Broderick Joseph P JP Sharp Frank R FR
Annals of neurology 20130801 2
<h4>Objective</h4>Hemorrhagic transformation (HT) is a major complication of ischemic stroke that worsens outcomes and increases mortality. Disruption of the blood-brain barrier is a central feature of HT pathogenesis, and leukocytes may contribute to this process. We sought to determine whether ischemic strokes that develop HT have differences in RNA expression in blood within 3 hours of stroke onset prior to treatment with thrombolytic therapy.<h4>Methods</h4>Stroke patient blood samples were ...[more]
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Project description:Disability or death occurs more frequently in patients with hemorrhagic transformation (HT) after ischemic stroke. In rat models of stroke, sulfonylurea (SU) drugs such as glibenclamide (adopted US name, glyburide) confer protection against swelling and HT through actions on the novel SUR1-regulated NC(Ca-ATP) channel. Here, we sought to determine whether the use of SU drugs in patients with diabetes mellitus (DM) presenting with acute ischemic stroke might influence the incidence of HT.We retrospectively analyzed data on 220 patients with DM who presented with acute ischemic stroke, 43 of whom were managed with and continued to receive SU drugs, and 177 of whom were managed without (controls).During a median length of stay in hospital of 11 days, 20 control patients (11%) experienced symptomatic HT (sHT), whereas no patient in the SU group experienced sHT (p = 0.016). No patient in the SU group died, compared to 18 (10%) in the control group (p = 0.027). Similarly favorable outcomes were observed after matching for baseline imbalances and excluding outliers. In support of the proposed mechanism, we present a case of sHT in which an analysis of brain tissues obtained intraoperatively showed prominent upregulation of SUR1, the target of SU drugs, in microvessels and neurons.We conclude that, in diabetic patients with acute ischemic stroke, prior and continued use of SU drugs is associated with reduced sHT compared to those whose treatment regimen does not include SU drugs.
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Project description:Intravenous recombinant tissue plasminogen activator (IV-rtPA) is given in acute ischemic stroke patients to achieve reperfusion. Hemorrhagic transformation (HT) is a serious complication of IV-rtPA treatment and related to blood-brain barrier (BBB) injury. It is unclear whether HT occurs secondary to reperfusion in combination with ischemic BBB injury or is caused by the negative effect of IV-rtPA on BBB integrity. The aim of this study was to establish the association between reperfusion and the occurrence of HT.From the DUST study, patients were selected with admission and follow-up non-contrast CT (NCCT) and CT perfusion (CTP) imaging, and a perfusion deficit in the middle cerebral artery territory on admission. Reperfusion was categorized qualitatively as reperfusion or no-reperfusion by visual comparison of admission and follow-up CTP. Occurrence of HT was assessed on follow-up NCCT. The association between reperfusion and occurrence of HT on follow-up was estimated by calculating odds ratios (ORs) and 95 % confidence intervals (CIs) with additional stratification for IV-rtPA treatment.Inclusion criteria were met in 299 patients. There was no significant association between reperfusion and HT (OR 1.2 95%CI 0.5-3.1). In patients treated with IV-rtPA (n?=?203), the OR was 1.3 (95%CI 0.4-4.0), and in patients not treated with IV-rtPA (n?=?96), the OR was 0.8 (95%CI 0.1-4.5). HT occurred in 14 % of the IV-rtPA patients and in 7 % of patients without IV-rtPA (95%CI of difference -1 to 14 %).Our results suggest that the increased risk of HT after acute ischemic stroke treatment is not dependent on the reperfusion status.
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Project description:BackgroundsThere have been neither appropriate guidelines nor clinical studies about the use of antithrombotics after hemorrhagic transformation (HT). We sought to find whether the use of antithrombotics after hemorrhagic infarction might be associated with aggravation of HT and neurological deterioration.MethodsThis retrospective study included prospectively registered consecutive patients with acute ischemic stroke and HT in our tertiary stroke center. We focused on the hemorrhagic infarction. Aggravation of HT was defined as either enlargement of the original HT or newly developed HT within the infarcted area by visual analysis. We analyzed relationships between antithrombotics and HT, and neurological deterioration after HT in patients with hemorrhagic infarction. In addition, we assessed composite outcomes including neurological deterioration, vascular events, and death at 1 month after HT. We analyzed relationships between antithrombotics after discharge and composite outcomes within 1 month after HT.Results222 patients were finally analyzed. Of the 150 patients with hemorrhagic infarction, 75 (50.0%) were type 1. The use of warfarin after detection of hemorrhagic infarction more frequently increased aggravation of HT than did the use of antiplatelets (4 of 24 vs 3 of 69; p = 0.094), but neither warfarin nor antiplatelets caused more HT than no medication. In addition, the use of antithrombotics after hemorrhagic infarction was not significantly associated with neurological deterioration after HT. The frequency of composite events at 1 months was significantly lower in patients treated with antithrombotics than those treated without (p = 0.041).ConclusionIn conclusion, the results of this study suggest that antithrombotics can safely be used after hemorrhagic infarction and may not be associated with neurological deterioration and aggravation of HT. Further studies are needed to confirm our results.
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Project description:Hemorrhagic transformation (HT) is a common complication in patients with acute ischemic stroke. It occurs when peripheral blood extravasates across a disrupted blood brain barrier (BBB) into the brain following ischemic stroke. Preventing HT is important as it worsens stroke outcome and increases mortality. Factors associated with increased risk of HT include stroke severity, reperfusion therapy (thrombolysis and thrombectomy), hypertension, hyperglycemia, and age. Inflammation and the immune system are important contributors to BBB disruption and HT and are associated with many of the risk factors for HT. In this review, we present the relationship of inflammation and immune activation to HT in the context of reperfusion therapy, hypertension, hyperglycemia, and age. Differences in inflammatory pathways relating to HT are discussed. The role of inflammation to stratify the risk of HT and therapies targeting the immune system to reduce the risk of HT are presented.
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Project description:Hemorrhagic transformation (HT) is one of the leading causes of a poor prognostic marker after acute ischemic stroke (AIS). We compared the performances of the several machine learning (ML) algorithms to predict HT after AIS using only structured data. A total of 2028 patients with AIS, who were admitted within seven days of symptoms onset, were included in this analysis. HT was defined based on the criteria of the European Co-operative Acute Stroke Study-II trial. The whole dataset was randomly divided into a training and a test dataset with a 7:3 ratio. Binary logistic regression, support vector machine, extreme gradient boosting, and artificial neural network (ANN) algorithms were used to assess the performance of predicting the HT occurrence after AIS. Five-fold cross validation and a grid search technique were used to optimize the hyperparameters of each ML model, which had its performance measured by the area under the receiver operating characteristic (AUROC) curve. Among the included AIS patients, the mean age and number of male subjects were 69.6 years and 1183 (58.3%), respectively. HT was observed in 318 subjects (15.7%). There were no significant differences in corresponding variables between the training and test dataset. Among all the ML algorithms, the ANN algorithm showed the best performance in terms of predicting the occurrence of HT in our dataset (0.844). Feature scaling including standardization and normalization, and the resampling strategy showed no additional improvement of the ANN's performance. The ANN-based prediction of HT after AIS showed better performance than the conventional ML algorithms. Deep learning may be used to predict important outcomes for structured data-based prediction.
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Project description:The prevalence and risk factors of hemorrhagic transformation (HT) after acute ischemic stroke HT have not been adequately delineated. We performed a systematic review and meta-analysis to identify English-language prospective observational MEDLINE and EMBASE-listed reports of acute ischemic stroke with HT published from 1985-2017. Studies that used the ECASS-2 definitions of hemorrhagic transformation subtypes, hemorrhagic infarction (HI), and parenchymal hematoma (PH) were included. Patients treated with intravenous thrombolysis with tissue plasminogen activator (IV-tPA) were compared with those who did not receive thrombolysis. A total of 65 studies with 17,259 patients met inclusion criteria. Overall, HT prevalence was 27%; 32% in patients receiving IV-tPA vs. 20% in those without. Overall PH prevalence was 9%; 12% in IV-tPA treated patients vs. 5% in those without. HT was associated with a history of atrial fibrillation (OR 2.94) and use of anticoagulants (OR 2.47). HT patients had higher NIHSS (Hedge's-G 0.96) and larger infarct volume (diffusion-weighted MRI, Hedge's-G 0.8). In IV-tPA treated patients, PH correlated with antiplatelet (OR 3) and statin treatment (OR 4). HT (OR 3) and PH (OR 8) were associated with a poor outcome at 90-day (mRS 5-6). Hemorrhagic transformation is a frequent complication of acute ischemic stroke and is associated with poor outcome. Recognition of risk factors for HT and PH may reduce their incidence and severity.
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Project description:Introduction: Hemorrhagic transformation (HT) is a complication of reperfusion therapy for acute ischemic stroke. Blood-brain barrier (BBB) disruption is a crucial step toward HT; however, in clinical studies, there is still uncertainty about this relation. Hence, we conducted a systematic review and meta-analysis to summarize the current evidence. Methods: We performed systematic review and meta-analysis of observational studies from January 1990 to March 2020 about the relation between BBB disruption and HT in patients with acute ischemic stroke with both computed tomography (CT) and magnetic resonance (MR) assessment of BBB. The outcome of interest was HT at follow-up imaging evaluation (within 48 h from symptom onset). We pooled data from available univariate odds ratios (ORs) in random-effects models with DerSimonian-Laird weights and extracted cumulative ORs. Results: We included 30 eligible studies (14 with CT and 16 with MR), N = 2,609 patients, with 88% and 70% of patients included in CT and MR studies treated with acute stroke therapy, respectively. The majority of studies were retrospective and had high or unclear risk of bias. BBB disruption was measured with consistent methodology in CT studies, whereas in MR studies, there was more variability. All CT studies provided a BBB disruption cutoff predictive of HT. Four CT and 10 MR studies were included in the quantitative analysis. We found that BBB disruption was associated with HT with both CT (OR = 3.42; 95%CI = 1.62-7.23) and MR (OR = 9.34; 95%CI = 3.16-27.59). There was a likely publication bias particularly for MR studies. Conclusion: Our results confirm that BBB disruption is associated with HT in both CT and MR studies. Compared with MR, CT has been more uniformly applied in the literature and has resulted in more consistent results. However, more efforts are needed for harmonization of protocols and methodology for implementation of BBB disruption as a neuroradiological marker in clinical practice.
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Project description:BackgroundAmong the patients with established coronary artery diseases, obese patients tend to have a more favorable prognosis, which is called as obesity paradox. Interestingly, mildly obese patients who underwent coronary revascularization had a lower risk of bleeding. In this context, we have investigated the association between obesity and hemorrhagic transformation (HTf) after acute ischemic stroke.MethodsA total of 365 patients with first-ever acute ischemic stroke were included in this study. Demographic, clinical and radiological information was collected and HTf was evaluated through follow-up T2*-weighted gradient-recalled echo MRI performed usually within 1 week after occurrence of stroke. Body mass index was calculated, and obesity was defined using the World Health Organization Western Pacific Regional Office criteria.ResultsThe HTf was identified in 59 patients (16.2%). As the severity of obesity increased, the occurrence of HTf decreased. Compared with the normal weight group and after controlling possible confounders including acute and previous treatment, stroke severity and subtype, the risk of HTf decreased significantly in the obese group (odds ratio, 0.39; 95% confidence interval, 0.17-0.87).ConclusionsThe better outcome for HTf seen in obese patients suggests the existence of a "bleeding-obesity paradox" in acute ischemic stroke.
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