Intracerebral Hemorrhage Stroke Research Articles

Establishment and validation of a predictive model for tracheotomy in critically ill patients and analysis of the impact of different tracheotomy timing on patient prognosis

BackgroundIn critically ill patients receiving invasive mechanical ventilation (IMV), it is unable to determine early which patients require tracheotomy and whether early tracheotomy is beneficial.MethodsClinical data of patients who were first admitted to the ICU and underwent invasive ventilation for more than 24 h in the Medical Information Marketplace in Intensive Care (MIMIC)-IV database were retrospectively collected. Patients were categorized into successful extubation and tracheotomy groups according to whether they were subsequently successfully extubated or underwent tracheotomy. The patients were randomly divided into model training set and validation set in a ratio of 7:3. Constructing predictive models and evaluating and validating the models. The tracheotomized patients were divided into the early tracheotomy group (< = 7 days) and the late tracheotomy group (> 7 days), and the prognosis of the two groups was analyzed.ResultsA total of 7 key variables were screened: Glasgow coma scale (GCS) score, pneumonia, traumatic intracerebral hemorrhage, hemorrhagic stroke, left and right pupil responses to light, and parenteral nutrition. The area under the receiver operator characteristic (ROC) curve of the prediction model constructed through these seven variables was 0.897 (95% CI: 0.876–0.919), and 0.896 (95% CI: 0.866–0.926) for the training and validation sets, respectively. Patients in the early tracheotomy group had a shorter length of hospital stay, IMV duration, and sedation duration compared to the late tracheotomy group (p < 0.05), but there was no statistically significant difference in survival outcomes between the two groups.ConclusionThe prediction model constructed and validated based on the MIMIC-IV database can accurately predict the outcome of tracheotomy in critically ill patients. Meanwhile, early tracheotomy in critically ill patients does not improve survival outcomes but has potential advantages in shortening the duration of hospitalization, IMV, and sedation.

A comparative study of real hospital costs and INA-CBG rates for stroke in Indonesia

Background: The claim payment method in JKN program uses the prospective Indonesian Case Base Groups (INA-CBG) method, in which the rate has been determined before health services are provided based on the diagnosis code group. This potentially causes a discrepancy in the costs incurred by health facilities. Objective: This systematic review aimed to provide an overview of the comparison of actual hospital costs with the INA-CBG rates of the JKN program for inpatient stroke. Method: The collection method used a PRISMA flowchart on several databases. This systematic review is a comparative study comparing the significance of the average actual direct medical costs with the INA-CBG rates. Result: Cost differences on intracerebral haemorrhage (I619) and unspecified stroke diagnosis (I64) consistently give a negative difference around IDR 110,659 – IDR 8,184,007/patient/episode. Medicine and medical equipment are the most significant components of stroke treatments. Factors that significantly influence direct medical costs are the length of stay (LOS), class of JKN, and age. Conclusion: Cost differences can be influenced by several factors that can affect the direct medical costs of hospitals. The factor that has the most influence on the amount of direct medical cost is LOS.

Association of lifestyle with reduced stroke risk in 41 314 individuals with diabetes: Two prospective cohort studies in China.

To investigate the associations of individual and combined healthy lifestyle factors (HLS) with the risk of stroke in individuals with diabetes in China. This prospective analysis included 41 314 individuals with diabetes [15 191 from the Comprehensive Research on the Prevention and Control of the Diabetes (CRPCD) project and 26 123 from the China Kadoorie Biobank (CKB) study]. Associations of lifestyle factors, including cigarette smoking, alcohol consumption, physical activity, diet, body shape and sleep duration, with the risk of stroke, intracerebral haemorrhage (ICH) and ischaemic stroke (IS) were assessed using Cox proportional hazard models. During median follow-up periods of 8.02 and 9.05 years, 2499 and 4578 cases of stroke, 2147 and 4024 of IS, and 160 and 728 of ICH were documented in individuals with diabetes in the CRPCD and CKB cohorts, respectively. In the CRPCD cohort, patients with ≥5 HLS had a 14% lower risk of stroke (hazard ratio (HR): 0.86, 95% confidence interval (CI): 0.75-0.98) than those with ≤2 HLS. In the CKB cohort, the adjusted HR (95% CI) for patients with ≥5 HLS were 0.74 (0.66-0.83) for stroke, 0.74 (0.66-0.83) for IS, and 0.57 (0.42-0.78) for ICH compared with those with ≤2 HLS. The pooled adjusted HR (95% CI) comparing patients with ≥5 HLS versus ≤2 HLS was 0.79 (0.69-0.92) for stroke, 0.80 (0.68-0.93) for IS, and 0.60 (0.46-0.78) for ICH. Maintaining a healthy lifestyle was associated with a lower risk of stroke, IS and ICH among individuals with diabetes.

Prehospital identification of intracerebral haemorrhage: a scoping review of early clinical features and portable devices

IntroductionPrehospital identification of intracerebral haemorrhage (ICH) in suspected stroke cases may enable the initiation of appropriate treatments and facilitate better-informed transport decisions. This scoping review aims to examine the literature...

Vagus nerve stimulation for enhanced stroke recovery after intracerebral hemorrhage: illustrative case.

Randomized controlled trial (RCT) evidence has revealed the efficacy of vagus nerve stimulation (VNS) paired with rehabilitation therapy, over therapy alone, for upper-limb functional recovery after ischemic stroke. However, this technique has not yet been described for the recovery of chronic motor deficits after hemorrhagic stroke. Three years after left putaminal intracerebral hemorrhagic stroke with chronic upper-limb functional deficits, a patient was treated with VNS for enhanced stroke recovery. VNS was paired with 6 weeks of in-clinic physical therapy, resulting in upper-limb functional improvement of 14 points on the Fugl-Meyer Assessment Upper Extremity (FMA-UE) index for stroke recovery (maximum score of 66 equating to normal function). This improvement was more than 1 standard deviation above the improvement documented in the first successful RCT of VNS paired with therapy for ischemic stroke (5.0 ± 4.4 improvement on FMA-UE). VNS is a promising therapy for enhanced recovery after hemorrhagic stroke and may offer greater improvement in function compared to that after ischemic stroke. Improvement in function can occur years after the time of intracerebral hemorrhage.

The role of gut microorganisms and metabolites in intracerebral hemorrhagic stroke: a comprehensive review.

Intracerebral hemorrhagic stroke, characterized by acute hemorrhage in the brain, has a significant clinical prevalence and poses a substantial threat to individuals' well-being and productivity. Recent research has elucidated the role of gut microorganisms and their metabolites in influencing brain function through the microbiota-gut-brain axis (MGBA). This article provides a comprehensive review of the current literature on the common metabolites, short-chain fatty acids (SCFAs) and trimethylamine-N-oxide (TMAO), produced by gut microbiota. These metabolites have demonstrated the potential to traverse the blood-brain barrier (BBB) and directly impact brain tissue. Additionally, these compounds have the potential to modulate the parasympathetic nervous system, thereby facilitating the release of pertinent substances, impeding the buildup of inflammatory agents within the brain, and manifesting anti-inflammatory properties. Furthermore, this scholarly analysis delves into the existing dearth of investigations concerning the influence of gut microorganisms and their metabolites on cerebral functions, while also highlighting prospective avenues for future research.

Abstract TP79: Vagal Nerve Stimulation for Enhanced Stroke Recovery: Real-World Application in a Multidisciplinary Program

Introduction: Randomized-controlled trial (RCT) evidence has demonstrated the efficacy of vagal nerve stimulation (VNS) with paired rehabilitation for upper limb functional recovery after ischemic stroke. There remains a need to assess the generalizability of these findings to a broader population of stroke patients with chronic functional deficits. Hypothesis: VNS for upper limb recovery after stroke may be safely and effectively applied to diverse populations of patients in a multidisciplinary program. Methods: Patients at one center not included in the original RCT of VNS for stroke recovery were implanted with left-sided VNS, paired with six weeks of in-clinic therapy, as implemented in the original RCT. At the conclusion of in-clinic therapy, clinical benefit was assessed by improvement from baseline in the validated Fugl-Meyer Assessment-Upper Extremity (FMA-UE) score for stroke recovery (maximum score of 66 equating to normal function). Results: All four patients included had chronic, stable functional deficits &gt;1.5 years after stroke when implanted with VNS at ages of 43, 61, 70, and 71. Three patients with ischemic stroke were included with FMA-UE improvements of 13 (baseline 45, left-sided deficits), 15 (baseline 36, right-sided deficits), and 6 (baseline 21, left-sided deficits). One patient was implanted 3.0 years after intracerebral hemorrhagic stroke, with an FMA-UE improvement of 14 (baseline 16, right-sided deficits). No procedural complications were seen. Conclusions: Vagal nerve stimulation paired with in-clinic therapy can have a profound impact on upper limb function in patients after stroke. All patients in this series achieved greater FMA-UE improvement than the mean improvement in the largest RCT of VNS for stroke recovery (5.0 ± 4.4 points). This pilot series of real world application of paired VNS for upper limb functional recovery after stroke demonstrates early feasibility, safety, and efficacy of this treatment.

Abstract TMP30: The Impact of Social Influences on Rehabilitation Services Utilization After Stroke

Introduction: Evidence supports that early initiation of rehabilitation is important for patient outcomes after stroke. Thus, determination of patients needing rehabilitation during their acute hospitalization is critical. We assessed the impact of demographic, clinical, and county-level social influences on rate of transfer to a rehabilitation facility after acute stroke hospitalizations. Methods: Using Get with the Guidelines-Stroke registry data and Institute for Health Metrics and Evaluation data, we fitted univariate and multivariate generalized linear mixed models (GLMM) with demographic, clinical, and social variables to determine how social influences of health impacted variances in transfers to rehabilitation facilities. Specific county-level variables assessed were related to education, income, employment, home ownership, and being foreign born. Results: Among 912,488 patients who were assessed or received rehabilitation services due to acute ischemic or intracerebral hemorrhagic stroke, 33.4% of them were transferred to rehabilitation facilities. Multivariate analyses of patient-level demographic and clinical variables achieved an Akaike Information Criterion (AIC) of 925780 (21.0% reduction from the base model) largely driven by clinical factors (mRS at discharge, initial NIHSS, and initial exam findings). When county-level variables related to social influences of health were incorporated, AIC decreased by 23.4% to 871806, indicating a better model fit largely driven by education level. Conclusions: Social influences of health impact transfer to rehabilitation facilities after acute stroke hospitalization. Future studies should focus on individual (versus county-level) metrics of social influences of health and their impact on access to rehabilitation. This information should be used to develop interventions to improve the equity of rehabilitation utilization after stroke.

Abstract 57: Rapid Prehospital Diagnosis of Intracerebral Hemorrhage by Measuring GFAP on a Point-of-Care Platform

Background: The rapid differentiation between intracerebral hemorrhage (ICH) and ischemic stroke (IS) in patients with symptoms of acute stroke is decisive for triage and initiation of targeted therapies. Glial fibrillary acidic protein (GFAP) is a highly promising blood biomarker indicating acute ICH. In this study we investigated the potential of a new GFAP plasma test on a point-of-care (POC) platform for rapidly distinguishing ICH from IS in the prehospital phase. Methods: Patients with symptoms of acute stroke admitted within 6 hours of symptom onset were enrolled. Blood samples were collected already in the prehospital phase in most patients. Plasma GFAP measurements were performed on the i-STAT Alinity® (Abbott) device (duration of analysis 15 min). The primary endpoint was the final diagnosis at hospital discharge categorized as ICH, IS or stroke mimics. Results: 155 patients were enrolled (mean age 75±13, 49% females; final diagnosis 33 ICH, 115 IS, 7 stroke mimics). Prehospital GFAP serum concentrations were strongly elevated in ICH patients compared to IS patients (mean 2283±3821 pg/mL, median 144 [IQR 52.5-2562] vs. mean 45±25 pg/mL, median 29 [IQR 29-53]; p&lt;0.001). In patients with a moderate to severe neurological deficit (NIHSS &gt; 7), GFAP values below 30 pg/mL were associated with a negative predictive value of 100% (i.e. ruling out ICH). The probability of ICH increased in parallel with higher GFAP levels. GFAP concentrations above 120 pg/mL indicated ICH with a positive predictive value of 94%. Conclusion: Rapid prehospital GFAP measurements on a point-of-care platform allow a reliable differentiation between patients with IS and ICH. This opens the potential for optimized triage and for the administration of antidots in severely affected patients with suspected anticoagulation-associated ICH.

Abstract WP288: Epidemiological Analysis of Incidence, Treatment, Mortality and Costs of Cerebrovascular Diseases in Brazil Between 2017 and 2022

Background: Cerebrovascular diseases (CVD) represent a Global Health concern, being the first cause of disability worldwide and second cause of mortality (first in Brazil). Despite that, detailed data from Brazil was scarce and this study found alarming results. Aims: The study aims to analyze incidence, mortality, treatment, procedures and costs related to the three most common cerebrovascular diseases: Subarachnoid Hemorrhage (SAH), Intracerebral Hemorrhage (ICH) and Ischemic Stroke in Brazil. Methods: This is an epidemiological study. Data was obtained through DataSUS, a public database. For the search, we utilized the CID-10 notification system from I60 until I64, including admissions, deaths, treatments and costs related to each CID-10. Results: Between 2017 and 2022, 1,283,435 CVD cases were notified (SAH=4,7%; ICH= 8.8%; and ischemic stroke=86.5%). 52.4% were Male and 47.6% were Female. Mortality percentages were: SAH=20.2%, ICH=25.3%, Ischemic Stroke=15.3%. Rates of Thrombolysis were alarming, but with an increasing tendency: 22969 were performed, from 1.6% in 2017 to 2.3% in 2022 of all ischemic strokes. 8290 aneurysms embolizations were performed (13.5% of all SAH cases). 4.9% of SAH cases were treated with neurosurgical clipping, demonstrating a decrease tendency after 2020, as well other procedures, such as Craniectomy and Angioplastia. Yearly costs related to these diseases increased steeply, from R$ 360,710,749.92 in 2017 to R$ 537,511,793.62 in 2022 (around US$107,502,358.00). Conclusions: This study has found increasing incidence and costs associated with low rates of thrombolysis and procedures in Brazil The results can direct Public Health policies in developing countries, and similar research in other low- and middle-income-countries are encouraged.

Abstract WMP55: Advance Care Planning and Decision Regret Among Stroke Surrogate Decision Makers

Introduction: There has been limited study of outcomes among surrogate decision makers who make decisions on life-sustaining treatments after severe stroke. We investigated surrogate reports of decision regret after stroke and investigated whether prior advance directives were associated with decision regret. Methods: Ischemic stroke and intracerebral hemorrhage stroke cases and their surrogate decision makers were enrolled in the Outcomes Among Surrogate Decision Makers in Stroke (OASIS). Surrogates reported the baseline presence of formal written advance care plans and the validated decision regret scale (range 0-100, higher=more regret, analyzed as “any” vs. “none” due to skewed data) in the year after stroke (post-discharge, 3-,6-, and 12-months). The association of advance care planning and decision regret was assessed with multilevel mixed effects logistic regression models, adjusted for pre-specified covariates. Results: A total of 317 surrogates for 255 stroke patients were enrolled (4/2016 to 10/2020). Patient characteristics were mean age: 74.6, Female: 51.8%, Mean NIHSS: 14.7, deceased at 3 months: 53.1%. Surrogate characteristics were mean age: 55.8, female: 76.7%, child of patient: 62.1%, and race-ethnicity (Mexican American 62.8%, non-Hispanic White 32.2%, other 5.1%). Overall, 132/317 (41.64%) surrogates reported advance care plans. Decision regret scores tended to be low overall (post-discharge mean score: 11.2, SD: 20.2, 39.1% had regret scores &gt;0). On both unadjusted (OR 0.42, 95% CI 0.22-0.79, p=0.01) and fully adjusted regression analyses (OR 0.46, 95% CI 0.24-0.89, p=0.02, see Table), advance care plans were associated with lower odds of decision regret. Prior surrogate discussion of patient wishes without formal written advance care plans did not affect decision regret (data not shown). Conclusions: Advance care plans were protective against decision regret among surrogate decision makers in the year after stroke.

Global burden of stroke attributable to secondhand smoke in 204 countries and territories from 1990 to 2019: analysis of the global burden of disease study.

Secondhand smoke (SHS) continues a significant public health concern globally. This study aimed to assess the global burden of stroke attributable to SHS exposure during 1990-2019. This analysis utilized data on stroke morbidity and mortality from the Global Burden of Disease (GBD) 2019 study covering 204 countries and territories. We estimated stroke burden indicators attributable to SHS exposure, including age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life-year rate (ASDR), stratified by age, sex, region, and stroke subtype. In 2019, global SHS exposure accounted for 2.01 [95% uncertainty interval (UI): 1.49-2.58] million stroke mortality. The ASMR and ASDR were 2.5 (95% UI: 1.9-3.2) and 61.5 (95% UI: 46-78.8) per 100,000 population, respectively. The disease burden was higher among women than men and higher among the elderly than younger populations. Intracerebral hemorrhage and ischemic stroke had a more significant burden than subarachnoid hemorrhage. From 1990 to 2019, the ASMR and ASDR declined [estimated annual percentage change: -2.08 (95% CI: -2.21% to -1.95%) and -2.08% (95% CI: -2.19% to -1.97%) for each], but the absolute number of mortalities increased along with population growth. Substantial disparities existed across regions and sociodemographic groups. Despite declining ASMR and ASDR over time, the absolute number of stroke deaths attributable to SHS continued to rise globally, imposing a considerable stroke burden worldwide. These findings can inform targeted interventions and policies aimed at SHS control.

Efektivitas Citicoline terhadap Perbaikan Status Fungsional dan Gangguan Neurologis pada Pasien dengan Stroke Perdarahan Intraserebral Supratentorial Akut

Supratentorial intracerebral hemorrhage (ICH) is the second most common stroke and can potentially have poor outcomes. Citicoline has been researched extensively for ischemic stroke yet has little evidence for hemorrhagic stroke. This study aims to critically appraise evidence regarding efficacy of citicoline in improving functional status and neurological deficit in supratentorial ICH. The literature search utilized 5 databases: PubMed, Embase, Cochrane, Scopus, EBSCOHost. From 802 studies identified at the start of the search, 5 articles were selected for critical appraisal. A study by Zang demonstrated improvement in the NIHSS score (p=0.015) and Barthel index (p=0.001). A study by Mousavi showed improvement in the Barthel index (p=0.008) when compared to the control, but no difference when compared to the baseline in both groups. A study by Iranmanesh demonstrated improvement in the motoric strength (p=0.019). A study by Chua demonstrated improvement in the Barthel index at 3 months follow-up (p&lt;0.05). However, there are no differences in the modified Rankin scale and NIHSS score. A study by Secades demonstrated improvement in the NIHSS score (p&lt;0.001) when compared to baseline, but no difference when compared to the control. Citicoline has the potential to improve patient mobility in supratentorial intracerebral hemorrhage stroke, but in terms of improvement in functional status and neurological impairment requires further research.

Gastrointestinal Dysbiosis in Neuro-Critically Ill Patients: A Systematic Review of Case-Control Studies.

The human gastrointestinal tract (GIT) has a rich and pre-programmed microbiome. This microbiome is essential for physiological functions such as digestion, immunity, metabolism, and structural integrity, andof prime concern to us in conducting this study is the nervous system communication. This two-way communication between the GIT and central nervous system (CNS) is known as the gut-brain axis (GBA) and has implications for neurocritical disease. A change in any factor relating to this microbiome is known as gut dysbiosis; this can lead to aberrant communication through the GBA and in turn, can contribute to disease states. The primary objectiveof this study is to determine the cause-specific dysbiotic organisms in neuro-critically ill patients and their effects. We performed this study by searching published literature as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies that defined gastrointestinal dysbiosis in neuro-critically ill patients were retrieved using Boolean search from 2000 to 2023 via PubMed and Google Scholar and narrowed the results down to five prospectivecase-control studies. We performed their quality assessment. The results concludedthat in neurocritical illnesses such as encephalitis, brain tumors, intracerebral hemorrhage, and ischemic stroke, fluctuations in specific microbiota correlated with disease severity and prognosis. Moreover, the inhabiting population of dysbiotic organisms in neuro-critically ill patients were different in different diseases and there were no similarities in the composition of gut microbiota in these diseases.Taking stroke patients as an example; increased Enterobacteriaceae and lower Lachnospiraceae microbiome levels were found in patients with a higher stroke dysbiosis index (SDI). Those patients who developed stroke-associated pneumonia (SAP) displayed higher levels of Enterococcus species. In conclusion, dysbiosis has a major effect on neuro-critically ill patients' disease states and dysbiotic organisms can be used as a biomarker for disease.Further prospective studieson this topic are warranted for potential neurological and prognostic correlations.

IL-10 protects against OPC ferroptosis by regulating lipid reactive oxygen species levels post stroke

Accumulation of reactive oxygen species (ROS), especially on lipids, induces massive cell death in neurons and oligodendrocyte progenitor cells (OPCs) and causes severe neurologic deficits post stroke. While small compounds, such as deferoxamine, lipostatin-1, and ferrostatin-1, have been shown to be effective in reducing lipid ROS, the mechanisms by which endogenously protective molecules act against lipid ROS accumulation and subsequent cell death are still unclear, especially in OPCs, which are critical for maintaining white matter integrity and improving long-term outcomes after stroke. Here, using mouse primary OPC cultures, we demonstrate that interleukin-10 (IL-10), a cytokine playing roles in reducing neuroinflammation and promoting hematoma clearance, significantly reduced hemorrhage-induced lipid ROS accumulation and subsequent ferroptosis in OPCs. Mechanistically, IL-10 activated the IL-10R/STAT3 signaling pathway and upregulated the DLK1/AMPK/ACC axis. Subsequently, IL-10 reprogrammed lipid metabolism and reduced lipid ROS accumulation. In addition, in an autologous blood injection intracerebral hemorrhagic stroke (ICH) mouse model, deficiency of the endogenous Il-10, specific knocking out Il10r or Dlk1 in OPCs, or administration of ACC inhibitor was associated with increased OPC cell death, demyelination, axonal sprouting, and the cognitive deficits during the chronic phase of ICH and vice versa. These data suggest that IL-10 protects against OPC loss and white matter injury by reducing lipid ROS, supporting further development of potential clinical applications to benefit patients with stroke and related disorders.

Risk Factors and Functional Outcome of Ischemic Stroke Vis-à-vis Hemorrhagic Stroke at a Tertiary Care Hospital in North India

Abstract Background: Worldwide, stroke is the most common cause of death after coronary artery disease (CAD). The risk factor stratification and prognostication of stroke patients are vital in planning and allocating health-care resources. Methods: We conducted a prospective, comparative observational study. Fifty age- and sex-matched cases each of ischemic stroke (IS) and intracerebral hemorrhage (ICH) stroke were enrolled, and baseline demographic, risk factor profile, Glasgow Coma Scale, modified Rankin scale (mRS), and Barthel Index (BI) were recorded, and the cases were followed up for 90 days or till death. We looked at the risk factors associated with IS and ICH and functional outcome of IS vis-à-vis ICH using mRS and BI at 90 days postenrollment. We also compared the mortality of IS vis-à-vis ICH. Results: The presence of hypertension (100% vs. 88%) and smoking (50% vs. 26%) was significantly higher in ICH (P &lt; 0.05). The presence of diabetes mellitus (40% vs. 18%) and CAD (12% vs. 2%) was significantly more in IS cases (P &lt; 0.05). Consumption of alcohol was more prevalent in ICH patients compared to IS patients (30% vs. 24%). Based on mRS and BI at 90 days, ICH cases had significantly poorer functional outcome compared to IS cases (P &lt; 0.0001). Mortality of IS cases (4%) was also significantly less compared to ICH cases (30%). Conclusions: A combination of hypertension, smoking, and history of alcohol consumption had a higher predilection for the occurrence of ICH, whereas a combination of hypertension, diabetes mellitus, and CAD favored the occurrence of IS. The functional outcome of cases of ICH 90 days poststroke was significantly poorer compared to IS cases. The most important factors for poor outcome of ICH cases were more stroke severity at baseline compared to IS cases and the presence of intraventricular hemorrhages in some cases. Mortality was also found to be more in patients with ICH compared to IS.

Targeting Pro-Oxidant Iron with Exogenously Administered Apotransferrin Provides Benefits Associated with Changes in Crucial Cellular Iron Gate Protein TfR in a Model of Intracerebral Hemorrhagic Stroke in Mice.

We have previously demonstrated that the post-stroke administration of iron-free transferrin (apotransferrin, ATf) is beneficial in different models of ischemic stroke (IS) through the inhibition of the neuronal uptake of pro-oxidant iron. In the present study, we asked whether ATf is safe and also beneficial when given after the induction of intracerebral hemorrhage (ICH) in mice, and investigated the underlying mechanisms. We first compared the main iron actors in the brain of IS- or collagenase-induced ICH mice and then obtained insight into these iron-related proteins in ICH 72 h after the administration of ATf. The infarct size of the IS mice was double that of hemorrhage in ICH mice, but both groups showed similar body weight loss, edema, and increased ferritin and transferrin levels in the ipsilateral brain hemisphere. Although the administration of human ATf (hATf) to ICH mice did not alter the hemorrhage volume or levels of the classical ferroptosis GPX4/system xc- pathways, hATf induced better neurobehavioral performance, decreased 4-hydroxynonenal levels and those of the second-generation ferroptosis marker transferrin receptor (TfR), and restored the mRNA levels of the recently recognized cytosolic iron chaperone poly(RC) binding protein 2. In addition, hATf treatment lowered the ICH-induced increase in both endogenous mouse transferrin mRNA levels and the activation of caspase-2. In conclusion, hATf treatment provides neurobehavioral benefits post-ICH associated with the modulation of iron/oxidative players.

Deep Resequencing of the 1q22 Locus in Non-Lobar Intracerebral Hemorrhage.

Genome-wide association studies have identified 1q22 as a susceptibility locus for cerebral small vessel diseases, including non-lobar intracerebral hemorrhage (ICH) and lacunar stroke. In the present study, we performed targeted high-depth sequencing of 1q22 in ICH cases and controls to further characterize this locus and prioritize potential causal mechanisms, which remain unknown. A total of 95,000 base pairs spanning 1q22, including SEMA4A, SLC25A44, and PMF1/PMF1-BGLAP were sequenced in 1,055 spontaneous ICH cases (534 lobar and 521 non-lobar) and 1,078 controls. Firth regression and Rare Variant Influential Filtering Tool analysis were used to analyze common and rare variants, respectively. Chromatin interaction analyses were performed using Hi-C, chromatin immunoprecipitation followed by sequencing, and chromatin interaction analysis with paired-end tag databases. Multivariable Mendelian randomization assessed whether alterations in gene-specific expression relative to regionally co-expressed genes at 1q22 could be causally related to ICH risk. Common and rare variant analyses prioritized variants in SEMA4A 5'-UTR and PMF1 intronic regions, overlapping with active promoter and enhancer regions based on ENCODE annotation. Hi-C data analysis determined that 1q22 is spatially organized in a single chromatin loop, and that the genes therein belong to the same topologically associating domain. Chromatin immunoprecipitation followed by sequencing and chromatin interaction analysis with paired-end tag data analysis highlighted the presence of long-range interactions between the SEMA4A-promoter and PMF1-enhancer regions prioritized by association testing. Multivariable Mendelian randomization analyses demonstrated that PMF1 overexpression could be causally related to non-lobar ICH risk. Altered promoter-enhancer interactions leading to PMF1 overexpression, potentially dysregulating polyamine catabolism, could explain demonstrated associations with non-lobar ICH risk at 1q22, offering a potential new target for prevention of ICH and cerebral small vessel disease. ANN NEUROL 2024;95:325-337.

Analysis of Factors Influencing Mortality in Patients with Intracerebral Hemorrhagic Stroke

Stroke is a cerebrovascular disease that causes sudden neurological deficits due to the interruption of blood supply to the brain, resulting in the disruption of brain function. It is ranked as the second most common cause of death worldwide and leads to the highest number of disabilities globally. The incidence of this disease is 10-20 cases per 100,000 population, reaching 15% of all strokes worldwide yearly. The highest mortality rate was 20.3% after 48 hours and 18.3% less than 48 hours. This number is greater than the death rate in stroke infarction. This study aims to analyze the factors influencing mortality in patients with intracerebral hemorrhage (ICH). This type of research is observational analytic research. The design used is cross-sectional. This study was approved by the Health Ethics Committee of the Jemursari Islamic Hospital in Surabaya. The sampling technique uses total sampling. The total sample of this study was 65 patients. The sample in this study were all ICH stroke patients who were treated at RSI JS Surabaya from January 2019 to December 2021. Statistical analysis in this study used the chi-square correlation test. The results showed that the duration of hospitalization and bleeding volume had a significant correlation with the mortality in stroke patients (p-value&lt;0.05) with OR (95% CI) are 0.243 (0.082-0.723) and 0.154 (0.048-0.500) respectively. Bleeding volume has a correlation with mortality in this study. However, this study has only fewer samples and it can’t be generalized.

Behavioral Effects of Repetitive Transcranial Magnetic Stimulation in Disorders of Consciousness: A Systematic Review and Meta-Analysis.

Traumatic brain injury, cardiac arrest, intracerebral hemorrhage, and ischemic stroke may cause disorders of consciousness (DoC). Repetitive transcranial magnetic stimulation (rTMS) has been used to promote the recovery of disorders of consciousness (DoC) patients. In this meta-analysis, we examined whether rTMS can relieve DoC patient symptoms. We searched through journal articles indexed in PubMed, the Web of Science, Embase, Scopus, and the Cochrane Library until 20 April 2023. We assessed whether studies used rTMS as an intervention and reported the pre- and post-rTMS coma recovery scale-revised (CRS-R) scores. A total of 207 patients from seven trials were included. rTMS significantly improved the recovery degree of patients; the weighted mean difference (WMD) of the change in the CRS-R score was 1.89 (95% confidence interval (CI): 1.39-2.39; p < 0.00001) in comparison with controls. The subgroup analysis showed a significant improvement in CRS-R scores in rTMS over the dorsolateral prefrontal cortex (WMD = 2.24; 95% CI: 1.55-2.92; p < 0.00001; I2 = 31%) and the primary motor cortex (WMD = 1.63; 95% CI: 0.69-2.57; p = 0.0007; I2 = 14%). Twenty-hertz rTMS significantly improved CRS-R scores in patients with DoC (WMD = 1.61; 95% CI: 0.39-2.83; p = 0.010; I2 = 31%). Furthermore, CRS-R scores in rTMS over 20 sessions significantly improved (WMD = 1.75; 95% CI: 0.95-2.55; p < 0.0001; I2 = 12%). rTMS improved the symptoms of DoC patients; however, the available evidence remains limited and inadequate.