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Background and aims: Endoscopic surgery (ES) and small bone window craniotomy (SBWC) are commonly used methods for hematoma removal in cases of intracerebral hemorrhage (ICH). However, their long-term efficacy and safety remain uncertain. Methods: A systematic search was performed in the PubMed, Embase, and Cochrane Library databases from inception to June 30, 2024. The primary outcomes assessed were the 6-month favorable functional outcome rate and the hematoma evacuation rate. Following the meta-analysis, a trial sequential analysis (TSA) was conducted to validate the findings. Results: Six randomized controlled trials were included in the meta-analysis. ES demonstrated a higher 6-month favorable functional outcome rate compared to SBWC (56.8% vs. 48.0%, relative risk [RR] 1.20, 95% confidence interval [CI] 1.05–1.38, I2 = 28%), with TSA supporting this result. The hematoma evacuation rate was also higher in the ES group (mean difference [MD] 6.41, 95% CI 1.83–10.99, I² = 95%); however, the TSA did not support this result due to the potential false-positive. Additionally, ES was associated with shorter operation times, less blood loss during surgery, and a lower pneumonia rate compared to SBWC (MD -112.35, 95% CI -165.27 to -59.43; MD -151.22, 95% CI -279.60 to -22.84; RR 0.68, 95% CI 0.51–0.91). Conclusions: The meta-analysis and TSA indicate that ES offers better long-term efficacy, shorter operation times, less blood loss, and a lower rate of pneumonia compared to SBWC. Therefore, prioritizing ES over SBWC for treating ICH appears to be a reasonable approach. [ABSTRACT FROM AUTHOR]

• HO-1 and p-NF-kB p65 were increased in brain tissue of ICH mice. • Tat-NBD enhanced protective effect of HO-1 on nerve injury and hematoma clearance after ICH. • Tat-NBD enhanced promoting effect of HO-1 on M2 polarization of microglia after ICH. • HO-1 induced M2 polarization and phagocytosis via inhibiting NF-kB. • HO-1/NF-kB reduced neuronal damage via inducing microglia M2 polarization and phagocytosis. Microglia polarization plays a crucial role in inflammatory injury of brain following intracerebral hemorrhage (ICH). Heme oxygenase-1 (HO-1) has demonstrated protective properties against inflammation and promote hematoma clearance after ICH. The objective of this study was to explore impacts of HO-1 on microglia polarization and phagocytosis after ICH, along with the underlying mechanism. ICH model was constructed in C57BL/6 mice. Neurological deficit of ICH mice was evaluated. HE detected pathological changes of mouse brain tissue. Immunofluorescence staining tested co-localization between HO-1 or NF-κB p65 and IBA1. The expressions of gene and proteins were detected by RT-qPCR and Western blot, respectively. Flow cytometry determined microglial polarization phenotype and neuron apoptosis. Cell viability of neuron was assessed by CCK-8. Red blood cells labeled by PKH-26 and co-cultured with microglia for examining microglial erythrophagocytosis. Both HO-1 and NF-κB p65 phosphorylation were elevated in brain tissues of ICH mice. ZnPP, a HO-1 inhibitor, could exacerbate microglial M1 polarization and nerve injury, as well as repress microglial erythrophagocytosis in vitro and hematoma clearance in vivo. On the contrary, Tat-NBD, a NF-κB inhibitor, greatly suppressed microglial M1 polarization, and induced M2 polarization and microglial erythrophagocytosis, thus improving nerve injury and hematoma clearance after ICH. Notably, it was observed that NF-κB p65 could be activated by ZnPP treatment, and the regulatory roles of ZnPP on microglial polarization and erythrophagocytosis after ICH in vivo and in vitro were all diminished by Tat-NBD. Therefore, our data demonstrated that HO-1 alleviated nerve injury and induced M2 polarization and phagocytosis of microglia after ICH via inhibiting NF-κB signaling pathway, which could provide deepen the pathological understanding of ICH and provide potential intervention targets and drug candidate for ICH. [ABSTRACT FROM AUTHOR]

Background: Anticoagulated patients with mild traumatic brain injury (mTBI) and a negative cerebral CT on admission, commonly undergo a repeated CT scan after observation in the emergency department (ED) to detect delayed intracranial hemorrhage (ICH). However, the utility of this practice is controversial, with recent evidence suggesting that the risk of delayed ICH in these patients is low. This study aims to evaluate incidence, outcomes, and risk factors of delayed ICH in patients receiving direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs) presenting to the ED with mTBI. Methods: A multicenter, observational, retrospective cohort study was conducted in the EDs of three hospitals in Northern Italy, from January 2017 to December 2021. All consecutive adult patients on DOACs or VKAs therapy, admitted for a mTBI, who underwent a second CT scan after 12–24 h from a negative first one, were enrolled. Results: A total of 1596 anticoagulated patients were enrolled, 869 (54%) on DOACs and 727 (46%) on VKAs therapy. The median age was 84 [79–88] and 56% of patients were females. The incidence of delayed ICH was 1.8% (95% CI: 1.1-3.0%; 14/869 patients) for DOACs, and 2.6% (95% CI: 1.6–4.1%; 19/727 patients) for VKAs patients, with no cases requiring neurosurgical intervention. Vomiting after head injury and the onset of new symptoms during observation were associated with a higher risk of delayed bleeding (OR 4.8; 95% CI: 1.4–16.5, and OR 4.7; 95% CI 1.2–23.7, respectively). At a 30-day follow-up, 2% of patients had a new ED admission related to their previous mTBI, with no significant difference between the groups. Conclusions: Delayed ICH is uncommon among anticoagulated patients with mTBI and has minimal impact on their outcome. Routine performance of a second CT scan may be unnecessary and may be considered only in presence of high-risk clinical risk factors or signs of deterioration. [ABSTRACT FROM AUTHOR]

Background: The relationship between lipid profiles and intracranial hemorrhage (ICH) has garnered increasing attention. The ratio of low-density lipoprotein to high-density lipoprotein (LHR) is one of the key lipid profile indices. However, studies investigating the association between LHR and the prognosis of critically ill ICH patients remain limited. Methods: Data for this study were obtained from the MIMIC-IV 3.1 database. Initially, the association between LHR and short-term outcomes in ICH patients, including ICU mortality, in-hospital mortality, and 28-day mortality, was analyzed using Cox regression in both continuous and categorical models. Additionally, restricted cubic spline (RCS), subgroup, and sensitivity analyses were conducted to further validate our findings. Results: The study included 873 critically ill ICH patients, among whom 20.3% (177/873) succumbed within 28 days. Higher LHR was independently associated with lower short-term mortality in ICH patients (28-day mortality: HR = 0.82, 95% CI: 0.68 ~ 0.99, P = 0.039; In-hospital mortality: HR = 0.7, 95% CI: 0.55 ~ 0.89, P = 0.004; ICU mortality: HR = 0.66, 95% CI: 0.48 ~ 0.92, P = 0.015). The RCS revealed a linear relationship between LHR and short-term all-cause mortality. Subgroup analyses demonstrated consistent results. The optimal cutoff value for LHR was determined to be 1.21. Comparing the mortality risk between the low-LHR and high-LHR groups, the high-LHR group exhibited higher survival rates (28-day mortality, P = 0.0052; In-hospital mortality, P = 0.019; ICU mortality, P = 0.044). Furthermore, higher LHR was also correlated with lower disease severity scores (SAPS-II: r = -0.158, P < 0.001, OASIS: r = -0.117, P = 0.006). Conclusion: LHR was negatively associated with short-term mortality in critically ill ICH patients. It may aid clinicians in identifying high-risk individuals and providing timely interventions. [ABSTRACT FROM AUTHOR]

Background and Objective: There is relatively little data on all-cause mortality within 3 months after successful mechanical thrombectomy for noncardioembolic acute cerebral infarction in the anterior circulation. The purpose of this study is to explore the predictive effect of emergency preoperative plasma D-dimer on all-cause mortality within 3 months after successful mechanical thrombectomy of anterior circulation noncardioembolic acute cerebral infarction. Methods: A retrospective analysis was conducted on the clinical data of 186 patients with anterior circulation noncardioembolic acute cerebral infarction who underwent successful mechanical thrombectomy. Results: Among 186 patients (aged 64.26 ± 11.62 years), 8 patients (4.30%) experienced all-cause mortality within 3 months after surgery. Compared with non deceased patients, deceased patients had a higher proportion of female, higher NIHSS score at admission, lower preoperative Alberta Stroke Program Early Computed Tomography (ASPECT) score, lower collateral circulation score, lower proportion of grade 3 reperfusion blood flow classification, and higher levels of emergency preoperative plasma D-dimer (P<0.05). After adjusting for confounding factors, female (odds ratio (OR)=15.389; 95% confidence interval (CI) 1.219-194.279; P=0.035) and emergency preoperative plasma D-dimer (OR=1.271; 95% CI 1.084-1.491; P=0.003) were significantly associated with all-cause mortality within 3 months after surgery. The area under the ROC curve for predicting all-cause mortality using plasma D-dimer is 0.822 (sensitivity 0.875, specificity 0.831), with a cutoff value of 2.065ug/ml. Conclusion: Preoperative plasma D-dimer is an independent predictor of all-cause mortality within 3 months after successful mechanical thrombectomy for noncardioembolic acute cerebral infarction of anterior circulation. Patients with plasma D-dimer level ≥ 2.065ug/ml have a greater chance of experiencing symptomatic cerebral hemorrhage, malignant cerebral edema, and cerebral herniation. [ABSTRACT FROM AUTHOR]

Objective: To explore the correlation between changes in serum neurofilament light chain protein and clinical prognosis in patients with hypertensive intracerebral hemorrhage, combined with other clinical indicators. This article provides evidence for clinicians to effectively evaluate the prognosis of patients with hypertensive intracerebral hemorrhage and formulate diagnosis and treatment plans. Methods: We selected 202 patients with hypertensive intracerebral hemorrhage admitted to different hospital from 2021 to 2022, and the clinical data of the patients were collected immediately after admission. Blood samples of the patients were collected, centrifuged, and the upper serum layer was collected and stored in the freezer at -80℃. During the same period, the sera of 30 age-matched healthy subjects were collected as the control group. The serum values of light chain protein of the experimental group and control group were measured by enzyme-linked immunosorbent assay. The Glasgow Outcome Scale of enrolled patients at 30 days of onset was recorded, and the collected data were statistically analyzed. Results: After statistical treatment, systolic blood pressure, admission Glasgow coma scale score, hematoma volume, and serum light chain protein values on day 3 and day 7 were statistically significant between the groups with good prognosis and those with poor prognosis (all P <.001). Conclusion: The serum light chain protein level of patients with hypertensive intracerebral hemorrhage was significantly higher than that of healthy people. The prognosis of the experimental group was correlated with the change trend of serum light chain protein. [ABSTRACT FROM AUTHOR]

The association between age and delayed cerebral ischemia (DCI) has long been controversial. This study aimed to explore the relationship between age and DCI in patients with aneurysmal subarachnoid hemorrhage (aSAH) requiring invasive mechanical ventilation (IMV). This study reanalyzed previously published data from a French university hospital. Chalard K et al. conducted a retrospective cohort study in the intensive care unit from 2010 to 2015. Univariate and multivariate logistic regression analyses were employed to identify risk factors for DCI. The non-linear relationship between age and DCI was estimated through a restricted cubic spline regression, and a two-piecewise linear regression model was further performed to calculate the threshold effect. The analysis included 222 patients with aSAH requiring IMV. Their median age was 56 years (range 19–84 years). Patients were equally divided into four groups: Q1 (19–45 years), Q2 (46–55 years), Q3 (56–63 years), and Q4 (64–84 years). The incidence of DCI was 27.48% (N = 61). After adjustment for potential confounders, patients in group Q2 were found to be more likely to develop DCI [odds ratio (OR), 4.91; 95% Confidence Interval (CI), 1.53–15.70] compared to those in group Q1. After adjusting for confounding variables, for patients aged < 53 years, the risk of DCI increased by 14% (OR, 1.14; 95% CI 1.05–1.23) for each 1-year increase in age. For patients aged 53 to 77 years, the risk of DCI decreased by 19% (OR, 0.81; 95% CI 0.73–0.88) for each 1-year increase. For patients aged > 77 years, the risk of DCI did not decrease with increasing age (OR, 1.42; 95% CI 0.47–4.34). Age was non-linearly associated with DCI in patients with aSAH requiring IMV. [ABSTRACT FROM AUTHOR]

Objectives: The use of anticoagulants in patients increases the risk of intracranial hemorrhage (ICH). Our aim was to identify factors associated with cerebral hemorrhage in patients using anticoagulants and to develop a predictive model that would provide an effective tool for the clinical assessment of cerebral hemorrhage. Methods: In our study, indications for patients receiving anticoagulation included AF, VTE, stroke/TIA, arteriosclerosis, peripheral vascular diseases (PVD), prosthetic mechanical valve replacement, etc. Data were obtained from the patient record hospitalization system. Logistic regression, area under the curve (AUC), and bar graphs were used to build predictive models in the development cohort. The models were internally validated, analytically characterized, and calibrated using AUC, calibration curves, and the Hosmer-Lemeshow test. Results: This single-center retrospective study included 617 patients treated with anticoagulants. Multifactorial analysis showed that male, leukoaraiosis, high risk of falls, APTT ≥ 45.4 s, and FIB ≥ 4.2 g/L were independent risk factors for cerebral hemorrhage, and β -blockers were protective factors. The model was constructed using these six factors with an AUC value of 0.883. In the validation cohort, the model had good discriminatory power (AUC = 0.801) and calibration power. Five-fold cross-validation showed Kappa of 0.483. Conclusion: Predictive models based on a patient's medical record hospitalization system can be used to identify patients at risk for cerebral hemorrhage. Identifying people at risk can provide proactive interventions for patients. [ABSTRACT FROM AUTHOR]

Introduction: Mixed Lineage Kinase Domain-Like Protein (MLKL), as the executor of necroptosis and a critical factor in the inflammation, has been shown to be associated with the progression of hemorrhagic stroke. Studies identified MLKL is a promoting factor in this process, suggesting its potential as a therapeutic target to mitigate posthemorrhagic stroke damage. However, the mechanisms by which MLKL functions in the process of intracerebral hemorrhage (ICH)-induced damage remain unclear. Methods: Here, we explored the correlation between MLKL and pathological damage in ICH patients through histopathological staining and RT-qPCR. Furthermore, we established an intracerebral hemorrhage model by collagenase IV injection in WT and Mlkl-/- mice. Subsequently, we investigated the impact of MLKL knockout on ICH pathological damage through behavioral tests, Western blotting, and RT-qPCR. Finally, we performed a proteomic analysis via LC-MS/MS to explore the potential interacting proteins of MLKL in the progression of ICH. Results: We found that MLKL is highly expressed in the brain tissue of ICH patients and is positively correlated with the extent of injury. However, we found that Mlkl knockout alone was insufficient to fully reverse neuroinflammation and pathological damage. Although Mlkl knockout has a limited effect on alleviating ICH damage, proteomics results indicate that MLKL can mitigate changes in proteins associated with inflammation, metabolism, and coagulation pathways, suggesting that MLKL may exert its effects through these pathways. Discussion: In summary, our results suggest that although MLKL is associated with the progression of ICH, single knockout of Mlkl is insufficient to fully reverse the pathological damage of ICH. Proteomic analysis indicates that co-targeting MLKL and its associated protein network may yield better therapeutic outcomes for hemorrhagic stroke. [ABSTRACT FROM AUTHOR]

Background: Intracerebral hemorrhage (ICH) is stroke caused by non-traumatic bleeding into the brain. Aim: This factsheet provides summary statistics for ICH from the 2021 Global of Burden of Diseases Study. Methods: Data were downloaded from the GBD results platform using "intracerebral hemorrhage" as a Level 4 cause of death or injury, extracting key metrics (number, percent, rate) for measures (incidence, disabilty adjusted life years [DALYs], deaths) described in this factsheet. Results: Globally, stroke was the third leading cause of death in 2021, and ICH accounted for 28.8% of incident strokes. There were estimated to be 7,252,678 deaths due to stroke in 2021 of which ICH accounted for 3,308,367 (45.6%). When considering the burden of ICH in terms of DALYs, ICH accounts for nearly half of the burden of stroke at 49.5%, compared to 43.8% caused by ischemic stroke. ICH must therefore be considered on an equal footing with ischemic stroke, so that efforts can be made to reduce its burden through public health, research, and healthcare provision. Although the overall age-standardized incidence of ICH has been decreasing since 1990, the rate of reduction has been much slower in regions with lower socio-demographic index (SDI). Most of the burden of ICH lies in areas with lower SDI, with 94.2% of DALYs lost to ICH outside areas of high SDI. Geographically, the majority of DALYs due to ICH occur in Southeast Asia, East Asia, and Oceania, with 53.3% of global DALYs lost in these regions alone. The risk factors for ICH are dominated by high systolic blood pressure, which accounts for at least 50% of the burden of ICH, regardless of SDI. Areas with middle or high-middle SDI have a greater proportion of the burden of ICH accounted for by ambient particulate pollution, smoking, and diets high in sodium, whereas household air pollution from solid fuels accounts for much more of the risk of ICH in low SDI regions. Conclusion: This World Stroke Organization (WSO) Global ICH Fact Sheet 2025 provides the most updated information on ICH that can be used to support communication with all internal and external stakeholders, inform healthcare policy, and raise public awareness. All statistics have been reviewed and approved for use by the WSO Executive Committee. [ABSTRACT FROM AUTHOR]

Background and aim: 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. Methods: Patients with intracerebral hemorrhage admitted within 24 h 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. Results: Of a total 9810 patients with intracerebral hemorrhage (4267 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 prestroke 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)) were 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, prestroke 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)) were not. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Background: The association between aspirin use and the risk of intracerebral hemorrhage (ICH) among individuals without previous stroke events is inconclusive. Aim: We investigated the association between regular aspirin use and ICH risk in middle-aged and older adults without previous stroke or transient ischemic attack (TIA). Methods: This prospective population-based study included participants older than 40 years with no history of stroke or TIA from the UK Biobank. The main exposure was regular aspirin use. Cox regression analyses and propensity score matching analyses estimated the hazard ratios (HRs) for aspirin use for incident fatal and non-fatal ICH. We conducted pre-specified subgroup analyses for selecting individuals at high risk of ICH when using aspirin. Multiple sensitivity analyses were performed to test the robustness of our results. Results: A total of 449,325 participants were included into final analyses (median (IQR) age 58 (50–63) years, 54.6% females), of whom 58,045 reported aspirin use. During a median follow-up of 12.75 (IQR: 12.03–13.47) years, 1557 (0.3%) incident ICH cases were identified, of which 399 (25.6%) were fatal. Aspirin was not associated with increased risk of overall (hazard ratio (HR): 1.11, 95% confidence interval (CI): 0.95–1.27, P = 0.188), fatal (HR: 1.03, 95% CI: 0.78–1.36, P = 0.846) and non-fatal (HR: 1.12, 95% CI: 0.95–1.33, P = 0.186) ICH. Propensity score matching analysis showed similar results. Subgroup analysis indicated that aspirin use in individuals older than 65 years or with concurrent anticoagulant use was correlated with increased risk of ICH. Conclusion: In this large cohort study of middle-aged and older adults without stroke or TIA events, there was no significant association between aspirin use and ICH risk in the real-world setting. However, it is possible that aspirin use in those aged over 65 years and concurrent anticoagulant treatment may increase the risk of ICH. [ABSTRACT FROM AUTHOR]

Background: Early repair of the ruptured cerebral aneurysm (RRCA), preferably within 24 h of onset, is endorsed by clinical guideline as the preferred management strategy for patients with aneurysmal subarachnoid hemorrhage (aSAH). However, a comprehensive picture of this guideline-recommended usage in contemporary clinical practice is not available. Aims: This study aimed to characterize trends over time and practice variation in the implementation of an early RRCA strategy among patients with aSAH in a large, national representative data. Methods: Using data from the 2012–2019 National Inpatient Sample, we measured trends in the proportion of early RRCA, defined as within day 1 of admission, overall, and by demographic and geographical subgroups. In addition, we created multilevel regression models to quantify hospital-level variation in the early RRCA rates. Results: We identified 82,615 aSAH hospitalizations (mean age = 56.1 years; 68.9% women) undergoing RRCA and, among these, 84.0% (95% confidence interval (CI) = 83.4–84.7%) receiving early RRCA. The proportion of early RRCA increased steadily from 82.5% in 2012 to 85.8% in 2019 (p for trend <0.001). The proportion of patients receiving early RRCA across geographic regions ranged from 78.7% to 87.9%, with a median (interquartile range (IQR)) of 84.2% (83.0–86.1%). In contrast, the delivery of early RRCA varied widely among hospitals, with a median (IQR) rate of 86.1% (75.0–100.0%) and a range from 0% to 100.0%. The median odds ratio for the early use of RRCA treatment was 1.24 (95% CI = 1.21–1.27) in 2019, indicating 24% increased odds of implementing early RRCA if moving from a lower-use to a higher-use hospital. Conclusions: Most patients in the United States with aSAH received early RRCA treatment and exhibited an upward trend over the recent 8-year period. However, substantial variation in access to early RRCA was observed across population subgroups, particularly at the hospital level. Future efforts are necessary to identify further sources of this variation and to develop initiatives that could represent an opportunity to optimize guideline-based quality of care in aSAH management. Data access statement: The data are available from the corresponding author upon reasonable request following completion of onboarding and verification procedures as specified by the HCUP. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage (ICH) is a severe subtype of stroke linked to high morbidity and mortality rates. However, the underlying mechanisms of neuronal injury post-ICH remain poorly understood. In this study, we investigated sphingolipid metabolism alterations in neurons using lipidomics and explored the regulatory mechanisms involved. Western blot and live-cell imaging were applied to detect mitochondrial quality and mitophagy level. We found a significant upregulation of ceramide synthase 6 (CERS6)-related C16 ceramide biosynthesis after hemin treatment. Knockdown of CERS6 notably ameliorated mitochondrial dysfunction and reduced neuronal apoptosis. Additionally, impaired neuronal mitophagy was observed after hemin treatment, which was restored by CERS6 knockdown. Mechanistically, CERS6 impaired mitophagy by interacting with sequestosome 1, leading to mitochondrial dysfunction and neuronal apoptosis. Our study explored the relationship between ceramide metabolism and mitophagy in neurons, revealing the pro-apoptotic role of CERS6 while providing a potential therapeutic target for patients with ICH. [Display omitted] • The autophagy flux of neurons is blocked post intracerebral hemorrhage, accompanied by severe mitochondrial dysfunction. • Hemin induces lipid metabolism reprogramming in neurons, elevating CERS6-derived C16-ceramide biosynthesis. • Knockdown of CERS6 notably ameliorates hemin-induced mitochondrial dysfunction and apoptosis in neurons. • CERS6 impairs mitophagy by interacting with SQSTM1, thus leading to excessive neuronal apoptosis. [ABSTRACT FROM AUTHOR]

Background: Hemorrhagic stroke is a potentially fatal condition with high mortality and morbidity. However, there is a lack of evidence for this relationship in critically ill patients with hemorrhagic stroke. This study aims to explore the relationship between hypomagnesemia and ICU mortality in severe hemorrhagic stroke patients. Methods: The study included 2,026 severe hemorrhagic stroke patients from the Electronic Intensive Care Unit Collaborative Study database, categorized into hypomagnesemia and non-hypomagnesemia groups based on serum magnesium levels. Primary outcome was ICU mortality. Secondary outcome was mechanical ventilation use. Multivariate Cox proportional hazards regression analyses were used to study the relationship between hypomagnesemia and the outcomes. We also performed a cumulative survival rate analysis by Kaplan–Meier curves. Results: A total of 2,026 severe hemorrhagic stroke patients, aged over 16 and hospitalized in the ICU for more than 24 h, were enrolled. Among them, 277 (13.7%) died in the ICU, and hypomagnesemia was observed in 489 patients. Multivariable Cox regression analyses demonstrated that hypomagnesemia was related to a 28% increased risk of ICU mortality (HR 1.28, 95% CI [1.02–1.68], p = 0.035) and a 15% increased risk of mechanical ventilation use (HR 1.15, 95% CI [1.04—1.33], p = 0.010) in severe hemorrhagic stroke patients. Conclusions: Our findings suggested that hypomagnesemia is associated with increased risks of ICU mortality and mechanical ventilation use in severe hemorrhagic stroke patients. Future randomized, prospective studies are needed to elucidate the role of hypomagnesemia and explore potential interventions. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage (ICH) represents one of the most devastating forms of stroke, characterized by spontaneous bleeding into the brain parenchyma. This neurological emergency carries a substantial burden of mortality and long-term disability worldwide. A comprehensive understanding of ICH's evolving global impact from 1990 to 2021 remains essential for healthcare planning and resource allocation. We conducted a systematic analysis of ICH burden utilizing data from the Global Burden of Disease (GBD) Study 2021. Key epidemiological indicators were extracted, including prevalence, incidence, mortality, and disability-adjusted life-years (DALYs). Temporal trends were quantified through estimated annual percentage changes (EAPCs) in age-standardized rates of prevalence (ASPR), incidence (ASIR), mortality (ASDR), and DALYs across the study period. The association between disease burden and socioeconomic development was examined using the sociodemographic index (SDI) as a metric of societal development. This analytical framework enabled assessment of ICH burden across global, regional, and national scales while accounting for demographic and socioeconomic variations. From 1990 to 2021, while absolute ICH cases increased globally, age-standardized incidence rates declined. Our novel geographic analysis revealed East Asia bearing the highest burden, with Eastern Europe showing the highest age-standardized rates. Gender analysis identified distinct age-specific patterns, with males above 35 showing higher risk, particularly in Eastern Europe, while South Asia demonstrated minimal gender differences. Our innovative analysis during COVID-19 revealed healthcare system strength significantly impacted ICH outcomes, with well-resourced countries maintaining better outcomes. Regional risk factor assessment showed varying impacts of high systolic blood pressure across regions, highest in Southern Sub-Saharan Africa and lowest in Oceania. Future projections through 2030 indicate improving survival rates in most regions, except in low-income areas, highlighting persistent healthcare disparities. While the absolute number of ICH cases, deaths, and DALYs increased globally from 1990 to 2021, age-standardized rates showed a decreasing trend. This suggests improvements in prevention and management strategies over time. However, the burden of ICH remains substantial and unevenly distributed across regions, with lower SDI areas facing a disproportionately higher burden. These findings highlight the need for targeted interventions and resource allocation, particularly in regions with higher ICH burden, to further reduce the global impact of this devastating condition. [ABSTRACT FROM AUTHOR]

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Intracerebral hemorrhage (ICH) is the most common subtype of hemorrhagic stroke causing significant morbidity and mortality. Previously clinical treatments for ICH have largely been based on a single pathophysiological perspective, and there remains a lack of curative interventions. Following the rupture of cerebral blood vessels, blood metabolites activate resident immune cells such as microglia and astrocytes, and infiltrate peripheral immune cells, leading to the release of a series of inflammatory mediators. Degradation of hemoglobin produces large amounts of iron ions, leading to an imbalance of iron homeostasis and the production of large quantities of harmful hydroxyl radicals. Neuroinflammation and dysregulation of brain iron metabolism are both important pathophysiological changes in ICH, and both can exacerbate secondary brain injury. There is an inseparable relationship between brain iron metabolism disorder and activated glial cells after ICH. Glial cells participate in brain iron metabolism through various mechanisms; meanwhile, iron accumulation exacerbates neuroinflammation by activating inflammatory signaling pathways modulating the functions of inflammatory cells, and so on. This review aims to explore neuroinflammation from the perspective of iron metabolism, linking the complex pathophysiological changes, delving into the exploration of treatment approaches for ICH, and offering insights that could enhance clinical management strategies. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage (ICH) is a major public health challenge worldwide, and is associated with elevated rates of mortality, disability, and morbidity, especially in low- and middle-income nations. However, our knowledge of the detailed molecular processes involved in ICH remains insufficient, particularly those involved in the secondary injury stage, resulting in a lack of effective treatments for ICH. Human platelet lysates (HPL) are abundant in bioactive factors, and numerous studies have demonstrated their beneficial effects on neurological diseases, including their anti-neuroinflammatory ability, anti-oxidant effects, maintenance of blood–brain barrier integrity, and promotion of neurogenesis. In this review, we thoroughly explore the potential of HPL for treating ICH from three critical perspectives: the rationale for selecting HPL as a treatment for ICH, the mechanisms through which HPL contributes to ICH management, and the additional measures necessary for HPL as a treatment for ICH. We elucidate the role of platelets in ICH pathophysiology and highlight the limitations of the current treatment options and advancements in preclinical research on the application of HPL in neurological disorders. Furthermore, historical developments and preparation methods of HPL in the field of biomedicine are discussed. Additionally, we summarize the bioactive molecules present in HPL and their potential therapeutic effects in ICH. Finally, we outline the issues that must be addressed regarding utilizing HPL as a treatment modality for ICH. [ABSTRACT FROM AUTHOR]

Neuropsychiatric adverse events (AEs) significantly impact the quality of life of patients using avapritinib. However, the majority of current data comes from pre-marketing, with limited real-world studies. Our research aimed to explore post-marketing data of avapritinib. We evaluated the signals of avapritinib-related neuropsychiatric AEs by data mining using the FDA Adverse Event Reporting System (FAERS). Reporting odds ratio (ROR) and information component (IC) were employed to quantify the signals from the first quarter of 2020 through the fourth quarter of 2023. Subsequently, stratified analyses were conducted to further explore the effect of different stratification schemes on the association between avapritinib and neuropsychiatric AEs. Finally, a combination medication analysis was conducted to explore the impact of the co-administration of neuropsychiatric AEs. A total of 2029 neuropsychiatric AEs were reported, and 49 signals were detected, of which 5 were determined to be new signals. Avapritinib was significantly associated with the occurrence of neuropsychiatric AEs (ROR: 1.52, 95% CI: 1.44–1.61; IC: 0.43, IC025: 0.35). The stratified analysis found that gender, age and eight preferred terms (PTs), including cerebral haemorrhage, may affect the severity of AEs. Combination medication analysis showed that combining avapritinib with 19 other medications, including prochlorperazine, may increase the risk of neuropsychiatric AEs. The median time-to-onset (TTO) of avapritinib-related neuropsychiatric AEs was 32 (interquartile range [IQR] 2-200) days, with about 65% of cases occurring within the first three months of treatment. An increase in the signal for neuropsychiatric AEs was identified in post-marketing studies of avapritinib. Clinicians are advised to remain vigilant for such events, particularly during the initial stages of treatment with avapritinib. [ABSTRACT FROM AUTHOR]

Patients with intracranial aneurysm (IA) are at high risk of cerebral hemorrhage, which is associated with high mortality. Craniotomy or interventional endovascular coiling are common treatment methods in clinical practice, depending on the patient's condition. However, the recurrence rate of IA after either method remains unclear. This meta-analysis was conducted to study the relationship between different treatment regimens and IA recurrence. PubMed, CNKI, Web of Science, Wan Fang, and VIP databases were used to identify studies on "intracranial aneurysm," "craniotomy," "endovascular coiling," and "recurrence rate." Included studies adhered to rigorous screening and diagnostic criteria, and statistical models were applied based on homogeneity testing. This study encompassed 28 articles, including five on craniotomy and 23 on endovascular coiling, published between 2007 and 2022; among 1,448 cases treated with craniotomy, 20 experienced recurrences (recurrence rate: 1.4%, 95% CI: 0.2%), while among 5,975 cases treated with endovascular coiling, 872 cases experienced recurrence (recurrence rate: 14.6%, 95% CI: 14%, 20%). High heterogeneity (87%) was observed in the endovascular coiling, likely due to differences in patient demographics and aneurysm characteristics. For IAs, although endovascular coiling has advantages in terms of lower trauma and faster recovery, its high recurrence rate warrants closer post-treatment monitoring. Despite being more invasive, Craniotomy may be preferable in specific cases, such as when treating aneurysms with complex shapes or challenging locations. Treatment choice should be individualized, and future advancements in endovascular coiling technologies may help reduce recurrence rates. [ABSTRACT FROM AUTHOR]

AbstractBACKGROUNDMETHODSRESULTSCONCLUSIONSPrevious studies have shown that an increased number of immune cells is closely associated with the onset and course changes of intracerebral hemorrhage, but the exact causal relationship has not been clarified. The aim of this study was to investigate the causal relationship between immune cells and intracerebral hemorrhage by a two-way Mendelian randomization method.Two sets of SNPs were used as instrumental variables and two-way Mendelian randomization analyses were performed and leave-one-out method were used to assess the validity and heterogeneity of the included genetic variation instruments. The level of multiplicity and heterogeneity of the included genetic variance instruments was assessed.The results showed a clear causal relationship between three immune cells and intracerebral hemorrhage, and no heterogeneity between SNPs related to intracerebral hemorrhage, while scatterplot and funnel plot confirmed that the causality was less likely to be biased; MR-Egger results suggested that no genetic pleiotropy was found. Leave-one-out analysis was applied to suggest that the MR analysis results for a single SNP were robust; meanwhile, Meta-analysis was applied to combine the two intracerebral hemorrhage datasets, and the analysis results suggested that in the fixed-effects model and random-effects model, the immunocyte CD66b on Granulocytic Myeloid-Derived Suppressor Cells and other three immune cells were significantly causally associated with intracerebral hemorrhage, while the heterogeneity test suggested that there was no significant difference between the different datasets.The present study found a significant causal relationship between specific immune cell phenotypes and intracerebral hemorrhage by Mendelian randomization analysis. [ABSTRACT FROM AUTHOR]

Central nervous system (CNS) injuries, such as ischemic stroke (IS), intracerebral hemorrhage (ICH) and traumatic brain injury (TBI), are a significant global burden. The complex pathophysiology of CNS injury is comprised of primary and secondary injury. Inflammatory secondary injury is incited by damage-associated molecular patterns (DAMPs) which signal a variety of resident CNS cells and infiltrating immune cells. Extracellular cold-inducible RNA-binding protein (eCIRP) is a DAMP which acts through multiple immune and non-immune cells to promote inflammation. Despite the well-established role of eCIRP in systemic and sterile inflammation, its role in CNS injury is less elucidated. Recent literature suggests that eCIRP is a pleiotropic inflammatory mediator in CNS injury. eCIRP is also being evaluated as a clinical biomarker to indicate prognosis in CNS injuries. This review provides a broad overview of CNS injury, with a focus on immune-mediated secondary injury and neuroinflammation. We then review what is known about eCIRP in CNS injury, and its known mechanisms in both CNS and non-CNS cells, identifying opportunities for further study. We also explore eCIRP's potential as a prognostic marker of CNS injury severity and outcome. Next, we provide an overview of eCIRP-targeting therapeutics and suggest strategies to develop these agents to ameliorate CNS injury. Finally, we emphasize exploring novel molecular mechanisms, aside from neuroinflammation, by which eCIRP acts as a critical mediator with significant potential as a therapeutic target and prognostic biomarker in CNS injury. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess the risk of death from non-traumatic intracerebral hemorrhage (ICH) using a machine learning model. Methods: 1274 ICH patients who met the specified inclusion and exclusion criteria were analyzed retrospectively in the MIMIC IV 3.0 database. Patients were randomly divided into training, validation, and testing datasets in a ratio of 6:2:2 based on the outcome distribution. Data from the Second Hospital of Lanzhou University were used as an external validation set. This study used LASSO regression and multivariable logistic regression analysis to screen for features. We then employed XGBoost to construct a machine-learning model. The model's performance was evaluated using ROC curve analysis, calibration curve analysis, clinical decision curve analysis, sensitivity, specificity, accuracy, and F1 score. Conclusively, the SHapley Additive exPlanations (SHAP) method was employed to interpret the model's predictions. Results: Deaths occurred in 572 out of the 1274 ICH cases included in the study, resulting in an incidence rate of 44.9%. The XGBoost model achieved a high AUC when predicting deaths in ICH patients (train: 0.814, 95%CI: 0.784 − 0.844; validation: 0.715, 95%CI: 0.653 − 0.777; test: 0.797, 95%CI: 0.743 − 0.851). The importance of SHAP variables in the model ranked from high to low was: 'GCS motor', 'Age', 'GCS eyes', 'Low density lipoprotein (LDL)', ' Albumin', ' Atrial fibrillation', and 'Gender'. The XGBoost model demonstrated good predictive performance in both the validation and external validation datasets. Conclusions: The XGBoost machine learning model we built has demonstrated strong performance in predicting the risk of death from ICH. Furthermore, the SHAP provides the possibility of interpreting machine learning results. [ABSTRACT FROM AUTHOR]

Background: Spontaneous intracerebral hemorrhage (SICH) is the second most common cause of cerebrovascular disease after ischemic stroke, with high mortality and disability rates, imposing a significant economic burden on families and society. This retrospective study aimed to develop and evaluate an interpretable machine learning model to predict functional outcomes 3 months after SICH. Methods: A retrospective analysis was conducted on clinical data from 380 patients with SICH who were hospitalized at three different centers between June 2020 and June 2023. Seventy percent of the samples were randomly selected as the training set, while the remaining 30% were used as the validation set. Univariate analysis, Least Absolute Shrinkage and Selection Operator (LASSO) regression, and Pearson correlation analysis were used to screen clinical variables. The selected variables were then incorporated into five machine learning models: complementary naive bayes (CNB), support vector machine (SVM), gaussian naive bayes (GNB), multilayer perceptron (MLP), and extreme gradient boosting (XGB), to assess their performance. Additionally, the area under the curve (AUC) values were evaluated to compare the performance of each algorithmic model, and global and individual interpretive analyses were conducted using importance ranking and Shapley additive explanations (SHAP). Results: Among the 380 patients, 95 ultimately had poor prognostic outcomes. In the validation set, the AUC values for CNB, SVM, GNB, MLP, and XGB models were 0.899 (0.816–0.979), 0.916 (0.847–0.982), 0.730 (0.602–0.857), 0.913 (0.834–0.986), and 0.969 (0.937–0.998), respectively. Therefore, the XGB model performed the best among the five algorithms. SHAP analysis revealed that the GCS score, hematoma volume, blood pressure changes, platelets, age, bleeding location, and blood glucose levels were the most important variables for poor prognosis. Conclusion: The XGB model developed in this study can effectively predict the risk of poor prognosis in patients with SICH, helping clinicians make personalized and rational clinical decisions. Prognostic risk in patients with SICH is closely associated with GCS score, hematoma volume, blood pressure changes, platelets, age, bleeding location, and blood glucose levels. [ABSTRACT FROM AUTHOR]

Objective: Intracerebral hemorrhage (ICH) is a common cerebrovascular disease characterized by high mortality and disability rates. Neuritin, significantly expressed in injured brain tissues, is implicated in the molecular mechanisms underlying acute brain injury. We aimed to explore the prognostic and predictive value of serum neuritin in ICH. Methods: In this prospective cohort study, serum neuritin levels were measured at admission in 202 patients, on post-ICH days 1, 3, 5, 7, and 10 in 54 of these patients, and at the time of enrollment in 100 healthy controls. The Glasgow Coma Scale (GCS) and hematoma volume were used as severity indicators. A poor prognosis was defined as a modified Rankin Scale (mRS) score of 3–6 at 90 days after ICH. END was defined as a decrease of ≥2 points in the GCS score within 24 h of admission. A multivariate logistic regression model was used to assess the independent relationships between serum neuritin levels, END, and poor prognosis. Results: Serum neuritin levels were significantly increased at the time of patient admission, continued to rise on day 1, peaked on day 3, and then gradually diminished from day 5 until day 10. The levels remained substantially higher in patients compared to healthy controls throughout the 10-day period. The levels were independently related to GCS scores and hematoma volume. In subgroup analyses, the levels showed a linear relationship with the likelihood of experiencing END and poor prognosis at the 90-day mark after ICH. Additionally, the levels were independently associated with END, ordinal mRS scores, and poor prognosis. Under receiver operating characteristic (ROC) curve analysis, serum neuritin levels effectively predicted both END and poor prognosis. Two models incorporating GCS, hematoma volume, and serum neuritin levels were developed and represented using two nomograms separately to estimate END risks and poor prognosis. These models demonstrated clinical efficiency, stability, and validity in ROC, calibration, and decision curve analyses. Internal validation of the models was conducted using a randomly extracted subset of 101 patients. Furthermore, two specific weighted scoring systems were developed to optimize clinical prediction of poor prognosis and END after ICH. Conclusion: Elevated serum neuritin levels are strongly associated with disease severity, END, and 90-day poor neurological outcomes following ICH, establishing serum neuritin as a potential prognostic biomarker for ICH. [ABSTRACT FROM AUTHOR]

Background: Amphetamines possess sympathomimetic properties that can affect cerebral vasculature though conflicting reports exist about their effect on vasospasm risk and clinical outcomes in aneurysmal subarachnoid hemorrhage. This study aimed to characterize the impact of recent amphetamine use on vasospasm development in aneurysmal subarachnoid hemorrhage as well as neurological outcomes. Methods: We retrospectively screened 441 consecutive patients admitted with a diagnosis of subarachnoid hemorrhage who underwent at least one cerebral digital subtraction angiogram. Patients were excluded if no urinary toxicology screen was performed within 24 h of admission, if there was a diagnosis of non-aneurysmal subarachnoid hemorrhage, or if ictus was greater than 72 h from hospital admission. Vasospasm characteristics were collected from digital subtraction angiography and transcranial Doppler studies. Results: 129 patients were included and 24 tested positive for amphetamines on urine drug screen. No significant differences were found in respect to patient age, sex, or admission clinical severity scales (Hunt-Hess and modified Fisher) based on amphetamine use. There was no difference in the severity of vasospasm or time to peak severity based on recent amphetamine use. A trend toward more isolated posterior circulation vasospasm was observed in the amphetamine present group (16.7% vs. 4.8%, p = 0.06), while there was higher incidence of anterior circulation vasospasm in the amphetamine absent group (79.2% vs. 94.3%, p = 0.03). There was no difference in delayed cerebral ischemia incidence, length of hospital stay, need for ventriculoperitoneal shunt placement, functional outcome at discharge or hospital mortality based on amphetamine use. Interpretation: Recent amphetamine use was not associated with worse vasospasm severity or delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage patients. Further investigations about localized effects in the posterior circulation and impact on long-term functional outcomes are warranted. [ABSTRACT FROM AUTHOR]

Background: Intracerebral hemorrhage (ICH) is the most lethal and devastating subtype of stroke. Basal ganglia hemorrhage and thalamic hemorrhage are the most common types of ICH, accounting for 50–70% of all ICH cases, leading to disability and death, and it involves the posterior limb of the internal capsule to varying degrees. In this study, we investigated the impact of varying degrees of the involvement of the posterior limb of the internal capsule on the prognosis of patients with basal ganglia and thalamic ICH and assessed whether it improves the predictive accuracy of the max-ICH score, an existing scale for ICH functional outcome. Methods: This is a multicenter, retrospective, observational study. We graded the involvement of the posterior limb of the internal capsule according to the degree of compression and injury (called iICH, ranging from 0 to 4). An unfavorable outcome was defined as a 90-day modified Rankin Scale (mRS) of > 2. Multivariate logistic regression analysis was used to identify independent risk factors associated with unfavorable prognosis. The discrimination was verified using receiver operating characteristic curve (ROC) analysis, while the calibration was verified by the Hosmer-Lemeshow test. Results: Of the 305 patients included, 188 from Nanfang Hospital were assigned to the development cohort, and 117 from Heyuan People's Hospital and Huadu District People's Hospital were assigned to the validation cohort. In the development cohort, iICH was identified as an independent factor of a 90-day unfavorable outcome, and the area under the ROC (AUC) was 0.774. When combined with the iICH, the AUC of max-ICH was significantly elevated from 0.816 to 0.866. Comparable results were found in the validation cohort. Conclusions: Increased involvement of the posterior limb of the internal capsule is associated with a worse outcome in patients with basal ganglia and thalamic ICH. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the clinical features and risk factors of the human immunodeficiency virus (HIV)-infected patients with intracerebral hemorrhage (ICH). Patients and methods: The patients with HIV-infected without ICH group were matched to the group of HIV-infected ICH patients. Logistic regression analysis using 1:1 propensity score matching (PSM) was performed to investigate the independent risk factors for ICH in HIV-infected patients. The receiver operating characteristic (ROC) curve was configured to calculate the optimal predictors of ICH in HIV-infected patients. Results: A total of 59 HIV-infected patients with ICH and 180 HIV-infected patients without ICH were included. A cohort of 118 patients was ascertained utilizing PSM. Multivariate binary logistic regression analysis revealed that drug abuse-related HIV-infected, prolonged prothrombin time (PT), and elevated triglyceride (TG) levels were independent risk factors of ICH in HIV-infected patients. The ROC curve demonstrated that the combined predictor, composed of drug abuse-related HIV-infected, prolonged PT, and elevated TG levels, exhibited the highest area under the curve (AUC), with a cut-off point at 0.426, sensitivity of 78%, and specificity of 81.4%. Conclusion: The present study revealed that a valuable factor combined with drug abuse-related HIV-infected, prolonged PT, and elevated serum TG levels could serve as predictors of ICH in HIV-infected patients. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage (ICH) is a leading cause of stroke-related mortality and long-term disability, with initial ICH volume, age, location of the hemorrhage, and clinical severity being key predictors of outcome. While clinical scores incorporating these elements are validated and exhibit good inter-rater reliability, their accuracy in predicting long-term recovery remains suboptimal. Non-invasive brain stimulation (NIBS) has emerged as a potential adjunct for improving both prognostication and functional recovery in ICH survivors. Despite promising results, heterogeneity in stimulation protocols, patients' populations, and outcome measures have prevented NIBS implementation in clinical practice. This narrative review summarizes the available evidence on the association between NIBS, outcome prediction and functional recovery, discussing current challenges and future perspectives. [ABSTRACT FROM AUTHOR]

Objective: This study aims to evaluate the clinical significance of ultrasound-based measurement of optic nerve sheath diameter (ONSD) in predicting intracerebral hemorrhage (ICH) complicated by cerebral-cardiac syndrome (CCS). Methods: Patients with ICH and who were treated in the intensive care unit (ICU) at Shijiazhuang People's Hospital between October 2021 and November 2022 were included in this study. Participants were divided into two groups: those with CCS and those without. Various clinical parameters, including sex, age, electrocardiogram (ECG) findings, myocardial markers, B-type natriuretic peptide (BNP) levels, Glasgow Coma Scale (GCS) score, ONSD, hematoma volume, and midline shift, were assessed. A binary logistic regression model and receiver operating characteristic (ROC) curve analysis were employed to determine the predictive value of each risk factor for ICH complicated by CCS. Results: ONSD measurements differed significantly between males and females, with males exhibiting larger ONSD values. Additionally, significant differences were observed in ONSD, hematoma volume, midline shift, and GCS scores between the CCS and non-CCS groups. A direct correlation was identified between ONSD and both hematoma volume and midline shift. Multiple regression analysis demonstrated that ONSD, hematoma volume, and GCS score are independent risk factors for predicting ICH complicated by CCS. ROC curve analysis for ONSD in predicting ICH with CCS revealed an area under the curve (AUC) of 0.80, with an optimal cutoff value of 5.88 cm, yielding a sensitivity of 83% and a specificity of 79%. When ONSD, hematoma volume, and GCS score were combined, the predictive accuracy improved, with an AUC of 0.880. Conclusion: Males tend to have larger ONSD measurements compared to females. Ultrasound is a valuable tool for measuring ONSD, comparable to computed tomography, and is useful in detecting intracranial hypertension and mass effect. ONSD, hematoma volume, and GCS score are independent predictors of ICH complicated by CCS, and their combined use enhances predictive accuracy. [ABSTRACT FROM AUTHOR]

Background: Numerous noncontrast computed tomography (NCCT) markers have been reported and validated as effective predictors of hematoma expansion (HE). Our objective was to develop and validate a score based on NCCT markers and clinical characteristics to predict risk of HE in acute intracerebral hemorrhage (ICH) patients. Methods: We prospectively collected spontaneous ICH patients at the First Affiliated Hospital of Chongqing Medical University to form the development cohort (n = 395) and at the Third Affiliated Hospital of Chongqing Medical University to establish the validation cohort (n = 139). We adopted a revised HE definition, incorporating the standard definition of HE (> 6 mL or > 33%) and intraventricular hemorrhage (IVH) expansion (any new IVH or IVH expansion ≥ 1 ml). The predictive score was formulated based on the parameter estimates derived from the multivariable logistic regression analysis. Result: The Glasgow Coma Scale, island sign, ventricular hemorrhage and time elapsed from onset to NCCT scan (GIVE) score was created as a total of individual points (0–6) based on Glasgow Coma Scale (2 points for ≤ 11), island sign (1 point for presence), ventricular hemorrhage (1 point for presence), and time elapsed from onset to NCCT scan (2 points for ≤ 2.5 h). The c statistic was 0.72(95% confidence interval [CI], 0.66–0.78) and 0.73(95% CI, 0.63–0.82) in the development and validation cohorts, respectively. Conclusion: A six-point scoring algorithm has been developed and validated to assess the risk of HE in patients with ICH. This scoring system facilitates the rapid and accurate identification of patients at increased risk for HE. [ABSTRACT FROM AUTHOR]

Basal ganglia hemorrhage (BGH) is a prevalent site for intracerebral hemorrhage. Although neuroendoscopy (NE) surgery has emerged as a less invasive alternative to craniotomy (CT), the optimal surgical method remains debatable. This systematic review and meta-analysis aimed to compare the efficacy and safety of NE versus CT in the management of BGH. A systematic search of PubMed, Embase, Cochrane Library, and Web of Science databases was conducted to identify eligible randomized controlled trials (RCTs) comparing NE surgery with CT in BGH patients. Outcomes included mortality, hematoma evacuation rate, good functional outcome (GFO), operative time, infection, pulmonary infection, and postoperative complication. Risk of bias was assessed with Cochrane's ROB-2 tool. Four RCTs were included, comprising 423 patients. NE surgery showed no significant benefit in mortality (p = 0.12) and GFO (p = 0.18). However, NE was associated with a higher hematoma evacuation rate (p = 0.007), shorter operative time (p < 0.00001), and lower rates of infection (p < 0.0001), pulmonary infection (p < 0.0001), and postoperative complications (p < 0.00001). Future research should be designed to assess whether hematoma evacuation using either technique improves outcomes in comparison to optimal medical management in this population. [ABSTRACT FROM AUTHOR]

Introduction: Patients with cerebral hemorrhage often require a tracheal intubation to protect the airway and maintain oxygenation. Due to the use of analgesic and sedative drugs during endotracheal intubation and the opening of the glottis may easily cause aspiration pneumonia. Ceftriaxone is a semi-synthetic third-generation cephalosporin with strong antimicrobial activity against most gram-positive and gram-negative bacteria. It can effectively prevent and treat aspiration pneumonia. Methods and analysis: This is a prospective, randomized, controlled, double-blind clinical study. Patients with intracerebral hemorrhage (ICH) undergoing endotracheal intubation in Dong E Hospital of Shandong Province from April 2023 to April 2025 will be enrolled and randomly assigned to the intervention group or control group. The intervention group will be treated using 100mL 0.9% sodium chloride with 2g ceftriaxone intravenously over the course of one hour beginning within two hours after endotracheal intubation. The control group will be given 100mL 0.9% sodium chloride injection intravenously of the course of one hour beginning within two hours after endotracheal intubation. The primary outcome is the incidence of aspiration pneumonia within 48 hours after endotracheal intubation. Secondary outcomes include: intensity of antimicrobial use, length of hospital stay, duration without mechanical ventilation, and 28-day mortality. Discussion: The primary objective of this study is to explore whether a single dose of ceftriaxone administered during endotracheal intubation in patients with ICH reduced the incidence of pneumonia within 48 hours and provide evidence for the prevention of aspiration pneumonia in patients with ICH with endotracheal intubation. Trial registration: The trial is registered at the Chinese Clinical Trial Registry: ChiCTR2200066837. Registered on December 19, 2022. [ABSTRACT FROM AUTHOR]

Cerebral microbleeds (CMBs) are small, hypointense hemosiderin deposits in the brain measuring 2–10 mm in diameter. As one of the important biomarkers of small vessel disease, they have been associated with various neurodegenerative and cerebrovascular diseases. Hence, automated detection, and subsequent extraction of clinically useful metrics (e.g., size and spatial distribution) from CMBs are essential for investigating their clinical impact, especially in large-scale studies. While some work has been done for CMB segmentation, extraction of clinically relevant information is not yet explored. Herein, we propose the first automated method to characterise CMBs using their size and spatial distribution, i.e., CMB count in three regions (and their substructures) used in Microbleed Anatomical Rating Scale (MARS): infratentorial, deep, and lobar. Our method uses structural atlases of the brain for determining individual regions. On an intracerebral haemorrhage study dataset, we achieved a mean absolute error of 2.5 mm for size estimation and an overall accuracy > 90% for automated rating. The code and the atlas of MARS regions in Montreal Neurological Institute—MNI space are publicly available. Relevance statement: Our method to automatically characterise cerebral microbleeds (size and location) showed a mean absolute error of 2.5 mm for size estimation and an over 90% accuracy for rating of infratentorial, deep and lobar regions. This is a promising approach to automatically provide clinically relevant cerebral microbleeds metrics. Key Points: We present a method to automatically characterise cerebral microbleeds according to size and location. The method achieved a mean absolute error of 2.5 mm for size estimation. Automated rating for infratentorial, deep, and lobar regions achieved an over 90% overall accuracy. We made the code and atlas of Microbleed Anatomical Rating Scale regions publicly available. [ABSTRACT FROM AUTHOR]

Background: There are sex disparities in the risk of ruptured intracranial aneurysm (IA), but which sex-specific factors are related to ruptured IA remains inconclusive. Methods: Data from electronic medical records from two tertiary hospitals, collected between January 2012 and December 2019, were analyzed for this study. All IAs were confirmed by computed tomographic angiography or digital subtraction angiography. Sex-specific factors associated with ruptured IA were analyzed using multivariable logistic models with a case–control study design. Age, aneurysm size, and aneurysm location subgroup analyses were conducted according to sex. Results: In total, 1883 patients [1,117 (59.32%) female, 766 (40.68%) male] with 2,423 IAs were included; 734 (38.98%) of patients had ruptured IAs. Compared with males, females had a higher risk of ruptured IA [odds ratio, 1.72 (95% confidence interval, 1.38–2.14)]. Age, aneurysm location, aneurysm size, multiple aneurysms, hypertension, history of intracerebral hemorrhage, and ischemic stroke were associated with risk of IA rupture in both sexes. In the subgroups based on the covariates used in this study, we only identified statistically significant interaction between sex and age. Although ruptured IAs were most common in males and females aged 50–59 and 60–69 years, respectively, risk of IA rupture peaked at ages 30 and 30–50 years in females and males, respectively, and decreased with age in both sexes. Conclusion: Females have an overall greater IA incidence and higher risk of IA rupture than males. Young age is one sex-specific risk factor associated with ruptured IA which could related to potential influence of hypertension, which might suggest more attention of IA rupture prevention in younger female. [ABSTRACT FROM AUTHOR]

Background: Intracerebral hemorrhage (ICH) is a common subtype of stroke, characterized by a high mortality rate and a tendency to cause neurological damage. This study aims to investigate the role and mechanisms of lncRNA HCP5 in ICH. Methods: We simulated ICH in vivo by injecting collagenase into rats and established an in vitro model using hemoglobin-treated BV2 cells. HCP5 and miR-195-5p levels were quantified by RT-qPCR. mNSS score was used to evaluate neurological deficits in the rats. The dry-wet weight method assessed the degree of brain edema. Cell viability and apoptosis rates were determined using the CCK-8 assay and flow cytometry, respectively. The targeting relationship between HCP5 and miR-195-5p was confirmed using dual-luciferase reporter assays and RNA immunoprecipitation. ELISA was utilized to measure inflammatory factors, and commercial kits were used to detect MDA and ROS levels. Results: In the ICH model rats, HCP5 levels were significantly elevated. It was also found that silencing HCP5 significantly alleviated brain edema and neurological deficits in the ICH rats, and there was a marked improvement in ICH-induced neuroinflammation and oxidative stress. Moreover, HCP5 was found to sponge miR-195-5p, and inhibiting miR-195-5p could counteract the neuroprotective effects of silencing HCP5. Similar results were obtained in the in vitro experiments with BV2 cells. Conclusions: Silencing HCP5 can alleviate brain edema, neurological dysfunction, neuroinflammation, and oxidative stress caused by ICH via miR-195-5p. [ABSTRACT FROM AUTHOR]

Background: Intracerebral hemorrhage (ICH) causes prominent deposition of extracellular matrix molecules, particularly the chondroitin sulphate proteoglycan (CSPG) member neurocan. In tissue culture, neurocan impedes the properties of oligodendrocytes. Whether therapeutic reduction of neurocan promotes oligodendrogenesis and functional recovery in ICH is unknown. Methods: Mice were retro-orbitally injected with adeno-associated virus (AAV-CRISPR/Cas9) to reduce neurocan deposition after ICH induction by collagenase. Other groups of ICH mice were treated with vehicle or a drug that reduces CSPG synthesis, 4-4-difluoro-N-acetylglucosamine (difluorosamine). Rota-rod and grip strength behavioral tests were conducted over 7 or 14 days. Brain tissues were investigated for expression of neurocan by immunofluorescence microscopy and western blot analysis. Brain cryosections were also stained for microglia/macrophage phenotype, oligodendrocyte lineage cells and neuroblasts by immunofluorescence microscopy. Tissue structural changes were assessed using brain magnetic resonance imaging (MRI). Results: The adeno-associated virus (AAV)-reduction of neurocan increased oligodendrocyte numbers and functional recovery in ICH. The small molecule inhibitor of CSPG synthesis, difluorosamine, lowered neurocan levels in lesions and elevated numbers of oligodendrocyte precursor cells, mature oligodendrocytes, and SOX2+ nestin+ neuroblasts in the perihematomal area. Difluorosamine shifted the degeneration-associated functional state of microglia/macrophages in ICH towards a regulatory phenotype. MRI analyses showed better fiber tract integrity in the penumbra of difluorosamine mice. These beneficial difluorosamine results were achieved with delayed (2 or 3 days) treatment after ICH. Conclusion: Reducing neurocan deposition following ICH injury is a therapeutic approach to promote histological and behavioral recovery from the devastating stroke. [ABSTRACT FROM AUTHOR]

BACKGROUND: Multiple studies have shown that early decompressive surgery in patients with intracerebral hemorrhage can effectively limit hematoma expansion, reduce perihematomal edema, and improve prognosis. However, these studies are limited by small sample sizes and short follow-up times. OBJECTIVE: To analyze the effect of early decompressive surgery on the long-term prognosis of patients with cerebral hemorrhage and identify the influencing factors for poor prognosis. METHODS: A retrospective analysis of 78 patients with cerebral hemorrhage admitted between January 2020 and December 2022 was conducted. Patients were divided into early and delayed surgery groups for comparison of outcomes such as mortality rate, modified Rankin Scale score, and Short Form-36 scores. Additionally, factors influencing long-term prognosis were analyzed through logistic regression based on significant differences observed between groups. RESULTS: The early decompressive surgery group showed superior outcomes with lower mortality rates, modified Rankin Scale (mRS) scores, hematoma expansion rates, and perihematomal edema volumes compared to the delayed surgery group (P < 0.05). Additionally, age, preoperative Glasgow Coma Scale (GCS) score, preoperative hematoma volume, and a history of hypertension or diabetes were identified as independent prognostic factors for patients with cerebral hemorrhage, with odds ratios (ORs) greater than 1. CONCLUSIONS: Early decompressive surgery can improve the long-term prognosis and quality of life of patients with cerebral hemorrhage, reduce mortality rates, and decrease hematoma expansion and perihematomal edema. Older patients, those with higher preoperative hematoma volume and GCS score, and those with coexisting hypertension and diabetes should be given special attention to decrease the occurrence of adverse prognosis. [ABSTRACT FROM AUTHOR]

Magnetic induction phase shift is a promising technology for the detection of cerebral hemorrhage, owing to its nonradioactive, noninvasive, and real-time detection properties. To enhance the detection sensitivity and linearity, a zero-flow sensor was proposed. The uniform primary magnetic field and its counteraction were achieved. Phase-change responses to solutions of varying conductivities and rabbits with cerebral hemorrhage were investigated and compared with traditional sensors. The sensitivities in detecting solutions with different conductivities were 1.84, 1.39, and 1.22 times higher than those for a low-pass birdcage coil, planar gradiometer, and Bx-sensor, respectively. The results for rabbits with cerebral hemorrhage showed that the sensitivities increased by 1.17, 1.67, and 6.3 times compared with a low-pass birdcage coil, symmetric cancelation-type sensor, and single co-axial coil, respectively. This sensor could accurately detect three stages in the pathological process. Blood loss of 1 mL meant that the compensatory mechanism of cerebrospinal fluid began to fail, and 1.4 mL of blood loss meant that the compensatory mechanism failed completely. The adjusted R-squared value of the first-order linear fit was above 0.98 in both physical and animal experiments, indicating that high detection linearity was achieved. The proposed sensor provides a more accurate method for cerebral hemorrhage detection and facilitates the practical application of magnetic induction phase shift in pre-hospital and bedside real-time detection. [ABSTRACT FROM AUTHOR]

Incidental dural tear (DT) during cervical spine surgery is a feared complication. However, its impact on patient-reported outcomes (PROs) remains unclear. To determine the influence of DTs on PROs 1 year after cervical spine surgery. Retrospective cohort. Patients undergoing elective cervical spine surgery for cervical spondylosis, ossification of the posterior longitudinal ligament (OPLL), and cervical disc herniation. Analysis included patients' characteristics, perioperative complications, and PROs both preoperatively and at 1 year postoperatively. This study enrolled consecutive patients who underwent elective cervical spine surgery at 13 high-volume spine centers. All patients were required to complete questionnaires both preoperatively and 1 year postoperatively, which included PROs such as numerical rating scales of pain or dysesthesia for each part of the body, Neck Disability Index NDI, and Core Outcome Measures Index. Patients were divided into 2 groups based on the presence (DT+) or absence (DT-) of dural injury. Comparisons were made regarding patient background, perioperative complications, and pre and postoperative PROs. Propensity score matching was also utilized to adjust for patient background, and further comparisons were made regarding complication rates and PROs. Out of 2,704 patients, dural tears were identified in 97 (3.6%) cases. The DT+ group had a significantly higher proportion of fixation surgeries, upper cervical surgeries, OPLL, and revision surgeries. Perioperative complications were significantly higher in the DT+ group, including intraoperative nerve damage, postoperative paralysis, surgical site infections (SSI), and cerebrovascular complications. Outcomes collected from 2,163 patients (79.9%) revealed significantly more severe neck and upper limb pain in the DT+ group. After propensity score matching, significant differences persisted in postoperative paralysis and SSI in the DT+ group, but no significant differences were observed in PROs. Patients with dural tears showed nearly equivalent postoperative outcomes at 1 year following cervical spine surgery compared to those without dural tears. However, the incidence of perioperative complications was higher, emphasizing the need for careful management. [ABSTRACT FROM AUTHOR]

Objectives: Spontaneous intracerebral hemorrhage (ICH) poses high mortality and morbidity rates with limited evidence‐based therapeutic approaches. We aimed to evaluate the current evidence for the role of minimally invasive surgery (MIS) in the management of ICH. Methods: This systematic review and meta‐analysis followed recommended guidelines and protocols. Medline, Embase, Scopus, and the Cochrane Library were searched from inception up to April 12, 2024. The inclusion was restricted to randomized clinical trials (RCTs) of high quality, ensuring they were not deemed to have a high risk of bias in any of the Cochrane risk of bias tool (RoB2) domains. Primary outcomes were good functional outcome (modified Rankin scale, 0–3) and mortality beyond 90 days. Secondary outcomes were early mortality within 30 days and rebleeding rates. We pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) using random‐effects models. Results: Fourteen high‐quality RCTs were included. There were 3,027 patients with ICH (1,475 randomized to MIS, and 1,452 randomized to medical management or craniotomy). Of included patients, 1,899 (62.7%) were males. MIS resulted in higher odds of achieving long‐term good functional outcome (OR, 1.51 [95% CI, 1.25–1.82]), lower odds of long‐term mortality (OR, 0.72 [95% CI, 0.57–0.90]) and lower odds of early mortality (OR, 0.73 [95% CI, 0.56–0.95]). Rebleeding rates were similar (OR, 1.10 [95% CI, 0.55–2.19]). The treatment effect of MIS was consistent across multiple sensitivity and subgroup analyses, including individuals with deep ICH. Interpretation: This meta‐analysis provides high‐quality clinical trial evidence supporting the use of MIS as a primary treatment strategy in the management of ICH. ANN NEUROL 2025;97:185–194 [ABSTRACT FROM AUTHOR]

Deep vein thrombosis and pulmonary embolism prophylaxis is an important part of trauma care. Despite an increased risk of thrombotic complications, the use of venous thrombosis chemoprophylaxis in penetrating traumatic brain injury (pTBI) patients is met with reluctance from neurosurgeons because of concern for the exacerbation of intracerebral hemorrhage. The objective of this study was to provide initial pre-clinical evidence of the effects of Lovenox (LVX) administration following pTBI with significant intracerebral hemorrhage. Sprague-Dawley rats received a penetrating ballistic-like brain injury. Animals were randomly divided into two groups following injury: LVX (25 mg/kg) or vehicle (VEH, saline). LVX or vehicle was administered subcutaneously beginning 24 h after the injury and continued daily for 7 days post-injury. A neurological assessment was performed daily and magnetic resonance imaging (MRI) was performed at baseline, 1, 2, 3, and 7 days post-injury. Following the final MRI, brains were isolated and prepared for histological analysis. Thromboelastography demonstrated dramatic anticoagulation effects which were confirmed by significant increases in partial thromboplastin time (p < 0.001). Daily neurological assessment revealed no worsening of functional deficits following LVX treatment. MRI analysis demonstrated no differences in cerebral edema or intracranial hemorrhage volumes between treatment groups at any tested post-injury time points. However, LVX elicited a significant reduction in fibrin deposition in the ipsilateral striatum and lesion site at 7 days post-injury (p < 0.05). Serum levels of beta-amyloid were decreased at 7 days following LVX treatment (p < 0.05) which may indicate neuroprotective effects but was not correlated to brain levels. The results presented indicate that administration of LVX at a dose capable of inducing anticoagulation is safe in a rodent model of pTBI without exacerbation of intracerebral hemorrhage within the first 7 days of injury. [ABSTRACT FROM AUTHOR]