Severe Intracerebral Hemorrhage Research Articles

Mitigating mitochondrial dysfunction and neuroinflammation by hematoma aspiration in a new surgical model for severe intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is associated with a large hematoma that causes compression, increased intracranial pressure (IICP), midline shift, and brain herniation, and may ultimately lead to death. Urgent surgical removal of the large hematoma can ameliorate these injuries, which would be life-saving, but has not improved clinical outcome. A suitable animal model that mimics the clinically relevant human severe ICH injury requiring surgical hematoma evacuation is urgently needed. Here, we established a novel model of severe ICH in rats allowing aspiration of the hematoma and studying the effects of mitochondrial dysfunction in ICH. Severe ICH was induced by intra-striatal injection of 0.6 U of collagenase in 3 μl sterile saline over 15 min. Aspiration of approximately 75 % of the total hematoma was performed 6 h after induction of severe ICH. The effects of hematoma aspiration on hematoma volume, mortality, oxidative stress, ATP levels, mitochondrial dysfunction, and neurological function were measured in rats. Severe ICH induction increased hematoma volume, neurological deficits, and mortality. Hematoma aspiration abolished mortality and significantly reduced hematoma volume, and neurological deficits. In addition, hematoma aspiration ameliorated the pronounced mitochondrial dysfunction responsible for the failure of energy production and excessive oxidative stress associated with severe hemorrhagic injury. Hematoma aspiration also modulated mitochondrial biogenesis and mitophagy, thereby promoting mitochondrial homeostasis. Markers of neuroinflammation, including iNOS, MMP9, and MPO, were elevated in severe ICH but attenuated by hematoma aspiration. This study established an animal model of severe ICH and provides valuable insights into the complex pathogenesis of severe ICH. The results showed that hematoma aspiration effectively ameliorates mitochondrial dysfunction, oxidative stress, and neuroinflammation, highlighting its potential as a therapeutic intervention.

Abstract 4145883: Elevated International Normalized Ratio Is Associated with Severity of Intracerebral Hemorrhage for Patients Taking Direct Oral Anticoagulants

Introduction/Background: While the international normalized ratio (INR), a marker of functioning of the extrinsic and final common pathways of the coagulation cascade is associated with increased intracerebral hemorrhage (ICH) mortality for patients taking warfarin, it is not understood how it might be associated with outcomes in patients taking direct oral anticoagulants (DOACs), given the inconsistent and variable effect of DOACs on INR. Research Questions/Hypothesis: To determine whether INR is associated with increased ICH severity in patients with recent exposure to a DOAC. Methods/Approach: We included patients taking Apixaban or Rivaroxaban prior to acute presentation with ICH to hospitals participating in the Get With the Guidelines - Stroke registry, a nationwide quality improvement registry. The primary exposure was INR, which we modeled as a continuous variable with restricted cubic splines. The primary endpoint was stroke severity on presentation, measured by the National Institutes of Health Stroke Scale (NIHSS). Secondary endpoints included Glasgow Coma Scale (GCS) <=8 on admission, in-hospital mortality, composite of in-hospital mortality and discharge to hospice, and modified Rankin Scale (mRS) at discharge. We adjusted for key confounding factors, specifically age, sex, race/ethnicity, insurance status, and medical history, while taking into account within-hospital clustering. Results/Data: In total, 13,251 patients were included of whom 7,545 were exposed to apixaban and 5,706 were exposed to rivaroxaban. As shown in Table 1, for patients taking Apixaban, elevated INR was associated with increased likelihood of NIHSS >=21 (aOR 1.02 [95% CI 1.00-1.04, p=0.03] per 0.1 above 1.1) and in-hospital mortality (aOR 1.11 [95% CI 1.05-1.16, p<.001) per 0.1 above 1.1). For patients taking Rivaroxaban, similar trends were seen (aOR 1.21 [95% CI 1.08-1.35, p<.001] per 0.1 up to 1.2 for NIHSS >=21, aOR 1.13, [95% CI 1.09-1.16, p<.001] per 0.1 up to 1.6, for in-hospital mortality). Conclusion(s): Elevated INR at admission is associated with worsened ICH severity for patients taking Apixaban or Rivaroxaban.

Association between serum glucose potassium ratio and mortality in critically ill patients with intracerebral hemorrhage

The effect of serum glucose-to-potassium ratio (GPR) on cerebrovascular diseases has been previously validated. However, the value of the GPR in patients with severe intracerebral hemorrhage (ICH) requiring ICU admission remains unclear. This study aimed to investigate the association between the GPR and the clinical prognosis of critically ill patients with ICH. This study identified patients with severe ICH requiring ICU admission from the Medical Information Mart for Intensive Care (MIMIC-IV) database and divided them into quartiles based on GPR levels. Outcomes included 30-day, 90-day, and 1-year mortality rates. The association between the GPR and clinical outcomes in critically ill patients with ICH was elucidated using Cox proportional hazards regression analysis and restricted cubic splines. In total, 2018 patients (53.8% male), with a median age of 70 years, were enrolled in the study. The 30-day, 90-day, and 1-year mortality rates were 23.9%, 30.1%, and 38.4%, respectively. Per multivariate Cox proportional hazards analysis, an elevated GPR was significantly associated with all-cause mortality. After adjusting for age, sex, Charlson Comorbidity Index, white blood cell count, red blood cell count, platelet count, and Glasgow Coma Scale, patients with an elevated GPR had a higher 30-day mortality (hazard ratio [HR]: 1.32; 95% confidence interval [CI]: 1.22–1.42; P < 0.001), 90-day mortality (HR: 1.27; 95% CI: 1.18–1.37; P < 0.001) and 1-year mortality (HR: 1.22; 95% CI: 1.14–1.31; P < 0.001) when analyzed as a continuous variable. Furthermore, analysis using restricted cubic splines demonstrated a consistent and progressive escalation in the risk of all-cause mortality with an elevated GPR. The GPR was significantly associated with short- and long-term all-cause mortality in critically ill patients with ICH. This finding demonstrates that GPR may be useful in identifying patients with ICH at a high risk of all-cause mortality.

Sex Modifies the Severity and Outcome of Spontaneous Intracerebral Hemorrhage.

The limited existing evidence on sex differences in the clinical characteristics of patients with spontaneous, non-traumatic intracerebral hemorrhage (ICH) comes from small, single-center studies. Here, we performed an individual patient data meta-analysis of 3 randomized clinical trials and 1 multi-ethnic observational study of ICH to investigate the impact of sex on ICH severity and outcome. Inclusion criteria in our study were a neuroimaging-confirmed ICH. We evaluated whether sex was associated with ICH severity (hematoma volume and expansion) and poor functional outcomes (modified Rankin Scale >3) 3 or 6 months after the ICH. A total of 4,812 ICH patients were evaluated (mean age 62, 40% female). Males with ICH were younger, more likely to be smokers and have diabetes, and less likely to be on anticoagulants (all p < 0.05). In multivariable analyses, male sex was associated with non-lobar location (odds ratio [OR]: 1.63; 95% confidence interval [CI]: [1.39-1.92]; p < 0.001), larger hemorrhages (beta: 0.16 [0.08-0.23]; p < 0.001) and a higher risk of hematoma expansion (OR: 1.43 [1.20-1.71]; p < 0.001). Despite the larger hemorrhage volume and higher risk of expansion, male sex was associated with a 24% lower risk of poor outcomes (OR: 0.76 [0.64-0.90]; p = 0.002). Compared to females, males with ICH have larger bleeds and higher risk of hematoma expansion. Despite the larger bleeds and higher risk of hematoma expansion, males with ICH have lower risk of poor outcomes. Our results suggest that the biology and clinical trajectory are different in females and males with ICH, supporting sex-specific research in this condition. ANN NEUROL 2024.

High-Volume Hospital Had Lower Mortality of Severe Intracerebral Hemorrhage Patients.

Intracerebral hemorrhage (ICH) accompanies higher mortality rates than other type of stroke. This study aimed to investigate the association between hospital volume and mortality for cases of ICH. We used nationwide data from 2013 to 2018 to compare high-volume hospitals (≥32 admissions/year) and low-volume hospitals (<32 admissions/year). We tracked patients' survival at 3-month, 1-year, 2-year, and 4-year endpoints. The survival of ICH patients was analyzed at 3-month, 1-year, 2-year, and 4-year endpoints using Kaplan-Meier survival analysis. Multivariable logistic regression analysis and Cox regression analysis were performed to determine predictive factors of poor outcomes at discharge and death. Among 9086 ICH patients who admitted to hospital during 18-month period, 6756 (74.4%) and 2330 (25.6%) patients were admitted to high-volume and low-volume hospitals. The mortality of total ICH patients was 18.25%, 23.87%, 27.88%, and 35.74% at the 3-month, 1-year, 2-year, and 4-year, respectively. In multivariate logistic analysis, high-volume hospitals had lower poor functional outcome at discharge than low-volume hospitals (odds ratio, 0.80; 95% confidence interval, 0.72-0.91; p<0.001). In the Cox analysis, high-volume hospitals had significantly lower 3-month, 1-year, 2-year, and 4-year mortality than low-volume hospitals (p<0.05). The poor outcome at discharge, short- and long-term mortality in ICH patients differed according to hospital volume. High-volume hospitals showed lower rates of mortality for ICH patients, particularly those with severe clinical status.

Cardiac troponin elevation in intracerebral hemorrhage patients may rather reflect acute myocardial damage than acute myocardial infarction

Abstract Background Patients with acute ischemic stroke (AIS) and elevated cardiac troponin (cTn) have worse functional and mortality-related outcome. While elevated cTn is also frequently observed in patients with intracerebral hemorrhage (ICH), routine invasive coronary angiography should not be performed on these patients. Existing data on correlation of cTn elevation with patient outcome and the underlying causes in this specific patient group are sparse and largely heterogeneous. Purpose To investigate the clinical variables that predict cTn elevation in patients with ICH and the impact of cTn elevation on intrahospital mortality and functional outcome. Methods Our long-term Stroke Database was screened for ICH patients with high-sensitivity (hs) cTn measurement on admission (from 2015 onwards). Baseline characteristics, intrahospital mortality and functional outcome at discharge were compared between the groups with and without cTn elevation (hs-cTnI &amp;gt; vs. ≤0.045 µg/L). In addition, clinical variables with suspected significance for cTn elevation were analyzed for their predictive value. Results A total of 93/498 patients with ICH (18.7%; mean age 73±15 years, 53.8% females) were found to have a cTn elevation. Regarding etiology, 38.7% had an ICH occurring after AIS and 31.2% had a hypertensive ICH (each p=NS between groups). Patients with cTn elevation did not have a more pronounced cardiovascular risk profile and had a comparably low prevalence of coronary artery disease (CAD; 18.5%, p=NS). However, they were significantly less likely to be on oral anticoagulation at the time of the bleeding event (7.5 vs. 18.0%, p=0.013). CTn elevation had no negative impact on intrahospital mortality (21.5 vs. 20.5%, p=NS) or functional outcome at discharge (NIHSS score 10 (2; 26) vs. 9 (2; 22) points, mRS 5 (3; 5) vs. 5 (3; 5) points, each p=NS). Increasing NIHSS score on admission (p=0.021, OR 1.084 [1.012-1.160]), mRS ≥4 on admission (p=0.005, OR 2.207 [1.180-2.826]), infratentorial bleeding localization (p=0.034, OR 4.899 [1.132-21.207]) and aortic valve stenosis ≥ intermediate (p&amp;lt;0.001, OR 8.435 [2.429-29.294]) predicted cTn elevation. In contrast, severely impaired left ventricular function, CAD, atrial fibrillation, intraventricular hemorrhage or ICH occurring after AIS had no predictive value. Conclusions Almost one fifth of patients with ICH had an elevated cTn. Unlike in AIS, in ICH cTn elevation was not associated with a worse functional or mortality-related intrahospital outcome. In particular, severe functional impairment on admission, reflecting severe ICH, or infratentorial hemorrhage localization, thought to affect the autonomic nervous system, was predictive of concomitant myocardial cell damage. CAD was rare overall. This could indicate that the cTn elevation in connection with ICH is primarily related to acute myocardial damage along the brain-heart axis and less to myocardial infarction.

Stroke severity and outcomes in patients with intracerebral hemorrhage on anticoagulants and antiplatelet agents: an analysis from the Japan Stroke Data Bank.

Some patients with intracerebral hemorrhage are on antithrombotic agents at the time of the event and these may worsen outcome, but the relative risk of different oral anticoagulants and antiplatelet agents is uncertain. We determined associations between pre-onset intake of antithrombotic agents and initial stroke severity, and outcomes, in patients with intracerebral hemorrhage. Patients with intracerebral hemorrhage admitted within 24 hours after onset between January 2017 and December 2020 and recruited to the Japan Stroke Data Bank, a hospital-based multicenter prospective registry, were included. Enrolled patients were classified into four groups based on the type of antithrombotic agents being used on admission. The outcomes were the National Institutes of Health Stroke Scale (NIHSS) score on admission and modified Rankin Scale (mRS) of 5-6 at discharge. Of a total 9,810 patients with intracerebral hemorrhage (4,267 females; mean age, 70±15 years), 77.1% were classified into the no-antithrombotic group, 13.2% into the antiplatelet group, 4.0% into the warfarin group, and 5.8% into the direct oral anticoagulant (DOAC) group. Median (interquartile range) NIHSS score on admission was 12 (5-22), 13 (5-26), 15 (5-30), and 13 (6-24), respectively, in the four groups. In multivariable analysis, the pre stroke warfarin use was associated with higher NIHSS score (adjusted incidence rate ratio, 1.09 [95%confidence interval (CI), 1.06-1.13], with the no-antithrombotic group as the reference), but the antiplatelet group (1.00 [95%CI, 0.98-1.02]) and DOAC group (0.98 [95%CI, 0.95-1.01]) was not. The rate of mRS 5-6 at discharge was 30.8%, 41.9%, 48.6%, and 41.5%, respectively, in the four groups. In multivariable analysis, pre stroke warfarin use was associated with mRS 5-6 (adjusted odds ratio: 1.90 [95%CI, 1.28-2.81], with the no-antithrombotic group as the reference), but the antiplatelet group (1.12 [95%CI, 0.91-1.37]) and DOAC group (1.25 [95%CI, 0.88-1.77]) was not. Patients who were taking warfarin prior to intracerebral hemorrhage onset suffered more severe intracerebral hemorrhage as evidenced by higher admission NIHSS and higher discharge mRS. In contrast, no increase in severity was seen with antiplatelet agents.

Patients with acute intracerebral hemorrhage and severe symptoms are highly sensitive to prehospital delay. A subgroup analysis from the RESIST and TRIAGE-STROKE trials

BackgroundPatients with a positive prehospital stroke severity score and underlying intracerebral hemorrhage (ICH) may be harmed by longer onset-to-admission time. We aimed to investigate the interaction between ICH severity and time from onset to admission on functional outcome.MethodsThis is an individual patient data analysis with data from two randomized prehospital stroke trials using the same prehospital stroke scale. Patients were stratified according to the presence of a positive stroke severity score. They were grouped into early arrivers (admitted ≤ 90 min from onset) and late arrivers (admitted ≥90 min after onset). The primary outcome was a shift toward a better functional outcome on the modified Rankin Scale (mRS).ResultsA total of 212 patients had ICH. A positive stroke severity score was seen in 123 of these patients. Patients with ICH and a positive prehospital stroke severity score had a significantly worse outcome if they arrived 90 min or later at the hospital (adjusted odds ratio [aOR]: 2.02, 95% CI [1.01, 4.12]). This difference was not observed in patients without a positive severity score (aOR: 0.50, 95% CI [0.22, 1.14]). Patients with a positive score also had an increased risk of death or severe dependency (mRS of 5–6) of 9.1 percentage points (95% CI [−1.6%, 19.8%]) per hour if they were diagnosed with ICH.ConclusionLonger onset-to-admission time was harmful for patients with ICH and a positive prehospital stroke severity score.

Heart Rate Variability and Functional Outcomes of Patients with Spontaneous Intracerebral Hemorrhage.

The relationship between heart rate variability (HRV) changes potentially indicating autonomic dysregulation following spontaneous intracerebral hemorrhage (ICH) and functional outcome has not yet been fully elucidated. This study investigated the effects of HRV during the initial 96 h after admission on 90-day functional outcome in ICH patients. We included patients with spontaneous ICH in a prospective cohort single-center study. Continuous HR data were retrieved from the Intellispace Critical Care and Anesthesia information system (Philips Healthcare) and analyzed within the following time intervals: 0-2, 0-8, 0-12, 0-24, 0-48, 0-72, and 8-16, 16-24, 24-48, 48-72, 72-96 h after admission. HRV was determined from all available HR values by calculating the successive variability (SV), standard deviation (SD), and coefficient of variation (CV). Low HRV was set as SD ≤ 11.4 ms, and high HRV as SD > 11.4 ms. The clinical severity of ICH was assessed using the National Institutes of Health Stroke Scale (NIHSS) and functional outcome using the modified Rankin Scale (mRS). Good functional outcome was defined as mRS 0-2. The cohort included 261 ICH patients (mean age ± SD 69.6 ± 16.5 years, 48.7% female, median NIHSS 6 (2, 12), median ICH score 1 (0, 2), of whom 106 (40.6%) had good functional outcome. All patients had the lowest HRV at admission, which increased during the first two days. Comparing ICH patients with low HRV (n = 141) and high HRV (n = 118), those with good outcome showed significantly lower HRV during the first three days (0-72 h: HRV SD good outcome 10.6 ± 3.5 ms vs. poor outcome 12.0 ± 4.0 ms; p = 0.004). Logistic regression revealed that advanced age, high premorbid mRS, and high NIHSS at admission were significant predictors of poor functional outcome, while reduced SD of HRV showed a non-significant trend towards good functional outcome (0-72 h: OR 0.898; CI 0.800-1.008; p = 0.067). Our results indicate autonomic dysfunction with sympathetic hyperactivity after spontaneous ICH, as reflected by the evidence of the lower HRV in the first days. Initially increased sympathetic tone appears to have a protective effect, as suggested by the comparatively lower HRV in patients with good functional outcome at the first days.

The Role of Systemic Inflammation in the Pathogenesis of Spontaneous Intracranial Hemorrhage in the Presence or Absence of Effective Cerebral Blood Flow.

Background: Spontaneous intracerebral hemorrhage (ICH) is one of the leading causes of mortality in intensive care units. The role of systemic hyperintense inflammation (SHI) in the pathogenesis of critical complications of ICH remains a poorly understood problem. There is a specific variant of severe ICH associated with increased intracranial pressure and occlusion of intracranial vessels, defined as ineffective cerebral blood flow (IECBF). Methods: To evaluate the role of SHI in the pathogenesis of severe (comatose) ICH in a dynamic comparison of patients with IECBF (n-26) and without IECBF (n-52). The SHI integral score criterion (SI scale) was used, including certain values of plasma concentrations of IL-6, IL-8, IL-10; TNF-α, PCT, cortisol, myoglobin, troponin I, D-dimer, and, additionally, SOFA scale values. Blood levels of ACTH and neuron-specific enolase (NSE) were also assessed. Results: Twenty-eight-day mortality in severe ICH reached 84.6% (without IECBF) and 96.2% (with IECBF). Clear signs of SHI were detected in 61.5%/87.8% (without IECBF) and 0.0%/8.7% (with IECBF) within 1-3/5-8 days from the onset of ICH manifestation. The lower probability of developing SHI in the IECBF group was associated with low blood NSE concentrations. Conclusions: The development of SHI in ICH is pathogenetically related to the permeability of the blood-brain barrier for tissue breakdown products and other neuroinflammatory factors.

Anemia From Inflammation After Intracerebral Hemorrhage and Relationships With Outcome.

Baseline anemia is associated with poor intracerebral hemorrhage (ICH) outcomes. However, underlying drivers for anemia and whether anemia development after ICH impacts clinical outcomes are unknown. We hypothesized that inflammation drives anemia development after ICH and assessed their relationship to outcomes. Patients with serial hemoglobin and iron biomarker concentrations from the HIDEF (High-Dose Deferoxamine in Intracerebral Hemorrhage) trial were analyzed. Adjusted linear mixed models assessed laboratory changes over time. Of 42 patients, significant decrements in hemoglobin occurred with anemia increasing from 19% to 45% by day 5. Anemia of inflammation iron biomarker criteria was met in 88%. A separate cohort of 521 patients with ICH with more granular serial hemoglobin and long-term neurological outcome data was also investigated. Separate regression models assessed whether (1) systemic inflammatory response syndrome (SIRS) scores related to hemoglobin changes over time and (2) hemoglobin changes related to poor 90-day outcome. In this cohort, anemia prevalence increased from 30% to 71% within 2 days of admission yet persisted beyond this time. Elevated systemic inflammatory response syndrome was associated with greater hemoglobin decrements over time (adjusted parameter estimate: -0.27 [95% CI, -0.37 to -0.17]) and greater hemoglobin decrements were associated with poor outcomes (adjusted odds ratio per 1 g/dL increase, 0.76 [95% CI, 0.62-0.93]) independent to inflammation and ICH severity. We identified novel findings that acute anemia development after ICH is common, rapid, and related to inflammation. Because anemia development is associated with poor outcomes, further work is required to clarify if anemia, or its underlying drivers, are modifiable treatment targets that can improve ICH outcomes. https://www.clinicaltrials.gov Unique identifier: NCT01662895.

The clinical value of nutritional and inflammatory indicators in predicting pneumonia among patients with intracerebral hemorrhage

Immunosuppression and malnutrition play pivotal roles in the complications of intracerebral hemorrhage (ICH) and are intricately linked to the development of stroke-associated pneumonia (SAP). Inflammatory markers, including NLR (neutrophil-to-lymphocyte ratio), SII (systemic immune inflammation index), SIRI (systemic inflammatory response index), and SIS (systemic inflammation score), along with nutritional indexes such as CONUT (controlling nutritional status) and PNI (prognostic nutritional index), are crucial indicators influencing the inflammatory state following ICH. In this study, our objective was to compare the predictive efficacy of inflammatory and nutritional indices for SAP in ICH patients, aiming to determine and explore their clinical utility in early pneumonia detection. Patients with severe ICH requiring ICU admission were screened from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. The outcomes included the occurrence of SAP and in-hospital death. Receiver operating characteristic (ROC) analysis, multivariate logistic regression, smooth curve analysis, and stratified analysis were employed to investigate the relationship between the CONUT index and the clinical outcomes of patients with severe ICH. A total of 348 patients were enrolled in the study. The incidence of SAP was 21.3%, and the in-hospital mortality rate was 17.0%. Among these indicators, multiple regression analysis revealed that CONUT, PNI, and SIRI were independently associated with SAP. Further ROC curve analysis demonstrated that CONUT (AUC 0.6743, 95% CI 0.6079–0.7408) exhibited the most robust predictive ability for SAP in patients with ICH. Threshold analysis revealed that when CONUT < 6, an increase of 1 point in CONUT was associated with a 1.39 times higher risk of SAP. Similarly, our findings indicate that CONUT has the potential to predict the prognosis of patients with ICH. Among the inflammatory and nutritional markers, CONUT stands out as the most reliable predictor of SAP in patients with ICH. Additionally, it proves to be a valuable indicator for assessing the prognosis of patients with ICH.

Serum secretoneurin as a promising biomarker for predicting poor prognosis in intracerebral hemorrhage: A prospective cohort study

ObjectiveSecretoneurin may play a brain-protective role. We aim to discover the relationship between serum secretoneurin levels and severity plus neurological outcome after intracerebral hemorrhage (ICH).MethodsIn this prospective cohort study, serum secretoneurin levels were measured in 110 ICH patients and 110 healthy controls. Glasgow Coma Scale (GCS) and hematoma volume were used to assess stroke severity. Poor prognosis was defined as Glasgow Outcome Scale (GOS) scores of 1–3 at 90 days after ICH. A multivariate logistic regression model was constructed to determine independent correlation of serum secretoneurin levels with severity and poor prognosis. Under receiver operating characteristic (ROC) curve, prognostic ability of serum secretoneurin levels was assessed. Restricted cubic spline (RCS) model and subgroups analysis were used for discovering association of serum secretoneurin levels with risk of poor prognosis. Calibration curve and decision curve were evaluated to confirm performance of nomogram.ResultsSerum secretoneurin levels of patients were significantly higher than those of healthy controls. Serum secretoneurin levels of patients were independently correlated with GCS scores and hematoma volume. There were 42 patients with poor prognosis at 90 days following ICH. Serum secretoneurin levels were significantly higher in patients with poor outcome than in those with good outcome. Under the ROC curve, serum secretoneurin levels significantly differentiated poor outcome. Serum secretoneurin levels ≥ 22.8 ng/mL distinguished patients at risk of poor prognosis at 90 days with a sensitivity of 66.2% and a specificity of 81.0%. Besides, serum secretoneurin levels independently predicted a 90-day poor prognosis. Subgroup analysis showed that serum secretoneurin levels had non-significant interactions with other variables. The nomogram, including independent prognostic predictors, showed reliable prognosis capability using calibration curve and decision curve. Area under the curve of the predictive model was significantly higher than those of GCS scores and hematoma volume.ConclusionSerum secretoneurin levels are strongly related to ICH severity and poor prognosis at 90 days after ICH. Thus, serum secretoneurin may be a promising prognostic biomarker in ICH.

A prospective cohort study regarding usability of serum RIPK3 as a biomarker in relation to early hematoma growth and neurological outcomes after acute intracerebral hemorrhage

ObjectiveThe receptor-interacting protein kinase 3 (RIPK3) is a pivotal component for triggering necroptosis. We intended to investigate predictive effects of serum RIPK3 levels on early hematoma growth (EHG) and poor neurological outcome after acute intracerebral hemorrhage (ICH). MethodsIn this prospective cohort study, 183 ICH patients and 100 controls were enrolled for measuring serum RIPK3 levels. National Institutes of Health Stroke Scale (NIHSS) and hematoma volume were recorded as the severity indicators. EHG and poststroke 6-month unfavorable outcome (modified Rankin Scale scores of 3–6) were registered as the two prognostic parameters. Multivariate analyses were implemented to discern relevance of serum RIPK3 to ICH severity and prognosis. ResultsSerum RIPK3 levels of patients, which were dramatically higher than those of controls, were independently related to NIHSS scores, hematoma volume, EHG, 6-month mRS scores and unfavorable outcome. Risks of EHG and unfavorable outcome were linearly pertinent to and efficiently discriminated by RIPK3 levels under restricted cubic spline and receiver operating characteristic curve respectively. RIPK3 levels nonsignificantly interacted with age, gender, hypertension, etc. Predictive ability of RIPK3 levels resembled those of NIHSS scores and hematoma volume. The prediction models, in which serum RIPK3, NIHSS scores and hematoma volume were integrated, were visually displayed via nomograms. The models’ predictive capabilities substantially surpassed that of serum RIPK3, NIHSS scores and hematoma volumes alone. The models kept stable under calibration curve. ConclusionA profound increase of serum RIPK3 levels after ICH is tightly relevant to severity, EHG and poor neurological outcomes, assuming that serum RIPK3 may emerge as a valuable prognostic predictor of ICH.

Admission Viscoelastic Hemostatic Assay Parameters Predict Poor Long-Term Intracerebral Hemorrhage Outcomes.

Viscoelastic hemostatic assays (VHAs) provide more comprehensive assessments of coagulation compared with conventional coagulation assays. Although VHAs have enabled guided hemorrhage control therapies, improving clinical outcomes in life-threatening hemorrhage, the role of VHAs in intracerebral hemorrhage (ICH) is unclear. If VHAs can identify coagulation abnormalities relevant for ICH outcomes, this would support the need to investigate the role of VHAs in ICH treatment paradigms. Thus, we investigated whether VHA assessments of coagulation relate to long-term ICH outcomes. Patients with spontaneous ICH enrolled into a single-center cohort study receiving admission Rotational Thromboelastometry (ROTEM) VHA testing between 2013 and 2020 were assessed. Patients with previous anticoagulant use or coagulopathy on conventional coagulation assays were excluded. Primary ROTEM exposure variables were coagulation kinetics and clot strength assessments. Poor long-term outcome was defined as modified Rankin Scale ≥ 4 at 6months. Logistic regression analyses assessed associations of ROTEM parameters with clinical outcomes after adjusting for ICH severity and hemoglobin concentration. Of 44 patients analyzed, the mean age was 64years, 57% were female, and the median ICH volume was 23mL. Poor 6-month outcome was seen in 64% of patients. In our multivariable regression models, slower, prolonged coagulation kinetics (adjusted odds ratio for every second increase in clot formation time 1.04, 95% confidence interval 1.00-1.09, p = 0.04) and weaker clot strength (adjusted odds ratio for every millimeter increase of maximum clot firmness 0.84, 95% confidence interval 0.71-0.99, p = 0.03) were separately associated with poor long-term outcomes. Slower, prolonged coagulation kinetics and weaker clot strength on admission VHA ROTEM testing, not attributable to anticoagulant use, were associated with poor long-term outcomes after ICH. Further work is needed to clarify the generalizability and the underlying mechanisms of these VHA findings to assess whether VHA-guided treatments should be incorporated into ICH care.

The Relationship between Vitamin D Serum Levels, Disease Severity, and Bleeding Volume in Patients with Intracerebral Hemorrhage

Background: Stroke is the main cause of death and disability worldwide. Intracerebral hemorrhage (ICH) is a subtype that contributes to 10 to 20% of all stroke events. Meanwhile, several studies in Indonesia show that the rates of vitamin D deficiency and insufficiency are still high, at 60.6% and 33.3% respectively in young adults. Several studies have shown vitamin D deficiency during hospital admission is a potential biomarker for poor functional outcomes in patients with acute ischemic stroke or ICH. This research aimed to analyze the relationship between serum vitamin D levels, disease severity, and bleeding volume of ICH patients. Methods: The study design was cross-sectional to assess the relationship between serum vitamin D levels, categorized as deficiency (&lt;20 ng/mL), insufficiency (20-30 ng/mL), and normal (&gt;30 ng/mL), with the severity of ICH as assessed by the NIHSS score and bleeding volume on head CT scans. Results: From a total of 31 patients, the Spearman correlation test of the relationship between vitamin D levels and NIHSS scores obtained a weak correlation (r=0.127; p=0.494). The Kruskal Wallis test showed that there was no significant difference in the mean value of NIHSS scores in the vitamin D level categories (p=0.310). The Spearman correlation test of the relationship between vitamin D levels and bleeding volume obtained a weak correlation with an (r=0.044; p=0.823). The Kruskal Wallis test showed there was no significant difference in the mean value of bleeding volume in the vitamin D level category (p=0.439). Conclusion: There is no relationship between serum vitamin D levels, disease severity, and bleeding volume in ICH patients. Further research is needed to analyze the relationship between vitamin D serum levels and the severity of ICH with a retrospective cohort study design and discuss the effect of vitamin D on long-term functional outcomes.

Higher blood glucose is associated with the severity of hemorrhagic transformation after endovascular therapy for stroke

ObjectivesHyperglycemia is associated with poor outcome in large vessel occlusion (LVO) stroke, with mechanism for this effect unknown. Materials and methodsWe used our prospective, multicenter, observational study, Blood Pressure After Endovascular Stroke Therapy (BEST), of anterior circulation LVO stroke undergoing endovascular therapy (EVT) from 11/2017-7/2018 to determine association between increasing blood glucose (BG) and intracerebral hemorrhage (ICH). Our primary outcome was degree of ICH, classified as none, asymptomatic ICH, or symptomatic ICH (≥4-point increase in National Institutes of Health Stroke Scale [NIHSS] at 24 h with any hemorrhage on imaging). Secondary outcomes included 24 h NIHSS, early neurologic recovery (ENR, NIHSS 0-1 or NIHSS reduction by ≥8 within 24 h), and 90-day modified Rankin Scale (mRS) using univariate and multivariable regression. ResultsOf 485 enrolled patients, increasing BG was associated with increasing severity of ICH (adjusted OR, aOR 1.06, 95 % CI 1.02-1.1, p < 0.001), higher 24 h NIHSS (aOR 1.22, 95 % CI 1.11-1.34, p < 0.001), ENR (aOR 0.90, 95 % CI 0.82-1.00, p < 0.002), and 90-day mRS (aOR 1.06, 95 % CI 1.03-1.09, p < 0.001) when adjusted for age, presenting NIHSS, ASPECTS, 24-hour peak systolic blood pressure, time from last known well, and successful recanalization. ConclusionsIn the BEST study, increasing BG was associated with greater odds of increasing ICH severity. Further study is warranted to determine whether treatment of will decrease ICH severity following EVT.

Continuous arterial blood pressure indices and early hematoma expansion in patients with spontaneous intracerebral hemorrhage

ObjectiveBlood pressure variability (BPV) and its potential association with early hematoma expansion (HE) in intracerebral hemorrhage (ICH) remains to be fully elucidated. Our study explores the potential link between BPV within the first 24 h after admission and HE in ICH. MethodsIn a prospective cohort single-center study, we analyzed consecutive patients with spontaneous ICH. Continuous BP data via an arterial line extracted from the Intellispace Critical Care and Anesthesia information system (Philips Healthcare) were analyzed over 0–2, 0–8, 0–12, and 0–24 h intervals post-admission. BPV was assessed through successive variability (SV), standard deviation (SD), and coefficient of variation (CV) using all available BP measurements. Early HE was defined as an absolute [≥ 6 ml] or relative [≥ 33 %] increase in ICH volume on 24-hours follow-up brain imaging. Secondary endpoints were the influence of BP on admission and other potential risk factors for HE. ResultsAmong 305 ICH-patients (mean age ± SD 70.1 ± 14.9 years, 47.9 % female, median NIHSS 6 (3, 13), median ICH score 1 (1, 2)), 41 (13.4 %) experienced HE. HE-patients had higher NIHSS (p = 0.015), ICH-score (p = 0.005), ICH volume (p < 0.001) and higher pre-anticoagulation treatment (p = 0.004) on admission. There was no difference in BPV comparing ICH-patients with HE to those without. However, patients with HE had significantly lower diastolic BP (76.6 ± 14.8 vs. 86.3 ± 19.7 mmHg, p = 0.005) and MAP (103.2 ± 22.4 vs. 112.2 ± 22.6, p = 0.027) on admission. This pattern of lower diastolic BP persisted across the first 24 h. Logistic regression revealed larger ICH volume and pre-existing anticoagulation as significant predictors of HE, with higher initial diastolic BP reducing HE risk. Hemorrhages ≥ 30 cm3 showed significantly lower initial diastolic BP, MAP, and BPV across all time frames compared to ICH < 30 cm3. ConclusionsBPV within the first 24 h was not associated with HE. Lower diastolic BP on admission, anticoagulation use, and larger ICH volume are potential predictors for HE. However, larger hemorrhage size (>30 cm3) experienced lower absolute BP and BPV indices and worse clinical outcomes. These findings suggest a nuanced relationship between BP dynamics and ICH severity, underscoring the need for individualized BP management in acute ICH care. Further research is necessary to explore these relationships and optimize treatment strategies.

Examining Transcriptomic Alterations in Rat Models of Intracerebral Hemorrhage and Severe Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is a life-threatening condition associated with significant morbidity and mortality. This study investigates transcriptomic alterations in rodent models of ICH and severe ICH to shed light on the genetic pathways involved in hemorrhagic brain injury. We performed principal component analysis, revealing distinct principal component segments of normal rats compared to ICH and severe ICH rats. We employed heatmaps and volcano plots to identify differentially expressed genes and utilized bar plots and KEGG pathway analysis to elucidate the molecular pathways involved. We identified a multitude of differentially expressed genes in both the ICH and severe ICH models. Our results revealed 5679 common genes among the normal, ICH, and severe ICH groups in the upregulated genes group, and 1196 common genes in the downregulated genes, respectively. A volcano plot comparing these groups further highlighted common genes, including PDPN, TIMP1, SERPINE1, TUBB6, and CD44. These findings underscore the complex interplay of genes involved in inflammation, oxidative stress, and neuronal damage. Furthermore, pathway enrichment analysis uncovered key signaling pathways, including the TNF signaling pathway, protein processing in the endoplasmic reticulum, MAPK signaling pathway, and Fc gamma R-mediated phagocytosis, implicated in the pathogenesis of ICH.

Unveiling the Hidden Impact: Hematoma Volumes Unravel Circuit Disruptions in Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) imposes a significant burden on patients, and the volume of hematoma plays a crucial role in determining the severity and prognosis of ICH. Although significant recent progress has been made in understanding the cellular and molecular mechanisms of surrounding brain tissue in ICH, our current knowledge regarding the precise impact of hematoma volumes on neural circuit damage remains limited. Here, using a viral tracing technique in a mouse model of striatum ICH, two distinct patterns of injury response were observed in upstream connectivity, characterized by both linear and nonlinear trends in specific brain areas. Notably, even low-volume hematomas had a substantial impact on downstream connectivity. Neurons in the striatum-ICH region exhibited heightened excitability, evidenced by electrophysiological measurements and changes in metabolic markers. Furthermore, a strong linear relationship (R2 = 0.91) was observed between hematoma volumes and NFL damage, suggesting a novel biochemical index for evaluating changes in neural injury. RNA sequencing analysis revealed the activation of the MAPK signaling pathway following hematoma, and the addition of MAPK inhibitor revealed a decrease in neuronal circuit damage, leading to alleviation of motor dysfunction in mice. Taken together, our study highlights the crucial role of hematoma size as a determinant of circuit injury in ICH. These findings have important implications for clinical evaluations and treatment strategies, offering opportunities for precise therapeutic approaches to mitigate the detrimental effects of ICH and improve patient outcomes.