Acute Intracerebral Hemorrhage Research Articles

Two weeks administration of tranexamic acid for acute intracerebral hemorrhage: A hospital-based pilot study.

A previous report suggested that functional status does not differ between patients who received tranexamic acid and those who received placebo within the early hours of intracerebral hemorrhage (ICH). Our pilot study tested the hypothesis that 2 weeks administration of tranexamic acid would contribute to functional improvement. Consecutive patients with ICH were administered 250 mg tranexamic acid 3 times a day continuously for 2 weeks. We also enrolled historical control consecutive patients. We collected clinical data that involved hematoma size, level of consciousness, and Modified Rankin Scale (mRS) scores. Univariate analysis showed that the mRS score on day 90 was better in the administration group (P = 0.0095). The mRS scores on the day of death or discharge suggested a favorable effect of the treatment (P = 0.0678). Multivariable logistic regression analysis also showed that the treatment was associated with good mRS scores on day 90 (odds ratio [OR] = 2.81, 95% confidence interval [CI]: 1.10-7.21, P = 0.0312). In contrast, ICH size was associated with poor mRS scores on day 90 (OR = 0.92, 95% CI: 0.88-0.97, P = 0.0005). After propensity score matching, there was no difference in the outcomes between the two groups. We did not detect mild and serious adverse events. The study could not show the significant effect of 2 weeks administration of tranexamic acid on functional outcomes of ICH patients after the matching; however, suggested that this treatment is at least safe and feasible. A larger and adequately powered trial is needed.

Systemic inflammation and immune index predicting outcomes in patients with intracerebral hemorrhage.

Recent evidence has suggested that systemic inflammatory and immune index (SIRI) and systematic inflammation index (SII) could predict prognosis in stroke patients. This study aimed to determine the effects of SIRI and SII on predicting in-hospital infections and unfavorable outcomes in patients with acute intracerebral hemorrhage (ICH). We used the data from a prospective and registry-based study recruiting ICH patients between January 2014 and September 2016 in a single comprehensive stroke center. All patients were stratified by quartiles of SIRI or SII. Logistic regression analysis was used to estimate the associations with follow-up prognosis. The receiver operating characteristics (ROC) curves were performed to examine the predictive utility of these indexes for infections and prognosis. Six hundred and forty spontaneous ICH patients were enrolled in this study. Compared with the lowest quartile (Q1), SIRI or SII values both showed positive correlations with increased risks for poor 1-month outcomes (adjusted ORs in Q4 was 2.162 [95% CI: 1.240-3.772] for SIRI, 1.797 [95% CI: 1.052-3.070] for SII). Additionally, a higher level of SIRI, but not SII, was independently associated with a higher risk of infections and an unfavorable 3-month prognosis. The C-statistic for the combined SIRI and ICH score was higher than SIRI or ICH score alone for predicting in-hospital infections and poor outcomes. Elevated SIRI values were associated with in-hospital infections and poor functional outcomes. It may provide a new biomarker for ICH prognosis prediction, especially in the acute stage.

Emerging role of miRNAs in the regulation of ferroptosis.

Ferroptosis is a kind of cell death which has distinctive features differentiating it from autophagy, necrosis and apoptosis. This iron-dependent form of cell death is described by an increase in lipid reactive oxygen species, shrinkage of mitochondria and decrease in mitochondrial cristae. Ferroptosis is involved in the initiation and progression of many diseases and is regarded as a hotspot of investigations on treatment of disorders. Recent studies have shown that microRNAs partake in the regulation of ferroptosis. The impact of microRNAs on this process has been verified in different cancers as well as intervertebral disc degeneration, acute myocardial infarction, vascular disease, intracerebral hemorrhage, preeclampsia, hemorrhagic stroke, atrial fibrillation, pulmonary fibrosis and atherosclerosis. miR-675, miR-93, miR-27a, miR-34a and miR-141 have been shown to affect iron metabolism, antioxidant metabolism and lipid metabolism, thus influencing all pivotal mechanisms in the ferroptosis process. In the current review, we summarize the role of microRNAs in ferroptosis and their involvement in the pathetiology of malignant and non-malignant disorders.

Gender disparity in stoke: Women have higher ICH scores than men at initial ED presentation for intracerebral hemorrhage

ObjectiveTo determine what if any differences in presentation exist between men and women who present with acute intracerebral hemorrhage (ICH) to the emergency department (ED). MethodsThis was an IRB approved prospective cohort study of ED patients presenting with acute intracerebral hemorrhage. Statistical analyses were performed in JMP 14.1. Non parametric methods were used for skewed variables. The study was conducted in a comprehensive stroke center. The independent variable was the ICH score, and the dependent variable of interest was ultimate disposition (death or hospice vs. home or skilled nursing facility). ResultsThe cohort consisted of 129 patients (54 women and 75 men). The median age was 71 years (IQR 58-81). The baseline co-morbidities were similar between both men and women and whether or not they were independent in their activities of daily living prior to experiencing their ICH. The overall median ICH score for women was 2, IQR 1-4, and 1 for men, IQR 1-2 (P = 0.0369) . A higher ICH score was significantly associated with in-hospital death and or hospice status (P = .0095, 95% CI 0.6340 – 0.4825). Conversely, a lower ICH score was significantly associated with being discharged home (P< 0.001, 95% CI -0.1694 to -0.0759). ConclusionWomen have higher ICH scores than men at initial ED presentation for intracerebral hemorrhage. A higher ICH score is significantly associated with the worse outcomes of death and/or hospice.

Development of Cloud-Based Telemedicine Platform for Acute Intracerebral Hemorrhage in Gangwon-do : Concept and Protocol.

We aimed to develop a cloud-based telemedicine platform for patients with intracerebral hemorrhage (ICH) at local hospitals in rural and underserved areas in Gangwon-do using artificial intelligence and non-face-to-face collaboration treatment technology. This is a prospective and multi-center development project in which neurosurgeons from four university hospitals in Gangwondo will participate. Information technology experts will verify and improve the performance of the cloud-based telemedicine collaboration platform while treating ICH patients in the actual medical field. Problems identified will be resolved, and the function, performance, security, and safety of the telemedicine platform will be checked through an accredited certification authority. The project will be carried out over 4 years and consists of two phases. The first phase will be from April 2022 to December 2023, and the second phase will be from April 2024 to December 2025. The platform will be developed by dividing the work of the neurosurgeons and information technology experts by setting the order of items through mutual feedback. This article provides information on a project to develop a cloud-based telemedicine platform for acute ICH patients in Gangwon-do.

Abstract TP117: Temporal Serum Iron And Hemoglobin Changes In Patients From The High Dose Deferoxamine In Intracerebral Hemorrhage Trial

Introduction: Following intracerebral hemorrhage (ICH), elevated cerebral tissue iron concentrations are seen. It is unclear how peripheral serum iron concentrations change over time and how they relate to anemia after ICH. Given the known impacts of iron concentrations and anemia on clinical outcomes, we explored serum iron biomarker and hemoglobin concentration changes after acute ICH. Methods: A post hoc analysis of patients with available serial (baseline and 5 day) serum biomarker data from the multicenter, High Dose Deferoxamine in Intracerebral Hemorrhage (HI-DEF) trial was performed. Changes of serum hemoglobin, iron, transferrin, and ferritin were assessed using repeated measure ANOVA analyses. Deferoxamine treatment and poor 90 day modified Rankin Scale 4-6 were separately assessed as between subject factors for these laboratory changes. Results: Of 42 ICH patients analyzed, the mean age was 64, 62% were male, median ICH volume was 15.7mL (IQR 5.7-37.5), and baseline anemia was seen in 19%. We identified significant decrements of hemoglobin (mean difference -1.4 g/dL; 95%CI: -1.9 to -0.9; p&lt;0.0001), iron (mean difference -16.9 ug/dL; 95%CI: -29.7 to -4.1; p=0.01), transferrin (mean difference -43.9 ng/mL; 95%CI: -56.6 to -31.3; p&lt;0.0001), and conversely, significant ferritin elevations (mean difference 104.5 ug/L; 95%CI: 52.5-156.6; p&lt;0.0001) at 5 days. Anemia was identified in 43% of patients at 5 days. Deferoxamine did not have a significant impact on these repeated measures. Patients with poor long-term outcomes had greater decrements in hemoglobin compared to those with good outcomes (mean difference: -1.5 g/dL; 95%CI: -2.6 to -0.3; p=0.01). Conclusions: Serum iron and hemoglobin concentrations decrease significantly over time following ICH. Patients with worse long term ICH outcomes had greater hemoglobin decrements during their hospitalization. The aggregate iron biomarker and hemoglobin concentration changes suggest anemia development may be due to anemia of inflammation. Further work is required to address the pathophysiologic difference between systemic and central iron homeostasis mechanisms following ICH and the impacts that ICH has on inflammation, systemic iron homeostasis, anemia, and clinical outcomes.

Abstract TMP47: IMPROVING Time To Anti-Coagulation Reversal For Hemorrhagic Strokes

Background: Oral anticoagulation (OAC) is a risk factor for intracerebral hemorrhage (ICH) which is an important source of disability and mortality. OAC-associated ICH (OAC-ICH) patients have worse outcomes as compared to ICH patients not on OAC, likely because of the associated larger stroke volumes, higher propensity to intraventricular hemorrhage, and a higher risk of rebleeding. Although current guidelines recommend that OAC should be reversed as quickly as possible, many health care systems have not developed a process for optimizing that aspect of care. Methods: Through the IMPROVE Stroke Care Consortium, a group of nine Hub hospitals and their regional community hospitals, a systems of care improvement project was implemented. Performance reviews identified best practices which were disseminated throughout all centers. We compared the median door-to-reversal (DTR) time before and after an institutional campaign to speed the process with a target time of 60 minutes. Results: Over two years of the study, there were 6,699 ischemic strokes, 152 subarachnoid hemorrhages, and 889 intracranial hemorrhages. During that time, 36 hemorrhagic stroke patients received reversal agents emergently. The baseline median DTR time was 123 minutes (IQR 99, 361 minutes) for all comers. By the end of the program, the median DTR time had been reduced to 92.5 minutes (IQR 59, 163 minutes) which is a trend towards 59% reduction of DTR from baseline (p=0.08). Conclusions: Utilizing an integrated stroke systems of care approach we were able to reduce DTR times for patients presenting with acute ICH and concurrent use of anticoagulants in spite of the lack of definitive guidelines as to how quickly reversing agents should be given.

Abstract 33: Risk Scores And Brain Mri Markers In Distinguishing Ischemic Stroke And Intracerebral Hemorrhage Risk Among Atrial Fibrillation Patients: The Neuro-Afib Study

Background: Recent studies cast doubt on the accuracy of the most-commonly used risk scores (CHA 2 DS 2 -VASC and HAS-BLED) in differentiating the risk of acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH) among patients with fibrillation (AF). Because of the importance of AIS/ICH risk determination for choice of proper preventive approaches, we aimed to compare the value of these risk scores and brain MRI markers to differentiate the occurrence of AIS and ICH in a large cohort of AF-related strokes. Methods: The Neuro-AFib study is a multicenter effort to elucidate the causes and consequences of AIS and ICH in AF patients. Demographics, CHA 2 DS 2 -VASC and HAS-BLED scores, and ischemic/hemorrhagic brain MRI markers were compared between AF patients admitted with AIS and ICH to 15 academic stroke centers in the US between 1/2018-12/2019. Results: Of 5694 stroke admissions with AF, 4826 (84.8%) had AIS and 868 (15.2%) ICH. Mean age was similar between groups (75.9±11.5 vs 76.6±11.9, p=0.1), more ICH patients were male (57% vs 50%). Pre-index event CHA 2 DS 2 -VASC (4.14±1.6 vs 4.22±1.6) and HAS-BLED (2.71±1.09 vs 2.68±1.13) were similar between groups [both p&gt;0.2]. Cerebral microbleeds (CMB, 56% vs 33.5%), cortical superficial siderosis (cSS, 15% vs 9.4%), and moderate-to-severe leukoaraiosis (41% vs 33.4%) were more commonly found among ICH patients compared to AIS (all p&lt;0.001). Chronic lacunar infarcts (43.5% vs 39.5%, p=0.03) and chronic non-lacunar infarcts (29% vs 18%, p&lt;0.001) were more commonly found in AIS. In a multivariable logistic regression model that included all variables above, male sex, presence of CMBs, cSS, moderate-to-severe leukoaraiosis were associated with ICH, chronic non-lacunar infarcts with AIS (all p&lt;0.005), while CHA 2 DS 2 -VASC (p=0.9) and HAS-BLED (p=0.9) were not related to the stroke type. Conclusions: Data from our multicenter study confirm the lack of specificity of CHA 2 DS 2 -VASC and HAS-BLED to categorize the risk of AIS vs ICH in AF patients. The chronic MRI findings (CMB, cSS, moderate-to-severe leukoaraiosis, chronic infarcts) should be incorporated into risk scores, and their predictive value for AIS and ICH should be investigated in prospective studies to select optimal stroke prevention methods in AF patients.

Abstract 14: Determinants Of Withdrawal Of Life-sustaining Therapy After Acute Stroke

Introduction: The decision to withhold or withdraw life-sustaining therapy (WLST) is common after acute stroke. Factors that may influence the decision are not well determined. We aimed to investigate factors associated with WLST in hospitalized acute stroke patients. Methods: Patients with acute ischemic stroke (AIS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH) were included across 152 Florida hospitals participating in the prospective Florida Stroke Registry from 2008-2021. Importance plots were performed to generate the predictive factors associated with WLST. AUC-ROC curves were generated for the performance of logistic regression (LR) and random forest (RF) models. We used 75/15/15 for training/testing/validation. Results: Among 309,393 AIS patients, 47,485 ICH patients, and 16,694 SAH patients; 9%, 28%, and 19% subsequently had WLST during hospitalization. Patients who had WLST were older (77 vs. 69 years), more women (57% vs. 49%), more White (76% vs. 67%), greater stroke severity at presentation NIHSS ≥ 5 (29% vs.19%), more likely to be treated in comprehensive stroke centers (52% vs. 44%), more likely to have Medicare insurance (53% vs. 44%), less likely to be uninsured (8% vs. 13%), more likely to undergo surgical treatments (1.2% vs 0.3%), and more likely to have impaired level of consciousness (38% vs. 12%). The most predictive factors associated with the decision to WLST in AIS were age, stroke severity, state region, insurance status, stroke center type, race, and level of consciousness (RF AUC of .93 and LR AUC of .85). The most predictive factors in ICH were age, impaired level of consciousness, state region, race, insurance status, stroke center type, and ambulation status at baseline (RF AUC of .76 and LR AUC of .71). Most predictive factors in SAH were age, impaired level of consciousness, state region, insurance status, race, and stroke center type (RF AUC of .82 and LR AUC of .72). Conclusion: Among acute hospitalized stroke patients; age, level of consciousness, state region, race, insurance status, ambulation status at baseline, and stroke center type could contribute to the decision to WLST.

Abstract 156: Establishing An Informatics Framework For Longitudinal Cerebrovascular And Neurological Disease Research

Background: Although developments in computational big data methods have enhanced the ability to meaningfully extract information from hospital EMRs, there are inherent gaps in understanding care utilization and long-term patient outcomes outside of in-patient milieu, particularly across hospital systems. Methods: Utilizing registry data from a 7-hospital stroke certified healthcare system serving a large metropolitan, cohorts were identified for Medicare-insured patients with primary discharge diagnoses of acute ischemic stroke (AIS), intracerebral hemorrhage (ICH), or cerebral amyloid angiopathy (CAA). In collaboration with a CMS Qualified Entity which houses health care utilization data for over 80% of the state population (including 100% of Medicare Fee-for-Service), patient records were securely matched and linked. Socio-demographic and enrollment characteristics for matched cohorts are reported. Results: Medical records and claims data were matched for 98.4% of patients (n=6,531) admitted between 05/2016 and 12/2020 (n=5,789 AIS; 696 ICH; 46 CAA). Across all matched patients, the median (IQR) age at hospital admission was 76.0 (69.0-84.0) (54% female; 56% non-Hispanic White; 24% non-Hispanic Black; 13% Hispanic/Latino; median [IQR] Area Deprivation Index: 4 [2-6]). Age-based standard enrollment represented 86% of patients, with the remainder enrolled due to disability or health complications. Median (IQR) number of total years for patients with Part AB and D coverage was 6.9 (5.0-7.0) and 5.4 (2.9-7.0) years, respectively. At the time of reporting, all-cause death rates among Medicare enrollees who sought care are: 33% (AIS), 55% (ICH), and 41% (CAA). Conclusion: In the absence of systematically captured long-term outcomes data, health informatic pipelines that create linkages across multimodal sources provide a valuable framework for enabling longitudinal research on patients throughout and after stroke hospitalizations.

Abstract TP87: Predictors Of Diffusion-weighted Imaging Lesion Burden In Patients After Minimally Invasive Surgery For Intracerebral Hemorrhage

Introduction: The etiology of diffusion-weighted imaging (DWI) lesions in patients after minimally invasive surgery (MIS) for acute intracerebral hemorrhage (ICH) remains unclear. Methods: Postoperative brain MRIs of patients with spontaneous ICH from 2016-2021 who underwent imaging within one month of MIS were reviewed. DWI lesions were quantified. Lesions within 10 mm of the hematoma were excluded. Siderosis and microbleeds were identified. Leukoaraiosis was quantified using the Fazekas score. Univariate analyses were conducted to determine predictors of DWI lesion burden, and variables with P≤0.1 were included in multivariate analyses. Results: DWI lesions were present in 84 (49%) postoperative MRIs. The average number of DWI lesions was 2.11 (range 0-74, SD 6.50). Factors associated with DWI burden in univariate analyses included increased presenting systolic blood pressure (SBP) (P=0.003), Fazekas score (P=0.004), delta SBP on day of admission (P=0.034), preoperative angiogram (P=0.062), microbleeds on MRI (P=0.065), increased presenting National Institutes of Health Stroke Score (P=0.066), presence of intraventricular hemorrhage (P=0.069), and decreased presenting Glasgow Coma Scale (P=0.076). Upon multivariate analysis, increased Fazekas score (OR 2.04, 95% CI 1.21-3.43, P=0.008), presenting SBP (OR 1.04, 95% CI 1.00-1.06, P=0.014), and preoperative angiogram (OR 10.35, 95% CI 1.44-74.36], P=0.020) were predictive of DWI burden. Conclusions: In this unique postoperative ICH cohort, white matter changes, presenting SBP, and preoperative angiogram predicted DWI lesion burden. Larger studies are needed to understand the implications of DWI burden after MIS for ICH recovery.

Abstract TP120: Noncontrast Ct, Single-phase Cta, And Multiphase Cta Intracerebral Hemorrhage Expansion Scores

Background: Several noncontrast computed tomography (NCCT), single-phase computed tomography angiography (CTA), and multiphase CTA markers of intracerebral hemorrhage (ICH) expansion have been previously proposed. We derived and validated three scores for the prediction of hematoma expansion depending on the use of NCCT, single-phase CTA, or multiphase CTA markers of hematoma expansion. Methods: We prospective studied 276 consecutive patients with ICH within 6 hours from symptom onset. After deriving NCCT, single-phase CTA, and multiphase CTA scores in a 5-year period population (n=156), we validated them in a different 3-year period population (n=120). Outcome parameters included substantial hematoma expansion &gt;6 mL or &gt;33% at 24 hours (primary outcome) and poor outcome (mRS score &gt;2) at 90 days. Results: The most accurate marker of hematoma expansion was spot sign in phase 1 of multiphase CTA (80.3%). The four independent predictors of substantial hematoma expansion included in the different scores were ultraearly hematoma growth (uHG) &gt;5 mL/h, heterogeneous density, spot sign in phase 1 of multiphase CTA, and spot sign in any phase of multiphase CTA (Table). On each of the three scores, the proportion of patients that experienced substantial hematoma expansion increased with each point increase. C-index for both substantial hematoma expansion and poor outcome in the derivation and validation cohort was lower in NCCT expansion score than in single-phase CTA expansion score which, in turn, was lower than in multiphase CTA expansion score (Table). Conclusions: This study demonstrates the added prognostic value of more advanced CT modalities in acute ICH evaluation. Single-phase CTA score and, especially, multiphase CTA score, are more robust than NCCT score in the prediction of hematoma expansion and poor outcome. These scores may help to refine the selection of patients at risk of expansion and poorest outcomes in different decision-making scenarios.

Acute Spontaneous Lobar Cerebral Hemorrhages Present a Different Clinical Profile and a More Severe Early Prognosis than Deep Subcortical Intracerebral Hemorrhages-A Hospital-Based Stroke Registry Study.

Acute spontaneous intracerebral hemorrhage (ICH) is the most severe stroke subtype, with a high risk of death, dependence, and dementia. Knowledge about the clinical profile and early outcomes of ICH patients with lobar versus deep subcortical brain topography remains limited. In this study, we investigated the effects of ICH topography on demographics, cerebrovascular risk factors, clinical characteristics, and early outcomes in a sample of 298 consecutive acute ICH patients (165 with lobar and 133 with subcortical hemorrhagic stroke) available in a single-center-based stroke registry over 24 years. The multiple logistic regression analysis shows that variables independently associated with lobar ICH were early seizures (OR 6.81, CI 95% 1.27−5.15), chronic liver disease (OR 4.55, 95% CI 1.03−20.15), hemianopia (OR 2.55, 95% CI 1.26−5.15), headaches (OR 1.90, 95% CI 1.90, 95% IC 1.06−3.41), alcohol abuse (>80 gr/day) (OR 0−10, 95% CI 0.02−0,53), hypertension (OR 0,41, 95% CI 0.23−0−70), sensory deficit (OR 0.43, 95% CI 0.25−0.75), and limb weakness (OR: 0.47, 95% CI 0.24−0.93). The in-hospital mortality was 26.7% for lobar and 16.5% for subcortical ICH. The study confirmed that the clinical spectrum, prognosis, and early mortality of patients with ICH depend on the site of bleeding, with a more severe early prognosis in lobar intracerebral hemorrhage.

Diagnostic imaging strategies of acute intracerebral hemorrhage in European academic hospitals-a decision-making analysis.

To evaluate and compare which factors are relevant to the diagnostic decision-making and imaging workup of intracerebral hemorrhages in large, specialized European centers. Expert neuroradiologists from ten large, specialized centers (where endovascular stroke treatment is routinely performed) in nine European countries were selected in cooperation with the European Society of Neuroradiology (ESNR). The experts were asked to describe how and when they would investigate specific causes in a patient who presented with an acute, atraumatic, intracerebral hemorrhage for two given locations: (1) basal ganglia, thalamus, pons or cerebellum; (2) lobar hemorrhage. Answers were collected, and decision trees were compared. Criteria that were considered relevant for decision-making reflect recommendations from current guidelines and were similar in all participating centers. CT Angiography or MR angiography was considered essential by the majority of centers regardless of other factors. Imaging in clinical practice tended to surpass guideline recommendations and was heterogeneous among different centers, e.g., in a scenario suggestive of typical hypertensive hemorrhage, recommendations ranged from no further follow-up imaging to CT angiography and MR angiography. In no case was a consensus above 60% achieved. In European clinical practices, existing guidelines for diagnostic imaging strategies in ICH evaluation are followed as a basis but in most cases, additional imaging investigation is undertaken. Significant differences in imaging workup were observed among the centers. Results suggest a high level of awareness and caution regarding potentially underlying pathology other than hypertensive disease.

Increased serum pannexin-1 concentrations reflect illness severity and predict a poor prognosis after acute supratentorial intracerebral hemorrhage: A prospective longitudinal cohort study

BackgroundPannexin-1 is a nonselective, large pore and voltage gated channel protein, whose activation may aggravate acute brain injury. We ascertained the clinical significance of serum pannexin-1 as a prognostic biomarker of acute intracerebral hemorrhage (ICH). MethodsIn this prospective, observational study of 124 acute supratentorial ICH patients and 124 healthy controls, serum pannexin-1 concentrations were determined. Admission National Institutes of Health Stroke Scale (NIHSS) score and hematoma volume were used for assessment of hemorrhagic severity, post-stroke 6-month modified Rankin scale (mRS) score was registered to reflect clinical outcome and early neurologic deterioration (END) and 6-month poor outcome (mRS score of 3–6) were regarded as the 2 prognostic parameters. Their associations with serum pannexin-1 concentrations were investigated using multivariate analysis. The predictive performance was evaluated in terms of area under receiver operating characteristic curve (AUC). ResultsIn comparison to controls, significantly increased serum pannexin-1 concentrations after ICH (median, 6.8 vs. 2.7 mg/ml) were independently correlative with NIHSS score (β, 0.193; 95% CI: 0.086–0.300), hematoma volume (β, 0.641; 95% CI: 0.423–0.859) and mRS score (β, 0.199; 95% CI: 0.065–0.174), were independently predictive of END (OR, 1.176; 95% CI: 1.081–1.280) and poor outcome (odds ratio, 1.218; 95% CI: 1.059–1.400), as well as were efficiently discriminative of END (AUC, 0.764; 95% CI: 0.663–0.864) and poor 6-month outcome (AUC, 0.790; 95% CI: 0.711–0.870). Serum pannexin-1 combined with NIHSS score and hematoma volume (AUC, 0.908; 95% CI: 0.857–0.960) displayed significantly higher predictive ability for poor 6-month outcome than NIHSS score and hematoma volume alone (both P < 0.05). ConclusionRising serum pannexin-1 concentrations following ICH, in strong correlation with hemorrhagic severity, independently distinguish the risk of END and 90-day poor outcome. Assumably, serum pannexin-1 may represent a valuable prognostic biomarker of ICH.

Difference of mean Hounsfield units (dHU) between follow-up and initial noncontrast CT scan predicts 90-day poor outcome in spontaneous supratentorial acute intracerebral hemorrhage with deep convolutional neural networks

ObjectivesThis study aimed to investigate the usefulness of a new non-contrast CT scan (NCCT) sign called the dHU, which represented the difference in mean Hounsfield unit values between follow-up and the initial NCCT for predicting 90-day poor functional outcomes in acute supratentorial spontaneous intracerebral hemorrhage(sICH) using deep convolutional neural networks. MethodsA total of 377 consecutive patients with sICH from center 1 and 91 patients from center 2 (external validation set) were included. A receiver operating characteristic (ROC) analysis was performed to determine the critical value of dHU for predicting poor outcome at 90 days. Modified Rankin score (mRS) >3 or >2 was defined as the primary and secondary poor outcome, respectively. Two multivariate models were developed to test whether dHU was an independent predictor of the two unfavorable functional outcomes. ResultsThe ROC analysis showed that a dHU >2.5 was a critical value to predict the poor outcomes (mRS >3) in sICH. The sensitivity, specificity, and accuracy of dHU >2.5 for poor outcome prediction were 37.5%, 86.0%, and 70.6%, respectively. In multivariate models developed after adjusting for all elements of the ICH score and hematoma expansion, dHU >2.5 was an independent predictor of both primary and secondary poor outcomes (OR = 2.61, 95% CI [1.32,5.13], P = 0.006; OR = 2.63, 95% CI [1.36,5.10], P = 0.004, respectively). After adjustment for all possible significant predictors (p < 0.05) by univariate analysis, dHU >2.5 had a positive association with primary and secondary poor outcomes (OR = 3.25, 95% CI [1.52,6.98], P = 0.002; OR = 3.42, 95% CI [1.64,7.15], P = 0.001). ConclusionsThe dHU of hematoma based on serial CT scans is independently associated with poor outcomes after acute sICH, which may help predict clinical evolution and guide therapy for sICH patients.

Lymphocyte-Related Immunomodulatory Therapy with Siponimod (BAF-312) Improves Outcomes in Mice with Acute Intracerebral Hemorrhage.

Modulators of the sphingosine-1-phosphate receptor (S1PR) have been proposed as a promising strategy for treating stroke. However, the detailed mechanisms and the potential translational value of S1PR modulators for intracerebral hemorrhage (ICH) therapy warrant exploration. Using collagenase VII-S-induced ICH in the left striatum of mice, we investigated the effects of siponimod on cellular and molecular immunoinflammatory responses in the hemorrhagic brain in the presence or absence of anti-CD3 monoclonal antibodies (Abs). We also assessed the severity of short- and long-term brain injury and evaluated the efficacy of siponimod in long-term neurologic function. Siponimod treatment significantly decreased brain lesion volume and brain water content on day 3 and the volume of the residual lesion and brain atrophy on day 28. It also inhibited neuronal degeneration on day 3 and improved long-term neurologic function. These protective effects may be associated with a reduction in the expression of lymphotactin (XCL1) and T-helper 1 (Th1)-type cytokines (interleukin 1β and interferon-γ). It may also be associated with inhibition of neutrophil and lymphocyte infiltration and alleviation of T lymphocyte activation in perihematomal tissues on day 3. However, siponimod did not affect the infiltration of natural killer cells (NK) or the activation of CD3-negative immunocytes in perihematomal tissues. Furthermore, it did not influence the activation or proliferation of microglia or astrocytes around the hematoma on day 3. Siponimod appears to have a profound impact on infiltration and activation of T lymphocytes after ICH. The effects of neutralized anti-CD3 Abs-induced T-lymphocyte tolerance on siponimod immunomodulation further confirmed that siponimod alleviated the cellular and molecular Th1 response in the hemorrhagic brain. This study provides preclinical evidence that encourages future investigation of immunomodulators, including siponimod, which target the lymphocyte-related immunoinflammatory reaction in ICH therapy.

Safety and efficacy of brain biopsy: Results from a single institution retrospective cohort study

IntroductionBrain biopsy provides important histopathological diagnostic information for patients with new intracranial lesions. Although a minimally invasive technique, previous studies report an associated morbidity and mortality between 0.6% and 6.8%. We sought to characterise the risk linked to this procedure, and to establish the feasibility of instigating a day-case brain biopsy pathway at our institution. Materials and methodsThis single-centre retrospective case series study included neuronavigation guided mini craniotomy and frameless stereotactic brain biopsies carried out between April 2019 and December 2021. Exclusion criteria were interventions performed for non-neoplastic lesions. Demographic data, clinical and radiological presentation, type of biopsy, histology and complications in the post-operative period were recorded. ResultsData from 196 patients with a mean age of 58.7 years (SD+/-14.4 years) was analysed. 79% (n=155) were frameless stereotactic biopsies and 21% (n=41) neuronavigation guided mini craniotomy biopsies. Complications resulting in acute intracerebral haemorrhage and death, or new persistent neurological deficits were observed in 2% of patients (n=4; 2 frameless stereotactic; 2 open). Less severe complications or transient symptoms were noted in 2.5% of cases (n=5). 8 patients had minor haemorrhages in the biopsy tract with no clinical ramifications. Biopsy was non-diagnostic in 2.5% (n=5) of cases. Two cases were subsequently identified as lymphoma. Other reasons included insufficient sampling, necrotic tissue, and target error. Discussion and conclusionThis study demonstrates that brain biopsy is a procedure with an acceptably low rate of severe complications and mortality, in line with previously published literature. This supports the development of day-case pathway allowing improved patient flow, reducing the risk of iatrogenic complications associated with hospital stay, such as infection and thrombosis.

S-06-3: EMERGENT BLOOD PRESSURE LOWERING WITH INTRAVENOUS NICARDIPINE FOR JAPANESE PATIENTS WITH ACUTE INTRACEREBRAL HEMORRHAGE: AN INDIVIDUAL PARTICIPANT DATA ANALYSIS

Objective: Intensive lowering of elevated blood pressure is one of the few promising therapies for acute intracerebral hemorrhage. The effects of acute systolic blood pressure levels achieved with intravenous nicardipine for Japanese patients with acute intracerebral hemorrhage on clinical outcomes were determined. Design and method: A systematic review and individual participant data analysis of articles before October 1, 2020 identified on PubMed were performed (PROSPERO: CRD42020213857). Prospective studies involving adults developing hyperacute intracerebral hemorrhage who were treated with intravenous nicardipine whose outcome was assessed using the modified Rankin Scale were eligible. Outcomes included death or disability at 90 days, defined as the modified Rankin Scale score of 4–6, and hematoma expansion, defined as an increase 6 mL or more from baseline to 24-h computed tomography. In this study, data on Japanese patients were extracted. The study is registered with PROSPERO (CRD42020213857). Results: Three studies, ATACH-1, ATACH-2, and SAMURAI-ICH, met the eligibility criteria. Of 1,271 patients enrolled, 500 were registered from Japan, and all of these were Japanese. A patient with available data on the hourly blood pressures only for &lt; 4 timepoints was excluded, and the other 449 patients (age 64.9 ± 11.8 years, 183 women, initial BP 203.5v± 18.3 / 109.1 ± 17.2 mmHg) were studied. Death or disability occurred in 35.6%, and hematoma expansion occurred in 15.6%. Mean hourly systolic blood pressure during the initial 24 h was positively associated with death or disability (adjusted odds ratio 1.26, 95% confidence interval 1.04–1.53 per 10 mmHg) and hematoma expansion (1.47, 1.17–1.85). These odds ratios were relatively high as compared to the reported ones for global patients of this individual participant data analysis [1.12 (95% confidence interval 1.00–1.26) and 1.16 (1.02–1.32), respectively] (Toyoda K, et al: Int J Stroke 2021). Conclusions: Rapid lowering of systolic blood pressure by continuous administration of intravenous nicardipine during the initial 24 h was associated with lower risks of hematoma expansion and 90-day death or disability in Japanese patients with hyperacute intracerebral hemorrhage. The impact of systolic blood pressure lowering on better outcome seemed to be stronger in Japanese patients than the global ones.

The neuroprotective effects of rosuvastatin vs. metformin in diabetic rats with brain injury induced by acute intracerebral hemorrhage

The neuroprotective effects of rosuvastatin vs. metformin in diabetic rats with brain injury induced by acute intracerebral hemorrhage