Stroke, as a neurological disorder with a poor overall prognosis, has long plagued the patients. Current stroke therapy lacks effective treatments. Ferroptosis has emerged as a prominent subject of discourse across various maladies in recent years. As an emerging therapeutic target, notwithstanding its initial identification in tumor cells associated with brain diseases, it has lately been recognized as a pivotal factor in the pathological progression of stroke. Acyl-CoA synthetase long-chain family member 4 (ACSL4) is a potential target and biomarker of catalytic unsaturated fatty acids mediating ferroptosis in stroke. Specifically, the upregulation of ACSL4 leads to heightened accumulation of lipid peroxidation products and reactive oxygen species (ROS), thereby exacerbating the progression of ferroptosis in neuronal cells. ACSL4 is present in various tissues and involved in multiple pathways of ferroptosis. At present, the pharmacological mechanisms of targeting ACSL4 to inhibit ferroptosis have been found in many drugs, but the molecular mechanisms of targeting ACSL4 are still in the exploratory stage. This paper introduces the physiopathological mechanism of ACSL4 and the current status of the research involved in ferroptosis crosstalk and epigenetics, and summarizes the application status of ACSL4 in modern pharmacology research, and discusses the potential application value of ACSL4 in the field of stroke.

Lactylation, a recently identified posttranslational modification (PTM), has emerged as a critical regulatory mechanism in cardiovascular diseases (CVDs). This PTM involves the addition of lactyl groups to lysine residues on histones and nonhistone proteins, influencing gene expression and cellular metabolism. The discovery of lactylation has revealed new directions for understanding metabolic and immune processes, particularly in the context of CVDs. This review describes the intricate roles of specific lactylated proteins and enzymes, such as H3K18, HMGB1, MCT1/4, and LDH, in the regulation of cardiovascular pathology. This study also highlights the unique impact of lactylation on myocardial hypertrophy and distinguishes it from other PTMs, such as SUMOylation and acetylation, underscoring its potential as a therapeutic target. Emerging drugs targeting lactate transporters and critical enzymes involved in lactylation offer promising avenues for novel CVD therapies. This review calls for further research to elucidate the mechanisms linking lactylation to CVDs, emphasizing the need for comprehensive studies at the molecular, cellular, and organismal levels to pave the way for innovative preventive, diagnostic, and treatment strategies in cardiovascular medicine.

Endovascular therapies (EVTs), including mechanical thrombectomy (MT) and intra-arterial thrombolysis (IAT) are becoming the standard of care for acute ischemic stroke management. However, little is known about the epidemiology of Post-stroke seizure (PSS) incidence in patients receiving EVT.

The aim of this study was to evaluate the incidence of PSS, including early symptomatic seizure (ES) and late seizure or post-stroke epilepsy (PSE) in patients treated with EVT for acute ischemic stroke. Also, to identify the factors that may influence the incidence of PSS in these patients.

We conducted a systematic review and meta-analysis of published studies indexed in PubMed, Web of Science, and Google Scholar, from inception to September 2023. A Meta-analysis was conducted using IBM SPSS 29 RESULTS: 18 articles were finally included in our review, with a pooled total of 41,056 participants. The cumulative incidence of PSS was 9.0 % (CI: [8.2 %-9.9 %]). The incidence of ES was 3.8 % [3.4 %-4.2 %], and late seizures (PSE) was 6.8 % [6.0 %-7.6 %]. Hemorrhagic transformation (OR: 2.04 CI: [1.59-2.62]), cortical involvement (OR: 1.71 [1.21-2.41]), and infarct size> 1/3 of the affected territories (OR: 4.15 [3.02-5.73]) were associated with an increased risk of PSS. Female sex (OR: 0.89[0.81-0.98]) and a 3 months mRS 0-2 (OR: 0.36 [0.22-0.60]) were both associated with a reduced PSS incidence.

This study suggests that PSS incidence is not higher in patients receiving EVT, and the associated risk factors are similar to those in patients treated by other therapeutic options.

Cerebral small vessel disease (SVD) is known to increase the risk of epilepsy, but the causal relationship between the two remains unclear. This study utilizes Mendelian Randomization (MR) to assess the genetic link between SVD and epilepsy, incorporating additional analyses including colocalization, gene-set, and pathway analysis to provide further evidence for shared mechanisms. We performed a two-sample MR study using 13 SNPs strongly associated with SVD as instrumental variables to assess their causal relationship with epilepsy. We also conducted colocalization analysis to identify shared genetic variants between SVD and epilepsy, gene-set enrichment analysis to explore common biological pathways, and protein-protein interaction (PPI) network analysis to investigate the molecular mechanisms. The MR analysis revealed a significant causal effect of SVD on epilepsy, with an odds ratio (OR) of 1.29 (95% CI: 1.09-1.53, P < 0.001). Colocalization analysis identified three genomic regions (chr1:100-600 kb, chr3:200-700 kb, and chr5:50-500 kb) with evidence of shared genetic variants. Pathway analysis highlighted endothelial cell signaling, blood-brain barrier function, and neuroinflammatory responses as enriched pathways, linking vascular health to neuronal excitability. The PPI network revealed key proteins involved in both vascular and neuronal processes, including ZNF646, PLEKHG1, and NOTCH3, further supporting shared mechanisms. This study provides strong genetic evidence for an association between SVD and epilepsy, with new insights from colocalization, gene-set, and pathway analyses while recognizing the limitations of Mendelian Randomization in establishing temporal causality. The findings suggest that genetic variants affecting vascular health, neuroinflammation, and blood-brain barrier integrity may contribute to both SVD and the risk of epilepsy. These results strengthen the understanding of the shared biological mechanisms underlying these two conditions and highlight SVD as an important risk factor for epilepsy.

Stroke recurrence is a serious and prevalent complication of ischemic stroke that warrants additional investigation.

A hospital-based retrospective observational study included acute-subacute ischemic stroke adult patients. The primary aim was to determine the risk factors associated with recurrent stroke within 365 days. Additionally, a combined outcome consisting of any stroke recurrence or all-cause mortality within 365 days was considered secondary outcome. Univariate and multivariable Cox proportional-hazards models were used to examine the association of risk factors with stroke recurrence and composite death/stroke recurrence.

Of 1,244 patients, 112 (9%) experienced stroke recurrence. The multivariable analysis identified risk factors for stroke recurrence including history of previous stroke (HR = 3.65, 95% CI:2.28-5.99, p = 0.0001), tissue plasminogen activator (tPA) treatment (HR = 2.84, 95% CI:1.57-4.86, p = 0.0003), seizure (HR = 1.96, 95% CI:1.14-3.22, p = 0.0105), and depression (HR = 2.26, 95% CI:1.33-3.69, p = 0.0016). Only previous stroke history (HR = 2.37, 95% CI:1.74-3.26, p = 0.0001) remained significantly associated with the combined outcome of stroke recurrence/death. Additional risk factors for the composite outcome included older age of patients (HR = 1.02, 95% CI:1.01-1.03, p = 0.0009), admission to the intensive care unit (ICU) (HR = 3.70, 95% CI:2.63-5.22, p = 0.0105), pneumonia (HR = 1.47, 95% CI:1.05-2.05, p = 0.0249), and brain edema (HR = 2.36, 95% CI:1.58-3.46, p = 0.0001).

Key findings include a stroke recurrence rate of 9.96% and a combined death/stroke recurrence rate of 21.83% within 365 days. Multivariable analysis confirmed that history of stroke, receiving tPA, experiencing seizures, and depression were significantly associated with stroke recurrence. Implementing additional preventive measures for individuals in these high-risk categories is essential. Further studies are needed to validate our findings.

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.

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.

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).

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.

Post-stroke epilepsy (PSE) is a common and significant complication that often occurs after stroke, and affects patients' prognosis and overall quality of life. In recent years, non-contrast computed tomography (NCCT) has become the preferred method for the clinical diagnosis of intracerebral hemorrhage (ICH). This study aimed to develop and validate a triple deep-learning model, simply named, the post-stroke epilepsy network (PSENet), to predict PSE in ICH patients based on NCCT.

A total of 1,130 patients (62 with PSE and 1,068 without PSE) who experienced an initial ICH at our hospital were enrolled in this study. Using five-fold cross-validation, all patients were randomly divided into training and validation sets at a ratio of 4:1. Next, the no-new-Net (nnU-Net) was used to automatically segment the ICH for the subsequent quantitative analysis. A triple deep-learning model was developed to extract the PSE-related features and incorporate the deep-learning features related to cortical involvement (FCI) and ICH volume to predict PSE. This model was compared with three clinical models constructed using random forest. Model performance was mainly evaluated using the area under the curve (AUC).

The nnU-Net had a high Dice score of 0.923. The proposed PSENet, which incorporated multiple features, showed excellent diagnostic performance, and had an accuracy of 0.876, a F1-score of 0.621, a recall of 0.716, a specificity of 0.897, and an AUC of 0.840, which significantly surpassed the AUC of the baseline clinical model (AUC =0.787).

Based on our findings, the developed PSENet could be used to predict PSE quickly after the first ICH, especially in scenarios in which reliable clinical information is lacking on admission.

Seizure is a relatively common neurological consequence after spontaneous intracerebral hemorrhage (SICH). This study aimed to investigate risk factors of early, late, and overall seizures in patients with SICH. Retrospective analysis was performed on all patients with SICH who completed two years of follow-up. The variables collected were obtained from demographic, clinical, radiographic and treatment data, in-hospital complications, and follow-up results. Univariate and multivariate analyzes were used to identify risk factors for post-hemorrhagic stroke seizure. Of 400 SICH patients recruited, 30 (7.5%) and 40 (10%) developed early and late seizures during the 2-year follow-up period, respectively. In the final result of the multivariate analysis, factors associated with the occurrence of the early seizure included lobar location of hematoma (p = 0.018), and GCS ≤ 12 on initial clinical presentation (p = 0.007). Factors associated with the occurrence of the late seizure included lobar location of hematoma (p = 0.001), volume of hematoma greater than 10 ml (p = 0.009), and midline shift on initial cranial CT (p = 0.036). Risk factors of the overall seizure after SICH included lobar location of hematoma (p < 0.001), volume of hematoma greater than 10 ml (p < 0.001), and craniotomy with evacuation of hematoma (p = 0.007). Furthermore, seizure was also associated with a poor functional outcome 2 years after the onset of SICH. Several factors associated with the appearance of post-ICH seizures were revealed. In patients with increased risk of post-SICH seizures, appropriate surveillance and management of seizures should be carried out.

Post-stroke epilepsy (PSE) is a major complication of stroke. However, data about the predictors of PSE in patients with acute ischemic stroke (AIS) undergoing mechanical thrombectomy are limited.

To evaluate the relationship between intraoperative angiographic signs and PSE risk in patients with anterior circulation AIS who underwent mechanical thrombectomy.

We conducted a retrospective study. A total of 800 patients with AIS who underwent mechanical thrombectomy were classified into case and control groups based on the occurrence of PSE. Propensity score matching (PSM) (1:4) was applied using covariates such as age, sex, National Institutes of Health Stroke Scale score at admission, and baseline modified Rankin Scale score. Conditional logistic regression and mediation analysis were performed. Subgroup analyses were conducted to assess the effect of modification. A diagnostic model based on the angiographic signs and clinical characteristics was developed.

After PSM, 67 and 234 patients with and without PSE, respectively, were selected. The PSE group had significantly higher incidences of hemorrhagic transformation, early seizures, early venous filling (EVF) sign, inferior frontal gyrus (IFG), hippocampus, basal ganglia blush sign, and larger infarct size. After adjusting for hypertension, diabetes, hemorrhagic transformation, infarct size, early seizure, IFG, and hippocampus involvement, EVF remained independently associated with PSE. Hemorrhagic transformation mediated 14.87% of the EVF-PSE associations. Comparison of the evaluation metrics of each model showed that model 3 exhibited the best overall performance.

Hemorrhagic transformation mediates the EVF-PSE association. EVF signs are key predictors of PSE following mechanical thrombectomy.

Postoperative seizures are a common complication after surgical drainage of nonacute chronic subdural hematomas (SDHs). The literature increasingly supports the use of prophylactic antiepileptic drugs for craniotomy, a procedure that is often associated with larger collections and worse clinical status at admission. This study aimed to compare the incidence of postoperative seizures in patients treated with burr-hole drainage and those treated with craniotomy through propensity score matching (PSM).

A retrospective cohort analysis was conducted on patients with surgical drainage of nonacute SDHs (burr-holes and craniotomies) between January 2017 to December 2021 at 2 academic institutions in the United States. PSM was performed by controlling for age, subdural thickness, subacute component, and preoperative Glasgow Coma Scale. Seizure rates and accompanying abnormalities on electroencephalographic tracing were evaluated postmatching.

A total of 467 patients with 510 nonacute SDHs underwent 474 procedures, with 242 burr-hole evacuations (51.0%) and 232 craniotomies (49.0%). PSM resulted in 62 matched pairs. After matching, univariate analysis revealed that burr-hole evacuations exhibited lower rates of seizures (1.6% vs 11.3%; P = .03) and abnormal electroencephalographic findings (0.0% vs 4.8%; P = .03) compared with craniotomies. No significant differences were observed in postoperative Glasgow Coma Scale ( P = .77) and length of hospital stay ( P = .61).

Burr-hole evacuation demonstrated significantly lower seizure rates than craniotomy using a propensity score-matched analysis controlling for significant variables.

Post-stroke seizure (PSS) increases morbidity and mortality after ischemic stroke, but a comprehensive understanding of its incidence and risk factors is lacking. We report the rate and risk factors of PSS at a single institution.

A retrospective cohort study of adult acute ischemic stroke patients between 2018 and 2022 at a comprehensive stroke center was conducted. Patients with a history of seizures, additional stroke during index admission, or death within 7 days of stroke onset were excluded. Early PSS was defined as a new seizure occurring ≤7 days after stroke onset, while late PSS occurred >7 days after stroke onset. Multivariable logistic regression and cox proportional hazard analysis was conducted.

1211 participants met inclusion criteria. Patients were a mean age of 67.82 and were primarily male (58.7 %), white (72.6 %), and non-Hispanic (91.9 %). Incidence of PSS was 8.8 % (n = 106), of which 53.8 % (n = 57) were early and 46.2 % (n = 49) were late. Bivariate analysis identified younger age, diabetes, baseline National Institutes of Health Stroke Scale (NIHSS), Alberta Stroke Program Early Computed Tomography Score ≤5, cortical involvement, and hemorrhagic transformation as significant in the development of PSS. Multivariable cox proportional hazard analysis identified cortical involvement (hazard ratio [HR]: 2.31, 95 % confidence interval [CI] [1,29, 4.14]), NIHSS ≥ 21 (HR: 1.82, 95 % CI [1.02, 3.22]),and younger age (HR: 0.97, 95 % CI [0.96, 0.98]) as significant PSS predictors.

PSS occurred in 8.8 % of patients presenting with ischemic stroke. Hemorrhagic transformation, cortical involvement, high NIHSS, and younger age were significant predictors of PSS.

Neurological impairments are the leading cause of post-stroke mortality, while stroke-related cardiovascular diseases rank second in significance. This study investigates the potential protective effects of MitoTEMPO (2,2,6,6-tetramethyl-4-[[2-(triphenylphosphonio) acetyl] amino]-1-piperidinyloxy, monochloride, monohydrate), a mitochondria-specific antioxidant, against cardiac and neurological complications following stroke. The objective is to assess whether MitoTEMPO can be utilized as a protective agent for individuals with a high risk of stroke.

Seventeen-week-old male Wistar Albino rats were randomly assigned to three groups: SHAM, ischemia-reperfusion and MitoTEMPO + ischemia-reperfusion (MitoTEMPO injection 0.7 mg/kg/day for 14 days). The SHAM group underwent a sham operation, while the ischemia-reperfusion group underwent 1-h middle cerebral artery occlusion followed by three days of reperfusion. Afterwards, noninvasive thoracic electrical bioimpedance and electrocardiography measurements were taken, and sample collection was performed for histological and biochemical examinations.

Our thoracic electrical bioimpedance and electrocardiography findings demonstrated that MitoTEMPO exhibited a protective effect on most parameters affected by ischemia-reperfusion compared to the SHAM group. Furthermore, our biochemical and histological data revealed a significant protective effect of MitoTEMPO against oxidative damage.

The findings suggest that both ischemia-reperfusion-induced cardiovascular abnormalities and the protective effect of MitoTEMPO may involve G-protein coupled receptor-mediated signaling mechanisms. This study was conducted with limitations including a single gender, a uniform age group, a specific stroke model limited to middle cerebral artery, and pre-scheduled only one ischemia-reperfusion period. In future studies, addressing these limitations may enable the implementation of preventive measures for individuals at high risk of stroke.

Sovateltide (Tycamzzi™), an endothelin-B (ET-B) receptor agonist, increases cerebral blood flow, has anti-apoptotic activity, and promotes neural repair following cerebral ischaemic stroke. The objectives of this study were to evaluate the efficacy and safety of sovateltide in adult participants with acute cerebral ischaemic stroke.

This was a randomised, double-blind, placebo-controlled, multicentre, Phase III clinical trial of sovateltide in participants with cerebral ischaemic stroke receiving standard of care (SOC) in India. Patients aged 18-78 years presenting up to 24 h after the onset of symptoms with radiologic confirmation of ischaemic stroke and a National Institutes of Health Stroke Scale score (NIHSS) of ≥ 6 were enrolled. Patients with recurrent stroke, receiving endovascular therapy, or with intracranial haemorrhage were excluded. The study drug (saline or sovateltide [0.3 µg/kg] was administered intravenously in three doses at 3 ± 1 h intervals on Days 1, 3, and 6, and follow-up was 90 days). The Multivariate Imputation by Chained Equations (MICE) was used to impute the missing assessments on the endpoints. An unpaired t-test, two-way analysis of variance with Tukey's multiple comparison test, and the Chi-square test were used for the statistical analysis. The objective was to determine at Day 90 (1) the number of patients with a modified Rankin Scale score (mRS) 0-2, and (2) the number of patients with an NIHSS 0-5 at 90 days.

Patients were randomised with 80 patients in the sovateltide and 78 in the control group. Patients received the investigational drug at about 18 h of stroke onset in both control and sovateltide groups. The median NIHSS at randomisation was 10.00 (95% CI 9.99-11.65) in the control group and 9.00 (95% CI 9.11-10.46) in the sovateltide group. Seventy patients completed the 90-day follow-up in the control group and 67 in the sovateltide group. The proportion of intention-to-treat (ITT) patients with mRS 0-2 score at Day 90 post-randomisation was 22.67% higher (odds ratio [OR] 2.75, 95% CI 1.37-5.57); similarly, the proportion of patients with NIHSS score of 0-5 at Day 90 was 17.05% more (OR 2.67, 95% CI 1.27-5.90) in the sovateltide group than in the control group. An improvement of ≥ 2 points on the mRS was observed in 51.28% and 72.50% of patients in the control and sovateltide groups, respectively (OR 2.50, 95% CI 1.29-4.81). Seven of 78 patients (8.97%) in the control group and 7 of 80 (8.75%) in the sovateltide group developed intracranial haemorrhage (ICH). The adverse events were not related to sovateltide.

The sovateltide group had a greater number of cerebral ischaemic stroke patients with lower mRS and NIHSS scores at 90 days post-treatment than the control group. This trial supported the regulatory approval of sovateltide in India, but a multinational RESPECT-ETB trial will be conducted for US approval.

Clinical Trials Registry, India (CTRI/2019/09/021373) and the United States National Library of Medicine, ClinicalTrials.gov (NCT04047563).

Background: Levetiracetam has a favorable pharmacology profile to be used subcutaneously. However, its subcutaneous use is still considered off-label as this is beyond its license. The evidence base for its safety, tolerability, and efficacy is limited to observational studies. Objectives: To report the safety and efficacy of subcutaneous levetiracetam in Latino patients on home care. Design: Observational retrospective case series study. Subjects: Consecutive sample of Latino adults with life-limiting illnesses. Methods: A case series framework with 4 domains (selection, ascertainment, causality, and reporting) to ensure reporting quality was used. Additionally, 8 relevant outcomes established in a previous comprehensive review, were collected and reported. Adverse reactions were documented using the Common Terminology Criteria for Adverse Events. Results: Fifteen Latino patients with oncological and non-oncological diagnoses received subcutaneous levetiracetam for a mean of 21 days on home care. Levetiracetam was most frequently initiated subcutaneously due to loss of the oral route. The average dosage of subcutaneous levetiracetam was 1200 mg. Only 1 patient required a dose adjustment, and only 2 patients experienced a total of 5 seizures during the therapy trial. No adverse reactions were reported. Conclusions: Subcutaneous levetiracetam appears to be effective and safe. This case series of Latino patients in home care expands the evidence of its use in the home care setting. The preliminary data reported by now on multiple case series warrants robust trials.

It is unclear which patients with non-traumatic (spontaneous) intracerebral haemorrhage (ICH) are at risk of developing acute symptomatic seizures (provoked seizures occurring within the first week after stroke onset; early seizures, ES) and whether ES predispose to the occurrence of remote symptomatic seizures (unprovoked seizures occurring more than 1 week after stroke; post-stroke epilepsy, PSE) and long-term mortality.

In the setting of the Multicenter Study on Cerebral Haemorrhage in Italy (MUCH-Italy) we examined the risk of ES and whether they predict the occurrence of PSE and all-cause mortality in a cohort of patients with first-ever spontaneous ICH and no previous history of epilepsy, consecutively hospitalized in 12 Italian neurological centers from 2002 to 2014.

Among 2570 patients (mean age, 73.4 ± 12.5 years; males, 55.4%) 228 (8.9%) had acute ES (183 (7.1%) short seizures and 45 (1.8%) status epilepticus (SE)). Lobar location of the hematoma (OR, 1.49; 95% CI, 1.06-2.08) was independently associated with the occurrence of ES. Of the 2,037 patients who were followed-up (median follow-up time, 68.0 months (25th-75th percentile, 77.0)), 155 (7.6%) developed PSE. ES (aHR, 2.34; 95% CI, 1.42-3.85), especially when presenting as short seizures (aHR, 2.35; 95% CI, 1.38-4.00) were associated to PSE occurrence. Unlike short seizures, SE was an independent predictor of all-cause mortality (aHR, 1.50; 95% CI, 1.005-2.26).

The long-term risk of PSE and death after an ICH vary according to ES subtype. This might have implications for the design of future clinical trials targeting post-ICH epileptic seizures.

Stroke is the second leading cause of global deaths. Post-stroke seizures (PSS) can lead to lasting complications, such as prolonged hospitalizations, increased disability rates, and higher mortality. Our study investigates the associated factors that contribute to post-stroke seizures in patients at a local tertiary hospital.

We designed a case-control study where patients admitted with PSS were recruited with consent. Controls admitted for stroke without seizure were then included. Suitability based on exclusion criteria was ensured before recording their sociodemographic and clinical data. An EEG was performed and read by two certified neurologists before the data was analyzed.

We recruited 180 participants, 90 cases and 90 matched controls. Gender (p=0.013), race (p=0.015), dyslipidemia (p<0.001), prior stroke (p<0.031), large artery atherosclerosis (p<0.001), small vessel occlusions (p<0.001), blood pressure on presentation (p<0.028) and thrombolysis administration (p<0.029) were significantly associated with the occurrence of PSS. An increase in odds of PSS was observed in the male gender (1.974), dyslipidemia (3.480), small vessel occlusions (4.578), and in participants with epileptiform changes on EEG (3.630). Conversely, lower odds of PSS were seen in participants with high blood pressure on presentation (0.505), large artery atherosclerosis (0.266), and those who underwent thrombolysis (0.319).

This study emphasized that identifying post-stroke seizures may be aided by EEGs and recognizing at-risk groups, which include males of Chinese descent in Asia, dyslipidemia, small vessel occlusions, those with low to normal blood pressure on presentation, and epileptiform changes in EEGs.

This study aimed to assess the knowledge, attitudes, and practices (KAP) among family caregivers of patients with cerebral infarction toward home-based care.

This web-based cross-sectional study was conducted between October 2023 and February 2024 at Yancheng Third People's Hospital. A self-designed questionnaire was developed to collect demographic information, and assess the KAP among family caregivers of patients with cerebral infarction toward home-based care.

A total of 761 questionnaires were included in the study. Among the participants, 453 (59.53%) were female, and 548 (72.01%) lived with the patients. The mean knowledge, attitudes and practices scores were 6.67 ± 1.73 (possible range: 0-9), 32.95 ± 2.46 (possible range: 9-45), and 28.64 ± 4.39 (possible range: 8-40), respectively. Path analysis showed the direct effect of knowledge on both attitudes (β = 0.885, p < 0.001) and practices (β = 1.295, p < 0.001), as well as of attitudes on practices (β = 0.838, p < 0.001).

Family caregivers of patients with cerebral infarction have sufficient knowledge, positive attitudes and proactive practices toward home-based care. However, they still exhibit deficiencies in certain aspects of knowledge, attitudes, and practice. Developing personalized educational strategies may be instrumental in enhancing family caregivers' knowledge of home-based care. This, in turn, could improve their attitudes and elevate their practice levels.

Hemorrhagic stroke, characterized by acute bleeding due to cerebrovascular lesions, is associated with plasma lipids and endothelial damage. The causal relationship between genetic plasma lipid levels and hemorrhagic stroke remains unclear. This study employs a two-sample Mendelian randomization (MR) analysis to explore the causal relationship between plasma lipid profiles with different fatty acid chains and the risk of intracerebral and subarachnoid hemorrhage, the two main subtypes of hemorrhagic stroke.

The datasets for exposure and outcome summary statistics were obtained from publicly available sources such as the GWAS Catalog, IEU OpenGWAS project, and FinnGen. The two-sample MR analysis was employed to initially assess the causal relationship between 179 plasma lipid species and the risk of intracerebral and subarachnoid hemorrhage in the Finnish population, leading to the identification of candidate lipids. The same methods were applied to reanalyze data from European populations and conduct a meta-analysis of the candidate lipids. The Inverse Variance Weighting (IVW) method served as the primary analysis for causal inference, with additional methods used for complementary analyses. Sensitivity analysis was conducted to clarify causal relationships and reduce biases.

Two analyses using Mendelian randomization were performed, followed by meta-analyses of the results. A causal relationship was established between 11 specific lipid species and the occurrence of intracerebral hemorrhage within the European population. Additionally, 5 distinct lipid species were associated with subarachnoid hemorrhage. Predominantly, lipids with linoleic acid and arachidonic acid side chains were identified. Notably, lipids containing arachidonic acid chains (C20:4) such as PC 18:1;0_20:4;0 consistently showed a decreased risk of both intracerebral hemorrhage [p < 0.001; OR(95% CI) = 0.892(0.835-0.954)] and subarachnoid hemorrhage [p = 0.002; OR(95% CI) = 0.794(0.689-0.916)]. Conversely, lipids with linoleic acid chains (C18:2) were associated with an increased risk of intracerebral hemorrhage.

This study identifies a potential causal relationship between lipids with different fatty acid side chains and the risk of intracerebral and subarachnoid hemorrhagic stroke, improving the understanding of the mechanisms behind the onset and progression of hemorrhagic stroke.

Previously, we reported the concept of a cloud-based telemedicine platform for patients with intracerebral hemorrhage (ICH) at local emergency rooms in rural and medically underserved areas in Gangwon state by combining artificial intelligence and remote consultation with a neurosurgeon. Developing a telemedicine ICH treatment protocol exclusively for doctors with less ICH expertise working in emergency rooms should be part of establishing this system. Difficulties arise in providing appropriate early treatment for ICH in rural and underserved areas before the patient is transferred to a nearby hub hospital with stroke specialists. This has been an unmet medical need for decade. The available reporting ICH guidelines are realistically possible in university hospitals with a well-equipped infrastructure. However, it is very difficult for doctors inexperienced with ICH treatment to appropriately select and deliver ICH treatment based on the guidelines. To address these issues, we developed an ICH telemedicine protocol. Neurosurgeons from four university hospitals in Gangwon state first wrote the guidelines, and professors with extensive ICH expertise across the country revised them. Guidelines and recommendations for ICH management were described as simply as possible to allow more doctors to use them easily. We hope that our effort in developing the telemedicine protocols will ultimately improve the quality of ICH treatment in local emergency rooms in rural and underserved areas in Gangwon state.

Gabapentinoid drugs (pregabalin and gabapentin) have been successfully used in the treatment of neuropathic pain and in focal seizure prevention. Recent research has demonstrated their potent activities in modulating neurotransmitter release in neuronal tissue, oxidative stress, and inflammation, which matches the mechanism of action via voltage-gated calcium channels. In this review, we briefly elaborate on the medicinal history and ligand-binding sites of gabapentinoids. We systematically summarize the preclinical and clinical research on gabapentinoids in stroke, including ischemic stroke, intracerebral hemorrhage, subarachnoid hemorrhage, seizures after stroke, cortical spreading depolarization after stroke, pain after stroke, and nerve regeneration after stroke. This review also discusses the potential targets of gabapentinoids in stroke; however, the existing results are still uncertain regarding the effect of gabapentinoids on stroke and related diseases. Further preclinical and clinical trials are needed to test the therapeutic potential of gabapentinoids in stroke. Therefore, gabapentinoids have both opportunities and challenges in the treatment of stroke.

First-seizure clinics (FSCs) aim to deliver prompt specialist care to patients with new-onset undifferentiated seizure events.

To determine whether FSC attendance and time to FSC are associated with subsequent health care utilization and mortality and to investigate factors associated with FSC nonattendance.

This was a record-linkage, retrospective, cohort study of patients who booked appointments at 2 FSCs between 2007 and 2018. Patients' records were linked to state-wide administrative databases between 2000 and 2021. The setting comprised the FSCs of 2 major metropolitan public hospitals in Melbourne, Australia, providing national inpatient and outpatient adult epilepsy services. Of patients who booked appointments at the FSCs, those who were successfully linked for analysis were included in the study. Patients who recorded only canceled appointments were excluded from analysis of outcomes. Study data were analyzed from January 2000 to December 2021.

FSC attendance.

Subsequent all-cause and seizure-related emergency department (ED) presentations and hospital admissions.

Of 10 162 patients with appointments at FSCs, 9392 were linked for analysis, with mean (SD) follow-up time 6.9 (2.8) years after FSC referral. A total of 703 patients were excluded. Among 9392 linked patients, 5398 were male (57.5%; mean [SD] age, 59.7 [11.2] years). FSC attendance was associated with reduced subsequent all-cause emergency presentations (adjusted incidence rate ratio [aIRR], 0.72; 95% CI, 0.66-0.79) and all-cause hospitalization (aIRR, 0.81; 95% CI, 0.75-0.88). Those who attended at the first-scheduled appointment, compared with those who attended only a rescheduled, delayed appointment, had reduced subsequent all-cause emergency presentations (aIRR, 0.83; 95% CI, 0.76-0.91), all-cause hospitalization (aIRR, 0.71; 95% CI, 0.65-0.79), seizure-related presentations (aIRR, 0.40; 95% CI, 0.33-0.49), and mortality (hazard ratio, 0.82; 95% CI, 0.69-0.98). Male sex was associated with nonattendance (adjusted relative risk [aRR], 1.12; 95% CI, 1.03-1.22), as were injury at emergency presentation (aRR, 1.12; 95% CI, 1.01-1.24), psychiatric comorbidity (aRR, 1.68; 95% CI, 1.55-1.81), previous seizure-related presentations (aRR, 1.35; 95% CI, 1.22-1.49), and delays (>14 days) between FSC referral and appointment (aRR, 1.35; 95% CI, 1.18-1.54). Hospitalization at referral was associated with reduced nonattendance (aRR, 0.80; 95% CI, 0.72-0.90), as were non-English language preference (aRR, 0.81; 95% CI, 0.69-0.94), distance greater than 6 mi from home to clinic (aRR, 0.85; 95% CI, 0.76-0.95), and physical comorbidity (aRR, 0.80; 95% CI, 0.72-0.89).

Results of this cohort study suggest that FSC attendance, particularly early attendance, was associated with reduced rates of subsequent hospital utilization. This knowledge may support adequately resourcing FSCs to improve equitable, timely access. Future study directions include assessing interventions that may support FSC attendance for at-risk groups.

Although previous studies have reported a bidirectional relationship between ischemic stroke (IS) and epilepsy, the existence of a causal nexus and its directionality remains a topic of controversy.

The single nucleotide polymorphisms (SNPs) associated with IS were extracted from the Genome-Wide Association Study (GWAS) database. Pooled genetic data encompassing all epilepsy cases, as well as generalized and focal epilepsy subtypes, were acquired from the International League Against Epilepsy's GWAS study. In this study, the primary analysis approach utilized the inverse variance weighting (IVW) method as the main analytical technique. To enhance the robustness of the findings against potential pleiotropy, additional sensitivity analyses were conducted.

In the forward analysis, the IVW method demonstrated that IS was associated with an increased risk of all epilepsy (odds ratio (OR) = 1.127, 95 % confidence interval (CI) = 1.038-1.224, P = 0.004) and generalized epilepsy (IVW: OR = 1.340, 95 % CI = 1.162-1.546, P = 5.70 × 10-5). There was no substantial causal relationship observed between IS and focal epilepsy (P > 0.05). Furthermore, generalized epilepsy, focal epilepsy, and all epilepsy did not show a causal relationship with IS.

This Mendelian randomization (MR) analysis demonstrates that IS increases the risk of developing epilepsy, especially generalized epilepsy. Conversely, no clear causal association was found between epilepsy and the onset of stroke. Therefore, the possible mechanisms of the effect of epilepsy on the pathogenesis of IS still need to be further investigated.

The blood-brain barrier (BBB) regulates the exchange of metabolites and cells between the blood and brain, and maintains central nervous system homeostasis. Various factors affect BBB barrier functions, including reactive oxygen species (ROS). ROS can act as stressors, damaging biological molecules, but they also serve as secondary messengers in intracellular signaling cascades during redox signaling. The impact of ROS on the BBB has been observed in multiple sclerosis, stroke, trauma, and other neurological disorders, making blocking ROS generation a promising therapeutic strategy for BBB dysfunction. However, it is important to consider ROS generation during normal BBB functioning for signaling purposes. This review summarizes data on proteins expressed by BBB cells that can be targets of redox signaling or oxidative stress. It also provides examples of signaling molecules whose impact may cause ROS generation in the BBB, as well as discusses the most common diseases associated with BBB dysfunction and excessive ROS generation, open questions that arise in the study of this problem, and possible ways to overcome them.

Despite previous research suggesting a potential association between cerebral small vessel disease (CSVD) and epilepsy, the precise causality and directionality between cerebral small vessel disease (CSVD) and epilepsy remain incompletely understood. We aimed to investigate the causal link between CSVD and epilepsy.

A bidirectional two-sample Mendelian randomization (MR) analysis was performed to evaluate the causal relationship between CSVD and epilepsy. The analysis included five dimensions of CSVD, namely small vessel ischemic stroke (SVS), intracerebral hemorrhage (ICH), white matter damage (including white matter hyperintensity [WMH], fractional anisotropy, and mean diffusivity), lacunar stroke, and cerebral microbleeds. We also incorporated epilepsy encompassing both focal epilepsy and generalized epilepsy. Inverse variance weighted (IVW) was used as the primary estimate while other four MR techniques were used to validate the results. Pleiotropic effects were controlled by adjusting vascular risk factors through multivariable MR.

The study found a significant association between SVS (odds ratio [OR] 1.117, PFDR = 0.022), fractional anisotropy (OR 0.961, PFDR = 0.005), mean diffusivity (OR 1.036, PFDR = 0.004), and lacunar stroke (OR 1.127, PFDR = 0.007) with an increased risk of epilepsy. The aforementioned correlations primarily occurred in focal epilepsy rather than generalized epilepsy on subgroup analysis and retained their significance in the multivariable MR analysis.

Our study demonstrated that genetic susceptibility to CSVD independently elevates the risk of epilepsy, especially focal epilepsy. Diffusion tensor imaging may help screen patients at high risk for epilepsy in CSVD. Improved management of CSVD may be a significant approach in reducing the overall prevalence of epilepsy.

Qingda granule (QDG) is effective for treating hypertension and neuronal damage after cerebral ischemia/reperfusion. However, the anti-neuroinflammatory effect of QDG on injury due to cerebral ischemia/reperfusion is unclear.

The objective was to evaluate the effectiveness and action of QDG in treating neuroinflammation resulting from cerebral ischemia/reperfusion-induced injury.

Network pharmacology was used to predict targets and pathways of QDG. An in vivo rat model of middle cerebral artery occlusion/reperfusion (MCAO/R) as well as an in vitro model of LPS-stimulated BV-2 cells were established. Magnetic resonance imaging (MRI) was used to quantify the area of cerebral infarction, with morphological changes in the brain being assessed by histology. Immunohistochemistry (IHC) was used to assess levels of the microglial marker IBA-1 in brain tissue. Bioplex analysis was used to measure TNF-α, IL-1β, IL-6, and MCP-1 in sera and in BV-2 cell culture supernatants. Simultaneously, mRNA levels of these factors were examined using RT-qPCR analysis. Proteins of the TLR4/NF-κB/NLRP3 axis were examined using IHC in vivo and Western blot in vitro, respectively. While NF-κB translocation was assessed using immunofluorescence.

The core targets of QDG included TNF, NF-κB1, MAPK1, MAPK3, JUN, and TLR4. QDG suppressed inflammation via modulation of TLR4/NF-κB signaling. In addition, our in vivo experiments using MCAO/R rats demonstrated the therapeutic effect of QDG in reducing brain tissue infarction, improving neurological function, and ameliorating cerebral histopathological damage. Furthermore, QDG reduced the levels of TNF-α, IL-1β, IL-6, and MCP-1 in both sera from MCAO/R rats and supernatants from LPS-induced BV-2 cells, along with a reduction in the expression of the microglia biomarker IBA-1, as well as that of TLR4, MyD88, p-IKK, p-IκBα, p-P65, and NLRP3 in MCAO/R rats. In LPS-treated BV-2 cells, QDG downregulated the expression of proinflammatory factors and TLR4/NF-κB/NLRP3 signaling-related proteins. Additionally, QDG reduced translocation of NF-κB to the nucleus in both brains of MCAO/R rats and LPS-induced BV-2 cells. Moreover, the combined treatment of the TLR4 inhibitor TAK242 and QDG significantly reduced the levels of p-P65, NLRP3, and IL-6.

QDG significantly suppressed neuroinflammation by inhibiting the TLR4/NF-κB/NLRP3 axis in microglia. This suggests potential for QDG in treating ischemia stroke.

Hemorrhagic stroke (HS), including non-traumatic intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH), constitutes a substantial proportion of cerebrovascular incidents, accounting for around 30% of stroke cases. The triglyceride-glucose index (TyG-i) represents a precise insulin resistance (IR) indicator, a crucial metabolic disturbance. Existing literature has demonstrated an association between TyG-i and all-cause mortality (ACM) among individuals suffering from ischemic stroke (IS). Yet, the TyG-i prognostic implications for severe HS patients necessitating intensive care unit (ICU) admission are not clearly understood. Considering the notably elevated mortality and morbidity associated with HS relative to IS, investigating this association is warranted. Our primary aim was to investigate TyG-i and ACM association among critically ill HS patients within an ICU context.

Herein, patients with severe HS were identified by accessing the Medical Information Mart for Intensive Care-IV (MIMIC-IV, version 2.2) database, using the International Classification of Diseases (ICD)-9/10 as diagnostic guidelines. Subsequently, we stratified the subjects into quartiles, relying on their TyG-i scores. Moreover, we measured mortality at ICU, in-hospital, 30 days, 90 days, and 1 year as the outcomes. Cox proportional hazards regression analysis and restricted cubic splines (RCS) were deployed for elucidating the relation between the TyG-i and ACM while utilizing the Kaplan-Meier (K-M) method to estimate survival curves. The findings' robustness was assessed by conducting subgroup analysis and interaction tests employing likelihood ratio tests.

The analysis included 1475 patients, with a male predominance of 54.4%. Observed mortality rates in the ICU, hospital, 30 days, 90 days, and 1 year were 7.3%, 10.9%, 13.8%, 19.7%, and 27.3%, respectively. Multivariate Cox regression analysis results manifested that heightened TyG-i was significantly related to ACM at 30 days (adjusted hazard ratio [aHR]: 1.32; 95% confidence interval [CI]: 1.05-1.67; P = 0.020), 90 days (aHR: 1.27; 95% CI: 1.04-1.55; P = 0.019), and 1 year (aHR: 1.22; 95% CI: 1.03-1.44; P = 0.023). The results of RCS analysis demonstrated a progressive elevation in ACM risk with rising TyG-i levels. Interaction tests found no significant effect modification in this relationship.

In summary, TyG-i exhibits a significant correlation with ACM among patients enduring critical illness due to HS. This correlation underscores the probable utility of TyG-i as a prognostic tool for stratifying HS patients according to their risk of mortality. Applying TyG-i in clinical settings could enhance therapeutic decision-making and the management of disease trajectories. Additionally, this investigation augments existing research on the linkage between the TyG-i and IS, elucidating the TyG-i's role in predicting mortality across diverse stroke categories.

The prevalence of longstanding chronic diseases has increased worldwide, along with the average age of the population. As a result, an increasing number of people is affected by two or more chronic conditions simultaneously, and healthcare systems are facing the challenge of treating multimorbid patients effectively. Current therapeutic strategies are suited to manage each chronic condition separately, without considering the whole clinical condition of the patient. This approach may lead to suboptimal clinical outcomes and system inefficiencies (e.g. redundant diagnostic tests and inadequate drug prescriptions). We develop a novel methodology based on the joint implementation of data reduction and clustering algorithms to identify patterns of chronic diseases that are likely to co-occur in multichronic patients. We analyse data from a large adult population of multichronic patients living in Tuscany (Italy) in 2019 which was stratified by sex and age classes. Results demonstrate that (i) cardio-metabolic, endocrine, and neuro-degenerative diseases represent a stable pattern of multimorbidity, and (ii) disease prevalence and clustering vary across ages and between women and men. Identifying the most common multichronic profiles can help tailor medical protocols to patients' needs and reduce costs. Furthermore, analysing temporal patterns of disease can refine risk predictions for evolutive chronic conditions.

Ethical dilemmas can occur in any situation in clinical medicine. In patients undergoing neuro-anesthesia for surgical procedure evacuation of intracerebral hemorrhage with a history of hemorrhagic stroke, anticoagulants should not be given because they can cause recurrent bleeding. Meanwhile, at the same time, the patient could also be infected with coronavirus disease 2019 (COVID-19), one of treatment is the administration of anticoagulants.

A case report. A 46-year-old male patient was admitted to hospital with a loss of consciousness and was diagnosed with intracerebral hemorrhage due to a hemorrhagic stroke and was confirmed positive for COVID-19. Giving anticoagulants to patients is considered counterproductive so, an ethical dilemma arises. For this reason, a joint conference was held to obtain the best ethical and medicolegal solutions for the patient.

By using several methods of resolving ethical dilemmas such as basic ethical principles, supporting ethical principles, and medicolegal considerations, it was decided that the patient was not to be given anticoagulants.

Giving anticoagulants to hemorrhagic stroke patients is dangerous even though it is beneficial for COVID-19 patients, so here the principle of risk-benefit balance is applied to patients who prioritize risk prevention rather than providing benefits. This is also supported by the prima facie principle by prioritizing the principle of non-maleficence rather than beneficence, the minus malum principle by seeking the lowest risk, and the double effect principle by making the best decision even in a slightly less favorable way as well as the medicolegal aspect by assessing patient safety and risk management.

Neuroelectric disruptions such as seizures and cortical spreading depolarization may contribute to the development of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH). However, effects of antiepileptic drug prophylaxis on outcomes remain controversial in SAH. The authors investigated if prophylactic administration of new-generation antiepileptic drugs levetiracetam and perampanel was beneficial against delayed neurovascular events after SAH. This was a retrospective single-center cohort study of 121 consecutive SAH patients including 56 patients of admission World Federation of Neurological Surgeons grades IV - V who underwent aneurysmal obliteration within 72 h post-SAH from 2013 to 2021. Prophylactic antiepileptic drugs differed depending on the study terms: none (2013 - 2015), levetiracetam for patients at high risks of seizures (2016 - 2019), and perampanel for all patients (2020 - 2021). The 3rd term had the lowest occurrence of delayed cerebral microinfarction on diffusion-weighted magnetic resonance imaging, which was related to less development of DCI. Other outcome measures were similar among the 3 terms including incidences of angiographic vasospasm, computed tomography-detectable delayed cerebral infarction, seizures, and 3-month good outcomes (modified Rankin Scale 0 - 2). The present study suggests that prophylactic administration of levetiracetam and perampanel was not associated with worse outcomes and that perampanel may have the potential to reduce DCI by preventing microcirculatory disturbances after SAH. Further studies are warranted to investigate anti-DCI effects of a selective α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor antagonist perampanel in SAH patients in a large-scale prospective study.

We conducted a systematic review and meta-analysis to evaluate the risk of early and late onset seizures following stroke mechanic thrombectomy (MT) compared with other systematic thrombolytic strategies.

A literature search was conducted to identify articles covering databases (PubMed, Embase, and Cochrane Library) published from 2000 to 2022. The primary outcome was the incidence of post-stroke epilepsy or seizures following MT or in combination with intravenous thrombolytics therapy. Risk of bias was assessed by recording study characteristics. The study was conducted according to the PRISMA guidelines.

There were 1346 papers in the search results, and 13 papers were included in the final review.We identified 29,793 patients with stroke, of which 695 had seizures. Pooled incidence of post-stroke seizures had no significant difference between mechanic thrombolytic group and other thrombolytic strategy group (OR=0.95 (95%CI= 0.75-1.21); Z=0.43; p=0.67). In subgroup analysis, mechanic group have a lower risk of post-stroke early onset of seizures (OR=0.59 (95%CI=0.36-0.95); Z=2.18; p<0.05) but showed no significant difference in post-stroke late onset of seizures (OR=0.95 (95%CI= 0.68-1.32); Z=0.32; p=0.75).

MT may be associated with a lower risk of post-stroke early onset of seizures, despite MT does not affect the pooled incidence of post-stroke seizures compared with other systematic thrombolytic strategies.

Decompressive craniectomy (DC) and craniotomy (CT) to treat increased intracranial pressure after brain injury are common but controversial choices in clinical practice. Studying a large cohort of patients with traumatic brain injury (TBI) and hemorrhagic stroke (HS) on rehabilitation pathways, we aimed to determine the impact of DC and CT on functional outcome/mortality, and on seizures occurrence. This observational retrospective study included patients with either TBI, or HS, who underwent DC or CT, consecutively admitted to our unit for 6-month neurorehabilitation programs between January 1, 2009 and December 31, 2018. Neurological status using Glasgow Coma Scale (GCS), and rehabilitation outcome with Functional Independence Measure, both assessed at baseline and on discharge, post-DC cranioplasty, prophylactic antiepileptic drug use, occurrence of early/late seizures, infectious complications, and death during hospitalization were evaluated and analyzed with linear and logistic regression models. Among 278 patients, DC was performed in 98 (66.2%) with HS, and in 98 (75.4%) with TBI, whilst CT in 50 (33.8%) with HS, and in 32 (24.6%) with TBI. On admission, GCS scores were lower in patients treated with CT than in those with DC (HS, p = 0.016; TBI, p = 0.024). Severity of brain injury and older age were the main factors affecting functional outcome, without between-group differences, but DC associated with worse functional outcome, independently from severity or type of brain injury. Unprovoked seizures occurred post-DC cranioplasty more frequently after HS (OR = 5.142, 95% CI 1.026-25.784, p = 0.047). DC and CT shared similar risk of mortality, which associated with sepsis (OR = 16.846, 95% CI 5.663-50.109, p < 0.0001), or acute symptomatic seizures (OR = 4.282, 95% CI 1.276-14.370, p = 0.019), independently from the neurosurgery procedures. Among CT and DC, the latter neurosurgical procedure is at major risk of worse functional outcome in patients with mild-to-severe TBI, or HS undergoing an intensive rehabilitation program. Complications with sepsis or acute symptomatic seizures increase the risk of death.

Chronic subdural hematoma (CSDH) is a common disease in neurosurgery, which usually occurs in the elderly. Seizure is one of the postoperative complications in CSDH patients and can affect patient outcomes. There is currently no consensus on whether antiepileptic drugs should be prescribed prophylactically. The aim of this study was to evaluate independent risk factors for postoperative seizures and unfavorable outcomes in CSDH patients.

We reviewed 1,244 CSDH patients who had undergone burr-hole craniotomy in this study. Patient clinical data, CT scan results, recurrence and outcome data were collected. We divided the patients into two groups based on whether they had a postoperative seizure. Percentages and χ² tests were applied for categorical variables. Standard deviations and two-sided unpaired t-tests were applied for continuous variables. Stepwise logistic regression analyses were performed to identify the independent factors of postoperative seizures and unfavorable outcomes.

The incidence of seizures after CSDH surgery was 4.2% in this study. There was no significant difference in recurrence rate between seizure and non-seizure patients (p = 0.948), and the outcome of seizure patients was significantly poor (p < 0.001). There are more postoperative complications in seizure patients (p < 0.001). Logistic regression analysis showed that the independent risk factors for postoperative seizures included drinking history (p = 0.031), cardiac disease (p = 0.037), brain infarction (p = 0.001) and trabecular hematoma (p < 0.001). The use of urokinase is a protective factor for postoperative seizures (p = 0.028). Hypertension is an independent risk factor for unfavorable outcome in seizure patients (p = 0.038).

Seizures after CSDH surgery were associated with postoperative complications, higher mortality and poorer clinical outcomes at follow-up. We believe that alcohol consumption, cardiac disease, brain infarction and trabecular hematoma are independent risk factors for seizures. The use of urokinase is a protective factor against seizures. Patients with postoperative seizures need more stringent management of their blood pressure. A prospective randomized study is necessary to determine which subgroups of CSDH patients would benefit from antiepileptic drugs prophylaxis.

The relationship between ischemic stroke site and occurrence of poststroke epilepsy (PSE) is incompletely understood. This study intended to evaluate incidence and temporal profiles of seizures and to correlate ischemic lesion sites with PSE using voxel-based lesion symptom mapping (VLSM).

Patients with imaging-confirmed first-ever ischemic stroke without prior history of epilepsy were prospectively included. Demographic data, cardiovascular risk factors, and National Institute of Health Stroke Scale (NIHSS) scores were assessed. Data on seizures and modified Rankin scale scores were determined within a 90-day period after stroke onset. Ischemic lesion sites were correlated voxel wise with occurrence of PSE using nonparametric permutation test. Age- and sex-matched patients with first-ever ischemic strokes without PSE after 90 days served as controls for the VLSM analysis.

The stroke database contained 809 patients (mean age: 68.4 ± 14.2 years) with first-ever imaging-confirmed ischemic strokes without history of epilep. Incidence of PSE after 90-day follow-up was 2.8%. Five additional patients were admitted to the emergency department with a seizure after 90-day follow-up. Fifty percent of the seizures occurred in the acute phase after stroke. PSE patients had higher NIHSS scores and infarct volumes compared to controls without PSE (p < .05). PSE patients had infarcts predominantly involving the cerebral cortex. The hemisphere-specific VLSM analysis shows associations between PSE and damaged voxels in the left-hemispheric temporo-occipital transition zone.

The data indicate that PSE occurs in a small proportion of patients with rather large ischemic strokes predominantly involving the cerebral cortex. Especially patients with ischemic lesions in the temporo-occipital cortex are vulnerable to develop PSE.

The apoptosis repressor with caspase recruitment domain (ARC) plays a critical role in extrinsic apoptosis initiation via death receptor ligands, physiological stress, infection response in a tissue-dependent manner, endoplasmic reticulum (ER) stress, genotoxic drugs, ionizing radiation, oxidative stress, and hypoxia. Recent studies have suggested that regulating apoptosis-related pathways can improve outcomes for patients with neurological diseases, such as hemorrhagic stroke. ARC expression is significantly correlated with acute cerebral hemorrhage. However, the mechanism by which it mediates the anti-apoptosis pathway remains poorly known. Here, we discuss the function of ARC in hemorrhagic stroke and argue that it could serve as an effective target for the treatment of hemorrhagic stroke.

Epigenetic changes, such as DNA methylation and miRNA-target gene mechanisms, have recently emerged as key provokers in Ischemic stroke (IS) onset. However, cellular and molecular events harboring these epigenetic alterations are poorly understood. Therefore, the present study aimed to explore the potential biomarkers and therapeutic targets for IS.

miRNAs, mRNAs and DNA methylation datasets of IS were derived from the GEO database and normalized by PCA sample analysis. Differentially expressed genes (DEGs) were identified, and GO and KEGG enrichment analyses were performed. The overlapped genes were utilized to construct a protein-protein interaction network (PPI). Meanwhile, differentially expressed mRNAs and miRNAs interaction pairs were obtained from the miRDB, TargetScan, miRanda, miRMap and miTarBase databases. We constructed differential miRNA-target gene regulatory networks based on mRNA-miRNA interactions.

A total of 27 up-regulated and 15 down-regulated differential miRNAs were identified. Dataset analysis identified 1053 and 132 up-regulated and 1294 and 9068 down-regulated differentially expressed genes in the GSE16561 and GSE140275 datasets, respectively. Moreover, 9301 hypermethylated and 3356 hypomethylated differentially methylated sites were also identified. Moreover, DEGs were enriched in terms related to translation, peptide biosynthesis, gene expression, autophagy, Th1 and Th2 cell differentiation, primary immunodeficiency, oxidative phosphorylation and T cell receptor signaling pathway. MRPS9, MRPL22, MRPL32 and RPS15 were identified as hub genes. Finally, a differential miRNA-target gene regulatory network was constructed.

RPS15, along with hsa-miR-363-3p and hsa-miR-320e have been identified in the differential DNA methylation protein interaction network and miRNA-target gene regulatory network, respectively. These findings strongly posit the differentially expressed miRNAs as potential biomarkers to improve ischemic stroke diagnosis and prognosis.

Post-stroke epilepsy (PSE) is one of the major sequelae of stroke. Inflammation has been implicated in the development of stroke. The study aimed to explore the relationship between neutrophil-to-lymphocyte ratio (NLR) levels and epilepsy in patients with primary intracerebral hemorrhage (ICH).

A retrospective study was performed on 1132 patients with first-time ICH. Blood samples were obtained at admission after ICH. Patients included in the study were classified into three groups according to NLR tertiles. Logistic regression was used to analyze the relationship between NLR levels and the occurrence of PSE.

The occurrence of PSE was significantly correlated with NLR levels (r = 0.118, P < 0.001). Patients with PSE had higher NLR levels than those without PSE. After adjusting for potential confounders, high NLR was independently associated with an increased risk of PSE (OR = 1.861, 95% CI 1.032-3.355, P = 0.039). Neutrophil-to-lymphocyte ratio levels were independently associated with the occurrence of PSE in the poor functional outcome group, while this association was not significant in the favorable functional outcome group. The model (cortical involvement + hematoma volume + early seizures + NLR) showed good prognostic performance.

High NLR at admission is associated with an increased risk of PSE, which suggests that NLR may play a role in risk stratification in patients with ICH.

Older adults occasionally receive seizure prophylaxis in an acute ischemic stroke (AIS) setting, despite safety concerns. There are no trial data available about the net impact of early seizure prophylaxis on post-AIS survival.

Using a stroke registry (American Heart Association's Get With The Guidelines) individually linked to electronic health records, we examined the effect of initiating seizure prophylaxis (ie, epilepsy-specific antiseizure drugs) within 7 days of an AIS admission versus not initiating in patients ≥65 years admitted for a new, nonsevere AIS (National Institutes of Health Stroke Severity score ≤20) between 2014 and 2021 with no recorded use of epilepsy-specific antiseizure drugs in the previous 3 months. We addressed confounding by using inverse-probability weights. We performed standardization accounting for pertinent clinical and health care factors (eg, National Institutes of Health Stroke Severity scale, prescription counts, seizure-like events).

The study sample included 151 patients who received antiseizure drugs and 3020 who did not. The crude 30-day mortality risks were 219 deaths per 1000 patients among epilepsy-specific antiseizure drugs initiators and 120 deaths per 1000 among noninitiators. After standardization, the estimated mortality was 251 (95% CI, 190-307) deaths per 1000 among initiators and 120 (95% CI, 86-144) deaths per 1000 among noninitiators, corresponding to a risk difference of 131 (95% CI, 65-200) excess deaths per 1000 patients. In the prespecified subgroup analyses, the risk difference was 52 (95% CI, 11-72) among patients with minor AIS and 138 (95% CI, 52-222) among moderate-to-severe AIS patients. Similarly, the risk differences were 86 (95% CI, 18-118) and 157 (95% CI, 57-219) among patients aged 65 to 74 years and ≥75 years, respectively.

There was a higher risk of 30-day mortality associated with initiating versus not initiating seizure prophylaxis within 7 days post-AIS. This study does not support the role of seizure prophylaxis in reducing 30-day poststroke mortality.