TAK1 inhibition mitigates intracerebral hemorrhage-induced brain injury through reduction of oxidative stress and neuronal pyroptosis via the NRF2 signaling pathway.

Introduction: Intracerebral hemorrhage (ICH) often triggers oxidative stress through reactive oxygen species (ROS). Transforming growth factor-ß-activated kinase 1 (TAK1) plays a pivotal role in regulating oxidative stress and inflammation across various diseases. 5Z-7-Oxozeaenol (OZ), a specific inhibitor of TAK1, has exhibited therapeutic effects in various conditions. However, the impact of OZ following ICH and its underlying molecular mechanisms remain elusive. This study aimed to explore the possible role of OZ in ICH and its underlying mechanisms by inhibiting oxidative stress-mediated pyroptosis. Methods: Adult male Sprague-Dawley rats were subjected to an ICH model, followed by treatment with OZ. Neurobehavioral function, blood-brain barrier integrity, neuronal pyroptosis, and oxidative stress markers were assessed using various techniques including behavioral tests, immunofluorescence staining, western blotting, transmission electron microscopy, and biochemical assays. Results: Our study revealed that OZ administration significantly inhibited phosphorylated TAK1 expression post-ICH. Furthermore, TAK1 blockade by OZ attenuated blood-brain barrier (BBB) disruption, neuroinflammation, and oxidative damage while enhancing neurobehavioral function. Mechanistically, OZ administration markedly reduced ROS production and oxidative stress by facilitating nuclear factor-erythroid 2-related factor 2 (NRF2) nuclear translocation. This was accompanied by a subsequent suppression of the NOD-like receptor protein 3 (NLRP3) activation-mediated inflammatory cascade and neuronal pyroptosis. Discussion: Our findings highlight that OZ alleviates brain injury and oxidative stress-mediated pyroptosis via the NRF2 pathway. Inhibition of TAK1 emerges as a promising approach for managing ICH.

Antithrombotic Treatment and Clinical Outcomes After Intracerebral Hemorrhage: A Retrospective Cohort Study from the Swedish Stroke Register.

BACKGROUND: A rapid shift has occurred from vitamin K antagonists toward direct oral anticoagulants, which have a lower risk of intracerebral hemorrhage (ICH). However, effects on clinical outcomes after ICH are understudied. We aimed to describe the prevalence of antithrombotic drugs and to study the prognosis among prestroke functionally independent Swedish patients with ICH. METHODS AND RESULTS: We identified all patients diagnosed with nontraumatic ICH in 2017 to 2021 from the Swedish Stroke Register (n=13 155) and assessed death and functional outcome at 3 months after ICH in prestroke functionally independent patients (n=10 014). Functional outcome was estimated among 3-month survivors on the basis of self-reported activities of daily living scores. Risks of outcomes were estimated using Poisson regression. In 13 155 patients, 14.5% used direct oral anticoagulant, 10.1% vitamin K antagonists, and 21.6% antiplatelets at ICH onset. Among 10 014 pre-stroke activities of daily living-independent patients, oral anticoagulants and antiplatelets were associated with increased mortality risk (adjusted risk ratio, 1.27 [95% CI, 1.13-1.43]; P<0.001; and adjusted risk ratio, 1.23 [95% CI, 1.13-1.34]; P<0.001 respectively). Mortality risk did not statistically differ between antiplatelets and oral anticoagulants nor between direct oral anticoagulant and vitamin K antagonists. Among 5126 patients with nonmissing functional outcome (69.1% of survivors), antiplatelets (adjusted risk ratio, 1.06 [95% CI, 0.99-1.13]; P=0.100) and oral anticoagulants (adjusted risk ratio, 1.01 [95% CI, 0.92-1.12]; P=0.768) were not statistically significantly associated with functional dependence. CONCLUSIONS: There was no statistically significant difference in mortality risk between direct oral anticoagulant and vitamin K antagonists in prestroke functionally independent patients (unadjusted for oral anticoagulant class indication). Furthermore, mortality risk in antiplatelet and oral anticoagulant users might differ less than previously suggested.

SGLT1 and SGLT2 inhibition, circulating metabolites, and cerebral small vessel disease: a mediation Mendelian Randomization study.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) and SGLT1 inhibitors may have additional beneficial metabolic effects on circulating metabolites beyond glucose regulation, which could contribute to a reduction in the burden of cerebral small vessel disease (CSVD). Accordingly, we used Mendelian Randomization (MR) to examine the role of circulating metabolites in mediating SGLT2 and SGLT1 inhibition in CSVD. METHODS: Genetic instruments for SGLT1/2 inhibition were identified as genetic variants, which were both associated with the expression of encoding genes of SGLT1/2 inhibitors and glycated hemoglobin A1c (HbA1c) level. A two-sample two-step MR was used to determine the causal effects of SGLT1/2 inhibition on CSVD manifestations and the mediating effects of 1400 circulating metabolites linking SGLT1/2 inhibition with CSVD manifestations. RESULTS: A lower risk of deep cerebral microbleeds (CMBs) and small vessel stroke (SVS) was linked to genetically predicted SGLT2 inhibition. Better white matter structure integrity was also achieved, as evidenced by decreased mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD), as well as lower deep (DWMH) and periventrivular white matter hyperintensity (PWMH) volume. Inhibiting SGLT2 could also lessen the incidence of severe enlarged perivascular spaces (EPVS) located at white matter, basal ganglia (BG) and hippocampus (HIP). SGLT1 inhibition could preserve white matter integrity, shown as decreased MD of white matter and DWMH volume. The effect of SGLT2 inhibition on SVS and MD of white matter through the concentration of 4-acetamidobutanoate and the cholesterol to oleoyl-linoleoyl-glycerol (18:1 to 18:2) ratio, with a mediated proportion of 30.3% and 35.5% of the total effect, respectively. CONCLUSIONS: SGLT2 and SGLT1 inhibition play protective roles in CSVD development. The SGLT2 inhibition could lower the risk of SVS and improve the integrity of white matter microstructure via modulating the level of 4-acetamidobutanoate and cholesterol metabolism. Further mechanistic and clinical studies research are needed to validate our findings.

Neurodevelopmental outcome in preterm infants with intraventricular hemorrhages: the potential of quantitative brainstem MRI.

OBJECTIVES: This retrospective study aimed to identify quantitative magnetic resonance imaging markers in the brainstem of preterm neonates with intraventricular hemorrhages. It delves into the intricate associations between quantitative brainstem magnetic resonance imaging metrics and neurodevelopmental outcomes in preterm infants with intraventricular hemorrhage, aiming to elucidate potential relationships and their clinical implications. MATERIALS AND METHODS: Neuroimaging was performed on preterm neonates with intraventricular hemorrhage using a multi-dynamic multi-echo sequence to determine T1 relaxation time, T2 relaxation time, and proton density in specific brainstem regions. Neonatal outcome scores were collected using the Bayley Scales of Infant and Toddler Development. Statistical analysis aimed to explore potential correlations between magnetic resonance imaging metrics and neurodevelopmental outcomes. RESULTS: Sixty preterm neonates (mean gestational age at birth 26.26 ± 2.69 wk; n = 24 [40%] females) were included. The T2 relaxation time of the midbrain exhibited significant positive correlations with cognitive (r = 0.538, P < 0.0001, Pearson's correlation), motor (r = 0.530, P < 0.0001), and language (r = 0.449, P = 0.0008) composite scores at 1 yr of age. CONCLUSION: Quantitative magnetic resonance imaging can provide valuable insights into neurodevelopmental outcomes after intraventricular hemorrhage, potentially aiding in identifying at-risk neonates. Multi-dynamic multi-echo sequence sequences hold promise as an adjunct to conventional sequences, enhancing the sensitivity of neonatal magnetic resonance neuroimaging and supporting clinical decision-making for these vulnerable patients.

Predicting early mortality and severe intraventricular hemorrhage in very-low birth weight preterm infants: a nationwide, multicenter study using machine learning.

Our aim was to develop a machine learning-based predictor for early mortality and severe intraventricular hemorrhage (IVH) in very-low birth weight (VLBW) preterm infants in Taiwan. We collected retrospective data from VLBW infants, dividing them into two cohorts: one for model development and internal validation (Cohort 1, 2016-2021), and another for external validation (Cohort 2, 2022). Primary outcomes included early mortality, severe IVH, and early poor outcomes (a combination of both). Data preprocessing involved 23 variables, with the top four predictors identified as gestational age, birth body weight, 5-min Apgar score, and endotracheal tube ventilation. Six machine learning algorithms were employed. Among 7471 infants analyzed, the selected predictors consistently performed well across all outcomes. Logistic regression and neural network models showed the highest predictive performance (AUC 0.81-0.90 in both internal and external validation) and were well-calibrated, confirmed by calibration plots and the lowest two mean Brier scores (0.0685 and 0.0691). We developed a robust machine learning-based outcome predictor using only four accessible variables, offering valuable prognostic information for parents and aiding healthcare providers in decision-making.

Development of a time-resolved immunochromatographic test strip for rapid and quantitative determination of GFAP in serum.

Glial fibrillary acidic protein (GFAP) in serum has been shown as a biomarker of traumatic brain injury (TBI) which is a significant global public health concern. Accurate and rapid detection of serum GFAP is critical for TBI diagnosis. In this study, a time-resolved fluorescence immunochromatographic test strip (TRFIS) was proposed for the quantitative detection of serum GFAP. This TRFIS possessed excellent linearity ranging from 0.05 to 2.5 ng/mL for the detection of serum GFAP and displayed good linearity (Y = 598723X + 797198, R2 = 0.99), with the lowest detection limit of 16 pg/mL. This TRFIS allowed for quantitative detection of serum GFAP within 15 min and showed high specificity. The intra-batch coefficient of variation (CV) and the inter-batch CV were both < 4.0%. Additionally, this TRFIS was applied to detect GFAP in the serum samples from healthy donors and patients with cerebral hemorrhage, and the results of TRFIS could efficiently discern the patients with cerebral hemorrhage from the healthy donors. Our developed TRFIS has the characteristics of high sensitivity, high accuracy, and a wide linear range and is suitable for rapid and quantitative determination of serum GFAP on-site.

Case report: Non-EBV associated cerebral vasculitis and cerebral hemorrhage in X-linked lymphoproliferative disease.

X-linked lymphoproliferative disease (XLP) is a rare genetic disorder characterized by immune dysregulation. The three most common clinical phenotypes are EBV-associated infectious mononucleosis (FIM), abnormal gammaglobulinemia, and lymphoma. We present a rare case of XLP1 with neurovasculitis, which is non-EBV-related and involves multiple systems, a condition rarely seen in children. The patient initially presented with an unsteady gait, which progressively evolved into language and consciousness disorders. Additionally, CT scans revealed multiple nodules in the lungs. Subsequent genetic testing and brain tissue biopsy confirmed the diagnosis: XLP1-related cerebral vasculitis and cerebral hemorrhage. Tragically, during the diagnostic process, the child experienced a sudden cerebral hemorrhage and herniation, ultimately resulting in fatality. This case offers a comprehensive insight into XLP1-related cerebral vasculitis and cerebral hemorrhage, underscoring the significance of early diagnosis and prompt treatment, while also imparting valuable clinical experience and lessons to the medical community.

Signature and function of plasma exosome-derived circular RNAs in patients with hypertensive intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is one of the major causes of death and disability, and hypertensive ICH (HICH) is the most common type of ICH. Currently, the outcomes of HICH patients remain poor after treatment, and early prognosis prediction of HICH is important. However, there are limited effective clinical treatments and biomarkers for HICH patients. Although circRNA has been widely studied in diseases, the role of plasma exosomal circRNAs in HICH remains unknown. The present study was conducted to investigate the characteristics and function of plasma exosomal circRNAs in six HICH patients using circRNA microarray and bioinformatics analysis. The results showed that there were 499 differentially expressed exosomal circRNAs between the HICH patients and control subjects. According to GO annotation and KEGG pathway analyses, the targets regulated by differentially expressed exosomal circRNAs were tightly related to the development of HICH via nerve/neuronal growth, neuroinflammation and endothelial homeostasis. And the differentially expressed exosomal circRNAs could mainly bind to four RNA-binding proteins (EIF4A3, FMRP, AGO2 and HUR). Moreover, of differentially expressed exosomal circRNAs, hsa_circ_00054843, hsa_circ_0010493 and hsa_circ_00090516 were significantly associated with bleeding volume and Glasgow Coma Scale score of the subjects. Our findings firstly revealed that the plasma exosomal circRNAs are significantly involved in the progression of HICH, and could be potent biomarkers for HICH. This provides the basis for further research to pinpoint the best biomarkers and illustrate the mechanism of exosomal circRNAs in HICH.

Circulating Blood Prognostic Biomarker Signatures for Hemorrhagic Cerebral Cavernous Malformations (CCMs).

Cerebral cavernous malformations (CCMs) are a neurological disorder characterized by enlarged intracranial capillaries in the brain, increasing the susceptibility to hemorrhagic strokes, a major cause of death and disability worldwide. The limited treatment options for CCMs underscore the importance of prognostic biomarkers to predict the likelihood of hemorrhagic events, aiding in treatment decisions and identifying potential pharmacological targets. This study aimed to identify blood biomarkers capable of diagnosing and predicting the risk of hemorrhage in CCM1 patients, establishing an initial set of circulating biomarker signatures. By analyzing proteomic profiles from both human and mouse CCM models and conducting pathway enrichment analyses, we compared groups to identify potential blood biomarkers with statistical significance. Specific candidate biomarkers primarily associated with metabolism and blood clotting pathways were identified. These biomarkers show promise as prognostic indicators for CCM1 deficiency and the risk of hemorrhagic stroke, strongly correlating with the likelihood of hemorrhagic cerebral cavernous malformations (CCMs). This lays the groundwork for further investigation into blood biomarkers to assess the risk of hemorrhagic CCMs.

Cumulative Systolic Blood Pressure and Incident Stroke Type Variation by Race and Ethnicity.

Importance: Stroke risk varies by systolic blood pressure (SBP), race, and ethnicity. The association between cumulative mean SBP and incident stroke type is unclear, and whether this association differs by race and ethnicity remains unknown. Objective: To examine the association between cumulative mean SBP and first incident stroke among 3 major stroke types-ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH)-and explore how these associations vary by race and ethnicity. Design, Setting, and Participants: Individual participant data from 6 US longitudinal cohorts (January 1, 1971, to December 31, 2019) were pooled. The analysis was performed from January 1, 2022, to January 2, 2024. The median follow-up was 21.6 (IQR, 13.6-31.8) years. Exposure: Time-dependent cumulative mean SBP. Main Outcomes and Measures: The primary outcome was time from baseline visit to first incident stroke. Secondary outcomes consisted of time to first incident IS, ICH, and SAH. Results: Among 40 016 participants, 38 167 who were 18 years or older at baseline with no history of stroke and at least 1 SBP measurement before the first incident stroke were included in the analysis. Of these, 54.0% were women; 25.0% were Black, 8.9% were Hispanic of any race, and 66.2% were White. The mean (SD) age at baseline was 53.4 (17.0) years and the mean (SD) SBP at baseline was 136.9 (20.4) mm Hg. A 10-mm Hg higher cumulative mean SBP was associated with a higher risk of overall stroke (hazard ratio [HR], 1.20 [95% CI, 1.18-1.23]), IS (HR, 1.20 [95% CI, 1.17-1.22]), and ICH (HR, 1.31 [95% CI, 1.25-1.38]) but not SAH (HR, 1.13 [95% CI, 0.99-1.29]; P = .06). Compared with White participants, Black participants had a higher risk of IS (HR, 1.20 [95% CI, 1.09-1.33]) and ICH (HR, 1.67 [95% CI, 1.30-2.13]) and Hispanic participants of any race had a higher risk of SAH (HR, 3.81 [95% CI, 1.29-11.22]). There was no consistent evidence that race and ethnicity modified the association of cumulative mean SBP with first incident stroke and stroke type. Conclusions and Relevance: The findings of this cohort study suggest that cumulative mean SBP was associated with incident stroke type, but the associations did not differ by race and ethnicity. Culturally informed stroke prevention programs should address modifiable risk factors such as SBP along with social determinants of health and structural inequities in society.

Peroxiredoxin II exerts neuroprotective effects by inhibiting endoplasmic reticulum stress and oxidative stress-induced neuronal pyroptosis.

BACKGROUND: Intracerebral hemorrhage (ICH) is a critical neurological condition with few treatment options, where secondary immune responses and specific cell death forms, like pyroptosis, worsen brain damage. Pyroptosis involves gasdermin-mediated membrane pores, increasing inflammation and neural harm, with the NLRP3/Caspase-1/GSDMD pathway being central to this process. Peroxiredoxin II (Prx II), recognized for its mitochondrial protection and reactive oxygen species (ROS) scavenging abilities, appears as a promising neuronal pyroptosis modulator. However, its exact role and action mechanisms need clearer definition. This research aims to explore Prx II impact on neuronal pyroptosis and elucidate its mechanisms, especially regarding endoplasmic reticulum (ER) stress and oxidative stress-induced neuronal damage modulation. METHODS AND RESULTS: Utilizing MTT assays, Microscopy, Hoechst/PI staining, Western blotting, and immunofluorescence, we found Prx II effectively reduces LPS/ATP-induced pyroptosis and neuroinflammation in HT22 hippocampal neuronal cells. Our results indicate Prx II's neuroprotective actions are mediated through PI3K/AKT activation and ER stress pathway inhibition, diminishing mitochondrial dysfunction and decreasing neuronal pyroptosis through the ROS/MAPK/NF-κB pathway. These findings highlight Prx II potential therapeutic value in improving intracerebral hemorrhage outcomes by lessening secondary brain injury via critical signaling pathway modulation involved in neuronal pyroptosis. CONCLUSIONS: Our study not only underlines Prx II importance in neuroprotection but also opens new therapeutic intervention avenues in intracerebral hemorrhage, stressing the complex interplay between redox regulation, ER stress, and mitochondrial dynamics in neuroinflammation and cell death management.

Advances in Cranial Surgery.

The landscape of the cranial neurosurgery has changed tremendously in past couple of decades. The main frontiers including introduction of neuro-endoscopy, minimally invasive skull base approaches, SRS, laser interstitial thermal therapy and use of tubular retractors have revolutionized the management of intracerebral hemorrhages, deep seated tumors other intracranial pathologies. Introduction of these novel techniques is based on smaller incisions with maximal operative corridors, decreased blood loss, shorter hospital stays, decreased post-operative pain and cosmetically appealing scars that improves patient satisfaction and clinical outcomes. The sophisticated tools like neuroendoscopy have improved light source, and better visualization around the corners. Advanced navigated tools and channel-based retractors help us to target deeply seated lesions with increased precision and minimal disruption of the surrounding neurovascular tissues. Advent of stereotactic radiosurgery has provided us alternative feasible, safe and effective options for treatment of patients who are otherwise not medically stable to undergo complex cranial surgical interventions. This paper review advances in treatment of intracranial pathologies, and how the neurosurgeons and other medical providers at the University of Missouri-Columbia (UMC) are optimizing these treatments for their patients.

Using 30-day modified rankin scale score to predict 90-day score in patients with intracranial hemorrhage: Derivation and validation of prediction model.

Whether 30-day modified Rankin Scale (mRS) scores can predict 90-day scores is unclear. This study derived and validated a model to predict ordinal 90-day mRS score in an intracerebral hemorrhage (ICH) population using 30-day mRS values and routinely available baseline variables. Adults enrolled in the Antihypertensive Treatment of Acute Cerebral Hemorrhage-2 (ATACH-2) trial between May 2011 and September 2015 with acute ICH, who were alive at 30 days and had mRS scores reported at both 30 and 90 days were included in this post-hoc analysis. A proportional odds regression model for predicting ordinal 90-day mRS scores was developed and internally validated using bootstrapping. Variables in the model included: mRS score at 30 days, age (years), hematoma volume (cm3), hematoma location (deep [basal ganglia, thalamus], lobar, or infratentorial), presence of intraventricular hemorrhage (IVH), baseline Glasgow Coma Scale (GCS) score, and National Institutes of Health Stroke Scale (NIHSS) score at randomization. We assessed model fit, calibration, discrimination, and agreement (ordinal, dichotomized functional independence), and EuroQol-5D ([EQ-5D] utility weighted) between predicted and observed 90-day mRS. A total of 898/1000 participants were included. Following bootstrap internal validation, our model (calibration slope = 0.967) had an optimism-corrected c-index of 0.884 (95% CI = 0.873-0.896) and R2 = 0.712 for 90-day mRS score. The weighted ĸ for agreement between observed and predicted ordinal 90-day mRS score was 0.811 (95% CI = 0.787-0.834). Agreement between observed and predicted functional independence (mRS score of 0-2) at 90 days was 74.3% (95% CI = 69.9-78.7%). The mean ± SD absolute difference between predicted and observed EQ-5D-weighted mRS score was negligible (0.005 ± 0.145). This tool allows practitioners and researchers to utilize clinically available information along with the mRS score 30 days after ICH to reliably predict the mRS score at 90 days.

Association of Antithrombotic Drug Use With Incident Intracerebral Hemorrhage Location.

BACKGROUND AND OBJECTIVES: Few population-based studies have assessed associations between the use of antithrombotic (platelet antiaggregant or anticoagulant) drugs and location-specific risks of spontaneous intracerebral hemorrhage (s-ICH). In this study, we estimated associations between antithrombotic drug use and the risk of lobar vs nonlobar incident s-ICH. METHODS: Using Danish nationwide registries, we identified cases in the Southern Denmark Region of first-ever s-ICH in patients aged 50 years or older between 2009 and 2018. Each verified case was classified as lobar or nonlobar s-ICH and matched to controls in the general population by age, sex, and calendar year. Prior antithrombotic use was ascertained from a nationwide prescription registry. We calculated odds ratios (aORs) for associations between the use of clopidogrel, aspirin, direct oral anticoagulants (DOACs) or vitamin K antagonists (VKA), and lobar and nonlobar ICH in conditional logistic regression analyses that were adjusted for potential confounders. RESULTS: A total of 1,040 cases of lobar (47.9% men, mean age [SD] 75.2 [10.7] years) and 1,263 cases of nonlobar s-ICH (54.2% men, mean age 73.6 [11.4] years) were matched to 41,651 and 50,574 controls, respectively. A stronger association with lobar s-ICH was found for clopidogrel (cases: 7.6%, controls: 3.5%; aOR 3.46 [95% CI 2.45-4.89]) vs aspirin (cases: 22.9%, controls: 20.4%; aOR 2.14 [1.74-2.63; p = 0.019). Corresponding estimates for nonlobar s-ICH were not different between clopidogrel (cases: 5.4%, controls: 3.4%; aOR 2.44 [1.71-3.49]) and aspirin (cases: 20.7%, controls: 19.2%; aOR 1.77 [1.47-2.15]; p = 0.12). VKA use was associated with higher odds of both lobar (cases: 14.3%, controls: 6.1%; aOR 3.66 [2.78-4.80]) and nonlobar (cases: 15.4%, controls: 5.5%; aOR 4.62 [3.67-5.82]) s-ICH. The association of DOAC use with lobar s-ICH (cases: 3.5%, controls: 2.7%; aOR 1.66 [1.02-2.70]) was weaker than that of VKA use (p = 0.006). Corresponding estimates for nonlobar s-ICH were not different between DOACs (cases: 5.1%, controls: 2.4%; aOR 3.44 [2.33-5.08]) and VKAs (p = 0.20). DISCUSSION: Antithrombotics were associated with higher risks of s-ICH, but the strength of the associations varied by s-ICH location and drug, which may reflect differences in the cerebral microangiopathies associated with lobar vs nonlobar hemorrhages and the mechanisms of drug action.

Paroxysmal sympathetic hyperexcitability after brain injury: A clinical analysis of case series.

BACKGROUND: Paroxysmal sympathetic hyperexcitability (PSH) is a group of complex syndromes with various etiologies. Previous studies were limited to the description of traumatic brain injury (TBI), and the description of PSH after other types of brain injury was rare. We explored the clinical features, treatment, and prognosis of PSH after various types of brain injuries. METHODS: Patients admitted to the neurosurgery intensive care unit with PSH after brain injury from July 2019 to December 2022 were included. Demographic data, clinical manifestations, drug therapy, and disease prognosis were retrospectively collected and analyzed. RESULTS: Fifteen male and 9 female patients with PSH after brain injury were selected. TBI was most likely to cause PSH (66.7%), followed by spontaneous intracerebral hemorrhage (25%). Glasgow coma scale scores of 19 patients (79.2%) were lower than 8 and 14 patients (58.3%) underwent tracheotomy. Electroencephalogram monitoring was performed in 12 individuals, none of which showed epileptic waves. Clinical symptom scale showed mild symptoms in 17 cases (70.8%). Almost all patients were administered a combination of drugs. After follow-up, most patients had a poor prognosis and 2 (8.3%) died after discharge. CONCLUSION: The etiology of PSH is complex. TBI may be the most common cause of PSH. Non-TBI may also be an important cause of PSH. Therefore, early identification, prevention and diagnosis are helpful for determining the prognosis and outcome of the disease.

Association of large core middle cerebral artery stroke and hemorrhagic transformation with hospitalization outcomes.

Historically, investigators have not differentiated between patients with and without hemorrhagic transformation (HT) in large core ischemic stroke at risk for life-threatening mass effect (LTME) from cerebral edema. Our objective was to determine whether LTME occurs faster in those with HT compared to those without. We conducted a two-center retrospective study of patients with ≥ 1/2 MCA territory infarct between 2006 and 2021. We tested the association of time-to-LTME and HT subtype (parenchymal, petechial) using Cox regression, controlling for age, mean arterial pressure, glucose, tissue plasminogen activator, mechanical thrombectomy, National Institute of Health Stroke Scale, antiplatelets, anticoagulation, temperature, and stroke side. Secondary and exploratory outcomes included mass effect-related death, all-cause death, disposition, and decompressive hemicraniectomy. Of 840 patients, 358 (42.6%) had no HT, 403 (48.0%) patients had petechial HT, and 79 (9.4%) patients had parenchymal HT. LTME occurred in 317 (37.7%) and 100 (11.9%) had mass effect-related deaths. Parenchymal (HR 8.24, 95% CI 5.46-12.42, p < 0.01) and petechial HT (HR 2.47, 95% CI 1.92-3.17, p < 0.01) were significantly associated with time-to-LTME and mass effect-related death. Understanding different risk factors and sequelae of mass effect with and without HT is critical for informed clinical decisions.

Triglyceride-glucose index as a potential predictor for in-hospital mortality in critically ill patients with intracerebral hemorrhage: a multicenter, case-control study.

BACKGROUND: The correlation between the triglyceride-glucose index (TyG) and the prognosis of ischemic stroke has been well established. This study aims to assess the influence of the TyG index on the clinical outcomes of critically ill individuals suffering from intracerebral hemorrhage (ICH). METHODS: Patients diagnosed with ICH were retrospectively retrieved from the Medical Information Mart for Intensive Care (MIMIC-IV) and the eICU Collaborative Research Database (eICU-CRD). Various statistical methods, including restricted cubic spline (RCS) regression, multivariable logistic regression, subgroup analysis, and sensitivity analysis, were employed to examine the relationship between the TyG index and the primary outcomes of ICH. RESULTS: A total of 791 patients from MIMIC-IV and 1,113 ones from eICU-CRD were analyzed. In MIMIC-IV, the in-hospital and ICU mortality rates were 14% and 10%, respectively, while in eICU-CRD, they were 16% and 8%. Results of the RCS regression revealed a consistent linear relationship between the TyG index and the risk of in-hospital and ICU mortality across the entire study population of both databases. Logistic regression analysis revealed a significant positive association between the TyG index and the likelihood of in-hospital and ICU death among ICH patients in both databases. Subgroup and sensitivity analysis further revealed an interaction between patients' age and the TyG index in relation to in-hospital and ICU mortality among ICH patients. Notably, for patients over 60 years old, the association between the TyG index and the risk of in-hospital and ICU mortality was more pronounced compared to the overall study population in both MIMIC-IV and eICU-CRD databases, suggesting a synergistic effect between old age (over 60 years) and the TyG index on the in-hospital and ICU mortality of patients with ICH. CONCLUSIONS: This study established a positive correlation between the TyG index and the risk of in-hospital and ICU mortality in patients over 60 years who diagnosed with ICH, suggesting that the TyG index holds promise as an indicator for risk stratification in this patient population.

Anticoagulation therapy in non-valvular atrial fibrillation after intracerebral hemorrhage: A propensity score-matched study.

BACKGROUND: The effect of antithrombotic therapy on patients with atrial fibrillation who sustained previous intracerebral hemorrhage (ICH) remains uncertain. Data regarding antithrombotic therapy use in these patients are limited. This study aims to compare the clinical and overall outcomes of antithrombotic therapy and usual care in patients with atrial fibrillation who sustained ICH. METHODS: We assembled consecutive patients with atrial fibrillation sustaining an ICH from our institution. Multivariable regression analysis and propensity-matched analysis were applied to assess associations of different antithrombotic therapies and outcomes. The primary outcome was mortality within the longest follow-up. Kaplan-Meier curves and log-rank tests of the time-to-event data were used to assess differences in survival. RESULTS: In total, 296 consecutive patients with atrial fibrillation who survived an ICH were included in this study. Our analysis demonstrated that antithrombotic therapy was associated with reduced mortality up to a 4-year duration of follow-up (OR, 0.49, 95 % CI 0.30-0.81). Similar results were obtained from the propensity-matched analysis (OR, 0.58, 95 % CI 0.34-0.98). Subgroup analysis showed that compared with usual care, direct oral anticoagulant (DOAC) with or without antiplatelet was associated with a lower risk of long-term mortality (OR, 0.34, 95 % CI 0.17-0.69). In addition, our analysis observed a significant interaction between cardiac insufficiency and treatment effect (P = 0.04). CONCLUSIONS: In patients with atrial fibrillation who have a history of ICH, administration of antithrombotic therapy, especially DOAC, was associated with lower mortality. Future randomized trials are warranted to test the positive net clinical benefit of DOAC therapy.

Synergistic promotion of angiogenesis after intracerebral hemorrhage by ginsenoside Rh2 and chrysophanol in rats.

BACKGROUND: Intracerebral hemorrhage (ICH) is a debilitating condition characterized by the rupture of cerebral blood vessels, resulting in profound neurological deficits. A significant challenge in the treatment of ICH lies in the brain's limited capacity to regenerate damaged blood vessels. This study explores the potential synergistic effects of Ginsenoside Rh2 and Chrysophanol in promoting angiogenesis following ICH in a rat model. METHODS: Network pharmacology was employed to predict the potential targets and pathways of Ginsenoside Rh2 and Chrysophanol for ICH treatment. Molecular docking was utilized to assess the binding affinity between these compounds and their respective targets. Experimental ICH was induced in male Sprague-Dawley rats through stereotactic injection of type VII collagenase into the right caudate putamen (CPu). The study encompassed various methodologies, including administration protocols, assessments of neurological function, magnetic resonance imaging, histological examination, observation of brain tissue ultrastructure, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunofluorescence staining, Western blot analysis, and statistical analyses. RESULTS: Network pharmacology analysis indicated that Ginsenoside Rh2 and Chrysophanol may exert their therapeutic effects in ICH by promoting angiogenesis. Results from animal experiments revealed that rats treated with Ginsenoside Rh2 and Chrysophanol exhibited significantly improved neurological function, reduced hematoma volume, and diminished pathological injury compared to the Model group. Immunofluorescence analysis demonstrated enhanced expression of vascular endothelial growth factor receptor 2 (VEGFR2) and CD31, signifying augmented angiogenesis in the peri-hematomal region following combination therapy. Importantly, the addition of a VEGFR2 inhibitor reversed the increased expression of VEGFR2 and CD31. Furthermore, Western blot analysis revealed upregulated expression of angiogenesis-related factors, including VEGFR2, SRC, AKT1, MAPK1, and MAPK14, in the combination therapy group, but this effect was abrogated upon VEGFR2 inhibitor administration. CONCLUSION: The synergistic effect of Ginsenoside Rh2 and Chrysophanol demonstrated a notable protective impact on ICH injury in rats, specifically attributed to their facilitation of angiogenesis. Consequently, this research offers a foundation for the utilization of Ginsenosides Rh2 and Chrysophanol in medical settings and offers direction for the advancement of novel pharmaceuticals for the clinical management of ICH.