Predicting who has delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage using machine learning approach: a multicenter, retrospective cohort study.

BACKGROUND: Early prediction of delayed cerebral ischemia (DCI) is critical to improving the prognosis of aneurysmal subarachnoid hemorrhage (aSAH). Machine learning (ML) algorithms can learn from intricate information unbiasedly and facilitate the early identification of clinical outcomes. This study aimed to construct and compare the ability of different ML models to predict DCI after aSAH. Then, we identified and analyzed the essential risk of DCI occurrence by preoperative clinical scores and postoperative laboratory test results. METHODS: This was a multicenter, retrospective cohort study. A total of 1039 post-operation patients with aSAH were finally included from three hospitals in China. The training group contained 919 patients, and the test group comprised 120 patients. We used five popular machine-learning algorithms to construct the models. The area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, precision, and f1 score were used to evaluate and compare the five models. Finally, we performed a Shapley Additive exPlanations analysis for the model with the best performance and significance analysis for each feature. RESULTS: A total of 239 patients with aSAH (23.003%) developed DCI after the operation. Our results showed that in the test cohort, Random Forest (RF) had an AUC of 0.79, which was better than other models. The five most important features for predicting DCI in the RF model were the admitted modified Rankin Scale, D-Dimer, intracranial parenchymal hematoma, neutrophil/lymphocyte ratio, and Fisher score. Interestingly, clamping or embolization for the aneurysm treatment was the fourth button-down risk factor in the ML model. CONCLUSIONS: In this multicenter study, we compared five ML methods, among which RF performed the best in DCI prediction. In addition, the essential risks were identified to help clinicians monitor the patients at high risk for DCI more precisely and facilitate timely intervention.

Ischemic Stroke in Young Tunisian Adults.

INTRODUCTION: Ischemic Stroke in young adults is a real public health problem; it's a major cause of disability, alters quality of life and has a great socio-economic impact. AIM: determine risk factors and specify the etiology of arterial ischemic stroke in young Tunisian adults. METHODS: In this 5 years retrospective study (2015-2020), we included all young adults (18-50 years) admitted for arterial ischemic stroke (AIS). Risk factors were registered and analyzed. All patients were investigated using a standard protocol: biological tests, brain imaging, carotid ultrasound and cardiac assessment. Additional investigations were carried out at the discretion of the treating physician. The cause of ischemic stroke was classified according to the TOAST criteria. RESULTS: We collected 200 patients with AIS. The mean age was 41.37 years ± 6.99. Traditional vascular risk factors were observed in more than 1/4 patients. A definite cause of stroke was identified in 120 patients. Cardio-embolic causes were the most common among our patients (19%) followed by atherosclerosis of the large arteries (11.5%). Other determined etiologies were found in 27.5% of patients. The etiology remained unclear in 40% of cases: undetermined despite complete investigation in 17.5%, undetermined and incompletely investigated 14.5 % and more than one potential pathomechanisms in 8%. CONCLUSION: Through this study, we demonstrated the diversity of etiology of stroke in young Tunisian adults. Changes of lifestyle are responsible for the occurrence of the traditional risk factors at an early age. Rheumatic heart diseases remain a frequent cause of AIS in our area.

Ischemic insular damage and stress ulcer in patients of acute ischemic stroke.

BACKGROUND AND AIMS: Stress ulcer (SU) is a common complication in patients with acute ischemic stroke. The relationship of infarction location and the incidence of SU was unclear. Herein, we aim to investigate the association between ischemic insular damage and the development of SU. METHODS: Data were retrieved from the SPARK study (Effect of Cardiac Function on Short-Term Functional Prognosis in Patients with Acute Ischemic Stroke). We included the patients who had experienced an ischemic stroke within 7 days. The diagnosis of SU was based on clinical manifestations, including hematemesis, bloody nasogastric tube aspirate, or hematochezia. Evaluation of ischemic insular damage was conducted through magnetic resonance imaging. Cyclo-oxygenase regression analysis and Kaplan-Meier survival curves were used to assess the relationship between ischemic insular damage and the occurrence of SU. RESULTS: Among the 1357 patients analyzed, 110 (8.1%) developed SUs during hospitalization, with 69 (6.7%) experiencing infarctions in the anterior circulation. After adjusting for potential confounders, patients with ischemic insular damage exhibited a 2.16-fold higher risk of developing SUs compared to those without insular damage (p = .0206). Notably, among patients with infarctions in the anterior circulation, those with insular damage had a 2.21-fold increased risk of SUs (p = .0387). Moreover, right insular damage was associated with a higher risk of SUs compared to left insular damage or no insular damage (p for trend = .0117). Kaplan-Meier curves demonstrated early separation among groups, persisting throughout the follow-up period (all p < .0001). CONCLUSIONS: This study identified a significant independent correlation between ischemic insular damage, particularly on the right side, and the development of SU during hospitalization, indicating the need to consider prophylactic acid-suppressive treatment for patients with ischemic insular damage.

Relationship between ω3 and ω6 polyunsaturated fatty acids and atrial fibrillation in acute ischemic stroke.

BACKGROUND & AIMS: Some ω3 polyunsaturated fatty acids (PUFAs) are said to demonstrate a dose-related risk of atrial fibrillation (AF), conversely, some ω6 PUFAs might have AF protective potential. However, few investigated the relation among ischemic strokes. Primarily, we aimed to examine a relation between ω3 and ω6 PUFAs and the presence of AF in ischemic strokes. Further, since, some PUFAs are said to affect the cardiac load, we secondarily aimed to investigate the association between ω3 and ω6 PUFAs and brain natriuretic peptide (BNP) and the occurrence of cerebral large vessel occlusion (LVO) in ischemic strokes with AF. METHODS: Consecutive patients with ischemic stroke admitted between 2012 and 2022 were retrospectively screened. Plasma levels of PUFAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid, dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA), were assayed. Data were analyzed using a Poisson regression analysis with a robust variance estimator and a multiple linear regression analysis. RESULTS: We screened 2112 consecutive ischemic strokes, including 1574 (1119 [71%] males, median age 69 years). Lower DGLA (prevalence ratio (PR) 0.885, 95% CI 0.811-0.966, p = 0.006), lower AA (PR 0.797, 95% CI 0.649-0.978, p = 0.030), and higher EPA/AA ratio (PR 1.353, 95% CI 1.036-1.767, p = 0.026) were associated with AF. Checking the linearity between AF and PUFAs, negative linear trends were observed between DGLA quartiles (Q1: PR 1.901, Q2: PR 1.550, Q3: PR 1.423, Q4: 1.000, p < 0.001 for trend) and AA quartiles (Q1: PR 1.499, Q2: PR 1.204, Q3: PR 1.125, Q4: 1.000, p = 0.004 for trend), with positive linear trends between EPA/AA ratio quartiles (Q1: 1.000, Q2: PR 1.555, Q3: PR 1.612, Q4: PR 1.797, p = 0.001 for trend). Among patients with AF, a negative association between AA and BNP (unstandardized coefficient -1.316, 95% CI -2.290∼-0.342, p = 0.008) was observed, and lower AA was associated with LVO (PR 0.707, 95% CI 0.527-0.950, p = 0.021). CONCLUSION: Lower DGLA and AA and a higher EPA/AA ratio might be related to the development of AF in ischemic strokes. Further, AA might have a cardio-cerebrovascular protective role in ischemic strokes with AF.

[Results of a pilot study of the structure and evaluation of the therapy for chronic sleep disorders in comorbid patients with chronic cerebral ischemia]. / Rezul'taty pilotnogo issledovaniya struktury i otsenki terapii khronicheskikh narushenii sna u komorbidnykh patsientov s khronicheskoi ishemiei golovnogo mozga.

OBJECTIVE: To evaluate the effect of the drug Cortexin on the clinical course and treatment of comorbid insomnia. MATERIAL AND METHODS: The study included 50 patients, average age 50.4±2.26 years, with CHI stage 1-2. with concomitant diseases arterial hypertension, atherosclerosis, diabetes mellitus (study CHRONAS). All patients were examined on the day of treatment, 11-15 days and 30-31 days after the end of therapy. At all visits, complaints, neurological status, and changes in physiological and laboratory parameters were assessed. The condition was assessed using the following scales: mental status assessment (MMSE), quality of life questionnaire (EQ-5D), assessment of general health, Pittsburgh Sleep Quality Index (PSQI), Epworth daytime sleepiness assessment, hospital anxiety and depression (HADS)).: Patients with additional diabetic polyneuropathy were assessed using the Central Sensitization Inventory (CSI). RESULTS: A high percentage of the prevalence of comorbid insomnia in patients was revealed. The structure of sleep disturbances in patients with chronic cerebral ischemia consisted of disturbances in sleep duration, difficulty falling asleep, frequent awakenings at night, and daytime sleepiness. After treatment, there was a regression of the main complaints, the severity of symptoms, including anxiety and depression, decreased, and a significant stabilization of cognitive status was observed. The positive dynamics persisted 1 month after the end of therapy. An additional normalizing effect of the drug on a number of biochemical parameters was revealed. Clinical dynamics were recorded already by the 11-15th day of treatment and persisted for up to 1 month. During observation, no patient had adverse drug interactions with other drugs (hypotensives, antiplatelet agents, statins). CONCLUSIONS: The clinical effectiveness of the drug Cortexin has been proven for all types of sleep disorders. The clinical effectiveness of the drug Cortexin at a dose of 10 mg IM for 10 days has been proven in patients with chronic sleep disorders due to CHI.

Favorable prognosis in posterior circulation ischemic stroke: Insights from a nationwide stroke databank.

INTRODUCTION: Clinical trials have historically underrepresented patients with posterior circulation ischemic stroke (PCIS). This study aimed to comprehensively assess the clinical characteristics and outcomes of PCIS patients compared to those with anterior circulation ischemic stroke (ACIS). METHODS: A retrospective analysis was conducted using data from the Japan Stroke Data Bank, encompassing 20 years across 130 stroke centers. The study focused on patients diagnosed with PCIS or ACIS. RESULTS: Among 37,069 patients reviewed, 7425 had PCIS, whereas 29,644 had ACIS. PCIS patients were younger and had a lower female representation than ACIS patients. Notably, PCIS patients had more favorable outcomes: 71% achieved a modified Rankin Scale of 0-2 or showed no deterioration at discharge (17 days at the median after admission), compared to 60% for ACIS patients (p < 0.001). Factors associated with an unfavorable outcome in the PCIS subgroup were older age, female sex (assigned at birth), history of hypertension, and higher National Institute of Health Stroke Scale (NIHSS) scores at admission. In both sexes, older age and higher NIHSS scores were negatively associated with favorable outcomes. CONCLUSIONS: PCIS patients demonstrated a more favorable prognosis than ACIS patients. Factors like older age, female sex, and higher NIHSS scores at admission were identified as independent predictors of unfavorable outcomes in PCIS patients. Older age and higher NIHSS scores at admission were common independent negative factors for a favorable outcome regardless of sex.

Prevalence and impact of SARS-CoV-2 infection among patients with acute ischaemic stroke: a nationwide register-based cohort study in Denmark.

OBJECTIVES: An increased risk of stroke has been reported among patients with COVID-19 caused by SARS-CoV-2. We aimed to investigate the nationwide prevalence of SARS-CoV-2 among patients with acute ischaemic stroke and to study the impact on stroke severity, quality of care and mortality on an individual patient level. DESIGN: This was a nationwide register-based cohort study. SETTING: We used data from several Danish registers which were linked at an individual patient level using the unique civil registration number assigned to all Danish citizens. Patients were identified from the Danish Stroke Registry and information on SARS-CoV-2 infection status was collected from the Danish National COVID-19 Registry. Concurrent SARS-CoV-2 infection was defined as a positive PCR test within 31 days prior to, and 1 day after, stroke admission. Information on comorbidity was collected from the Danish National Patient Registry and information on vital status was collected from the Danish Civil Registration System. PARTICIPANTS: A total of 11 502 patients admitted with acute ischaemic stroke from 10 March 2020 to 31 May 2021 were included in the study. RESULTS: Among the included patients, the majority (84.6%) were tested for SARS-CoV-2, but only 68 had a positive test. These patients were more prone to have atrial fibrillation and were more often treated with reperfusion therapy. They had a significantly increased risk of severe stroke (adjusted relative risk (aRR) 1.93, 95% CI: 1.22 to 3.04) and a significantly increased 30-day mortality risk (aRR 2.29, 95% CI: 1.19 to 4.39). There was no difference in the proportion of patients fulfilling relevant performance measures on quality of care. CONCLUSION: In this nationwide study, only 0.6% of patients with acute ischaemic stroke were tested positive for a concurrent SARS-CoV-2 infection. The patients with SARS-CoV-2 presented with more severe strokes.

Frequency of ischaemic stroke and intracranial haemorrhage in patients with reversible cerebral vasoconstriction syndrome (RCVS) and posterior reversible encephalopathy syndrome (PRES) - A systematic review.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS) may cause ischaemic stroke and intracranial haemorrhage. The aim of our study was to assess the frequency of the afore-mentioned outcomes. METHODS: We performed a PROSPERO-registered (CRD42022355704) systematic review and meta-analysis accessing PubMed until 7 November 2022. The inclusion criteria were: (1) original publication, (2) adult patients (≥18 years), (3) enrolling patients with PRES and/or RCVS, (4) English language and (5) outcome information. Outcomes were frequency of (1) ischaemic stroke and (2) intracranial haemorrhage, divided into subarachnoid haemorrhage (SAH) and intraparenchymal haemorrhage (IPH). The Cochrane Risk of Bias tool was used. RESULTS: We identified 848 studies and included 48 relevant studies after reviewing titles, abstracts and full text. We found 11 studies on RCVS (unselected patients), reporting on 2746 patients. Among the patients analysed, 15.9% (95% CI 9.6%-23.4%) had ischaemic stroke and 22.1% (95% CI 10%-39.6%) had intracranial haemorrhage. A further 20.3% (95% CI 11.2%-31.2%) had SAH and 6.7% (95% CI 3.6%-10.7%) had IPH. Furthermore, we found 28 studies on PRES (unselected patients), reporting on 1385 patients. Among the patients analysed, 11.2% (95% CI 7.9%-15%) had ischaemic stroke and 16.1% (95% CI 12.3%-20.3%) had intracranial haemorrhage. Further, 7% (95% CI 4.7%-9.9%) had SAH and 9.7% (95% CI 5.4%-15%) had IPH. CONCLUSIONS: Intracranial haemorrhage and ischaemic stroke are common outcomes in PRES and RCVS. The frequency reported in the individual studies varied considerably.

Nature of Neurological Complications and Outcome After Surgery for Type A Aortic Dissection.

Surgery for type A aortic dissection (TAAD) is frequently complicated by neurologic complications. The prognostic impact of neurologic complications of different nature has been investigated in this study. The subjects of this analysis were 3,902 patients who underwent surgery for acute TAAD from the multicenter European Registry of Type A Aortic Dissection (ERTAAD). During the index hospitalization, 722 patients (18.5%) experienced stroke/global brain ischemia. Ischemic stroke was detected in 539 patients (13.8%), hemorrhagic stroke in 76 patients (1.9%) and global brain ischemia in 177 patients (4.5%), with a few patients having had findings of more than 1 of these conditions. In-hospital mortality was increased significantly in patients with postoperative ischemic stroke (25.6%, adjusted odds ratio [OR] 2.422, 95% confidence interval [CI] 1.825 to 3.216), hemorrhagic stroke (48.7%, adjusted OR 4.641, 95% CI 2.524 to 8.533), and global brain ischemia (74.0%, adjusted OR 22.275, 95% CI 14.537 to 35.524) compared with patients without neurologic complications (13.5%). Similarly, patients who experienced ischemic stroke (46.3%, adjusted hazard ratio [HR] 1.719, 95% CI 1.434 to 2.059), hemorrhagic stroke (62.8%, adjusted HR 3.236, 95% CI 2.314 to 4.525), and global brain ischemia (83.9%, adjusted HR 12.777, 95% CI 10.325 to 15.810) had significantly higher 5-year mortality than patients without postoperative neurologic complications (27.5%). The negative prognostic effect of neurologic complications on survival vanished about 1 year after surgery. In conclusion, postoperative ischemic stroke, hemorrhagic stroke, and global cerebral ischemia increased early and midterm mortality after surgery for acute TAAD. The magnitude of risk of mortality increased with the severity of the neurologic complications, with postoperative hemorrhagic stroke and global brain ischemia being highly lethal complications.

Geographic differences in pharmacotherapy patterns and outcomes of acute ischemic stroke in China.

BACKGROUND: Vast economic and healthcare status discrepancies exist among regions in China, contributing to different treatment patterns. This study was aimed to investigate the current status of pharmacotherapy for acute ischemic stroke (AIS) and outcomes in China and explore the geographic variation in stroke care. METHODS: This study was a multicenter prospective registry study, which collected the data of patients with AIS from 80 hospitals in 46 cities in 2015-2017 across China. Poor functional outcome defined as a modified Rankin Scale score of 3-6 was assessed at 3 and 12 months. Multivariate logistic regression was used. RESULTS: Among 9973 eligible patients, the number of receiving intravenous thrombolysis (IVT), antiplatelet agents, anticoagulants, statin and human urinary kallidinogenase was 429 (4.3%), 9363 (93.9%), 1063 (10.7%), 6828 (74.7%) and 5112 (51.2%), respectively. Multivariable analysis showed IVT use in northeastern was significantly more frequent than in eastern region (OR = 3.17, 95% CI, 2.53-3.99), while the antiplatelets agents use were less frequent (OR = 0.46, 95%CI: 0.38-0.57). The proportions of poor outcomes at 3 and 12 months were 20.7% and 15.8%, respectively. Multivariate analysis showed AIS patients from northeastern and central region had significantly lower risk of poor outcome at month 3 and 12 than those from eastern region (all P < 0.05). CONCLUSIONS: There was a low IVT use and a high antiplatelet agent and statin use for AIS in China. The pharmacotherapy and prognosis of AIS had variation by geographic region. TRIAL REGISTRATION: This study was registered with ClinicalTrials.gov (NCT02470624).

Effect of acupuncture on ischaemic stroke in patients with rheumatoid arthritis: a nationwide propensity score-matched study.

OBJECTIVE: To demonstrate that acupuncture is beneficial for decreasing the risk of ischaemic stroke in patients with rheumatoid arthritis (RA). DESIGN: A propensity score-matched cohort study. SETTING: A nationwide population-based study. PARTICIPANTS: Patients with RA diagnosed between 1 January 1997 and 31 December 2010, through the National Health Insurance Research Database in Taiwan. INTERVENTIONS: Patients who were administered acupuncture therapy from the initial date of RA diagnosis to 31 December 2010 were included in the acupuncture cohort. Patients who did not receive acupuncture treatment during the same time interval constituted the no-acupuncture cohort. PRIMARY OUTCOME MEASURES: A Cox regression model was used to adjust for age, sex, comorbidities, and types of drugs used. We compared the subhazard ratios (SHRs) of ischaemic stroke between these two cohorts through competing-risks regression models. RESULTS: After 1:1 propensity score matching, a total of 23 226 patients with newly diagnosed RA were equally subgrouped into acupuncture cohort or no-acupuncture cohort according to their use of acupuncture. The basic characteristics of these patients were similar. A lower cumulative incidence of ischaemic stroke was found in the acupuncture cohort (log-rank test, p<0.001; immortal time (period from initial diagnosis of RA to index date) 1065 days; mean number of acupuncture visits 9.83. In the end, 341 patients in the acupuncture cohort (5.95 per 1000 person-years) and 605 patients in the no-acupuncture cohort (12.4 per 1000 person-years) experienced ischaemic stroke (adjusted SHR 0.57, 95% CI 0.50 to 0.65). The advantage of lowering ischaemic stroke incidence through acupuncture therapy in RA patients was independent of sex, age, types of drugs used, and comorbidities. CONCLUSIONS: This study showed the beneficial effect of acupuncture in reducing the incidence of ischaemic stroke in patients with RA.

Three-year incidence and acute setting predictors of epilepsy after neonatal and childhood arterial ischaemic stroke: a disease-based cohort study.

To assess the association between clinical and MRI characteristics of arterial ischaemic stroke (AIS) and the 3-year risk of post-stroke epilepsy (PSE) in paediatric patients. Retrospective cohort study. Database from a single tertiary referral centre for paediatric stroke in Chile. Two hundred seven neonates and children (1 day to 18 years) with a first-ever supratentorial AIS diagnosed between January 2003 and December 2019 were evaluated. Diagnosis of PSE and explanatory variables were consecutively recorded from hospital inpatient and annual outpatient records in a predesigned database. Competing risk analysis (competing events: death and loss to follow-up) of multiple Cox proportional hazards regression was performed to estimate adjusted subhazard ratios (SHRs) of PSE. Confidence intervals (95% CI) were calculated using bootstrap resampling (1000 replications). Interaction terms were added to investigate moderating effects. The 3-year incidence rate of PSE was 166.5 per 1000 person-years (neonatal: 150.1; childhood: 173.9). The 3-year cumulative incidence was 33%. Patients with acute symptomatic non-status seizures (SHR = 3.13; 95% CI = 1.43-6.82), status epilepticus (SHR = 5.16; 95% CI = 1.90-13.96), abnormal discharge neurological status (SHR = 2.52; 95% CI = 1.12-5.63), cortical lesions (SHR = 2.93; 95% CI = 1.48-5.81), and multifocal infarcts with stroke size < 5% of supratentorial brain volume (SHR = 3.49; 95% CI = 1.44-8.46) had a higher risk of PSE. CONCLUSION: This study identified specific and reliable acute clinical and imaging predictors of PSE in paediatric patients, helping clinicians identify high-risk patients with potential implications for treatment decisions. WHAT IS KNOWN: • Numerous risk factors have been proposed for post-stroke epilepsy, but there is a lack of studies evaluating these variables while accounting for confounding factors and competing risks over time. WHAT IS NEW: • After adjustment for competing events, acute symptomatic seizures, both non-status and status epilepticus, abnormal mental status or motor neurological examination at hospital discharge, cortical involvement, and multifocal ischaemic lesions in small strokes are all independent predictors of post-stroke epilepsy. • Knowing the predictors of post-stroke epilepsy is essential for clinicians to make well-informed and effective decisions about treatment.

Thrombolytic Treatment in Wake-Up Stroke: A Propensity Score-Matched Analysis of Treatment Effectiveness in the Norwegian Stroke Registry.

BACKGROUND: Previous clinical trials found improved outcome of thrombolytic treatment in patients with ischemic wake-up stroke (WUS) selected by advanced imaging techniques. The authors assessed the effectiveness of thrombolytic treatment in patients with WUS in a nationwide stroke registry. METHODS AND RESULTS: Using propensity score matching, the authors assessed the effectiveness and safety of thrombolytic treatment versus no thrombolytic treatment in 726 patients (363 matched pairs) with WUS in the Norwegian Stroke Registry in 2014 to 2019. Thrombolytic treatment in WUS versus known-onset stroke was compared in 730 patients (365 matched pairs). Functional outcomes were assessed by the modified Rankin Scale (mRS) at 3 months. A significant benefit of thrombolytic treatment in WUS was seen in ordinal analysis (odds ratio [OR], 1.48 [95% CI, 1.15-1.91]; P=0.003) and for mRS 0 to 2 (OR, 1.81 [95% CI, 1.29-2.52]; P=0.001) but not for mRS 0 or 1 (OR, 1.32 [95% CI, 1.00-1.74]; P=0.050). The proportion of patients with mRS 0 or 1 was lower in patients with WUS who underwent thrombolysis versus those with known-onset stroke (50.4% versus 59.5%; OR, 0.69 [95% CI, 0.52-0.93]; P=0.013), while outcomes were similar between groups for mRS 0 to 2 and ordinal analysis. Symptomatic intracranial hemorrhage after thrombolytic treatment occurred in 4.4% of patients with WUS and 3.9% of patients with known-onset stroke (OR, 1.14 [95% CI, 0.54-2.41]; P=0.726). CONCLUSIONS: Thrombolytic treatment in patients with WUS was associated with improved functional outcome compared with patients with no thrombolytic treatment and was not associated with increased rates of symptomatic intracranial hemorrhage compared with known-onset stroke. The results indicate that thrombolytic treatment is effective and safe in WUS in a real-life setting.

Association of covert brain infarct phenotype with stroke recurrence in first-ever manifest ischemic stroke according to etiology.

INTRODUCTION: Covert brain infarcts (CBI) are frequent incidental findings on MRI and associated with future stroke risk in patients without a history of clinically evident cerebrovascular events. However, the prognostic value of CBI in first-ever ischemic stroke patients is unclear and previous studies did not report on different etiological stroke subtypes. We aimed to test CBI phenotypes and their association with stroke recurrence in first-ever ischemic stroke patients according to stroke etiology. PATIENTS AND METHODS: This study is a pooled data analysis of two prospectively collected cohorts of consecutive first-ever ischemic stroke patients admitted to the comprehensive stroke centers of Bern (Switzerland) and Graz (Austria). CBI phenotypes were identified on brain MRI within 72 h after admission. All patients underwent a routine follow-up (median: 12 months) to identify stroke recurrence. RESULTS: Of 1577 consecutive ischemic stroke patients (median age: 71 years), 691 patients showed CBI on brain MRI (44%) and 88 patients had a recurrent ischemic stroke (6%). Baseline CBI were associated with stroke recurrence in multivariable analysis (HR 1.9, 95% CI 1.1-3.3). CBI phenotypes with the highest risk for stroke recurrence were cavitatory CBI in small vessel disease (SVD)-related stroke (HR 7.1, 95% CI 1.6-12.6) and cortical CBI in patients with atrial fibrillation (HR 3.0, 95% CI 1.1-8.1). DISCUSSION AND CONCLUSION: This study reports a ≈ 2-fold increased risk for stroke recurrence in first-ever ischemic stroke patients with CBI. The risk of recurrent stroke was highest in patients with cavitatory CBI in SVD-related stroke and cortical CBI in patients with atrial fibrillation.Subject terms: Covert brain infarcts, stroke.

First-ever acute ischemic strokes in HIV-infected persons: A case-control study from stroke units.

OBJECTIVE: The stroke risk for persons living with human immunodeficiency virus (PLHIVs) doubled compared to uninfected individuals. Stroke-unit (SU)-access, acute reperfusion therapy-use and outcome data on PLHIVs admitted for acute ischemic stroke (AIS) are scarce. METHODS: AIS patients admitted (01 January 2017 to 31 January 2021) to 10 representative Paris-area SUs were screened retrospectively from the National Hospitalization Database. PLHIVs were compared to age-, initial NIHSS- and sex-matched HIV-uninfected controls (HUCs). Outcome was the 90-day modified Rankin Scale score. RESULTS: Among 126 PLHIVs with confirmed first-ever AIS, ~80% were admitted outside the thrombolysis-administration window. Despite antiretrovirals, uncontrolled plasma HIV loads exceeded 50 copies/mL (26% of all PLHIVs; 38% of those ≤55 years). PLHIVs' stroke causes by decreasing frequency were large artery atherosclerosis (LAA), undetermined, other cause, cerebral small-vessel disease (CSVD) or cardioembolism. No stroke etiology was associated with HIV duration or detectable HIVemia. MRI revealed previously unknown AIS in one in three PLHIVs, twice the HUC rate (p = 0.006). Neither group had optimally controlled modifiable cardiovascular risk factors (CVRFs): 20%-30% without specific hypertension, diabetes, and/or dyslipidemia treatments. Their stroke outcomes were comparable. Multivariable analyses retained good prognosis associated solely with initial NIHSS or reperfusion therapy. Older age and hypertension were associated with CSVD/LAA for all PLHIVs. Standard neurovascular care and reperfusion therapy were well-tolerated. INTERPRETATION: The high uncontrolled HIV-infection rate and suboptimal CVRF treatment support heightened vigilance to counter suboptimal HIV suppression and antiretroviral adherence, and improve CVRF prevention, mainly for younger PLHIVs. Those preventive, routine measures could lower PLHIVs' AIS risk.

PDE4D single nucleotide polymorphism rs918592 is associated with ischemic Stroke risk in Chinese populations: a meta-analysis.

BACKGROUND: Several studies have investigated the correlation between phosphodiesterase 4D (PDE4D) single nucleotide polymorphism (SNP) rs918592 and the risk of ischemic stroke (IS) in Chinese populations. But the results were inconsistent and inconclusive. Therefore, to resolve this conflict, we conducted a meta-analysis to further elucidate their relationship in Chinese populations. METHODS: Studies focused on SNP rs918592 and IS risk were electronic searched in the databases of PubMed, Embase, ISI Web of Science, Weipu, China National Knowledge Infrastructure (CNKI), Chinese Biomedical (CBM) and Wanfang. The association between SNP rs918592 and IS risk was expressed by odds ratio (OR) with its confidence interval (CI). Begg's and Egger's linear regression tests were used to assess publication bias. The meta-analysis was performed with STATA 11.0 statistical software. Two online prediction websites (HaploReg and RegulomeDB) were adopted to explore the functions of SNP rs918592. RESULTS: The meta-analysis ultimately included 10 studies involving 2,348 cases and 2,289 controls. The results showed that there was a significant correlation between SNP rs918592 and IS risk in Chinese individuals. The G allele had reduced risk of developing IS compared to the A allele (OR 0.83, 95% CI 0.74-0.95, P = 0.005). HaploReg and RegulomeDB analyses suggested that SNP rs918592 and its strongly linked SNPs (e.g. rs34168777) might have regulatory functions. CONCLUSION: This study shows that SNP rs918592 in PDE4D may be a contributor of IS risk in Chinese populations. It offers a good answer for the association of PDE4D SNP rs918592 with IS risk in Chinese populations for the first time.

Epilepsy and the risk of adverse cardiovascular events: A nationwide cohort study.

BACKGROUND AND PURPOSE: Epilepsy is associated with higher morbidity and mortality compared to people without epilepsy. We performed a retrospective cross-sectional and longitudinal cohort study to evaluate cardiovascular comorbidity and incident vascular events in people with epilepsy (PWE). METHODS: Data were extracted from the French Hospital National Database. PWE (n = 682,349) who were hospitalized between January 2014 and December 2022 were matched on age, sex, and year of hospitalization with 682,349 patients without epilepsy. Follow-up was conducted from the date of first hospitalization with epilepsy until the date of each outcome or date of last news in the absence of the outcome. Primary outcome was the incidence of all-cause death, cardiovascular death, myocardial infarction, hospitalization for heart failure, ischaemic stroke (IS), new onset atrial fibrillation, sustained ventricular tachycardia or fibrillation (VT/VF), and cardiac arrest. RESULTS: A diagnosis of epilepsy was associated with higher numbers of cardiovascular risk factors and adverse cardiovascular events compared to controls. People with epilepsy had a higher incidence of all-cause death (incidence rate ratio [IRR] = 2.69, 95% confidence interval [CI] = 2.67-2.72), cardiovascular death (IRR = 2.16, 95% CI = 2.11-2.20), heart failure (IRR = 1.26, 95% CI = 1.25-1.28), IS (IRR = 2.08, 95% CI = 2.04-2.13), VT/VF (IRR = 1.10, 95% CI = 1.04-1.16), and cardiac arrest (IRR = 2.12, 95% CI = 2.04-2.20). When accounting for all-cause death as a competing risk, subdistribution hazard ratios for ischaemic stroke of 1.59 (95% CI = 1.55-1.63) and for cardiac arrest of 1.73 (95% CI = 1.58-1.89) demonstrated higher risk in PWE. CONCLUSIONS: The prevalence and incident rates of cardiovascular outcomes were significantly higher in PWE. Targeting cardiovascular health could help reduce excess morbidity and mortality in PWE.

Refining prediction of stroke in sinus node dysfunction patients without atrial fibrillation using a P-combined score: a multi-centre study.

AIMS: Isolated sinus node dysfunction (ISND) is a sinus node dysfunction without atrial fibrillation. A high risk of ischaemic stroke (IS) has been reported in ISND populations. However, current guidelines do not recommend anticoagulation in ISND management. P-wave indicates ISND-related atrial remodelling. P-wave indices and the CHA2DS2-VASc score may contribute to risk stratification for ISND-related IS. METHODS AND RESULTS: In this multi-centre longitudinal cohort, ISND patients were divided into development (n = 1185) and external validation (n = 988) cohorts. Ischaemic stroke prediction capacity of the P-combined score was assessed with regard to discrimination, calibration, and clinical effectiveness. The cut-off value of the score was confirmed by using a restricted cubic spline curve. One hundred and twenty-four (10.46%) ISND patients developed IS [1.63%/year; 95% confidence interval (CI): 1.49-1.78%/year] after a median 3.02-year follow-up in the development cohort. The P-wave terminal force in electrocardiogram-lead V1 (PTFV1) was the only significantly abnormal P-wave index (adjusted hazard ratio: 2.56; 95% CI: 1.72-3.80). Therefore, we incorporated the PTFV1 with the CHA2DS2-VASc score to generate a P-combined score. For a 5-year IS risk, the P-combined score improved Harrell's C-statistic (95% CI) from 0.678 (0.618-0.738) to 0.716 (0.657-0.774) and 0.747 (0.677-0.816) to 0.808 (0.747-0.868) in the development and validation cohorts, respectively, along with calibration and decision curve analyses. The cut-off value of the score was 3 in the development cohort and well-discriminated in the validation cohort. CONCLUSION: Chinese ISND patients have a higher IS risk than the general population. Compared with the CHA2DS2-VASc score, the PTFV1-combined CHA2DS2-VASc score shows a better risk-stratification capacity for ISND-related IS.

By screening the risk factors of ischaemic stroke for isolated sinus node dysfunction (sinus node dysfunction without atrial fibrillation), we developed and validated a new scoring system­P-combined score, which is a combination of an abnormal P-wave terminal force in electrocardiogram-lead V1 (PTFV1) and the CHA2DS2-VASc score. We constructed the P-combined score in the following way: abnormal PTFV1 (2 points), age (1 point for 65­74 years and 2 points for ≥75 years), sex (1 point for female), congestive heart failure (1 point), hypertension (1 point), diabetes mellitus (1 point), vascular disease (1 point), and thrombotic event (2 points). Based on our analysis, we found that the P-combined score showed a strong performance (with a C-statistic of 0.716 for 5 years), which was better than the CHA2DS2-VASc score (C-statistic of 0.678 for 5 years). We also found that the performance of the P-combined score was rigorous in an independent cohort from two external centres (with a C-statistic of 0.808 for 5 years) and outperformed the CHA2DS2-VASc score (C-statistic of 0.747 for 5 years).

CSF-Based Volumetric Imaging Biomarkers Highlight Incidence and Risk Factors for Cerebral Edema After Ischemic Stroke.

BACKGROUND: Cerebral edema has primarily been studied using midline shift or clinical deterioration as end points, which only captures the severe and delayed manifestations of a process affecting many patients with stroke. Quantitative imaging biomarkers that measure edema severity across the entire spectrum could improve its early detection, as well as identify relevant mediators of this important stroke complication. METHODS: We applied an automated image analysis pipeline to measure the displacement of cerebrospinal fluid (ΔCSF) and the ratio of lesional versus contralateral hemispheric cerebrospinal fluid (CSF) volume (CSF ratio) in a cohort of 935 patients with hemispheric stroke with follow-up computed tomography scans taken a median of 26 h (interquartile range 24-31) after stroke onset. We determined diagnostic thresholds based on comparison to those without any visible edema. We modeled baseline clinical and radiographic variables against each edema biomarker and assessed how each biomarker was associated with stroke outcome (modified Rankin Scale at 90 days). RESULTS: The displacement of CSF and CSF ratio were correlated with midline shift (r = 0.52 and - 0.74, p < 0.0001) but exhibited broader ranges. A ΔCSF of greater than 14% or a CSF ratio below 0.90 identified those with visible edema: more than half of the patients with stroke met these criteria, compared with only 14% who had midline shift at 24 h. Predictors of edema across all biomarkers included a higher National Institutes of Health Stroke Scale score, a lower Alberta Stroke Program Early CT score, and lower baseline CSF volume. A history of hypertension and diabetes (but not acute hyperglycemia) predicted greater ΔCSF but not midline shift. Both ΔCSF and a lower CSF ratio were associated with worse outcome, adjusting for age, National Institutes of Health Stroke Scale score, and Alberta Stroke Program Early CT score (odds ratio 1.7, 95% confidence interval 1.3-2.2 per 21% ΔCSF). CONCLUSIONS: Cerebral edema can be measured in a majority of patients with stroke on follow-up computed tomography using volumetric biomarkers evaluating CSF shifts, including in many without visible midline shift. Edema formation is influenced by clinical and radiographic stroke severity but also by chronic vascular risk factors and contributes to worse stroke outcomes.

Sex-based differences in risk factors for incident myocardial infarction and stroke in the UK Biobank.

AIM: This study examined sex-based differences in associations of vascular risk factors with incident cardiovascular events in the UK Biobank. METHODS: Baseline participant demographic, clinical, laboratory, anthropometric, and imaging characteristics were collected. Multivariable Cox regression was used to estimate independent associations of vascular risk factors with incident myocardial infarction (MI) and ischaemic stroke for men and women. Women-to-men ratios of hazard ratios (RHRs), and related 95% confidence intervals, represent the relative effect-size magnitude by sex. RESULTS: Among the 363 313 participants (53.5% women), 8470 experienced MI (29.9% women) and 7705 experienced stroke (40.1% women) over 12.66 [11.93, 13.38] years of prospective follow-up. Men had greater risk factor burden and higher arterial stiffness index at baseline. Women had greater age-related decline in aortic distensibility. Older age [RHR: 1.02 (1.01-1.03)], greater deprivation [RHR: 1.02 (1.00-1.03)], hypertension [RHR: 1.14 (1.02-1.27)], and current smoking [RHR: 1.45 (1.27-1.66)] were associated with a greater excess risk of MI in women than men. Low-density lipoprotein cholesterol was associated with excess MI risk in men [RHR: 0.90 (0.84-0.95)] and apolipoprotein A (ApoA) was less protective for MI in women [RHR: 1.65 (1.01-2.71)]. Older age was associated with excess risk of stroke [RHR: 1.01 (1.00-1.02)] and ApoA was less protective for stroke in women [RHR: 2.55 (1.58-4.14)]. CONCLUSION: Older age, hypertension, and smoking appeared stronger drivers of cardiovascular disease in women, whereas lipid metrics appeared stronger risk determinants for men. These findings highlight the importance of sex-specific preventive strategies and suggest priority targets for intervention in men and women.