Intracerebral Hemorrhage Research Articles

Prognostic Value of Blood Parameters in Patients Diagnosed with Ischemic and Hemorrhagic Cerebrovascular Events

INTRODUCTION Cerebral infarction is defined as an acute neurological injury stroke that occurs as a result of intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). 80-85% of stroke cases are ischemic group. Hemorrhagic stroke is responsible for approximately 10-30% of these cases. Studies have shown that the inflammatory response that occurs exacerbates ischemic brain injury and neurological dysfunction. MATERIALS AND METHODS Patients who were admitted to a tertiary state hospital in Istanbul in the last six months and diagnosed with stroke were retrospectively analyzed. Blood samples taken at the time of admission of 116 patients with stroke diagnosed in the study were examined and neutrophil and lymphocyte values in the complete blood count were used in the study. Neutrophil/Lymphocyte ratios (NLR) were calculated by subtracting these values. Hospitalization times of the patients were recorded. The correlation of NLR values of the cases with the length of hospital stay was examined. RESULTS Of the 116 patients included in the study, 100 had ischemic stroke and 16 had hemorrhagic stroke. Of the cases examined, 63 were male and 53 were female. The mean age was 71.6±11.6 years. There was no statistically significant difference between hemorrhagic stroke and ischemic stroke groups in terms of age and gender. We examined the correlation between the length of hospital stay and NLR values of the patients. We found that there was no statistically significant correlation between length of stay and NLR in ischemic stroke and hemorrhagic stroke patient groups. Likewise, when we examined the length of hospitalization and NLR levels, we showed that there was no weak and statistically significant correlation. CONCLUSION Although there are many studies in the literature showing that high neutrophil and low lymphocyte values have a negative effect on mortality and morbidity, there are also studies that have not been shown to have an effect as in our study.

Elevated tissue factor pathway inhibitor is associated with intracerebral haemorrhage of unknown cause in young adults

Elevated tissue factor pathway inhibitor is associated with intracerebral haemorrhage of unknown cause in young adults

Clinical Study of Lipid Profile in Intracerebral Haemorrhage in Tertiary care Center

Background: Stroke caused by Intracerebral haemorrhage (ICH) has high mortality rate. Among various risk factors for ICH, hypertension is the most important factor. Certain population studies have reported a paradox of inverse association between serum cholesterol and risk of ICH. Aims and objectives: The study aim was to evaluate the serum lipid profile total cholesterol (TC), triglycerides (TGL), high density cholesterol (HDL-C), very low density cholesterol (VLDL-C) and low density cholesterol (LDL-C) in intracerebral haemorrhage patients and look for correlation. Methods: 50 patients with ICH admitted in Chalmeda Anand Rao Institute of Medical Sciences, Karimnagar who fulfilled the inclusion and exclusion criteria were selected. The study design was a hospital based observational clinical study. History, clinical examination and investigations (CT & MRI Brain and basic blood biochemistry with serum lipid profile) were collected and the data were analysed statistically. Results: Majority of the ICH patients in our study were >55 years and were males. The total serum cholesterol was < 200mg/dl in 72 % of our patients, with a mean of 168.09 ±43.74mg%. Serum triglyceride level was patients, with mean of 108.26±43.31mg%. HDL-C was < 40 mg/dl in 76% of patients and VLDL-C was < 30mg/dl in 72% patients. The various lipid fractions observed were found to be low in majority of our ICH patients (p value < 0.05), suggesting a negative association between the two. The results obtained were comparable to other similar studies. Conclusion: Majority of intracerebral haemorrhage patients in our study had lower levels of total cholesterol, triglyceride, HDL-C, LDL-C and VLDL-C. Whether the inverse association between serum lipid levels and ICH is a true causal association or only by chance due to other common confounding factors needs to be evaluated with large scale studies.

EGCG activates Keap1/P62/Nrf2 pathway, inhibits iron deposition and apoptosis in rats with cerebral hemorrhage

Intracerebral hemorrhage (ICH) is a common cerebrovascular disease characterized by a high incidence, disability rate, and mortality. Epigallocatechin gallate (EGCG), a key catechin compound found in green tea, has received increasing attention for its potential neuroprotective and therapeutic effects in neurological disorders. Studies have indicated that EGCG may influence various signaling pathways and molecular targets, including the inhibition of oxidative stress, reduction of inflammatory responses, suppression of cell apoptosis, regulation of cell survival, and enhancement of autophagy. Although the exact mechanism of action of EGCG is not fully understood, it has become a focal point of research in various disciplines due to its promising potential. This study aims to investigate the effects of EGCG on oxidative stress, iron deposition, and cell apoptosis in rats with ICH, as well as to uncover the underlying mechanisms. An ICH rat model was created to simulate cerebral hemorrhage, while an in vitro model utilizing primary cortical neurons was developed. The neurons were pre-treated with EGCG before being exposed to Erastin and RSL3 to induce iron death. The levels of oxidative stress, iron deposition, and cell apoptosis were evaluated in both models. In the ICH model, EGCG was discovered to enhance the activation of the Keap1/P62/Nrf2 signaling pathway in both in vivo and in vitro studies. Furthermore, EGCG significantly elevated the levels of GPX4 and XCT proteins, as well as the nuclear expression of Nrf2. It was noted that the Nrf2 inhibitor ML385 partially decreased the expression of these proteins. Through the activation of the Keap1/P62/Nrf2 pathway, EGCG inhibits inflammation, oxidative stress and iron deposition in rats with cerebral hemorrhage. EGCG inhibits oxidative stress, iron deposition and apoptosis in rats with ICH by activating Keap1/P62/Nrf2 pathway.

Resolvin D1 combined with exercise rehabilitation alleviates neurological injury in mice with intracranial hemorrhage via the BDNF/TrkB/PI3K/AKT pathway

Resolvin D1 (RvD1) is an endogenous anti-inflammatory mediator that modulates the inflammatory response and promotes inflammation resolution. RvD1 has demonstrated neuroprotective effects in various central nervous system contexts; however, its role in the pathophysiological processes of intracerebral hemorrhage (ICH) and the potential protective mechanisms when combined with exercise rehabilitation remain unclear. A mouse model of ICH was established using collagenase, and treatment with RvD1 combined with three weeks of exercise rehabilitation significantly improved neurological deficits, muscle strength, learning, and memory in ICH mice while reducing anxiety-like behavior. RvD1 combined with exercise rehabilitation upregulated anti-inflammatory factors, inhibited the inflammatory state, and activated the BDNF/TrkB/PI3K/AKT pathway. TUNEL staining confirmed a decrease in residual apoptotic neurons, while transmission electron microscopy showed an increase in mitochondrial autophagosomes with combined treatment. Mendelian randomization and molecular docking further confirmed the association of RvD1 with targets related to mitophagy and inflammatory factors, clarifying the mechanism of RvD1 involvement. In summary, RvD1 combined with exercise rehabilitation activates the BDNF/TrkB/PI3K/AKT signaling pathway, effectively reduces neuronal apoptosis and inflammatory responses following ICH in mice, and participates in mitochondrial autophagy-related states. This comprehensive therapeutic strategy promotes neurological recovery and provides insights for clinical management of this condition.

Neutrophil Extracellular Traps Induce Brain Edema Around Intracerebral Hematoma via ERK-Mediated Regulation of MMP9 and AQP4.

Perihematomal edema (PHE) significantly aggravates secondary brain injury in patients with intracerebral hemorrhage (ICH), yet its detailed mechanisms remain elusive. Neutrophil extracellular traps (NETs) are known to exacerbate neurological deficits and worsen outcomes after stroke. This study explores the potential role of NETs in the pathogenesis of brain edema following ICH. The rat ICH model was created, immunofluorescence and Western blot were used to examine neutrophil accumulation, NET markers citrullinated histone H3 (CitH3) and myeloperoxidase (MPO), tight junction proteins (ZO-1 and Occludin), Aquaporin-4 (AQP4), matrix metalloproteinase-9 (MMP-9), and ERK phosphorylation (p-ERK) in brain tissues surrounding the hematoma. TUNEL staining and behavioral tests were employed to evaluate neuronal apoptosis and neurological dysfunction, while blood-brain barrier (BBB) permeability and brain edema were also measured by Evans blue and brain water content. Furthermore, the molecular mechanisms related to NETs-induced PHE were investigated using NETs, ERK, MMP-9 and AQP4 regulators, respectively. Ly6G+ neutrophils surrounding the hematoma developed NETs within 3days post-ICH. NETs decreased tight junction proteins, destroyed BBB integrity, promoted brain edema, increased neuronal apoptosis, and exacerbated neurological deficits. Conversely, inhibition of NETs mitigated PHE, reduced neuronal apoptosis, and improved neurological functions. Mechanistically, NET-induced PHE was originated from impairment of BBB tight junction via ERK/MMP9 pathway, coupled with ERK-mediated AQP4 downregulation in perihematomal regions. These findings elucidated the effects of NETs on PHE, which offered promising insights for targeting NETs to relieve brain edema and secondary brain injury post-ICH.

Updated imaging markers in cerebral amyloid angiopathy: What radiologists need to know.

Cerebral amyloid angiopathy (CAA) is an age-related small vessel disease pathologically characterized by the progressive accumulation of amyloid-beta (Aβ) peptide in cerebrovascular walls, affecting both cortical and leptomeningeal vessels. Amyloid deposition results in fragile vessels, which may lead to lobar intracerebral hemorrhage (ICH) and cognitive impairment. To evaluate the probability and severity of CAA, the imaging markers depicted on CT and MRI techniques are crucial, as brain pathological examination is highly invasive. Although the Boston criteria have established diagnostic value and have been updated to version 2.0, due to an aging population, the patients with CAA should also be assessed for their risk of future ICH or cognitive impairment. Furthermore, an increased awareness of CAA is essential when introducing anticoagulants for infarct in elderly patients or anti-amyloid antibodies for Alzheimer's disease, as these may worsen CAA-related hemorrhagic lesions. However, the radiological literature on CAA has not been comprehensively updated. Here, we review the imaging markers of CAA and clinical significance. We also discuss the clinical and imaging characteristics of CAA-related inflammation, amyloid-related imaging abnormalities, and iatrogenic-CAA.

Impact of COVID-19 pandemic on acute stroke care in a tertiary stroke centre

The aim of this study was to evaluate how COVID-19 affected acute stroke care and outcome in patients with acute ischemic or hemorrhagic stroke. We performed a retrospective analysis on patients who were admitted with acute ischemic (AIS) or hemorrhagic (ICH) stroke from September 2020 to May 2021 with and without COVID-19. We recorded demographic and clinical data, imaging parameters, functional outcome and mortality at one year. Beside descriptive statistics we performed χ2-probe, Mann-Witney U-test, Student t-probe and multivariate testing. We found a 29%-reduction in the number of AIS cases during the pandemic. The number of the large vessel occlusions /LVOs/ (N = 83, 41.7%), from them 37 (17.7%) had mechanical thrombectomy (MT), was higher than before the COVID-19 period (p = 0.02 and p = 0.001, respectively). From all patients needing acute revascularization therapy (N = 137) 118 patients received it, among them 20 (16.9%) had COVID-19. Those positive for COVID-19 were more likely to have a higher median NIHSS score at baseline and at 24 h (p = 0.02 and p = 0.03, respectively). They also had a lower rate of favourable outcome at discharge (15% vs. 41.8%; p = 0.024) and at three months (25% vs. 52%, p = 0.02), longer median hospitalization (p < 0.0001), and a higher mortality rate (52% vs. 25%; p = 0.03). The incidence of symptomatic intracerebral hemorrhage (sICH) did not differ between the groups. Regarding the ICH patients, NIHSS score at 24 h (p = 0.036), mortality at 3 months (p = 0.004) and at one year (p = 0.00) were higher in the COVID-19 group. We concluded that the pandemic resulted fewer admission due to AIS with an increased number of LVOs and MTs. AIS patients with concomitant SARS-CoV-2 infection have more severe strokes and unfavorable long term outcome. The risk of sICH was not increased in COVID-19 positive patients therefore reperfusion therapies appear to be safe and beneficial for some individuals. Patients with ICH and comorbid COVID-19 have a very poor prognosis.

Associated Factors of Long-Term Functional Outcome and Recovery Pattern After Intracerebral Hemorrhage: A Prospective Population-Based Study in Ulaanbaatar, Mongolia.

Long-term patterns of functional outcome after intracerebral hemorrhage (ICH) have not been well elucidated in population-based studies from low- and middle-income countries. The aim of this study was to define long-term functional outcomes, associated prognostic factors, and recovery patterns for patients with acute ICH. We conducted a prospective population-based stroke incidence study in Ulaanbaatar, Mongolia, with prospective follow-up. Multiple overlapping strategies were used to prospectively ascertain all strokes over 2 years. Patients were followed up at 28, 90, and 365 days. Associated factors of unfavorable outcome (defined as modified Rankin Scale scores, 3-6) and death at 365 days were identified using separate binary logistic regressions. Recovery pattern in terms of the proportions of patients with favorable outcomes (defined as modified Rankin Scale scores, 0-2) as the outcome was analyzed over time at 28, 90, and 365 days using generalized estimating equations with baseline covariates. A total of 1172 first-ever ICH cases were registered. Among these patients, 625 (56.4% of available modified Rankin Scale) cases had died and 853 (77.0%) had an unfavorable outcome at 365 days. The proportion of favorable outcomes increased from 12.1% at day 28 to 17.4% at day 90 and then to 23.0% at 1 year. Multivariable analysis revealed that older age, low socioeconomic status, absence of hypertension, hospital admission, neurosurgical intervention, and ICH severity, side, and intraventricular extension were independently associated with death/unfavorable outcome 365 days post-ICH. Most of these factors were also associated with the recovery pattern. The prognosis from ICH in low- and middle-income countries is dismal, with 56% of patients dead and 77% having an unfavorable functional outcome at 365 days, although there was a pattern of continuous recovery over this time period. These findings stress the importance of developing effective primary prevention and continuous active care for survivors to reduce the burden of ICH in low- and middle-income countries.

Global, regional, and national burdens of intracerebral hemorrhage and its risk factors from 1990 to 2021.

The aim of this study was to assess the intracerebral hemorrhage (ICH) burden in 204 countries and territories worldwide from 1990 to 2021, disaggregated by sex, age, and sociodemographic index (SDI) at the global, regional, and country levels. Data from the 2021 Global Burden of Disease Study (GBD) were used to calculate age-standardized prevalence (ASPR), incidence (ASIR), death (ASDR), and disability-adjusted life year (DALY) rates for ICH. The estimated annual percentage change (EAPC) was used to assess time patterns. The Bayesian age-period-cohort (BAPC) model was employed to predict future ICH burden. In 2021, the global ICH burden remained high, with a total of 16.6 million cases and an ASPR of 194.51 cases per 100,000 people. The ASIR was 40.83 cases per 100,000 people, the ASDR was 39.09 cases per 100,000 people, and the age-standardized DALY rate was 923.64 per 100,000 people. The low-SDI regions had the highest ASPR, ASIR, ASDR, and DALY rates. Geographically, western sub-Saharan Africa had the highest ASPR, Central Asia had the highest ASIR, and Oceania had the highest ASDR and DALY rates. High systolic blood pressure was the leading risk factor for ICH death, contributing to 57.9% of global fatalities. Despite the decline in the ASIR, there is an ongoing increase in the absolute number of ICH cases, with significant differences observed across age, sex, region, country, and SDI. More attention and emphasis should be placed on improving the ICH burden in low-SDI areas.

Optimizing Automated Hematoma Expansion Classification from Baseline and Follow-Up Head Computed Tomography

Hematoma expansion (HE) is an independent predictor of poor outcomes and a modifiable treatment target in intracerebral hemorrhage (ICH). Evaluating HE in large datasets requires segmentation of hematomas on admission and follow-up CT scans, a process that is time-consuming and labor-intensive in large-scale studies. Automated segmentation of hematomas can expedite this process; however, cumulative errors from segmentation on admission and follow-up scans can hamper accurate HE classification. In this study, we combined a tandem deep-learning classification model with automated segmentation to generate probability measures for false HE classifications. With this strategy, we can limit expert review of automated hematoma segmentations to a subset of the dataset, tailored to the research team’s preferred sensitivity or specificity thresholds and their tolerance for false-positive versus false-negative results. We utilized three separate multicentric cohorts for cross-validation/training, internal testing, and external validation (n = 2261) to develop and test a pipeline for automated hematoma segmentation and to generate ground truth binary HE annotations (≥3, ≥6, ≥9, and ≥12.5 mL). Applying a 95% sensitivity threshold for HE classification showed a practical and efficient strategy for HE annotation in large ICH datasets. This threshold excluded 47–88% of test-negative predictions from expert review of automated segmentations for different HE definitions, with less than 2% false-negative misclassification in both internal and external validation cohorts. Our pipeline offers a time-efficient and optimizable method for generating ground truth HE classifications in large ICH datasets, reducing the burden of expert review of automated hematoma segmentations while minimizing misclassification rate.

Machine learning-based pipeline for automated intracerebral hemorrhage and drain detection, quantification, and classification in non-enhanced CT images (NeuroDrAIn).

External drainage represents a well-established treatment option for acute intracerebral hemorrhage. The current standard of practice includes post-operative computer tomography imaging, which is subjectively evaluated. The implementation of an objective, automated evaluation of postoperative studies may enhance diagnostic accuracy and facilitate the scaling of research projects. The objective is to develop and validate a fully automated pipeline for intracerebral hemorrhage and drain detection, quantification of intracerebral hemorrhage coverage, and detection of malpositioned drains. In this retrospective study, we selected patients (n = 68) suffering from supratentorial intracerebral hemorrhage treated by minimally invasive surgery, from years 2010-2018. These were divided into training (n = 21), validation (n = 3) and testing (n = 44) datasets. Mean age (SD) was 70 (±13.56) years, 32 female. Intracerebral hemorrhage and drains were automatically segmented using a previously published artificial intelligence-based approach. From this, we calculated coverage profiles of the correctly detected drains to quantify the drains' coverage by the intracerebral hemorrhage and classify malpositioning. We used accuracy measures to assess detection and classification results and intraclass correlation coefficient to assess the quantification of the drain coverage by the intracerebral hemorrhage. In the test dataset, the pipeline showed a drain detection accuracy of 0.97 (95% CI: 0.92 to 0.99), an agreement between predicted and ground truth coverage profiles of 0.86 (95% CI: 0.85 to 0.87) and a drain position classification accuracy of 0.88 (95% CI: 0.77 to 0.95) resulting in area under the receiver operating characteristic curve of 0.92 (95% CI: 0.85 to 0.99). We developed and statistically validated an automated pipeline for evaluating computed tomography scans after minimally invasive surgery for intracerebral hemorrhage. The algorithm reliably detects drains, quantifies drain coverage by the hemorrhage, and uses machine learning to detect malpositioned drains. This pipeline has the potential to impact the daily clinical workload, as well as to facilitate the scaling of data collection for future research into intracerebral hemorrhage and other diseases.

Predictors and Outcomes of Hematoma Expansion and Neurological Decline in Intracerebral Hemorrhage: A Multisite Mobile Stroke Unit Study

BACKGROUND Hemorrhagic stroke, particularly intracerebral hemorrhage, is one of the leading causes of permanent disability worldwide. Early hematoma expansion (HE) is a key factor in neurological deterioration (ND) and functional outcomes post intracerebral hemorrhage. This observational cohort study examines the predictors and outcomes of HE and ND in spontaneous intracerebral hemorrhage patients using data from 3 Mobile Stroke Units (MSUs) in the United States. METHODS Patients diagnosed with spontaneous intracerebral hemorrhage within 4 hours of last known well were included. Data collection involved initial and follow‐up non‐contrast (computerized tomography) CT scans from MSUs and emergency departments, from which the rate of HE and ND were determined. The interrater reliability for radiographic signs of HE was also assessed. Predictive factors were analyzed using multiple logistic regression models. RESULTS Of the 55 patients who met the inclusion criteria, 27% experienced HE within the first 4 hours from last known well with the majority of HE occurring within the first 60 to120 minutes. Significant predictors of HE were a history of diabetes and blend sign on initial MSU CT scans. Predictors of ND included initial hematoma volume and the presence of hydrocephalus. Patients with HE and ND had a higher discharge modified‐Rankin Scale score and mortality rates. Interrater agreement on radiographic signs of HE varied, with moderate agreement on some signs and little to none on others. CONCLUSION Highest HE was seen within 60 to120 minutes from last known well for patients between MSU and emergency department transport. The blend sign and a history of diabetes emerged as key predictors of HE, whereas initial hematoma volume and hydrocephalus were significant for ND. Interventions to prevent HE and ND should be tested on the MSU in future studies.

Tranexamic Acid Within 4.5 Hours of Intracerebral Hemorrhage With the CTA Spot Sign: Systematic Review and Individual Patient Meta-analysis.

The antifibrinolytic agent tranexamic acid has been tested in intracerebral hemorrhage trials with overall neutral results. Ongoing contrast extravasation on CT angiography (spot sign) can identify individuals with ongoing bleeding who may benefit from anti-fibrinolytic therapy. We aimed to investigate the effect of tranexamic acid on hematoma growth in patients with spot signs treated within 4.5 hours of onset. We conducted a systematic review and individual patient meta-analysis, which we report according to the Preferred Reporting Items for Systematic Review and Meta-analyses of Individual Participant Data guidelines. PubMed and Embase were searched from inception to May 29, 2023, using the terms ((stroke) AND (randomised OR randomized) AND (tranexamic acid) AND (haemorrhage OR hemorrhage)). We included randomized trials comparing tranexamic acid with placebo in participants with primary intracerebral hemorrhage who had a spot sign and who had follow-up imaging within the required timeframe. Individual patient data were provided by each study and were integrated by the coordinating center. Data were pooled using a random-effects model. The primary endpoint was hematoma growth within 24 hours, defined as ≥33% relative or ≥6 mL absolute hematoma expansion compared with baseline, analyzed using mixed-effects-modified Poisson regression with robust standard errors, adjusted for baseline hematoma volume. Safety outcomes were mortality and major thromboembolic events within 90 days. Of 197 studies identified, 3 were eligible, contributing 162 participants for the primary analysis (60 female and 102 male). Hematoma growth occurred in 36 of 74 (49%) participants treated with tranexamic acid, compared with 48 of 88 (55%) participants treated with placebo (adjusted risk ratio 0.86, 95% CI 0.84-0.89, p < 0.001). Adjusted median absolute hematoma growth was 1.60 mL (95% CI 0.77-2.43) lower with tranexamic acid vs placebo. No differences in functional outcome or safety were observed. Tranexamic acid modestly reduced hematoma growth in patients with CT angiography spot signs treated within 4.5 hours of onset. Given the trials in the meta-analysis were individually neutral, these results require further validation before clinical application.

Outcomes of Mechanical Thrombectomy in Patients With Acute Basilar Artery Occlusion With Mild to Moderate Symptoms.

The benefit of mechanical thrombectomy (MT) in patients with acute ischemic stroke (AIS) with basilar artery occlusion (BAO) and a baseline National Institute of Health Stroke Scale (NIHSS) score <10 is unclear because this subpopulation has been substantially excluded from large clinical trials. The aim of our study was to determine whether MT ± IV thrombolysis (IVT) improves functional outcomes compared with IVT alone in patients with BAO and a NIHSS score <10. We emulated a hypothetical trial including adult patients with BAO, a baseline NIHSS score <10, and prestroke modified Rankin scale (mRS) scores 0-2, comparing MT (±IVT) with IVT alone. We acquired data from patients receiving MT (±IVT) within 24 hours of onset from the Italian Registry of Endovascular Treatment in Acute Stroke and data from patients treated only with IVT within 9 hours of symptom onset from the SITS International Stroke Thrombolysis Register, from 2011 until 2021. We used inverse probability weighting (IPW) adjusted for prespecified covariates to weight each individual's contribution to the outcome. The primary outcome was 90-day mRS scores 0-2. Secondary outcomes included 90-day mRS scores 0-1, 90-day mRS scores 4-5, mortality at 90 days, in-hospital death, and symptomatic intracerebral hemorrhage. Among the 764 patients recruited from the 2 databases (477 men [62.4%]; mean age [±SD] 67.88 [±13.9] years), 410 (53.7%) received MT±IVT and 354 (46.3%) only IVT. After applying IPW, our population was composed of 710 MT and 707 IVT patients. Of these, 454 MT-treated (63.9%) and 383 IVT-treated (54.2%) patients had a 90-day mRS score of 0-2 (adjusted odds ratio (aOR) 1.56 [95% CI 1.04-2.03]). MT was also associated with a higher rate of mRS scores 0-1 (aOR 2.01 [95% CI 1.37-2.95]) and a lower rate of in-hospital death (aOR 0.45 [95% CI 0.25-0.78]). Among the subgroups tested, MT had a larger effect on 90-day mRS scores 0-2 for patients with NIHSS scores 6-9 than for patients with a NIHSS score <6 (p for interaction 0.02). In a large-scale target trial emulation on patients with stroke from BAO and a NIHSS score <10, MT was associated with better functional outcomes compared with IVT alone. Further research is needed to confirm the benefit of MT in patients with a NIHSS score <6. This study provides Class III evidence that MT ± intravenous thrombolysis is associated with better 90-day functional outcomes in patients with BAO and a NIHSS score < 10 compared with intravenous thrombolysis alone.

Sulcal Hyperintensity as an Early Imaging Finding in Cerebral Amyloid Angiopathy-Related Inflammation.

Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a subtype of CAA with distinct clinical and radiologic features. Existing diagnostic criteria require the presence of characteristic asymmetrical white matter hyperintensity (WMH), together with classical hemorrhagic neuroimaging markers of CAA. There are limited data for other diagnostic neuroimaging markers of CAA-ri. This is a case series from a specialist hospital intracerebral hemorrhage service. We describe 4 patients with CAA-ri who had regions of sulcal hyperintensity, with or without gyral swelling at clinical presentation, but did not fulfill current diagnostic criteria because of the absence of typical asymmetric WMH on brain MRI. All 4 patients were subsequently diagnosed with CAA-ri; three later developed asymmetric WMHs with disease relapse, and 2 had pathologically proven CAA-ri; 1 patient had both. Regions of sulcal hyperintensity, sometimes with associated gyral swelling, can be an early imaging finding in CAA-ri. These neuroimaging markers could potentially improve the accuracy of existing diagnostic criteria for CAA-ri to allow earlier diagnosis and treatment without biopsy in patients with atypical presentations.

Indexes of systemic inflammation in hemorrhagic stroke with effective blood flow: a dynamic observation

Increasing evidence suggests that stroke is a systemic disease affecting multiple organs. Systemic inflammatory response and immune dysregulation associated with hemorrhagic stroke, may play an important role in brain injury, its recovery, and stroke outcomes. However, it is worth of note that, from our point of view, the classical concepts about inflammation in pathophysiology and general pathology do not entirely meet the needs of modern medical practice. The existence of this problem is also typical for assessing pathogenesis, as well as for optimizing pathogenetic therapy of severe strokes. Therefore, within the framework of this work, a dynamic observation and assessment of pathogenesis in severe intracerebral hemorrhage was carried out using the criteria of a systemic inflammation scale. The study included patients with intracerebral hemorrhage and effective cerebral blood flow. Blood sampling was carried out on days 1-3 and 5-7 after clinical manifestation of intracerebral hemorrhage. To determine markers of systemic inflammation in the blood plasma of patients, the levels of IL-6, IL-8, IL-10, TNFá, procalcitonin, cortisol, myoglobin, troponin I and D-dimers were examined using an enzyme-linked immunosorbent assay. The Kolmogorov–Smirnov test was used to confirm the normal data distribution. Further comparison of quantitative data was carried out using the nonparametric Wilcoxon test for paired comparisons. All results were considered statistically significant at p 0.05. In patients on days 1-3 and 5-7, statistically significant differences were not observed in almost all studied markers of systemic inflammation, except for IL-8 and tumor necrosis factor-á. Such increased contents of pro-inflammatory cytokines may indicate increased systemic inflammation over time in the patients with intracerebral hemorrhage and effective cerebral blood flow. Hence, the condition of such patients may worsen on days 5-7 after manifestations of intracerebral hemorrhage, thus requiring more careful monitoring of patients’ blood counts and therapy aimed at suppression of increasing inflammation.

Sphk1/S1P pathway promotes blood-brain barrier breakdown after intracerebral hemorrhage through inducing Nlrp3-mediated endothelial cell pyroptosis

AbstractIntracerebral hemorrhage (ICH) is a severe stroke subtype with high mortality and limited therapeutic options. The blood-brain barrier (BBB) breakdown post-ICH exacerbates secondary brain injury, highlighting the need for targeted therapies to preserve the BBB integrity. We aim to investigate the role of the Sphk1/S1P pathway in BBB breakdown following ICH and to evaluate the therapeutic potential of Sphk1 inhibition in mitigating this breakdown. Using a combination of human patient samples, mouse models of ICH, and in vitro cellular assays, we assessed the expression levels of Sphk1/S1P after ICH and changes of the BBB after ICH. The Sphk1 inhibitor PF543 and siRNAs were utilized to explore the pathway’s impact on BBB integrity and the underlying mechanisms. The results indicate significant upregulation of Sphk1/S1P in the peri-hematomal brain tissue after ICH, which correlates with increased BBB leakage. Pharmacological inhibition of Sphk1 with PF543 attenuates BBB leakage, reduces hematoma volume, and improves neurological outcomes in mice. At the molecular and ultrastructural level, Sphk1 inhibition protects the BBB integrity by preserving tight junction proteins and suppressing endothelial transcytosis. Furthermore, mechanistic studies reveal that Sphk1 promotes Nlrp3-mediated pyroptosis of brain endothelial cells through the ERK1/2 signaling pathway. Taken together, the Sphk1/S1P pathway plays a critical role in ICH-induced BBB breakdown, and its inhibition represents a promising therapeutic strategy for ICH management.

Guidelines for Seizure Prophylaxis in Patients Hospitalized with Nontraumatic Intracerebral Hemorrhage: A Clinical Practice Guideline for Health Care Professionals from the Neurocritical Care Society.

There is practice heterogeneity in the use, type, and duration of prophylactic antiseizure medications (ASM) in patients hospitalized with acute nontraumatic intracerebral hemorrhage (ICH). We conducted a systematic review and meta-analysis assessing ASM primary prophylaxis in adults hospitalized with acute nontraumatic ICH. The following population, intervention, comparison, and outcome (PICO) questions were assessed: (1) Should ASM versus no ASM be used in patients with acute ICH with no history of clinical or electrographic seizures? (2) If an ASM is used, should levetiracetam (LEV) or phenytoin/fosphenytoin (PHT/fPHT) be preferentially used? and (3) If an ASM is used, should a long (> 7days) versus short (≤ 7days) duration of prophylaxis be used? The main outcomes assessed were early seizure (≤ 14days), late seizures (> 14days), adverse events, mortality, and functional and cognitive outcomes. We used Grading of Recommendations Assessment, Development, and Evaluation methodology to generate recommendations. The initial literature search yielded 1,988 articles, and 15 formed the basis of the recommendations. PICO 1: although there was no significant impact of ASM on the outcomes of early or late seizure or mortality, meta-analyses demonstrated increased adverse events and higher relative risk of poor functional outcomes at 90days with prophylactic ASM use. PICO 2: we did not detect any significant positive or negative effect of PHT/fPHT compared to LEV for early seizures or adverse events, although point estimates tended to favor LEV. PICO 3: based on one decision analysis, quality-adjusted life-years were increased with a shorter duration of ASM prophylaxis. We suggest avoidance of prophylactic ASM in hospitalized adult patients with acute nontraumatic ICH (weak recommendation, very low quality of evidence). If used, we suggest LEV over PHT/fPHT (weak recommendation, very low quality of evidence) for a short duration (≤ 7days; weak recommendation, very low quality of evidence).

The Potential of Hair-Follicle-Associated Pluripotent (HAP) Stem Cells for Regenerative Medicine.

Nestin-expressing hair-follicle-associated pluripotent (HAP) stem cells from mouse and human have been shown to differentiate into neurons, glia, keratinocytes, smooth muscle cells, cardiac muscle cells, and melanocytes in vitro. HAP stem cells have promoted the recovery of peripheral nerve and spinal cord injuries in mouse models by differentiating into glial fibrillary acidic protein (GFAP)-positive Schwann cells. HAP stem cells enclosed on polyvinylidene fluoride membranes (PFM) were transplanted into the severed thoracic spinal cord of nude mice. After implantation, HAP stem cells differentiated into neurons and glial cells, which effected complete reattachment of the thoracic spinal cord.HAP stem cells were implanted into the injured brain of C57BL/6J or nude mice with induced intracerebral hemorrhage (ICH). After implantation, HAP stem cells differentiated into neurons, astrocytes, oligodendrocytes, and microglia in the ICH site, and demonstrated a significant functional improvement in mice. HAP-cell-sheets implanted on wounds in diabetic db/db mice effected wound healing. The levels of inflammation in the wound was suppressed by HAP-cell-sheet implantation. These results suggest autologous HAP stem cells can be used to heal refractory diabetic ulcers. HAP stem cells can differentiate into mature beating atrial and ventricular cardiomyocytes when cultured with specific supplements and have the potential for heart regeneration. HAP stem cells are readily obtained from scalp hair follicles, they do not develop teratomas and do not lose differentiation ability when cryopreserved. These results suggest that HAP stem cells have the potential as be a better source for regenerative medicine compared to induced pluripotent stem cells (iPS) or embryonic stem (ES) cells.