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Background: This aimed to elucidate the impact of stress hyperglycemia on early neurological deterioration (END) in patients with acute non-cardiogenic cerebral infarction who did not experience hemorrhagic transformation following intravenous thrombolysis to identify risk factors associated with END. Methods: This retrospective case-control study analyzed data from consecutive patients who received intravenous thrombolysis for acute ischemic stroke (AIS) without hemorrhagic transformation at the Stroke Center of The Fifth Affiliated Hospital of Sun Yat-sen University from January 2018 to February 2023. END was defined as an increase of more than 2 points on the National Institutes of Health Stroke Scale (NIHSS) within 7 days of admission. Results: A total of 250 patients (56 males, 22.4%) were included, with a mean age of 63.34 ± 12.90 years. Of them, 41 were classified into the END group and 209 into the non-END group. Stress hyperglycemia ratio (SHR) demonstrated a significant correlation with END (r=-0.003, P = 0.003). HbA1c (OR = 0.68, 95% CI: 0.481–0.921) and SHR (OR = 0.00, 95% CI: 0.0-0.051) were independently associated with END. Receiver-operating characteristic (ROC) curve analysis indicated that SHR had a sensitivity of 79.9%, specificity of 88.8%, and an area under the curve (AUC) of 0.857 for predicting END. Conclusions: SHR was significantly associated with END in patients with acute non-cardioembolic cerebral infarction who did not undergo hemorrhagic transformation after intravenous thrombolysis. [ABSTRACT FROM AUTHOR]

Background: Hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) with rt-PA can precipitate rapid neurological deterioration, poor prognosis, and even death. The HALP score (hemoglobin, albumin, lymphocyte, and platelet) is a novel indicator developed to reflect both systemic inflammation and the nutritional status of patients. The goal of this study was to reveal the relationship between the HALP score and the risk of HT after IVT in people with acute ischemic stroke (AIS). Methods: A total of 753 patients with AIS were included in this study. Patients were divided into quartiles according to baseline HALP score. The HALP score was calculated as follows: hemoglobin (g/L) × albumin (g/L) × lymphocytes (/L)/platelets (/L). Binary logistic regression was used to reveal the connection between HALP score and HT. Results: The baseline HALP score were significantly lower in the HT than non-HT patients (p < 0.001). The HALP score were divided into four quartiles: Q1 (<27.4), Q2 (27.4–37.6), Q3 (37.7–49.6), Q4 (>49.6), respectively. Moreover, the severity of HT increased with decreasing HALP level (p < 0.001). In multivariable logistic regression, taking the Q4 as the reference, the association between Q1 and HT remained, after adjusting for confounding variables [odds ratio (OR) = 3.197, 95% confidence interval (CI) = 1.634–6.635, p = 0.003]. Conclusion: The HALP value can predict the HT risk after IVT in patients with AIS. A lower HALP level was associated with an increased severity of HT post-IVT. [ABSTRACT FROM AUTHOR]

The authors present a case of an acute right middle cerebral artery infarct in a 65-year-old male with a history of diabetes, hypertension, and cardiovascular disease. The timeline of treatment and the evolution of the stroke is described. This case highlights the significant burden of right-sided cerebral artery stroke, even when intervention is swift. [ABSTRACT FROM AUTHOR]

Background: Ischemic stroke is a leading cause of mortality worldwide, and intravenous thrombolysis, while improving functional outcomes, still leaves a significant mortality rate. This study aimed to investigate the clinical and pathological data of thrombolysed stroke patients who subsequently died and underwent autopsy, focusing on hemorrhagic transformation (HT). Methods: Over a 10-year period, 1426 acute ischemic stroke patients received thrombolysis at our center, with an in-hospital mortality rate of 11.7%. Autopsies were performed on 98 of the 167 deceased patients. Results: HT was found in 47% of these cases, only less than half occurring within a day of thrombolysis. Significant independent predictors of HT included higher lactate dehydrogenase (LD) levels and higher INR values at admission. HT directly caused death in 30% of cases, often through herniation, while other complications (pulmonary embolism, pneumonia) were also common. Conclusions: These findings highlight the importance of postmortem investigations to accurately determine the incidence of HT and contributing factors. Our data indicate that in the vast majority of HT cases, the role of contributing factors other than rt-PA may be important. Of the routinely assessed clinical and laboratory parameters at admission, only LD and INR were found to be independent predictors of HT in the autopsied studied cohort. [ABSTRACT FROM AUTHOR]

Objective To investigate the association between serum Caveolin-1 level and hemorrhagic transformation (HT) in patients with acute ischemic stroke (AIS) after intravenous thrombolysis with alteplase. Methods A total of 124 patients with AIS who underwent intravenous thrombolysis with alteplase in our hospital from June 2020 to November 2021 were enrolled as subjects, and according to the presence or absence of HT, they were divided into HT group with 19 patients and non-HT group with 105 patients. A total of 40 individuals who underwent physical examination during the same period of time were enrolled as control group. Serum Caveolin-1 level was measured and compared between groups, and the HT group and the non-HT group were compared in terms of the clinical indices including sex, age, body mass index, smoking history, hypertension history, diabetes history, coronary heart disease history, atrial fibrillation history, blood pressure on admission, random venous blood glucose on admission, serum low-density lipoprotein on admission, TOAST classification, and baseline NIHSS score. A logistic regression analysis was used to investigate the influencing factors for HT in AIS patients after intravenous thrombolysis with alteplase. Results The HT group and the non-HT group had a significantly higher serum level of Caveolin-1 than the control group on admission (t=10.937,7.873,P

Abstract Background This aimed to elucidate the impact of stress hyperglycemia on early neurological deterioration (END) in patients with acute non-cardiogenic cerebral infarction who did not experience hemorrhagic transformation following intravenous thrombolysis to identify risk factors associated with END. Methods This retrospective case-control study analyzed data from consecutive patients who received intravenous thrombolysis for acute ischemic stroke (AIS) without hemorrhagic transformation at the Stroke Center of The Fifth Affiliated Hospital of Sun Yat-sen University from January 2018 to February 2023. END was defined as an increase of more than 2 points on the National Institutes of Health Stroke Scale (NIHSS) within 7 days of admission. Results A total of 250 patients (56 males, 22.4%) were included, with a mean age of 63.34 ± 12.90 years. Of them, 41 were classified into the END group and 209 into the non-END group. Stress hyperglycemia ratio (SHR) demonstrated a significant correlation with END (r=-0.003, P = 0.003). HbA1c (OR = 0.68, 95% CI: 0.481–0.921) and SHR (OR = 0.00, 95% CI: 0.0-0.051) were independently associated with END. Receiver-operating characteristic (ROC) curve analysis indicated that SHR had a sensitivity of 79.9%, specificity of 88.8%, and an area under the curve (AUC) of 0.857 for predicting END. Conclusions SHR was significantly associated with END in patients with acute non-cardioembolic cerebral infarction who did not undergo hemorrhagic transformation after intravenous thrombolysis.

Nan Chen, Jiadi Gao, Hanshu Zhao, Sihan Liu, Yubing Zhou, Yushuang Liu, Zhongling Zhang, Shanshan Yang Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People’s Republic of ChinaCorrespondence: Shanshan Yang; Zhongling Zhang, Department of Neurology, The First Affiliated Hospital of Harbin Medical University, No. 23 Youzheng Stree, Nangang District, Harbin, Heilongjiang Province, 150001, People’s Republic of China, Tel +86-451-85553681 ; + 86-451-85555918, Fax +86-451-85555918, Email yangshanshan81@163.com; zhangzhongling7@126.comObjective: Stroke is a leading cause of disability and mortality worldwide, posing a significant public health challenge. While treatment of acute ischemic stroke (AIS) with recombinant tissue plasminogen activator (rt-PA) is effective but increases the risk of hemorrhagic transformation (HT). This study aimed to explore the determinants of HT in AIS patients treated with rt-PA and investigate the association between blood glucose levels and HT risk.Methods: We conducted a prospective cohort study at the First Affiliated Hospital of Harbin Medical University from January 2018 to December 2021. Patients with AIS and who received rt-PA within 4.5 hours of symptom onset were included. Demographic, clinical, laboratory, and imaging data were collected.Results: Of the 426 patients, 15% experienced HT post-rt-PA, occurred more frequently in patients with a history of cardiac embolism, higher prethrombolysis NIHSS scores, and elevated fasting blood glucose (FBG) levels. The frequency of HT was higher in non-diabetic patients with FBG levels ≥ 7.0 mmol/L compared to diabetic patients. Elevated blood glucose levels were significantly associated with HT, regardless of diabetes history.Conclusion: The findings suggest importance of precise glycemic control during AIS management to improve patient outcomes, particularly in non-diabetic patients. Future protocols for AIS treatment should incorporate these findings to reduce HT risks. Further large-scale studies are needed to confirm these associations and guide clinical practices.Keywords: Acute ischemic stroke, thrombolytic therapy, rt-PA, hemorrhagic transformation, blood glucose, outcomes

Abstract The authors present a case of an acute right middle cerebral artery infarct in a 65-year-old male with a history of diabetes, hypertension, and cardiovascular disease. The timeline of treatment and the evolution of the stroke is described. This case highlights the significant burden of right-sided cerebral artery stroke, even when intervention is swift.

Jiahuan Guo,1 Dandan Wang,1 Jiaokun Jia,1 Jia Zhang,1 Yanfang Liu,1 Jingjing Lu,1,2 Xingquan Zhao,1– 4,&ast; Jing Yan1,&ast; 1Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Research Unit of Artificial Intelligence in Cerebrovascular Disease, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 4Center of Stroke, Beijing Institute for Brain Disorders, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xingquan Zhao; Jing Yan, Email zxq@vip.163.com; joyce_yj@163.comPurpose: Inflammatory response plays essential roles in the pathophysiology of both ischemic stroke and atrial fibrillation (AF). We aimed to investigate whether composite inflammatory markers, including neutrophil to lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR) and platelet-to-lymphocyte ratio (PLR), can serve as early predictors of short- and long-term outcomes in ischemic stroke patients with AF.Patients and Methods: Ischemic stroke patients with AF were enrolled in this cohort study. The primary outcome was 1-year functional dependence or death (modified Rankin scale (mRS) score 3– 6). Secondary outcomes included hemorrhagic transformation (HT) and early neurological deterioration (END, increase in the National Institutes of Health Stroke Scale (NIHSS) ≥ 4 within 7 days). Partial correlations were performed to assess the correlation between systemic inflammation markers and admission NIHSS scores. Univariate and multivariate logistic analyses were performed to investigate whether systemic inflammatory markers were independent predictors of adverse outcomes.Results: A total of 408 patients were included. Partial correlation analysis revealed statistically significant but weak correlations between the NLR (r = 0.287; P < 0.001), PLR (r = 0.158; P = 0.001) and admission NIHSS score. Compared with patients without HT or END, patients who developed HT or END had higher NLR and PLR, and lower LMR. Patients in the functional dependence or death group had significantly higher NLR and PLR, and lower LMR than those in the functional independence group (all P < 0.001). Multivariate logistic analysis indicated that NLR, LMR and PLR were independent predictors of HT (OR = 1.069, 0.814 and 1.003, respectively), END (OR = 1.100, 0.768 and 1.006, respectively) and adverse 1-year functional outcome (OR = 1.139, 0.760 and 1.005, respectively).Conclusion: NLR, LMR and PLR were independent predictors for in-hospital HT, END and long-term functional outcome in ischemic stroke patients with AF. Close monitoring of these inflammatory markers may help guide risk stratification and clinical treatment strategies.Keywords: inflammation, ischemic stroke, atrial fibrillation, hemorrhagic transformation, early neurological deterioration, functional outcome

Abstract Background Hemorrhagic transformation (HT) is a serious complication of thrombolytic therapy for acute ischemic stroke, limiting its indications and affecting treatment plans and clinical prognosis. Identifying risk factors for HT could help improve the risk–benefit ratio of thrombolytic therapy. We aimed to analyze the predictors of HT after reperfusion therapy with recombinant tissue plasminogen activator (rTPA) in patients with acute ischemic stroke. This study included 115 patients who received rTPA. All patients underwent history taking, clinical examination, neurological examination including Glasgow Coma Scale and National Institutes of Health Stroke Scale scores (NIHSS), radiological investigation, and cardiac investigation. Patients were followed up strictly every 2 h for 1st 24 h then for two weeks clinically using the NIHSS and radiologically using CT or MRI to detect HT. Results Patients with HT represented 21.7% of all patients receiving rTPA, while symptomatic intracranial hemorrhage (sICH) represented 6.9%. Patients with HT had significantly higher blood pressure, respiratory rate, atrial fibrillation rate, NIHSS score, INR, prothrombin time, neutrophil-to-lymphocyte ratio (NLR), and lower platelet count, LDL level, higher Fazekas score, lower ASPECT score, and prolonged onset-to-needle time. Conclusion Predicting HT in acute ischemic stroke patients is crucial for optimizing management and potentially improving outcomes. In our study, six predictors were associated with HT: higher respiratory rate, higher atrial fibrillation rate, higher NLR, lower LDL level, higher Fazekas score, lower ASPECT score, and onset-to-needle time greater than 180 min.

Abstract Acute ischemic stroke (AIS) is a major global health concern due to its high mortality and disability rates. Hemorrhagic transformation, a common complication of AIS, leads to poor prognosis yet lacks effective treatments. Preclinical studies indicate that hyperbaric oxygen (HBO) treatment within 12 h of AIS onset alleviates ischemia/reperfusion injuries, including hemorrhagic transformation. However, clinical trials have yielded conflicting results, suggesting some underlying mechanisms remain unclear. In this study, we confirmed that HBO treatments beginning within 1 h post reperfusion significantly alleviated the haemorrhage and neurological deficits in hyperglycemic transient middle cerebral arterial occlusion (tMCAO) mice, partly due to the inhibition of the NLRP3 inflammasome-mediated pro-inflammatory response in microglia. Notably, reactive oxygen species (ROS) mediate the anti-inflammatory and protective effect of early HBO treatment, as edaravone and N-Acetyl-l-Cysteine (NAC), two commonly used antioxidants, reversed the suppressive effect of HBO treatment on NLRP3 inflammasome-mediated inflammation in microglia. Furthermore, NAC countered the protective effect of early HBO treatment in tMCAO mice with hyperglycemia. These findings support that early HBO treatment is a promising intervention for AIS, however, caution is warranted when combining antioxidants with HBO treatment. Further assessments are needed to clarify the role of antioxidants in HBO therapy for AIS.

Abstract Intravenous thrombolysis using recombinant tissue plasminogen activator (tPA) remains the primary treatment for patients with acute ischemic stroke (AIS). However, the mechanism of tPA-related hemorrhagic transformation (HT) remains poorly understood. Elevation of histidine-rich glycoprotein (HRG) expression was detected by nano-liquid chromatography tandem mass spectrometry at 1 h following tPA infusion as compared to baseline prior to tPA infusion (discovery cohort, n = 10), which was subsequently confirmed in a validation cohort (n = 157) by ELISA. Surprisingly, no elevation of HRG was detected in individuals who subsequently developed HT. During in vitro experiments, HRG reduced neutrophil NETosis, inflammatory cytokine production, and migration across the blood–brain barrier induced by tPA. In a photothrombotic murine AIS model, HRG administration ameliorated HT with delayed thrombolysis, by inhibiting neutrophil immune infiltration and downregulating pro-inflammatory signaling pathways. Neutrophil depletion or NETosis inhibition also alleviated HT, whereas HRG siRNA treatment exacerbated HT. In conclusion, fluctuations in HRG levels may reflect tPA therapy and its associated HT. The inhibitory effect of HRG on neutrophils may counteract tPA-induced immune abnormalities and HT in patients with AIS.

Cerebral edema (CE) and hemorrhagic transformation (HT) are frequent and unpredictable events in patients with acute ischemic stroke (AIS), even when an effective vessel recanalization has been achieved. These complications, related to blood-brain barrier (BBB) disruption, remain difficult to prevent or treat and may offset the beneficial effect of recanalization, and lead to poor outcomes. The aim of this translational study is to evaluate the association of circulating and imaging biomarkers with subsequent CE and HT in stroke patients with the dual purpose of investigating possible predictors as well as molecular dynamics underpinning those events and functional outcomes. Concurrently, the preclinical study will develop a new mouse model of middle cerebral artery (MCA) occlusion and recanalization to explore BBB alterations and their potentially harmful effects on tissue. The clinical section of the study is based on a single-center observational design enrolling consecutive patients with AIS in the anterior circulation territory, treated with recanalization therapies from October 1, 2015 to May 31, 2020. The study will employ an innovative evaluation of routine CT scans: in fact, we will assess and quantify the presence of CE and HT after stroke in CT scans at 24 h, through the quantification of anatomical distortion (AD), a measure of CE and HT. We will investigate the relationship of AD and several blood biomarkers of inflammation and extracellular matrix, with functional outcomes at 3 months. In parallel, we will employ a newly developed mouse model of stroke and recanalization, to investigate the emergence of BBB changes 24 h after the stroke onset. The close interaction between clinical and preclinical research can enhance our understanding of findings from each branch of research, enabling a deeper interpretation of the underlying mechanisms of reperfusion injury following recanalization treatment for AIS.

Purpose: Machine learning (ML) models were constructed according to noncontrast computed tomography (NCCT) images as well as clinical and laboratory information to assess risk stratification for the occurrence of hemorrhagic transformation (HT) in acute ischemic stroke (AIS) patients. Methods: A retrospective cohort was constructed with 180 AIS patients who were diagnosed at two centers between January 2019 and October 2023 and were followed for HT outcomes. Patients were analyzed for clinical risk factors for developing HT, infarct texture features were extracted from NCCT images, and the radiomics score (Rad-score) was calculated. Then, five ML models were established and evaluated, and the optimal ML algorithm was used to construct the clinical, radiomics, and clinical-radiomics models. Receiver operating characteristic (ROC) curves were used to compare the performance of the three models in predicting HT. Results: Based on the outcomes of the AIS patients, 104 developed HT, and the remaining 76 had no HT. The HT group consisted of 27 hemorrhagic infarction (HI) and 77 parenchymal-hemorrhage (PH). Patients with HT had a greater neutrophil-to-lymphocyte ratio (NLR), baseline National Institutes of Health Stroke Scale (NIHSS) score, infarct volume, and Rad-score and lower Alberta stroke program early CT score (ASPECTS) (all p < 0.01) than patients without HT. The best ML algorithm for building the model was logistic regression. In the training and validation cohorts, the AUC values for the clinical, radiomics, and clinical-radiomics models for predicting HT were 0.829 and 0.876, 0.813 and 0.898, and 0.876 and 0.957, respectively. In subgroup analyses with different treatment modalities, different infarct sizes, and different stroke time windows, the assessment accuracy of the clinical-radiomics model was not statistically meaningful (all p > 0.05), with an overall accuracy of 79.5%. Moreover, this model performed reliably in predicting the PH and HI subcategories, with accuracies of 82.9 and 92.9%, respectively. Conclusion: ML models based on clinical and NCCT radiomics characteristics can be used for early risk evaluation of HT development in AIS patients and show great potential for clinical precision in treatment and prognostic assessment. [ABSTRACT FROM AUTHOR]

Acute ischemic stroke (AIS) is a major global health concern due to its high mortality and disability rates. Hemorrhagic transformation, a common complication of AIS, leads to poor prognosis yet lacks effective treatments. Preclinical studies indicate that hyperbaric oxygen (HBO) treatment within 12 h of AIS onset alleviates ischemia/reperfusion injuries, including hemorrhagic transformation. However, clinical trials have yielded conflicting results, suggesting some underlying mechanisms remain unclear. In this study, we confirmed that HBO treatments beginning within 1 h post reperfusion significantly alleviated the haemorrhage and neurological deficits in hyperglycemic transient middle cerebral arterial occlusion (tMCAO) mice, partly due to the inhibition of the NLRP3 inflammasome-mediated pro-inflammatory response in microglia. Notably, reactive oxygen species (ROS) mediate the anti-inflammatory and protective effect of early HBO treatment, as edaravone and N-Acetyl-l-Cysteine (NAC), two commonly used antioxidants, reversed the suppressive effect of HBO treatment on NLRP3 inflammasome-mediated inflammation in microglia. Furthermore, NAC countered the protective effect of early HBO treatment in tMCAO mice with hyperglycemia. These findings support that early HBO treatment is a promising intervention for AIS, however, caution is warranted when combining antioxidants with HBO treatment. Further assessments are needed to clarify the role of antioxidants in HBO therapy for AIS. [ABSTRACT FROM AUTHOR]

Background: Hemorrhagic transformation (HT) is a serious complication of thrombolytic therapy for acute ischemic stroke, limiting its indications and affecting treatment plans and clinical prognosis. Identifying risk factors for HT could help improve the risk–benefit ratio of thrombolytic therapy. We aimed to analyze the predictors of HT after reperfusion therapy with recombinant tissue plasminogen activator (rTPA) in patients with acute ischemic stroke. This study included 115 patients who received rTPA. All patients underwent history taking, clinical examination, neurological examination including Glasgow Coma Scale and National Institutes of Health Stroke Scale scores (NIHSS), radiological investigation, and cardiac investigation. Patients were followed up strictly every 2 h for 1st 24 h then for two weeks clinically using the NIHSS and radiologically using CT or MRI to detect HT. Results: Patients with HT represented 21.7% of all patients receiving rTPA, while symptomatic intracranial hemorrhage (sICH) represented 6.9%. Patients with HT had significantly higher blood pressure, respiratory rate, atrial fibrillation rate, NIHSS score, INR, prothrombin time, neutrophil-to-lymphocyte ratio (NLR), and lower platelet count, LDL level, higher Fazekas score, lower ASPECT score, and prolonged onset-to-needle time. Conclusion: Predicting HT in acute ischemic stroke patients is crucial for optimizing management and potentially improving outcomes. In our study, six predictors were associated with HT: higher respiratory rate, higher atrial fibrillation rate, higher NLR, lower LDL level, higher Fazekas score, lower ASPECT score, and onset-to-needle time greater than 180 min. [ABSTRACT FROM AUTHOR]

Background and Purpose: Early and reliable prediction of hemorrhagic transformation (HT) in patients with acute ischemic stroke (AIS) is crucial for treatment decisions and early intervention. The purpose of this study was to conduct a systematic review and meta‐analysis on the performance of artificial intelligence (AI) and machine learning (ML) models that utilize neuroimaging to predict HT. Methods: A systematic search of PubMed, EMBASE, and Web of Science was conducted until February 19, 2024. Inclusion criteria were as follows: patients with AIS who received reperfusion therapy; AI/ML algorithm using imaging to predict HT; or presence of sufficient data on the predictive performance. Exclusion criteria were as follows: articles with less than 20 patients; articles lacking algorithms that operate solely on images; or articles not detailing the algorithm used. The quality of eligible studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies‐2 and Checklist for Artificial Intelligence in Medical Imaging. Pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated using a random‐effects model, and a summary receiver operating characteristic curve was constructed using the Reitsma method. Results: We identified six eligible studies, which included 1640 patients. Aside from an unclear risk of bias regarding flow and timing identified in two of the studies, all studies showed low risk of bias and applicability concerns in all categories. Pooled sensitivity, specificity, and DOR were.849,.878, and 45.598, respectively. Conclusion: AI/ML models can reliably predict the occurrence of HT in AIS patients. More prospective studies are needed for subgroup analyses and higher clinical certainty and usefulness. [ABSTRACT FROM AUTHOR]

Background: The hyperdense lesion on non-contrast CT (NCCT) is a common postoperative phenomenon in acute ischemic stroke patients who are treated with endovascular therapy (EVT). Both contrast extravasation and hemorrhagic transformation presented hyperdense lesions on NCCT, which are sometimes difficult to distinguish them. Summary of Review: Radiographic findings are important for identifying contrast extravasation and hemorrhagic transformation. We recommended a standardized follow-up protocol involving imaging and clinical evaluation as it will allow neurologists and neuroradiologists to reveal the relationships between these hyperdensities and various clinical outcomes. Key Messages: Dual-energy CT and susceptibility-weighted imaging are capable of distinguishing contrast extravasation and hemorrhagic transformation at an early stage after EVT. However, in institutions without access to such technology, a follow-up protocol based on NCCT is crucial. [ABSTRACT FROM AUTHOR]

Objectives: Blood-brain barrier (BBB) disruption is an important pathological change after cerebral infarction that exacerbates brain injury. We aimed to investigate and compare the predictive utility of pre-treatment BBB permeability (BBBP) and BBBP within 1 h after endovascular treatment (EVT) for hemorrhagic transformation (HT) and 90-day prognosis. Methods: Patients underwent preoperative computed tomography perfusion (CTP) and non-contrast CT (NCCT) within 1 h after EVT. Preoperative BBBP was determined by the relative permeability surface area product (rPS) in the hypoperfusion area. Postoperative BBBP was determined by the post-EVT Alberta Stroke Program Early CT Score (Post-ASPECTS), which is based on brain parenchymal hyperdensity on the postoperative NCCT. Outcomes: We included 100 patients. Univariate logistic regression analysis revealed correlations of preoperative rPS with HT, poor outcomes, and death. However, these correlations were not observed in multivariate logistic regression. A Post-ASPECTS ≤7 and could independently predict poor outcomes, while Post-ASPECTS ≤6 could independently predict death and HT. The baseline National Institutes of Health Stroke Scale (NIHSS) score could independently predict poor outcomes and death but not HT. A combined model using the baseline NIHSS and Post-ASPECTS scores had better predictive performance for poor outcomes and death than baseline NIHSS score alone; however, it was not superior to the predictive performance of the Post-ASPECTS score. Conclusion: The preoperative rPS cannot independently predict clinical outcomes in EVT-treated patients; contrastingly, the Post-ASPECTS score could independently predict poor outcomes, death, and HT. This parameter could inform prompt postoperative treatment decisions. [ABSTRACT FROM AUTHOR]

Intravenous thrombolysis using recombinant tissue plasminogen activator (tPA) remains the primary treatment for patients with acute ischemic stroke (AIS). However, the mechanism of tPA-related hemorrhagic transformation (HT) remains poorly understood. Elevation of histidine-rich glycoprotein (HRG) expression was detected by nano-liquid chromatography tandem mass spectrometry at 1 h following tPA infusion as compared to baseline prior to tPA infusion (discovery cohort, n = 10), which was subsequently confirmed in a validation cohort (n = 157) by ELISA. Surprisingly, no elevation of HRG was detected in individuals who subsequently developed HT. During in vitro experiments, HRG reduced neutrophil NETosis, inflammatory cytokine production, and migration across the blood–brain barrier induced by tPA. In a photothrombotic murine AIS model, HRG administration ameliorated HT with delayed thrombolysis, by inhibiting neutrophil immune infiltration and downregulating pro-inflammatory signaling pathways. Neutrophil depletion or NETosis inhibition also alleviated HT, whereas HRG siRNA treatment exacerbated HT. In conclusion, fluctuations in HRG levels may reflect tPA therapy and its associated HT. The inhibitory effect of HRG on neutrophils may counteract tPA-induced immune abnormalities and HT in patients with AIS. Synopsis: Histidine-rich glycoprotein (HRG) was found to be increased in plasma following thrombolysis by tissue plasminogen activator (tPA) infusion, which counteracted the hemorrhagic-prone state through inhibiting neutrophil NETosis and migration, ultimately reducing the risk of hemorrhage. Plasma levels of HRG increase following tPA treatment in patients with acute ischemic stroke. Elevated HRG levels in patients with AIS correlated with reduced hemorrhagic transformation after thrombolysis. HRG administration inhibited neutrophil NETosis and migration through the blood–brain barrier in vitro and in an animal model of middle cerebral artery occlusion, ultimately reducing hematoma and neurological deficits. Histidine-rich glycoprotein (HRG) was found to be increased in plasma following thrombolysis by tissue plasminogen activator (tPA) infusion, which counteracted the hemorrhagic-prone state through inhibiting neutrophil NETosis and migration, ultimately reducing the risk of hemorrhage. [ABSTRACT FROM AUTHOR]

Background: The relationship between hemorrhagic transformation (HT) and uric acid (UA) remains controversial. This study aimed to investigate the relationship between UA concentrations and the risk of HT following acute ischemic stroke (AIS). Methods: Electronic databases were searched for studies on HT and UA from inception to October 31, 2023. Two researchers independently reviewed the studies for inclusion. STATA Software 16.0 was used to compute the standardized mean difference (SMD) and 95% confidence interval (CI) for the pooled and post-outlier outcomes. Heterogeneity was evaluated using the I2 statistic and the Galbraith plot. Additionally, sensitivity analysis was performed. Lastly, Begg's funnel plot and Egger's test were used to assess publication bias. Results: A total of 11 studies involving 4,608 patients were included in the metaanalysis. The pooled SMD forest plot (SMD = -0.313, 95% CI = -0.586--0.039, p = 0.025) displayed that low UA concentrations were linked to a higher risk of HT in post-AIS patients. However, heterogeneity (I2 = 89.8%, p < 0.001) was high among the studies. Six papers fell outside the Galbraith plot regression line, and there exclusive resulted in the absence of heterogeneity (I2 = 52.1%, p = 0.080). Meanwhile, repeated SMD analysis (SMD = -0.517, 95% CI = -0.748--0.285, p = 0.000) demonstrated that the HT group had lower UA concentrations. Finally, Begg's funnel plot and Egger's test indicated the absence of publication bias in our meta-analysis. Conclusion: This meta-analysis illustrated a substantial connection between UA concentrations and HT, with lower UA concentrations independently linked with a higher risk of HT post-AIS. These results lay a theoretical reference for future studies. [ABSTRACT FROM AUTHOR]

Introduction: Hemorrhagic transformation (HT) is a serious complication that can occur spontaneously after an acute ischemic stroke (AIS) or after a thrombolytic/mechanical thrombectomy. Our study aims to explore the potential correlations between fibrinogen levels and the occurrence of spontaneous HT (sHT) and HT after mechanical thrombectomy (tHT). Methods: A total of 423 consecutive AIS patients diagnosed HT who did not undergone thrombolysis and 423 age- and sex-matched patients without HT (non-HT) were enrolled. Fibrinogen levels were measured within 24 h of admission after stroke. The cohorts were trisected according to fibrinogen levels. The HT were further categorized into hemorrhagic infarction (HI) or parenchymal hematoma (PH) based on their imaging characteristics. Results: In sHT cohort, fibrinogen levels were higher in HT patients than non-HT patients (p < 0.001 versus p = 0.002). High fibrinogen levels were associated with the severity of HT. HT patients without atrial fibrillation (AF) had higher levels of fibrinogen compared to non-HT (median 3.805 vs. 3.160, p < 0.001). This relationship did not differ among AF patients. In tHT cohort, fibrinogen levels were lower in HT patients than non-HT patients (p = 0.002). Lower fibrinogen levels were associated with the severity of HT (p = 0.004). The highest trisection of fibrinogen both in two cohorts were associated with HT [sHT cohort: OR= 2.515 (1.339-4.725), p = 0.016; that cohort: OR= 0.238 (0.108-0.523), p = 0.003]. Conclusion: Our study suggests that lower fibrinogen level in sHT without AF and higher fibrinogen level in tHT are associated with more severe HT. [ABSTRACT FROM AUTHOR]

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Background: This study explores the predictive value of Computerized Tomography (CT) perfusion imaging, serum D-dimer (D-D), and serum matrix metalloproteinase-9 (MMP-9) levels for hemorrhagic transformation (HT) in patients with acute cerebral infarction post-thrombolysis. Materials and Methods: Patients with acute cerebral infarction who underwent thrombolytic therapy from February 2021 to February 2022 were included. CT perfusion imaging was conducted within a week post-operation. The study compared CT perfusion parameters and serum markers, analyzing differences and conducting univariate and multivariate analyses to explore their predictive value for HT. Results: No significant differences were found in hypertension, hyperlipidemia, stroke history, mean arterial pressure, fasting blood glucose, and platelet count pre-thrombolysis (P > 0.05). However, infarct diameter = 5 cm and atrial fibrillation were more common in the study group, with higher pre-thrombolysis National Institutes of Health Stroke Scale (NIHSS) score, D-D, and MMP-9 levels (P < 0.05). CT perfusion showed lower relative cerebral blood volume (rCBV, relative cerebral blood flow (rCBF, and higher relative mean transit time (rMTT), relative time to peak (rTTP) in the study group (P < 0.05). D-D and MMP-9 levels were negatively correlated with rCBV, rCBF, and positively with rTTP, CTP integration index (P < 0.05). Conclusion: CT perfusion imaging, serum D-D, and MMP-9 levels are effective predictors of hemorrhagic transformation in acute cerebral infarction patients postthrombolysis. These findings are valuable for guiding clinical treatment and monitoring. [ABSTRACT FROM AUTHOR]

BackgroundThe incidence of stroke in China is approximately 343 per 100,000 people each year, the highest rate worldwide. Hemorrhagic transformation (HT), particularly symptomatic intracerebral hemorrhage (sICH) following acute ischemic stroke (AIS) with or without intravenous thrombolysis (IVT), can lead to rapid neurological deterioration, poor prognosis, and even death. Non-alcoholic fatty liver disease (NAFLD) has been identified as a risk factor for stroke occurrence and associated with poor long-term functional outcomes. Nonetheless, no studies have examined the association between liver fibrosis and HT in AIS patients who underwent IVT.MethodA total of 826 patients with AIS who underwent IVT were included in this study. We calculated nine validated liver fibrosis indices to assess the extent of liver fibrosis. HT was detected by follow-up cranial CT/MRI within 24 h post-IVT and was classified as either hemorrhagic infarction (HI) or parenchymal hematoma (PH). Symptomatic intracranial hemorrhage was defined as a sudden symptomatic neurological deterioration, indicated by an increase in (National Institutes of Health Stroke Scale) NIHSS score of 4 points or more.ResultThe median values of fibrosis-4 (FIB-4), modified FIB-4 (mFIB-4), aspartate aminotransferase (AST)-platelet ratio index (APRI), Forns index, alanine aminotransferase (ALT)/AST (ARR), AST/ALT ratio-platelet ratio index (AARPRI), fibrosis quotient (FibroQ), and Fibrosis Index were significantly higher, while the fibrosis-5 (FIB-5) was significantly lower in the HT and sICH groups (all P < 0.001). After adjusting for potential confounders, all nine liver fibrosis indices remained associated with HT and sICH. Receiver operating characteristic (ROC) curve analysis revealed that the FibroQ score had the best predictive ability for HT (AUC = 0.707, CI = 0.652–0.762, P < 0.001), while FIB-4 had the best predictive ability for sICH (AUC = 0.802, CI = 0.711–0.892, P < 0.001).ConclusionLiver fibrosis, as validated by FIB-4, mFIB-4, FIB-5, APRI, Forns index, ARR, AARPRI, FibroQ, and Fibrosis Index, was associated with HT and sICH in AIS patients after IVT.

BACKGROUND Recent advancements in animal studies have demonstrated the potential of normobaric hyperoxia (NBO) as a promising intervention for preserving the integrity of the blood–brain barrier (BBB). However, there is still limited understanding of the effects of NBO on BBB function in patients with clinical stroke. Therefore, the objective of this study was to investigate the efficacy of NBO therapy in attenuating BBB damage and reducing brain injury in individuals undergoing endovascular treatment (EVT) for acute stroke. METHODS AND RESULTS This study enrolled patients from the OPENS‐1 (Normobaric Hyperoxia Combined With Reperfusion for Acute Ischemic Stroke) study, with 43 patients receiving NBO combined with EVT and 43 patients receiving EVT alone. The main outcome measures included serum levels of occludin, MMP‐9 (matrix metalloproteinase‐9), NSE (neuron‐specific enolase), and S100b at 24 hours and 7 days, as well as the intracranial extravasation rate at 24 hours. Serum markers were assessed using ELISA, and intracranial contrast extravasation was visualized using dual‐energy computed tomography scan. We analyzed a total of 86 patients and found that the 24‐hour serum markers levels of BBB damage and brain injury were significantly lower in the group receiving NBO therapy combined with EVT compared with the group receiving EVT alone. Similarly, at 7 days, the levels of occludin, MMP‐9, and NSE were lower in the NBO+EVT group. We also found that the 24‐hour serum levels of occludin and MMP‐9 were correlated with intracranial contrast extravasation. Additionally, the incidence of intracranial contrast extravasation was lower in the NBO+EVT group compared with the EVT group (35.9% versus 60.5%, P=0.031). CONCLUSIONS This study offers valuable insights into the positive impact of NBO on maintaining BBB integrity and reducing brain injury in patients with acute stroke undergoing EVT.

Background The characterization of hemorrhage following acute stroke intervention has largely been computed tomography (CT) based. We sought to compare magnetic resonance imaging‐ (MRI‐) and CT‐based scoring of hemorrhage after acute endovascular therapy (EVT) applying the Heidelberg Bleeding Classification (HBC) to assess intermodal agreement and quantify interrater agreement. Methods Consecutive patients with acute stroke were included in this retrospective study if they (1) had MRI and CT ≤12 hours of each other OR (2) had CT bracketed by MRI pre‐ and post‐CT (ie, MRI‐CT‐MRI) ≤7 days post‐EVT. The concordance of the HBC ratings by consensus panel were compared between CT and T2* gradient recalled echo MRI. Results For the 87 EVT‐treated patients included, median age was 68 years [60–74], admission National Institutes of Health Stroke Scale score 18 [13–23], 47% were treated with intravenous/intraarterial thrombolytics, and 93% were successfully recanalized (modified Thrombolysis in Cerebral Infarction 2b/3). Hemorrhage was detected on at least 1 modality in 60% (52/87) of patients. We found a 68% (59/87, 95% CI [57%–77%]) agreement overall between CT and MRI for hemorrhage classification post‐EVT. MRI had the best interrater agreement for HBC 0 (no hemorrhage) with excellent concordance (ĸ = 0.882), compared with CT (ĸ = 0.683). T2* gradient recalled echo MRI tended to have increased sensitivity to scattered petechial hemorrhage (HBC 1a) as compared with CT with 17% (2/12) intermodal agreement. The interrater agreement of HBC class 2 (ie, parenchymal hematoma grade 2 was substantial for MRI (ĸ = 0.781) and excellent in CT (ĸ = 0.951), with 67% (8/12) intermodal agreement. Subarachnoid hemorrhage was detected in 24% (21/87) of patients on CT and/or MRI with 29% (6/21) intermodal agreement. Conclusion With the exception of subarachnoid hemorrhage and minor petechial hemorrhagic transformation, we found that MRI and CT are overall interchangeable for detecting and classifying hemorrhage after EVT. These findings are reassuring for both clinical decision‐making and research application. Given the complexity of hemorrhage subtypes post‐EVT, work to further refine a post‐EVT hemorrhage classification scale with clinical correlation would be beneficial.

BackgroundHemorrhagic transformation (HT) after intravenous thrombolysis (IVT) with rt-PA can precipitate rapid neurological deterioration, poor prognosis, and even death. The HALP score (hemoglobin, albumin, lymphocyte, and platelet) is a novel indicator developed to reflect both systemic inflammation and the nutritional status of patients. The goal of this study was to reveal the relationship between the HALP score and the risk of HT after IVT in people with acute ischemic stroke (AIS).MethodsA total of 753 patients with AIS were included in this study. Patients were divided into quartiles according to baseline HALP score. The HALP score was calculated as follows: hemoglobin (g/L) × albumin (g/L) × lymphocytes (/L)/platelets (/L). Binary logistic regression was used to reveal the connection between HALP score and HT.ResultsThe baseline HALP score were significantly lower in the HT than non-HT patients (p 49.6), respectively. Moreover, the severity of HT increased with decreasing HALP level (p

Background: Disruption of the blood-brain barrier (BBB) is a major contributor to hemorrhagic transformation (HT) in patients with acute ischemic stroke (AIS) following intravenous thrombolysis (IVT). However, the clinical therapies aimed at BBB protection after IVT remain limited. Methods: One hundred patients with AIS who underwent IVT were enrolled (42 with HT and 58 without HT 24 h after IVT). Based on the cytokine chip, the serum levels of several AIS-related proteins, including LCN2, ferritin, matrix metalloproteinase-3, vascular endothelial-derived growth factor, and X-linked inhibitor of apoptosis, were detected upon admission, and their associations with HT were analyzed. After finding that LCN2 was related to HT in patients with IVT, we clarified whether the modulation of LCN2 influenced BBB dysfunction and HT after thrombolysis and investigated the potential mechanism. Results: In patients with AIS following IVT, logistic regression analysis showed that baseline serum LCN2 (p = 0.023) and ferritin (p = 0.046) levels were independently associated with HT. A positive correlation between serum LCN2 and ferritin levels was identified in patients with HT. In experimental studies, recombinant LCN2 (rLCN2) significantly aggravated BBB dysfunction and HT in the thromboembolic stroke rats after thrombolysis, whereas LCN2 inhibition by ZINC006440089 exerted opposite effects. Further mechanistic studies showed that, LCN2 promoted endothelial cell ferroptosis, accompanied by the induction of high mobility group box 1 (HMGB1) and the inhibition of nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) proteins. Ferroptosis inhibitor ferrostatin-1 (fer-1) significantly restricted the LCN2-mediated BBB disruption. Transfection of LCN2 and HMGB1 siRNA inhibited the endothelial cell ferroptosis, and this effects was reversed by Nrf2 siRNA. Conclusion: LCN2 aggravated BBB disruption after thrombolysis by promoting endothelial cell ferroptosis via regulating the HMGB1/Nrf2/HO-1 pathway, this may provide a promising therapeutic target for the prevention of HT after IVT.

Jingping Sun,1,2,&ast; Jun Zhang,3,&ast; Bailong Xin,1 Zekang Ye,1,2 Yaozhuo Cai,2 Ke Lu,2 Yuzhen Wang,2 Xueyao Lei,2 Chanjuan Zheng,2 Xueli Cai3 1Department of Neurology, the Municipal Central Hospital of Lishui, Fifth Affiliated Hospital of Wenzhou Medical College, Lishui, Zhejiang, People’s Republic of China; 2Lishui Clinical Research Center for Neurological Diseases, Lishui, Zhejiang, People’s Republic of China; 3Zhejiang University, School of Medicine, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xueli Cai, Department of Neurology, the Municipal Central Hospital of Lishui, Fifth Affiliated Hospital of Wenzhou Medical College, Lishui, Zhejiang, People’s Republic of China, Email xueli_cai_official@126.comPurpose: Lipid-lowering therapy is integral in acute ischemic stroke (AIS), yet the connection between lipid parameters and parenchymal hemorrhage (PH) after endovascular treatment (EVT) for AIS is not well-defined. This research aims to assess the association between various lipid parameters and the PH risk following EVT.Patients and Methods: We examined a database of patients who underwent EVT for AIS between September 2021 and May 2023 retrospectively. Traditional and non-traditional lipid parameters were documented. PH was identified on dual energy computed tomography images within 48 h. We employed logistic regression analysis and restricted cubic splines to examine the association between various lipid parameters and the risk of PH. The predictive capacity of the lipid parameters for PH was evaluated by comparing the area under the curve.Results: The study included 384 patients, 65 of whom (17.7%) developed PH. After adjusting for potential confounders, only triglyceride was associated with PH among the traditional lipid parameters, while all non-traditional lipid parameters were related to PH. Based on ROC curve, the ratio of remnant cholesterol to high-density lipoprotein cholesterol (RC/HDL-C) exhibited the highest predictive capability for PH. Furthermore, our analysis revealed a significant nonlinear correlation between triglyceride, non-high-density lipoprotein cholesterol, RC, RC/HDL-C and PH risk.Conclusion: In assessing the risk of PH after EVT, non-traditional lipid parameters are often superior to traditional lipid parameters. It is recommended that routine evaluation of non-traditional lipid parameters could also be conducted in clinical practice as well.Keywords: endovascular treatment, hemorrhagic transformation, serum lipids

Background: Hemorrhagic transformation (HT) in acute ischemic stroke is likely to occur in patients treated with intravenous thrombolysis (IVT) and may lead to neurological deterioration and symptomatic intracranial hemorrhage (sICH). Despite the complex inclusion and exclusion criteria for IVT and some useful tools to stratify HT risk, sICH still occurs in approximately 6% of patients because some of the risk factors for this complication remain unknown. Objective: This study aimed to explore whether there are any differences in circulating microRNA (miRNA) profiles between patients who develop HT after thrombolysis and those who do not. Methods: Using qPCR, we quantified the expression of 84 miRNAs in plasma samples collected prior to thrombolytic treatment from 10 individuals who eventually developed HT and 10 patients who did not. For miRNAs that were downregulated (fold change (FC) <0.67) or upregulated (FC >1.5) with p < 0.10, we investigated the tissue specificity and performed KEGG pathway annotation using bioinformatics tools. Owing to the small patient sample size, instead of multivariate analysis with all major known HT risk factors, we matched the results with the admission NIHSS scores only. Results: We observed trends towards downregulation of miR-1-3p, miR-133a-3p, miR-133b and miR-376c-3p, and upregulation of miR-7-5p, miR-17-3p, and miR-296-5p. Previously, the upregulated miR-7-5p was found to be highly expressed in the brain, whereas miR-1, miR-133a-3p and miR-133b appeared to be specific to the muscles and myocardium. Conclusion: miRNA profiles tend to differ between patients who develop HT and those who do not, suggesting that miRNA profiling, likely in association with other omics approaches, may increase the current power of tools predicting thrombolysis-associated sICH in acute ischemic stroke patients. This study represents a free hypothesis-approach pilot study as a continuation from our previous work. Herein, we showed that applying mathematical analyses to extract information from raw big data may result in the identification of new pathophysiological pathways and may complete standard design works. [ABSTRACT FROM AUTHOR]

Thrombolytic therapy with the tissue plasminogen activator (tPA) is a therapeutic option for acute ischemic stroke. However, this approach is subject to several limitations, particularly the increased risk of hemorrhagic transformation (HT). Lithium salts show neuroprotective effects in stroke, but their effects on HT mechanisms are still unknown. In our study, we use the models of photothrombosis (PT)-induced brain ischemia and oxygen-glucose deprivation (OGD) to investigate the effect of Li+ on tPA-induced changes in brain and endothelial cell cultures. We found that tPA did not affect lesion volume or exacerbate neurological deficits but disrupted the blood–brain barrier. We demonstrate that poststroke treatment with Li+ improves neurological status and increases blood–brain barrier integrity after thrombolytic therapy. Under conditions of OGD, tPA treatment increased MMP-2/9 levels in endothelial cells, and preincubation with LiCl abolished this MMP activation. Moreover, we observed the effect of Li+ on glycolysis in tPA-treated endothelial cells, which we hypothesized to have an effect on MMP expression. [ABSTRACT FROM AUTHOR]

Purpose: In the treatment of intracranial arterial stenosis (ICAS), controversies remain regarding the optimal treatment strategy. Our study aims to conduct an individual patient-level data meta-analysis of existing RCTs comparing PTAS versus best medical therapy and to identify differences in outcomes such as incidence of ischemic stroke or death. Methods: Randomised controlled trials comparing the outcomes of stenting versus best medical therapy for patients who had symptomatic ICAS of >50%. Excluded studies included case reports, case series, reviews, observational studies, letters or studies evaluating isolated angioplasty techniques without stenting. Data was extracted in accordance with PRISMA guidelines. Results: 7 studies involving 1425 participants were included. There was an increased risk in the incidence of stroke and death within the first 30 days post-procedure for patients treated with PTAS over best medical therapy (RR = 2.22 [1.28–3.86], I² = 0%). Patients who underwent stenting also had a significantly higher risk of intracranial haemorrhage (RR = 12.66 [2.41–66.45], I² = 0%) and death (RR = 5.41 [1.20–24.28], I² = 0%). Under the shared frailty model, stenting when compared to medical therapy has a HR of 1.81 (95% CI:1.25–2.6) of stroke or death across 1 year. Under the parametric Royston-Parmar model, stenting has a significant decrease in the RMST(–0.83 months; 95% CI: –1.30–0.37). Stenting continued to show worse outcomes up to the 3 year mark with a HR of 1.60 (95% CI: 1.11–2.32). Conclusions and Relevance: There is an increased risk of peri- and post-procedural stroke and death over best medical therapy in patients with symptomatic ICAS who undergo PTAS. Further work is required to refine patient selection and mitigate peri-procedural risks. [ABSTRACT FROM AUTHOR]

Background: Lipid-lowering therapies are mainstays in reducing recurrence after acute ischemic stroke (AIS). Evolocumab, a Proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitor, is a promising lipid-lowering agent known to decrease LDL cholesterol and mitigate vascular events alongside statins. However, its effects on the early functional outcomes post-mechanical thrombectomy (MT) remain unclear. This study aimed to assess the short-term effects and incidence of bleeding events after the early, off-label use of PCSK9 inhibitors in AIS patients undergoing MT. Methods: We retrospectively analyzed patients who had MT at a Regional Stroke Center from December 2018 to April 2023. Our primary outcome was discharge functional outcomes. Secondary outcomes included early neurologic deterioration (END), symptomatic intracerebral hemorrhage (sICH), 3-month functional outcomes, 3-month recurrence rate, and lipid profiles. Results: Of 261 patients (mean age 69.2 ± 11.7, men 42.9%), 42 were administered evolocumab peri-procedurally. While baseline characteristics were similar between the two groups, evolocumab group demonstrated improved discharge outcomes, with a lower mean NIHSS (8.8 ± 6.8 vs. 12.4 ± 9.8, p = 0.02) and a higher percentage of patients with discharge mRS ≤ 3 (52.4% vs. 35.6%, p = 0.041). The 3-month follow-up show a non-significant trend toward an improved outcome in the evolocumab group. Multivariable analysis indicated that evolocumab had a potential impact on favorable discharge outcomes (aOR 1.98[0.94-4.22] for mRS ≤ 3 and 0.47[0.27-0.84] for lower ordinal mRS). Notably, evolocuamb users exhibited fewer instances of END and sICH, although they do not reach statistical significance. Additionally, the evolocumab group demonstrated potential benefits in LDL cholesterol reduction over time. Conclusion: Early use of evolocumab in AIS patients undergoing MT appeared to be safe and associated with better early functional outcomes. The potential benefit of the PCSK9 inhibitor shown here warrants further prospective studies. [ABSTRACT FROM AUTHOR]

Background: Hemorrhagic transformation (HT) is a serious complication after endovascular thrombectomy (EVT) for patients with acute ischemic stroke (AIS). We analyzed the plasma levels of MMP-9 before and after EVT and assessed the temporal changes of MMP-9 that may be associated with, and therefore predict, HT after EVT. Methods: We enrolled 30 AIS patients who received EVT, and 16 (53.3%) developed HT. The levels of MMP-9 in plasma collected from the arteries of AIS patients before and immediately after EVT were measured using ELISA. The percent change in MMP-9 after EVT (after/before) was calculated and compared between patients with and without HT. Results: The median age of the AIS patients was 70 years, and 13 patients (43.3%) were men. The median National Institutes of Health Stroke Scale (NIHSS) scores of patients with HT were 18 on admission and 18 after EVT. The median NIHSS scores of patients without HT were 17 on admission and 11 after EVT. Patients with HT demonstrated significantly greater percentage increases in arterial MMP-9 levels after EVT. Conclusion: Patients with AIS who developed HT had significantly increased arterial MMP-9 levels after EVT, suggesting that the upregulation of MMP-9 following EVT could serve as a predictive biomarker for HT. [ABSTRACT FROM AUTHOR]

Background and purpose: Early blood-brain barrier (BBB) disruption in patients with acute ischemic stroke (AIS) can be detected on perfusion computed tomography (PCT) images before undergoing reperfusion therapy. In this study, we aimed to determine whether early disruption of the BBB predicts intracranial hemorrhage transformation (HT) in patients with AIS undergoing endovascular therapy and further identify factors influencing BBB disruption. Methods: We retrospectively analyzed general clinical and imaging data derived from 159 consecutive patients with acute anterior circulation stroke who were admitted to the Department of Neurology of the First Hospital of Jilin University, and who underwent endovascular treatment between January 1, 2021, and March 31, 2023. We evaluated the relationship between BBB destruction and intracranial HT before endovascular reperfusion therapy and examined the risk factors for early BBB destruction. Results: A total of 159 patients with assessable BBB leakage were included. The median (interquartile range, IQR) age was 63 (54-70) years, 108 (67.9%) patients were male, and the median baseline National Institutes of Health Stroke Scale (NHISS) score was 12 (10-15). Follow-up non-contrast computed tomography (NCCT) detected HT in 63 patients. After logistic regression modeling adjustment, we found that BBB leakage in the true leakage area was slightly more than 2-fold risk of HT (odds ratio [OR], 2.01; 95% confidence interval [CI] 1.02-3.92). Heart rate was also associated with HT (OR, 1.03, 95% CI, 1.001.05). High Blood-brain barrier permeability (BBBP) in the true leakage area was positively correlated with infarct core volume (OR, 1.03; 95% CI, 1.01-1.05). Conclusion: Early BBB destruction before endovascular reperfusion therapy was associated with HT, whereas high BBBP correlated positively with infarct core volume. [ABSTRACT FROM AUTHOR]

Background and Purpose: Hemorrhagic transformation (HT) is a common complication of endovascular thrombectomy (EVT) in patients with acute ischemic stroke (AIS). Our study aims to investigate the clinical and imaging predictors of HT and symptomatic intracranial hemorrhage (sICH) in patients who underwent EVT. Methods: A retrospective analysis of 118 patients undergoing EVT for acute anterior circulation stroke was performed. Potential clinical and imaging predictors of all patients were collected and multivariate logistic regression was performed. The risk prediction system was constructed according to the multivariate logistic regression results. Results: The incidence of HT and sICH after EVT were 46.6% and 15.3%, respectively. The multivariate logistic regression results showed that Alberta Stroke Program Early CT Score (ASPECTS) (p =.001, odds ratio [OR] = 0.367, 95% [confidence interval] CI, 0.201‐0.670), collateral status (p<.001, OR = 0.117, 95% CI, 0.042‐0.325), relative cerebral blood flow (CBF) ratio (p =.025, OR = 0.943, 95% CI, 0.895‐0.993), and blood glucose on admission (p =.012, OR = 1.258, 95% CI, 1.053‐1.504) were associated with HT. While for sICH, collateral circulation (p =.007, OR = 0.148, 95% CI, 0.037‐0.589), ASPECTS (p =.033, OR = 0.510, 95% CI, 0.274‐0.946), and blood glucose (p =.005, OR = 1.304, 95% CI, 1.082‐1.573) were independent factors. The predictive model for HT after EVT was established, and the sensitivity and specificity of it were 90.9% and 79.4%, respectively, with the area under the curve of 90.0% (84.5%‐95.4%). Conclusion: Collateral status, ASPECTS, relative CBF ratio, and blood glucose on admission were predictors for HT in AIS patients, while collateral status, ASPECTS, and blood glucose on admission were also predictors for sICH. In addition, the established predictive model showed good diagnostic value for prediction of HT after EVT. [ABSTRACT FROM AUTHOR]

Background: Hemorrhagic transformation (HT) following reperfusion therapies is a serious complication for patients with acute ischemic stroke. Segmentation and quantification of hemorrhage provides critical insights into patients' condition and aids in prognosis. This study aims to automatically segment hemorrhagic regions on follow-up non-contrast head CT (NCCT) for stroke patients treated with endovascular thrombectomy (EVT). Methods: Patient data were collected from 10 stroke centers across two countries. We propose a semi-automated approach with adaptive thresholding methods, eliminating the need for extensive training data and reducing computational demands. We used Dice Similarity Coefficient (DSC) and Lin's Concordance Correlation Coefficient (Lin's CCC) to evaluate the performance of the algorithm. Results: A total of 51 patients were included, with 28 Type 2 hemorrhagic infarction (HI2) cases and 23 parenchymal hematoma (PH) cases. The algorithm achieved a mean DSC of 0.66 ± 0.17. Notably, performance was superior for PH cases (mean DSC of 0.73 ± 0.14) compared to HI2 cases (mean DSC of 0.61 ± 0.18). Lin's CCC was 0.88 (95% CI 0.79-0.93), indicating a strong agreement between the algorithm's results and the ground truth. In addition, the algorithm demonstrated excellent processing time, with an average of 2.7 s for each patient case. Conclusion: To our knowledge, this is the first study to perform automated segmentation of post-treatment hemorrhage for acute stroke patients and evaluate the performance based on the radiological severity of HT. This rapid and effective tool has the potential to assist with predicting prognosis in stroke patients with HT after EVT. [ABSTRACT FROM AUTHOR]

Background: There are few data on hemorrhagic transformation in posterior circulation strokes (PCS) compared to anterior circulation strokes (ACS). The aim of this study was to retrospectively analyze the incidence of hemorrhagic transformation, its different subtypes, the associations with different risk factors, and the outcome of ACS and PCS patients. Methods: A retrospective analysis of consecutive ischemic stroke patients with hemorrhagic transformation was performed. Clinical and demographic data were collected from electronic patient records. Results: Included were 186 ACS patients and 67 PCS patients. The median age was 77 years, with PCS patients being slightly younger than ACS patients. ACS patients were more likely to be treated with acetylsalicylic acid before stroke. ACS and PCS patients had comparable frequencies and severity of hemorrhagic transformation. After excluding ACS patients who received thrombectomy, PCS patients developed hemorrhagic transformation more frequently compared to ACS patients. Risk factors for hemorrhagic transformation did not differ between ACS and PCS patients and included vitamin K antagonist use before stroke and thrombectomy in ACS patients. There was no correlation between hemorrhagic transformation and stroke outcome. Conclusions: Hemorrhagic transformation occurs with similar frequency in PCS and ACS patients but is more common in PCS patients after the exclusion of ACS patients undergoing thrombectomy. [ABSTRACT FROM AUTHOR]

Background. Hemorrhagic transformation (HT) is a serious complication that can arise in individuals experiencing acute ischemic stroke (AIS), whether it occurs spontaneously or following thrombolytic therapy, resulting in considerable morbidity and mortality. Hemorrhagic changes are associated with several risk factors, including excessive blood sugar levels, hypertension, the severity of a stroke, and reperfusion. Aim. To assess the commonly available blood parameters such as lipid profile, serum magnesium, and serum ferritin as tools to identify patients who are at risk of hemorrhagic transformation after an acute ischemic stroke. Materials and methods. The study was conducted at the Saveetha Medical College, Chennai, Tamil Nadu, in India, as a cross-sectional study, and a total of 142 patients diagnosed with acute ischemic stroke were enrolled for this study from January 2023 to January 2024. Results. Among the 32 patients who had a hemorrhagic transformation, all 32 (100%) patients had elevated serum ferritin levels and the remaining 110 patients who had no hemorrhagic transformation were found to have normal serum ferritin levels and the difference was statically significant (p<0.001). Total cholesterol, serum LDL, serum HDL, and serum triglycerides had no statistically significant association with hemorrhagic transformation among the patients. Conclusion. The present study concludes that people with lower serum magnesium on admission and higher serum ferritin were found to be at risk. Serum lipid profile had no statistically significant association with hemorrhagic transformation among the patients. [ABSTRACT FROM AUTHOR]

Background: It is challenging yet critical to differentiate between hemorrhagic transformation (HT) and contrast extravasation on non-contrast-enhanced computed tomography (NCCT) scans following mechanical thrombectomy (MT) in patients with acute ischemic stroke. We propose a new method called the ratio of maximum density values (RMDV) to minimize the confusion of contrast extravasation and to evaluate the diagnostic significance of RMDV in predicting HT on immediate post-interventional NCCT scans. Methods: We conducted a retrospective analysis of the prospective patients' database who received MT for acute ischemic stroke caused by occlusion of the intracranial large artery and showed postinterventional cerebral hyperdensities (PCHDs) on NCCT scans immediately after MT. Based on the subsequent NCCT scans, we divided patients with PCHDs into the HT and the non-HT groups. The clinical characters and radiological details were collected and compared to the two groups. We assessed the ability of RMDV >1 to predict HT by analyzing the receiver operating characteristic curve. Results: One hundred and three patients showed PCHDs; 58 (56.31%) were classified as HT, while 45 (43.69%) were classified as non-HT. The only notable distinction between the two groups was the proportion of RMDV >1 in the HT group. The correlation between HT and RMDV >1 with an area under the curve of 0.826 (95% confidence interval, 0.739 to 0.894). The sensitivity, specificity, positive, and negative predictive values of RMDV >1 on NCCT for predicting HT were 89.66, 75.56, 82.54, and 85.00%, respectively. Conclusion: The utilization of RMDV >1 on immediate NCCT scans after MT can predict early HT with good sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Objective: Analysis of the dynamics of systolic blood pressure (SBP) and the results of various types of carotid endarterectomy (СЕЕ) (classical with plasty of the reconstruction zone with a patch, eversion, formation of a new bifurcation, autoarterial reconstruction, glomus-saving techniques) in patients with resistant arterial hypertension (RAH). Materials and methods: The actual cohort, comparative, retrospective, open research for the period from January 2013 to December 2021 includes 1577 patients with significant hemodynamic stenosis of the internal carotid artery Depending on revascularization strategy five groups were formed: Group 1: 18.3% (n = 289) – classical Carotid endarterectomy with plasty of the reconstruction zone with a patch (from diepoxy-treated xenopericardium or synthetic); Group 2: 29.9% (n = 472) – eversional CEE with cut-off of carotid gloomus (CG); Group 3: 6.9% (n = 109) – the formation of a new bifurcation; Group 4: 7.4% (n = 117) - autoarterial reconstruction; Group 5: 37.4% (n = 590) – glomus-saving CEE (1 technique – according to A. N. Kazantsev; two technicians – according to R.A. Vinogradov; three technicians – according to K.A.Antsupov). According to the 24-h blood pressure monitor in the preoperative period, the following degrees of AH were identified: 1° – 5.7% (n = 89); 2° – 64.2% (n = 1013); and 3° – 30.1% (n = 475). Results: In the postoperative period, no significant differences were obtained in the frequency of deaths, myocardial infarction, stroke, hemorrhagic transformation. However, according to the frequency of the combined endpoint (death + myocardial infarction + ischemic stroke + hemorrhagic transformation), the lowest rates were observed in the group of classical carotid endarterectomy with plasty of the reconstruction zone with a patch and glomus-sparing CEE (group 1: 1.03% (n = 3); group 2: 3.6% (n = 17); group 3: 3.67% (n = 4); group 4: 2.56% (n = 3); group 5: 0.5% (n = 3); p = 0.10). This is due to the absence of cases of labile AH and hypertensive crises among patients of groups 1 and 5, which was ensured by the preservation of carotid glomus (CG). As a result, the number of patients with 2 and 3 degrees of hypertension in these groups decreased statistically significantly. The vast majority of patients after these operations achieved a stable target SBP. In groups 2, 3, and 4, there was a statistically significant increase in the number of patients with 2 and 3 degrees of AH, which is associated with excision of the CG Conclusion: Classical CEE and glomus-sparing CEE techniques make it possible to achieve a stable target SBP level in patients with RAH as a result of CG preservation. Removal or traumatization of the latter during eversional CEE, the formation of a new bifurcation, autoarterial reconstruction is accompanied by the development of labile hypertension, an increase in the degree of hypertension and a high risk of hemorrhagic transformation in the brain. Thus, the most effective and safe types of CEE in the presence of RAH are classical CEE with plasty of the reconstruction zone with a patch and glomus-sparing CEE, accompanied by the lowest incidence of adverse cardiovascular events caused by postoperative hypertensive crisis and hyperperfusion syndrome. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) predisposes individuals to vascular injury, leading to poor outcomes after ischemic stroke and symptomatic hemorrhagic transformation (SHT) after thrombolytic and endovascular treatment (EVT). Metformin (MET), an oral antidiabetic drug, has shown potential neuroprotective effects, but its impact on stroke prognosis in DM patients undergoing EVT remains unclear. In a multicenter study, 231 patients with DM undergoing EVT for acute ischemic stroke were enrolled. Prior MET use was identified, and patients were stratified into MET+ and MET− groups. Demographics, clinical data, and outcomes were compared between groups. Multivariate analysis was used to assess the effect of MET on stroke prognosis. Of the enrolled patients, 59.3% were previously on MET. MET+ patients had lower initial infarct volumes and NIHSS scores compared to MET-taking patients. Multivariate analysis showed that MET+ was associated with a lower risk of stroke progression and SHT (with stroke progression as follows: odd ratio [OR] 0.24, 95% confidence interval [CI] [0.12–0.48], p < 0.001; SHT: OR 0.33, 95% CI [0.14–0.75], p = 0.01) and was also associated with better 3-month functional outcomes (mRS 0–2) after EVT. Prestroke MET use in DM patients undergoing EVT is associated with improved stroke prognosis, including reduced risk of stroke progression and SHT and better functional outcomes. These findings suggest the potential neuroprotective role of MET in this population and highlight its clinical utility as an adjunctive therapy in the management of ischemic stroke. Further research is warranted to elucidate the underlying mechanisms and to optimize MET therapy in this setting. [ABSTRACT FROM AUTHOR]

Cerebral infarction is the second leading cause of death in the world, and has become the most serious cause of disability and death in China. Acute ischemic stroke (AIS) is the most common type of cerebral infarction, accounting for about 80% of all cerebral infarctions. Hemorrhagic transformation (HT) is one of the natural regression processes in patients with AIS, and is the most serious complication after treatments [such as intravenous thrombolysis (IVT) or endovascular thrombectomy (EVT)], which brings a heavy burden for patients and their families and even the all society. Accurate prediction and evaluation are of important clinical significance. In recent years, imaging research has focused on the value of CT and MRI in evaluating HT. The diagnostic value of CT plain scan is limited. Before AIS treatment, an early diagnostic score ≤ 7 points in the Alberta Cerebral Infarction Plan is associated with the occurrence of HT (P=0.033), and high-density middle cerebral artery sign is an independent risk factor for the occurrence of HT (OR=10.334). For AIS patients treated with thrombectomy within 2-7 days, dual energy CT scanning at 24 hours after therapy had a high efficacy for prediction of HT occurrence, with a sensitivity of 82.5% and specificity of 100%. CT angiography suggests that patients with high thrombus burden had a higher probability of developing HT (OR=1.28). The incidence of HT in AIS patients with good collateral circulation is low. CT perfusion imaging parameters, including surface permeability, cerebral blood volume, Tmax, etc., have good predictive value for predicting HT occurence. In MRI plain scan, high signal on FLAIR can predict the occurrence of HT. The volume of high signal areas on MRI diffusion-weighted imaging can predict HT, with area under the ROC curve of 0.78.Brush like sign, and micro bleeding lesions on sensitivity weighted MRI indicate the occurrence of HT. Enhanced T1 weighted imaging of MRI shows a significant correlation between brain parenchymal enhancement and HT occurrence (P

Hemorrhagic transformation is a major complication of large-artery atherosclerotic stroke (a major ischemic stroke subtype) that worsens outcomes and increases mortality. Disruption of the gut microbiota is an important feature of stroke, and some specific bacteria and bacterial metabolites may contribute to hemorrhagic transformation pathogenesis. We aimed to investigate the relationship between the gut microbiota and hemorrhagic transformation in large-artery atherosclerotic stroke. An observational retrospective study was conducted. From May 2020 to September 2021, blood and fecal samples were obtained upon admission from 32 patients with first-ever acute ischemic stroke and not undergoing intravenous thrombolysis or endovascular thrombectomy, as well as 16 healthy controls. Patients with stroke who developed hemorrhagic transformation (n = 15) were compared to those who did not develop hemorrhagic transformation (n = 17) and with healthy controls. The gut microbiota was assessed through 16S ribosomal ribonucleic acid sequencing. We also examined key components of the lipopolysaccharide pathway: lipopolysaccharide, lipopolysaccharide-binding protein, and soluble CD14. We observed that bacterial diversity was decreased in both the hemorrhagic transformation and non-hemorrhagic transformation group compared with the healthy controls. The patients with ischemic stroke who developed hemorrhagic transformation exhibited altered gut microbiota composition, in particular an increase in the relative abundance and diversity of members belonging to the Enterobacteriaceae family. Plasma lipopolysaccharide and lipopolysaccharide-binding protein levels were higher in the hemorrhagic transformation group compared with the non-hemorrhagic transformation group. lipopolysaccharide, lipopolysaccharide-binding protein, and soluble CD14 concentrations were associated with increased abundance of Enterobacteriaceae. Next, the role of the gut microbiota in hemorrhagic transformation was evaluated using an experimental stroke rat model. In this model, transplantation of the gut microbiota from hemorrhagic transformation rats into the recipient rats triggered higher plasma levels of lipopolysaccharide, lipopolysaccharide-binding protein, and soluble CD14. Taken together, our findings demonstrate a noticeable change in the gut microbiota and lipopolysaccharide-related inflammatory response in stroke patients with hemorrhagic transformation. This suggests that maintaining a balanced gut microbiota may be an important factor in preventing hemorrhagic transformation after stroke.

Cardioembolic stroke is a major cause of morbidity, with a high risk of recurrence, and anticoagulation represents the mainstay of secondary stroke prevention in most patients. The implementation of endovascular treatment in routine clinical practice complicates the decision to initiate anticoagulation, especially in patients with early hemorrhagic transformation who are considered at higher risk of hematoma expansion. Late hemorrhagic transformation in the days and weeks following stroke remains a potentially serious complication for which we still do not have any established clinical or radiological prediction tools. The optimal time to initiate therapy is challenging to define since delaying effective secondary prevention treatment exposes patients to the risk of recurrent embolism. Consequently, there is clinical equipoise to define and individualize the optimal timepoint to initiate anticoagulation combining the lowest risk of hemorrhagic transformation and ischemic recurrence in cardioembolic stroke patients. In this narrative review, we will highlight and critically outline recent observational and randomized relevant evidence in different subtypes of cardioembolic stroke with a special focus on anticoagulation initiation following endovascular treatment. We will refer mainly to the commonest cause of cardioembolism, non-valvular atrial fibrillation, and examine the possible risk and benefit of anticoagulation before, during, and shortly after the acute phase of stroke. Other indications of anticoagulation after ischemic stroke will be briefly discussed. We provide a synthesis of available data to help clinicians individualize the timing of initiation of oral anticoagulation based on the presence and extent of hemorrhagic transformation as well as stroke severity.