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      Hemorrhagic Transformations after Thrombectomy: Risk Factors and Clinical Relevance

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          Abstract

          Background: Hemorrhagic transformation (HT) is a major complication of acute ischemic stroke, potentially associated with clinical deterioration. We attempted to identify risk factors and evaluated clinical relevance of minor and major HTs following endovascular thrombectomy (ET) in isolated middle cerebral artery (MCA) occlusions. Methods: This is a retrospective single-center analysis of 409 patients with isolated MCA occlusion treated with ET. Patients' and procedural characteristics, severity of HT according to the European Cooperative Acute Stroke Study criteria, and clinical outcomes were analyzed. Multivariate logistic regression models with standard retention criteria ( p < 0.1) were used to determine risk factors and clinical relevance of HT. Results are shown as adjusted OR (aOR) and respective 95% CIs. Good neurologic short-term outcome was defined as National Institutes of Health Stroke Scale (NIHSS) score <5 at the day of discharge. Results: Of 299 patients included, hemorrhagic infarction (HI) was detected in 87 patients, while 13 patients developed parenchymal hematoma (PH). Higher age (aOR 0.970, 95% CI 0.947-0.993, p = 0.012), eligibility for intravenous recombinant tissue plasminogen activator (IV rtPA; aOR 0.512, 95% CI 0.267-0.982, p = 0.044), and complete recanalization (TICI 3, aOR 0.408, 95% CI 0.210-0.789, p = 0.008) were associated with a lower risk of HI. Risk factors for HI included higher admission NIHSS score (aOR 1.080, 95% CI 1.010-1.153, p = 0.024) and higher admission glucose levels (aOR 1.493, 95% CI 1.170-1.904, p = 0.001). Further, female sex tended to be associated with a lower risk of HI (aOR 0.601, 95% CI 0.316-1.143, p = 0.121), while a statistical trend was observable for proximal MCA occlusion (aOR 1.856, 95% CI 0.945-3.646, p = 0.073) and a history of hypertension (aOR 2.176, 95% CI 0.932-5.080, p = 0.072) to increase risk of HI. Longer intervals from symptom onset to first digital subtraction angiography runs (aOR 1.013, 95% CI 1.003-1.022, p = 0.009), lower preinterventional Alberta Stroke Program Early CT score (aOR 0.536, 95% CI 0.307-0.936, p = 0.028) and wake-up stroke (aOR 18.540, 95% CI 1.352-254.276, p = 0.029) were associated with PH. Both, PH and HI were independently associated with lower rates of good neurologic outcome (aOR 0.086, 95% CI 0.008-0.902, p = 0.041 and aOR 0.282, 95% CI 0.131-0.606, p = 0.001). Conclusion: Risk of HI following MCA occlusion and subsequent ET is mainly determined by factors influencing infarct severity. Good recanalization results seem to be protective against subsequent HI. Our results support the notion that occurrence of PH after ET is time dependent and risk increases with more extensive early ischemic damage. Both, HI and PH do not seem to be facilitated by bridging therapy with IV rtPA or the use of oral anticoagulants, but were independently associated with more severe neurologic disability. These results support the notion that HI is not a “benign” imaging sign.

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          Most cited references56

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          Hemorrhagic transformation within 36 hours of a cerebral infarct: relationships with early clinical deterioration and 3-month outcome in the European Cooperative Acute Stroke Study I (ECASS I) cohort.

          The clinical correlates of the varying degrees of early hemorrhagic transformation of a cerebral infarct are unclear. We investigated the cohort of a randomized trial of thrombolysis to assess the early and late clinical course associated with different subtypes of hemorrhagic infarction (HI) and parenchymal hematoma (PH) detected within the first 36 hours of an ischemic stroke. We exploited the database of the European Cooperative Acute Stroke Study I (ECASS I), a randomized, placebo-controlled, phase III trial of intravenous recombinant tissue plasminogen activator in acute ischemic stroke. Findings on 24- to 36- hour CT were classified into 5 categories: no hemorrhagic transformation, HI types 1 and 2, and PH types 1 and 2. We assessed the risk of concomitant neurological deterioration and of 3-month death and disability associated with subtypes of hemorrhagic transformation, as opposed to no bleeding. Risks were adjusted for age and extent of ischemic damage on baseline CT. Compared with absence of hemorrhagic transformation, HI1, HI2, and PH1 did not modify the risk of early neurological deterioration, death, and disability, whereas, in both the placebo and the recombinant tissue plasminogen activator groups, PH2 had a devastating impact on early neurological course (odds ratio for deterioration, 32.3; 95% CI, 13. 4 to 77.7), and on 3-month death (odds ratio, 18.0; 95% CI, 8.05 to 40.1). Risk of disability was also higher, but not significantly, after PH2. Risk of early neurological deterioration and of 3-month death was severely increased after PH2, indicating that large hematoma is the only type of hemorrhagic transformation that may alter the clinical course of ischemic stroke.
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            Glucose-potassium-insulin infusions in the management of post-stroke hyperglycaemia: the UK Glucose Insulin in Stroke Trial (GIST-UK).

            Hyperglycaemia after acute stroke is a common finding that has been associated with an increased risk of death. We sought to determine whether treatment with glucose-potassium-insulin (GKI) infusions to maintain euglycaemia immediately after the acute event reduces death at 90 days. Patients presenting within 24 h of stroke onset and with admission plasma glucose concentration between 6.0-17.0 mmol/L were randomly assigned to receive variable-dose-insulin GKI (intervention) or saline (control) as a continuous intravenous infusion for 24 h. The purpose of GKI infusion was to maintain capillary glucose at 4-7 mmol/L, with no glucose intervention in the control group. The primary outcome was death at 90 days, and the secondary endpoint was avoidance of death or severe disability at 90 days. Additional planned analyses were done to determine any differences in residual disability or neurological and functional recovery. The trial was powered to detect a mortality difference of 6% (sample size 2355), with 83% power, at the 5% two-sided significance level. This study is registered as an International Standard Randomised Controlled Trial (number ISRCTN 31118803) The trial was stopped due to slow enrolment after 933 patients were recruited. For the intention-to-treat data, there was no significant reduction in mortality at 90 days (GKI vs control: odds ratio 1.14, 95% CI 0.86-1.51, p=0.37). There were no significant differences for secondary outcomes. In the GKI group, overall mean plasma glucose and mean systolic blood pressure were significantly lower than in the control group (mean difference in glucose 0.57 mmol/L, p<0.001; mean difference in blood pressure 9.0 mmHg, p<0.0001). GKI infusions significantly reduced plasma glucose concentrations and blood pressure. Treatment within the trial protocol was not associated with significant clinical benefit, although the study was underpowered and alternative results cannot be excluded.
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              Risk score for intracranial hemorrhage in patients with acute ischemic stroke treated with intravenous tissue-type plasminogen activator.

              There are few validated models for prediction of risk of symptomatic intracranial hemorrhage (sICH) after intravenous tissue-type plasminogen activator treatment for ischemic stroke. We used data from Get With The Guidelines-Stroke (GWTG-Stroke) to derive and validate a prediction tool for determining sICH risk. The population consisted of 10 242 patients from 988 hospitals who received intravenous tissue-type plasminogen activator within 3 hours of symptom onset from January 2009 to June 2010. This sample was randomly divided into derivation (70%) and validation (30%) cohorts. Multivariable logistic regression identified predictors of intravenous tissue-type plasminogen activator-related sICH in the derivation sample; model β coefficients were used to assign point scores for prediction. sICH within 36 hours was noted in 496 patients (4.8%). Multivariable adjusted independent predictors of sICH were increasing age (17 points), higher baseline National Institutes of Health Stroke Scale (42 points), higher systolic blood pressure (21 points), higher blood glucose (8 points), Asian race (9 points), and male sex (4 points). The C-statistic was 0.71 in the derivation sample and 0.70 in the independent internal validation sample. Plots of observed versus predicted sICH showed good model calibration in the derivation and validation cohorts. The model was externally validated in National Institute of Neurological Disorders and Stroke trial patients with a C-statistic of 0.68. The GWTG-Stroke sICH risk "GRASPS" score provides clinicians with a validated method to determine the risk of sICH in patients treated with intravenous tissue-type plasminogen activator within 3 hours of stroke symptom onset.
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                Author and article information

                Journal
                CED
                Cerebrovasc Dis
                10.1159/issn.1015-9770
                Cerebrovascular Diseases
                Cerebrovasc Dis
                S. Karger AG (Basel, Switzerland karger@ 123456karger.com http://www.karger.com )
                1015-9770
                1421-9786
                June 2017
                25 March 2017
                : 43
                : 5-6
                : 294-304
                Affiliations
                aDepartment of Neuroradiology, and bDepartment of Radiology, cDepartment of Neurology, Klinikum rechts der Isar, TU München, Munich, and dDepartment of Neuroradiology, Vivantes Klinikum Neukölln, Berlin, Germany
                Author notes
                *Johannes Kaesmacher, MD, Department of Neuroradiology, Klinikum rechts der Isar, Technical University of Munich, Ismaninger Str. 22, DE-81675 Munich (Germany), E-Mail j.kaesmacher@tum.de
                Article
                460265 Cerebrovasc Dis 2017;43:294-304
                10.1159/000460265
                28343220
                e5b34ae0-4c1c-4d25-a1a4-d7c39e5660f0
                © 2017 S. Karger AG, Basel

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                History
                : 26 October 2016
                : 28 January 2017
                Page count
                Tables: 4, References: 65, Pages: 11
                Categories
                Original Paper

                Medicine,General social science
                Stroke,Endovascular,Thrombectomy,Hemorrhagic transformation
                Medicine, General social science
                Stroke, Endovascular, Thrombectomy, Hemorrhagic transformation

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