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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]

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]

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]

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.

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: 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]

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: 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: 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]

Background: Hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) might worsen the clinical outcomes, and a reliable predictive system is needed to identify the risk of hemorrhagic transformation after IVT. Methods: Retrospective collection of patients with acute cerebral infarction treated with intravenous thrombolysis in our hospital from 2018 to 2022. 197 patients were included in the research study. Multivariate logistic regression analysis was used to screen the factors in the predictive nomogram. The performance of nomogram was assessed on the area under the receiver operating characteristic curve (AUC-ROC), calibration plots and decision curve analysis (DCA). Results: A total of 197 patients were recruited, of whom 24 (12.1%) developed HT. In multivariate logistic regression model National Institute of Health Stroke Scale (NIHSS) (OR, 1.362; 95% CI, 1.161-1.652; p = 0.001), N-terminal pro-brain natriuretic peptide (NT-pro BNP) (OR, 1.012; 95% CI, 1.004-1.020; p = 0.003), neutrophil to lymphocyte ratio (NLR) (OR, 3.430; 95% CI, 2.082-6.262; p < 0.001), systolic blood pressure (SBP) (OR, 1.039; 95% CI, 1.009-1.075; p = 0.016) were the independent predictors of HT which were used to generate nomogram. The nomogram showed good discrimination due to AUC-ROC values. Calibration plot showed good calibration. DCA showed that nomogram is clinically useful. Conclusion: Nomogram consisting of NIHSS, NT-pro BNP, NLR, SBP scores predict the risk of HT in AIS patients treated with IVT. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to investigate the clinical value of radiomics based on non-enhanced head CT in the prediction of hemorrhage transformation in acute ischemic stroke (AIS). Materials and methods: A total of 140 patients diagnosed with AIS from January 2015 to August 2022 were enrolled. Radiomic features from infarcted areas on non-enhanced CT images were extracted using ITK-SNAP. The max-relevance and min-redundancy (mRMR) and the least absolute shrinkage and selection operator (LASSO) were used to select features. The radiomics signature was then constructed by multiple logistic regressions. The clinicoradiomics nomogram was constructed by combining radiomics signature and clinical characteristics. All predictive models were constructed in the training group, and these were verified in the validation group. All models were evaluated with the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA). Results: Of the 140 patients, 59 experienced hemorrhagic transformation, while 81 remained stable. The radiomics signature was constructed by 10 radiomics features. The clinicoradiomics nomogram was constructed by combining radiomics signature and atrial fibrillation. The area under the ROC curve (AUCs) of the clinical model, radiomics signature, and clinicoradiomics nomogram for predicting hemorrhagic transformation in the training group were 0.64, 0.86, and 0.86, respectively. The AUCs of the clinical model, radiomics signature, and clinicoradiomics nomogram for predicting hemorrhagic transformation in the validation group were 0.63, 0.90, and 0.90, respectively. The DCA curves showed that the radiomics signature performed well as well as the clinicoradiomics nomogram. The DCA curve showed that the clinical application value of the radiomics signature is similar to that of the clinicoradiomics nomogram. Conclusion: The radiomics signature, constructed without incorporating clinical characteristics, can independently and effectively predict hemorrhagic transformation in AIS patients. [ABSTRACT FROM AUTHOR]

Background: There has been intensive research into enhancing the effects of reperfusion therapy to mitigate hemorrhagic transformation (HT) in stroke patients. Using neuroprotective agents alongside intravenous thrombolysis (IVT) appears a promising approach. Cerebrolysin is one of the candidates since it consists of neuropeptides mimicking the action of neurotrophic factors on brain protection and repair. Objectives: We looked at treatment effects of Cerebrolysin as an early add-on to IVT in stroke patients with varying HT risk. Methods: It was post hoc analysis of the CEREHETIS trial (ISRCTN87656744). Patients with middle cerebral artery infarction (n = 238) were selected from the intention-to-treat population. To stratify participants according to their HT risk, the DRAGON, SEDAN and HTI scores were computed for each eligible subject using on-admission data. The study endpoints were any and symptomatic HT, and functional outcome measured with the modified Rankin Scale (mRS) on day 90. Favorable functional outcome (FFO) was defined as an mRS ≤2. The performance of each stratification tool was estimated with regression approaches. Heterogeneous treatment effect analysis was conducted using techniques of meta-analysis and the matching-smoothing method. Results: The HTI score outperformed other tools in terms of HT risk stratification. Heterogeneity of Cerebrolysin treatment effects was moderate (I2, 35.8%--56.7%; H2, 1.56--2.31) and mild (I2, 10.9%; H2, 1.12) for symptomatic and any HT, respectively. A significant positive impact of Cerebrolysin on HT and functional outcome was observed in the moderate (HTI = 1) and high (HTI ≥2) HT risk patients, but it was neutral in those with the low (HTI = 0) risk. In particular, there was a steady decline in the rate of symptomatic (HTI = 0 vs. HTI = 4: by 4.3%, p = 0.077 vs. 21.1%, p < 0.001) and any HT (HTI = 0 vs. HTI = 4: by 1.2%, p = 0.737 vs. 32.7%, p < 0.001). Likewise, an mRS score reduction (HTI = 0 vs. HTI = 4: by 1.8%, p = 0.903 vs. 126%, p < 0.001) with a reciprocal increase of the fraction of FFO patients (HTI = 0 vs. HTI = 4: by 1.2% p = 0.757 vs. 35.5%, p < 0.001) was found. Conclusion: Clinically meaningful heterogeneity of Cerebrolysin treatment effects on HT and functional outcome was established in stroke patients. The beneficial effects were significant in those whose estimated on-admission HT risk was either moderate or high. [ABSTRACT FROM AUTHOR]

Stroke is a devastating condition that can lead to significant morbidity and mortality. The aftermath of a stroke, particularly hemorrhagic transformation (HT) and brain edema, can significantly impact the prognosis of patients. Early detection and effective management of these complications are crucial for improving outcomes in stroke patients. This review highlights the emerging diagnostic markers and therapeutic targets including claudin, occludin, zonula occluden, s100β, albumin, MMP-9, MMP-2, MMP-12, IL-1β, TNF-α, IL-6, IFN-γ, TGF-β, IL-10, IL-4, IL-13, MCP-1/CCL2, CXCL2, CXCL8, CXCL12, CCL5, CX3CL1, ICAM-1, VCAM-1, P-selectin, E-selectin, PECAM-1/CD31, JAMs, HMGB1, vWF, VEGF, ROS, NAC, and AQP4. The clinical significance and implications of these biomarkers were also discussed. [ABSTRACT FROM AUTHOR]

BackgroundHemorrhagic 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.ObjectiveThis 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.MethodsUsing 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) 1.5) with p

Background: There has been intensive research into enhancing the effects of reperfusion therapy to mitigate hemorrhagic transformation (HT) in stroke patients. Using neuroprotective agents alongside intravenous thrombolysis (IVT) appears a promising approach. Cerebrolysin is one of the candidates since it consists of neuropeptides mimicking the action of neurotrophic factors on brain protection and repair.Objectives: We looked at treatment effects of Cerebrolysin as an early add-on to IVT in stroke patients with varying HT risk.Methods: It was post hoc analysis of the CEREHETIS trial (ISRCTN87656744). Patients with middle cerebral artery infarction (n = 238) were selected from the intention-to-treat population. To stratify participants according to their HT risk, the DRAGON, SEDAN and HTI scores were computed for each eligible subject using on-admission data. The study endpoints were any and symptomatic HT, and functional outcome measured with the modified Rankin Scale (mRS) on day 90. Favorable functional outcome (FFO) was defined as an mRS ≤2. The performance of each stratification tool was estimated with regression approaches. Heterogeneous treatment effect analysis was conducted using techniques of meta-analysis and the matching-smoothing method.Results: The HTI score outperformed other tools in terms of HT risk stratification. Heterogeneity of Cerebrolysin treatment effects was moderate (I2, 35.8%–56.7%; H2, 1.56–2.31) and mild (I2, 10.9%; H2, 1.12) for symptomatic and any HT, respectively. A significant positive impact of Cerebrolysin on HT and functional outcome was observed in the moderate (HTI = 1) and high (HTI ≥2) HT risk patients, but it was neutral in those with the low (HTI = 0) risk. In particular, there was a steady decline in the rate of symptomatic (HTI = 0 vs. HTI = 4: by 4.3%, p = 0.077 vs. 21.1%, p < 0.001) and any HT (HTI = 0 vs. HTI = 4: by 1.2%, p = 0.737 vs. 32.7%, p < 0.001). Likewise, an mRS score reduction (HTI = 0 vs. HTI = 4: by 1.8%, p = 0.903 vs. 126%, p < 0.001) with a reciprocal increase of the fraction of FFO patients (HTI = 0 vs. HTI = 4: by 1.2% p = 0.757 vs. 35.5%, p < 0.001) was found.Conclusion: Clinically meaningful heterogeneity of Cerebrolysin treatment effects on HT and functional outcome was established in stroke patients. The beneficial effects were significant in those whose estimated on-admission HT risk was either moderate or high.

Stroke is a devastating condition that can lead to significant morbidity and mortality. The aftermath of a stroke, particularly hemorrhagic transformation (HT) and brain edema, can significantly impact the prognosis of patients. Early detection and effective management of these complications are crucial for improving outcomes in stroke patients. This review highlights the emerging diagnostic markers and therapeutic targets including claudin, occludin, zonula occluden, s100β, albumin, MMP-9, MMP-2, MMP-12, IL-1β, TNF-α, IL-6, IFN-γ, TGF-β, IL-10, IL-4, IL-13, MCP-1/CCL2, CXCL2, CXCL8, CXCL12, CCL5, CX3CL1, ICAM-1, VCAM-1, P-selectin, E-selectin, PECAM-1/CD31, JAMs, HMGB1, vWF, VEGF, ROS, NAC, and AQP4. The clinical significance and implications of these biomarkers were also discussed.

Background: Bilirubin has both antioxidative and prooxidative properties. The study aimed to explore the relationship between serum bilirubin and hemorrhagic transformation (HT) after intravenous thrombolysis in patients with acute ischemic stroke. Methods: The patients receiving intravenous thrombolysis with alteplase were retrospectively analyzed. HT was defined as new intracerebral hemorrhage in follow-up computed tomography images within 24-36 h after thrombolysis. Symptomatic intracranial hemorrhage (sICH) was defined as HT accompanied by worsening neurological function. Multivariate logistic regression and spline regression models were performed to investigate the relationship between serum bilirubin levels and the risk of HT and sICH. Results: Among 557 included patients, 71 (12.7%) were diagnosed with HT and 28 (5.0%) developed sICH. Patients with HT had significant higher baseline serum total bilirubin, direct bilirubin, and indirect bilirubin levels than those without HT. Multivariable logistic regression analysis indicated that patients with higher serum bilirubin levels, including total bilirubin (OR 1.05, 95% CI 1.01-1.08, p = 0.006), direct bilirubin (OR 1.18, 95% CI 1.05-1.31, p = 0.004), and indirect bilirubin (OR 1.06, 95% CI 1.02-1.10, p = 0.005) had increased risk of HT. Furthermore, multipleadjusted spline regression models excluded nonlinear association between serum bilirubin levels and HT (p > 0.05 for nonlinearity). Similar results were present between serum bilirubin and sICH. Conclusion: The data showed the positively linearly relationship between serum bilirubin levels and the risk of HT and sICH in patients with acute ischemic stroke undergoing intravenous thrombolysis. [ABSTRACT FROM AUTHOR]

Background: Hemorrhagic transformation (HT) is common among acute ischemic stroke patients after treatment with intravenous thrombolysis (IVT). We analyzed potential relationships between markers of cerebral small vessel disease (CSVD) and HT in patients after IVT. Methods: This study retrospectively analyzed computed tomography (CT) data for acute ischemic stroke patients before and after treatment with recombinant tissue plasminogen activator at a large Chinese hospital between July 2014 and June 2021. Total CSVD score were summed by individual CSVD markers including leukoaraiosis, brain atrophy and lacune. Binary regression analysis was used to explore whether CSVD markers were related to HT as the primary outcome or to symptomatic intracranial hemorrhage (sICH) as a secondary outcome. Results: A total of 397 AIS patients treated with IVT were screened for inclusion in this study. Patients with missing laboratory data (n = 37) and patients treated with endovascular therapy (n = 42) were excluded. Of the 318 patients included, 54 (17.0%) developed HT within 24-36 h of IVT, and 14 (4.3%) developed sICH. HT risk was independently associated with severe brain atrophy (OR 3.14, 95%CI 1.43-6.92, P = 0.004) and severe leukoaraiosis (OR 2.41, 95%CI 1.05-5.50, P = 0.036), but not to severe lacune level (OR 0.58, 95%CI 0.23-1.45, P = 0.250). Patients with a total CSVD burden ≥1 were at higher risk of HT (OR 2.87, 95%CI 1.38-5.94, P = 0.005). However, occurrence of sICH was not predicted by CSVD markers or total CSVD burden. Conclusion: In patients with acute ischemic stroke, severe leukoaraiosis, brain atrophy and total CSVD burden may be risk factors for HT after IVT. These findings may help improve efforts to mitigate or even prevent HT in vulnerable patients. [ABSTRACT FROM AUTHOR]

Objective: To investigate the value of the MRI arterial spin labeling (ASL) in evaluating the blood-brain barrier permeability of anterior circulation ischemic lesions in subacute ischemic stroke (SIS) and the risk of hemorrhage transformation (HT) after endovascular recanalization. Materials and methods: Patients with anterior circulation SIS treated with endovascular recanalization were prospectively enrolled. The imaging presentations in the MRI ASL sequences, dynamic contrast-enhanced (DCE) sequence, and Xper CT were studied. The relative cerebral blood flow (rCBF), volume transfer constant (Ktrans), and the weighted Kappa coefficient (rKtrans) were analyzed. Results: Among 27 eligible patients, HT occurred in 7 patients (25.92%). Patients with HT had significantly higher rCBF value (1.56 ± 0.16 vs. 1.16 ± 0.16), Ktrans, (0.08 ± 0.03 min vs. 0.03 ± 0.01 min) and rKtrans (3.02 ± 0.89 vs. 1.89 ± 0.56). The ASL imaging sequence had a high consistency with the DCE sequence and Xper CT with a high weighted Kappa coefficient of 0.91 for the DCE sequence and 0.70 for the Xper CT imaging. The DCE sequence was also highly consistent with the Xper CT in imaging classification with a high weighted Kappa coefficient of 0.78. The rCBF value in the 21 patients with the subcortical and basal ganglia infarction was significantly lower than that in the other 6 patients with the cortical infarction (1.222 ± 0.221 vs. 1.413 ± 0.259, t = 1.795, P = 0.004). Conclusion: The MRI ASL sequence has an important role in evaluating the bloodbrain barrier permeability and the risk of hemorrhagic transformation of anterior circulation SIS following endovascular recanalization. [ABSTRACT FROM AUTHOR]

Objective: The association between serum uric acid (UA) and spontaneous hemorrhagic transformation (HT) has been seldom studied, and the role of UA in spontaneous HT remains unclear. This study aims to investigate the sex-dependent association between UA and spontaneous HT in patients with ischemic stroke. Method: We retrospectively included patients with ischemic stroke in a tertiary academic hospital between December 2016 and May 2020. Patients were included if they presented within 24 h after the onset of symptoms and did not receive reperfusion therapy. Spontaneous HT was determined by an independent evaluation of neuroimaging by three trained neurologists who were blinded to clinical data. A univariate analysis was performed to identify factors related to spontaneous HT. Four logistic regression models were established to adjust each factor and assess the association between UA and spontaneous HT. Results: A total of 769 patients were enrolled (64.6% were male patients and 3.9% had HT). After adjusting the confounders with a P < 0.05 (model A) in the univariate analysis, the ratio of UA and its interquartile range (RUI) was independently associated with spontaneous HT in male patients (OR: 1.85; 95% CI: 1.07--3.19; P = 0.028), but not in female patients (OR: 1.39; 95% CI: 0.28--6.82; P = 0.685). In models B--D, the results remain consistent with model A after the adjustment for other potential confounders. Conclusions: Higher serum UA was independently associated with a higher occurrence of spontaneous HT in male patients who were admitted within 24 h after the stroke onset without receiving reperfusion therapy. [ABSTRACT FROM AUTHOR]

BackgroundIn patients with acute ischemic stroke, hemorrhagic transformation (HT) is a common complication after intravenous thrombolysis (IVT). In this study, we evaluated the relationship between the ratio of C-reactive protein to albumin (CAR) before thrombolysis, HT, and functional outcomes in patients with acute ischemic stroke.MethodsWe retrospectively analyzed data from 354 patients who received thrombolytic therapy at the Second Affiliated Hospital of the Wenzhou Medical University in China between July 2014 and May 2022. CAR was measured on admission, and HT was identified by cranial computed tomography (CT) within 24–36 h after treatment. Poor outcome was defined as a score on the modified Rankin Scale (mRS) > 2 at discharge. The multivariate logistic regression model was used to investigate the association between CAR, HT, and poor outcome after thrombolysis, respectively.ResultsA total of 354 patients were analyzed, and their median CAR was 0.61 (interquartile range, 0.24–1.28). CAR was significantly higher in the 56 patients (15.8%) who experienced HT than in those who did not (0.94 vs. 0.56, p

BackgroundHemorrhagic transformation (HT) following reperfusion therapies for acute ischaemic stroke often predicts a poor prognosis. This systematic review and meta-analysis aims to identify risk factors for HT, and how these vary with hyperacute treatment [intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT)].MethodsElectronic databases PubMed and EMBASE were used to search relevant studies. Pooled odds ratio (OR) with 95% confidence interval (CI) were estimated.ResultsA total of 120 studies were included. Atrial fibrillation and NIHSS score were common predictors for any intracerebral hemorrhage (ICH) after reperfusion therapies (both IVT and EVT), while a hyperdense artery sign (OR = 2.605, 95% CI 1.212–5.599, I2 = 0.0%) and number of thrombectomy passes (OR = 1.151, 95% CI 1.041–1.272, I2 = 54.3%) were predictors of any ICH after IVT and EVT, respectively. Common predictors for symptomatic ICH (sICH) after reperfusion therapies were age and serum glucose level. Atrial fibrillation (OR = 3.867, 95% CI 1.970–7.591, I2 = 29.1%), NIHSS score (OR = 1.082, 95% CI 1.060–1.105, I2 = 54.5%) and onset-to-treatment time (OR = 1.003, 95% CI 1.001–1.005, I2 = 0.0%) were predictors of sICH after IVT. Alberta Stroke Program Early CT score (ASPECTS) (OR = 0.686, 95% CI 0.565–0.833, I2 =77.6%) and number of thrombectomy passes (OR = 1.374, 95% CI 1.012–1.866, I2 = 86.4%) were predictors of sICH after EVT.ConclusionSeveral predictors of ICH were identified, which varied by treatment type. Studies based on larger and multi-center data sets should be prioritized to confirm the results.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=268927, identifier: CRD42021268927.

Background and purpose: Patients with ischemic stroke frequently develop hemorrhagic transformation (HT), which could potentially worsen the prognosis. The objectives of the current study were to determine the incidence and predictors of HT, to evaluate predictor interaction, and to identify the optimal predicting models. Methods: A prospective study included 360 patients with ischemic stroke, of whom 354 successfully continued the study. Patients were subjected to thorough general and neurological examination and T2 diffusion-weighted MRI, at admission and 1 week later to determine the incidence of HT. HT predictors were selected by a filter-based minimum redundancy maximum relevance (mRMR) algorithm independent of model performance. Several machine learning algorithms including multivariable logistic regression classifier (LRC), support vector classifier (SVC), random forest classifier (RFC), gradient boosting classifier (GBC), and multilayer perceptron classifier (MLPC) were optimized for HT prediction in a randomly selected half of the sample (training set) and tested in the other half of the sample (testing set). The model predictive performance was evaluated using receiver operator characteristic (ROC) and visualized by observing case distribution relative to the models' predicted three-dimensional (3D) hypothesis spaces within the testing dataset true feature space. The interaction between predictors was investigated using generalized additive modeling (GAM). Results: The incidence of HT in patients with ischemic stroke was 19.8%. Infarction size, cerebral microbleeds (CMB), and the National Institute of Health stroke scale (NIHSS) were identified as the best HT predictors. RFC (AUC: 0.91, 95% CI: 0.85-0.95) and GBC (AUC: 0.91, 95% CI: 0.86-0.95) demonstrated significantly superior performance compared to LRC (AUC: 0.85, 95% CI: 0.79--0.91) and MLPC (AUC: 0.85, 95% CI: 0.78-0.92). SVC (AUC: 0.90, 95% CI: 0.85-0.94) outperformed LRC and MLPC but did not reach statistical significance. LRC and MLPC did not show significant differences. The best models' 3D hypothesis spaces demonstrated non-linear decision boundaries suggesting an interaction between predictor variables. GAM analysis demonstrated a linear and non-linear significant interaction between NIHSS and CMB and between NIHSS and infarction size, respectively. Conclusion: Cerebral microbleeds, NIHSS, and infarction size were identified as HT predictors. The best predicting models were RFC and GBC capable of capturing nonlinear interaction between predictors. Predictor interaction suggests a dynamic, rather than, fixed cutoff risk value for any of these predictors. [ABSTRACT FROM AUTHOR]

Background and purposePatients with ischemic stroke frequently develop hemorrhagic transformation (HT), which could potentially worsen the prognosis. The objectives of the current study were to determine the incidence and predictors of HT, to evaluate predictor interaction, and to identify the optimal predicting models.MethodsA prospective study included 360 patients with ischemic stroke, of whom 354 successfully continued the study. Patients were subjected to thorough general and neurological examination and T2 diffusion-weighted MRI, at admission and 1 week later to determine the incidence of HT. HT predictors were selected by a filter-based minimum redundancy maximum relevance (mRMR) algorithm independent of model performance. Several machine learning algorithms including multivariable logistic regression classifier (LRC), support vector classifier (SVC), random forest classifier (RFC), gradient boosting classifier (GBC), and multilayer perceptron classifier (MLPC) were optimized for HT prediction in a randomly selected half of the sample (training set) and tested in the other half of the sample (testing set). The model predictive performance was evaluated using receiver operator characteristic (ROC) and visualized by observing case distribution relative to the models' predicted three-dimensional (3D) hypothesis spaces within the testing dataset true feature space. The interaction between predictors was investigated using generalized additive modeling (GAM).ResultsThe incidence of HT in patients with ischemic stroke was 19.8%. Infarction size, cerebral microbleeds (CMB), and the National Institute of Health stroke scale (NIHSS) were identified as the best HT predictors. RFC (AUC: 0.91, 95% CI: 0.85–0.95) and GBC (AUC: 0.91, 95% CI: 0.86–0.95) demonstrated significantly superior performance compared to LRC (AUC: 0.85, 95% CI: 0.79–0.91) and MLPC (AUC: 0.85, 95% CI: 0.78–0.92). SVC (AUC: 0.90, 95% CI: 0.85–0.94) outperformed LRC and MLPC but did not reach statistical significance. LRC and MLPC did not show significant differences. The best models' 3D hypothesis spaces demonstrated non-linear decision boundaries suggesting an interaction between predictor variables. GAM analysis demonstrated a linear and non-linear significant interaction between NIHSS and CMB and between NIHSS and infarction size, respectively.ConclusionCerebral microbleeds, NIHSS, and infarction size were identified as HT predictors. The best predicting models were RFC and GBC capable of capturing nonlinear interaction between predictors. Predictor interaction suggests a dynamic, rather than, fixed cutoff risk value for any of these predictors.

Background and aimsMalnutrition is a prevalent problem occurring in different diseases. Hemorrhagic transformation (HT) is a severe complication of acute ischemic stroke (AIS). Few studies have evaluated the association between malnutrition risk and hemorrhagic transformation in patients with acute stroke. We aim to investigate the influence of malnutrition risk on the risk of hemorrhagic transformation in patients with AIS.MethodsA total of 182 consecutive adults with HT and 182 age- and sex-matched patients with stroke were enrolled in this study. The controlling nutritional status (CONUT) score was calculated to evaluate the malnutrition risk. HT was detected by follow-up imaging assessment and was radiologically classified as hemorrhagic infarction type 1 or 2 or parenchymal hematoma type 1 or 2. Logistic regression models were conducted when participants were divided into different malnutrition risk groups according to the objective nutritional score to assess the risk for HT.ResultsThe prevalence of moderate to severe malnutrition risk in patients with AIS was 12.5%, according to the CONUT score. Univariate analysis showed that the CONUT score is significantly higher in patients with HT than those without HT. After adjusting for potential covariables, the patients with mild risk and moderate to severe malnutrition risk were associated with a higher risk of HT compared to the patients in the normal nutritional status group [odds ratio, 3.180 (95% CI, 1.139–8.874), P = 0.027; odds ratio, 3.960 (95% CI, 1.015–15.453), P = 0.048, respectively].ConclusionMalnutrition risk, measured by CONUT score, was significantly associated with an increased risk of hemorrhagic transformation in patients with AIS.

Objective: To develop and validate a model based on the radiomics features of the infarct areas on non-contrast-enhanced CT to predict hemorrhagic transformation (HT) in acute ischemic stroke. Materials and methods: A total of 118 patients diagnosed with acute ischemic stroke in two centers from January 2019 to February 2022 were included. The radiomics features of infarcted areas on non-contrast-enhanced CT were extracted using 3D-Slicer. A univariate analysis and the least absolute shrinkage and selection operator (LASSO) were used to select features, and the radiomics score (Rad-score) was then constructed. The predictive model of HT was constructed by analyzing the Rad-score and clinical and imaging features in the training cohort, and it was verified in the validation cohort. The model was evaluated with the receiver operating characteristic curve, calibration curve and decision curve, and the prediction performance of the model in different scenarios was further discussed hierarchically. Results: Of the 118 patients, 52 developed HT, including 21 cases of hemorrhagic infarct (HI) and 31 cases of parenchymal hematoma (PH). The Rad-score was constructed from five radiomics features and was the only independent predictor for HT. The predictive model was constructed from the Rad-score. The area under the curve (AUCs) of the model for predicting HT in the training and validation cohorts were 0.845 and 0.750, respectively. Calibration curve and decision curve analyses showed that the model performed well. Further analysis found that the model predicted HT for different infarct sizes or treatment methods in the training and validation cohorts with 78.3 and 71.4% accuracy, respectively. For all samples, the model predicted an AUC of 0.754 for HT in patients within 4.5 h since stroke onset, and predicted an AUC of 0.648 for PH. Conclusion: This model, which was based on CT radiomics features, could help to predict HT in the setting of acute ischemic stroke for any infarct size and provide guiding suggestions for clinical treatment and prognosis evaluation. [ABSTRACT FROM AUTHOR]

Background: Hemorrhagic transformation (HT) is the most serious complication of ischemic stroke patients after intravenous thrombolysis and leads to a poor clinical prognosis. This study aimed to determine the independent predictors associated with HT in stroke patients with intravenous thrombolysis and to establish and validate a nomogram that combines with predictors to predict the probability of HT after intravenous thrombolysis in patients with ischemic stroke. Method: This study enrolled ischemic stroke patients with intravenous thrombolysis from December 2016 to June 2022. All the patients were divided into training and validation cohorts. The nomogram was composed of the significant predictors for HT in the training cohort as obtained by the multivariate logistic regression analysis. The area under the receiver operating characteristic curve was used to assess the discriminative performance of the nomogram. The calibration performance of the nomogram was assessed by the Hosmer-Lemeshow goodness-of-fit test and calibration plots. Decision curve analysis was used to test the clinical validity of the nomogram. Results: A total of 394 patients with intravenous thrombolysis were enrolled in the study. In the training cohort (n = 257), 45 patients had HT after intravenous thrombolysis. Multivariate logistic regression analysis demonstrated early infarct signs (OR, 7.954; 95% CI, 3.553-17.803; P < 0.001), NIHSS scores (OR, 1.110; 95% CI, 1.054-1.168; P < 0.001), uric acid (OR, 0.993; 95% CI, 0.989-0.997; P = 0.001), and albumin-to-globulin ratio (OR, 0.109; 95% CI, 0.023-0.508; P = 0.005) were independent predictors for HT and constructed the nomogram. In the training and validation cohorts, the AUC of the nomogram was 0.859 and 0.839, respectively. The Hosmer-Lemeshow goodness-of-fit test and calibration plot showed good concordance between predicted and observed probability in the training and validation cohorts. Decision curve analysis indicated that the nomogram was significantly useful for predicting HT in the training and further confirmed in the validation cohort. Conclusion: This study proposes a novel and practical nomogram based on early infarct signs, NIHSS scores, uric acid, and albumin-to-globulin ratio that can well predict the probability of HT after intravenous thrombolysis in patients with ischemic stroke. [ABSTRACT FROM AUTHOR]

Background: Hemorrhagic transformation (HT) is a frequent, serious complication in acute ischemic stroke patients on intravenous thrombolysis. Here we investigated whether risk of HT is associated with the ratio of monocyte count to high-density lipoprotein level (MHR). Materials and methods: Medical records were retrospectively examined for consecutive patients with acute ischemic stroke who received thrombolytic therapy. HT was diagnosed by computed tomography at 24–36 h after therapy. Potential association between MHR and HT was examined using logistic regression. Results: A total of 340 patients were analyzed, and their median MHR was 0.44 (0.31–0.59). MHR was higher in the 51 patients (15.0%) with HT than in those who did not suffer HT (0.53 vs. 0.42, P = 0.001). Multivariate logistic regression showed that, after adjusting for potential confounders, MHR was an independent risk factor for HT (OR 7.50, 95% CI 1.64 to 34.35, P = 0.009). Risk of HT was significantly higher among patients whose MHR fell in the third quartile (0.42–0.53) and the fourth quartile (> 0.53) than among those with MHR in the first quartile (< 0.31; OR 3.53, 95% CI 1.11 to 11.20, P = 0.032; OR 4.79, 95% CI 1.49 to 15.42, P = 0.009). Conclusion: High MHR may be independently associated with higher risk of HT in patients with acute ischemic stroke on intravenous thrombolysis. [ABSTRACT FROM AUTHOR]

Background and Purpose: Almost half of the patients exhibit futile recanalization after thrombectomy; however, the early postoperative predictors of futile recanalization remain unclear. We analyzed the relationship of post-thrombectomy ASPECTS (Post-ASPECTS) with 90-day prognosis and hemorrhagic transformation (HT). Methods: We collected data from patients with acute ischemic stroke (AIS) with anterior-circulation large vessel occlusion (ACLVO) who were treated via thrombectomy within 10 h in 3 hospitals. Successful endovascular recanalization was achieved (modified thrombolysis in cerebral ischemia [mTICI] 2b/3). Non-contrast computed tomography (NCCT) examination was performed immediately (within 1 h) after thrombectomy. Post-ASPECTS were scored based on the brain parenchymal hyperdensity in NCCT according to the ASPECTS scoring method. HT was defined according to the ECASS II classification criteria. Linear correlation, logistic regression, and receiver operating characteristic curve analyses were used to determine the influencing factors and best predictive value of 90-day prognosis, 90-day death, and HT. Results: A total of 231 patients were enrolled. The good prognosis rate, mortality rate, and HT rate were 57.1, 9.5, and 38.3%, respectively. The Post-ASPECTS affected poor prognosis, death, and HT. The best predictive value of Post-ASPECTS for poor prognosis, death, and HT was 7. The specificities of Post-ASPECTS for predicting HT, poor prognosis, and death were 87.6% (AUC, 0.811; P < 0.001), 87.1% (AUC, 0.768; P < 0.001), and 73.7% (AUC, 0.748; P < 0.001), with positive predictive values of 74.2, 75.7, and 21.4%, respectively. Conclusion: Post-ASPECTS predicted 90-day prognosis, death, and HT with high specificity and high positive predictive value in patients with AIS with ACLVO. Post-ASPECTS may be an ultra-early predictor of prognosis after thrombectomy. [ABSTRACT FROM AUTHOR]

Massive cerebral infarction (MCI) is a devastating condition and associated with high rate of morbidity and mortality. Hemorrhagic transformation (HT) is a common complication after acute MCI, and often results in poor outcomes. Although several predictors of HT have been identified in acute ischemic stroke (AIS), the association between the predictors and HT remains controversial. Therefore, we aim to explore the value of texture analysis on magnetic resonance image (MRI) for predicting HT after acute MCI. This retrospective study included a total of 98 consecutive patients who were admitted for acute MCI between January 2019 and October 2020. Patients were divided into the HT group (n = 44) and non-HT group (n = 54) according to the follow-up computed tomography (CT) images. A total of 11 quantitative texture features derived from images of diffusion-weighted image (DWI) or T2-weighted-Fluid-Attenuated Inversion Recovery (T2/FLAIR) were extracted for each patient. Receiver operating characteristic (ROC) analysis were performed to determine the predictive performance of textural features, with HT as the outcome measurement. There was no significant difference in the baseline demographic and clinical characteristics between the two groups. The distribution of atrial fibrillation and National Institutes of Health Stroke Scale (NIHSS) were significantly higher in patients with HT than those without HT. Among the textural parameters extracted from DWI images, six parameters, f2 (contrast), f3 (correlation), f4 (sum of squares), f5 (inverse difference moment), f10 (difference variance), and f11 (difference entropy), differs significantly between the two groups (p < 0.05). Moreover, five of six parameters (f2, f3, f5, f10, and f11) have good predictive performances of HT with the area under the ROC curve (AUC) values of 0.795, 0.779, 0.791, 0.780, and 0.797, respectively. However, the texture features f2, f3, and f10 in T2/FLAIR images were the only three significant predictors of HT in patients with acute MCI, but with a relatively low AUC values of 0.652, 0.652, and 0.670, respectively. In summary, our preliminary results showed DWI-based texture analysis has a good predictive validity for HT in patients with acute MCI. Multiparametric MRI texture analysis model should be developed to improve the prediction performance of HT following acute MCI. [ABSTRACT FROM AUTHOR]

ObjectiveHyponatremia is the most common electrolyte disorder encountered in patients with neurological conditions, such as stroke. Studies have shown that it is associated with worse clinical outcomes and increased mortality in acute ischemic stroke (AIS). However, the role of hyponatremia has not been elucidated in patients with AIS who received intravenous thrombolysis (IVT) therapy. Therefore, this study aimed to investigate the effect of serum sodium levels on the clinical outcome and hemorrhagic transformation (HT) in patients with AIS who received thrombolytic therapy.MethodsPatients diagnosed with AIS who received IVT therapy between May 2015 and December 2020 were included in this study. All patients were screened for serum sodium levels immediately after hospital admission, before IVT therapy. The occurrence of HT was evaluated using computed tomography (CT) 24 ± 2 h after thrombolysis. Then, 3-month clinical outcomes were obtained by telephone calls or outpatient visits, and poor 3-month clinical outcomes were defined as modified Rankin Scale scores ≥3. The effects of serum sodium levels on the clinical outcome and HT were assessed using the multivariate logistic regression analysis.ResultsOf the 963 included patients, 82 (8.5%) had hyponatremia, 157 (16.3%) developed HT, and 333 (34.6%) had poor 3-month outcomes. Of the 82 patients with hyponatremia, 21 (25.6%) developed HT, and 39 (47.6%) had poor 3-month outcomes. Patients with hyponatremia had a higher incidence of post-thrombolysis HT (25.6 vs. 15.4%, p = 0.017) and worse clinical outcome (47.6 vs. 33.4%, p = 0.01) than those with normal serum sodium levels. Patients had significantly lower serum sodium levels in those with HT [138.4 (136.4–140.3, IQR) vs. 139.0 (137.2–140.7, IQR) mmol/L, p = 0.019] and poor 3 month outcome [139.0 (137.2–140.7) vs. 138.4 (136.7–140.3) mmol/L, p = 0.005] than those without. After adjusting for major covariates, the multivariate logistic regression analysis revealed that lower serum sodium levels were independently associated with an increased risk of HT [odds ratio (OR) = 1.804; 95% CI: 1.048–3.105] and poor 3-month outcome (OR = 1.647; 95% CI: 1.012–2.679).ConclusionLower serum sodium level was an independent risk factor for post-thrombolysis HT and poor clinical outcome in patients with AIS who received thrombolytic therapy.

In order to explore the epigenetic characteristics of hemorrhagic transformation (HT) after acute ischemic stroke, we used transcriptome sequencing technology to analyze the global transcriptome expression profile of patients with and without HT after acute ischemic stroke and to study the differential expression of messenger RNA (mRNA), long noncoding RNA (lncRNA), circular RNA (circRNA) and mircoRNA (miRNA) between the two groups. To further explore the role of differentially expressed genes in HT, we annotated the function of differentially expressed genes by using gene ontology (GO) and pathway analysis on the results and showed that there were 1,051 differential expressions of lncRNAs, 2,575 differential expressions of mRNAs, 447 differential expressions of circRNAs and 47 miRNAs in patients with HT compared with non-HT patients. Pathway analysis showed that ubiquitin-mediated proteolysis, MAPK signal pathway, axon guidance, HIF-1 signal pathway, NOD-like receptor signal pathway, beta-alanine metabolism, Wnt signal pathway, sphingolipid signal pathway, neuroactive ligand-receptor interaction, and intestinal immune network used in IgA production play an important role in HT. Terms such as iron homeostasis, defense response, immune system process, DNA conformational change, production of transforming growth factor beta-2, and oxidoreductase activity were enriched in the gene list, suggesting a potential correlation with HT. A total of 261 lncRNA-miRNA relationship pairs and 21 circRNA-miRNA relationship pairs were obtained; additionally, 5 circRNAs and 13 lncRNAs were screened, which can be used as competing endogenous RNA (ceRNA) to compete with miRNA in the co-expression network. Co-expression network analysis shows that these differentially expressed circRNA and lncRNA may play a vital role in HT and provide valuable information for new biomarkers or therapeutic targets. [ABSTRACT FROM AUTHOR]

Objective: To investigate the current management of thrombolysis related hemorrhagic transformation (HT) in real-world practice, and whether these treatments would reduce the risk of 3-month death and hematoma expansion after HT. Methods: A multicenter retrospective study was performed in three comprehensive stroke centers in China (West China Hospital, The First People's Hospital of Ziyang, and Mianyang Central Hospital) between January 1st 2012 and December 31th 2020. Participants were patients diagnosed with HT after intravenous thrombolytics on brain computed tomography (CT) within 36 h after stroke onset. The treatment after thrombolysis related HT included aggressive therapy (procoagulant, neurosurgical treatment) and dehydration therapy (mannitol or glycerin and fructose). The primary clinical outcome was 3-month death. The primary radiographic outcome was hematoma expansion, defined as a 33% increase in the hematoma volume using the (A × B × C)/2 method on follow-up imaging. Results: Of 538 patients with ischemic stroke receiving thrombolysis included during the study period, 94 patients (17.4%) were diagnosed with HT, 50% (47/94) of whom were symptomatic HT. The 3-month death was 31.5% (29/92), with two patients having been lost to follow up. A total of 68 patients (72.3%) had follow-up brain CT scans after HT detection for evaluating hematoma expansion, of whom 14.7% (10/68) had hematoma expansion. Among the 10 patients with hematoma expansion, 7 patients were from symptomatic HT group, and 3 patients were from the asymptomatic hematoma group. In regard to escalation in therapy, six patients received neurosurgical treatment and three patients had a fresh frozen plasma infusion. In addition, dehydration therapy was the most common management after HT diagnosis [87.2% (82 of 94)]. In the multivariable models, refusing any treatment after HT diagnosis was the sole factor associated with increased 3-month death (odds ratio, 13.6; 95% CI, 3.98–56.9) and hematoma expansion risk (odds ratio, 8.54; 95% CI, 1.33–70.1). In regard to the effects of aggressive therapy, a non-significant association of receiving hemostatic/neurosurgery therapy with a lower 3-month death and hematoma expansion risk was observed (all P > 0.05). Conclusion: Refusing any treatment after HT detection had a significant trend of increasing 3-month death and hematoma expansion risk after HT. Our finding of hematoma expansion among patients with asymptomatic HT in non-western populations suggests an opportunity for intervention. Very few patients after thrombolysis related HT diagnosis received procoagulant or neurosurgical therapies. Large multicenter studies enrolling diverse populations are needed to examine the efficacy of these therapies on different HT subtypes. [ABSTRACT FROM AUTHOR]

Background: Hemorrhagic transformation is one of the most serious complications in intravenous thrombolysis. Studies show that the existence of more than 10 cerebral microbleeds is strongly associated with hemorrhagic transformation. The current study attempts to develop and validate a clinical prediction model of more than 10 cerebral microbleeds. Methods: We reviewed the computed tomography markers of cerebral small vessel diseases and the basic clinical information of acute ischemic stroke patients who were investigated using susceptibility weighted imaging from 2018 to 2021. A clinical prediction model of more than 10 cerebral microbleeds was established. Discrimination, calibration, and the net benefit of the model were assessed. Finally, a validation was conducted to evaluate the accuracy and stability of the model. Results: The multivariate logistic regression model showed hypertension, and some computed tomography markers (leukoaraiosis, lacunar infarctions, brain atrophy) were independent risk factors of more than 10 cerebral microbleeds. These risk factors were used for establishing the clinical prediction model. The area under the receiver operating characteristic curve (AUC) was 0.894 (95% CI: 0.870–0.919); Hosmer–Lemeshow chi-squared test yielded χ2 = 3.946 (P = 0.862). The clinical decision cure of the model was higher than the two extreme lines. The simplified score of the model ranged from 0 to 12. The model in the internal and external validation cohort also had good discrimination (AUC 0.902, 95% CI: 0.868–0.937; AUC 0.914, 95% CI: 0.882–0.945) and calibration (P = 0.157, 0.247), and patients gained a net benefit from the model. Conclusions: We developed and validated a simple scoring tool for acute ischemic stroke patients with more than 10 cerebral microbleeds; this tool may be beneficial for paradigm decision regarding intravenous recombinant tissue plasminogen activator therapy of acute ischemic stroke. [ABSTRACT FROM AUTHOR]

In order to explore the epigenetic characteristics of hemorrhagic transformation (HT) after acute ischemic stroke, we used transcriptome sequencing technology to analyze the global transcriptome expression profile of patients with and without HT after acute ischemic stroke and to study the differential expression of messenger RNA (mRNA), long noncoding RNA (lncRNA), circular RNA (circRNA) and mircoRNA (miRNA) between the two groups. To further explore the role of differentially expressed genes in HT, we annotated the function of differentially expressed genes by using gene ontology (GO) and pathway analysis on the results and showed that there were 1,051 differential expressions of lncRNAs, 2,575 differential expressions of mRNAs, 447 differential expressions of circRNAs and 47 miRNAs in patients with HT compared with non-HT patients. Pathway analysis showed that ubiquitin-mediated proteolysis, MAPK signal pathway, axon guidance, HIF-1 signal pathway, NOD-like receptor signal pathway, beta-alanine metabolism, Wnt signal pathway, sphingolipid signal pathway, neuroactive ligand-receptor interaction, and intestinal immune network used in IgA production play an important role in HT. Terms such as iron homeostasis, defense response, immune system process, DNA conformational change, production of transforming growth factor beta-2, and oxidoreductase activity were enriched in the gene list, suggesting a potential correlation with HT. A total of 261 lncRNA-miRNA relationship pairs and 21 circRNA-miRNA relationship pairs were obtained; additionally, 5 circRNAs and 13 lncRNAs were screened, which can be used as competing endogenous RNA (ceRNA) to compete with miRNA in the co-expression network. Co-expression network analysis shows that these differentially expressed circRNA and lncRNA may play a vital role in HT and provide valuable information for new biomarkers or therapeutic targets.

ObjectiveTo investigate the current management of thrombolysis related hemorrhagic transformation (HT) in real-world practice, and whether these treatments would reduce the risk of 3-month death and hematoma expansion after HT.MethodsA multicenter retrospective study was performed in three comprehensive stroke centers in China (West China Hospital, The First People’s Hospital of Ziyang, and Mianyang Central Hospital) between January 1st 2012 and December 31th 2020. Participants were patients diagnosed with HT after intravenous thrombolytics on brain computed tomography (CT) within 36 h after stroke onset. The treatment after thrombolysis related HT included aggressive therapy (procoagulant, neurosurgical treatment) and dehydration therapy (mannitol or glycerin and fructose). The primary clinical outcome was 3-month death. The primary radiographic outcome was hematoma expansion, defined as a 33% increase in the hematoma volume using the (A × B × C)/2 method on follow-up imaging.ResultsOf 538 patients with ischemic stroke receiving thrombolysis included during the study period, 94 patients (17.4%) were diagnosed with HT, 50% (47/94) of whom were symptomatic HT. The 3-month death was 31.5% (29/92), with two patients having been lost to follow up. A total of 68 patients (72.3%) had follow-up brain CT scans after HT detection for evaluating hematoma expansion, of whom 14.7% (10/68) had hematoma expansion. Among the 10 patients with hematoma expansion, 7 patients were from symptomatic HT group, and 3 patients were from the asymptomatic hematoma group. In regard to escalation in therapy, six patients received neurosurgical treatment and three patients had a fresh frozen plasma infusion. In addition, dehydration therapy was the most common management after HT diagnosis [87.2% (82 of 94)]. In the multivariable models, refusing any treatment after HT diagnosis was the sole factor associated with increased 3-month death (odds ratio, 13.6; 95% CI, 3.98–56.9) and hematoma expansion risk (odds ratio, 8.54; 95% CI, 1.33–70.1). In regard to the effects of aggressive therapy, a non-significant association of receiving hemostatic/neurosurgery therapy with a lower 3-month death and hematoma expansion risk was observed (all P > 0.05).ConclusionRefusing any treatment after HT detection had a significant trend of increasing 3-month death and hematoma expansion risk after HT. Our finding of hematoma expansion among patients with asymptomatic HT in non-western populations suggests an opportunity for intervention. Very few patients after thrombolysis related HT diagnosis received procoagulant or neurosurgical therapies. Large multicenter studies enrolling diverse populations are needed to examine the efficacy of these therapies on different HT subtypes.

BackgroundHemorrhagic transformation is one of the most serious complications in intravenous thrombolysis. Studies show that the existence of more than 10 cerebral microbleeds is strongly associated with hemorrhagic transformation. The current study attempts to develop and validate a clinical prediction model of more than 10 cerebral microbleeds.MethodsWe reviewed the computed tomography markers of cerebral small vessel diseases and the basic clinical information of acute ischemic stroke patients who were investigated using susceptibility weighted imaging from 2018 to 2021. A clinical prediction model of more than 10 cerebral microbleeds was established. Discrimination, calibration, and the net benefit of the model were assessed. Finally, a validation was conducted to evaluate the accuracy and stability of the model.ResultsThe multivariate logistic regression model showed hypertension, and some computed tomography markers (leukoaraiosis, lacunar infarctions, brain atrophy) were independent risk factors of more than 10 cerebral microbleeds. These risk factors were used for establishing the clinical prediction model. The area under the receiver operating characteristic curve (AUC) was 0.894 (95% CI: 0.870–0.919); Hosmer–Lemeshow chi-squared test yielded χ2 = 3.946 (P = 0.862). The clinical decision cure of the model was higher than the two extreme lines. The simplified score of the model ranged from 0 to 12. The model in the internal and external validation cohort also had good discrimination (AUC 0.902, 95% CI: 0.868–0.937; AUC 0.914, 95% CI: 0.882–0.945) and calibration (P = 0.157, 0.247), and patients gained a net benefit from the model.ConclusionsWe developed and validated a simple scoring tool for acute ischemic stroke patients with more than 10 cerebral microbleeds; this tool may be beneficial for paradigm decision regarding intravenous recombinant tissue plasminogen activator therapy of acute ischemic stroke.

Objective: In patients with acute ischemic stroke (AIS), hemorrhagic transformation (HT) is a major complication after mechanical thrombectomy (MT). This study aimed to investigate the relationship between serum magnesium levels and HT after MT. Methods: We collected 199 cases of consecutive AIS that received MT due to acute anterior circulation occlusions in our institution between January 2017 and January 2020. Baseline serum magnesium was obtained from all patients on admission before MT. The patients were divided into two groups based on the occurrence of HT. Univariate and multivariate analyses were performed to investigate whether magnesium was an independent predictor of HT. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were determined. Results: Of the 199 enrolled patients, 40 (20.1%) presented with HT, and 12 (6%) developed symptomatic intracranial hemorrhage (sICH). Patients with HT had lower serum magnesium levels compared to those without HT (0.76 [0.69–0.80] vs. 0.84 [0.80–0.90], p < 0.001). The multivariate logistic analysis showed that the serum magnesium level (odds ratio, [OR]: 0.000, 95% confidence interval [CI]: 0.000–0.001, p < 0.001) was significantly associated with the occurrence of HT. The ROC curve analysis revealed that the serum magnesium level could predict HT with an AUC of.820 (95% CI: 0.750–0.891 p < 0.001). Serum magnesium ≤ 0.80 mmol/L could predict HT with a sensitivity of 79.2% and a specificity of 70.0%. Of interest, the serum magnesium level was not associated with HT when the baseline of serum magnesium was higher than the cut-off value (0.80 mmol/L) in the subgroup analysis. Conclusions: Lower baseline serum magnesium levels (<0.80 mmol/L) on admission are associated with increased risk of HT in AIS patients receiving MT. [ABSTRACT FROM AUTHOR]

The blood–brain barrier (BBB) acts as a physical and biochemical barrier that plays a fundamental role in regulating the blood-to-brain influx of endogenous and exogenous components and maintaining the homeostatic microenvironment of the central nervous system (CNS). Acute stroke leads to BBB disruption, blood substances extravasation into the brain parenchyma, and the consequence of brain edema formation with neurological impairment afterward. Caspase-1, one of the evolutionary conserved families of cysteine proteases, which is upregulated in acute stroke, mainly mediates pyroptosis and compromises BBB integrity via lytic cellular death and inflammatory cytokines release. Nowadays, targeting caspase-1 has been proven to be effective in decreasing the occurrence of hemorrhagic transformation (HT) and in attenuating brain edema and secondary damages during acute stroke. However, the underlying interactions among caspase-1, BBB, and stroke still remain ill-defined. Hence, in this review, we are concerned about the roles of caspase-1 activation and its associated mechanisms in stroke-induced BBB damage, aiming at providing insights into the significance of caspase-1 inhibition on stroke treatment in the near future. [ABSTRACT FROM AUTHOR]

Background: The main and well-defined complication of intravenous administration of recombinant tissue plasminogen activator (tPA) in patients with acute ischemic stroke (AIS) is symptomatic intracranial hemorrhage (sICH). However, rtPA might also be connected with the formation of cerebral microbleeds (CMBs), located remotely from the ischemic lesions, that may remain clinically silent. This association might be important because the load of CMBs has been associated with cognitive impairment. We investigated whether administration of rtPA in AIS results in the appearance of new CMBs and if the initial load of CMBs is associated with hemorrhagic transformation. Methods: A total of fifty-nine consecutive patients with AIS treated with rtPA underwent MRI including T2*-weighted Echo Planar Imaging (T2*-EPI) shortly before and 7–9 days after rtPA administration. We calculated the load of new CMBs located outside the MR diffusion restriction area in the follow-up imaging and assessed hemorrhagic transformation with ECASS-II scoring. Results: A total of forty-nine patients were included for the final analysis. On initial T2*-EPI-GRE, 37 baseline microbleeds (CMBs) were observed in 14 patients (28.6%). On follow-up T2*-EPI-GRE amount of CMBs increased to a total number of 103. New CMBs were found in 5 (14.3%) of 35 patients without and in 9 (64.3%) of 14 with any baseline CMBs. Multiple logistic regression analysis indicated that presence of baseline CMBs (risk ratio [RR] 5.95, 95% CI 2.69–13.20, p < 0.001) and lower platelets level (risk ratio [RR] 0.992, 95% CI 0.986–0.998, p = 0.007) were independently associated with new CMBs. The baseline load of CMBs was not associated with the risk of hemorrhagic transformation. Conclusion: In this study, new CMBs were found in nearly 30% of patients with AIS on the 7–9 days after rtPA treatment. Baseline CMBs correlated with a higher risk of new CMBs appearing after the rtPA treatment, independently of other factors. At the same time, in our sample, baseline CMBs did not correlate with an increased risk of hemorrhagic transformation. Since the associations between the CMBs load and cognitive impairment have already been proved, further studies are warranted to investigate possible associations between the thrombolytic treatment of patients with AIS, mainly those with baseline CMBs, and the risk of earlier cognitive decline. [ABSTRACT FROM AUTHOR]

Background and Purpose: The evolution of total brain volume early after stroke is not well understood. We investigated the associations between age and imaging features and brain volume change in the first month after stroke. Methods: We retrospectively studied patients with acute ischemic stroke enrolled in the AXIS-2 trial. Total brain volume change from hyperacute MRI data to the first month after stroke was assessed using unified segmentation in SPM12. We hypothesized that age, ischemic brain lesion size, and white matter (WM) changes were associated with larger brain volume change. Enlarged perivascular spaces (EPVSs) and white matter hyperintensities (WMHs) were rated visually and the presence of lacunes was assessed. Results: We enrolled 173 patients with a mean age of 67 ± 11 years, 44% were women. There was a median 6 ml decrease in volume (25th percentile −1 ml to 75th percentile 21 ml) over time, equivalent to a median 0.5% (interquartile range [IQR], −0.07%−1.4%), decrease in brain volume. Age was associated with larger brain volume loss (per 10 years of age, 5 ml 95% CI 2–8 ml). Baseline diffusion weighted imaging (DWI) lesion volume was not associated with greater volume loss per 10 ml of lesion volume, change by 0 ml (95% CI −0.1 to 0.1 ml). Increasing Fazekas scores of deep WMH were associated with greater tissue loss (5 ml, 95% CI 1–10 ml). Conclusions: Total brain volume changes in a heterogenous fashion after stroke. Volume loss occurs over 1 month after stroke and is associated with age and deep WM disease. We did not find evidence that more severe strokes lead to increased early tissue loss. [ABSTRACT FROM AUTHOR]

ObjectiveIn patients with acute ischemic stroke (AIS), hemorrhagic transformation (HT) is a major complication after mechanical thrombectomy (MT). This study aimed to investigate the relationship between serum magnesium levels and HT after MT.MethodsWe collected 199 cases of consecutive AIS that received MT due to acute anterior circulation occlusions in our institution between January 2017 and January 2020. Baseline serum magnesium was obtained from all patients on admission before MT. The patients were divided into two groups based on the occurrence of HT. Univariate and multivariate analyses were performed to investigate whether magnesium was an independent predictor of HT. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were determined.ResultsOf the 199 enrolled patients, 40 (20.1%) presented with HT, and 12 (6%) developed symptomatic intracranial hemorrhage (sICH). Patients with HT had lower serum magnesium levels compared to those without HT (0.76 [0.69–0.80] vs. 0.84 [0.80–0.90], p < 0.001). The multivariate logistic analysis showed that the serum magnesium level (odds ratio, [OR]: 0.000, 95% confidence interval [CI]: 0.000–0.001, p < 0.001) was significantly associated with the occurrence of HT. The ROC curve analysis revealed that the serum magnesium level could predict HT with an AUC of.820 (95% CI: 0.750–0.891 p < 0.001). Serum magnesium ≤ 0.80 mmol/L could predict HT with a sensitivity of 79.2% and a specificity of 70.0%. Of interest, the serum magnesium level was not associated with HT when the baseline of serum magnesium was higher than the cut-off value (0.80 mmol/L) in the subgroup analysis.ConclusionsLower baseline serum magnesium levels (

BackgroundThe main and well-defined complication of intravenous administration of recombinant tissue plasminogen activator (tPA) in patients with acute ischemic stroke (AIS) is symptomatic intracranial hemorrhage (sICH). However, rtPA might also be connected with the formation of cerebral microbleeds (CMBs), located remotely from the ischemic lesions, that may remain clinically silent. This association might be important because the load of CMBs has been associated with cognitive impairment. We investigated whether administration of rtPA in AIS results in the appearance of new CMBs and if the initial load of CMBs is associated with hemorrhagic transformation.MethodsA total of fifty-nine consecutive patients with AIS treated with rtPA underwent MRI including T2*-weighted Echo Planar Imaging (T2*-EPI) shortly before and 7–9 days after rtPA administration. We calculated the load of new CMBs located outside the MR diffusion restriction area in the follow-up imaging and assessed hemorrhagic transformation with ECASS-II scoring.ResultsA total of forty-nine patients were included for the final analysis. On initial T2*-EPI-GRE, 37 baseline microbleeds (CMBs) were observed in 14 patients (28.6%). On follow-up T2*-EPI-GRE amount of CMBs increased to a total number of 103. New CMBs were found in 5 (14.3%) of 35 patients without and in 9 (64.3%) of 14 with any baseline CMBs. Multiple logistic regression analysis indicated that presence of baseline CMBs (risk ratio [RR] 5.95, 95% CI 2.69–13.20, p < 0.001) and lower platelets level (risk ratio [RR] 0.992, 95% CI 0.986–0.998, p = 0.007) were independently associated with new CMBs. The baseline load of CMBs was not associated with the risk of hemorrhagic transformation.ConclusionIn this study, new CMBs were found in nearly 30% of patients with AIS on the 7–9 days after rtPA treatment. Baseline CMBs correlated with a higher risk of new CMBs appearing after the rtPA treatment, independently of other factors. At the same time, in our sample, baseline CMBs did not correlate with an increased risk of hemorrhagic transformation. Since the associations between the CMBs load and cognitive impairment have already been proved, further studies are warranted to investigate possible associations between the thrombolytic treatment of patients with AIS, mainly those with baseline CMBs, and the risk of earlier cognitive decline.

Background and PurposeThe evolution of total brain volume early after stroke is not well understood. We investigated the associations between age and imaging features and brain volume change in the first month after stroke.MethodsWe retrospectively studied patients with acute ischemic stroke enrolled in the AXIS-2 trial. Total brain volume change from hyperacute MRI data to the first month after stroke was assessed using unified segmentation in SPM12. We hypothesized that age, ischemic brain lesion size, and white matter (WM) changes were associated with larger brain volume change. Enlarged perivascular spaces (EPVSs) and white matter hyperintensities (WMHs) were rated visually and the presence of lacunes was assessed.ResultsWe enrolled 173 patients with a mean age of 67 ± 11 years, 44% were women. There was a median 6 ml decrease in volume (25th percentile −1 ml to 75th percentile 21 ml) over time, equivalent to a median 0.5% (interquartile range [IQR], −0.07%−1.4%), decrease in brain volume. Age was associated with larger brain volume loss (per 10 years of age, 5 ml 95% CI 2–8 ml). Baseline diffusion weighted imaging (DWI) lesion volume was not associated with greater volume loss per 10 ml of lesion volume, change by 0 ml (95% CI −0.1 to 0.1 ml). Increasing Fazekas scores of deep WMH were associated with greater tissue loss (5 ml, 95% CI 1–10 ml).ConclusionsTotal brain volume changes in a heterogenous fashion after stroke. Volume loss occurs over 1 month after stroke and is associated with age and deep WM disease. We did not find evidence that more severe strokes lead to increased early tissue loss.

Background: N-terminal pro-brain natriuretic peptide (NT-proBNP) levels are a promising biomarker for predicting stroke outcomes; however, their prognostic validity is not well-understood in patients who have undergone intravenous thrombolysis. This study was designed to evaluate the prognostic value of NT-proBNP levels in patients with acute ischemic stroke treated with intravenous thrombolysis. Methods: Patients with ischemic stroke who underwent intravenous thrombolysis between April 2015 and December 2020 were analyzed. Demographic information, information related to intravenous thrombolysis, medical history, and laboratory test results were collected. Outcomes, such as hemorrhagic transformation, early neurologic deterioration, poor 3-month functional outcomes, and 3-month mortality were recorded. Correlations between NT-proBNP levels and the above outcomes were analyzed, an individualized prediction model based on NT-proBNP levels for functional outcomes was developed, and a nomogram was drafted. Results: A total of 404 patients were included in the study. Elevated NT-proBNP levels were independently associated with hemorrhagic transformation, poor 3-month functional outcomes, and 3-month mortality, while early neurological deterioration was not. An association between NT-proBNP levels and hemorrhagic transformation was noted. An individualized prediction model for poor functional outcomes was established, which was composed of ln(NT-proBNP), National Institutes of Health Stroke Scale (NIHSS), and baseline glucose, with good discrimination [area under the curve (AUC) 0.764] and calibration (P > 0.05). Conclusion: To the best of our knowledge, this is the first report on the association between NT-proBNP levels and hemorrhagic transformation in patients who have undergone intravenous thrombolysis. The 3-month functional outcomes and mortality were found to be associated with NT-proBNP levels. An individualized prediction model based on NT-proBNP levels to predict the 3-month functional outcomes was established. Our results suggest that NT-proBNP levels could be used as a prognostic biomarker in patients with acute ischemic stroke treated with intravenous thrombolysis. [ABSTRACT FROM AUTHOR]

Background and Purpose: Recent studies have shown that several proteins, including Axl, are related to hemorrhagic transformation (HT) following intravenous thrombolysis by affecting blood-brain barrier (BBB) function. However, the effects of these proteins on BBB function have been studied primarily in animal models. In this study, we aimed to identify serum protein markers that predict HT following intravenous thrombolysis in patients with acute ischemic stroke (AIS) and verify whether these serum proteins regulate BBB function and HT in animal stroke models. Methods: First, 118 AIS patients were enrolled in this study, including 52 HT patients and 66 non-HT patients. In Step 1, baseline serum levels of Axl, angiopoietin-like 4, C-reactive protein, ferritin, hypoxia-inducible factor-1 alpha, HTRA2, Lipocalin2, matrix metallopeptidase 9, platelet-derived growth factor-BB, and tumor necrosis factor alpha were measured using a quantitative cytokine chip. Next, sequence mutations and variations in genes encoding the differentially expressed proteins identified in Step 1 and subsequent function-related proteins were detected. Finally, we verified whether manipulation of differentially expressed proteins affected BBB function and HT in a hyperglycemia-induced rat stroke model. Results: Serum Axl levels were significantly lower in the HT group than in the non-HT group; none of the other protein markers differed significantly between the two groups. Genetic testing revealed that sequence variations of GAS6 (the gene encoding the Axl ligand)-derived long non-coding RNA, GAS6-AS1 , were significantly correlated with an increased risk of HT after intravenous thrombolysis. In animal studies, administration of recombinant GAS6 significantly reduced brain infarction and neurological deficits and attenuated BBB disruption and HT. Conclusions: Lower serum Axl levels, which may result from sequence variations in GAS6-AS1 , are correlated with an increased risk of HT after intravenous thrombolysis in stroke patients. Activation of the Axl signaling pathway by the GAS6 protein may serve as a therapeutic strategy to reduce HT in AIS patients. [ABSTRACT FROM AUTHOR]