Mismatch of Low Perfusion and High Permeability Predicts Hemorrhagic Transformation Region in Acute Ischemic Stroke Patients Treated with Intra-arterial Thrombolysis.
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ABSTRACT:
SUBMITTER: Chen H
PROVIDER: S-EPMC4908417 | biostudies-other | 2016
REPOSITORIES: biostudies-other
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Project description:Background and purposeSHT and ME are feared complications in patients with acute ischemic stroke. They occur >10 times more frequently in tPA-treated versus placebo-treated patients. Our goal was to evaluate the sensitivity and specificity of admission BBBP measurements derived from PCT in predicting the development of SHT and ME in patients with acute ischemic stroke.Materials and methodsWe retrospectively analyzed a dataset consisting of 32 consecutive patients with acute ischemic stroke with appropriate admission and follow-up imaging. We calculated admission BBBP by using delayed-acquisition PCT data and the Patlak model. Collateral flow was assessed on the admission CTA, while recanalization and reperfusion were assessed on the follow-up CTA and PCT, respectively. SHT and ME were defined according to ECASS III criteria. Clinical data were obtained from chart review. In our univariate and forward selection-based multivariate analysis for predictors of SHT and ME, we incorporated both clinical and imaging variables, including age, admission NIHSS score, admission blood glucose level, admission blood pressure, time from symptom onset to scanning, treatment type, admission PCT-defined infarct volume, admission BBBP, collateral flow, recanalization, and reperfusion. Optimal sensitivity and specificity for SHT and ME prediction were calculated by using ROC analysis.ResultsIn our sample of 32 patients, 3 developed SHT and 3 developed ME. Of the 3 patients with SHT, 2 received IV tPA, while 1 received IA tPA and treatment with the Merci device; of the 3 patients with ME, 2 received IV tPA, while 1 received IA tPA and treatment with the Merci device. Admission BBBP measurements above the threshold were 100% sensitive and 79% specific in predicting SHT and ME. Furthermore, all patients with SHT and ME--and only those with SHT and ME--had admission BBBP measurements above the threshold, were older than 65 years of age, and received tPA. Admission BBBP, age, and tPA were the independent predictors of SHT and ME in our forward selection-based multivariate analysis. Of these 3 variables, only BBBP measurements and age were known before making the decision of administering tPA and thus are clinically meaningful.ConclusionsAdmission BBBP, a pretreatment measurement, was 100% sensitive and 79% specific in predicting SHT and ME.
| S-EPMC7964964 | biostudies-literature
Project description:Previous studies have identified a diverse set of predisposing factors for the occurrence of hemorrhagic transformation (HT), but the independent clinical predictors of HT after intraarterial thrombolysis have not been determined. In this retrospective study, we investigated the characteristics of patients with or without HT who had received intra-arterial thrombolysis therapy, using biochemical analysis, renal function test, routine blood test, blood lipid test, coagulation blood test, liver function test, random blood glucose test, time-window for intra-arterial thrombolysis, recanalization, National Institutes of Health Stroke Scale (NIHSS) score and systolic blood pressure before intra-arterial thrombolysis. The mortality rates were similar in the HT and non-HT groups (P = 0.944). In the single-factor analysis, patients with a higher globulin level (P <0.002), prothrombin time activity percentage (PTA; P = 0.026), and NIHSS score (P = 0.002), had a significantly increased risk of developing HT. In the multifactor logistic regression model involving globulin level, PTA, white blood cell count, and NIHSS score, the globulin level (P <0.001; OR, 1.185; 95% confidence interval [CI], 1.090-1.288), PTA (P = 0.018; OR, 1.016; 95% CI, 1.003-1.029), white blood cell count (P = 0.025; OR, 1.097; 95% CI, 1.012-1.190) and NIHSS score (P = 0.003; OR, 1.097; 95% CI, 1.031-1.166) were significantly increased in the HT group. The increase in globulin level is an independent risk factor for HT in patients receiving intra-arterial thrombolysis. The possible mechanisms may involve inflammatory cytokines, matrix metalloproteinase 9, and positive acute-phase reactants synthesized by the liver.
| S-EPMC5562614 | biostudies-other
Project description:Background and Purpose: Hyperhomocysteinemia (Hhcy) is a well-known risk factor for ischemic stroke. However, the role of Hhcy in the clinical outcome of ischemic stroke has not been fully elucidated. In addition, previous studies have found that Hhcy was implicated in the disruption of the blood-brain barrier, which may increase the risk of hemorrhagic transformation (HT) after thrombolysis. Thus, the aim of this study was to investigate the effect of Hhcy on the clinical outcome and HT after thrombolysis in ischemic stroke patients. Methods: Patients who were diagnosed with ischemic stroke and received intravenous thrombolytic therapy between January 2016 and September 2018 were included in this study. Multivariate logistic regression analysis was used to assess the association between Hhcy, clinical outcome, and HT after thrombolysis. Furthermore, the potential interaction between Hhcy and hypertension on the clinical outcome and HT after thrombolysis was also assessed. Results: Of 568 patients, 455 (80.1%) had Hhcy, 66 (11.6%) had HT, and 219 (38.6%) had poor outcome. Patients with Hhcy had a higher incidence of poor outcome than the patients with non-Hhcy (40.9 vs. 29.2%, p = 0.022). However, there was no significant difference in the incidence of HT (11.9 vs. 10.6%, p = 0.711) between patients with Hhcy and non-Hhcy. After adjustment for major covariates, multivariate logistic regression analysis disclosed that Hhcy was independently associated with increased risk of poor outcome (OR = 1.760; 95% CI: 1.069-2.896) but was not associated with the risk of HT (OR = 1.017; 95% CI: 0.495-2.087). In addition, we found no significant interaction between Hhcy and hypertension on the clinical outcome (p = 0.513) or HT (p = 0.170) after thrombolysis. Conclusion: We found that Hhcy was an independent risk factor for poor outcome, but not an independent risk factor for HT after thrombolysis in ischemic stroke patients. In addition, there was no significant interaction of Hhcy and hypertension on the clinical outcome or HT after thrombolysis.
| S-EPMC6584786 | biostudies-literature
Project description:Background: In patients with acute ischemic stroke, hemorrhagic transformation is a major complication after intravenous thrombolysis. This study aimed to investigate the relationship between serum magnesium levels and hemorrhagic transformation (HT) after thrombolytic therapy. Methods: We retrospectively analyzed data from 242 patients who received thrombolytic therapy at the Second Affiliated Hospital of the Wenzhou Medical University in China. Baseline serum magnesium levels were measured before intravenous thrombolysis, and the occurrence of HT was evaluated using computed tomography images reviewed within 24-36 h after therapy. The relationship between serum magnesium levels and HT was examined using multivariate logistic regression, subgroup analysis, and restricted cubic spline models. Results: Of the 242 included patients, 43 (17.8%) developed HT. Patients with HT had significant lower serum magnesium levels than those without HT (0.81 ± 0.08 vs. 0.85 ± 0.08 mmol/L, p = 0.007). Multivariable logistic regression analysis indicated that patients with higher serum magnesium levels had lower risk of HT (OR per 0.1-mmol/L increase 0.43, 95% CI 0.27-0.73, p = 0.002). However, this association did not persist when baseline levels of serum magnesium were higher than the median value (0.85 mmol/L) in subgroup analysis (OR per 0.1-mmol/L increase 0.58, 95% CI 0.14-2.51, p = 0.47). This threshold effect was also observed in the restricted cubic spline model when serum magnesium levels were above 0.88 mmol/L. No association between symptomatic HT and serum magnesium levels was observed in our study (OR per 0.1-mmol/L increase 0.52, 95% CI 0.25-1.11, p = 0.092). Conclusions: Lower serum magnesium levels in patients with ischemic stroke are associated with an increased risk of HT after intravenous thrombolysis, but perhaps only when serum magnesium is below a certain minimal concentration.
| S-EPMC7492199 | biostudies-literature
Project description:BACKGROUND:Reperfusion following ischemic stroke can be attained by either intravenous thrombolysis (IVT) or intra-arterial thrombolysis (IAT). Only a limited number of randomized prospective studies have compared the efficacy and safety of IVT and IAT. This meta-analysis investigated possible clinical benefits of IAT relative to IVT in patients with acute ischemic stroke. METHODS:We searched the PubMed, Cochrane, and Google Scholar databases through October 2013 for manuscripts that describe the findings of randomized controlled or prospective studies that evaluated the outcomes of patients with ischemic stroke who were treated with IVT or IAT. The clinical outcome measures were score on the modified Rankin scale (mRS) and mortality at 90 days. A favorable outcome was defined as an mRS score of 0 to 2. RESULTS:For the mRS, the combined odds ratio (OR) of 3.28 (95% confidence interval (CI), 1.91 to 5.65, P < 0.001) indicated that patients who received IAT had a significantly higher chance for a favorable outcome than did those who received IVT. For mortality, the OR indicated that IAT therapy significantly reduced the proportion of patients who died within 90 days of the procedure (combined OR, 0.40; 95%CI, 0.17 to 0.92; P = 0.032). CONCLUSION:This meta-analysis determined that IAT conferred a significantly greater probability of achieving a favorable outcome compared with IVT. There was also a significant difference in mortality rates between IAT and IVT. The studies included in this analysis were small and heterogeneous; therefore, larger randomized prospective clinical studies are necessary to further investigate this issue.
| S-EPMC4287629 | biostudies-literature
Project description:AimsThe canonical Wnt signaling pathway plays an essential role in blood-brain barrier integrity and intracerebral hemorrhage in preclinical stroke models. Here, we sought to explore the association between canonical Wnt signaling and hemorrhagic transformation (HT) following intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients as well as to determine the underlying cellular mechanisms.Methods355 consecutive AIS patients receiving IVT were included. Blood samples were collected on admission, and HT was detected at 24 hours after IVT. 117 single-nucleotide polymorphisms (SNPs) of 28 Wnt signaling genes and exon sequences of 4 core cerebrovascular Wnt signaling components (GPR124, RECK, FZD4, and CTNNB1) were determined using a customized sequencing chip. The impact of identified genetic variants was further studied in HEK 293T cells using cellular and biochemical assays.ResultsDuring the study period, 80 patients experienced HT with 27 parenchymal hematoma (PH). Compared to the non-PH patients, WNT7A SNPs (rs2163910, P = .001, OR 2.727; rs1124480, P = .002, OR 2.404) and GPR124 SNPs (rs61738775, P = .012, OR 4.883; rs146016051, P < .001, OR 7.607; rs75336000, P = .044, OR 2.503) were selectively enriched in the PH patients. Interestingly, a missense variant of GPR124 (rs75336000, c.3587G>A) identified in the PH patients resulted in a single amino acid alteration (p.Cys1196Tyr) in the intracellular domain of GPR124. This variant substantially reduced the activity of WNT7B-induced canonical Wnt signaling by decreasing the ability of GPR124 to recruit cytoplasmic DVL1 to the cellular membrane.ConclusionVariants of WNT7A and GPR124 are associated with increased risk of PH in patients with AIS after intravenous thrombolysis, likely through regulating the activity of canonical Wnt signaling.
| S-EPMC7804912 | biostudies-literature
Project description:IntroductionThe neutrophil-to-lymphocyte ratio (NLR) has been shown to be a marker associated with inflammation and is independently associated with the adverse clinical outcomes of symptomatic intracranial hemorrhage, cancer, and cardiovascular disease. Hemorrhagic transformation (HT) is a serious complication of ischemic cerebral infarction and can be intensified by therapeutic interventions for acute ischemic stroke (AIS). The purpose of our research was to explore the predictive effect of NLR for HT in patients with AIS and to determine the best predictive value.MethodsPubMed, Web of Science, EMBASE, MEDLINE, Cochrane, and Google Scholar were searched. The primary endpoint was HT, and subgroup analysis was performed. Review Manager software version 5.3 was used to statistically analyze the outcomes.ResultsA total of seven studies including 3,726 patients met the inclusion criteria. The pooled odds ratio (OR) value of the high NLR that predicted HT in AIS patients was 1.53 (95% CI, 1.21-1.92; p = .0003). In addition, 1.10 (95% CI, 1.05-1.15; p < .0001) was the pooled OR of the high NLR associated with increased 3-month mortality in patients with AIS. In the subgroup analysis with an NLR cutoff value of 7.5-11, the correlation between NLR above the cutoff value and the rate of HT in patients with AIS was statistically significant (OR, 7.93; 95% CI, 2.25-27.95; p = .001).ConclusionA high NLR can predict HT and 3-month mortality in patients with AIS. Regardless of the country of origin and the sampling time, an NLR with a cutoff value of 7.5-11 was independently associated with HT in AIS patients.
| S-EPMC6749596 | biostudies-literature
Project description:BackgroundThe efficacy and safety of mechanical thrombectomy (MT) in acute large vessel occlusion (LVO) patients with minor stroke (NIHSS ≤ 5) remains undetermined. We aimed to compare the efficacy and safety of intra-arterial thrombolysis (IAT) alone vs. MT for LVO patients with minor stroke.MethodsPatients were selected from the Acute Ischemic Stroke Cooperation Group of Endovascular Treatment (ANGEL) registry, a prospective multicenter registry study, and divided into MT and IAT alone groups. We compared the outcome measures between the two groups, including 90-day functional outcome evaluated by the modified Rankin Scale (mRS), the final recanalization level, intracranial hemorrhage, and mortality within 90-days by logistic regression models with adjustment. Besides the conventional multivariable analysis, we performed a sensitivity analysis by adjusting the propensity score to confirm our results. The propensity score was derived using a logistic regression model.ResultsOf the 120 patients, 63 received IAT alone and 57 received MT as the first-line treatment strategy. As compared to MT group, patients in the IAT alone group were associated with a higher chance of 90-day mRS 0-2 [93.7% vs. 71.9%, odds ratio (OR) = 4.75, 95% confidence interval (CI): 1.20-18.80, P = 0.027], a high chance of 90-day mRS 0-3 (96.8% vs. 86.7%, OR = 11.35, 95% CI: 1.93-66.86, P = 0.007), a shorter median time from puncture to recanalization (PTR) (60 min vs. 100 min, β = -63.70, 95% CI: -81.79- -45.61, P < 0.001), a lower chance of any intracranial hemorrhage (ICH) within 48 h (3.2% vs. 19.3%, OR = 0.15, 95% CI: 0.03-0.79, P = 0.025), and a lower chance of mortablity within 90 days (1.6% vs. 9.2%, OR = 0.05, 95% CI: 0.01-0.57, P = 0.016). Similarly, the sensitivity analysis showed the robustness of the primary analysis.ConclusionsCompared with MT, IAT may improve 90-day clinical outcomes with decreased ICH rate and mortality in LVO patients with minor stroke.
| S-EPMC9315389 | biostudies-literature
Project description:The purpose of this study was to investigate the relationship between hyperperfusion and hemorrhagic transformation (HT) in acute ischemic stroke (AIS). Pseudo-continuous arterial spin labeling (ASL) with background suppressed 3D GRASE was performed during routine clinical magnetic resonance imaging (MRI) on AIS patients at various time points. Arterial spin labeling cerebral blood flow (CBF) maps were visually inspected for the presence of hyperperfusion. Hemorrhagic transformation was followed during hospitalization and was graded on gradient recalled echo (GRE) scans into hemorrhagic infarction (HI) and parenchymal hematoma (PH). A total of 361 ASL scans were collected from 221 consecutive patients with middle cerebral artery stroke from May 2010 to September 2013. Hyperperfusion was more frequently detected posttreatment (odds ratio (OR) = 4.8, 95% confidence interval (CI) 2.5 to 8.9, P < 0.001) and with high National Institutes of Health Stroke Scale (NIHSS) scores at admission (P<0.001). There was a significant association between having hyperperfusion at any time point and HT (OR = 3.5, 95% CI 2.0 to 6.3, P < 0.001). There was a positive relationship between the grade of HT and time-hyperperfusion with the Spearman's rank correlation of 0.44 (P = 0.003). Arterial spin labeling hyperperfusion may provide an imaging marker of HT, which may guide the management of AIS patients post tissue-type plasminogen activator (tPA) and/or endovascular treatments. Late hyperperfusion should be given more attention to prevent high-grade HT.
| S-EPMC4420881 | biostudies-other
Project description:BACKGROUND:A reliable scoring tool to detect the risk of intracerebral hemorrhage (ICH) after intravenous thrombolysis for ischemic stroke is warranted. The present study was designed to develop and validate a new nomogram for individualized prediction of the probability of hemorrhagic transformation (HT) in patients treated with intravenous (IV) recombinant tissue plasminogen activator (rt-PA). METHODS:We enrolled patients who suffered from acute ischemic stroke (AIS) with IV rt-PA treatment in our emergency green channel between August 2016 and July 2018. The main outcome was defined as any type of intracerebral hemorrhage according to the European Cooperative Acute Stroke Study II (ECASS II). All patients were randomly divided into two cohorts: the primary cohort and the validation cohort. On the basis of multivariate logistic model, the predictive nomogram was generated. The performance of the nomogram was evaluated by Harrell's concordance index (C-index) and calibration plot. RESULTS:A total of 194 patients with complete data were enrolled, of whom 131 comprised the primary cohort and 63 comprised the validation cohort, with HT rate 12.2, 9.5% respectively. The score of chronic disease scale (CDS), the global burden of cerebral small vascular disease (CSVD), National Institutes of Health Stroke Scale (NIHSS) score???13, and onset-to-treatment time (OTT)???180 were detected important determinants of ICH and included to construct the nomogram. The nomogram derived from the primary cohort for HT had C- Statistics of 0.9562 and the calibration plot revealed generally fit in predicting the risk of HT. Furthermore, we made a comparison between our new nomogram and several other risk-assessed scales for HT with receiver operating characteristic (ROC) curve analysis, and the results showed the nomogram model gave an area under curve of 0.9562 (95%CI, 0.9221-0.9904, P?<?0.01) greater than HAT (Hemorrhage After Thrombolysis), SEDAN (blood Sugar, Early infarct and hyper Dense cerebral artery sign on non-contrast computed tomography, Age, and NIHSS) and SPAN-100 (Stroke Prognostication using Age and NIHSS) scores. CONCLUSIONS:This proposed nomogram based on the score of CDS, the global burden of CSVD, NIHSS score???13, and OTT???180 gives rise to a more accurate and more comprehensive prediction for HT in patients with ischemic stroke receiving IV rt-PA treatment.
| S-EPMC7685652 | biostudies-literature