Hemorrhagic Transformation in Patients With Large-artery Atherosclerotic Stroke Is Associated With Gut Microbiota and LPS-TLR4 Signaling Pathway

2021 ◽  
Author(s):  
Qin Huang ◽  
Min-Ping Wei ◽  
Xian-Jing Feng ◽  
Fang Yu ◽  
Di Liao ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Gut Microbiota ◽  
Intravenous Thrombolysis ◽  
Major Complication ◽  
Hemorrhagic Transformation ◽  
Experimental Stroke ◽  
Large Artery ◽  
Healthy Controls ◽  
Colon Tissue ◽  
Abundance And Diversity

Abstract Objective: Hemorrhagic transformation (HT) is a major complication of ischemic stroke that worsens outcomes and increases mortality. Disruption of gut microbiota is an important feature of stroke, and some special bacteria combined with bacterial metabolites may contribute to HT pathogenesis. we aimed to study the relationship between gut microbiota and HT of large-artery atherosclerotic stroke. Methods: From May-2020 through September-2021, the blood and fecal samples in patients with acute first-ever ischemic stroke and not undergoing intravenous thrombolysis or endovascular were obtained on admission, and gut microbiota was assessed by 16s ribosomal ribonucleic acid (rRNA) sequence. Stroke that developed HT (n=15) were compared to those without HT (n=17) and healthy controls (n=16). We also examined the key components of lipopolysaccharide (LPS) pathway: LPS, LPS-binding protein (LBP), and solube CD14 (sCD14). The role of gut microbiota in HT was evaluated using experimental stroke model. Results: We observed that bacterial diversity was decreased in both HT and non-HT group compared to the healthy controls. The patients of ischemic stroke that developed HT had differential composition of gut microbiota, in particular, an increase in the relative abundance and diversity of members belonging to the Enterobacteriaceae family. Plasma LPS and LBP levels were higher in HT group compared to non-HT group. The concentrations of LPS, LBP and sCD14 were associated with increased abundance of Enterobacteriaceae. In experimental study, the antibiotics treatment diminished HT-induced increase in the levels of LPS and LBP as well as upregulated expression of Toll-like receptor 4 (TLR4) and NF-κB in colon tissue. Transplant of microbiota from HT rats triggered higher level of LPS, LBP and sCD14 in plasma and increased expression of TLR4 and NF-κB in colon tissue.Conclusion: Stroke patients who developed with HT exhibit an obvious change in gut microbiota and LPS-induced inflammatory response. This suggests that maintaining a balance of gut microbiota may be an important factor in preventing HT after stroke.

Abstract WP78: Intracranial Calcification is Predictive for Hemorrhage Transformation and Prognosis After Intravenous Thrombolysis

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Yao Yu ◽  
Fu-Liang Zhang ◽  
Yin-Meng Qu ◽  
Hong-Wei Zhou ◽  
Zhenni Guo ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Poor Prognosis ◽  
Intravenous Thrombolysis ◽  
Major Complication ◽  
Third Party ◽  
Intracranial Calcification ◽  
Stroke Patients ◽  
Anterior Circulation ◽  
Cerebrovascular Function ◽  
Lesion Side

Introduction: Hemorrhage transformation is the major complication of intravenous thrombolysis, which can deteriorate the prognosis of ischemic stroke patients. Calcification is widely used as an imaging indicator of atherosclerotic burden and cerebrovascular function. The relationship between intracranial calcification and hemorrhage transformation has not been fully explained. Here, we aimed to identify and quantify calcification in the main cerebral vessels to investigate the correlations between quantitative calcification parameters, hemorrhage transformation, and prognosis. Methods: Acute noncardiogenic ischemic stroke patients with anterior circulation who received intravenous thrombolysis therapy in the First Hospital of Jilin University from July 2015 to June 2017 were retrospectively consecutively included. All the patients included underwent a baseline CT before intravenous thrombolysis and a follow-up CT at 24 hours. A third-party software, ITK-SNAP, was used for segmentation and measurement of the calcification volume. A vascular non-bone component with a CT value >130 HU was judged to be calcified. The criterion for poor prognosis was an mRS score > 2 at 3 months. Results: A total of 146 patients were included, among which 128 patients were identified to have calcification. Twenty-one patients developed hemorrhage transformation. The risk of hemorrhage transformation in the extreme group of calcification volume on the lesion side was 10.018 times that of the none to mild groups (OR=10.018, 95% CI: 1.030-97.396). Sixty-one patients had poor prognosis. The risk of poor prognosis increased by 54.7% for each additional calcified vessel (OR=1.547, 95% CI: 1.038-2.305). Conclusions: High calcification volume burden on the lesion side is associated with hemorrhage transformation after intravenous thrombolysis. The higher the number of calcified vessels, the greater is the risk of poor prognosis.

Abstract 3268: Ct Perfusion As A Tool To Predict The Risk Of Hemorrhagic Transformation In Ischemic Stroke Treated With Tissue Plasminogen Activator: A Single Center Experience.

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Tareq Kass-Hout ◽  
Maxim Mokin ◽  
Omar Kass-Hout ◽  
Emad Nourollahzadeh ◽  
David Wack ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Acute Stroke ◽  
Brain Tissue ◽  
Cerebral Blood Volume ◽  
Ct Perfusion ◽  
Intravenous Thrombolysis ◽  
Hemorrhagic Transformation ◽  
Stroke Therapy ◽  
Two Phase ◽  
The Mean

Objective: To use the Computed Tomography Perfusion (CTP) parameters at the time of hospital admission, including Cerebral Blood Volume (CBV) and Permeability Surface area product (PS), to identify patients with higher risk to develop hemorrhagic transformation in the setting of acute stroke therapy with intravenous thrombolysis. Methods: Retrospective study that compared admission CTP variables between patients with Hemorrhagic Transformation (HT) acute stroke and those with no hemorrhagic transformation. Both groups received standard of care intravenous thrombolysis with tPA. Twenty patients presented to our stroke center between the years 2007 - 2011 within 3 hours after stroke symptoms onset. All patients underwent two-phase 320 slice CTP which creates CBV and PS measurements. Patients were divided into two groups according to whether or not they had HT on a follow up CT head without contrast, done within 36 hours of the thrombolysis therapy. Clinical, demographic and CTP variables were compared between the HT and non-HT groups using logistic regression analyses. Results: HT developed in 8 (40%) patients. Patients with HT had lower ASPECT score ( P =.03), higher NIHSS on admission ( P= .01) and worse outcome ( P= .04) compared to patients who did not develop HT. Baseline blood flow defects were comparable between the two groups. The mean PS for the HT group was 0.53 mL/min/100g brain tissue, which was significantly higher than that for the non-HT group of 0.04 mL/min/100g brain tissue ( P <.0001). The mean area under the curve was 0.92 (95% CI). The PS threshold of 0.26 mL/min/100g brain tissue had a sensitivity of 80% and a specificity of 92% for detecting patients with high risk of hemorrhagic transformation after intravenous thrombolysis. Conclusions: Admission CTP measurements might be useful to predict patients who are at higher risk to develop hemorrhagic transformation after acute ischemic stroke therapy.

Abstract P12: Alteplase Reduces Mortality in Patients With Ischemic Stroke and Atrial Fibrillation: Analysis of the IAC Study

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Shadi Yaghi ◽  
Eva Mistry ◽  
Adam H De Havenon ◽  
Christopher Leon Guerrero ◽  
Amre Nouh ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Infarct Volume ◽  
Intravenous Thrombolysis ◽  
The United States ◽  
Hemorrhagic Transformation ◽  
Stroke Patients ◽  
Increased Risk ◽  
Significant Difference

Background and Purpose: Multiple studies have established that intravenous thrombolysis with alteplase improves outcome after acute ischemic stroke. However, assessment of thrombolysis’ efficacy in stroke patients with atrial fibrillation (AF) has yielded mixed results. We sought to determine the association of alteplase with mortality, hemorrhagic transformation (HT), infarct volume, and mortality in patients with AF and acute ischemic stroke. Methods: We retrospectively analyzed consecutive acute ischemic stroke patients with AF included in the Initiation of Anticoagulation after Cardioembolic stroke (IAC) study, which pooled data from 8 comprehensive stroke centers in the United States. 1889 (90.6%) had available 90-day follow up data and were included. For our primary analysis we used a cohort of 1367/1889 (72.4%) patients who did not undergo mechanical thrombectomy (MT). Secondary analyses were repeated in the patients that underwent MT (n=522). Binary logistic regression was used to determine whether alteplase use was independently associated with risk of HT, final infarct volume, and 90-day mortality, respectively, adjusting for potential confounders. Results: In our primary analyses we found that alteplase use was independently associated with an increased risk for HT (adjusted OR 2.14, 95% CI 1.49 - 3.07, p <0.001) but overall reduced risk of 90-day mortality (adjusted OR 0.58, 95% CI 0.39 - 0.87, p = 0.009). Among patients undergoing MT, alteplase use was associated with a trend towards a reduction in 90-day mortality (adjusted OR 0.68 95% CI 0.45 - 1.04, p = 0.077). In the subgroup of patients prescribed DOAC treatment (n = 327; 24 received alteplase), alteplase treatment was associated with a trend towards smaller infarct size (< 10 mL), (adjusted OR 0.40, 95% CI 0.15 - 1.12, p = 0.082) without a significant difference in the odds of 90-day mortality (adjusted OR 0.51, 95% CI 0.12 - 2.13, p = 0.357) or hemorrhagic transformation (adjusted OR 0.27, 95% CI 0.03 - 2.07, p = 0.206). Conclusion: Thrombolysis with intravenous alteplase was associated with reduced 90-day mortality in AF patients with acute ischemic stroke not undergoing MT. Further study is required to assess the safety and efficacy of alteplase in AF patients undergoing MT and those on DOACs.

Abstract W P63: Intravenous Thrombolysis for Acute Ischemic Stroke in Nonagenarians

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Raul Guisado ◽  
Reza Malek ◽  
Ursula Kelly-Tolley ◽  
Arash Padidar ◽  
Harmeet Sachdev
Keyword(s):  
Ischemic Stroke ◽  
Mortality Rate ◽  
Acute Ischemic Stroke ◽  
Ct Perfusion ◽  
Intravenous Thrombolysis ◽  
Hemorrhagic Transformation ◽  
Early Improvement ◽  
Hospital Patients ◽  
Contrast Ct ◽  
Overall Mortality

The safety and effectiveness of intravenous thrombolysis for acute ischemic stroke (AIS) has been established for populations older than 80 years of age . However, management of AIS in nonagenerians is not clear. Previous reports suggest that the rate of ICH after i.v. alteplase is not increased and the rate of early improvement is similar in nonagenerians compared to younger groups, but there is concern with overall mortality and functional outcomes. We report on 20 consecutive patients with AIS treated with i.v. alteplase within 3 hours of onset in two Comprehensive Stroke Centers in San Jose, CA. Methods: Patients were immediately evaluated by members of the Stroke Team of each hospital. . Patients were eligible if they had disabling neurological symptoms, no contraindications for i.v.alteplase and were independent in ADLs prior to the index event. Non-contrast CT brain scan, CT perfusion and CT angiography of head and neck were used to determine the presence of potentially salvageable brain. Results (Table): Mean age was 91 years (range 90 - 98 years). The initial NIHSS was 15.7 ± 6.8. The median NIHSS at hospital discharge was 7.4 ± 8.4 (p <0.001). The median door to needle time was 50.5 minutes (range 36 - 74 minutes). There was no hemorrhagic transformation and no in-hospital mortality. The overall mortality rate at 90 days was 30% (6 of 20 patients) and the rate of good outcome in survivors, defined as mRS ≤ 3 at 90 days was 35.7% (5 of 14 patients). Comment: Intravenous thrombolysis for ischemic stroke in nonagenerians is safe and effective, with good rates of immediate improvement. However, the l90 days mortality rate is high and the long term functional outcome is poor. This data can be useful in helping families make treatment decisions in the most elderly patients with acute ischemic stroke.

scholarly journals Neutrophil-to-Lymphocyte Ratio and Symptomatic Hemorrhagic Transformation in Ischemic Stroke Patients Undergoing Revascularization

2020 ◽  
Vol 10 (11) ◽  
pp. 771
Author(s):  
Milena Świtońska ◽  
Natalia Piekuś-Słomka ◽  
Artur Słomka ◽  
Paweł Sokal ◽  
Ewa Żekanowska ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Multivariable Analysis ◽  
Area Under The Curve ◽  
Intravenous Thrombolysis ◽  
Hemorrhagic Transformation ◽  
Neutrophil To Lymphocyte Ratio ◽  
Study Endpoint ◽  
Stroke Treatment ◽  
Lymphocyte Ratio ◽  
Increased Risk

Objectives: Symptomatic hemorrhagic transformation (sHT) is a life-threatening complication of acute ischemic stroke (AIS). The early identification of the patients at increased risk of sHT can have clinically relevant implications. The aim of this study was to explore the validity and accuracy of the neutrophil-to-lymphocyte ratio (NLR) in predicting sHT in patients with AIS undergoing revascularization. Methods: Consecutive patients hospitalized for AIS who underwent intravenous thrombolysis, mechanical thrombectomy or both were identified. The NLR values were estimated at admission. The study endpoint was the occurrence of sHT within 24 h from stroke treatment. Results: Fifty-one patients with AIS were included, with a median age of 67 (interquartile range, 55–78) years. sHT occurred in 10 (19.6%) patients. Patients who developed sHT had higher NLR at admission. NLR was an independent predictor of sHT and showed good discriminatory power (area under the curve 0.81). In a multivariable analysis, NLR and systolic blood pressure were independently associated with sHT. Conclusions: NLR at admission can accurately predict sHT in patients with AIS undergoing revascularization.

scholarly journals A new nomogram for individualized prediction of the probability of hemorrhagic transformation after intravenous thrombolysis for ischemic stroke patients

BMC Neurology ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yaya Wu ◽  
Hui Chen ◽  
Xueyun Liu ◽  
Xiuying Cai ◽  
Yan Kong ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Intracerebral Hemorrhage ◽  
Validation Cohort ◽  
Treatment Time ◽  
Intravenous Thrombolysis ◽  
Hemorrhagic Transformation ◽  
Calibration Plot ◽  
Global Burden ◽  
Nihss Score ◽  
Individualized Prediction

Abstract 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.

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