sICH Patients Research Articles

Relationship Between Liver Fibrosis and Increased Risk of Symptomatic Intracranial Hemorrhage in Ischemic Stroke Patients Undergoing Mechanical Thrombectomy.

Liver fibrosis has been reported to be associated with hematoma expansion and mortality in patients with intracerebral hemorrhage. This study aimed to detect the association between liver fibrosis and symptomatic intracranial hemorrhage (sICH) in ischemic stroke after mechanical thrombectomy (MT). We retrospectively included patients with large artery occlusion in the anterior circulation and treated with MT at a single stroke center. The fibrosis-4 index (FIB-4) was used to assess the severity of liver fibrosis. sICH was diagnosed according to the Heidelberg Bleeding Classification criteria. Multivariate logistic regression and restricted cubic spline analysis were conducted to examine the relationship between liver fibrosis and sICH. Among the 578 patients (mean age, 70.1 years; 58.5% male) included in the study, 65 (11.2%) individuals were diagnosed with sICH. After adjusting for demographic characteristics and other potential confounders, a higher FIB-4 index was found to be independently associated with an increased risk of sICH (odds ratio: 1.306, 95% confidence interval: 1.127-1.512, P=0.001). Similar results were obtained when analyzing FIB-4 as a categorical variable. This study demonstrated that there is a significant association between FIB-4 and the risk of sICH in patients with acute ischemic stroke who underwent MT. Therefore, liver fibrosis could serve as a valuable parameter in monitoring the risk of sICH following MT.

Diffusion-weighted Imaging Detection of Acute Ischemia Brain Lesions in Spontaneous Intracerebral Hemorrhage Associated with White Matter Hyperintensities, Enlarged Perivascular Spaces and Diabetes Mellitus.

Diffusion-weighted imaging (DWI) is commonly detected after spontaneous intracerebral hemorrhage (sICH) and is associated with poor functional outcomes. However, the etiology and significance of DWI lesions remain unclear. Thus, our study aimed to explore the prevalence and risk factors of acute ischemic lesions in sICH and discussed the possible mechanisms. We conducted a retrospective review of a consecutive cohort of 408 patients from June 2013 to October 2019 with sICH, who had brain computed tomography (CT) and magnetic resonance imaging (MRI) within 14 days of symptoms onset. Acute ischemic lesions were assessed on MRI using DWI lesions. We compared the clinical and imaging characteristics of patients with and without DWI lesions. The data were analyzed by univariate and multivariate logistic regression. Among the enrolled 408 patients, the mean age was 56.8 ± 14.5 years, 68 (16.7%) of them had been diagnosed with diabetes mellitus (DM). DWI lesions were observed in 89 (21.8%) patients, and most of them had a history of lacunar infarctions, which were located in cortical or subcortical. In multivariate logistic regression analysis, DM (odds ratio (OR) 3.962, p <0.001), severe deep white matter hypertensities (DWMH) (OR 2.463, p =0.001) and severe centrum semiovale enlarged perivascular spaces (CSO-EPVS) (OR 2.679, p =0.001) were independently associated with the presence of DWI lesions. In our cohort, we found DM, severe DWMH and severe CSO-EPVS were the independent risk factors in sICH patients with DWI lesions.

A Novel Nomogram to Predict Symptomatic Intracranial Hemorrhage in Ischemic Stroke Patients After Intravenous Thrombolysis.

This study aimed to create and validate a novel nomogram to predict the risk of symptomatic intracranial hemorrhage (sICH) in patients with acute ischemic stroke (AIS) who underwent intravenous thrombolysis (IVT). In this retrospective study, 784 patients with AIS who received IVT were enrolled. The patients were randomly divided into two groups: a training set (n=550, 70%) and a testing set (n=234, 30%). Utilizing multivariable logistic regression analysis, relevant factors for the predictive nomogram were selected. The performance of the nomogram was evaluated using various metrics, including the area under the receiver operating characteristic curve (AUC-ROC), the Hosmer-Lemeshow goodness-of-fit test, calibration plots, and decision curve analysis (DCA). Multivariable logistic regression analysis showed that specific factors, including National Institutes of Health Stroke Scale (NIHSS) scores, Early infarct signs (EIS), and serum sodium, were identified as independent predictors of sICH. Subsequently, a nomogram was constructed using these predictors. The AUC-ROC values of the nomogram were 0.864 (95% CI: 0.810-0.919) and 0.831 (95% CI: 0.770-0.891) in the training and the validation sets, respectively. Both the calibration plots and the Hosmer-Lemeshow goodness-of-fit test showed favorable agreement in both the training and the validation sets. Additionally, the DCA indicated the practical clinical utility of the nomogram. The novel nomogram, which included NIHSS, EIS and serum sodium as variables, had the potential for predicting the risk of sICH in patients with AIS after IVT.

Leukoaraiosis and stroke severity scores in post-rtPA intracerebral haemorrhage

IntroductionPost thrombolytic symptomatic intracerebral haemorrhage (sICH) is a major concern in patients who had acute ischaemic stroke. Leukoaraiosis (LA) is reported to be related with sICH after intravenous thrombolytic treatment....

Increased Neuron-Specific Enolase Level Predicts Symptomatic Intracranial Hemorrhage in Patients with Ischemic Stroke Treated with Endovascular Treatment

Neuron-specific enolase (NSE), which is a highly specific marker for neurons, could be a predictor for prognosis in patients with symptomatic intracranial hemorrhage (sICH) with acute ischemic stroke who are receiving endovascular treatment (EVT). This study aimed to investigate the relationship between NSE and sICH in patients with acute anterior circulation stroke undergoing EVT. A total of 215 consecutive patients with acute stroke treated with EVT were included. Patients with stroke and acute anterior circulation occlusion, receiving EVT treated at our hospital, were enrolled between January 2017 and August 2021. NSE level was measured on arrival at the neurology intensive care unit after EVT. The patients were divided into 2 groups according to whether sICH was present. Univariate and multivariate analyses were performed. NSE level was also incorporated into the TAG score (modified Thrombolysis in Cerebral Infarction score, Alberta Stroke Program Early CT Score, and glucose level), which was developed as a scoring system to predict sICH, and the prediction capability was compared with the TAG score alone. Causal inference was performed using the package DoWhy in Python to evaluate the causal relationship between NSE and sICH. The area under the curve (AUC) value of NSE showed moderate accuracy, with an AUC value of 0.729 (95% confidence interval, 0.655-0.795; P < 0.001). The NSE cutoff value was set at 23.88 ng/mL. When the NSE level ≥23.88 ng/mL, the sensitivity was 58.33% and the specificity was 78.72% (P < 0.001). The AUC for the TAG+ NSE score was 0.801 compared with an AUC of 0.632 for the TAG score (Z= 2.034; P= 0.042). A causal inference model using the DoWhy library shows a proportional relationship between NSE and the diagnosis of sICH. This study is the first to show that increased NSE level is an independent predictor of sICH in patients with acute anterior circulation stroke who are undergoing endovascular treatment.

Effect of edaravone on symptomatic intracranial hemorrhage in patients with acute large vessel occlusion on apixaban for non-valvular atrial fibrillation

BackgroundEdaravone administration was associated with lower incidence of symptomatic intracranial hemorrhage (sICH) in patients with acute large vessel occlusion (LVO). However, its protective effect on sICH in patients with LVO who receive direct oral anticoagulants for non-valvular atrial fibrillation (NVAF) is uncertain. ObjectivesTo explore the effect of edaravone administration on the incidence of sICH in patients with acute LVO receiving apixaban for NVAF. MethodsA Japanese multicenter registry of apixaban on clinical outcome of the patients with LVO or stenosis (ALVO study) included patients who were admitted within 24 h after stroke onset and were received apixaban within 14 days of stroke onset. Patients were divided into two groups according to edaravone administration (Edaravone and No-Edaravone groups). The incidence of sICH within one year and infarct growth before apixaban administration were compared between these groups. ResultsOf the 686 enrolled patients, 622 were included and edaravone was administered to 407 (65.4%). The incidences of sICH in Edaravone and No-Edaravone groups were 1.3% and 5.0%, respectively (p = 0.01). The inverse probability of treatment-weighting (IPTW) hazard ratio (HR) (95% confidence interval [CI]) of Edaravone group for sICH within one year was 0.36 (0.15–0.80) compared to No-Edaravone group. The incidences of infarct growth in Edaravone and No-Edaravone groups were 35.3% and 42.0%, respectively (p = 0.13). IPTW HR (95% CIs) for infarct growth was 0.76 (0.60–0.97). ConclusionsEdaravone administration was associated with a lower incidence of sICH in patients with LVO and NVAF who administrated apixaban.

Endovascular Thrombectomy With or Without Thrombolysis for Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

To this date, whether to administer intravenous thrombolysis (IVT) prior to endovascular thrombectomy (EVT) for stroke patients still stirs some debate. We aimed to systematically update the evidence from randomized trials comparing EVT alone vs EVT with bridging IVT. We searched MEDLINE, EMBASE, and the Cochrane Library to identify randomized controlled trials (RCTs) comparing EVT with or without IVT in patients presenting with stroke secondary to a large vessel occlusion. We conducted meta-analyses using random-effects models to compare functional independence, mortality, and symptomatic intracranial hemorrhage (sICH), between EVT and EVT with IVT. We assessed risk of bias using the Cochrane risk-of-bias tool and certainty of evidence for each outcome using the GRADE approach. Of 11,111 citations, we included 6 studies with a total of 2336 participants. We found low-certainty evidence of possibly a small decrease in the proportion of patients with functional independence (risk difference [RD] -2.0%, 95% CI -5.9% to 2.0%), low-certainty evidence that there is possibly a small increase in mortality (RD 1.0%, 95% CI -2.2% to 4.7%), and moderate-certainty evidence that there is probably a decrease in sICH (RD -1.0%, 95% CI -1.6% to .7%) for patients with EVT alone compared to EVT plus IVT, respectively. Low-certainty evidence shows that there is possibly a small decrease in functional independence, low-certainty evidence shows that there is possibly a small increase in mortality, and moderate-certainty evidence that there is probably a decrease in sICH for patients with EVT alone compared to EVT plus IVT.

Short-term surgical outcomes of spontaneous intracerebral hemorrhage in China from 2019 to 2021: a retrospective cohort study

China has the highest prevalence of spontaneous intracerebral hemorrhage (sICH) worldwide. To date, no national-level report has revealed sICH surgical performance. We aimed to investigate the current status and short-term outcomes of patients who underwent surgical treatment for sICH between 2019 and2021. Data from 7451 patients undergoing sICH surgical treatment in China between 2019 and 2021, including demographic information, disease severity, surgical treatments for sICH, complications, and follow-up information, were retrieved from the Bigdata Observatory Platform for Stroke of China. Propensity score matching (PSM) was applied to balance the baseline characteristics. The surgical treatment performance on 3-month mortality and functional outcome were then explored by regression analysis. The influence of stroke center level and region on surgical performance was then explored. The numbers of sICH patients undergoing open craniotomy (OC), cranial puncture (CP), decompressive craniectomy (DC) and endoscopic evacuation (EE) were 2404 (32.3%), 3030 (40.7%), 1700 (22.8%) and 317 (4.3%), respectively. The 3-month mortality rate was 20.2%. Among the surviving patients, the 3-month poor functional prognosis (mRS 3-5) rate was 46.5%. After PSM, regression analysis showed that DC was associated with a higher mortality risk (OR=1.31, 95% CI 1.06-1.61) than OC. CP was associated with a lower risk of poor mRS scores than OC (OR=0.84, 95% CI 0.70-1.01), especially in stroke prevention centers and specific regions. Outcome improvements in Chinese sICH patients undergoing surgical treatment are worth expecting. Inconsistent surgical performance, especially functional outcome, affected by inhomogeneity of the hospital should be addressed. This work was supported by the Beijing Hospitals Authority Youth Programme (QML20230804), the National Natural Science Foundation of China (81701796, 82030037, 81871009), Capital Health Research and Development of Special Fund (2020-2Z-2019), Science and Technology Innovation 2030-Major Project (2021ZD0201801), and the Translational and Application Project of Brain-inspired and Network Neuroscience on Brain Disorders (11000022T000000444685).

Tranexamic acid in a mouse model of cerebral amyloid angiopathy: setting the stage for a novel stroke treatment approach

BackgroundSymptomatic intracerebral hemorrhage (sICH) commonly occurs in patients with cerebral amyloid angiopathy (CAA). Amyloid also initiates plasminogen activation and might promote sICH. ObjectivesAs amyloid-driven plasmin formation can be blocked by tranexamic acid (TXA), we aimed to evaluate the biodistribution and long-term consequences of TXA on brain amyloid-beta (Aβ) levels, inflammation, and neurologic function in APP/PS1 mice. MethodsAPP/PS1 mice overexpressing the mutant human amyloid precursor protein and wild-type littermates were randomized to TXA (20 mg/mL) or placebo in the drinking water for 6 months. TXA in plasma and various organs was determined by liquid chromatography-mass spectrometry. Plasmin activity assays were performed to evaluate changes in fibrinolytic activity. Neurologic function was evaluated by Y-maze and parallel rod floor testing. Proximity ligation–based immunoassays were used to quantitate changes of 92 biomarkers of inflammation. Brain Aβ levels were assessed by immunohistochemistry. ResultsLong-term oral TXA administration inhibited fibrinolysis. TXA accumulated in the kidney (19.4 ± 11.2 μg/g) with 2- to 5-fold lower levels seen in the lung, spleen, and liver. TXA levels were lowest in the brain (0.28 ± 0.01 μg/g). Over 6 months, TXA had no discernible effect on motor coordination, novelty preference, or brain Aβ levels. TXA reduced plasma levels of epithelial cell adhesion molecule and increased CCL20. ConclusionLong-term TXA treatment does not alter brain Aβ levels or impact neurologic behavior in mice predisposed to amyloid deposition and had minor effects on the levels of inflammatory mediators. This finding supports the safety of TXA and lays the foundation for TXA as a novel treatment to reduce sICH in patients with CAA.

IV thrombolysis plus thrombectomy versus IV thrombolysis alone for minor stroke with anterior circulation large vessel occlusion from the IRETAS and Italian SITS-ISTR cohorts.

The aim of this study was to compare the outcomes of patients treated with intravenous thrombolysis (IVT) <4.5 h after symptom onset plus mechanical thrombectomy (MT) <6 h with those treated with IVT alone <4.5 h for minor stroke (NIHSS ≤5) with large vessel occlusion (LVO) in the anterior circulation. Patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke (IRETAS) and in the Italian centers included in the SITS-ISTR were analyzed. Among the patients with complete data on 24-h ICH type, 236 received IVT plus MT and 382 received IVT alone. IVT plus MT was significantly associated with unfavorable shift on 24-h ICH types (from no ICH to PH-2) (OR, 2.130; 95% CI, 1.173-3.868; p=0.013) and higher rate of PH (OR, 4.363; 95% CI, 1.579-12.055; p=0.005), sICH per ECASS II definition (OR, 5.527; 95% CI, 1.378-22.167; p=0.016), and sICH per NINDS definition (OR, 3.805; 95% CI, 1.310-11.046; p=0.014). Among the patients with complete data on 3-month mRS score, 226 received IVT plus MT and 262 received IVT alone. No significant difference was reported between IVT plus MT and IVT alone on mRS score 0-1 (72.1% versus 69.1%), mRS score 0-2 (79.6% versus 79%), and death (6.2% versus 6.1%). Compared with IVT alone, IVT plus MT was associated with unfavorable shift on 24-h ICH types and higher rate of 24-h PH and sICH in patients with minor stroke and LVO in the anterior circulation. However, no difference was reported between the groups on 3-month functional outcome measures.

Venous thromboembolism after spontaneous intracerebral hemorrhage and the status quo of anticoagulation in this population: A retrospective case[sbnd]control study from a tertiary hospital in China

ObjectivePatients with spontaneous intracerebral hemorrhage (sICH) are susceptible to venous thromboembolism (VTE) including pulmonary embolism (PE) and deep venous thrombosis (DVT) due to a variety of risk factors. There are few studies regarding the predictive value of D-dimer for VTE in patients with sICH, and the anticoagulation therapy for these patients are still controversial. The objective of this study is to study the independent predictors of VTE in sICH patients. The rates of anticoagulation therapy and hemorrhagic evens were also investigated. MethodsRetrospective review of patients with sICH admitted to the First Affiliated Hospital of Dalian Medical University from 2012 to 2022 and who developed VTE (PE and/or DVT) during hospitalization. A similar number of sICH patients without VTE were randomly selected into the control group. A variety of clinical characteristics were compared between groups. Univariate and multivariate analyses were performed to identify independent predictors of VTE in patients with sICH. ResultsA total of 270 sICH patients were enrolled in this study, including 132 patients with VTE and 138 patients without VTE. After adjusting for other confounders, the maximum level of D-dimer during hospitalization (odds ratio [OR] 1.061, 95 % confidence interval (CI) 1.014–1.110), Glasgow coma scale (GCS) on admission (OR 1.347, 95 % CI 1.110–1.634), modified Rankin Scale (mRS) at discharge (OR 2.578, 95 % CI 1.546–4.298), neutrophil count (OR 1.056, 95 % CI 1.025–1.088) and hospitalization time (OR 1.089, 95 % CI 1.018–1.164) were independently associated with the sICH patients who developed VTE. The maximum D-dimer plasma level of 5.655 mg/L during hospitalization was the optimal threshold to indicate sICH patients developing VTE with a sensitivity of 83.3 % and a specificity of 67.4 %. No patients with sICH received prophylactic anticoagulation therapy against VTE in the present study. A total of 57.6 % (76/132) of the sICH patients with VTE were administered anticoagulant therapy and the rate of hemorrhagic complication was 9.2 %. ConclusionssICH patients with increased levels of D-dimer, higher GCS scores, higher mRS scores, increased neutrophil counts and longer hospitalization time are more likely to develop VTE complications. Routine and serial monitoring of the D-dimer values may be useful in patients with sICH, and VTE should be considered when the plasma level of D-dimer increases to 5.655 mg/L during hospitalization. In tertiary hospitals in China, the rate of sICH patients with VTE receiving anticoagulation treatment is low. Further studies are necessary to explore the safety and efficacy of VTE therapeutic anticoagulation in patients with sICH.

Mechanical Thrombectomy Versus Combined Thrombectomy and Intravenous Thrombolysis in Tandem Lesions (S24.003)

Mechanical Thrombectomy Versus Combined Thrombectomy and Intravenous Thrombolysis in Tandem Lesions (S24.003)

Higher serum bilirubin levels are associated with hemorrhagic transformation after intravenous thrombolysis in acute ischemic Stroke.

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. 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. 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, multiple-adjusted 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. 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.

Anesthesiology Performance Improvement and Reporting Exchange (ASPIRE) Quality Metrics in Patients Undergoing Decompressive Craniectomy and Endoscopic Clot Evacuation after Spontaneous Supratentorial Intracerebral Hemorrhage: A Retrospective Observational Study.

We report adherence to 6 Anesthesiology Performance Improvement and Reporting Exchange (ASPIRE) quality metrics (QMs) relevant to patients undergoing decompressive craniectomy or endoscopic clot evacuation after spontaneous supratentorial intracerebral hemorrhage (sICH). In this retrospective observational study, we describe adherence to the following ASPIRE QMs: acute kidney injury (AKI-01); mean arterial pressure < 65 mm Hg for less than 15 minutes (BP-03); myocardial injury (CARD-02); treatment of high glucose (> 200 mg/dL, GLU-03); reversal of neuromuscular blockade (NMB-02); and perioperative hypothermia (TEMP-03). The study included 95 patients (70% male) with median (interquartile range) age 55 (47 to 66) years and ICH score 2 (1 to 3) undergoing craniectomy (n=55) or endoscopic clot evacuation (n=40) after sICH. In-hospital mortality attributable to sICH was 23% (n=22). Patients with American Society of Anesthesiologists physical status class 5 (n=16), preoperative reduced glomerular filtration rate (n=5), elevated cardiac troponin (n=21) and no intraoperative labs with high glucose (n=71), those who were not extubated at the end of the case (n=62) or did not receive a neuromuscular blocker given (n=3), and patients having emergent surgery (n=64) were excluded from the analysis for their respective ASPIRE QM based on predetermined ASPIRE exclusion criteria. For the remaining patients, the adherence to ASPIRE QMs were: AKI-01, craniectomy 34%, endoscopic clot evacuation 1%; BP-03, craniectomy 72%, clot evacuation 73%; CARD-02, 100% for both groups; GLU-03, craniectomy 67%, clot evacuation 100%; NMB-02, clot evacuation 79%, and; TEMP-03, clot evacuation 0% with hypothermia. This study found variable adherence to ASPIRE QMs in sICH patients undergoing decompressive craniectomy or endoscopic clot evacuation. The relatively high number of patients excluded from individual ASPIRE metrics is a major limitation.

Abstract Number ‐ 176: Mechanical thrombectomy with or without bridging in stroke: A systematic review and meta‐analysis of RCTs

Introduction Current published guidelines and meta‐analyses comparing direct mechanical thrombectomy (MT) alone versus MT with bridging intravenous thrombolysis (IVT) suggested that MT alone is non‐inferior to MT with bridging thrombolysis in achieving favorable functional outcome. Because of this controversy, we aimed to systematically update the evidence and meta‐analyze data from randomized trials comparing MT alone versus MT with bridging thrombolysis. Methods We searched MEDLINE (through Ovid), EMBASE, and the Cochrane Library from inception to December 14, 2021 without any language restrictions to identify randomized controlled trials (RCTs) and post‐hoc analyses of RCTs comparing direct MT with or without bridging IVT in patients presenting with acute ischemic stroke secondary to a large vessel occlusion. We conducted meta‐analyses using random‐effects models to compare the rates for favorable functional outcome (defined as modified Rankin scale [mRS] score of 0 to 2) and mortality at 90 days, and symptomatic intracranial hemorrhage (sICH), between MT and MT with IVT. We also assessed the risk of bias using the Cochrane risk‐of‐bias tool (RoB) and the certainty of evidence for each outcome using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Results Of 11,111 citations, we identified 53 eligible studies, and included 8 studies with a total of 3,008 participants. We found low‐certainty evidence suggesting that there is probably a small increase in the proportion of patients with favorable functional outcome with an mRS of 0 to 2 at 90 days for those who underwent MT with IVT compared to those with MT alone (risk ratio [RR] 1.08, 95% CI 0.99 to 1.19); moderate‐certainty evidence that there is probably a small decrease in mortality at 90 days for patients with MT plus IVT compared to MT alone (RR 0.86, 95% CI 0.71 to 1.03); and very low‐certainty evidence that there is possibly an increase in sICH for patients with MT plus IVT compared to MT alone (RR 1.17, 95% CI 0.85 to 1.61). When we restricted the analyses to RCTs only, we found no significant differences in favorable functional outcome (RR 2.05, 95% CI 0.97 to 1.13), mortality (RR 0.94, 95% CI 0.78 to 1.14), or sICH (RR 1.20, 95% CI 0.85 to 1.70). Conclusions Low‐certainty evidence shows that there is probably a small increase in the proportion of patients with favorable functional outcome, moderate‐certainty evidence shows that there is probably a small decrease in mortality, and very low‐certainty evidence that there is possibly an increase in sICH for patients with MT plus IVT compared to MT alone.

A nomogram predictive model for long-term survival in spontaneous intracerebral hemorrhage patients without cerebral herniation at admission

Stratification of spontaneous intracerebral hemorrhage (sICH) patients without cerebral herniation at admission, to determine the subgroups may be suffered from poor outcomes or benefit from surgery, is important for following treatment decision. The aim of this study was to establish and verify a de novo nomogram predictive model for long-term survival in sICH patients without cerebral herniation at admission. This study recruited sICH patients from our prospectively maintained ICH patient database (RIS-MIS-ICH, ClinicalTrials.gov Identifier: NCT03862729) between January 2015 and October 2019. All eligible patients were randomly classified into a training cohort and a validation cohort according to the ratio of 7:3. The baseline variables and long-term survival outcomes were collected. And the long-term survival information of all the enrolled sICH patients, including the occurrence of death and overall survival. Follow-up time was defined as the time from the onset to death of the patient or the last clinical visit. The nomogram predictive model was established based on the independent risk factors at admission for long-term survival after hemorrhage. The concordance index (C-index) and ROC curve were used to evaluate the accuracy of the predictive model. Discrimination and calibration were used to validate the nomogram in both the training cohort and the validation cohort. A total of 692 eligible sICH patients were enrolled. During the average follow-up time of 41.77 ± 0.85 months, a total of 178 (25.7%) patients died. The Cox Proportional Hazard Models showed that age (HR 1.055, 95% CI 1.038–1.071, P < 0.001), Glasgow Coma Scale (GCS) at admission (HR 2.496, 95% CI 2.014–3.093, P < 0.001) and hydrocephalus caused by intraventricular hemorrhage (IVH) (HR 1.955, 95% CI 1.362–2.806, P < 0.001) were independent risk factors. The C index of the admission model was 0.76 and 0.78 in the training cohort and validation cohort, respectively. In the ROC analysis, the AUC was 0.80 (95% CI 0.75–0.85) in the training cohort and was 0.80 (95% CI 0.72–0.88) in the validation cohort. SICH patients with admission nomogram scores greater than 87.75 were at high risk of short survival time. For sICH patients without cerebral herniation at admission, our de novo nomogram model based on age, GCS and hydrocephalus on CT may be useful to stratify the long-term survival outcomes and provide suggestions for treatment decision-making.

Anti-DEspR antibody treatment improves survival and reduces neurologic deficits in a hypertensive, spontaneous intracerebral hemorrhage (hsICH) rat model

Progressive secondary brain injury—induced by dysregulated neuroinflammation in spontaneous intracerebral hemorrhage (sICH)—underlies high sICH-mortality and remains without FDA-approved pharmacotherapy. Clinical insight that hematoma-directed interventions do not improve mortality prioritizes resolving acute secondary brain injury in sICH. As neutrophils are implicated in sICH secondary brain injury, we tested whether inhibition of a rogue neutrophil-subset expressing the dual endothelin-1/signal peptide receptor (DEspR) and associated with secondary tissue injury, DEspR+ CD11b+ immunotype, will attenuate mortality in a hypertensive-sICH (hsICH) rat model. We confirmed sICH-related deaths in hsICH-rats by T2*-weighted 9.4 T MRI and DEspR+ neutrophils in hsICH-rat brain perihematomal areas by immunostaining. At acute sICH, anti-DEspR muIgG1-antibody, mu10a3, treatment increased median survival in hsICH rats vs controls (p < 0.0001). In pre-stroke sICH, weekly 10a3-treatment did not predispose to infection and delayed sICH-onset vs controls (p < 0.0001). As potential sICH-therapeutic, we tested humanized anti-DEspR IgG4S228P-mAb, hu6g8. In vitro, hu6g8 reversed delayed-apoptosis in DEspR+ CD11b+ neutrophils. In vivo, hu6g8 increased median survival and reduced neurologic symptoms in male/female hsICH-rats vs controls (p < 0.0001). Altogether, preclinical efficacy of inhibition of DEspR+ CD11b+ neutrophils in acute sICH—without infection complications, supports the potential of anti-DEspR therapy in sICH. Data provide basis for clinical study of DEspR+ CD11b+ neutrophil-subset in sICH patients.

A Novel Metabolic Score for Insulin Resistance and Symptomatic Intracranial Hemorrhage in Ischemic Stroke Patients After Endovascular Thrombectomy.

Insulin resistance plays a pivotal role in the pathophysiology of ischemic stroke. This study aimed to determine the relationship between the novel metabolic score for insulin resistance (METS-IR) and symptomatic intracranial hemorrhage (sICH) after endovascular thrombectomy (EVT) in stroke patients. We retrospectively included patients with large artery occlusion in the anterior circulation and treated by EVT from 2 stroke centers (Nanjing First Hospital from September 2019 to April 2022, and Jinling Hospital from September 2019 to July 2021). The METS-IR was used as an alternative marker of insulin resistance and calculated using laboratory data after admission. sICH was diagnosed according to the Heidelberg Bleeding Classification. Of the 410 enrolled patients (mean age, 69.8 ± 11.7 years; 60.7% men), 50 (12.2%) were diagnosed as sICH. After adjusting for demographic characteristics, poor collateral status, and other potential confounders, higher METS-IR was revealed to be independently associated with sICH (odds ratio, 1.076; 95% confidence interval, 1.034-1.120; P = 0.001). Similar significant results were obtained when defining METS-IR as a categorical variable. The restricted cubic spline uncovered a linear relationship between METS-IR and sICH (P < 0.001 for linearity). Furthermore, adding METS-IR to the conventional model significantly improved the risk prediction for sICH (net reclassification improvement = 15.8%, P = 0.035; integrated discrimination index = 2.6%; P = 0.017). This study demonstrated a significant association between METS-IR score and sICH in ischemic stroke patients treated with EVT. It could help monitor and manage sICH in patients after EVT.

Abstract TP14: Does Atrial Fibrillation (Afib) Impact The Rate Of 90 Days Modified Rankin Scale (mRS) In Patients Who Received Intravenous Thrombolytic (IVT) Before Endovascular Treatment (EVT)?results From A Large Health System In Six Western States Of The United States

Introduction: Previous studies indicate patients with acute ischemic stroke (AIS) due to Afib may not respond well to intravenous thrombolysis (IVT) compared to those without Afib. We assessed the association between a history of atrial Afib, good 90-day mRS (≤2), and the rate of symptomatic intracerebral hemorrhage (sICH) in patients treated with IVT and/or EVT. Methods: Data from a multi-state health system’s stroke registry for patients who received acute stroke treatment and were discharged between 2018 and 2022 were used. Patients were stratified into groups 1:EVT only with or without Afib; 2: IVT plus EVT with or without Afib; 3:IVT only with or without Afib.Multivariable mixed-effect logistic regression was performed and adjusted for baseline NIHSS, age, sex, race, and ethnicity, NIHSS on admission, blood glucose on admission, SBP at admission, and history of diabetes, CAD/prior MI, carotid stenosis, smoking, dyslipidemia, heart failure, being overweight, or renal insufficiency Results: Overall, 2558 patients who underwent AIS treatment had a 90-day mRS, of whom 30% had a history of AFib, 48% had a 90-day mRS 0-2; with the median age at arrival 72 years,73% white, median NIHSS was 9, 27% diabetes, 21% CAD, 4% carotid stenosis, 13% smoker, 60% dyslipidemia, 13% HF, 62% overweight, 11% chronic renal insufficiency, median SBP 153 mmHg, median glucose 124.Among group 1(n=978): 39.4% had Afib, 36.1% had a 90-day mRS 0-2 and 5% had sICH .In group 2 (n=402): 28.1% had Afib, 44.3% had a 90-day mRS 0-2 and 5.9% had sICH. In group 3(n=1178): 16.1% had Afib, 59.9% had a 90-day mRS of 0-2, and 2.6% had sICH.After adjustment, there was no association between Afib and 90-day mRS in any group. Also, the rate of sICH did not significantly differ between Afib and non-Afib patients. Conclusions: History of Afib did not significantly impact favorable functional outcomes or the rate of sICH in patients who underwent EVT with or without intravenous thrombolytics.

Abstract WMP1: Complications Of Intravenous Tenecteplase For The Treatment Of Acute Ischemic Stroke: A Systematic Review And Meta-Analysis

Introduction: Prior systematic reviews have focused on a comparison of efficacy endpoints between tenecteplase (TNK) and alteplase. The objectives of this study are to determine whether the rate of treatment complications differs between patients treated with the two agents. Methods: This systematic review (CRD42022303835) was performed according to PRISMA guidelines. We included prospective, interventional studies and prospective and retrospective observational studies. We searched MEDLINE, the Cochrane Central Register of Controlled Trials, Embase, Web of Science and the ClinicalTrials.gov registry from inception through June 3 rd 2022. The primary endpoint was symptomatic intracranial hemorrhage (sICH) and secondary endpoints included any ICH, mortality, angioedema, gastrointestinal hemorrhage and other extracranial hemorrhage. We performed separate random effects meta analyses for each endpoint. Evidence was synthesized as relative risks, comparing subjects exposed to TNK versus alteplase as well as absolute risks in those treated with TNK. Results: Of 2,226 records identified, 26 were eligible for inclusion including 7,921 patients. Seventeen studies included alteplase as a comparator group and 10 were non-comparative. The relative risk of sICH in patients treated with TNK compared with alteplase was 0.93 (95% CI: 0.68-1.28). Across those treated with low, medium and high doses of TNK, the relative risks were 0.78 (95% CI: 0.22-2.82), 0.84 (95% CI: 0.58-1.20) and 2.31 (0.69-7.75) respectively. The unadjusted rate of sICH, including comparative and non-comparative studies, was 1%, 2% and 4% within the low, medium and high dose groups. Discussion: To-date, this is the most comprehensive systematic review examining relative complications of TNK and alteplase. The rate of treatment harms is broadly comparable between those treated with the two agents. We present evidence that the rate of sICH may be increased in those treated with higher doses of TNK.